title: microRNAs in Wnt/b-catenin dependent murine HCC

status: Public on Aug 31 2017

city: Glasgow

first: Chiara

last: Braconi

address: Switchback road

department: Wolfson Wohl Cancer Research Centre

country: United Kingdom

institute: University of Glasgow

summary: Wnt/b-catening dependent HCC mouse models was used to assess microRNA profiles  downstream of Wnt/b-catening pathway in mice HCC

overall_design: APC fl/fl (n=3) mice developed Wnt/b-catenin dependent HCC and were compared to APC +/+ (n=3) control mice (no tumour)


title: Tthe transcriptional profile analysis of mice liver CD8+ T cells from dnTGFβRII (TG) mice VS.dnTGFβRII CXCR3-/- (TGC3) mice

city: Hefei

first: Hong-Di

last: Ma

address: Huangshan Road 443

country: China

institute: University of Science and Technology of China

summary: Based on the data we obtained we next focused on potential intrinsic changes of CD8+ T cells. Gene expression proﬁles of CD8+ T cells isolated from livers of both the TG and TGC3 mice were analyzed by gene microarray.

overall_design: The gene expression proﬁles of liver CD8+ T cells from two groups of mice (TG VS.TGC3) were analyzed using an oligonucleotide microarray, to identify the role of chemokine receptor CXCR3 in CD8+ T cell activation and proliferation.

first: Zhe-Xiong

last: Lian


title: Long non-coding RNA in liver of HCC mouse model

type:
Expression profiling by array
Non-coding RNA profiling by array

summary: Wnt/b-catening dependent HCC mouse models was used to assess T-UCR profiles in mice HCC downstream of Wnt/b-catening pathway.

overall_design: APC fl/fl (n=3) mice developed Wnt/b-catenin dependent HCC and were compared to APC +/+ (n=3) control mice (no tumour). Sample tables include normalized data for both mRNA and lncRNA probes.


title: Glutamine supplementation suppresses herpes simplex virus reactivation I

status: Public on Aug 30 2017

city: Bethesda

first: Timothy

middle: G

last: Myers

state: MD

address: 50 South Drive, Room 5509

department: Research Technologies Branch

country: USA

institute: National Institute of Allergy and Infectious Diseases

summary: Chronic viral infections are difficult to treat and new approaches, particularly those involving enhancing immune responses are needed.  Herpes simplex virus (HSV) establishes latency, reactivates frequently, and breakthrough reactivation can occur despite suppressive antiviral therapy.  Virus-specific T cells are important to control HSV, and activated T cells require increased metabolism of glutamine for their proliferation.  We found that treatment of HSV-1 latently infected mice and HSV-2 infected guinea pigs with supplemental oral glutamine reduced virus reactivation.  Transcriptome analysis of mice treated with glutamine showed that several interferon (IFN)-γ inducible genes were upregulated.  Unlike wild-type mice, supplemental glutamine was ineffective in reducing the rate of HSV-1 reactivation in IFN-γ knock-out mice.  Mice treated with glutamine had higher numbers of HSV-specific IFN-γ producing CD8 T cells in latently infected ganglia.  Thus, glutamine may enhance the IFN-γ-associated immune response and reduce the rate of reactivation of latent virus infection.

overall_design: RNA from HSV-1 latently infected  trigeminal ganglia of mice receiving dietary supplement of glutamine (test) were compared to those that received supplemental glycine (control); RNA from 5 pairs of test/control mice co-hybridized to microarray. One of the pairs has  dye label orientation oppposite the other 4.

first: Kening

last: Wang

first: Yo

last: Hoshino

first: Kennichi

last: Dowdell

first: Marta

last: Bosch-Marce

first: Mayra

last: Sarmiento

first: Lesley

last: Pesnicak

first: Philip

middle: R

last: Krause

first: Jeffrey

middle: I

last: Cohen


title: Expression data from Saccharomyces cerevisiae

city: Göteborg

first: Xin

last: Chen

address: Kemigården 4

department: Department of Biology and Biological Engineering

country: Sweden

institute: Chalmers University of Technology

summary: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder. Oligomers of Amyloid-β peptides (Aβ) are thought to play a pivotal role in AD pathogenesis, yet the mechanisms involved remain unclear. Two major isoforms of Aβ associated with AD are Aβ40 and Aβ42, the latter being more prone to form oligomers and toxic. Humanized yeast models are currently applied to unravel the cellular mechanisms behind Aβ toxicity. Here, we took a systems biology approach to study two yeast AD models which expressed either Aβ40 or Aβ42 in bioreactor cultures. Strict control of oxygen availability and culture pH, strongly affected the chronological lifespan and reduced confounding effects of variations during cell growth. Reduced growth rates and biomass yields were observed upon expression of Aβ42, indicating a redirection of energy from growth to maintenance. Quantitative physiology analyses furthermore revealed reduced mitochondrial functionality and ATP generation in Aβ42 expressing cells, which matched with observed aberrant fragmented mitochondrial structures. Genome-wide expression levels analysis showed that Aβ42 expression triggers strong ER stress and unfolded protein responses (UPR). Expression of Aβ40 induced only mild ER stress, leading to activation of UPR target genes that cope with misfolded proteins, which resulted in hardly affected physiology. The combination of well-controlled cultures and AD yeast models strengthen our understanding of how cells translate different levels of Aβ toxicity signals into particular cell fate programs, and further enhance their role as a discovery platform to identify potential therapies.

platform_organism:
Schizosaccharomyces pombe
Saccharomyces cerevisiae

overall_design: The goal of the present study is to evaluate the impact of  Aβ peptides expression on yeast physiology and transcriptome profiles following the growth phases. Saccharomyces cerevisiae expressing Aβ42 and Aβ40 peptide respectively was cultivated in well controlled bioreactors. Samples were taken from duplicate cultures during exponential phase (EX), post-diauxic shift phase (PD), early stationary phase (SP1), late stationary phase (SP2).

first: Markus

middle: M

last: Bisschops

first: Nisha

last: Agarwal

first: Boyang

last: Ji

first: Kumaravel

middle: P

last: Schanmugavel

first: Dina

last: Petranovic


title: Molecular indicators of stress-induced neuroinflammation in a mouse model simulating features of post-traumatic stress disorder

city: Silver Spring

first: Aarti

last: Gautam

address: 503 Robert Grant Avenue

department: Medical Readiness Systems Biology

institute: WRAIR

type: Methylation profiling by genome tiling array

summary:
A social-stress mouse model, involving exposure of an intruder (male C57BL/6) mouse to a resident aggressor (male SJL) mouse followed by exposure to trauma reminders with post-trauma periods, was used to simulate features of human PTSD.  Transcriptome changes in blood, brain regions and spleen, and DNA methylome changes in hemi-brain of aggressor-exposed and control C57BL/6 mice were assayed at one, 10 and 42 days of post-trauma periods.
Assessments of activation patterns for differentially expressed transcripts (overlapping among hemi-brain, blood and spleen), and differentially methylated promoter regions showed increased activations of inflammatory pathways, and inhibited pathways related to neurogenesis and synaptic plasticity at longer post-trauma days.  In amygdala, hippocampus and medial pre-frontal cortext, these pathways were activated at earlier post-trauma periods. But at longer post-trauma periods, neurogenesis and synaptic plasticity were inhibited while lower level of activated inflammation persisted in hippocampus and medial pre-frontal cortex.  Pathways implicated in diabetes, insulin signaling, metabolic disorder, mitochondrial dysfunctions, circadian disruption, oxidative stress and inhibited telomere maintenance were significantly enriched.  Identification of brain – blood overlapping molecular signatures provide increased confidence in using blood as brain surrogate sample for clinical translation. Our findings suggest that stress-induced inflammation triggers impaired neurogenesis, cognitive decline, and chronic pain (physical complaints in PTSD patients).  Signaling pathways implicated in neurogenesis and synaptic plasticity seem to be mediating the effect of neuroinflammation in the development and maintenance of behavioral manifestations of PTSD.  While inflammation seems to be directly involved in tissue damage triggering, exacerbating or maintaining the somatic comorbid pathologies of PTSD.

overall_design:
Transcriptome changes in blood, brain regions and spleen, and DNA methylome changes in hemi-brain of aggressor-exposed and control C57BL/6 mice were assayed at one, 10 and 42 days of post-trauma periods.

This series includes the methylome data only. The transcriptome data was submitted previously and is available in GEO through series GSE45035.

first: Seid

last: Muhie

first: Nabarun

last: Chakraborty

first: James

last: Meyerhoff

first: Rasha

last: Hammamieh

first: Marti

last: Jett


title: Temporal Gene Expression Analysis of the intracellular pathogen Brucella melitensis following bovine Peyer's patch infection.

city: College Station

first: Leslie

middle: Garry

last: Adams

state: TX

address: 402 Raymond Stotzer Blvd.

department: Veterinary Pathobiology

institute: Texas A&M University

summary: In a time course study, we characterized global gene expression profile of B. melitensis infection in bovine Peyer patches in the first 4 h p.i. Statistical analysis of microarray results reveal that 2,356 B. melitensis genes were detected as differentially expressed (z-score p < 0.025) compared with control between 15 min and 4 h post-infection. A group of 1,740 genes that were differentially expressed in at least 4 out of 5 time points was considered the core set of genes that reflect the major changes in B. melitensis gene expression during the early in vivo bovine Peyer’s patch infection and therefore important in understanding key events in the modulation of host response. From this set of 1,740 differentially expressed genes, 925 (53%) were up-regulated and 815 (47%) were down-regulated compared with the in vitro grown culture. These results reflect significant Brucella metabolic modifications and adaptation from an extracellular to an intracellular lifestyle. Specific genes and biological processes identified in this study will further help elucidate how both host and Brucella interact during the early infectious process to the eventual benefit of the pathogen and to the detriment of the naïve host.

overall_design: Microarrays were used to examine the transcriptional profiles of wild type Brucella melitensis 16M intraluminally inoculated in bovine ileal loops across five time points (15 min, 30 min, 1, 2 and 4 hours).  To account for the possibility of the cross-hybridization from the surgery samples, the original total RNA from B. melitensis-infected bovine Peyer’s patches (i.e. non-enriched non-amplified) (n = 20) were also hybridized against B. melitensis gDNA on the B. melitensis oligo-arrays, and those oligospots with signal were considered non-specific and eliminated from all analyses to avoid false positive pathogen gene detection. The intracellular B. melitensis gene expression at every time point was compared to the gene expression of the inoculum (i.e. in vitro-grown cultures of B. melitensis at late-log phase of growth) (n = 4). Experiments and controls were performed in quadruplicate (bovine ligated ileal loops surgeries were performed with four calves), generating a total of 44 arrays.

first: Carlos

middle: A

last: Rossetti

first: Kenneth

last: Drake

first: Sara

middle: D

last: Lawhon

first: Jairo

middle: E

last: Nunes

first: Tamara

last: Gull

first: Sangeeta

last: Khare

first: Robin

last: Everts

first: Harris

last: Lewin

first: L


title: Expression analysis of Danio rerio semaphorin6a and plexinA2 morpholino-injected embryos

status: Public on Aug 28 2017

city: Northfield

first: Heather

middle: Elizabeth

last: Driscoll

state: VT

address: 158 Harmon Drive

department: Biology

institute: Norwich University

summary:
Investigation of whole genome gene expression level changes in Danio rerio semaphorin6A and plexinA2 morphant animals, compared to the wild-type strain.
The morphants analyzed in this study are further described in Ebert AM, Childs SJ, Hehr C, Cechmanek PB, McFarlane S. 2014. Sema6a and Plxna2 mediate spatially regulated repulsion within the developing eye to promote eye vesicle cohesion. Development 141(12):2473-2482.

