Antibody landscape of C57BL/6 mice cured of B78 melanoma via immunotherapy.

Hoefges et al. utilized a whole-proteome peptide array approach to show that C57BL/6 mice develop a large repertoire of antibodies against linear peptide sequences of their melanoma after receiving a curative immunotherapy regimen consisting of radiation and an immunocytokine. Antibodies can play an important role in innate and adaptive immune responses against cancer, and in preventing infectious disease.

Diversifying Amino Acids and Peptides via Deaminative Reductive Cross-Couplings Leveraging High-Throughput Experimentation.

A deaminative reductive coupling of amino acid pyridinium salts with aryl bromides has been developed to enable efficient synthesis of noncanonical amino acids and diversification of peptides. This method transforms natural, commercially available lysine, ornithine, diaminobutanoic acid, and diaminopropanoic acid to aryl alanines and homologated derivatives with varying chain lengths. Attractive features include ability to transverse scales, tolerance of pharma-relevant (hetero)aryls and biorthogonal functional groups, and the applicability beyond monomeric amino acids to short and macrocyclic peptide substrates.

Exploration of the Nuclear Proteomes in the Ciliate .

Nuclear dimorphism is a fundamental feature of ciliated protozoa, which have separate somatic and germline genomes in two distinct organelles within a single cell. The transcriptionally active somatic genome, contained within the physically larger macronucleus, is both structurally and functionally different from the silent germline genome housed in the smaller micronucleus. This difference in genome architecture is particularly exaggerated in , in which the somatic genome comprises tens of thousands of gene-sized nanochromosomes maintained at a high and variable ploidy, while the germline has a diploid set of megabase-scale chromosomes.

Limits to Gauge Coupling in the Dark Sector Set by the Nonobservation of Instanton-Induced Decay of Super-Heavy Dark Matter in the Pierre Auger Observatory Data.

Instantons, which are nonperturbative solutions to Yang-Mills equations, provide a signal for the occurrence of quantum tunneling between distinct classes of vacua. They can give rise to decays of particles otherwise forbidden. Using data collected at the Pierre Auger Observatory, we search for signatures of such instanton-induced processes that would be suggestive of super-heavy particles decaying in the Galactic halo.

Implications of Social Determinants of Health Characteristics on Fetal Growth Restriction Among Various Racial/Ethnic Groups.

Objectives: Current knowledge regarding the relationship between social determinants of health (SDOH) characteristics of hospitalized American pregnant women and fetal growth restriction (FGR) reveals a dearth in the literature. Therefore, we examined the impact of SDOH on FGR among hospitalized American women in this study.

Methods: Using the Nationwide Inpatient Sample (NIS) dataset for the years 2016-2018, we conducted this cross-sectional study.

Anti-CRISPR Protein AcrIIC5 Inhibits CRISPR-Cas9 by Occupying the Target DNA Binding Pocket.

Anti-CRISPR proteins inhibit CRISPR-Cas immune systems through diverse mechanisms. Previously, the anti-CRISPR protein AcrIIC5 was shown to potently inhibit a type II-C Cas9 from Neisseria meningitidis (Nme1Cas9). In this work, we explore the mechanism of activity of the AcrIIC5 homologue from Neisseria chenwenguii (AcrIIC5) and show that it prevents Cas9 binding to target DNA.

Factors Associated With Unplanned Reoperation After 4-Corner Arthrodesis: A Study of 478 Wrists.

Purpose: The 4-corner arthrodesis (FCA) is a reliable, motion-sparing technique used to treat scapholunate advanced collapse and scaphoid nonunion advanced collapse arthritis, particularly in stage III wrists in which the capitolunate articulation is compromised. Surgical technique and patient-level variables may influence complications following FCA. We sought to evaluate the rate of complications in a large, combined database and manual chart review study.

GWAS on Imputed Whole-Genome Sequence Variants Reveal Genes Associated with Resistance to in Rainbow Trout ().

Genome-wide association studies (GWAS) allow the identification of associations between genetic variants and important phenotypes in domestic animals, including disease-resistance traits. Whole Genome Sequencing (WGS) data can help increase the resolution and statistical power of association mapping. Here, we conduced GWAS to asses he facultative intracellular bacterium , which affects farmed rainbow trout, , in Chile using imputed genotypes at the sequence level and searched for candidate genes located in genomic regions associated with the trait.

Soluble CD25 imposes a low-zone IL-2 signaling environment that favors competitive outgrowth of antigen-experienced CD25 regulatory and memory T cells.

This study focused on soluble (s)CD25-mediated regulation of IL-2 signaling in murine and human CD4 T cells. Recombinant sCD25 reversibly sequestered IL-2 to limit acute maximal proliferative responses while preserving IL-2 bioavailability to subsequently maintain low-zone IL-2 signaling during prolonged culture. By inhibiting IL-2 signaling during acute activation, sCD25 suppressed T-cell growth and inhibited IL-2-evoked transmembrane CD25 expression, thereby resulting in lower prevalence of CD25 T cells.

Loss of epigenetic information as a cause of mammalian aging.

