Higher order interaction analysis quantifies coordination in the epigenome revealing novel biological relationships in Kabuki syndrome.

Complex direct and indirect relationships between multiple variables, termed higher order interactions (HOIs), are characteristics of all natural systems. Traditional differential and network analyses fail to account for the omic datasets richness and miss HOIs. We investigated peripheral blood DNA methylation data from Kabuki syndrome type 1 (KS1) and control individuals, identified 2,002 differentially methylated points (DMPs), and inferred 17 differentially methylated regions, which represent only 189 DMPs.

Archival mitogenomes identify invasion by the CAPE lineage caused an African amphibian extinction in the wild.

Outbreaks of emerging infectious diseases are influenced by local biotic and abiotic factors, with host declines occurring when conditions favour the pathogen. Deterioration in the population of the micro-endemic Tanzanian Kihansi spray toad () occurred after the construction of a hydropower dam, implicating habitat modification in this species decline. Population recovery followed habitat augmentation; however, a subsequent outbreak of chytridiomycosis caused by () led to the spray toad's extinction in the wild.

Developing the 'omic toolkit of comparative physiologists.

Typical 'omic analyses reduce complex biological systems to simple lists of supposedly independent variables, failing to account for changes in the wider transcriptional landscape. In this commentary, we discuss the utility of network approaches for incorporating this wider context into the study of physiological phenomena. We highlight opportunities to build on traditional network tools by utilising cutting-edge techniques to account for higher order interactions (i.

Standard methods for marking caudate amphibians do not impair animal welfare over the short term: An experimental approach.

Major advancements in ecology and biodiversity conservation have been made thanks to methods for marking and individually tracking animals. Marking animals is both widely used and controversial due to the potential consequences for animal welfare, which are often incompletely evaluated prior to implementation. Two outstanding knowledge gaps concerning the welfare consequences of individual marking are their short-term behavioural impacts and the relative impacts from marking versus the handling of animals while carrying out procedures.

Environment predicts lineage distribution and zones of recombination in South Africa.

The amphibian-infecting chytrid fungus, (), is widespread throughout Africa and is linked to declines of populations and species across the continent. While it is well established that the lineage of encodes traits which determine disease severity, knowledge around how lineages are distributed according to environmental envelope is unclear. We here studied the distribution of in South Africa based on the two lineages found, GPL and CAPE, in terms of their genome and environmental envelope statistically associated with their distribution.

Gene Expression Signatures Predict First-Year Response to Somapacitan Treatment in Children With Growth Hormone Deficiency.

Context: The pretreatment blood transcriptome predicts growth response to daily growth hormone (GH) therapy with high accuracy.

Objective: Investigate response prediction using pretreatment transcriptome in children with GH deficiency (GHD) treated with once-weekly somapacitan, a novel long-acting GH.

Methods: REAL4 is a randomized, multinational, open-label, active-controlled parallel group phase 3 trial, comprising a 52-week main phase and an ongoing 3-year safety extension (NCT03811535).

Human Mast Cells Upregulate Cathepsin B, a Novel Marker of Itch in Psoriasis.

Mast cells (MCs) contribute to skin inflammation. In psoriasis, the activation of cutaneous neuroimmune networks commonly leads to itch. To dissect the unique contribution of MCs to the cutaneous neuroinflammatory response in psoriasis, we examined their density, distribution, relation to nerve fibres and disease severity, and molecular signature by comparing RNA-seq analysis of MCs isolated from the skin of psoriasis patients and healthy volunteers.

Warming during embryogenesis induces a lasting transcriptomic signature in fishes.

Exposure to elevated temperatures during embryogenesis can influence the plasticity of tissues in later life. Despite these long-term changes in plasticity, few differentially expressed genes are ever identified, suggesting that the developmental programming of later life plasticity may occur through the modulation of other aspects of transcriptomic architecture, such as gene network organisation. Here, we use network modelling approaches to demonstrate that warm temperatures during embryonic development (developmental warming) have consistent effects in later life on the organisation of transcriptomic networks across four diverse species of fishes: Scyliorhinus canicula, Danio rerio, Dicentrarchus labrax, and Gasterosteus aculeatus.

Diagnosis of childhood and adolescent growth hormone deficiency using transcriptomic data.

Background: Gene expression (GE) data have shown promise as a novel tool to aid in the diagnosis of childhood growth hormone deficiency (GHD) when comparing GHD children to normal children. The aim of this study was to assess the utility of GE data in the diagnosis of GHD in childhood and adolescence using non-GHD short stature children as a control group.

Methods: GE data was obtained from patients undergoing growth hormone stimulation testing.

Non-Lethal Detection of -Like (RUK13) and -Like (PDE18) Ranaviruses in Two UK-Native Amphibian Species.

Ranaviruses have been involved in amphibian mass mortality events worldwide. Effective screening to control this pathogen is essential; however, current sampling methods are unsuitable for the detection of subclinical infections. Non-lethal screening is needed to prevent both further spread of ranavirus and losses of at-risk species.

Host Identity Matters-Up to a Point: The Community Context of Transmission.

