Single-cell analysis of the epigenome and 3D chromatin architecture in the human retina.

Most genetic risk variants linked to ocular diseases are non-protein coding and presumably contribute to disease through dysregulation of gene expression, however, deeper understanding of their mechanisms of action has been impeded by an incomplete annotation of the transcriptional regulatory elements across different retinal cell types. To address this knowledge gap, we carried out single-cell multiomics assays to investigate gene expression, chromatin accessibility, DNA methylome and 3D chromatin architecture in human retina, macula, and retinal pigment epithelium (RPE)/choroid. We identified 420,824 unique candidate regulatory elements and characterized their chromatin states in 23 sub-classes of retinal cells.

Associations of cord blood concentrations of perfluoroalkyl substances with autistic traits in Singaporean children: The growing up in Singapore towards healthy outcomes study.

Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by social deficits and repetitive behaviors. Environmental pollutants may contribute to the etiology of ASD, but studies of perfluoroalkyl substances (PFAS) have shown conflicting results.

Objectives: We assessed associations between cord blood concentrations of PFAS with autistic traits at age seven years in a Singaporean birth cohort.

Epigenetic and 3D genome reprogramming during the aging of human hippocampus.

Age-related cognitive decline is associated with altered physiology of the hippocampus. While changes in gene expression have been observed in aging brain, the regulatory mechanisms underlying these changes remain underexplored. We generated single-nucleus gene expression, chromatin accessibility, DNA methylation, and 3D genome data from 40 human hippocampal tissues spanning adult lifespan.

Targeted variant prevalence of FBXW7 gene mutation in colorectal carcinoma propagation. The first systematic review and meta-analysis.

Unlabelled: FBXW7 is a tumour suppressor gene that functions as E3-ubiquitin-ligase, targeting numerous oncoproteins for degradation, i.e., Cyclin-E, c-Myc, and Notch.

Lattice QCD Calculation of Electroweak Box Contributions to Superallowed Nuclear and Neutron Beta Decays.

We present the first lattice QCD calculation of the universal axial γW-box contribution □_{γW}^{VA} to both superallowed nuclear and neutron beta decays. This contribution emerges as a significant component within the theoretical uncertainties surrounding the extraction of |V_{ud}| from superallowed decays. Our calculation is conducted using two domain wall fermion ensembles at the physical pion mass.

Activation of feedforward wiring in adult hippocampal neurons by the basic-helix-loop-helix transcription factor Ascl4.

Although evidence indicates that the adult brain retains a considerable capacity for circuit formation, adult wiring has not been broadly considered and remains poorly understood. In this study, we investigate wiring activation in adult neurons. We show that the basic-helix-loop-helix transcription factor Ascl4 can induce wiring in different types of hippocampal neurons of adult mice.

Zinc Localization and Speciation in Rice Grain Under Variable Soil Zinc Deficiency.

Background And Aims: Rice accounts for around 20% of the calories consumed by humans. Essential nutrients like zinc (Zn) are crucial for rice growth and for populations relying on rice as a staple food. No well-established study method exists.

Model-Independent Determination of Nuclear Weak Form Factors and Implications for Standard Model Precision Tests.

We analyze the recoil corrections in superallowed beta decays of T=1, J^{P}=0^{+} nuclei by fixing the mean square charged weak radius model independently using the data of multiple charge radii across the nuclear isotriplet. By comparing to model estimations, we argue that the existing theory uncertainty in the statistical rate function f might have been substantially underestimated. We discuss the implications of our proposed strategy for precision tests of the standard model, including a potential alleviation of the first-row CKM unitarity deficit, and motivate new experiments for charge radii measurements.

Evaluation of Candidates for Systemic Analgesia and General Anesthesia in the Emerging Model Cephalopod, .

Cephalopods' remarkable behavior and complex neurobiology make them valuable comparative model organisms, but studies aimed at enhancing welfare of captive cephalopods remain uncommon. Increasing regulation of cephalopods in research laboratories has resulted in growing interest in welfare-oriented refinements, including analgesia and anesthesia. Although general and local anesthesia in cephalopods have received limited prior study, there have been no studies of systemic analgesics in cephalopods to date.

controls target specification of mossy fiber sprouting.

Circuit formation is a defining characteristic of the developing brain. However, multiple lines of evidence suggest that circuit formation can also take place in adults, the mechanisms of which remain poorly understood. Here, we investigated the epilepsy-associated mossy fiber (MF) sprouting in the adult hippocampus and asked which cell surface molecules define its target specificity.

Tiny changes in cytoplasmic [Ca] cause large changes in mitochondrial Ca: what are the triggers and functional implications?

Ca is an integral component of the functional and developmental regulation of the mitochondria. In skeletal muscle, Ca is reported to modulate the rate of ATP resynthesis, regulate the expression of peroxisome proliferator-activated receptor-gamma coactivator 1 (PGC1α) following exercise, and drive the generation of reactive oxygen species (ROS). Due to the latter, mitochondrial Ca overload is recognized as a pathophysiological event but the former events represent important physiological functions in need of tight regulation.

A Systematic Review and Meta-analysis on the Occurrence of Biomarker Mutation in Colorectal Cancer among the Asian Population.

Globally, colorectal carcinoma (CRC) is the third most common cancer and the third major cause of cancer-related death in both sexes. KRAS and BRAF mutations are almost mutually exclusively involved in the pathogenesis of CRC. Both are major culprits in treatment failure and poor prognosis for CRC.

Circuit formation in the adult brain.

