Harnessing natural variation to identify cis regulators of sex-biased gene expression in a multi-strain mouse liver model.

Sex differences in gene expression are widespread in the liver, where many autosomal factors act in tandem with growth hormone signaling to regulate individual variability of sex differences in liver metabolism and disease. Here, we compare hepatic transcriptomic and epigenetic profiles of mouse strains C57BL/6J and CAST/EiJ, representing two subspecies separated by 0.5-1 million years of evolution, to elucidate the actions of genetic factors regulating liver sex differences.

Impact of 3D genome organization, guided by cohesin and CTCF looping, on sex-biased chromatin interactions and gene expression in mouse liver.

Several thousand sex-differential distal enhancers have been identified in mouse liver; however, their links to sex-biased genes and the impact of any sex-differences in nuclear organization and chromatin interactions are unknown. To address these issues, we first characterized 1847 mouse liver genomic regions showing significant sex differential occupancy by cohesin and CTCF, two key 3D nuclear organizing factors. These sex-differential binding sites were primarily distal to sex-biased genes but rarely generated sex-differential TAD (topologically associating domain) or intra-TAD loop anchors, and were sometimes found in TADs without sex-biased genes.

Computational prediction of CTCF/cohesin-based intra-TAD loops that insulate chromatin contacts and gene expression in mouse liver.

CTCF and cohesin are key drivers of 3D-nuclear organization, anchoring the megabase-scale Topologically Associating Domains (TADs) that segment the genome. Here, we present and validate a computational method to predict cohesin-and-CTCF binding sites that form intra-TAD DNA loops. The intra-TAD loop anchors identified are structurally indistinguishable from TAD anchors regarding binding partners, sequence conservation, and resistance to cohesin knockdown; further, the intra-TAD loops retain key functional features of TADs, including chromatin contact insulation, blockage of repressive histone mark spread, and ubiquity across tissues.

Hepatic Dysfunction Caused by Consumption of a High-Fat Diet.

Obesity is a major human health crisis that promotes insulin resistance and, ultimately, type 2 diabetes. The molecular mechanisms that mediate this response occur across many highly complex biological regulatory levels that are incompletely understood. Here, we present a comprehensive molecular systems biology study of hepatic responses to high-fat feeding in mice.

Sea anemone model has a single Toll-like receptor that can function in pathogen detection, NF-κB signal transduction, and development.

In organisms from insects to vertebrates, Toll-like receptors (TLRs) are primary pathogen detectors that activate downstream pathways, specifically those that direct expression of innate immune effector genes. TLRs also have roles in development in many species. The sea anemone is a useful cnidarian model to study the origins of TLR signaling because its genome encodes a single TLR and homologs of many downstream signaling components, including the NF-κB pathway.

Hyper- and hypo- nutrition studies of the hepatic transcriptome and epigenome suggest that PPARα regulates anaerobic glycolysis.

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.

CHORIORETINAL BIOPSY FOR THE DIAGNOSIS OF ENDOGENOUS ENDOPHTHALMITIS DUE TO ESCHERICHIA COLI.

Purpose: To describe the novel use of a chorioretinal biopsy technique to confirm the microbiological diagnosis of endogenous Escherichia coli (E. coli) endophthalmitis, when other investigations have been proven nondiagnostic.

Methods: Case report of an 82-year-old white man with endogenous endophthalmitis without a clearly identifiable source of infection.

Elucidating MicroRNA Regulatory Networks Using Transcriptional, Post-transcriptional, and Histone Modification Measurements.

MicroRNAs (miRNAs) regulate diverse biological processes by repressing mRNAs, but their modest effects on direct targets, together with their participation in larger regulatory networks, make it challenging to delineate miRNA-mediated effects. Here, we describe an approach to characterizing miRNA-regulatory networks by systematically profiling transcriptional, post-transcriptional and epigenetic activity in a pair of isogenic murine fibroblast cell lines with and without Dicer expression. By RNA sequencing (RNA-seq) and CLIP (crosslinking followed by immunoprecipitation) sequencing (CLIP-seq), we found that most of the changes induced by global miRNA loss occur at the level of transcription.