overall_design: A twelve chip study using total RNA recovered from four replicates of control, semaphorin6a morpholino-injected and plexinA2 morpholino-injected 18 hour postfertilization rx3:GFP zebrafish embryos. Samples were run on a NimbleGen Zebrafish Gene Expression 385K Microarray

first: Alicia

last: Ebert

first: Sarah

last: McFarlane


title: Validation of a novel Mho microarray for characterization of the Mycoplasma hominis-action at different stages of HeLa cell infection

city: Duesseldorf

first: Karl

last: Koehrer

address: Universitaetsstr. 1

department: BMFZ

country: Germany

institute: University of Duesseldorf

summary: For a comprehensive characterisation of the M. hominis-action in infection a customized Mho microarray, which was based on two genome sequences (PG21 and LBD-4), was newly designed and validated for M. hominis strain FBG, to analyze the dynamics of the mycoplasma transcriptome during infection. RNA-preparation was evaluated and adopted for highest recovery of mycoplasmal mRNAs from in vitro HeLa cell infection assays. Following cRNA hybridization, the read out strategy of the hybridization results was optimized and confirmed by RT-PCR. A statistically robust infection assay with M. hominis strain FBG enabled the identification of regulated key effector molecules such as critical cytoadhesins (4 h post infection (pI)), invasins (48h pI) and proteins associated with establishing chronic infection of the host (336h pI). Of the 304 differentially regulated genes 130 (43%) encoded hypothetical proteins, including lipoproteins that seem to play a central role as virulence factors at each stage of infection: P75 as novel cytoadhesin candidate, which is also upregulated in the chronic infection, the MHO_2100-protein as postulated invasin and the MHO_730-protein as novel ecto-nuclease and domain of a novel ABC transporter, whose function in chronic infection has to be elucidated in the future.  Implementation of the M. hominis microarray strategy led to a comprehensive identification of to date unknown candidates for virulence-factors at relevant stages of host cell infection.

overall_design: A customized Mho microarray was designed with 13,708 non redundant Mho oligos in total, validated and used for hybridization of cRNA of total RNA from HeLa infection assays, which were prepared in duplicates after 1h, 4h, 48h and 336 h post infection with 50 MOI of M. hominis strain FBG. RNA of time point 1h of infection was used as a reference.

first: Birgit

last: Henrich

first: Freya

last: Kretzmer

first: René

last: Deenen

last: Köhrer


title: Differential gene expression in ATZ-globule-free and ATZ-globule-containing hepatocytes in PIZ mouse liver

status: Public on Aug 25 2017

city: Pittsburgh

first: George

middle: K

last: Michalopoulos

state: Pennsylvania

address: 411 SBST, 200 Lothrop Street

institute: University of Pittsburgh

summary:
Alpha-1-antitrypsin deficiency is a disease of the liver and lung where accumulation of misfolded ATZ protein forms large protein aggregates or globules that result in significant cellular stess.  From Birth to 2 months of age, virtually every hepatocyte has numerous globules of the mutant ATZ protien.  At 2 months of age small colonies of globule free hepatocytes arise and over time the liver becomes largely globule free. this analysis aims to identify differential gene expression profiles in the globule free vs the globule containing cells to idenitfy key factors and pathways regulating clearance of the mutant ATZ protien.
We used Laser Capture Microdisection to isolate RNA from ATZ-globule-free hepatocytes and ATZ-globule-containing hepatocytes and subjected them to microarray analysis to detail the differential global gene expression profiles.

overall_design: PIZ mice 3 months of age were sacrificed and their livers were mounted in OCT compound and fresh frozen in methylbutane.  Liver sections were placed on slides and counterstained with Cresyl Violet to visualize globules.  The slides were then subjected to laser capture micro-disection of globule free and globule containing areas.

first: Aaron

middle: W

last: Bell

first: Michael

last: Oertel

first: Jianhua

last: Luo


title: The Increased Toxicity of UV-Degraded Nitroguanidine and IMX-101 Exposures in Zebrafish Larvae: Evidence Implicating Oxidative Stress [6]

city: Vicksburg

first: Kurt

last: Gust

state: MS

address: 3909 Halls Ferry Rd.

department: Environmental Laboratory

institute: US Army ERDC

summary: Abstract —  Insensitive munitions (IMs) improve soldier safety by decreasing sympathetic detonation during training and use in theatre.  The environmental effects of IM constituents such as nitroguanidine (NQ) and IM mixture formulations such as IMX-101 remain largely unknown.  In the present study, we investigated the acute (96h) toxicity of NQ and IMX-101 to zebrafish larvae, both in the parent IMs and in IMs irradiated with environmentally-relevant levels of ultraviolet (UV) energy.  Zebrafish were exposed to control and ten concentrations of NQ ranging from 1 to 732 mg/L (measured concentrations) or seven concentrations of IMX-101 ranging from 2 to 122 mg/L (measured concentrations) of the parent material or material that had been UV-irradiated (UV-treated) at the equivalent of 24 hours of sunlight.  The UV-treatment increased the toxicity of NQ by 17-fold, indicated by a decreased LC50 from 1323 mg/L (parent compound) to 77.2 mg/L.  Similarly, UV-treatment increased the toxicity of IMX-101 by nearly two fold (LC50 decreased from 131.3 to 67.6 mg/L).  Molecular responses to parent and UV-treated IMs were assessed using global transcript expression assays.  Both gene set enrichment analysis (GSEA) and differential transcript expression analysis coupled with pathway and annotation cluster enrichment were conducted to provide functional interpretations of expression results and hypothetical modes of toxicity.  The parent NQ exposure caused significant enrichment of functions related to immune responses and proteasome-mediated protein metabolism occurring primarily at low, sublethal exposure levels (5.5 and 45.6 mg/L).  Enriched functions in the IMX-101 exposure were indicative of increased xenobiotic metabolism, oxidative stress mitigation, protein degradation, and anti-inflammatory responses, each of which displayed predominantly positive concentration-response relationships.  UV-treated NQ had a fundamentally different transcriptomic expression profile relative to parent NQ where positive concentration-response relationships were observed for genes involved in oxidative-stress mitigation pathways whereby we hypothesize that the increased toxicity of UV-treated NQ resulted from increased oxidative stress.  This hypothesis was supported by transcriptomic responses indicative of oxidative-stress responses involved in zebrafish development, especially neurological development of visual systems and the brain.  Transcriptomic profiles were similar between UV-treated versus parent IMX-101 exposures, however, more significant and diverse enrichment as well as greater magnitudes of differential expression for oxidative stress responses were observed in UV-treated IMX-101 exposures.  Further, transcriptomics indicated potential for cytokine signaling suppression providing potential connections between oxidative stress and anti-inflammatory responses.  Given these result, we hypothesize that the increased toxicity of UV-irradiated NQ and the IMX-101 mixture result from breakdown products with increased potential to elicit oxidative stress.

overall_design: Six separate microarray analyses were conducted within this study.  The 6 designs were conduced as follows:  1. NQ parent compound, 2. UV-Treated NQ, 3. Two-way design, NQ Parent x UV-Treated NQ, 4. IMX-101 parent material, 5. UV-treated IMX-101, 6. Two way design, IMX-101 parent x UV-Treated IMX-101.  This GEO entry represents analysis number 6. - Two way design, IMX-101 parent x UV-Treated IMX-101:  Zebrafish larvae were exposed to IMX-101 at 0 (control), 1.9, 3.8, 7.6, 15.2, 30.2, 85.2, and 121.9 mg/L (measured concentrations) as the parent or UV-irradiated IMX-101. The UV-treatment was performed by exposing the prepared stock solutions of IMX-101 in a photo-reactor for 4 h.   This duration of UV-treatment correlated to the UV-content of 48 h of sunlight in Vicksburg, Mississippi, USA at 450 lux (UV range only).  Briefly, a fan cooled Rayonet Reactor RPR-100 (Southern New England Ultraviolet Company, CT) equipped with a carousel and sixteen 14 W black lamps (SNE Ultraviolet Company k = 300 ± 50 nm) to create a photo-intensity of 0.05 mW cm-2nm-1 was used for all UV-degradation experiments.  These conditions were selected in accordance with EPA standard method 712-C-08-13 and represent the most active portion of light associated with photo-degradation.   All bioassays using the UV-treated IMs were initiated within 3 hours of completion of the UV-treatment, where standard exposure methods were conducted free of UV-light.  Exposure and control water was dechlorinated tap water (Vicksburg, MS USA municipal dechlorinated via activated carbon filtration) amended with artificial sea salts (Instant Ocean, Blacksburg, VA, USA) to a conductivity of 600 µS/cm.  Danio rerio larvae were exposed in static nonrenewal acute 96-h bioassays.  Exposure chambers were 300-ml high-form lipless beakers with a test solution volume of 250 ml.  Ten larval fish per beaker were exposed in the parent or UV-treated IMX-101 where all treatments included 4 exposure replicates.  Larval zebrafish were fed newly hatched Artemia nauplii two hours before the initiation of exposures and at the 48-h timepoint.  Surviving fish were enumerated daily and any fish found to be deceased were promptly removed from exposure chambers.

first: Jacob

last: Stanley

first: Mitchell

middle: S

last: Wilbanks

middle: L

last: Mayo

first: Pornsawan

last: Chappell

first: Shinita

last: Jordan

first: Lee

middle: C

last: Moores

first: Alan

middle: J

last: Kennedy

first: Natalie

last: Barker


title: The Increased Toxicity of UV-Degraded Nitroguanidine and IMX-101 Exposures in Zebrafish Larvae: Evidence Implicating Oxidative Stress [3]

overall_design: Six separate microarray analyses were conducted within this study.  The 6 designs were conduced as follows:  1. NQ parent compound, 2. UV-Treated NQ, 3. Two-way design, NQ Parent x UV-Treated NQ, 4. IMX-101 parent material, 5. UV-treated IMX-101, 6. Two way design, IMX-101 parent x UV-Treated IMX-101.  This GEO entry represents analysis number 3. - Two-way design, NQ Parent x UV-Treated NQ:  Zebrafish larvae were exposed to NQ at 0 (control), 1.4, 2.8, 5.5, 11.0, 22.7, 45.6, 90.4, 181, 348, and 732 mg/L (measured concentrations) as the parent or UV-irradiated NQ.  The UV-treatment was performed by exposing the prepared stock solutions of NQ in a photo-reactor for 4 h.   This duration of UV-treatment correlated to the UV-content of 48 h of sunlight in Vicksburg, Mississippi, USA at 450 lux (UV range only).  Briefly, a fan cooled Rayonet Reactor RPR-100 (Southern New England Ultraviolet Company, CT) equipped with a carousel and sixteen 14 W black lamps (SNE Ultraviolet Company k = 300 ± 50 nm) to create a photo-intensity of 0.05 mW cm-2nm-1 was used for all UV-degradation experiments.  These conditions were selected in accordance with EPA standard method 712-C-08-13 and represent the most active portion of light associated with photo-degradation.   All bioassays using the UV-treated IMs were initiated within 3 hours of completion of the UV-treatment, where standard exposure methods were conducted free of UV-light.  Exposure and control water was dechlorinated tap water (Vicksburg, MS USA municipal dechlorinated via activated carbon filtration) amended with artificial sea salts (Instant Ocean, Blacksburg, VA, USA) to a conductivity of 600 µS/cm.  Danio rerio larvae were exposed in static nonrenewal acute 96-h bioassays.  Exposure chambers were 300-ml high-form lipless beakers with a test solution volume of 250 ml.  Eight larval fish per beaker were exposed in the parent or UV-treated NQ treatments each including at least 4 exposure replicates and 6 control exposure replicates.  Larval zebrafish were fed newly hatched Artemia nauplii two hours before the initiation of exposures and at the 48-h timepoint.  Surviving fish were enumerated daily and any fish found to be deceased were promptly removed from exposure chambers.