Neurons in the mammalian central nervous system display an enormous capacity for circuit formation during development but not later in life. In principle, new circuits could be also formed in adult brain, but the absence of the developmental milieu and the presence of growth inhibition and hundreds of working circuits are generally viewed as unsupportive for such a process. Here, we bring together evidence from different areas of neuroscience-such as neurological disorders, adult-brain neurogenesis, innate behaviours, cell grafting, and in vivo cell reprogramming-which demonstrates robust circuit formation in adult brain.

Ryanodine receptor activity and store-operated Ca entry: Critical regulators of Ca content and function in skeletal muscle.

Store-operated Ca entry (SOCE) is critical to cell function. In skeletal muscle, SOCE has evolved alongside excitation-contraction coupling (EC coupling); as a result, it displays unique properties compared to SOCE in other cells. The plasma membrane of skeletal muscle is mostly internalized as the tubular system, with the tubules meeting the sarcoplasmic reticulum (SR) terminal cisternae, forming junctions where the proteins that regulate EC coupling and SOCE are positioned.

Neurexin-3 defines synapse- and sex-dependent diversity of GABAergic inhibition in ventral subiculum.

Ventral subiculum (vSUB) is integral to the regulation of stress and reward; however, the intrinsic connectivity and synaptic properties of the inhibitory local circuit are poorly understood. Neurexin-3 (Nrxn3) is highly expressed in hippocampal inhibitory neurons, but its function at inhibitory synapses has remained elusive. Using slice electrophysiology, imaging, and single-cell RNA sequencing, we identify multiple roles for Nrxn3 at GABAergic parvalbumin (PV) interneuron synapses made onto vSUB regular-spiking (RS) and burst-spiking (BS) principal neurons.

Ryanodine receptor leak triggers fiber Ca redistribution to preserve force and elevate basal metabolism in skeletal muscle.

Muscle contraction depends on tightly regulated Ca release. Aberrant Ca leak through ryanodine receptor 1 (RyR1) on the sarcoplasmic reticulum (SR) membrane can lead to heatstroke and malignant hyperthermia (MH) susceptibility, as well as severe myopathy. However, the mechanism by which Ca leak drives these pathologies is unknown.

Recurrent rewiring of the adult hippocampal mossy fiber system by a single transcriptional regulator, Id2.

Circuit formation in the central nervous system has been historically studied during development, after which cell-autonomous and nonautonomous wiring factors inactivate. In principle, balanced reactivation of such factors could enable further wiring in adults, but their relative contributions may be circuit dependent and are largely unknown. Here, we investigated hippocampal mossy fiber sprouting to gain insight into wiring mechanisms in mature circuits.

Transverse Colostomy Differs in Outcomes Compared to Sigmoid Colostomy: A Cohort Analysis.

Purpose: Our aim was to identify any differences in outcomes following transverse versus sigmoid colostomy creation for management of cancer.

Methods: Transverse and sigmoid colostomies are used to manage cancer-related complications including obstruction, perforation, and fistulation. The decision to use either colostomy is largely based on the surgeon's preference and the location of the cancer complication.

Author Correction: Surfaceome dynamics reveal proteostasis-independent reorganization of neuronal surface proteins during development and synaptic plasticity.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Surfaceome dynamics reveal proteostasis-independent reorganization of neuronal surface proteins during development and synaptic plasticity.

Neurons are highly compartmentalized cells with tightly controlled subcellular protein organization. While brain transcriptome, connectome and global proteome maps are being generated, system-wide analysis of temporal protein dynamics at the subcellular level are currently lacking. Here, we perform a temporally-resolved surfaceome analysis of primary neuron cultures and reveal dynamic surface protein clusters that reflect the functional requirements during distinct stages of neuronal development.

First-Principles Calculation of Electroweak Box Diagrams from Lattice QCD.

We present the first realistic lattice QCD calculation of the γW-box diagrams relevant for beta decays. The nonperturbative low-momentum integral of the γW loop is calculated using a lattice QCD simulation, complemented by the perturbative QCD result at high momenta. Using the pion semileptonic decay as an example, we demonstrate the feasibility of the method.

Pre-Operative Embolisation of Musculoskeletal Tumours - A Single Centre Experience.

Introduction: The management of musculoskeletal tumours is complex and requires a multi-disciplinary approach. Preoperative embolisation can be often employed to reduce intra-operative blood loss and complication rates from surgery. We report our experience with the safety, technical success and efficacy of pre-operative embolisation in musculoskeletal tumours.

Serum albumin level predicts survival after surgical treatment of metastatic femur fractures: a retrospective study.

Background: Surgical treatment for metastatic pathological femur fractures is associated with high mortality. Correct estimation of prognosis helps in determining the palliative value of surgical treatment and informs surgical decision. This study evaluates the risk factors for mortality in these patients who were surgically treated.

Nanopore Sequencing Reveals Novel Targets for Detection and Surveillance of Human and Avian Influenza A Viruses.

Accurate detection of influenza A virus (IAV) is crucial for patient management, infection control, and epidemiological surveillance. The World Health Organization and the Centers for Disease Control and Prevention have recommended using the M gene as the diagnostic gene target for reverse-transcription-PCR (RT-PCR). However, M gene RT-PCR has reduced sensitivity for recent IAV due to novel gene mutations.

Effect of Severity of Deformity on Clinical Outcomes of Scarf Osteotomies.

Background: Literature is sparse on whether severity of hallux valgus affects outcomes of surgery. We thus aimed to evaluate the impact of hallux valgus severity on the clinical outcomes of surgery.

Methods: 83 consecutive scarf osteotomies performed by a single surgeon for symptomatic hallux valgus between 2007 and 2011 were divided into 3 groups (mild, moderate, and severe) based on severity of their preoperative hallux valgus using the hallux valgus and intermetatarsal angles.