Limited inbreeding avoidance at the gamete level despite inbreeding depression in Atlantic salmon (Salmo salar).

Inbreeding and the associated increase in homozygosity and potential accumulation of deleterious alleles may reduce fitness in a process known as inbreeding depression. Mechanisms to mitigate reproduction between close relatives, ranging from pre-mating mate choice to post-mating gamete selection, have evolved across taxa. In external fertilisers like Atlantic salmon (Salmo salar), where females have limited control over paternity, mechanisms of inbreeding avoidance can be expected to evolve at the gamete level.

A Multi-Institutional Evaluation of Billing for Tobacco-Cessation Services: Opportunities to Improve Quality and Enhance Revenue Capture.

A recent paper identified significant gaps in billing for tobacco-cessation services for a multihospital health system. Underbilling can reflect poor billing practices, low rates of tobacco-cessation counseling, or a combination of both. The study design was applied to 2 academic medical centers.

Polyglycine-mediated aggregation of FAM98B disrupts tRNA processing in GGC repeat disorders.

Aggregation-prone polyglycine-containing proteins produced from expanded GGC repeats are implicated in an emerging family of neurodegenerative disorders. In this study, we showed that polyglycine itself forms aggregates that incorporate endogenous glycine-rich proteins, including FAM98B, a component of the transfer RNA (tRNA) ligase complex (tRNA-LC) that harbors the most glycine-rich sequence in the human proteome. Through this glycine-rich intrinsically disordered region (IDR), polyglycine sequesters and depletes the tRNA-LC, disrupting tRNA processing.

Acquired resistance to molecularly targeted therapies for cancer.

Acquired resistance to molecularly targeted therapies remains a formidable challenge in the treatment of cancer, despite significant advancements over the last several decades. We critically evaluate the evolving landscape of resistance mechanisms to targeted cancer therapies, with a focus on the genetic, molecular, and environmental contributors across a variety of malignancies. Intrinsic mechanisms such as mutations, drug and drug target modifications, and, notably, the activation of the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/Akt pathways are mechanisms different malignancies use to combat therapeutic effectiveness.

Syntheses of benzothiazole amidoximes and arylimidamides and evaluation of their ADME and DNA binding properties and activity against Trypanosoma brucei.

Novel 6-amidoxime- and 6-arylimidamide-substituted benzothiazoles were synthesised to investigate their activity against Trypanosoma brucei, the causative agent of African trypanosomiasis. Benzothiazole amidoxime 12b, with diethylaminoethyl and fluorine substituents on a phenoxymethylene linker exhibited pronounced (IC = 0.92 μM) and selective (SI = 18) antitrypanosomal activity.

Stage-specific MCM protein expression in : insights into metacyclogenesis and G1 arrested epimastigotes.

is a protozoan parasite that is the etiological agent of Chagas disease, which is endemic to Latin America with reported cases in non-endemic regions such as Europe, Asia, and Oceania due to migration. During its lifecycle, alternates between replicative and non-replicative infective lifeforms. Metacyclogenesis is the most studied transition of the life cycle, where replicative epimastigotes differentiate into infective metacyclic trypomastigotes inside the gut of the triatomine vector.

Low genetic variation and strong genetic structure across a range of geographical scales in European smelt (Osmerus eperlanus L.).

Populations of anadromous European smelt (Osmerus eperlanus L.) are declining across its range with mitigation efforts for this ecologically important species hindered by a lack of demographic information. Here, mitochondrial DNA (mtDNA) and microsatellite analyses were used to describe historical and recurrent demographics for the species across a large part of its range.

New acting derivatives incorporating 1-(4-phenyl)adamantane and 1-(4-phenoxyphenyl)adamantane.

