Translation efficiency driven by CNOT3 subunit of the CCR4-NOT complex promotes leukemogenesis.

Protein synthesis is frequently deregulated during tumorigenesis. However, the precise contexts of selective translational control and the regulators of such mechanisms in cancer is poorly understood. Here, we uncovered CNOT3, a subunit of the CCR4-NOT complex, as an essential modulator of translation in myeloid leukemia.

Rat spatial memory and foraging on dual radial mazes.

Three experiments are reported that used a new test of spatial memory in rats. The apparatus used was dual eight-arm radial mazes that were connected at one arm of each maze, with a start arm and doors to each maze. Rats could be forced to go to one maze or the other or could make a free choice between mazes.

The relationships between pain-associated psychological distress, pain intensity, patient expectations, and physical function in individuals with musculoskeletal pain: A retrospective cohort study.

Introduction: The presence of pain-associated psychological distress (PAPD) in musculoskeletal disorders, including negative mood, fear-avoidance, and lack of positive affect/coping, is associated with prolonged disability. The importance of considering psychological influence on pain is well known, but practical ways of addressing it are not as straightforward. Identifying relationships between PAPD and pain intensity, patient expectations, and physical function may guide the development of future studies that assess causality and inform clinical practice.

Soluble TNF mediates amyloid-independent, diet-induced alterations to immune and neuronal functions in an Alzheimer's disease mouse model.

Increasing evidence indicates that neurodegenerative diseases, including Alzheimer's disease (AD), are a product of gene-by-environment interplay. The immune system is a major contributor mediating these interactions. Signaling between peripheral immune cells and those within the microvasculature and meninges of the central nervous system (CNS), at the blood-brain barrier, and in the gut likely plays an important role in AD.

RNA modifications in hematological malignancies.

RNA modifications play an important role in various cancers including blood cancers by controlling gene expression programs critical for survival, proliferation and differentiation of cancer cells. While hundreds of RNA modifications have been identified, many have not been functionally characterized. With development of enabling technologies to identify and map RNA modifications, tremendous advancement has been made in our understanding of the biological functions of these molecular markers in diverse cellular contexts.

Discrimination of Classical and Atypical BSE by a Distinct Immunohistochemical PrP Profile.

Bovine spongiform encephalopathy (BSE) belongs to the group of transmissible spongiform encephalopathies and is associated with the accumulation of a pathological isoform of the host-encoded glycoprotein, designated prion protein (PrP). Classical BSE (C-type) and two atypical BSE forms (L- and H-type) are known, and can be discriminated by biochemical characteristics. The goal of our study was to identify type-specific PrP profiles by using Immunohistochemistry.

Predictors of clinical experience performance in occupational therapy and physiotherapy: A scoping review.

Introduction: Successful completion of clinical education experiences is a graduation requirement for students in occupational therapy and physical therapy programmes. A scoping review was conducted to determine what is known about possible clinical experience performance predictors and to find associated research gaps.

Methods: The search included one hand-searched journal and seven databases, which were used to identify related relevant studies: CINAHL, Education Database, Education Source, Education Resources Information Center (ERIC), PubMed, REHABDATA, and Web of Science.

BET inhibitors rescue anti-PD1 resistance by enhancing TCF7 accessibility in leukemia-derived terminally exhausted CD8 T cells.

Many acute myeloid leukemia (AML) patients exhibit hallmarks of immune exhaustion, such as increased myeloid-derived suppressor cells, suppressive regulatory T cells and dysfunctional T cells. Similarly, we have identified the same immune-related features, including exhausted CD8 T cells (TEx) in a mouse model of AML. Here we show that inhibitors that target bromodomain and extra-terminal domain (BET) proteins affect tumor-intrinsic factors but also rescue T cell exhaustion and ICB resistance.

Progranulin loss results in sex-dependent dysregulation of the peripheral and central immune system.

Introduction: Progranulin (PGRN) is a secreted glycoprotein, the expression of which is linked to several neurodegenerative diseases. Although its specific function is still unclear, several studies have linked it with lysosomal functions and immune system regulation. Here, we have explored the role of PGRN in peripheral and central immune system homeostasis by investigating the consequences of PGRN deficiency on adaptive and innate immune cell populations.

Reproducibility of resistance exercise therapy interventions in trials for chronic low back pain is challenging: A systematic review.

Objective: Determine reproducibility of resistance exercise regimens in trials for CLBP and determine if recently available checklists are effective.

Methods: Four databases (Medline, PubMed, Cochrane and CINAHL) were searched for keywords related to back pain and resistance exercise. Reproducibility was assessed using two checklists, the 12-item Template for Intervention Description and Replication (TIDieR) and the 19-item Consensus on Exercise Reporting Template (CERT).

Atmospheric waves and global seismoacoustic observations of the January 2022 Hunga eruption, Tonga.

The 15 January 2022 climactic eruption of Hunga volcano, Tonga, produced an explosion in the atmosphere of a size that has not been documented in the modern geophysical record. The event generated a broad range of atmospheric waves observed globally by various ground-based and spaceborne instrumentation networks. Most prominent was the surface-guided Lamb wave (≲0.