AbstractThe level of detail on host communities needed to understand multihost parasite invasions is an unresolved issue in disease ecology. Coarse community metrics that ignore functional differences between hosts, such as host species richness, can be good predictors of invasion outcomes. Yet if host species vary in the extent to which they maintain and transmit infections, then explicitly accounting for those differences may be important.

Ad libitum feeding alters mRNA abundance in the ovarian cortex of broiler breeder hens.

Ad Libitum: feeding in broiler breeder (BB) hens causes reduced egg production, lower fertility, and improper eggshell deposition. Restricted feeding (RF) is the only effective intervention available to normalize ovarian function and improve reproductive efficiency. This study aimed to assess the transcriptional changes in ovarian cortex of BB hens with free access to feed compared to those on a RF diet.

Global antimicrobial stewardship and the need for pharmaceutical system strengthening for antimicrobials within a One Health approach.

Objectives: The COVID-19 pandemic has highlighted both the vulnerabilities and the critical role of global pharmaceutical systems in enabling equitable access to medicines. In this personal view, we position the pharmaceutical system as a missed research and investment opportunity that, if integrated properly, would benefit antimicrobial stewardship (AMS) programmes within a One Health approach.

Key Findings: The pharmaceutical supply management cycle (PSMC) illustrates the continuous interdependence between four key phases: selection, procurement, distribution and use.

Monocarboxylate Transporters Are Involved in Extracellular Matrix Remodelling in Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a five-year survival rate of <8%. PDAC is characterised by desmoplasia with an abundant extracellular matrix (ECM) rendering current therapies ineffective. Monocarboxylate transporters (MCTs) are key regulators of cellular metabolism and are upregulated in different cancers; however, their role in PDAC desmoplasia is little understood.

Challenging a host-pathogen paradigm: Susceptibility to chytridiomycosis is decoupled from genetic erosion.

The putatively positive association between host genetic diversity and the ability to defend against pathogens has long attracted the attention of evolutionary biologists. Chytridiomycosis, a disease caused by the chytrid fungus Batrachochytrium dendrobatidis (Bd), has emerged in recent decades as a cause of dramatic declines and extinctions across the amphibian clade. Bd susceptibility can vary widely across populations of the same species, but the relationship between standing genetic diversity and susceptibility has remained notably underexplored so far.

Trophectoderm differentiation to invasive syncytiotrophoblast is promoted by endometrial epithelial cells during human embryo implantation.

Study Question: How does the human embryo breach the endometrial epithelium at implantation?

Summary Answer: Embryo attachment to the endometrial epithelium promotes the formation of multinuclear syncytiotrophoblast from trophectoderm, which goes on to breach the epithelial layer.

What Is Known Already: A significant proportion of natural conceptions and assisted reproduction treatments fail due to unsuccessful implantation. The trophectoderm lineage of the embryo attaches to the endometrial epithelium before breaching this barrier to implant into the endometrium.

Impact of an Elementary School-Based Wellness Initiative on Child Obesity Prevalence: LiveWell Kids.

Despite major public health investments over the past several decades, little progress has been made in reducing the prevalence of obesity among school-aged children in the United States. In 2007, the Redondo Beach Unified School District (RBUSD) and the Beach Cities Health District launched a wellness initiative, LiveWell Kids, that included multi-level interventions to improve nutrition and increase physical activity. The initiative also included annual measurements of height and weight among all kindergartners and first, third, and fifth graders in the eight elementary schools in the RBUSD.

Exposure to Batrachochytrium dendrobatidis affects chemical defences in two anuran amphibians, Rana dalmatina and Bufo bufo.

Background: Batrachochytrium dendrobatidis (Bd) is the causative agent of chytridiomycosis, one of the major causes of worldwide amphibian biodiversity loss. Many amphibians exhibit skin-based chemical defences, which may play an important role against invading pathogens, but whether the synthesis of these chemical compounds is enhanced or suppressed in the presence of pathogens is largely unknown. Here we investigated direct and indirect effects of larval exposure to the globally distributed and highly virulent Bd-GPL strain on skin secreted chemical defences and life history traits during early ontogeny of agile frogs (Rana dalmatina) and common toads (Bufo bufo).

Revising Endosomal Trafficking under Insulin Receptor Activation.

The endocytosis of ligand-bound receptors and their eventual recycling to the plasma membrane (PM) are processes that have an influence on signalling activity and therefore on many cell functions, including migration and proliferation. Like other tyrosine kinase receptors (TKR), the insulin receptor (INSR) has been shown to be endocytosed by clathrin-dependent and -independent mechanisms. Once at the early endosome (EE), the sorting of the receptor, either to the late endosome (LE) for degradation or back to the PM through slow or fast recycling pathways, will determine the intensity and duration of insulin effects.

Gene expression signatures predict response to therapy with growth hormone.

Recombinant human growth hormone (r-hGH) is used as a therapeutic agent for disorders of growth including growth hormone deficiency (GHD) and Turner syndrome (TS). Treatment is costly and current methods to model response are inexact. GHD (n = 71) and TS patients (n = 43) were recruited to study response to r-hGH over 5 years.