Maternal Western-style diet has a persistent effect on offspring gene expression in skeletal muscle of Japanese macaques.

The cellular mechanisms underlying a greater risk of cardiometabolic disease in adult offspring exposed to maternal obesity are not known. Our prior work found reduced skeletal muscle mitochondrial metabolism and insulin sensitivity in offspring exposed to maternal (m) Western-style diet (WD), even when weaned onto a control diet (CD) in Japanese macaques. Here, we performed multiple comparisons of differentially expressed (DE) genes in skeletal muscle from lean juvenile offspring to test hypotheses specific to (1) the lasting effects of maternal diet composition and/or maternal adiposity on gene expression and (2) the transcriptional response to a chronic postweaning (pw)WD with and without prior exposure to mWD.

Maternal Western-style diet programs skeletal muscle gene expression in lean adolescent Japanese macaque offspring.

Early-life exposure to maternal obesity or a maternal calorically dense Western-style diet (WSD) is strongly associated with a greater risk of metabolic diseases in offspring, most notably insulin resistance and metabolic dysfunction-associated steatotic liver disease (MASLD). Prior studies in our well-characterized Japanese macaque model demonstrated that offspring of dams fed a WSD, even when weaned onto a control (CTR) diet, had reductions in skeletal muscle mitochondrial metabolism and increased skeletal muscle insulin resistance compared to offspring of dams on CTR diet. In the current study, we employed a nested design to test for differences in gene expression in skeletal muscle from lean 3-year-old adolescent offspring from dams fed a maternal WSD in both the presence and absence of maternal obesity or lean dams fed a CTR diet.

Essential amino acid supplementation alters the p53 transcriptional response and cytokine gene expression following total knee arthroplasty.

Reducing muscle atrophy following orthopedic surgery is critical during the postoperative period. Our previous work in patients who underwent total knee arthroplasty (TKA) showed that the vast majority of atrophy occurs within 2 wk following surgery and that essential amino acid (EAA) supplementation attenuates this atrophy. We used RNA-sequencing (RNA-seq) to identify genes associated with atrophy after TKA with and without EAAs.

Evidence of a broad histamine footprint on the human exercise transcriptome.

Key Points: Histamine is a primordial signalling molecule, capable of activating cells in an autocrine or paracrine fashion via specific cell surface receptors, in a variety of pathways that probably predate its more recent role in innate and adaptive immunity. Although histamine is normally associated with pathological conditions or allergic and anaphylactic reactions, it may contribute beneficially to the normal changes that occur within skeletal muscle during the recovery from exercise. We show that the human response to exercise includes an altered expression of thousands of protein-coding genes, and much of this response appears to be driven by histamine.

Transcriptional profiling and muscle cross-section analysis reveal signs of ischemia reperfusion injury following total knee arthroplasty with tourniquet.

Total knee arthroplasty (TKA) is the most common and cost-effective treatment for older adults with long-standing osteoarthritis. Projections indicate that nearly 3.5 million older adults will undergo this procedure annually by the year 2030.

Rapid mapping and identification of mutations in Caenorhabditis elegans by restriction site-associated DNA mapping and genomic interval pull-down sequencing.

Forward genetic screens provide a powerful approach for inferring gene function on the basis of the phenotypes associated with mutated genes. However, determining the causal mutation by traditional mapping and candidate gene sequencing is often the rate-limiting step, especially when analyzing many mutants. We report two genomic approaches for more rapidly determining the identity of the affected genes in Caenorhabditis elegans mutants.

A survey of new temperature-sensitive, embryonic-lethal mutations in C. elegans: 24 alleles of thirteen genes.

To study essential maternal gene requirements in the early C. elegans embryo, we have screened for temperature-sensitive, embryonic lethal mutations in an effort to bypass essential zygotic requirements for such genes during larval and adult germline development. With conditional alleles, multiple essential requirements can be examined by shifting at different times from the permissive temperature of 15°C to the restrictive temperature of 26°C.

Elevated CO2 suppresses specific Drosophila innate immune responses and resistance to bacterial infection.

Elevated CO(2) levels (hypercapnia) frequently occur in patients with obstructive pulmonary diseases and are associated with increased mortality. However, the effects of hypercapnia on non-neuronal tissues and the mechanisms that mediate these effects are largely unknown. Here, we develop Drosophila as a genetically tractable model for defining non-neuronal CO(2) responses and response pathways.

Induction of the heat shock pathway during hypoxia requires regulation of heat shock factor by hypoxia-inducible factor-1.

Activation of heat shock proteins (Hsps) is critical to adaptation to low oxygen levels (hypoxia) and for enduring the oxidative stress of reoxygenation. Hsps are known to be regulated by heat shock factor (Hsf), but our results demonstrate an unexpected regulatory link between the oxygen-sensing and heat shock pathways. Hsf transcription is up-regulated during hypoxia due to direct binding by hypoxia-inducible factor-1 (HIF-1) to HIF-1 response elements in an Hsf intron.