Toenail speciation biomarkers in arsenic-related disease: a feasibility study for investigating the association between arsenic exposure and chronic disease.

Long-term exposure to environmental arsenic has been associated with many chronic diseases, including several cancers, and diabetes. Urinary studies have implicated arsenic speciation as an important risk factor, however, such associations have not been replicated using toenail samples: a relatively new biosample for estimating long-term internal dose-exposure to arsenic. Despite having several advantages over conventional biosamples such as ease of collection and storage, standard methods for arsenic speciation analysis in toenails have not yet been established.

Experiences of living with long COVID and of accessing healthcare services: a qualitative systematic review.

Objective: To explore the experiences of people living with long COVID and how they perceive the healthcare services available to them.

Design: Qualitative systematic review.

Data Sources: Electronic literature searches of websites, bibliographic databases and discussion forums, including PubMed LitCovid, Proquest COVID, EPPI Centre living systematic map of evidence, medRxiv, bioRxiv, Medline, Psychinfo and Web of Science Core Collection were conducted to identify qualitative literature published in English up to 13 January 2021.

A scoping review of patient and public perspectives on cell and gene therapies.

The development and introduction of cell and gene therapies presents complex social and economic issues. Fully addressing these challenges requires engagement with patients and the public. A systematically conducted scoping review was undertaken to gauge current patient and public knowledge and perspectives, and as such inform requirements for future research, education and engagement activities.

Central amygdala micro-circuits mediate fear extinction.

Fear extinction is an adaptive process whereby defensive responses are attenuated following repeated experience of prior fear-related stimuli without harm. The formation of extinction memories involves interactions between various corticolimbic structures, resulting in reduced central amygdala (CEA) output. Recent studies show, however, the CEA is not merely an output relay of fear responses but contains multiple neuronal subpopulations that interact to calibrate levels of fear responding.

Scottish Health Technologies Group: enhancing patient engagement.

Objectives: The Scottish Health Technologies Group (SHTG) provides evidence support and advice to the National Health Service in Scotland on the use of new and existing health technologies, which, although not medicines, are likely to have significant implications for people's care. The purpose of this paper is to highlight the developments that have taken place in the SHTG's patient involvement processes in the years 2017 to 2019, focusing primarily on specific engagement with patient organizations and considering how the new approaches have been received by stakeholders.

Methods: Feedback from patient organizations that participated in the SHTG submission process, alongside SHTG committee members' views on patient organizations contributions, was gathered primarily via online questionnaires.

Patient and public perspectives on cell and gene therapies: a systematic review.

Cell and gene therapies offer opportunities for treating disease with potential to restore function, and cure disease. However, they are not without risk and pose complex logistical, economic, ethical and social challenges for health systems. Here we report our systematic review of the current evidence on patient and public knowledge and perspectives of cell and gene therapies, to inform future research, education and awareness raising activities.

Optimization of an MMPB Lemieux Oxidation method for the quantitative analysis of microcystins in fish tissue by LC-QTOF MS.

Microcystins are toxic heptapeptides produced by cyanobacteria in marine and freshwater environments. In biological samples such as fish, microcystins can be found in the free form or covalently bound to protein phosphatases type I and II. Total microcystins in fish have been quantified in the past using the Lemieux Oxidation approach, where all toxins are oxidated to a common fragment (2-methyl-3-methoxy-4-phenylbutyric acid, MMPB) regardless of their initial amino acid configuration or form (free or protein bound).

Microglia depletion rapidly and reversibly alters amyloid pathology by modification of plaque compaction and morphologies.

Alzheimer's disease (AD) is a prominent neurodegenerative disorder characterized by deposition of β-amyloid (Aβ)-containing extracellular plaques, accompanied by a microglial-mediated inflammatory response, that leads to cognitive decline. Microglia perform many disease-modifying functions such as phagocytosis of plaques, plaque compaction, and modulation of inflammation through the secretion of cytokines. Microglia are reliant upon colony-stimulating factor receptor-1 (CSF1R) activation for survival.

Three-dimensional nanoscopy of whole cells and tissues with in situ point spread function retrieval.

Single-molecule localization microscopy is a powerful tool for visualizing subcellular structures, interactions and protein functions in biological research. However, inhomogeneous refractive indices inside cells and tissues distort the fluorescent signal emitted from single-molecule probes, which rapidly degrades resolution with increasing depth. We propose a method that enables the construction of an in situ 3D response of single emitters directly from single-molecule blinking datasets, and therefore allows their locations to be pinpointed with precision that achieves the Cramér-Rao lower bound and uncompromised fidelity.

An isolation effect in rat spatial memory.

Rats' working memory for locations previously visited and not visited was tested on the radial maze. Trials consisted of a study phase followed by a test phase. In the study phase, rats were forced to visit half the arms on the maze, with the other half of the arms blocked.

Information preferences across species: Pigeons, rats, and dogs.

We tested the information preferences of three different species; pigeons, rats and dogs. Eight animals of each species received forced trials that produced one of two stimulus sequences. In the first sequence, response to an initial stimulus led to one of two other stimuli, one of which guaranteed a food reward was coming and the other of which guaranteed no food reward was coming.