Concurrent analysis of genome and transcriptome in one single cell.

Thus far, multiple techniques for single cell analysis have been developed, yet we lack a relatively simple tool to assess DNA and RNA from the same cell at whole-transcriptome and whole-genome depths. Here we present an updated method for physical separation of cytoplasmic RNA from the nuclei, which allows for simultaneous studies of DNA and RNA from the same single cell. The method consists of three steps-(1) immobilization of a single cell on solid substrate, (2) hypotonic lysis of immobilized single cell, and (3) separation of cytosol containing aqueous phase and immobilized nucleus.

Dietary linoleic acid lowering alone does not lower arachidonic acid or endocannabinoids among women with overweight and obesity: A randomized, controlled trial.

The linoleic acid (LA)-arachidonic acid (ARA)-inflammatory axis suggests dietary LA lowering benefits health because it lowers ARA and ARA-derived endocannabinoids (ECB). Dietary LA reduction increases concentrations of omega-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and DHA derived ECB. The aim of this study was to examine targeted reduction of dietary LA, with and without EPA and DHA, on plasma EPA and DHA and ECB (2-arachidonoyl glycerol [2-AG], anandamide [AEA], and docosahexaenoyl ethanolamide [DHA-EA]).

Experiences of Indigenous Patients Receiving Dialysis: Systematic Review of Qualitative Studies.

Rationale & Objective: Indigenous People suffer a high burden of kidney disease. Those receiving maintenance dialysis have worse outcomes compared with similarly treated non-Indigenous patients. We characterized the experiences of Indigenous patients receiving dialysis in British-colonized countries to gain insights into which aspects of kidney care may benefit from improvement.

Concurrent analysis of genome and transcriptome in one single cell.

Thus far, multiple techniques for single cell analysis have been developed, yet we lack a relatively simple tool to assess DNA and RNA from the same cell at whole-transcriptome and whole-genome depths. Here we present an updated method for physical separation of cytoplasmic RNA from the nuclei, which allows for simultaneous studies of DNA and RNA from the same single cell. The method consists of three steps - 1) immobilization of a single cell on solid substrate, 2) hypotonic lysis of immobilized single cell, and 3) separation of cytosol containing aqueous phase and immobilized nucleus.

Dynamic network-guided CRISPRi screen identifies CTCF-loop-constrained nonlinear enhancer gene regulatory activity during cell state transitions.

Comprehensive enhancer discovery is challenging because most enhancers, especially those contributing to complex diseases, have weak effects on gene expression. Our gene regulatory network modeling identified that nonlinear enhancer gene regulation during cell state transitions can be leveraged to improve the sensitivity of enhancer discovery. Using human embryonic stem cell definitive endoderm differentiation as a dynamic transition system, we conducted a mid-transition CRISPRi-based enhancer screen.

Quantifying social performance: A review with implications for further work.

Human social performance has been a focus of theory and investigation for more than a century. Attempts to quantify social performance have focused on self-report and non-social performance measures grounded in intelligence-based theories. An expertise framework, when applied to individual differences in social interaction performance, offers novel insights and methods of quantification that could address limitations of prior approaches.

Dynamic network-guided CRISPRi screen reveals CTCF loop-constrained nonlinear enhancer-gene regulatory activity in cell state transitions.

Comprehensive enhancer discovery is challenging because most enhancers, especially those affected in complex diseases, have weak effects on gene expression. Our network modeling revealed that nonlinear enhancer-gene regulation during cell state transitions can be leveraged to improve the sensitivity of enhancer discovery. Utilizing hESC definitive endoderm differentiation as a dynamic transition system, we conducted a mid-transition CRISPRi-based enhancer screen.

Functional comparison of human ACVR1 and zebrafish Acvr1l FOP-associated variants in embryonic zebrafish.

