Quantitative Analysis of Nonhistone Lysine Methylation Sites and Lysine Demethylases in Breast Cancer Cell Lines.

Growing evidence shows that lysine methylation is a widespread protein post-translational modification (PTM) that regulates protein function on histone and nonhistone proteins. Numerous studies have demonstrated that the dysregulation of lysine methylation mediators contributes to cancer growth and chemotherapeutic resistance. While changes in histone methylation are well-documented with extensive analytical techniques available, there is a lack of high-throughput methods to reproducibly quantify changes in the abundances of the mediators of lysine methylation and nonhistone lysine methylation (Kme) simultaneously across multiple samples.

Quantitative analysis of non-histone lysine methylation sites and lysine demethylases in breast cancer cell lines.

Growing evidence shows that lysine methylation is a widespread protein post-translational modification that regulates protein function on histone and non-histone proteins. Numerous studies have demonstrated that dysregulation of lysine methylation mediators contributes to cancer growth and chemotherapeutic resistance. While changes in histone methylation are well documented with extensive analytical techniques available, there is a lack of high-throughput methods to reproducibly quantify changes in the abundances of the mediators of lysine methylation and non-histone lysine methylation (Kme) simultaneously across multiple samples.

Lifespan analysis of repeat expression reveals age-dependent upregulation of HERV-K in the neurotypical human brain.

DNA repetitive sequences (or repeats) comprise over 50% of the human genome and have a crucial regulatory role, specifically regulating transcription machinery. The human brain is the tissue with the highest detectable repeat expression and dysregulations on the repeat activity are related to several neurological and neurodegenerative disorders, as repeat-derived products can stimulate a pro-inflammatory response. Even so, it is unclear how repeat expression acts on the aging neurotypical brain.

Serum Levels of Interleukins in Endometriosis Patients: A Systematic Review and Meta-analysis.

Objective: The aims of this systematic review and meta-analysis were to produce a comprehensive survey of the serum levels of interleukins (ILs) in untreated people with endometriosis compared with people without endometriosis.

Data Sources: A systematic literature search of English language studies within Cinahl, Medline Complete, PubMed, and Scopus from inception to May 2023 was performed.

Methods Of Study Selection: We included studies that compared IL serum levels in people with endometriosis to those without endometriosis.

Real-time teaching and learning: Caregivers teaching infants to descend stairs.

Learning to descend stairs requires motor and cognitive capacities on the part of infants and opportunities for practice and assurance of safety offered by caregivers. The American Academy of Pediatrics prescribes the age strategy to teach toddlers to safely descend stairs but without much consideration for individual differences in infants' skills or caregivers' techniques. The purpose of this study was to observe the natural ways in which caregivers teach infants to descend stairs at home and the extent to which infants abide.

Variation in TAF1 expression in female carrier induced pluripotent stem cells and human brain ontogeny has implications for adult neostriatum vulnerability in X-linked Dystonia Parkinsonism.

X-linked Dystonia-Parkinsonism (XDP) is an inherited, X-linked, adult-onset movement disorder characterized by degeneration in the neostriatum. No therapeutics alter disease progression. The mechanisms underlying regional differences in degeneration and adult onset are unknown.

Lifetime stability of social traits in bottlenose dolphins.

Behavioral phenotypic traits or "animal personalities" drive critical evolutionary processes such as fitness, disease and information spread. Yet the stability of behavioral traits, essential by definition, has rarely been measured over developmentally significant periods of time, limiting our understanding of how behavioral stability interacts with ontogeny. Based on 32 years of social behavioral data for 179 wild bottlenose dolphins, we show that social traits (associate number, time alone and in large groups) are stable from infancy to late adulthood.

Congee for the Soul.

Provision of adequate nutrition to elderly patients who develop dysphagia after a stroke can be quite challenging, often leading to the placement of a percutaneous entero-gastrostomy (PEG) tube for nutritional support. This hypothetical case describes the additional challenge of cross-cultural belief that leads a daughter to provide oral feeding to her mother, an act that the medical team believes is dangerous and the daughter sees as salubrious. In this case, what is the proper balance between patient safety and deference to cultural traditions and norms? Where are the limits? Two commentaries offer insights for conflict resolution, including recommending that the medical team seek to understand the cultural motivations of the family, balancing safety and respect for cultural norms.

