Silver Oxide Promoted Synthesis of Alpha -GalNAc Containing Glyco-Amino Acids: Synthesis of Core 2 Containing Glyco-Amino Acids for Solid Phase Synthesis of Glycopeptides.

-GalNAc glycans on glycoproteins with eight different core structures sharing a common α-glycosidic linkage (-GalNAc-α-Ser/Thr) are critical in various physiological and pathological processes. Among the eight -GalNAc glycan cores, core 2 characterized by a GlcNAcβ1-6(Galβ1-3)GalNAc structural motif plays a significant role in regulating diverse biological processes, such as immune response modulation, adhesive properties of selectins, and gastrointestinal tract protection. However, the large-quantity synthesis of core 2 containing glyco-amino acids for downstream solid-phase peptide synthesis is challenging.

Design of high specificity binders for peptide-MHC-I complexes.

Class I MHC molecules present peptides derived from intracellular antigens on the cell surface for immune surveillance, and specific targeting of these peptide-MHC (pMHC) complexes could have considerable utility for treating diseases. Such targeting is challenging as it requires readout of the few outward facing peptide antigen residues and the avoidance of extensive contacts with the MHC carrier which is present on almost all cells. Here we describe the use of deep learning-based protein design tools to design small proteins that arc above the peptide binding groove of pMHC complexes and make extensive contacts with the peptide.

Tracking flaviviral protease conformational dynamics by tuning single-molecule nanopore tweezers.

The flaviviral NS2B/NS3 protease is a conserved enzyme required for flavivirus replication. Its highly dynamic conformation poses major challenges but also offers opportunities for antiviral inhibition. Here, we established a nanopore tweezers-based platform to monitor NS2B/NS3 conformational dynamics in real time.

Lysosomal enzyme binding to the cation-independent mannose 6-phosphate receptor is regulated allosterically by insulin-like growth factor 2.

The cation-independent mannose 6-phosphate receptor (CI-MPR) is clinically significant in the treatment of patients with lysosomal storage diseases because it functions in the biogenesis of lysosomes by transporting mannose 6-phosphate (M6P)-containing lysosomal enzymes to endosomal compartments. CI-MPR is multifunctional and modulates embryonic growth and fetal size by downregulating circulating levels of the peptide hormone insulin-like growth factor 2 (IGF2). The extracellular region of CI-MPR comprises 15 homologous domains with binding sites for M6P-containing ligands located in domains 3, 5, 9, and 15, whereas IGF2 interacts with residues in domain 11.

Telephone cord blister formation in solvent swollen elastomer films.

Video imaging was used to study large-slope folded telephone cord blister formation in solvent swollen films of polydimethylsiloxane (PDMS) elastomers. Chlorobenzene, chloroform, heptane and toluene were used to swell PDMS films with thickness values in the range 15 μm < < 223 μm supported on glass substrates. Measurements of the blister width, corrugation wavelength and blister growth speed were studied as a function of the film thickness for all four solvents.

Hypertonic Saline Nasal Rinse Intervention: Immunomodulatory Effects in Dairy Workers.

Objective: Increased risk of occupational exposure to bioaerosols has long been recognized in livestock operations including dairy facilities. Spanning the inhalable fraction (0-100 μm), dairy bioaerosols comprise a wide variety of inflammatory components that deposit in the nasopharyngeal region. The resultant inflammatory response from bioaerosol exposure is likely driving the increased prevalence of respiratory disease observed in dairy workers.

Glycopolymeric Nanoparticles Enrich Less Immunogenic Protein Coronas, Reduce Mononuclear Phagocyte Clearance, and Improve Tumor Delivery Compared to PEGylated Nanoparticles.

Nanoparticles (NPs) offer significant promise as drug delivery vehicles; however, their efficacy is often hindered by the formation of a protein corona (PC), which influences key physiological responses such as blood circulation time, biodistribution, cellular uptake, and intracellular localization. Understanding NP-PC interactions is crucial for optimizing NP design for biomedical applications. Traditional approaches have utilized hydrophilic polymer coatings like polyethylene glycol (PEG) to resist protein adsorption, but glycopolymer-coated nanoparticles have emerged as potential alternatives due to their biocompatibility and ability to reduce the adsorption of highly immunogenic proteins.

A pilot study to establish feasibility and acceptability of a yoga and self-management education intervention to support caregivers and care receivers with persistent pain.

Introduction: Approximately 75% of caregivers providing unpaid care to family members or friends experience persistent pain. Simultaneously, individuals who require caregiving commonly experience pain. The inherent complexity of pain is enhanced by relationship dynamics of two closely tied individuals (i.

Role of the SAF-A SAP domain in X inactivation, transcription, splicing, and cell proliferation.

SAF-A is conserved throughout vertebrates and has emerged as an important factor regulating a multitude of nuclear functions, including lncRNA localization, gene expression, and splicing. SAF-A has several functional domains, including an N-terminal SAP domain that binds directly to DNA. Phosphorylation of SAP domain serines S14 and S26 are important for SAF-A localization and function during mitosis, however whether these serines are involved in interphase functions of SAF-A is not known.

Surface water quality database for five watersheds in the Arequipa region of Southern Peru.