title: Role of the MicroRNA Machinery in Fasting-Induced Gene Expression Changes and Longevity in C. elegans (mRNA)

city: Kyoto

first: Eisuke

last: Nishida

address: Kitashirakawa, Sakyo-ku

department: Department of Cell and Developmental Biology

country: Japan

institute: Graduate School of Biostudies, Kyoto University

summary:
Intermittent fasting (IF), a dietary restriction regimen, extends the lifespans of C. elegans and mammals by inducing gene expression changes. How fasting induces gene expression changes and longevity remains unclear. MicroRNAs (miRNAs) are small non-coding RNAs (approximately 22 nucleotides) that repress gene expression, and the expression of several miRNAs has been reported to be altered by fasting. In this study, we examined the role of the miRNA machinery in fasting-induced transcriptional changes and longevity in C. elegans. Our miRNA array analyses revealed that the expression levels of numerous miRNAs changed in adult worms after 48 hours of fasting. In addition to these changes, miRNA-mediated silencing complex (miRISC) components, including Argonaute proteins and GW182 proteins, and the miRNA-processing enzyme Drosha/DRSH-1, were up-regulated by fasting. Our lifespan measurements demonstrated that IF-induced longevity was suppressed by knockout or knockdown of miRISC components and was completely inhibited by drsh-1 ablation. Remarkably, drsh-1 ablation inhibited the fasting-induced changes in the expression of the target genes of DAF-16, the insulin/IGF-1 signaling effector. Fasting-induced transcriptome alterations were substantially and modestly suppressed in the drsh-1 null mutant and the null mutant of ain-1, a gene encoding GW182, respectively. These results indicate that components of the miRNA machinery, especially the miRNA-processing enzyme Drosha, play an important role in mediating IF-induced longevity via the regulation of fasting-induced gene expression changes.
To validate the involvement of drsh-1, ain-1 and daf-16 in fasting-induced gene expression changes, we compared the induction rates of all genes in the mutants with the induction rates of all genes in WT worms

overall_design: We synchronized wild type (WT), drsh-1, ain-1 and daf-16 mutants raised them under normal conditions. The 2 day adult animals were transferred to the new plate with (Fed) or without food (Fasting). After 2 days incubation, we collected the animals and extracted total RNA and subject them to microarray.

first: Akiko

last: Kogure

first: Masaharu

last: Uno

first: Takako

last: Ikeda


title: HIF Prolyl Hydroxylase Inhibition Protects Skeletal Muscle from Contraction-Induced Injury

status: Public on Aug 23 2017

city: Collegeville

first: Johannes

last: Freudenberg

address: 1250 S Collegeville Rd

department: Human Genetics

institute: GlaxoSmithKline

summary:
Skeletal muscle has an impressive ability to repair itself after a damaging insult and this response is essential to the process of muscle adaptation.  In conditions such as muscular dystrophy and the sarcopenia of old age, repair is compromised leading to fibrosis and fatty tissue accumulation.  Hypoxia-inducible factors (HIFs) are highly conserved regulators of gene transcription under conditions of low oxygen tension and HIF target genes such as EPO and VEGF have been associated with muscle protection and repair.  We sought to interrogate the importance of HIF activation to skeletal muscle repair through the use of prolyl hydroxylase inhibitors (PHI) that stabilize HIF and activate target gene transcription in a mouse eccentric exercise limb damage model.
We used microarrays to detail the global effects of prolyl hydroxylase inhibitors (PHI) in a mouse eccentric exercise limb damage model.

overall_design: Normal C57Bl6/NJ mice were housed individually and fed standard chow and water ad libitum. Right hind limbs were injured while left hind limbs were used as control.  Animals were treated either with PHI or vehicle.  Gastrocnemius samples were collected after 3 hrs, 6hrs, and 9hrs, respectively.

first: Andrew

last: Billin

first: Guizhen

last: Hinken

first: Deepak

last: Rajpal

first: Henning

middle: F

last: Kramer

last: Russell


title: Analysis of initial step of multiciliogenesis during the differentiation of adult airway progenitors

city: New York

first: Munemasa

last: Mori

state: New York

address: Black Building 801

department: Department of Medicine

institute: The Columbia Center for Human Development

summary: Multiciliated cells are crucial for fluid and ion transport in epithelia of a variety of organs and their impaired development and function are seen in human diseases affecting the brain, respiratory, and reproductive tracts. Multiciliogenesis requires activation of a specialized transcription program coupled to complex cytoplasmic events that lead to large-scale centriole amplification to generate multicilia. Yet, it remains unclear how these events are coordinated to initiate multiciliogenesis in epithelial progenitors. Here we identify an unsuspected mechanism orchestrated by the transcription factor E2f4 essential to integrate these processes. We show that after inducing a transcriptional program of centriole biogenesis, E2f4 translocates to the cytoplasm to become a core component of structures classically identified as fibrous granules (FG), acting as organizing centers for deuterosome assembly and centriole amplification. Remarkably, loss of cytoplasmic E2f4 prevents FG aggregation, deuterosome assembly and multicilia formation even when E2f4’s transcriptional function is preserved. Moreover, in E2f4-deficient cells multiciliogenesis is rescued only if both nuclear and cytoplasmic E2f4 activities are restored. Thus, E2f4 integrates previously unrelated nuclear and cytoplasmic events of the multiciliated cell program.

overall_design: E2f4f/f; R26 CreERT2 derived mTECs were cultured on transwells and treated with vehicle or 4-hydroxytamoxifen (Tm) from day -5 to day 0. Triplicate samples (each 2 wells/sample) of each treatment were incubated at 4 degree with RNA-later (Sigma) overnight at each time point (day 0, day 2, day 4). We used Affymetrix mouse GeneChip® Gene 1.0 ST arrays.

first: Paul

last: Danielian

first: John

last: Mahoney

first: Jining

last: Lu

first: Emily

last: Miller

first: Xueliang

last: Zhu

first: Jacqueline

last: Lees

first: Wellington

middle: V

last: Cardoso


title: Role of the MicroRNA Machinery in Fasting-Induced Gene Expression Changes and Longevity in C. elegans (miRNA)

first: Eisuke

last: Nishida

summary:
Intermittent fasting (IF), a dietary restriction regimen, extends the lifespans of C. elegans and mammals by inducing gene expression changes. How fasting induces gene expression changes and longevity remains unclear. MicroRNAs (miRNAs) are small non-coding RNAs (approximately 22 nucleotides) that repress gene expression, and the expression of several miRNAs has been reported to be altered by fasting. In this study, we examined the role of the miRNA machinery in fasting-induced transcriptional changes and longevity in C. elegans. Our miRNA array analyses revealed that the expression levels of numerous miRNAs changed in adult worms after 48 hours of fasting. In addition to these changes, miRNA-mediated silencing complex (miRISC) components, including Argonaute proteins and GW182 proteins, and the miRNA-processing enzyme Drosha/DRSH-1, were up-regulated by fasting. Our lifespan measurements demonstrated that IF-induced longevity was suppressed by knockout or knockdown of miRISC components and was completely inhibited by drsh-1 ablation. Remarkably, drsh-1 ablation inhibited the fasting-induced changes in the expression of the target genes of DAF-16, the insulin/IGF-1 signaling effector. Fasting-induced transcriptome alterations were substantially and modestly suppressed in the drsh-1 null mutant and the null mutant of ain-1, a gene encoding GW182, respectively. These results indicate that components of the miRNA machinery, especially the miRNA-processing enzyme Drosha, play an important role in mediating IF-induced longevity via the regulation of fasting-induced gene expression changes.
To examine the fasting-induced changes in miRNA expression in adult worms, we performed miRNA array experiments.

overall_design: We synchronized WT (N2) worms and raised under normal conditions. The 2 day adult animals were transferred to the new plate with (Fed) or without food (Fasting). We collected 2 day adult animals and the 4 day animals under fed or fasting conditions, then we extracted total RNA from them and subject them to microarray.

last: Kogure


title: Human dermal fibroblast subpopulations display distinct gene signatures related to cell behaviours and matrisome.

city: SAINT-VIANCE

first: VINCENT

last: BARRUCHE

state: If applicable (USA / Canada)

address: ZI de la Nau

department: R&D

country: France

institute: SILAB

summary: The upper papillary and deeper reticular dermis differ structurally and functionally. Although the papillary and reticular fibroblasts produced distinct extracellular matrix (ECM), the matrisome of these two fibroblast subpopulations has not been defined. Therefore we performed a transcriptomic analysis of papillary and reticular fibroblasts freshly isolated from skin of young donors around 20, at a time they produced high level of ECM. Bioinformatics analysis delivered 230 upregulated and 139 downregulated transcripts in papillary vs reticular fibroblasts. Expression of various selected genes was validated by q-PCR. The papillary fibroblasts were characterized by a higher expression of genes involved in the defense function, in the regulation of cell motility and proliferation and in the MAPK cascade whereas reticular fibroblasts showed higher expression of genes related to the development of connective tissues. Papillary fibroblasts were characterized by the expression of a high number of matrisome-associated genes whereas reticular fibroblasts gene signature mainly related to the core matrisome and ECM regulators. The regulation of selected genes was validated at protein level attesting to the robustness of the transcriptome analysis. Altogether, our data brought new insights into an ECM signature that is coherent with the organization and function of the papillary and reticular dermis.

overall_design:
The papillary fibroblasts (Fp) and reticular fibroblasts (Fr) sub-populations isolated from breast skin of young donors at P1 were used to identify their gene expression profiles. Three independ donnors were used to each sub population.
contributor: Institut de Génomique Fonctionnelle de Lyon, ENS de Lyon, CNRS, France and R&D department, SILAB, France


title: Epigenomic study of Post-traumatic Stress Disorder among OIF/OEF veterans

first: Aarti

last: Gautam

summary: Emerging knowledge suggests that post-traumatic stress disorder (PTSD) is causally associated with epigenetic changes although its molecular underpinnings are still largely elusive. We postulate that differentially methylated probes mined from peripheral whole blood could be candidates for potential PTSD diagnostic signatures. Working within the Systems Biology PTSD Biomarker Consortium (SBPBC), we compared 52 PTSD male veterans (CAPS > 40) and 52 age/ethnicity matched controls (CAPS < 20) and detected ~5,600 differentially methylated CpG islands (CpGI) annotated to ~2,800 differentially methylated genes (DMG). The majority (84.5%) of these DMGs was hypermethylated in PTSD veterans, and nearly 30% of those representing the focus group of the present study were differentially methylated in their promoter regions. These promoter-bound DMGs were significantly enriched in four major network-clusters comprising PTSD-associated complications, PTSD-relevant endocrine signaling, nervous system development and nervous system functions. The severity of some current PTSD symptoms was correlated with the increased risk of medical problems, which was captured in epigenetically perturbed networks associated with insulin resistance, circadian rhythm, innate immunity and telomere management. DMGs involved with addiction, fear sensitization and neurotransmissions were enriched in the networks of long term potentiation, depression and fear memory consolidation, and thereby potentially induced lasting impacts on brain. Finally, we curated a set of DMGs that co-enrich multiple PTSD-relevant networks, and we speculate that these genes are cooperative associated with PTSD risk. The present study emphasizes the need to validate these potential PTSD signatures by probing independent cross-sectional and prospective human cohorts.

overall_design: Working within the Systems Biology PTSD Biomarker Consortium (SBPBC), we compared 52 PTSD male veterans (CAPS > 40) and 49 age/ethnicity matched controls (CAPS < 20) and detected ~5,600 differentially methylated CpG islands (CpGI) annotated to ~2,800 differentially methylated genes (DMG).

