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Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Stress-Responsive And Metabolic Gene Regulation Are Altered In Low S-Adenosylmethionine, Wei Ding, Daniel P. Higgins, Dilip K. Yadav, Adwait A. Godbole, Read Pukkila-Worley, Amy K. Walker Nov 2018

Stress-Responsive And Metabolic Gene Regulation Are Altered In Low S-Adenosylmethionine, Wei Ding, Daniel P. Higgins, Dilip K. Yadav, Adwait A. Godbole, Read Pukkila-Worley, Amy K. Walker

Open Access Articles

S-adenosylmethionine (SAM) is a donor which provides the methyl groups for histone or nucleic acid modification and phosphatidylcholine production. SAM is hypothesized to link metabolism and chromatin modification, however, its role in acute gene regulation is poorly understood. We recently found that Caenorhabditis elegans with reduced SAM had deficiencies in H3K4 trimethylation (H3K4me3) at pathogen-response genes, decreasing their expression and limiting pathogen resistance. We hypothesized that SAM may be generally required for stress-responsive transcription. Here, using genetic assays, we show that transcriptional responses to bacterial or xenotoxic stress fail in C. elegans with low SAM, but that expression of heat ...


Biology Of Exosomes And Their Microrna Cargos In Human And Bovine Milk, Amy Lynn Leiferman Jun 2018

Biology Of Exosomes And Their Microrna Cargos In Human And Bovine Milk, Amy Lynn Leiferman

Public Access Theses and Dissertations from the College of Education and Human Sciences

Exosomes are small, cargo-containing vesicles secreted by cells to facilitate intercellular communication. Of exosome cargos, microRNAs are especially interesting because of their involvement in gene regulation. Recently, our lab has shown that exosomes and their microRNA cargo are absorbed through the diet and elicit effects exogenously. Human and animal milk contain exosomes, which may have implications in infant and adult nutrition. There is evidence that bovine milk exosomes enhance growth of murine C2C12 myotube cell cultures, but whether this translates to muscle in vivo is unknown. The USDA National Nutrient Database for Standard Reference is lacking up-to-date information about human ...


The Cjun Nh2-Terminal Kinase (Jnk) Pathway Contributes To Mouse Mammary Gland Remodeling During Involution, Nomeda A. Girnius, Yvonne J. K. Edwards, Roger J. Davis Mar 2018

The Cjun Nh2-Terminal Kinase (Jnk) Pathway Contributes To Mouse Mammary Gland Remodeling During Involution, Nomeda A. Girnius, Yvonne J. K. Edwards, Roger J. Davis

University of Massachusetts Medical School Faculty Publications

Involution returns the lactating mammary gland to a quiescent state after weaning. The mechanism of involution involves collapse of the mammary epithelial cell compartment. To test whether the cJUN NH2-terminal kinase (JNK) signal transduction pathway contributes to involution, we established mice with JNK deficiency in the mammary epithelium. We found that JNK is required for efficient involution. JNK deficiency did not alter the STAT3/5 or SMAD2/3 signaling pathways that have been previously implicated in this process. Nevertheless, JNK promotes the expression of genes that drive involution, including matrix metalloproteases, cathepsins, and BH3-only proteins. These data demonstrate that JNK ...


Mitochondrial Retrograde Signaling Connects Respiratory Capacity To Thermogenic Gene Expression, Minwoo Nam, Thomas E. Akie, Masato Sanosaka, Siobhan M. Craige, Shashi Kant, John F. Keaney Jr., Marcus P. Cooper May 2017

Mitochondrial Retrograde Signaling Connects Respiratory Capacity To Thermogenic Gene Expression, Minwoo Nam, Thomas E. Akie, Masato Sanosaka, Siobhan M. Craige, Shashi Kant, John F. Keaney Jr., Marcus P. Cooper

UMass Metabolic Network Publications

Mitochondrial respiration plays a crucial role in determining the metabolic state of brown adipose tissue (BAT), due to its direct roles in thermogenesis, as well as through additional mechanisms. Here, we show that respiration-dependent retrograde signaling from mitochondria to nucleus contributes to genetic and metabolic reprogramming of BAT. In mouse BAT, ablation of LRPPRC (LRP130), a potent regulator of mitochondrial transcription and respiratory capacity, triggers down-regulation of thermogenic genes, promoting a storage phenotype in BAT. This retrograde regulation functions by inhibiting the recruitment of PPARgamma to the regulatory elements of thermogenic genes. Reducing cytosolic Ca2+ reverses the attenuation of thermogenic ...