Retroelement-derived RNA and its role in the brain.

Comprising ~40% of the human genome, retroelements are mobile genetic elements which are transcribed into RNA, then reverse-transcribed into DNA and inserted into a new site in the genome. Retroelements are referred to as "genetic parasites", residing among host genes and relying on host machinery for transcription and evolutionary propagation. The healthy brain has the highest expression of retroelement-derived sequences compared to other somatic tissue, which leads to the question: how does retroelement-derived RNA influence human traits and cellular states? While the functional importance of upregulating retroelement expression in the brain is an active area of research, RNA species derived from retroelements influence both self- and host gene expression by contributing to chromatin remodeling, alternative splicing, somatic mosaicism and translational repression.

Evaluation of both exonic and intronic variants for effects on RNA splicing allows for accurate assessment of the effectiveness of precision therapies.

Elucidating the functional consequence of molecular defects underlying genetic diseases enables appropriate design of therapeutic options. Treatment of cystic fibrosis (CF) is an exemplar of this paradigm as the development of CFTR modulator therapies has allowed for targeted and effective treatment of individuals harboring specific genetic variants. However, the mechanism of these drugs limits effectiveness to particular classes of variants that allow production of CFTR protein.

Potentially lethal cystic fibrosis gene variant in the orangutan.

A syndrome of chronic upper and lower airway disease leading to increased morbidity and mortality occurs primarily in captive orangutans. Similarities in symptoms to the inherited human respiratory disease, cystic fibrosis, led us to hypothesize that orangutan respiratory disease is a result of variants in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. We identified the nonsense variant, c.

Prioritizing Health Equity: Patient Perspectives from a Clinic-Based PhotoVoice Qualitative Study.

This article explores the results of community-engaged PhotoVoice research with the Family Tree Clinic (FTC) in St. Paul, MN. FTC has >45 years of experience providing sexual, reproductive, and primary health care, with a central mission of overcoming issues for their patients including those of poverty, oppression, lack of access, and discrimination in meeting health care needs.

Correlating Cystic Fibrosis Transmembrane Conductance Regulator Function with Clinical Features to Inform Precision Treatment of Cystic Fibrosis.

The advent of precision treatment for cystic fibrosis using small-molecule therapeutics has created a need to estimate potential clinical improvements attributable to increases in cystic fibrosis transmembrane conductance regulator (CFTR) function. To derive CFTR function of a variety of genotypes and correlate with key clinical features (sweat chloride concentration, pancreatic exocrine status, and lung function) to develop benchmarks for assessing response to CFTR modulators. CFTR function assigned to 226 unique genotypes was correlated with the clinical data of 54,671 individuals enrolled in the Clinical and Functional Translation of CFTR (CFTR2) project.

Capitalizing on the heterogeneous effects of CFTR nonsense and frameshift variants to inform therapeutic strategy for cystic fibrosis.

CFTR modulators have revolutionized the treatment of individuals with cystic fibrosis (CF) by improving the function of existing protein. Unfortunately, almost half of the disease-causing variants in CFTR are predicted to introduce premature termination codons (PTC) thereby causing absence of full-length CFTR protein. We hypothesized that a subset of nonsense and frameshift variants in CFTR allow expression of truncated protein that might respond to FDA-approved CFTR modulators.

Functional Assays Are Essential for Interpretation of Missense Variants Associated with Variable Expressivity.

Missense DNA variants have variable effects upon protein function. Consequently, interpreting their pathogenicity is challenging, especially when they are associated with disease variability. To determine the degree to which functional assays inform interpretation, we analyzed 48 CFTR missense variants associated with variable expressivity of cystic fibrosis (CF).

Systematic Computational Identification of Variants That Activate Exonic and Intronic Cryptic Splice Sites.