first: Rasha

last: Hammamieh

first: Nabarun

last: Chakraborty

first: Seid

last: Muhie

first: Ruoting

last: Yang

first: Duncan

last: Donohue

first: Bernie

last: Daigle

first: Yuanyang

last: Zhang

first: Duna

last: Amara

first: Rachel

last: Yehuda

first: Linda

last: Petzold

first: Frank

last: Doyle

first: Owen

last: Wolkowitz

first: Sindy

last: Mellon

first: Charles

last: Marmar

first: Marti

last: Jett


title: Expression of cell cycle related-genes after early cerebral ischemia in a mouse thrombotic stroke model: a transcriptomic coexpression analysis.

status: Public on Aug 27 2017

city: Paris

first: Pierre

last: de la Grange

address: 29, rue du Faubourg Saint-Jacques

department: Paris Biotech Santé

institute: GenoSplice technology

overall_design: Cerebral ischemia was perfomed on Swiss male mice. Middle cerebral artery occlusion was performed by FeCl3 application on the intact dura mater. Mice were sacrified at 6 hours post-occlusion. Five independent experiments were performed.

first: Marie-Lise

last: Quillé


title: Role of the MicroRNA Machinery in Fasting-Induced Gene Expression Changes and Longevity in C. elegans

first: Eisuke

last: Nishida

summary: This SuperSeries is composed of the SubSeries listed below.

platform_organism:
Caenorhabditis elegans
synthetic construct

overall_design: Refer to individual Series


title: The Increased Toxicity of UV-Degraded Nitroguanidine and IMX-101 Exposures in Zebrafish Larvae: Evidence Implicating Oxidative Stress [2]

first: Kurt

last: Gust

overall_design: Six separate microarray analyses were conducted within this study.  The 6 designs were conduced as follows:  1. NQ parent compound, 2. UV-Treated NQ, 3. Two-way design, NQ Parent x UV-Treated NQ, 4. IMX-101 parent material, 5. UV-treated IMX-101, 6. Two way design, IMX-101 parent x UV-Treated IMX-101.  This GEO entry represents analysis number 2. - UV-Treated NQ:   Zebrafish larvae were exposed to UV-treated NQ where initial measured concentrations prior to UV-treatement included: 0 (control), 1.4, 2.8, 5.5, 11.0, 22.7, 45.6, 90.4, 181, 348, and 732 mg/L.   The UV-treatment was performed by exposing the prepared stock solutions of IMX-101 in a photo-reactor for 4 h.  This duration of UV-treatment correlated to the UV-content of 48 h of sunlight in Vicksburg, Mississippi, USA at 450 lux (UV range only).  Briefly, a fan cooled Rayonet Reactor RPR-100 (Southern New England Ultraviolet Company, CT) equipped with a carousel and sixteen 14 W black lamps (SNE Ultraviolet Company k = 300 ± 50 nm) to create a photo-intensity of 0.05 mW cm-2nm-1 was used for all UV-degradation experiments.  These conditions were selected in accordance with EPA standard method 712-C-08-13 and represent the most active portion of light associated with photo-degradation.   All bioassays using the UV-treated IMs were initiated within 3 hours of completion of the UV-treatment, where standard exposure methods were conducted free of UV-light.  Exposure and control water was dechlorinated tap water (Vicksburg, MS USA municipal dechlorinated via activated carbon filtration) amended with artificial sea salts (Instant Ocean, Blacksburg, VA, USA) to a conductivity of 600 µS/cm.  Danio rerio larvae were exposed in static nonrenewal acute 96-h bioassays.  Exposure chambers were 300-ml high-form lipless beakers with a test solution volume of 250 ml.  Eight larval fish per beaker were exposed in the parent or UV-treated NQ treatments each including at least 4 exposure replicates and 6 control replicates.  Larval zebrafish were fed newly hatched Artemia nauplii two hours before the initiation of exposures and at the 48-h timepoint.  Surviving fish were enumerated daily and any fish found to be deceased were promptly removed from exposure chambers.

first: Jacob

last: Stanley

first: Mitchell

last: Wilbanks

first: Michael

last: Mayo

first: Pornsawan

last: Chappell

first: Shinita

last: Jordan

first: Lee

last: Moores

first: Alan

last: Kennedy

first: Natalie

last: Barker


title: Exon level expression profile of MCF7 cells with p53β splice variant knocked out 4hr post 20gy irradiation

city: Durham

middle: Barry

last: Kastan

state: NORTH CAROLINA

address: 2424 Erwin Road

department: Duke Cancer Institute

institute: Duke University

summary:
In order to explore the funciton of p53β splice variant in DNA damage response, we utilized CRISPR-cas9 genome editing technique to specifically knock out this variant in MCF7 cells.
Microarray analysis is then performed to compare gene expression before and after 20gy irradiation in these cells.

overall_design: control and p53βCRISPR cells in triplicate are subjected to 20gy ionizing irradiation (IR) and 4 hrs post IR, cells are collected for RNA extraction and cDNA systhesis and microarray hybridization.

first: Jing

last: Chen

first: Dadong

last: Zhang

first: Kouros

last: Owzar

middle: B


title: The Increased Toxicity of UV-Degraded Nitroguanidine and IMX-101 Exposures in Zebrafish Larvae: Evidence Implicating Oxidative Stress [4]

overall_design: Six separate microarray analyses were conducted within this study.  The 6 designs were conduced as follows:  1. NQ parent compound, 2. UV-Treated NQ, 3. Two-way design, NQ Parent x UV-Treated NQ, 4. IMX-101 parent material, 5. UV-treated IMX-101, 6. Two way design, IMX-101 parent x UV-Treated IMX-101.  This GEO entry represents analysis number 4. - IMX-101 parent material:   Zebrafish larvae were exposed to IMX-101 at 0 (control),1.9, 3.8, 7.6, 15.2, 30.2, 85.2, and 121.9 mg/L (measured concentrations).    Exposure and control water was dechlorinated tap water (Vicksburg, MS USA municipal dechlorinated via activated carbon filtration) amended with artificial sea salts (Instant Ocean, Blacksburg, VA, USA) to a conductivity of 600 µS/cm.  Danio rerio larvae were exposed in static nonrenewal acute 96-h bioassays.  Exposure chambers were 300-ml high-form lipless beakers with a test solution volume of 250 ml.  Ten larval fish per beaker were exposed to IMX-101 where all treatments included 4 exposure replicates.  Larval zebrafish were fed newly hatched Artemia nauplii two hours before the initiation of exposures and at the 48-h timepoint.  Surviving fish were enumerated daily and any fish found to be deceased were promptly removed from exposure chambers.


title: The Increased Toxicity of UV-Degraded Nitroguanidine and IMX-101 Exposures in Zebrafish Larvae: Evidence Implicating Oxidative Stress [5]

overall_design: Six separate microarray analyses were conducted within this study.  The 6 designs were conduced as follows:  1. NQ parent compound, 2. UV-Treated NQ, 3. Two-way design, NQ Parent x UV-Treated NQ, 4. IMX-101 parent material, 5. UV-treated IMX-101, 6. Two way design, IMX-101 parent x UV-Treated IMX-101.  This GEO entry represents analysis number 5. - UV-treated IMX-101:   Zebrafish larvae were exposed to IMX-101 that had been irradiated with UV-light where initial measured concentrations of the exposures included: 0 (control),1.9, 3.8, 7.6, 15.2, 30.2, 85.2, and 121.9 mg/L (measured concentrations).  The UV-treatment was performed by exposing the prepared stock solutions of IMX-101 in a photo-reactor for 4 h.  This duration of UV-treatment correlated to the UV-content of 48 h of sunlight in Vicksburg, Mississippi, USA at 450 lux (UV range only).  Briefly, a fan cooled Rayonet Reactor RPR-100 (Southern New England Ultraviolet Company, CT) equipped with a carousel and sixteen 14 W black lamps (SNE Ultraviolet Company k = 300 ± 50 nm) to create a photo-intensity of 0.05 mW cm-2nm-1 was used for all UV-degradation experiments.  These conditions were selected in accordance with EPA standard method 712-C-08-13 and represent the most active portion of light associated with photo-degradation.   All bioassays using the UV-treated IMs were initiated within 3 hours of completion of the UV-treatment, where standard exposure methods were conducted free of UV-light.  Exposure and control water was dechlorinated tap water (Vicksburg, MS USA municipal dechlorinated via activated carbon filtration) amended with artificial sea salts (Instant Ocean, Blacksburg, VA, USA) to a conductivity of 600 µS/cm.  Danio rerio larvae were exposed in static nonrenewal acute 96-h bioassays.  Exposure chambers were 300-ml high-form lipless beakers with a test solution volume of 250 ml.  Ten larval fish per beaker were exposed to IMX-101 where all treatments included 4 exposure replicates.  Larval zebrafish were fed newly hatched Artemia nauplii two hours before the initiation of exposures and at the 48-h timepoint.  Surviving fish were enumerated daily and any fish found to be deceased were promptly removed from exposure chambers.


title: 1-MCP effect on the transcriptional profiling of  apple flesh (Malus x domestica Borkh, Gala variety) maintained in cold storage

city: Beaucouzé

first: Mathilde

last: ORSEL

address: 42, rue Georges Morel

institute: IRHS

summary: Apples (Malus x domestica Borkh, Gala variety) grown in commercial orchards were harvested at maturity and maintained 2 months in cold storage with or without 1-MCP treatment.

overall_design: 6 biological samples, including 2 biological replicates, were analysed in dye-swap. Samples are flesh from 5 fruits. Biological replicates are fruits from 2 different harvest year. Each sample was compared to the 2 others from the same harvest year in 6 dye-swap.

first: Tatiane

last: Storch

first: François

last: Laurens

first: Cesar-Luis

last: Girardi

last: Orsel

first: Jean-Pierre

last: Renou

first: Maryline

last: Bruneau


title: Differentiating Staphylococcus aureus from Escherichia coli mastitis: S. aureus triggers unbalanced immune-dampening and host cell invasion immediately after udder infection

city: Dummerstorf

first: Juliane

last: Guenther

address: Wilhelm-Stahl-Allee 2

institute: Leibniz-Institute for Farm Animal Biology (FBN)

summary: Outcome and resolution of an udder inflammation (mastitis) depends on the type of the invading pathogen. Gram-negative pathogens, such as Escherichia coli mostly trigger strong inflammation and full local activation of the immune defense eventually resulting in  pathogen elimination. Staphylococcus aureus and other Gram-positive pathogens elicit only weak immune reactions possibly allowing for pathogen persistence. Little is known about the very early molecular determinants of this pathogen-species specific immune response of the udder. We therefore infected healthy mid-lactating heifers with a high dose of defined E. coli1303 or S. aureus1027 pathogens, sampled udder tissues at 1, 2, and 3 h post infection and globally profiled the transcriptome of samples from the gland cistern. We expectedly found that the E. coli infection elicited a fast and strong immune response. Bioinformatics analyses suggested that pathogen recognizing receptors triggered the activation of the IkB/NF-kB signaling cascade inducing the expression of a wealth of inflammation related genes, but also many immune dampeners. S. aureus infection failed to elicit inflammation and activate IkB/NF-kB signaling. Instead, it triggered immune suppressive mechanisms which were, however not outweighed by strong induction of inflammatory genes. Moreover, it activated the wnt/b-catenin signaling cascade resulting in active suppression of NF-kB signaling and rearrangement of the actin-cytoskeleton through modulating expression of the Rho GTPases. These alterations facilitate invasion of pathogens into host cells. We validated experimentally that pathogenic S. aureus, but not E. coli may invade mammary epithelial cells (MEC). Microscopy revealed an altered structure of the actin-cytoskeleton of primary MEC having internalized live GFP-tagged S. aureus pathogens. Our study reveals for the first time the earliest host responses in the udder differentiating E. coli from S. aureus mastitis. The latter is characterized by eliciting immune suppression rather than inflammation and invasion of S. aureus into the epithelial cells of the host.