In this work, we describe the design, synthesis and evaluation of novel functionalised 1-(4-phenyl)adamantane and 1-(4-phenoxyphenyl)adamantane derivatives. Based on previous findings, we incorporated a phenyl ring between the adamantane core and the pharmacophoric side chain to enhance the activity and selectivity index (SI). The aromatic imidazolines 1a-d and the linear amidines 2a,b and 3a,b exhibited notable activity against .

Intermittent suppressive posaconazole therapy is ineffective at mitigating cardiac and digestive tract pathologies in an experimental model of chronic Chagas disease.

Infections with cause Chagas disease, a chronic condition that can give rise to debilitating cardiac and/or gastrointestinal damage. However, it is unclear why only ~30% of individuals progress to symptomatic pathology, why this can take decades to become apparent, and why there is such a wide range of disease outcomes. Disease pathology is a long-term cumulative process resulting from collateral damage caused by inflammatory immune responses that continually eliminate transient parasite infections in the heart and/or gastrointestinal tract.

deficiency partially restores defects in -deficient mouse corpus luteum.

Objective: ATP6V0d2 is a subunit of the vacuolar-type H-ATPase (V-ATPase) that pumps H ions into lysosomes. TRPML1 (/) transports cations out of lysosomes. mice recapitulate the lysosomal storage disorder mucolipidosis type IV (MLIV) phenotype.

FcγRIIB (CD32B) antibodies enhance immune responses through activating FcγRs.

Fc receptors (FcR) play a key role in coordinating responses from both the innate and adaptive immune system. The inhibitory Fc gamma receptor (FcγRIIB/CD32B; referred to as FcγRII/CD32 in mice) restrains the immune response, specifically through regulating immunoglobulin G (IgG) effector functions. FcγRII-deficient mice demonstrate elevated incidence and severity of autoimmunity and increased responses to immunization and infections.

Signaling pathway dysregulation in breast cancer.

This article provides a comprehensive analysis of the signaling pathways implicated in breast cancer (BC), the most prevalent malignancy among women and a leading cause of cancer-related mortality globally. Special emphasis is placed on the structural dynamics of protein complexes that are integral to the regulation of these signaling cascades. Dysregulation of cellular signaling is a fundamental aspect of BC pathophysiology, with both upstream and downstream signaling cascade activation contributing to cellular process aberrations that not only drive tumor growth, but also contribute to resistance against current treatments.

LINE-1 ORF1p expression occurs in clear cell ovarian carcinoma precursors and is a candidate blood biomarker.

Long interspersed element 1 (LINE-1) retrotransposons are repetitive sequences that can move within the genome by an autonomous mechanism. To limit their mutagenic potential, benign cells restrict LINE-1 expression through molecular mechanisms such as DNA methylation and histone modification, but these mechanisms are usually impaired in cancer. Clear cell ovarian carcinoma (CCOC) represents 5-10% of ovarian cancers and is thought to arise from endometriosis.

Longer Acting Injectable: Continuous, Linear Release of a Progestin Contraceptive From an Oxidized Porous Silicon Host.

Maintaining stable drug concentrations in the bloodstream is a challenge for injectable hydrophobic progestin contraceptives. This work investigates porous silicon dioxide (pSiO) microparticles as a delivery vehicle for progestins via melt-infiltration of drugs into the mesopores. The pSiO is prepared through electrochemical anodization of single-crystalline silicon followed by thermal oxidation, yielding vertically oriented pores (≈50 nm diameter) with porosity varied (between 35-75%) to optimize drug loading and release.

LINE-1 ORF1p Mimics Viral Innate Immune Evasion Mechanisms in Pancreatic Ductal Adenocarcinoma.

This study uncovers PDAC-specific mechanisms that dampen immune responses to viral-repeat RNA via long interspersed nuclear element 1 ORF1p. Suppression of ORF1p activates antiviral responses, reducing tumor growth and epithelial-mesenchymal transition. High ORF1p expression correlates with poor prognosis, highlighting its potential as a therapeutic target for PDAC.

Targeted detection of endogenous LINE-1 proteins and ORF2p interactions.

