Computational analysis of the alpha-2 domain of apolipoprotein B - 100, a potential triggering factor in LDL aggregation.

Atherosclerosis, the major underlying cause of cardiovascular disease, is believed to arise from the accumulation of low-density lipoprotein (LDL) in the arterial subendothelial space, ultimately leading to plaque formation. It is proposed that the accumulation of LDL is linked to its intrinsic aggregation propensity. Although the native LDL is not prone to aggregation, LDL(-), an electronegative LDL characterized in the plasma, has been shown to prime LDL aggregation in a domino-like behavior similar to amyloidogenic proteins.

Effect of a SARS-CoV-2 Protein Fragment on the Amyloidogenic Propensity of Human Islet Amyloid Polypeptide.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the onset of COVID-19 have been linked to an increased risk of developing type 2 diabetes. While a variety of mechanisms may ultimately be responsible for the onset of type 2 diabetes under these circumstances, one mechanism that has been postulated involves the increased aggregation of human islet amyloid polypeptide (hIAPP) through direct interaction with SARS-CoV-2 viral proteins. Previous computational studies investigating this possibility revealed that a nine-residue peptide fragment known as SK9 (SFYVYSRVK) from the SARS-CoV-2 envelope protein can stabilize the native conformation of hIAPP by interacting with the N-terminal region of amylin.

Key charged residues influence the amyloidogenic propensity of the helix-1 region of serum amyloid A.

Increased plasma levels of serum amyloid A (SAA), an acute-phase protein that is secreted in response to inflammation, may lead to the accumulation of amyloid in various organs thereby obstructing their functions. Severe cases can lead to a systemic disorder called AA amyloidosis. Previous studies suggest that the N-terminal helix is the most amyloidogenic region of SAA.

Emerging from the pandemic: instructor reflections and students' perceptions on an introductory programming course in blended learning.

Teaching an introductory programming course to first-year students has long been a challenge for many college instructors. The COVID-19 pandemic, which caused unprecedented shifts in learning modality across the globe, has worsened the learning experience of novice programmers. Instructors have to find innovative ways to keep students engaged and learning.

Engagement in Care Among Newly Diagnosed HIV-Positive Gay, Bisexual, and Other Men Who Have Sex With Men in the United States: Results From the Together 5,000 Study.

One-quarter of gay, bisexual, and other men who have sex with men (GBMSM) with diagnosed HIV are not engaged in HIV care. Between 2018 and 2019, 50 GBMSM completed qualitative interviews 3 months after receiving an HIV-positive result. Interviews explored barriers to and facilitators of engagement and retention in HIV testing and care.

A Non-Invasive Determination of Ketosis-Induced Elimination of Chronic Daytime Somnolence in a Patient with Late-Stage Dementia (Assessed with Type 3 Diabetes): A Potential Role of Neurogenesis.

Background: The study involved a female patient diagnosed with late-stage dementia, with chronic daytime somnolence (CDS) as a prominent symptom.

Objective: To explore whether her dementia resulted from Type 3 diabetes, and whether it could be reversed through ketosis therapy.

Methods: A ketogenic diet (KD) generating low-dose 100 μM Blood Ketone Levels (BKL) enhanced by a brief Ketone Mono Ester (KME) regimen with high-dose 2-4 mM BKLs was used.

Dynamic residential movement and depression among the World Trade Center Health Registry enrollees.

Purpose: Residential instability is associated with poor mental health, but its causal inference is challenging due to time-varying exposure and confounding, and the role of changing social environments. We tested the association between frequent residential moving and depression risk among adults exposed to the 9/11 disaster.

Methods: We used four waves of survey data from the World Trade Center Health Registry.

Clickable, selective, and cell-permeable activity-based probe of human cathepsin B - Minimalistic approach for enhanced selectivity.

Human cathepsin B is a cysteine-dependent protease whose roles in both normal and diseased cellular states remain yet to be fully delineated. This is primarily due to overlapping substrate specificities and lack of unambiguously annotated physiological functions. In this work, a selective, cell-permeable, clickable and tagless small molecule cathepsin B probe, KDA-1, is developed and kinetically characterized.