overall_design: 48 samples from 12 animals were analyzed. Three of four quarters per animal were sequentially inoculated with either 5 x E+06 CFU E. coli (n=6) or 5 x E+06CFU S. aureus (n=6) for 1, 2 and 3 h. One control quarter (front right quarter) remained untreated and was used to measure baseline expression values. Transcripts were defined as differentially expressed during infection if the fold change of the infected quarters relative to the unstimulated control quarter exceeded > 1.5 and the p-value of the univariate t-test paired according the individual animal was < 0.05.

last: Günther

first: Wolfram

last: Petzl

first: Isabel

last: Bauer

first: Siriluk

last: Ponsuksili

first: Holm

last: Zerbe

first: Hans-Joachim

last: Schuberth

first: Ronald

middle: M

last: Brunner

first: Hans-Martin

last: Seyfert


title: The Increased Toxicity of UV-Degraded Nitroguanidine and IMX-101 Exposures in Zebrafish Larvae: Evidence Implicating Oxidative Stress

first: Kurt

last: Gust


title: The Biomarkers of Lupus Disease Study (BOLD)

city: Cambridge

first: Andrew

last: Hill

state: MA

address: 300 Technology Square

department: Research Business Technology

institute: Pfizer

summary: Objectives: Molecular medicine raised expectations for strategically targeted biologics in systemic lupus erythematosus (SLE), but clinical trials have been disappointing and difficult to interpret. Most studies add investigational agents to various, often effective, standard of care (SoC) immunosuppressants used at baseline, with unknown treatment interactions. Eliminating polypharmacy in trials of active lupus patients remains controversial. The BOLD study tested immunosuppressant withdrawal as a novel approach to interpretable SLE trials.  Methods: In 41 patients with active, non-organ threatening SLE flare (Group A), temporary steroids were given while background immunosuppressants were withdrawn. Time to loss of disease suppression (“flare”) and safety were evaluated; SoC was immediately resumed when symptoms recurred. Immunologic impacts of SoC treatments were studied at baseline by multiplex assay, ELISA, and mRNA array in Group A plus 62 additional patients donating a single sample (Group B).  Results: Patients with lower or higher baseline disease had median times-to-flare of 71 or 45 days, respectively; 98% (40/41) flared by six months. All flares were treated and resolved within six weeks. No serious adverse events occurred from flare or infection. Type I interferon, TH17, and BLyS pathways tracked together. Baseline immunosuppressants had distinct impacts on TH17 and BLyS, depending on interferon signature.   Conclusion: Trials in active, non-organ-threatening SLE can safely withdraw background treatments if patients who flare are designated non-responders and returned to SoC. Immunologic effects of SoC vary between interferon-defined subsets. These findings provide a strategy for minimizing or optimizing treatment combinations in lupus trials and clinical care.

overall_design: This series of samples comprises mRNA from whole blood, assayed using Taqman Low Density Arrays (Applied Biosystems, Grand Island, NY USA).  Subjects included SLE patients (Group A and B) and Healthy Volunteers (Group C).

first: Joan

middle: T

last: Merrill

first: Frederick

last: Immermann

first: Maryann

last: Whitley

first: Tianhui

last: Zhou

first: Margot

last: O'Toole

first: Padmalatha

last: Reddy

first: Marek

last: Honczarenko

first: Aikaterini

last: Thanou

first: Joe

last: Rawdon

first: Joel

last: Guthridge

first: Judith

last: James

first: Sudhakar

last: Sridharan


title: Investigation of gene expression of Pseudomonas putida (NBAII RPF 9) under abiotic stress

city: Bangalore

first: Rajagopal

last: Rangeshwaran

state: Karnataka

address: Bellary Road

department: Molecular Entomology

country: India

institute: National Bureau of Agricutural Insect resource


title: Identifying microRNAs targeting WNT/β-catenin pathway in end-stage idiopathic pulmonary arterial hypertension

city: Baltimore

first: Li

last: Gao

address: 5501 Hopkins Bayview Circle, Rm. 3B.65B

department: Clinical Immunology

institute: Johns Hopkins University School of Medicine

summary: Whole genome microRNA microarray expression profiling was employed as a discovery platform to identify microRNAs dysregulated in end-stage idiopathic pulmonary arterial hypertension (IPAH) patients. Lung tissue from seven IPAH patients and eight failed donor controls were subjected to microarray screening.  Twenty-one miRNAs were identified dyeregulated in IPAH patients compared to controls. In miRNA real-time PCR validation, 22 IPAH patients and 22 control subjects were enrolled, including the 7 IPAH and 8 controls in microarray screening. Expression levels of five miRNAs (let-7a-5p, miR-199a-3p, miR-199b-5p, miR-26b-5p and miR-27b-3p) were upregulated in technical validation. Tissue miRNA levels had positive correlation with pulmonary vascular remodeling and hemodynamic changes in IPAH patients compared to controls.

overall_design: Seven IPAH patients and eight failed donor controls were enrolled. Lung tissue was obatined from lung transplantation.


title: The cross talk occurring between bifidobacteria in the mammalian’s gut microbiota [ATCC15697]

city: Parma

first: Marco

last: Ventura

address: Viale delle Scienze 11/A

department: Dept. Life Sciences

country: Italy

institute: University of Parma

summary: We describe the molecular cross talk established under in vivo conditions between a set of human gut bifidobacterial commensals. Eleven groups of five conventional female 8-wk-old BALB/c mice taking a standard polysaccharide-rich Chow diet were administered a single daily dose of 109 CFU of either B. bifidum PRL2010, B. breve 12L , B. adolescentis 22L , B. longum subsp. infantis ATCC15697, or bifidobacterial couples, i.e., PRL2010-12L, PRL2010-22L, PRL2010-ATCC15696, 12L-22L, 12L-ATCC15697, 22L-ATCC15697, or a combination of all bifidobacterial strains. The transcriptome of bifidobacterial strains under in vivo conditions was analyzed. The transcripts expressed in B. bifidum PRL2010, B. breve 12L, B. adolescentis 22L and B. longum subsp. infantis ATCC15697 were profiled using a custom-made PRL2010-12L-22L-ATCC15697 (multibifido)-array representing 100%, 99%, 96%, 99% of the identified genes of these organisms, respectively.The observed functional changes in the trascriptomes of bifidobacteria might be caused by the possible shifts of the mice cecum microbiota upon colonization with bifidobacteria. Thus, we assessed if the presence of B. bifidum PRL2010, B. breve 12L, B. adolescentis 22L and B. longum subsp. infantis ATCC15697 on mono-, bi- or multi-association in the cecum of mice affects the overall composition of the microbiota of this environment.

sample_organism: Bifidobacterium longum subsp. infantis ATCC 15697 = JCM 1222 = DSM 20088

overall_design: Microarray analysis was performed with an oligonucleotide array based on the B. adolescentis 22L, B. bifidum PRL2010, B. breve 12L and B. longum subsp. infantis ATCC15697 genomes for a total of 45220 oligonucleotide probes of 60 bp in length were designed on 7679 ORFs using eArray5.0 (Agilent Technologies). 5 Oligos were designed for each gene on a 4x44k Agilent Microarrays (Agilent Technologies, Santa Clara, CA, USA). Replicates were distributed on the chip at random, non-adjacent positions. A set of 152 negative control probes designed on phage and plant sequences were also included on the chip. Reverse transcription and amplification of 500 ng of total RNA was performed with ImProm-IITM Reverse Transcriptase (Promega, Madison, USA) according to the manufacturer’s instructions. Five µg of cDNA was then labeled with ULS Labeling kit with Cy5 or Cy3 (Kreatech, The Netherlands).   Labeled cDNA was hybridized using the Agilent Gene Transcription hybridization kit (part number 5188-5242) as described in the Agilent Two-Color Microarray-Based Gene Transcription Analysis v4.0 manual (G4140-90050). Following hybridization, microarrays were washed in accordance with Agilent's standard procedures.

first: Francesca

last: Turroni


title: The cross talk occurring between bifidobacteria in the mammalian’s gut microbiota [22L]

platform_organism: Bifidobacterium longum subsp. infantis ATCC 15697 = JCM 1222 = DSM 20088


title: The cross talk occurring between bifidobacteria in the mammalian’s gut microbiota [PRL]

summary: We describe the molecular cross talk established under in vivo conditions between a set of human gut bifidobacterial commensals. Eleven groups of five conventional female 8-wk-old BALB/c mice taking a standard polysaccharide-rich Chow diet were administered a single daily dose of 109 CFU of either B. bifidum PRL2010, B. breve 12L , B. adolescentis 22L , B. longum subsp. infantis ATCC15697, or bifidobacterial couples, i.e., PRL2010-12L, PRL2010-22L, PRL2010-ATCC15696, 12L-22L, 12L-ATCC15697, 22L-ATCC15697, or a combination of all bifidobacterial strains. The transcriptome of bifidobacterial strains under in vivo conditions was analyzed.  The transcripts expressed in B. bifidum PRL2010, B. breve 12L, B. adolescentis 22L and B. longum subsp. infantis ATCC15697 were profiled using a custom-made PRL2010-12L-22L-ATCC15697 (multibifido)-array representing 100%, 99%, 96%, 99% of the identified genes of these organisms, respectively.The observed functional changes in the trascriptomes of bifidobacteria might be caused by the possible shifts of the mice cecum microbiota upon colonization with bifidobacteria. Thus, we assessed if the presence of B. bifidum PRL2010, B. breve 12L, B. adolescentis 22L and B. longum subsp. infantis ATCC15697 on mono-, bi- or multi-association in the cecum of mice affects the overall composition of the microbiota of this environment.


title: The cross talk occurring between bifidobacteria in the mammalian's gut microbiota


title: Shelterin Mediates Genome Reorganization in Response to Replication Stress (Microarray CGH)

status: Public on Aug 22 2017

city: Bethesda

first: Shiv

last: Grewal

address: NCI bldg 37 Rm 6068 9000 Rockville Pike

department: LBMB

institute: NCI

type: Genome variation profiling by genome tiling array

summary: The dynamic nature of genome organization impacts critical nuclear functions including the regulation of gene expression, replication and DNA damage repair. Despite significant progress, the mechanisms responsible for reorganization of the genome in response to cellular stress, such as aberrant DNA replication, are poorly understood. Here we show that fission yeast cells carrying a mutation in the DNA-binding protein Sap1 show defects in DNA replication progression and genome stability, and display extensive changes in genome organization. Chromosomal regions such as subtelomeres that show defects in replication progression associate with the nuclear envelope in sap1 mutant cells. Moreover, high-resolution Hi-C analysis revealed prominent new interactions between telomeres and chromosomal arm regions containing replication origins proximal to binding sites for Taz1, a component of the Shelterin telomere protection complex. Strikingly, we find that Shelterin components promote interactions between Taz1-associated chromosomal arm regions and telomeres. These analyses reveal an unexpected role for Shelterin in genome reorganization in cells experiencing replication stress, which has important implications for understanding mechanisms governing replication and genome stability.

overall_design:
Microarray CGH analysis in fission yeast cell.
Copy number analysis: WT vs. sap1-1 revertant.