Background: Both the expression and activities of LINE-1 (L1) retrotransposons are known to occur in numerous cell-types and are implicated in pathobiological contexts such as aging-related inflammation, autoimmunity, and in cancers. L1s encode two proteins that are translated from bicistronic transcripts. The translation product of ORF1 (ORF1p) has been robustly detected by immunoassays and shotgun mass spectrometry (MS).

A novel DNA repair protein, N-Myc downstream regulated gene 1 (NDRG1), links stromal tumour microenvironment to chemoresistance.

Unlabelled: In pancreatic ductal adenocarcinoma cancer (PDAC) drug resistance is a severe clinical problem and patients relapse within a few months after receiving the standard-of-care chemotherapy. One contributing factor to treatment resistance is the desmoplastic nature of PDAC; the tumours are surrounded by thick layers of stroma composing up to 90% of the tumour mass. This stroma, which is mostly comprised of extracellular matrix (ECM) proteins, is secreted by cancer-associated fibroblasts (CAFs) residing in the tumour microenvironment.

Increased plugging latency in cycling epiERα -/- (Esr1 f/- Wnt7a Cre/+ ) mice.

Wnt7a-Cre is a commonly used driver for generating uterine epithelial conditional knockout mice, such as epiERα -/- (Esr1 f/- Wnt7a Cre/+ ) and epiPR -/- (Pgr f/- Wnt7a Cre/+ ). We noticed that epiERα -/- females, but not epiPR -/- females, have prolonged plugging latency, which is the duration between continuous cohabitation and detection of the first vaginal plug (a sign of mating). Mating occurs in proestrus and/or estrus stages of the estrous cycle.

Exogenous estrogen partially rescues progesterone deficiency and autophagosome enlargement in mouse model with lysosomal storage disorder.

Objective: Female mice exhibit progressive progesterone (P4) deficiency, luteal cell degeneration, and premature embryo implantation failure at 5 months old. We attempted to rescue embryo implantation in non-virgin mice (5-6 months old) with exogenous P4 treatment on days 1.5 post-coitum (D1.

Evaluation of Natural Organic Additives as Eco-friendly Inhibitors for Calcium and Magnesium Scale Formation in Water Systems.

Mineral scale formation reduces the heat transfer efficiency and clogs pipes and valves, increasing power consumption. To address the environmental concerns of conventional scale inhibitors, this paper explores biodegradable and eco-friendly alternatives. It examines the effects of organic additives on calcium (Ca) and magnesium (Mg) scaling in water vaporization.

Optimizing Resident Charge Capture with Disappearing Help Text in Note Templates.

Objective:  This study aimed to assist residents in selecting the correct Current Procedural Terminology (CPT) code for evaluation and management (E/M) services through the addition of disappearing help text into a standardized note template.

Methods:  We created a disappearing text block that summarizes E/M requirements and embedded it into the note template used by residents at a pediatric urgent care clinic. An intervention cohort composed of postgraduate year 1 (PGY 1) residents was instructed to use this note template, while senior residents (PGY 2-3) were instructed to use an identical template that lacked the help text.

Animal models for exploring Chagas disease pathogenesis and supporting drug discovery.

Infections with the parasitic protozoan cause Chagas disease, which results in serious cardiac and/or digestive pathology in 30%-40% of individuals. However, symptomatic disease can take decades to become apparent, and there is a broad spectrum of possible outcomes. The complex and long-term nature of this infection places a major constraint on the scope for experimental studies in humans.

Patient self rated pain: headache versus migraine a retrospective chart review.

Background: The International Classification of Headache Disorders (ICHD-3) uses moderate or severe pain intensity in the diagnostic criterion for migraine. However, few studies have analyzed pain rating on a visual analog scale to identify the numerical intensity that correlates with migraine.

Objective: To evaluate the impact of daily self-rated headache pain among patients with either episodic or chronic migraine.