Alterations of elastin in female reproductive tissues arising from advancing parity.

Female reproductive tissues undergo significant alterations during pregnancy, which may compromise the structural integrity of extracellular matrix proteins. Here, we report on modifications of elastic fibers, which are primarily composed of elastin and believed to provide a scaffold to the reproductive tissues, due to parity and parturition. Elastic fibers from the upper vaginal wall of virgin Sprague Dawley rats were investigated and compared to rats having undergone one, three, or more than five pregnancies.

Cell penetrable, clickable and tagless activity-based probe of human cathepsin L.

Human cathepsin L is a ubiquitously expressed endopeptidase and is known to play critical roles in a wide variety of cellular signaling events. Its overexpression has been implicated in numerous human diseases, including highly invasive forms of cancer. Inhibition of cathepsin L is therefore considered a viable therapeutic strategy.

Nanobody-Facilitated Multiparametric PET/MRI Phenotyping of Atherosclerosis.

Objectives: This study sought to develop an integrative positron emission tomography (PET) with magnetic resonance imaging (MRI) procedure for accurate atherosclerotic plaque phenotyping, facilitated by clinically approved and nanobody radiotracers.

Background: Noninvasive characterization of atherosclerosis remains a challenge in clinical practice. The limitations of current diagnostic methods demonstrate that, in addition to atherosclerotic plaque morphology and composition, disease activity needs to be evaluated.

Quantification of desmosine and isodesmosine using MALDI-ion trap tandem mass spectrometry.

Desmosine (Des) and isodesmosine (Isodes), cross-linking amino acids in the biomolecule elastin, may be used as biomarkers for various pathological conditions associated with elastin degradation. The current study presents a novel approach to quantify Des and Isodes using matrix-assisted laser desorption ionization (MALDI)-tandem mass spectrometry (MS) in a linear ion trap coupled to a vacuum MALDI source. MALDI-MS analyses of Des and Isodes are performed using stable-isotope-labeled desmosine d (labeled-Des) as an internal standard in different biological fluids, such as urine and serum.

Development and Multiparametric Evaluation of Experimental Atherosclerosis in Rabbits.

Several animal models have been developed to study atherosclerosis. Here we present a rabbit atherosclerosis model generated by surgical denudation of the aortic endothelium in combination with a high-fat and cholesterol-enriched diet. This model is characterized by the formation of vascular lesions that exhibit several hallmarks of human atherosclerosis.

The Association Between Fraternal Birth Order and Anal-Erotic Roles of Men Who Have Sex with Men.

The fraternal birth order effect (FBOE) describes the phenomenon that homosexual men tend to have a greater number of older brothers than do heterosexual men. The FBOE is a marker for an innate, biological predisposition for androphilia in genotypic males. The FBOE has been studied since the 1930s and is the most consistent biodemographic correlate of sexual orientation in men.

PET/MR Imaging of Malondialdehyde-Acetaldehyde Epitopes With a Human Antibody Detects Clinically Relevant Atherothrombosis.

Background: Oxidation-specific epitopes (OSEs) are proinflammatory, and elevated levels in plasma predict cardiovascular events.

Objectives: The purpose of this study was to develop novel positron emission tomography (PET) probes to noninvasively image OSE-rich lesions.

Methods: An antigen-binding fragment (Fab) antibody library was constructed from human fetal cord blood.

Substitutions in conserved regions preceding and within the linker affect activity and flexibility of tRNase ZL, the long form of tRNase Z.

The enzyme tRNase Z, a member of the metallo-β-lactamase family, endonucleolytically removes 3' trailers from precursor tRNAs, preparing them for CCA addition and aminoacylation. The short form of tRNase Z, tRNase ZS, functions as a homodimer and is found in all prokaryotes and some eukaryotes. The long form, tRNase ZL, related to tRNase ZS through tandem duplication and found only in eukaryotes, possesses ~2,000-fold greater catalytic efficiency than tRNase ZS.

Ultraviolet radiation reduces desmosine cross-links in elastin.