Divergent Responses Of Larval And Juvenile Blue Mussels To Low Salinity Exposure, Melissa A. May May 2017

Divergent Responses Of Larval And Juvenile Blue Mussels To Low Salinity Exposure, Melissa A. May

Electronic Theses and Dissertations

In this study, we compared the osmotic stress response of larval and juvenile blue mussels (Mytilus edulis) at the transcriptomic, metabolomic, and whole organism levels. Blue mussels inhabit coastal areas, where they face climate-induced reductions in nearshore salinity. Despite their ecological and economic importance, scientists do not fully understand the underlying transcriptomic and cellular mechanisms of the osmotic stress response in blue mussels or how the ability to respond to stress changes throughout development. Blue mussels spend the first weeks of life developing through several larval stages in the plankton. These early life history stages are more vulnerable to environmental ...


Hyper- And Hypo- Nutrition Studies Of The Hepatic Transcriptome And Epigenome Suggest That Pparα Regulates Anaerobic Glycolysis, Anthony R. Soltis, Shmulik Motola, Santiago Vernia, Christopher W. Ng, Norman J. Kennedy, Simona Dalin, Bryan J. Matthews, Roger J. Davis, Ernest Fraenkel Mar 2017

Hyper- And Hypo- Nutrition Studies Of The Hepatic Transcriptome And Epigenome Suggest That Pparα Regulates Anaerobic Glycolysis, Anthony R. Soltis, Shmulik Motola, Santiago Vernia, Christopher W. Ng, Norman J. Kennedy, Simona Dalin, Bryan J. Matthews, Roger J. Davis, Ernest Fraenkel

Davis Lab Publications

Diet plays a crucial role in shaping human health and disease. Diets promoting obesity and insulin resistance can lead to severe metabolic diseases, while calorie-restricted (CR) diets can improve health and extend lifespan. In this work, we fed mice either a chow diet (CD), a 16 week high-fat diet (HFD), or a CR diet to compare and contrast the effects of these diets on mouse liver biology. We collected transcriptomic and epigenomic datasets from these mice using RNA-Seq and DNase-Seq. We found that both CR and HFD induce extensive transcriptional changes, in some cases altering the same genes in the ...


No Current Evidence For Widespread Dosage Compensation In S. Cerevisiae, Eduardo M. Torres, Michael Springer, Angelika Amon Mar 2016

No Current Evidence For Widespread Dosage Compensation In S. Cerevisiae, Eduardo M. Torres, Michael Springer, Angelika Amon

UMass Metabolic Network Publications

Previous studies of laboratory strains of budding yeast had shown that when gene copy number is altered experimentally, RNA levels generally scale accordingly. This is true when the copy number of individual genes or entire chromosomes is altered. In a recent study, Hose et al. (2015) reported that this tight correlation between gene copy number and RNA levels is not observed in recently isolated wild Saccharomyces cerevisiae variants. To understand the origins of this proposed difference in gene expression regulation between natural variants and laboratory strains of S. cerevisiae, we evaluated the karyotype and gene expression studies performed by Hose ...


Molecular Mechanisms Underlying The Contralateral Repeated Bout Effect (Crbe) In Human Skeletal Muscle, Ling Xin Jan 2015

Molecular Mechanisms Underlying The Contralateral Repeated Bout Effect (Crbe) In Human Skeletal Muscle, Ling Xin

Doctoral Dissertations

Eccentric (muscle lengthening) exercise induces temporary muscle damage that can lead to long-term muscle adaptation, a process known as the repeated bout effect where subsequent exercise results in less damage. The existence of a contralateral repeated bout effect (CRBE) has been controversial. The primary goals of this study were to: 1) validate the existence of the CRBE; and 2) define the underlying molecular mechanisms.

Thirty-six young men performed 100 maximal eccentric actions of the knee extensors using one leg (bout 1) and repeated the exercise with the contralateral leg five weeks later (bout 2). Vastus lateralis muscle biopsies were ...