Initiation and stability of self-harm in adolescence and early adulthood: investigating social and aetiological factors in twins.

Background: Almost one in five (18.8%) UK adolescents are estimated to self-harm and many young people initiate self-harm early (average age 13 years). Prevention of self-harm should be informed by knowledge about risk factors (e.

Proteomic characterization of a foraminiferal test's organic matrix.

Foraminifera are unicellular protists capable of precipitating calcite tests, which fossilize and preserve geochemical signatures of past environmental conditions dating back to the Cambrian period. The biomineralization mechanisms responsible for the mineral structures, which are key to interpreting palaeoceanographic signals, are poorly understood. Here, we present an extensive analysis of the test-bound proteins.

Numerical simulation on 90° impact test of aluminium alloy wheel with the effect of tyre.

Car wheels are crucial to automobile safety, requiring a rigorous test before production. A 90° impact test simulates the frontal impact and its influences on the wheel structure, replicating dynamic driving conditions. A novel modelling approach is illustrated for the 90° impact test simulation and investigates the feasibility of excluding the tyre.

EspH utilizes phosphoinositide and Rab binding domains to interact with plasma membrane infection sites and Rab GTPases.

Enteropathogenic (EPEC) is a Gram-negative bacterial pathogen that causes persistent diarrhea. Upon attachment to the apical plasma membrane of the intestinal epithelium, the pathogen translocates virulence proteins called effectors into the infected cells. These effectors hijack numerous host processes for the pathogen's benefit.

Purification and Quality Control of Recombinant Proteins Expressed in Mammalian Cells: A Practical Review.

In the recent years, there has been a rapid development of new technologies and strategies when it comes to protein purification and quality control (QC), but the basic technologies for these processes go back a long way, with many improvements over the past few decades. The purpose of this chapter is to review these approaches, as well as some other topics such as the advantages and disadvantages of various purification methods for intracellular or extracellular proteins, the most effective and widely used genetically engineered affinity tags, solubility-enhancing tags, and specific proteases for removal of nontarget sequences. Affinity chromatography (AC), like Protein A or G resins for the recovery of antibodies or Fc fusion proteins or immobilized metals for the recovery of histidine-tagged proteins, will be discussed along with other conventional chromatography techniques: ion exchange (IEC), hydrophobic exchange (HEC), mixed mode (MMC), size exclusion (SEC), and ultrafiltration (UF) systems.

Machine-Learning Assisted Screening of Correlated Covariates: Application to Clinical Data of Desipramine.

Stepwise covariate modeling (SCM) has a high computational burden and can select the wrong covariates. Machine learning (ML) has been proposed as a screening tool to improve the efficiency of covariate selection, but little is known about how to apply ML on actual clinical data. First, we simulated datasets based on clinical data to compare the performance of various ML and traditional pharmacometrics (PMX) techniques with and without accounting for highly-correlated covariates.

Deep sequencing of Phox2a nuclei reveals five classes of anterolateral system neurons.

The anterolateral system (ALS) is a major ascending pathway from the spinal cord that projects to multiple brain areas and underlies the perception of pain, itch, and skin temperature. Despite its importance, our understanding of this system has been hampered by the considerable functional and molecular diversity of its constituent cells. Here, we use fluorescence-activated cell sorting to isolate ALS neurons belonging to the Phox2a-lineage for single-nucleus RNA sequencing.

CISD3/MiNT is required for complex I function, mitochondrial integrity, and skeletal muscle maintenance.

Mitochondria play a central role in muscle metabolism and function. A unique family of iron-sulfur proteins, termed CDGSH Iron Sulfur Domain-containing (CISD/NEET) proteins, support mitochondrial function in skeletal muscles. The abundance of these proteins declines during aging leading to muscle degeneration.

The status of drug evaluation in older adults in the United Kingdom: Bridging the representation gap.

Older adults are persistently underrepresented in clinical drug trials worldwide, despite increasing multiple long-term conditions and significant prescribing in this demographic. We discuss systemic challenges such as the exclusion of people with comorbid conditions and the lack of assessment for comorbidities as modifiers of treatment effects and highlight the rising trend of polypharmacy, especially among the oldest age groups, which is linked to a significant percentage of unplanned hospitalizations and medication errors. The consequences of these trends prompted the United Kingdom National Overprescribing review, culminating in a set of recommendations for drug development tailored to older adults.

Deletion Modulates Cytokine and Extracellular Matrix Expression in Chronic Spinal Cord Injury, Leading to Improved Secondary Damage and Functional Recovery.

Toll-like receptors (TLRs) play an important role in the innate immune response after CNS injury. Although TLR4 is one of the best characterized, its role in chronic stages after spinal cord injury (SCI) is not well understood. We examined the role of TLR4 signaling in injury-induced responses at 1 d, 7 d, and 8 weeks after spinal cord contusion injury in adult female TLR4 null and wild-type mice.

