The levels of the long noncoding RNA MALAT1 affect cell viability and modulate TDP-43 binding to mRNA in the nucleus.

TAR DNA-binding protein (TDP-43) and metastasis-associated lung adenocarcinoma transcript (MALAT1) RNA are both abundantly expressed in the human cell nucleus. Increased interaction of TDP-43 and MALAT1, as well as dysregulation of TDP-43 function, was previously identified in brain samples from patients with neurodegenerative disease compared to healthy brain tissues. We hypothesized that TDP-43 function may depend in part on MALAT1 expression levels.

Removal of dissolved organic carbon in the West Pacific hadal zones.

The deep oceans are environments of complex carbon dynamics that have the potential to significantly impact the global carbon cycle. However, the role of hadal zones, particularly hadal trenches (water depth > 6 km), in the oceanic dissolved organic carbon (DOC) cycle is not thoroughly investigated. Here we report distinct DOC signatures in the Japan Trench bottom water.

A mystery solved: human high-frequency middle-ear motion.

The middle ear transforms sound from low-impedance external air to high-impedance cochlear fluid. However, the human stapes - the input to the cochlea - has been reported to have minimal or no motion above ~ 4 kHz. For decades, this lack of observed high-frequency stapes motion has been puzzling, as it is inconsistent with our ability to hear up to 20 kHz.

Suppression of Huntington's Disease Somatic Instability by Transcriptional Repression and Direct CAG Repeat Binding.

Huntington's disease (HD) arises from a CAG expansion in the () gene beyond a critical threshold. A major thrust of current HD therapeutic development is lowering levels of mutant mRNA (m) and protein (mHTT) with the aim of reducing the toxicity of these product(s). Human genetic data also support a key role for somatic instability (SI) in 's CAG repeat - whereby it lengthens with age in specific somatic cell types - as a key driver of age of motor dysfunction onset.

The UmboMic: A PVDF Cantilever Microphone.

Objective: We present the "UmboMic," a prototype piezoelectric cantilever microphone designed for future use with totally-implantable cochlear implants.

Methods: The UmboMic sensor is made from polyvinylidene difluoride (PVDF) because of its low Young's modulus and biocompatibility. The sensor is designed to fit in the middle ear and measure the motion of the underside of the eardrum at the umbo.

People, places, things and communities: expanding behaviour settings theory in the twenty-first century.

Trends and developments in recent behavioural and cognitive sciences demonstrate the need for a well-developed theoretical and empirical framework for examining the ecology of human behaviour. The increasing recognition of the role of the environment and interaction with the environment in the organization of behaviour within the cognitive sciences has not been met with an equally disciplined and systematic account of that environment (Heft 2018 . , 99-123 (doi:10.

Multi-omic analysis of Huntington's disease reveals a compensatory astrocyte state.

The mechanisms underlying the selective regional vulnerability to neurodegeneration in Huntington's disease (HD) have not been fully defined. To explore the role of astrocytes in this phenomenon, we used single-nucleus and bulk RNAseq, lipidomics, HTT gene CAG repeat-length measurements, and multiplexed immunofluorescence on HD and control post-mortem brains. We identified genes that correlated with CAG repeat length, which were enriched in astrocyte genes, and lipidomic signatures that implicated poly-unsaturated fatty acids in sensitizing neurons to cell death.

Creation of the Youth Integration Project Framework: A Narrative Synthesis of the Youth Mental Health Integrated Care Literature.

Introduction: Integrated care has been posited as a potential solution to the global burden of youth mental health (YMH), but there is limited evidence on how best to design, staff, and evaluate different integrated care models. Our review aimed to consolidate the evidence on integrated models of mental healthcare for young people, to identify the core components of integration, and create a framework that can be used to analyse levels of YMH integration.

Methods: We conducted a systematic review of literature across PubMed, SCOPUS, and PsycINFO databases and the grey literature We performed a narrative synthesis extracting core components of integrated YMH care.

Integrated care models for youth mental health: A systematic review and meta-analysis.

Objectives: To evaluate the effectiveness of integrated models of mental healthcare in enhancing clinical outcomes, quality of life, satisfaction with care and health service delivery outcomes in young people aged 12-25 years. A secondary objective was to identify common components of integrated mental health interventions.

Methods: A systematic review and meta-analysis of studies published 2001-2023 that assessed clinical or health service use outcomes of integrated care, relative to treatment as usual, for any mental health condition in 12-25 years old accessing community-based care.

GRAS1 non-coding RNA protects against DNA damage and cell death by binding and stabilizing NKAP.

Non-coding RNA (ncRNA) gene products are involved in diverse biological processes including splicing, epigenetic regulation, gene expression, proliferation, and metabolism. The biological mechanisms by which ncRNAs contribute to cell survival remain poorly understood. We found that the Growth Regulator Antisense 1 (GRAS1) long non-coding RNA (lncRNA) transcript promotes growth in multiple human cell types by protecting against DNA damage.

Regulation of host metabolic health by parasitic helminths.

Obesity is a worldwide pandemic and major risk factor for the development of metabolic syndrome (MetS) and type 2 diabetes (T2D). T2D requires lifelong medical support to limit complications and is defined by impaired glucose tolerance, insulin resistance (IR), and chronic low-level systemic inflammation initiating from adipose tissue. The current preventative strategies include a healthy diet, controlled physical activity, and medication targeting hyperglycemia, with underexplored underlying inflammation.

A multi-cohort genome-wide association study in African ancestry individuals reveals risk loci for primary open-angle glaucoma.

Primary open-angle glaucoma (POAG), the leading cause of irreversible blindness worldwide, disproportionately affects individuals of African ancestry. We conducted a genome-wide association study (GWAS) for POAG in 11,275 individuals of African ancestry (6,003 cases; 5,272 controls). We detected 46 risk loci associated with POAG at genome-wide significance.

An Implantable Piezofilm Middle Ear Microphone: Performance in Human Cadaveric Temporal Bones.

Purpose: One of the major reasons that totally implantable cochlear microphones are not readily available is the lack of good implantable microphones. An implantable microphone has the potential to provide a range of benefits over external microphones for cochlear implant users including the filtering ability of the outer ear, cosmetics, and usability in all situations. This paper presents results from experiments in human cadaveric ears of a piezofilm microphone concept under development as a possible component of a future implantable microphone system for use with cochlear implants.

The UmboMic: A PVDF Cantilever Microphone.

Objective: We present the "UmboMic," a prototype piezoelectric cantilever microphone designed for future use with totally-implantable cochlear implants.

Methods: The UmboMic sensor is made from polyvinylidene difluoride (PVDF) because of its low Young's modulus and biocompatibility. The sensor is designed to fit in the middle ear and measure the motion of the underside of the eardrum at the umbo.

N-Nitrosodimethylamine investigations in Muta™Mouse define point-of-departure values and demonstrate less-than-additive somatic mutant frequency accumulations.

The N-nitrosamine, N-nitrosodimethylamine (NDMA), is an environmental mutagen and rodent carcinogen. Small levels of NDMA have been identified as an impurity in some commonly used drugs, resulting in several product recalls. In this study, NDMA was evaluated in an OECD TG-488 compliant Muta™Mouse gene mutation assay (28-day oral dosing across seven daily doses of 0.