We developed a variant-annotation method that combines sequence-based machine-learning classification with a context-dependent algorithm for selecting splice variants. Our approach is distinctive in that it compares the splice potential of a sequence bearing a variant with the splice potential of the reference sequence. After training, classification accurately identified 168 of 180 (93.

Community pharmacist-delivered Medicare Annual Wellness Visits within a family medicine practice.

Objective: To identify the steps to implement a community pharmacist into a family medicine practice to deliver Medicare Annual Wellness Visits (AWVs).

Setting: Medicine Mart Pharmacy is a locally owned and operated pharmacy that has served the West Columbia, SC, area for over 30 years. The services offered by the pharmacy have expanded over the past 3 years through the addition of a community pharmacy resident.

A sequence upstream of canonical PDZ-binding motif within CFTR COOH-terminus enhances NHERF1 interaction.

The development of cystic fibrosis transmembrane conductance regulator (CFTR) targeted therapy for cystic fibrosis has generated interest in maximizing membrane residence of mutant forms of CFTR by manipulating interactions with scaffold proteins, such as sodium/hydrogen exchange regulatory factor-1 (NHERF1). In this study, we explored whether COOH-terminal sequences in CFTR beyond the PDZ-binding motif influence its interaction with NHERF1. NHERF1 displayed minimal self-association in blot overlays (NHERF1, K = 1,382 ± 61.

Catalytic, Cascade Ring-Opening Benzannulations of 2,3-Dihydrofuran O,O- and N,O-Acetals.

An Al(OTf)3 -catalyzed intramolecular cascade ring-opening benzannulation of 2,3-dihydrofuran O,O- and N,O-acetals is described. The cascade sequence involves the dihydrofuran ring-opening by acetal hydrolysis, an intramolecular Prins-type cyclization, and aromatization to generate an array of benzo-fused (hetero)aromatic systems in up to 95 % yield. This method represents the first example of dihydrofuran acetal usage in benzannulation reactions.

Loss of carbonic anhydrase XII function in individuals with elevated sweat chloride concentration and pulmonary airway disease.

Elevated sweat chloride levels, failure to thrive (FTT), and lung disease are characteristic features of cystic fibrosis (CF, OMIM #219700). Here we describe variants in CA12 encoding carbonic anhydrase XII in two pedigrees exhibiting CF-like phenotypes. Exome sequencing of a white American adult diagnosed with CF due to elevated sweat chloride, recurrent hyponatremia, infantile FTT and lung disease identified deleterious variants in each CA12 gene: c.

Electrochemical Synthesis of Binary and Ternary Niobium-Containing Oxide Electrodes Using the p-Benzoquinone/Hydroquinone Redox Couple.

New electrochemical synthesis methods have been developed to obtain layered potassium niobates, KNb3O8 and K4Nb6O17, and perovskite-type KNbO3 as film-type electrodes. The electrodes were synthesized from aqueous solutions using the redox chemistry of p-benzoquinone and hydroquinone to change the local pH at the working electrode to trigger deposition of desired phases. In particular, the utilization of electrochemically generated acid via the oxidation of hydroquinone for inorganic film deposition was first demonstrated in this study.

Catalytic, formal homo-Nazarov-type cyclizations of alkylidene cyclopropane-1,1-ketoesters: access to functionalized arenes and heteroaromatics.

A catalytic, formal homo-Nazarov-type cyclization of alkylidene cyclopropanes (ACPs) to give functionalized arenes and heteroaromatics is reported. In the presence of a Lewis acid catalyst, the ACP 1,1-ketoesters undergo distal bond cleavage to afford an allyl cation intermediate. Adjacent π-attack on the allyl cation then provides a six-membered ring that undergoes rapid aromatization.

Parenting with a disability and child mental health: a propensity score analysis.

Little research has examined the impact of having a parent with a disability on child mental health. This study used data from 7,116 families of children who participated in the 2006 National Health Interview Survey and propensity score matching (PSM) to investigate this question. Prior to PSM, differences in Child Mental Health Brief scores were significant with a moderate effect size.