Though surface water quality has been monitored in southern Peru over the past and current century, it has been implemented by multiple organizations. The data lacks a centralized repository and access requires logistical and temporal hurdles associated with official requests. A substantial portion of the data has not been quality assured and is in difficult-to-access formats such as scanned PDF documents.

Clinical, pharmacological, and qualitative characterization of drug-drug interactions in pregnant women initiating HIV therapy in Sub-Saharan Africa.

Background: We investigated the impact of Drug-Drug Interactions (DDIs) on virologic control among HIV-positive pregnant women initiating antiretroviral therapy while identifying drivers for Traditional Medicine (TM) use and exploring the nature and extent of TM-related DDIs.

Methods: Employing a three-pronged approach, we examined DDIs arising from comedication, including TM, in ART. The DolPHIN-2 trial (NCT03249181) randomized 268 HIV-positive pregnant women in Uganda and South Africa to dolutegravir (DTG)-based (135) or efavirenz-based (133) regimens while systematically recording comedications and screening for DDIs.

A mapped dataset of surface ocean acidification indicators in large marine ecosystems of the United States.

Mapped monthly data products of surface ocean acidification indicators from 1998 to 2022 on a 0.25° by 0.25° spatial grid have been developed for eleven U.

Validation of an Instrument That Measures Factors Affecting Saudi Parents' Tolerance of Risky Play: A Rasch Analysis.

Importance: Benefits of children's participation in risky play are broadly recognized. However, most related research originates in Western countries; none focuses on outdoor play in Eastern countries, including Saudi Arabia. Furthermore, although the literature identifies varying perspectives on risky play among parents, there is no objective measure to assess personal, situational, and cultural factors shaping their risk tolerance.

Tuning single-molecule ClyA nanopore tweezers for real-time tracking of the conformational dynamics of West Nile viral NS2B/NS3 protease.

The flaviviral NS2B/NS3 protease is a conserved enzyme required for flavivirus replication. Its highly dynamic conformation poses major challenges but also offers opportunities for antiviral inhibition. Here, we established a nanopore tweezers-based platform to monitor NS2B/NS3 conformational dynamics in real-time.

Evaluation of hospital-onset bacteraemia and fungaemia in the USA as a potential healthcare quality measure: a cross-sectional study.

Background: Hospital-onset bacteraemia and fungaemia (HOB) is being explored as a surveillance and quality metric. The objectives of the current study were to determine sources and preventability of HOB in hospitalised patients in the USA and to identify factors associated with perceived preventability.

Methods: We conducted a cross-sectional study of HOB events at 10 academic and three community hospitals using structured chart review.

The Intersection of Chronic Kidney Disease and Depression.

Chronic kidney disease (CKD) and depression often coexist, resulting in a complex interaction that can be detrimental to patient outcomes. This article examines the reciprocal association between CKD and depression, with a focus on the increased incidence of depression and the harmful effects of depressive symptoms among patients with CKD. Next, it investigates the role CKD plays as a risk factor for the onset and worsening of depression because symptoms of depression may interfere with the progression of CKD.

Opt-Out Syphilis Screening at an Urgent Care Center in Atlanta: Evaluation of a Pilot Program.

Background: Human immunodeficiency virus (HIV) and syphilis disproportionately impact communities with low access to primary care, who often utilize urgent care centers (UCCs) for sexual health care. UCC visits represent an opportunity for identification and treatment of syphilis and linkage to HIV testing and prevention services. We describe a universal, opt-out syphilis screening program pilot at an Atlanta UCC.

Transcatheter Edge-to-Edge Mitral Valve Repair in a Patient With Anderson-Fabry Disease.

Severe degenerative mitral regurgitation (DMR) is one cardiac manifestation of the multiorgan metabolic enzyme disorder Anderson-Fabry Disease (AFD). Although DMR is normally managed surgically, many patients with AFD are unsuitable for this. We present the first case of mitral transcatheter edge-to-edge repair in a patient with AFD.

Hyaluronidase impacts exposures of long-acting injectable paliperidone palmitate in rodent models.

A significant challenge in the development of long-acting injectable drug formulations, especially for anti-infective agents, is delivering an efficacious dose within a tolerable injection volume. Co-administration of the extracellular matrix-degrading enzyme hyaluronidase can increase maximum tolerable injection volumes but is untested for this benefit with long-acting injectable formulations. One concern is that hyaluronidase could potentially alter the tissue response surrounding an injection depot, a response known to be important for drug release kinetics of long-acting injectable formulations.

Response to Dabrafenib Plus Trametinib in a Patient With an Uncommon Activating BRAF Mutation: A First in Non-Small Cell Lung Cancer.

Mutations in BRAF are present in 4% of non-small cell lung cancer (NSCLC), of which half are well-characterized activating variants affecting codon 600 (classified as class I). These mutations, most commonly BRAF V600E, have been associated with response to BRAF/MEK-directed small molecule kinase inhibitors. NSCLC with kinase-activating BRAF mutations occurring at other codons (class II variants) represent a substantial portion of BRAF-mutated NSCLC, but use of targeted therapy in these tumors is still under investigation.