Veterinarians' knowledge and experience of avian influenza and perspectives on control measures in the UK.

Background: The scale of the outbreak of highly pathogenic avian influenza (HPAI) in 2021-23 due to the influenza A/H5N1 virus is unprecedented.

Methods: An online survey was designed to explore veterinarians' experiences of and confidence in treating avian species, experiences of dealing with suspected HPAI and perspectives on control measures in the UK. The survey ran between December 2021 and March 2022.

ADRA2A and IRX1 are putative risk genes for Raynaud's phenomenon.

Raynaud's phenomenon (RP) is a common vasospastic disorder that causes severe pain and ulcers, but despite its high reported heritability, no causal genes have been robustly identified. We conducted a genome-wide association study including 5,147 RP cases and 439,294 controls, based on diagnoses from electronic health records, and identified three unreported genomic regions associated with the risk of RP (p < 5 × 10). We prioritized ADRA2A (rs7090046, odds ratio (OR) per allele: 1.

Deep sequencing of Phox2a nuclei reveals five classes of anterolateral system neurons.

The anterolateral system (ALS) is a major ascending pathway from the spinal cord that projects to multiple brain areas and underlies the perception of pain, itch and skin temperature. Despite its importance, our understanding of this system has been hampered by the considerable functional and molecular diversity of its constituent cells. Here we use fluorescence-activated cell sorting to isolate ALS neurons belonging to the Phox2a-lineage for single-nucleus RNA sequencing.

Orbivirus NS4 Proteins Play Multiple Roles to Dampen Cellular Responses.

Non-structural protein 4 (NS4) of insect-borne and tick-borne orbiviruses is encoded by genome segment 9, from a secondary open reading frame. Though a protein dispensable for bluetongue virus (BTV) replication, it has been shown to counter the interferon response in cells infected with BTV or African horse sickness virus. We further explored the functional role(s) of NS4 proteins of BTV and the tick-borne Great Island virus (GIV).

3D Printing of Personalised Carvedilol Tablets Using Selective Laser Sintering.

Selective laser sintering (SLS) has drawn attention for the fabrication of three-dimensional oral dosage forms due to the plurality of drug formulations that can be processed. The aim of this work was to employ SLS with a CO laser for the manufacturing of carvedilol personalised dosage forms of various strengths. Carvedilol (CVD) and vinylpyrrolidone-vinyl acetate copolymer (Kollidon VA64) blends of various ratios were sintered to produce CVD tablets of 3.

Exploring the responses of smallscale poultry keepers to avian influenza regulations and guidance in the United Kingdom, with recommendations for improved biosecurity messaging.

Understanding how smallscale ('backyard') poultry keepers interpret and respond to governmental directives designed to reduce the transmission of highly pathogenic avian influenza (HPAI) is of paramount importance in preparing for future HPAI outbreaks. Qualitative insights from open questions in an online survey conducted during the 2021-22 HPAI season (1,559 responses) shed light on smallscale poultry keepers' understanding of, and responses to, governmental directives to control HPAI exposure and onwards transmission. A follow-up participatory workshop (21 participants) explored the HPAI-related information sources used by smallscale poultry keepers, their trust in these sources, perceptions of HPAI-related risk, and interpretation of, opinions on and adherence to government regulations and communications regarding biosecurity and housing measures.

Improved Optimization of a Coextrusion Die with a Complex Geometry Using the Coupling Inverse Design Method.

The main challenge in a polymer coextrusion process is to have a good die design prior to the process, which can minimize the geometric errors that are caused by extrusion swell and interface motion. For this purpose, a coupling method of optimization and inverse design for a coextrusion die was studied for a medical striped catheter. In the study, the main material was thermoplastic polyurethane (TPU), and the auxiliary material was TPU filled with 30 wt% barium sulfate.

A conserved arginine within the αC-helix of Erk1/2 is a latch of autoactivation and of oncogenic capabilities.

Eukaryotic protein kinases (EPKs) adopt an active conformation following phosphorylation of a particular activation loop residue. Most EPKs spontaneously autophosphorylate this residue. While structure-function relationships of the active conformation are essentially understood, those of the "prone-to-autophosphorylate" conformation are unclear.

A "Bundle of Care" to Improve Anticoagulation Control in Patients Receiving Warfarin in Uganda and South Africa: Protocol for an Implementation Study.

Background: The quality of warfarin anticoagulation among Sub-Saharan African patients is suboptimal. This is due to several factors, including a lack of standardized dosing algorithms, difficulty in providing timely international normalized ratio (INR) results, a lack of patient feedback on their experiences with treatment, a lack of education on adherence, and inadequate knowledge and training of health care workers. Low quality of warfarin anticoagulation, expressed as time in therapeutic range (TTR), is associated with higher adverse event rates, including bleeding and thrombosis, and ultimately, increased morbidity and mortality.