Background: Fibrodysplasia ossificans progressiva (FOP), a rare disease characterized by progressive heterotopic ossification of muscle and connective tissues, is caused by autosomal dominant activating mutations in the type I receptor, ACVR1/ALK2. The classic human FOP variant, ACVR1 , shows increased bone morphogenetic protein (BMP) signaling and activation by activins.

Results: Here, we performed in vivo functional characterization of human ACVR1 and orthologous zebrafish Acvr1l using early embryonic zebrafish dorsoventral patterning as a phenotypic readout for receptor activity.

A mechanism for inheriting radiation-induced DNA damage.

Radiation-damaged paternal DNA has been found to cause embryos of the second generation of nematode worms, but not the first, to die. The proposed mechanisms help to explain the observed lack of such an effect in humans.

Global Level Quantification of Histone Post-Translational Modifications in a 3D Cell Culture Model of Hepatic Tissue.

Flat cultures of mammalian cells are a widely used in vitro approach for understanding cell physiology, but this system is limited in modeling solid tissues due to unnaturally rapid cell replication. This is particularly challenging when modeling mature chromatin, as fast replicating cells are frequently involved in DNA replication and have a heterogeneous polyploid population. Presented below is a workflow for modeling, treating, and analyzing quiescent chromatin modifications using a three-dimensional (3D) cell culture system.

Randomised controlled trial of intermittent vs continuous energy restriction during chemotherapy for early breast cancer.

Background: Excess adiposity at diagnosis and weight gain during chemotherapy is associated with tumour recurrence and chemotherapy toxicity. We assessed the efficacy of intermittent energy restriction (IER) vs continuous energy restriction (CER) for weight control and toxicity reduction during chemotherapy.

Methods: One hundred and seventy-two women were randomised to follow IER or CER throughout adjuvant/neoadjuvant chemotherapy.

Impact of a Multicomponent Digital Therapeutic Mobile App on Medication Adherence in Patients with Chronic Conditions: Retrospective Analysis.

Background: Strategies to improve medication adherence are widespread in the literature; however, their impact is limited in real practice. Few patients persistently engage long-term to improve health outcomes, even when they are aware of the consequences of poor adherence. Despite the potential of mobile phone apps as a tool to manage medication adherence, there is still limited evidence of the impact of these innovative interventions.

Hyperactivation of TORC1 Drives Resistance to the Pan-HER Tyrosine Kinase Inhibitor Neratinib in HER2-Mutant Cancers.

We developed neratinib-resistant HER2-mutant cancer cells by gradual dose escalation. RNA sequencing identified TORC1 signaling as an actionable mechanism of drug resistance. Primary and acquired neratinib resistance in HER2-mutant breast cancer patient-derived xenografts (PDXs) was also associated with TORC1 hyperactivity.

The presence of multidrug-resistant staphylococcal isolates outside of a major hospital in London, United Kingdom.

Objective: Drug-resistant staphylococci have been a growing threat to the community and hospitals due to the misuse of antibiotics by humans, industrialisation and lack of novel antimicrobials currently available. Little is known about the prevalence of drug-resistant staphylococci in non-healthcare environments outside hospitals in the London area. Staphylococci can spread via contact with contaminated objects.

Rejuvenating subventricular zone neurogenesis in the aging brain.

Neural stem cells exist in specialized regions of the brain and have the capacity to give rise to neurons and glia over the lifespan. The process of giving rise to new neurons, also known as neurogenesis, is thought to be important in cognition and certain types of brain repair. However, during aging, neural stem cell number and function is reduced resulting in fewer new neurons and declines in learning, memory and repair.

Searching for Semantic Knowledge: A Vector Space Semantic Analysis of the Feature Generation Task.

A recent neuropsychological study found that amnesic patients with hippocampal damage (HP) and severe declarative memory impairment produce markedly fewer responses than healthy comparison (CO) participants in a semantic feature generation task (Klooster and Duff, 2015), consistent with the idea that hippocampal damage is associated with semantic cognitive deficits. Participants were presented with a target word and asked to produce as many features of that word as possible (e.g.