first: Takeshi

last: Mizuguchi

first: Nitika

last: Taneja

first: Emiko

last: Matsuda

first: Jon

last: Belton

first: Peter

last: FitzGerald

first: Job

last: Dekker

last: IGrewal


title: Effects of IDH1-R132H on mouse neural stem cells

first: Hai

last: Yan

state: NC

address: 199B-MSRB, Research Drive

department: Pathology

summary:
Mouse neural stem cells were generated from conditional knock-in mice.  Mutant IDH1 is conditionally expressed following expression of Cre-recombinase.  Cre-recombinase was incorporated in vitro
via adenoviral-Cre recombinase.  Addtionally, adenoviral-GFP was also used to control for effects of adenoviral infection.  D-2HG, the metabolic product of IDH1-R132H, was detected in cell lines post-cre transduction

overall_design: A total of three cell lines were used for this study.  Each of the three cell lines were transduced with either adenoviral-GFP (Control) or adenoviral-Cre recombinase (induces expression of mutant IDH).

first: Christopher

last: Pirozzi

first: Austin

last: Carpenter

first: Matthew

last: Waitkus

first: Catherine

middle: Y

last: Wang

first: Huishan

last: Zhu

first: Landon

middle: H

last: Hansen

first: Lee

last: Chen

first: Paula

last: Greer

first: Jie

last: Feng

first: Yu

first: Cheryl

last: Bock

first: Ping

last: Fan

first: Ivan

last: Spasojevic

first: Roger

last: McLendon

first: Darell

last: Bigner

first: Yiping

last: He


title: Shelterin Mediates Genome Reorganization in Response to Replication Stress (ChIP-chip)

first: Shiv

last: Grewal

type: Genome binding/occupancy profiling by genome tiling array

overall_design:
Occupancy profiling of GFP-Bqt3, Mcm6, Sap1, Taz1-GFP and Psc3-GFP proteins in fission yeast.
GFP-Bqt3: WT and sap1-1, Mcm6: WT and sap1-1, Sap1: WT and sap1-1, Taz1-GFP: WT, Psc3-GFP:WT and sap1-1.

first: Takeshi

last: Mizuguchi

first: Nitika

last: Taneja

first: Emiko

last: Matsuda

first: Jon

last: Belton

first: Peter

last: FitzGerald

first: Job

last: Dekker

last: IGrewal


title: Shelterin Mediates Genome Reorganization in Response to Replication Stress (BrdU IP)

overall_design:
BrdU profiling of replication activity in hydroxyurea-treated synchronous culture of fission yeast.
BrdU profiling: WT and sap1-1.


title: The histone variant H2A.Z promotes splicing of weak introns (array)

city: San Francisco

first: Kelly

last: Nissen

state: CA

address: 600 16th Street

department: Biochemistry and Biophysics

institute: UCSF

type:
Expression profiling by array
Other

summary: Multiple lines of evidence implicate chromatin in the regulation of pre-mRNA splicing. However, the influence of chromatin factors on co-transcriptional splice-site usage remains unclear. Here we investigated the function of the highly conserved histone variant H2A.Z in pre-mRNA splicing using the intron-rich model yeast, Schizosaccharomyces pombe. Using Epistatic Mini-Array Profiles (EMAPs) to survey the genetic interaction landscape of the Swr1 nucleosome remodeling complex, which deposits H2A.Z, we uncovered evidence for functional interactions with components of the spliceosome. In support of these genetic connections, splicing-specific microarrays show that H2A.Z and the Swr1 ATPase are required during temperature stress for the efficient splicing of a sub-set of introns. Notably, affected introns are enriched for H2A.Z occupancy, and more likely to contain non-consensus splice sites. To test the significance of the latter correlation, we mutated the splice sites in an affected intron to consensus and found this suppressed the requirement for H2A.Z in splicing of that intron. These data suggest that H2A.Z occupancy promotes co-transcriptional splicing of sub-optimal introns that may otherwise be discarded via proofreading ATPases. Consistent with this model, we show that over-expression of splicing ATPase Prp16 suppresses both the growth and splicing defects seen in the absence of H2A.Z.

overall_design: S. pombe splicing-specific microarrays (Agilent-027365) to compare multiple genotypes in Schizosaccharomyces pombe

first: Christina

last: Homer

first: Colm

last: Ryan

first: Michael

last: Shales

first: Nevan

last: Krogan

first: Kristin

last: Patrick

first: Christine

last: Guthrie


title: Genome-wide analysis of gene expression from murine right ventricle subjected to pressure and volume loading (PSPI)

city: Stanford

first: Joseph

last: Wu

state: Carlifornia

address: Stanford University School of Medicine

institute: Stanford University School of Medicine

summary: Performed a transcriptome analysis of control right ventricle and right ventricle subject to pressure and volume overload and demonstrated significant enrichment of genes involved in fibrosis with downregulation of metabolism in late stages of disease.

overall_design: Total RNA isolated from 4-5 control right ventricles vs. 4-5 pressure and volume overload right ventricles.

first: Sushma

last: Reddy


title: Genome-wide association study of abnormal Paneth cell phenotype in Japanese patients with Crohn's disease

city: Sendai

first: Yoichi

last: Kakuta

state: Miyagi

address: 1-1 Seiryo Aoba

institute: Tohoku University

summary: Morphological patterns of Paneth cells are a cellular biomarker in western Crohn’s disease (CD) patients. They integrate genetics and environmental factors, and are associated with outcomes. To broaden the applications of Paneth cell phenotype, identification of novel genetic determinants and clinical validation in other ethnic groups is critical.

overall_design: We performed a genome-wide linear regression analysis of percentages of normal Paneth cell  in Japanese patients with Crohn disease (n=98).


title: The cross talk occurring between bifidobacteria in the mammalian’s gut microbiota [12L]

first: Marco

last: Ventura

first: Francesca

last: Turroni


title: Effects of isoxazole (ISX) on long-term cultured human islets

city: Indianapolis

middle: A

last: Kalwat

state: IN

address: 1210 Waterway Blvd Suite 2000

department: Lilly Diabetes Center of Excellence

institute: Indiana Biosciences Research Institute

summary: Novel strategies are needed to modulate β-cell differentiation and function as potential β-cell replacement or restorative therapies for diabetes. We previously demonstrated that small molecules based on the isoxazole scaffold drive neuroendocrine phenotypes. The nature of the effects of isoxazole compounds on β cells was incompletely defined.  We find that isoxazole largely induced genes that support neuroendocrine and β-cell phenotypes, and suppressed a set of genes important for proliferation.  Isoxazole alters β-cell metabolites and protects glucose-responsive signaling pathways under lipotoxic conditions.  Finally, we show that isoxazole improves glycemia in a mouse model of β-cell regeneration.  Isoxazole is a prime candidate for altering cell fate in different contexts.

overall_design: We analyzed 3 pairs of long-term cultured human islet cells treated with either DMSO or ISX (20uM) for 7 days prior to RNA extraction using the Affymetrix GeneChip Human Transcriptome Array 2.0 platform. Data was analyzed in the Affymetrix Expression Console and Transcriptome Analysis Console v2.0. No technical replicates were performed.

first: Zhimin

last: Huang

first: Chonlarat

last: Wichaidit

first: Kathleen

last: McGlynn

first: Claudia

last: Savoia

first: Elhadji

last: Dioum

first: Jay

last: Schneider

first: Michele

middle: R

last: Hutchison

first: Melanie

last: Cobb


title: Exploring the effect and mechanism of roselle drink on the urinary tract infection in clinics and the lipopolysaccharide-induced renal inflammation in mice

status: Public on Aug 21 2017

city: Taichung

first: Chien-Yun

last: Hsiang

address: 91 Hsueh-Shih Road

country: Taiwan

institute: China Medical University

summary: Urinary tract infection (UTI) is a common problem in long-term care facilities. Roselle (Hibiscus sabdariffa Linn.) has been used in fold medicine as an anti-inflammatory agent. In this study, we surveyed the effect of roselle drink on the prevention of UTI in long-term care facilities and analyzed the anti-inflammatory potential of roselle on lipopolysaccharide (LPS)-induced renal inflammation. By survey questionnaires, we found that roselle drink was the most commonly used treatment for the routine care of residents. In addition, taking roselle drink in residents with urinary catheters reduced the incidence of UTI by 36%. Roselle suppressed LPS-induced nuclear factor-κB (NF-κB) activation in cells in a dose-dependent manner, and the maximal inhibition (73.75±4.11%) was observed at 100 μg/ml roselle drink. Roselle also suppressed LPS-induced interleukin-1β (IL-1β) production in mice. Gene expression profile of roselle in kidney showed that roselle downregulated the expression of inflammatory genes, and NF-κB was the main transcription factor involved in the regulation of roselle-regulated gene expression. Immunohistochemical staining further showed that roselle inhibited LPS-induced NF-κB activation and inflammatory cell infiltration in kidney. In conclusion, our findings suggested that roselle drink might be a potent benefit herbal supplement for UTI. Moreover, roselle ameliorated LPS-induced renal inflammation via regulating inflammatory gene expression and NF-κB pathway.

overall_design: Balb/c mice were orally administrated roselle drink for 7 consecutive days, challenged with LPS, and then sacrificed 4 hours later.


title: iPSCs from patients with NBS as a model uncovering disease mechanisms and a screening platform for anti-oxidants modifying genomic stability [fibroblasts]

status: Public on Aug 18 2017

city: Düsseldorf

first: Wasco

last: Wruck

address: Moorenstr. 5

institute: Universitätsklinikum Düsseldorf

summary: Nijmegen Breakage Syndrome (NBS) is a rare autosomal recessive genetic disorder, first described 1981 in Nijmegen, Holland. The characteristics of NBS include genomic instability (resulting in early onset of malignancies), premature aging, microcephaly and other growth retardations, immune deficiency, and impaired puberty and fertility in females. The consequence of these manifestations is a severe decrease in average life span, caused by cancer or infection of the respiratory and urinary tract.  We reprogrammed fibroblasts from NBS patients into induced pluripotent stem cells (iPSCS) to bypass premature senescence and to generate an unlimited cell source for modeling purposes.  We screened the influence of antioxidants on intracellular levels of ROS and DNA damage and found that EDHB was able to decrease DNA damage in the presence of high oxidative stress.  Furthermore, we found that NBS fibroblasts, but not NBS-iPSCs were more susceptible to the induction of DNA damage than their normal counterparts.  We performed global transcriptome analysis comparing NBS to normal fibroblasts and NBS-iPSCs to hESCs. There, we found, that TP53 was activated and cell cycle genes broadly down-regulated in NBS fibroblasts and up-regulation of glycolysis specifically in NBS-iPSCs.

overall_design: Total RNA obtained from fibroblasts of patients with Nijmegen-Breakage Syndrome reprogrammed to induced pluripotent stem cells

first: Barbara

last: Mlody


title: mRNA expression in Extensor Digitorum longus (EDL) muscle of adult F2 female offspring from F0-fathers fed a chow or high-fat diet

status: Public on Aug 15 2017

city: Stockholm

first: Thais

last: de Castro Barbosa

state: Stockholm

address: von Eulers väg 4a

department: Physiology and Pharmacology

institute: Karolinska Institutet

summary:
The purpose of this study was to investigate whether grandpaternal high-fat diet (HFD) transgenerationally remodels the transcriptome of skeletal muscle
EDL muscle mRNA expression profiling of F2-female offspring from F0-founders fed either a chow or a chronic HFD challenged. Adult females were challenge or not a high-fat diet for 12 weeks. EDL muscle was dissected at an endpoint experiment. Rats were subjected to 4 hours fasting prior to anesthesia with pentobarbital and tissue collection.

overall_design: F2-females Sprague-Dawley rats from F0 founders fed or not a high-fat diet were also subjeted to high-fat consumption for 12 weeks. At terminal experiment, EDL from 4-5 animals per group was collected, prepared and subjeted to the array analysis.