All living things experience an increase in entropy, manifested as a loss of genetic and epigenetic information. In yeast, epigenetic information is lost over time due to the relocalization of chromatin-modifying proteins to DNA breaks, causing cells to lose their identity, a hallmark of yeast aging. Using a system called "ICE" (inducible changes to the epigenome), we find that the act of faithful DNA repair advances aging at physiological, cognitive, and molecular levels, including erosion of the epigenetic landscape, cellular exdifferentiation, senescence, and advancement of the DNA methylation clock, which can be reversed by OSK-mediated rejuvenation.

Active visual search in naturalistic environments reflects individual differences in classic visual search performance.

Visual search is a ubiquitous activity in real-world environments. Yet, traditionally, visual search is investigated in tightly controlled paradigms, where head-restricted participants locate a minimalistic target in a cluttered array that is presented on a computer screen. Do traditional visual search tasks predict performance in naturalistic settings, where participants actively explore complex, real-world scenes? Here, we leverage advances in virtual reality technology to test the degree to which classic and naturalistic search are limited by a common factor, set size, and the degree to which individual differences in classic search behavior predict naturalistic search behavior in a large sample of individuals (N = 75).

Characterizing crosstalk in epigenetic signaling to understand disease physiology.

Epigenetics, the inheritance of genomic information independent of DNA sequence, controls the interpretation of extracellular and intracellular signals in cell homeostasis, proliferation and differentiation. On the chromatin level, signal transduction leads to changes in epigenetic marks, such as histone post-translational modifications (PTMs), DNA methylation and chromatin accessibility to regulate gene expression. Crosstalk between different epigenetic mechanisms, such as that between histone PTMs and DNA methylation, leads to an intricate network of chromatin-binding proteins where pre-existing epigenetic marks promote or inhibit the writing of new marks.

The influence of accessory dwelling unit (ADU) policy on the contributing factors to ADU development: an assessment of the city of Los Angeles.

Since the accessory dwelling unit (ADU) has emerged as a policy alternative to increase housing stock and provide affordable options for areas impacted by housing shortages, many local governments recently adopted ADU policies that promote the construction of ADUs. Taking the City of Los Angeles as the study area, this paper examines how the city's ADU ordinance impacts the relationship of the characteristics of the properties and neighborhoods with ADU development by constructing multilevel logistic regression models. The outputs of the models suggest that the ordinance contributes to diversifying the types and locations of the properties and neighborhoods where ADUs are built.

Targets, Mechanisms and Cytotoxicity of Half-Sandwich Ir(III) Complexes Are Modulated by Structural Modifications on the Benzazole Ancillary Ligand.

Cancers are driven by multiple genetic mutations but evolve to evade treatments targeting specific mutations. Nonetheless, cancers cannot evade a treatment that targets mitochondria, which are essential for tumor progression. Iridium complexes have shown anticancer properties, but they lack specificity for their intracellular targets, leading to undesirable side effects.

Experiential values are underweighted in decisions involving symbolic options.

Standard models of decision-making assume each option is associated with subjective value, regardless of whether this value is inferred from experience (experiential) or explicitly instructed probabilistic outcomes (symbolic). In this study, we present results that challenge the assumption of unified representation of experiential and symbolic value. Across nine experiments, we presented participants with hybrid decisions between experiential and symbolic options.

Unknown Metabolite Identification Using Machine Learning Collision Cross-Section Prediction and Tandem Mass Spectrometry.

Ion mobility (IM) spectrometry provides semiorthogonal data to mass spectrometry (MS), showing promise for identifying unknown metabolites in complex non-targeted metabolomics data sets. While current literature has showcased IM-MS for identifying unknowns under near ideal circumstances, less work has been conducted to evaluate the performance of this approach in metabolomics studies involving highly complex samples with difficult matrices. Here, we present a workflow incorporating molecular formula annotation and MS/MS structure elucidation using SIRIUS 4 with experimental IM collision cross-section (CCS) measurements and machine learning CCS predictions to identify differential unknown metabolites in mutant strains of .

Does Size Matter? On the Role of Stereotactic Radiosurgery for Large Vestibular Schwannomas as Seen in an Institutional Experience of Gamma Knife Radiosurgery for High-Grade Tumors.

Objective: Management of large vestibular schwannoma (VS) is controversial. Surgery has historically been the treatment of choice, but emerging literature suggests that definitive stereotactic radiosurgery is feasible. We report our institutional experience of control and morbidity outcomes treating Koos grade 3-4 VS with Gamma Knife radiosurgery (GKRS).

Is anticholinergic and sedative drug burden associated with postdischarge institutionalization in community-dwelling older patients acutely admitted to hospital? A Norwegian registry-based study.

Purpose: Investigate the association between anticholinergic (AC) and sedative (SED) drug burden before hospitalization and postdischarge institutionalization (PDI) in community-dwelling older patients acutely admitted to hospital.

Methods: A cross-sectional study using data from the Norwegian Patient Registry and the Norwegian Prescription Database. We studied acutely hospitalized community-dwelling patients ≥70 years during 2013 (N = 86 509).

Corrigendum: Modulation of leukocyte subsets mobilization in response to exercise by water immersion recovery.

[This corrects the article DOI: 10.3389/fphys.2022.