Elastic fibers, a major component of the extracellular matrix of the skin, are often exposed to ultraviolet (UV) radiation throughout mammalian life. We report on an study of the alterations in bovine nuchal ligament elastic fibers resulting from continuous UV-A exposure by the use of transmission electron microscopy (TEM), histology, mass spectrometry, and solid state C NMR methodologies. TEM images reveal distinct cracks in elastic fibers as a result of UV-A irradiation and histological measurements show a disruption in the regular array of elastic fibers present in unirradiated samples; elastic fibers appear shorter, highly fragmented, and thinner after UV-A treatment.

A systematic comparison of clinically viable nanomedicines targeting HMG-CoA reductase in inflammatory atherosclerosis.

Atherosclerosis is a leading cause of worldwide morbidity and mortality whose management could benefit from novel targeted therapeutics. Nanoparticles are emerging as targeted drug delivery systems in chronic inflammatory disorders. To optimally exploit nanomedicines, understanding their biological behavior is crucial for further development of clinically relevant and efficacious nanotherapeutics intended to reduce plaque inflammation.

Prefrontal and parietal correlates of cognitive control related to the adult outcome of attention-deficit/hyperactivity disorder diagnosed in childhood.

The protracted and highly variable development of prefrontal cortex regions that support cognitive control has been purported to shape the adult outcome of attention-deficit/hyperactivity disorder (ADHD). This neurodevelopmental model was tested in a prospectively followed sample of 27 adult probands who were diagnosed with ADHD in childhood and 28 carefully matched comparison subjects aged 21-28 years. Probands were classified with persistent ADHD or remitted ADHD.

Subcellular Parkinson's Disease-Specific Alpha-Synuclein Species Show Altered Behavior in Neurodegeneration.

Parkinson's disease and other synucleinopathies are characterized by the presence of intra-neuronal protein aggregates enriched in the presynaptic protein α-synuclein. α-synuclein is considered an intrinsically disordered 14 kDa monomer, and although poorly understood, its transition to higher-order multimeric species may play central roles in healthy neurons and during Parkinson's disease pathogenesis. In this study, we demonstrate that α-synuclein exists as defined, subcellular-specific species that change characteristics in response to oxidative stress in neuroblastoma cells and in response to Parkinson's disease pathogenesis in human cerebellum and frontal cortex.

Mediators of Outcome in Complicated Grief Treatment.

Objective: In this study, we examined the mechanisms of action of complicated grief treatment (CGT), an efficacious psychotherapy for complicated grief.

Method: We explored 3 putative mediators (guilt/self-blame related to the deceased, negative thoughts about the future, and avoidance) among treatment completers assigned to either CGT (n = 35) or interpersonal psychotherapy (n = 34) in a previously reported randomized controlled trial. Antidepressant use was examined as a moderator of mediation effects.

Graduate Nurse Education in Haiti: Lessons Taught and Learned.

The plight of the people of Haiti that came to the world's attention following the devastating earthquake there in 2010 has for the most part receded into the background amid other issues despite their continuing economic and health problems. The purpose of this article is to explore the experiences of the first graduate nurse students in Haiti. The program is funded and operated by a nonprofit, nongovernment nursing organization, Promoting Health in Haiti, based in New York City.

Promoting weight loss methods in parenting magazines: Implications for women.

Weight gain before and after pregnancy is important for women's health. The purpose of this study was to assess articles and advertisements related to weight loss in three widely read parenting magazines, "Parenting School Years," "Parenting Early Years," and "Parenting," which have an estimated combined readership of approximately 24 million (mainly women readers). Almost a quarter (23.

An Evaluation of the Effectiveness of School-Based Breastfeeding Education.

School-based interventions aimed at modifying the knowledge, attitudes, social norms, and intended future practice regarding breastfeeding may be an effective way of improving breastfeeding rates. A systematic review of relevant literature was conducted to identify scientifically rigorous studies on school-based interventions and promotion activities that focus on breastfeeding. Of the 1990 citations reviewed, only 6 empirical articles on school-based interventions to promote breastfeeding were found and these interventions vary greatly in terms of format, duration, outcome measures, and significance of the results.