A unique case of phaeohyphomycosis subretinal abscess in a patient with arthropathy and lung pathology.

A 67-year-old former gold miner with rheumatoid arthritis, treated with steroids and methotrexate, presented to eye casualty with a painful right eye. Examination revealed an anterior uveitis and despite an initial response to topical steroids, the intraocular inflammation worsened with anterior and posterior uveitis development. Re-examination showed a white mass in the peripheral nasal retina initially suspected of being active Toxoplasmosis infection and anti-toxoplasmosis treatment commenced.

Extensive changes in DNA methylation are associated with expression of mutant huntingtin.

The earliest stages of Huntington disease are marked by changes in gene expression that are caused in an indirect and poorly understood manner by polyglutamine expansions in the huntingtin (HTT) protein. To explore the hypothesis that DNA methylation may be altered in cells expressing mutated HTT, we use reduced representation bisulfite sequencing (RRBS) to map sites of DNA methylation in cells carrying either wild-type or mutant HTT. We find that a large fraction of the genes that change in expression in the presence of mutant huntingtin demonstrate significant changes in DNA methylation.

Isotocin regulates paternal care in a monogamous cichlid fish.

While the survival value of paternal care is well understood, little is known about its physiological basis. Here we investigate the neuroendocrine contributions to paternal care in the monogamous cichlid, Amatitlania nigrofasciata. We first explored the dynamic range of paternal care in three experimental groups: biparental males (control fathers housed with their mate), single fathers (mate removed), or lone males (mate and offspring removed).

Trans-corneal fine cannula aspiration: Rycroft cannula aspiration technique for sampling iris tumours.

Aim: To demonstrate a novel surgical technique for the accurate diagnosis of iris lesions using a minimally invasive aspiration cannula.

Method: 12 consecutive patients underwent biopsy of iris lesions at the Ocular Oncology Service, Royal Hallamshire Hospital, Sheffield, UK. Samples were obtained using a novel technique called trans-corneal fine cannula aspiration.

ER-α agonist induces conversion of fibroblasts into myofibroblasts, while ER-β agonist increases ECM production and wound tensile strength of healing skin wounds in ovariectomised rats.

Oestrogen deprivation is one of the major factors responsible for many age-related processes, including poor wound healing in women. Previously, it has been shown that oestrogens have a modulatory effect in different wound-healing models. Therefore, in this study, the effect of selective oestrogen receptor (ER) agonists (PPT - ER-α agonist, DPN - ER-β agonist) on excisional and incisional wound-healing models was compared in ovariectomised rats in vivo as well as on human dermal fibroblasts (HDF) and human umbilical endothelial cells (HUVEC) in vitro.

Molecular characterization and brain distribution of the progesterone receptor in whiptail lizards.

Progesterone and its nuclear receptor are critical in modulating reproductive physiology and behavior in female and male vertebrates. Whiptail lizards (genus Cnemidophorus) are an excellent model system in which to study the evolution of sexual behavior, as both the ancestral and descendent species exist. Male-typical sexual behavior is mediated by progesterone in both the ancestral species and the descendant all-female species, although the molecular characterization and distribution of the progesterone receptor protein throughout the reptilian brain is not well understood.

Characterization of the dopamine system in the brain of the túngara frog, Physalaemus pustulosus.

Dopamine is an evolutionarily ancient neurotransmitter that plays an essential role in mediating behavior. In vertebrates, dopamine is central to the mesolimbic reward system, a neural network concerned with the valuation of stimulus salience, and to the nigrostriatal motor system and hypothalamic nuclei involved in the regulation of locomotion and social behavior. In amphibians, dopaminergic neurons have been mapped out in several species, yet the distribution of dopaminoreceptive cells is unknown.