first: Romain

last: Barres

first: Juleen

last: Zierath

first: Anna

last: Krook

first: Petter

last: Alm


title: microRNA data in human metastatic versus non-metastatic colorectal cancer tissues

city: Shanghai

first: Yihua

last: Bei

address: 133 Nanchen Road

department: School of Life Science

institute: Shanghai University

summary: This study was to identify microRNAs responsible for colorectal cancer

overall_design: Total RNAs were extracted from paraffin-embedded human metastatic versus non-metastatic colorectal cancer tissues (n=3 per group), and then subjected to microRNA array analysis (Agilent Human miRNA 8×60K V18.0).

first: Junjie

last: Xiao

first: Qi


title: Effect of Itolizumab on Th17 polarized cells

status: Public on Aug 17 2017

first: Pradip

last: Nair

address: SEZ unit, Plot no 2 & 3, Phase IV B.I.A, Bommasandra-Jigani Link Road,

institute: Biocon Research Ltd

summary: In this study the Itolizumab treated group is compared to control treated group across days in polarizing conditions

overall_design: Agilent Custom Human Gene Expression 8X15k (AMADID: 16332) designed by Genotypic Technology Private Limited, Labeling kit: Agilent Quick-Amp labeling Kit (p/n5190-0442)

first: Usha

last: Bughani

first: Rasika

last: Venkataraman

first: Reshmi

first: Ravindra

last: BS

first: Anshu

last: Kuriakose

last: Kumar

first: Ramakrishnan

last: Melarkode

first: Enrique

last: Montero


title: LncRNA from metastatic clear cell renal cell carcinoma (ccRCC) compared with non-metastatic clear cell renal carcinoma

first: Jia-kuan

last: Li

address: Fengyang Road

department: Urology

institute: Changzheng Hospital

summary:
A total of 3 metastatic and 3 non-metastatic ccRCC tissues were collected from patients. These tissues were flash frozen in liquid nitrogen immediately after surgery and subsequently stored at -80℃. All the resected nodules or metastatic masses were identified as renal tumor by pathologic examination. No patients received anticancer treatments before surgery in this study.
We analyzed gene expression microarray data from our gene chip with 3 metastatic ccRCC tissues compared with 3 non-metastatic ccRCC tissues.

overall_design: 3 metastatic ccRCC tissues compared with 3 non-metastatic ccRCC tissues were selected for RNA extraction on Affymetrix microarrays. We sought to obtain different expression profiles for LncRNA, microRNA and mRNA between metastatic and non-metastatic ccRCC tissues. To that end, we identified differently expressed 320 lncRNAs, 27 microRNA and 560 mRNAs from the gene chip test series tissues.

first: Lin-hui

last: Wang


title: MicroRNA expression profiling of hepatocellular carcinoma cell line BEL-7402 treated with baicalein

city: Xi'an

first: Zongfang

state: Shaanxi

address: 157 W 5th Road

department: the second affiliated hospital

institute: Xi’ an Jiaotong University

summary: Baicalein, a purified flavonoid compound with defined chemical structure extracted from the dry roots of Scutellaria radix that is a broadly used herb in China, has been proved to possess significant anti-hepatoma activity by inhibiting cell proliferation, invasion, metastasis and inducing apoptosis, autophagy via several cancer-related signaling molecules. In recent years, emerging studies have demonstrated that  Chinese medicinal herbs can exert their anti-tumor effects through targeting miRNAs，such as curcumin, camptothecin, resveratrol. However, there is still no related report about the effects of baicalein on miRNA expression profile when it exerts its inhibition on hepatoma tumor growth. To investigate whether the antitumor effect of baicalein is related to its modulation of miRNA expression in hepatocellular carcinoma (HCC), we profiled the miRNA expression in HCC cell line Bel-7402 treated with baicalein (0, 40, 80μM) for 24 hours using miRNA microarray and detected the changes by comparing the miRNA expression profile of HCC cell line Bel-7402 treated with baicalein (40 and 80 μM) and its DMSO control (0  μM). These findings suggest that modulation of miRNA expression may be an important mechanism underlying the anti-hepatoma effects of baicalein and lay the groundwork for further investigations.

overall_design: In this study, we profiled the miRNA expression in hepatocellular carcinoma cell line Bel-7402 treated with baicalein (40 μM), baicalein (80 μM) and and DMSO control (0 μM) for 24 hours using miRNA microarray, and each of three groups have three biological replicates.

first: Beibei

last: Bie


title: Treating the placenta to prevent adverse effects of gestational hypoxia on fetal brain development [microRNA]

city: Cardiff

first: Hannah

last: Scott

address: Hadyn Ellis Building, Maindy Road

department: UK Dementia Research Institute

institute: Cardiff University

summary: Some neuropsychiatric disease, including schizophrenia, may originate during prenatal development, following periods of gestational hypoxia and placental oxidative stress. Here we investigated if gestational hypoxia promotes damaging secretions from the placenta that affect fetal development and whether a mitochondria-targeted antioxidant MitoQ might prevent this. Gestational hypoxia caused low birth-weight and changes in young adult offspring brain, mimicking those in human neuropsychiatric disease. Exposure of cultured neurons to fetal plasma or to secretions from the placenta or from model trophoblast barriers that had been exposed to altered oxygenation caused similar morphological changes. The secretions and plasma contained altered microRNAs whose targets were linked with changes in gene expression in the fetal brain and with human schizophrenia loci. Molecular and morphological changes in vivo and in vitro were prevented by a single dose of MitoQ bound to nanoparticles, which were shown to localise and prevent oxidative stress in the placenta but not in the fetus. We suggest the possibility of developing preventative treatments that target the placenta and not the fetus to reduce risk of psychiatric disease in later life.

overall_design: Total RNA extracted from rat foetal E20 plasma or culture medium conditioned by rat placenta was analysed for microRNA content. Samples were derived from 4 different in vivo conditions (maternal normoxia+saline injection = Control, maternal hypoxia+saline injection, maternal normoxia+MitoQ-NP injections, maternal hypoxia+MitoQ-NP injection). For placenta-conditioned media, samples underwent furher in vitro conditions (expsoure to 21% oxygen, exposure to 2% oxygen, expsosure to 8% oxygen). 4 biological replicates were measured per condition, except for maternal hypoxia+saline injection (foetal plasma), maternal normoxia+saline injection+2%oxygen (placenta-conditioned media) and all placenta-conditioned media samples exposed to 8% oxygen, for which 3 replicates were measured.

first: Tom

last: Phillips

first: David

last: Menassa

first: Ashleigh

last: Bignell

first: Aman

last: Sood

first: Jude

last: Morton

first: Takami

last: Akagi

first: Koki

last: Azuma

first: Mark

last: Rogers

first: Catherine

middle: E

last: Gilmore

first: Gareth

last: Inman

first: Simon

last: Grant

first: Yealin

last: Chung

first: Mais

last: Aljunaidy

first: Christy-Lynn

last: Cooke

first: Bruno

last: Steinkraus

first: Andrew

last: Pocklington

first: Angela

last: Logan

first: Gavin

middle: P

last: Collett

first: Helena

last: Kemp

first: Peter

last: Holmans

first: Michael

last: Murphy

first: Tudor

last: Fulga

last: Coney

first: Misturu

last: Akashi

first: Sandra

last: Davidge

first: Charles

last: Case


title: The effects of depleting mtDNA by using 2'-3' dideoxycytidine (ddC) for 30 days on chromosome stability of Holstein fibroblast cells.

city: Clayton

first: Justin

last: St. John

state: Vic

address: 27-31 Wright St

department: Centre for Genetic Diseases

country: Australia

institute: Hudson Institute of Medical Research

summary: We have used a Comparative Genomic Hybridization (CGH) microarray to determine the effects of mtDNA depletion using ddC on chromosome stability of Holstein cells that were used as the donor cells for embryo production by Somatic Cell Nuclear Transfer. The results showed that there is no duplications or deletions on chromosomes of mtDNA depleted cells when compared with that of non-depleted cells. In conclusion, depleting mtDNA by using ddC had no negative effect on chromosome stability in the donor cells.

overall_design: Depleted cells vs non-depleted cells, Biological replicates: 3

last: St John

first: Kanokwan

last: Srirattana


title: The estrogenic activity of triclosan

status: Public on Aug 13 2017

city: Daegue

first: Jieon

last: Lee

address: 333. Techno Jungang-daero Hyeongpung-myeon, Dalseong-gun

department: Chemical Engineering

country: South Korea

institute: POSTECH

summary: Triclosan is a commonly used antibacterial and antifungal agent. However, safety of TCS has been disputed. We performed gene expression profiling of TCS and estrogen-administrered rat uterus to compare genes and cellular processes to find the effects of TCS and estrogen.

overall_design: Gene expression in rat Uterus was measured after treating with Triclosan and estradiol. Two replicates were taken for each treatment.

first: Seong

last: Kwack

first: Daehee

last: Hwang


title: Exosomes derived from pancreatic cancer cells induce insulin resistance in C2C12 myotube cells through the PI3K/Akt/FoxO1 pathway

status: Public on Aug 11 2017

city: Hangzhou

first: Wang

last: Lantian

state: Zhejiang

address: 88 Jiefang Road

department: Department of Surgery

institute: The Second Affiliated Hospital, Zhejiang University School of Medicine

summary: Prospective epidemiological studies have consistently supported that pancreatic cancer associated new-onset diabetes mellitus (PC-DM) is probably an important clue for early diagnosis of pancreatic cancer (PC). However, the mechanism underlying remains fragmentary. In this study, two types of exosomes released by murine pancreatic cancer cells and murine pancreatic ductal epithelial cells were isolated，and their effects on skeletal muscle cells were invested. The results showed that PC-derived exosomes can readily enter C2C12 myotubes, and then induce lipidosis, glucose intake inhibition. We also found that PC-derived exosomes can inhibit Insulin and PI3K/Akt signaling, in which insulin-induced FoxO1 nuclear exclusion is preserved while Glut4 trafficking is impaired. In addition, further microarray and Kyoto encyclopedia of genes and genomes (KEGG) analysis prompted that exosomal microRNAs (miRNAs) probably play an critical role in this process, which also has been preliminarily demonstrated in vitro. Taking together, these results suggest that PC-derived exosomes induce insulin resistance (IR) of skeletal muscle cells through Insulin and PI3K/Akt/FoxO1 signaling pathway, and exosomal miRNAs are probably involved. The novel findings also support the theories of cancer “metabolic reprogramming” and “metabolic crosstalk”.

overall_design: two types of exosomes released by murine pancreatic cancer cells (KPC cells) and murine pancreatic ductal epithelial cells (MPDC) were isolated. MPDC-exosomes were used as a control.

first: Lantian

last: Wang

first: Bo

last: Zhang

first: Wen

last: Zheng


title: Identification of plasma microRNA as a novel diagnostic and prognostic biomarker in pancreatic cancer

city: Kamakura

first: Satoshi

last: Kondo

state: Kanagawa

address: Tebiro 6-10-1

department: New Projects Development Division

institute: Toray Industries,Inc.

summary: We identified plasma microRNA as a useful biomarker for Pancrearic cancer through miRNA-based approach comparing plasma levels between PCa patients and healthy volunteers.

overall_design: Through our strategy using genome-wide miRNA microarray analyses to detect depleted tumor suppressor miRNAs in the plasma of PCa patients, we identified a novel plasma miRNA, which has tumor suppressor functions and was significantly depleted in the plasma of PCa patients compared with healthy volunteers.

first: Shuhei

last: Komatsu

first: Taisuke

last: Imamura


title: The prognostic and predictive value of a three-microRNA-based classifier in NSCLC

city: Guangzhou

first: Heng-Ying

last: Pu

address: 651, Dongfeng East Road

institute: Cancer Centre, Sun Yat-sen University

summary: MicroRNA expression profiles were sucessfully contructed in 397 patients with NSCLC and 151 corresponding adjacent noncancerous tissues using a custom microarray containing probes for 1888 miRNAs and an outcome prediction of miRNA signature was successfully identified for predicting prognosis in NSCLC.

overall_design: In the study presented here, a consecutively operated, well-defined cohort of 397 NSCLC cases, followed up more than three years, was used to acquire miRNA expression profiles of 1888 miRNAs and identify a miRNA signature, leading to the successfully for predicting prognosis in NSCLC.

first: Hengying

first: Huiyun


title: Expression data from MOLM-14 human acute myeloid leukemia cell line after mTORC1 inhibition by rapamycin

status: Public on Aug 14 2017

city: Paris

first: Franck

last: Letourneur

address: 22 rue mechain

institute: INSERM

summary:
The objective of the sudy is to evalute the role of mTORC1 signalling in the regulation of the metabolism of MOLM-14 cells.
We used microarrays to investigate gene expression in MOLM-14 cells after down-regulation of mTORC1 signalling by rapamycin.

overall_design: MOLM-14 cells (biological replicates) were treated or not by rapamycin 10nM (24 hours)

first: Laury

last: Poulain

first: Pierre

last: Sujobert

first: Nicolas

last: Chapuis

first: Jérôme

last: Tamburini


title: Effect of Metformin and AICAR treatments in the prostate cancer cell line LNCaP

city: Valbonne - Sophia-Antipolis

first: Kevin

last: Lebrigand

address: 660 route des lucioles

institute: IPMC/CNRS

summary: Transcriptional profiling of human prostate cancer cell line LNCaP treated with Metformin or AICAR compared to control non-stimulated LNCaP.

overall_design: Total RNA of human prostate cancer cell line (LNCaP) were treated with Metformin (5mM) during 24h or AICAR (5mM) during 24h and compared to control untreated cells. Two independent cell culture experiments for each treatment condition were performed for microarray analysis (marked rep1 or rep2). Each experiment was repeated with a switch in fluorescent Cy3/Cy5 labels to account for dye effects to produce four data points per hybridization spot. Total of 12 samples.

first: F

last: Bost

first: N

last: Nottet

first: I

last: Ben-Sahra

first: B

last: Mari

first: K

first: P

last: Barbry


title: Modulation of reversibility by DNA Methyltransferases during hepatogenic differentiation in Mesenchymal Stromal Cells [protein expression]

city: Taipei

first: Chien-Wei

last: Lee

address: No.155, Sec.2, Linong Street

institute: National Yang-Ming University

summary: Mesenchymal stromal cells (MSCs) hold great promise in the field of liver regenerative medicine. However, the mechanisms and reversibility of hepatogenic differentiation in MSCs are poorly understood. Here, we demonstrate that hepatogenic differentiation of MSCs is a reversible process and is modulated by the transforming growth factor beta 1- DNA methyltransferases (TGF-β1-Dnmts) axis. Dnmt1 and Dnmt3a differentially regulate hepatogenic differentiation and de-differentiation in response to the alternation of TGF-β1 concentration. Knockdown of Dnmt1 accelerates the hepatogenic differentiation in MSCs-derived hepatocyte-like cells (dHeps) whereas Knockdown of Dnmt3a represses hepatogenic differentiation. Conclusions: Our finding first demonstrates that epigenetic regulation by Dnmts in response to stimulation from the surrounding microenvironment controls the reversibility of hepatogenic differentiation in MSCs. Manipulation of Dnmts provides a rapid and efficient differentiation protocol to generate functional dHeps from MSCs that may provide clinical potential for regenerative medicine.

overall_design: Protein expression analysis of hepatogenic differentiation: MSC, HD 28, dHD 28, and Hepatocytes (Heps) sample and MSC-like cells (MLCs)

first: Wei-Chih

last: Huang

first: Hsien-Da

first: Yi-Hsiang

first: Jennifer

last: Ho

first: Muh-Hwa

last: Yang

first: Vincent

first: Oscar

middle: K


title: miRNA expression of tube forming HUVECs

city: Osaka

first: Hiroyuki

last: Mizuguchi

address: Suita Yamadaoka 1-6

institute: Osaka university

summary: To identify the miRNAs specifically upregulated during tube formation of primary endothelial cells , HUVECs were cultured in culture plates with or without matrigel-coating and the miRNAs from them were compared.

overall_design: HUVECs Plate culture reps 1-3 are control and compared to HUVECs Matrigel culture reps 1-3.

first: Emi

last: Suzuki-Kouyama


title: Expression data from Staphylococcus aureus MR23 treated with norgestimate

status: Public on Aug 04 2017

city: Tokyo

first: Yutaka

last: Yoshii

address: 3-25-8 Nishi-Shimbashi, Minato-ku

department: Department of Bacteriology

institute: The Jikei University School of Medicine

summary:
We found that norgestimate effectively inhibits staphylococcal biofilm formation.
We used microarrays to clarify gene expressions of S. aureus MR23 culture treated with norgestimate.

overall_design: S. aureus MR23 was grown at 37C for 12 h in the presence or absence of norgestimate for RNA extraction and hybridization on Affymetrix microarrays.

first: Ken-ichi

last: Okuda


title: MicroRNA profiling in gingival crevicular fluid of periodontitis

first: Akira

last: Saito

address: 7-31-, Hongo, Bunkyo

institute: Tokyo University

summary:
We profiled miRNAs in gingival crevicular fluid (GCF) by a PCR-based method that yielded quantitative measures of more than 600 miRNAs.
We found that miRNA profiles in GCF of periodontitis patients are distinct from those of healthy controls.

overall_design: Comprehensive miRNA profiling of GCF derived from ten subjects (5 healthy and 5 periodontitis).

first: Hisami

last: Iwamoto

first: Ysauo

last: Takeuchi

first: Keiko

last: Akazawa

first: Akinori

last: Nakazato

first: Rina

last: Komazaki

first: Anri

last: Ohtsu

first: Yujin

last: Ohsugi

first: Naoki

middle: G

last: Sasaki

first: Takae

last: Shimoda

first: Masafumi

last: Horie

first: Kenichiro

last: Ejiri

last: Aoki

first: Sayaka

last: Katagiri

first: Shogo

last: Maekawa

first: Shinta

last: Suzuki

first: Sophannary

last: Kong

first: Tsuneto

last: Yamauchi

first: Yoko

last: Yamaguchi

first: Yuichi

last: Izumi

first: Mitsuhiro

last: Ohshima


title: Interleukin-6 mediated signaling in adrenal medullary chromaffin cells

status: Public on Aug 01 2017

city: Bethesda

first: Babru

middle: Bahan

last: Samal

state: MD

address: 9000 Rockville Pike

department: SMN

institute: NIMH/NIH

summary: Pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNFalpha) and interleukin-1beta/alpha (IL1beta/alpha) modulate catecholamine secretion, and long-term gene regulation, in chromaffin cells of the adrenal medulla. Interleukin-6 (IL6), also released during inflammation, affects transcriptional responses in primary chromaffin cells, and may coordinate immune and autonomic adrenomedullary responses via an autocrine mechanism, as TNFalpha itself strongly induces IL6 expression in chromaffin cells, which in turn express receptors responsive to IL6. We have examined the signaling mechanisms employed by IL6 to affect tyrosine hydroxylase (TH) enzymatic activation, and adrenomedullary gene transcription, in cultured bovine chromaffin cells. IL6 caused acute tyrosine/threonine phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), and serine phosphorylation of signal transducer and activator of transcription 3 (STAT3), as do several other first messengers acting on the chromaffin cell, including histamine, nicotine and angiotensin II. IL6 uniquely activated tyrosine phosphorylation of STAT3. Consistent with a short-term ERK1/2 activation, IL6 treatment caused prompt regulation of TH phosphorylation, and up-regulation of genes encoding secreted proteins of the adrenal medulla including galanin, vasoactive intestinal peptide (VIP), gastrin releasing peptide (GRP) and parathyroid hormone-like hormone (PTHLH). We further examined the effects of IL6 treatment on the entire bovine chromaffin cell transcriptome. Of 90 genes up-regulated by IL6, only 16 of which are known targets of IL6 in the immune system. The remaining genes likely represent a combination of novel IL6/STAT3 targets, targets of ERK1/2 shared by other first messengers, and, potentially, IL6-dependent genes activated in a secondary cascade via transcription mediated by IL6-induced transcription factors, such as HIF-1alpha. Notably, genes induced by IL6 represent a cohort with a profile that includes both neuroendocrine-specific genes, including several that are activated by G-protein couple receptor (GPCR) signaling pathways initiated by histamine and pituitary adenylate cyclase-activating polypeptide (PACAP), and some transcripts also activated by cytokines including interferon-alpha (INFalpha and TNFalpha. These results suggest an integrative role for IL6 in overall fine-tuning of the chromaffin cell response to a wide range of physiological and paraphysiological stressors, particularly when immune and endocrine stimuli converge in the adrenal medulla.

overall_design: Bovine chromaffin cells (BCC) were incubated with no treatment (n=3), IL6 (n=3), human INFalpha (n=3), or histamine (n=3). Triplicate samples were technical repeats.


title: Dysregulation of a miR-23b/27b-p53 axis impairs muscle differentiation in humans with type 2 diabetes

status: Public on Aug 12 2017

city: Copenhagen

first: Søren

last: Nielsen

address: Blegdamsvej 9

department: Section 7641

country: Denmark

institute: Rigshospitalet

summary: Impaired skeletal muscle function is a central feature in the pathophysiology of type 2 diabetes (T2DM). The disease phenotype could be due to immature muscle cell development, which in turn may occur as the result of disturbed microRNA-mediated regulation of muscle differentiation in T2DM. To address this hypothesis, we assessed global miRNA expression during in vitro differentiation of muscle stem cells derived from T2DM patients and healthy controls. We identified the mir-23b/27b cluster to be downregulated in the patients, and further demonstrated that a pro-myogenic effect of these miRNAs occurs through targeting of several genes in the p53 pathway, which was concordantly dysregulated in the muscle cells derived from humans with T2DM. In conclusion, we have identified a novel myogenesis-controlling pathway, the miR-23b/27b-p53 axis, potentially contributing to the sustained multiple muscular dysfunctions in T2DM in humans.

platform_organism:
Homo sapiens
Human alphaherpesvirus 1
Human alphaherpesvirus 2
Macacine alphaherpesvirus 1
Human betaherpesvirus 5
human gammaherpesvirus 4
Saimiriine gammaherpesvirus 2
JC polyomavirus
Human immunodeficiency virus 1
Human betaherpesvirus 6B
Human gammaherpesvirus 8
Merkel cell polyomavirus
Betapolyomavirus hominis
Betapolyomavirus macacae

overall_design: Muscle stem cells were isolated from healthy donors (n=8) and donors with type 2 diabetes (n=8). RNA was harvested from proliferating myoblasts, during early myocyte differentiation and late myocyte differentiation.

first: Tora

middle: I

last: Henriksen

first: Peter

last: Davidsen

first: Maria

last: Pedersen

first: Heidi

middle: S

last: Schultz

first: Ninna

last: S Hansen

first: Therese

last: Larsen

first: Allan

last: Vaag

first: Bente

first: Camilla

last: Scheele


title: Expression data from early stage CRC patients' tumors [NanoString-Test]

status: Public on Aug 02 2017

city: Singapore

first: Steve

last: Rozen

address: 8 College Road

country: Singapore

institute: Duke-NUS

summary: This study was conducted in order to identify biomarkers for a prognostic gene expression signature for metastases in early stage CRC.

overall_design: Expression profiles from 94 metastasis negative and 37 metastasis positive early stage CRC tumors were obtained.

first: Yee-Syuen

last: Low

first: Christopher

last: Blöcker

first: Iain

last: Tan

first: Steven

first: Peh-Yean

last: Cheah