Glycoproteogenomics: A Frequent Gene Polymorphism Affects the Glycosylation Pattern of the Human Serum Fetuin/α-2-HS-Glycoprotein.

Fetuin, also known as α-2-HS-glycoprotein (gene name: AHSG), is one of the more abundant glycoproteins secreted into the bloodstream. There are two frequently occurring alleles of human AHSG, resulting in three genotypes (AHSG*1, AHSG*2, and heterozygous AHSG1/2). The backbone amino acid sequences of fetuin coded by the AHSG*1 and AHSG*2 genes differ in two amino acids including one known O-glycosylation site (aa position 256).

Androgens Drive Sex Biases in Hypothalamic Corticotropin-Releasing Hormone Gene Expression After Adrenalectomy of Mice.

Although prominent sex differences exist in the hypothalamic-pituitary-adrenal axis's response to stressors, few studies of its regulation in the hypothalamic paraventricular nucleus (PVN) have compared both male and female subjects. In this study, we sought to explore sex differences in the acute regulation of PVN neuropeptide expression following glucocorticoid (GC) removal and the underlying role of gonadal hormones. We first examined the effects of short-term adrenalectomy (ADX) on PVN Crh and arginine vasopressin (Avp) expression in mice using in situ hybridization.

First Community-Wide, Comparative Cross-Linking Mass Spectrometry Study.

The number of publications in the field of chemical cross-linking combined with mass spectrometry (XL-MS) to derive constraints for protein three-dimensional structure modeling and to probe protein-protein interactions has increased during the last years. As the technique is now becoming routine for in vitro and in vivo applications in proteomics and structural biology there is a pressing need to define protocols as well as data analysis and reporting formats. Such consensus formats should become accepted in the field and be shown to lead to reproducible results.

Serine 25 phosphorylation inhibits RIPK1 kinase-dependent cell death in models of infection and inflammation.

RIPK1 regulates cell death and inflammation through kinase-dependent and -independent mechanisms. As a scaffold, RIPK1 inhibits caspase-8-dependent apoptosis and RIPK3/MLKL-dependent necroptosis. As a kinase, RIPK1 paradoxically induces these cell death modalities.

Gaining Confidence in the Elusive Histidine Phosphoproteome.

Recent technological advances have made it possible to investigate the hitherto rather elusive protein histidine phosphorylation. However, confident site-specific localization of protein histidine phosphorylation remains challenging. Here, we address this problem, presenting a mass-spectrometry-based approach that outperforms classical HCD fragmentation without compromising sensitivity.

An Integrated Global Analysis of Compartmentalized HRAS Signaling.

Modern omics technologies allow us to obtain global information on different types of biological networks. However, integrating these different types of analyses into a coherent framework for a comprehensive biological interpretation remains challenging. Here, we present a conceptual framework that integrates protein interaction, phosphoproteomics, and transcriptomics data.

Experimental Evidence of Structural Representation of Hands in Early Infancy.

Hands convey important social information, such as an individual's emotions, goals, and desires, are used to direct attention through pointing, and are a major organ for haptic perception. However, very little is known about infants' representation of human hands. In Experiment 1, infants tested in a familiarization/novelty preference task discriminated between images of intact hands and ones that contained first-order structure distortions (i.

Sex-specific scanning in infancy: Developmental changes in the use of face/head and body information.

The current investigation sought to differentiate between contrasting perspectives of body knowledge development by determining whether infants' adult-like scanning of male and female bodies is dependent on relevant information from the face/head alone, the body alone, or a combination of both sources. Scanning patterns of 3.5-, 6.

Categorical Perception of Facial Emotions in Infancy.

Categorical perception, indicated by superior discrimination between stimuli that cross categorical boundaries than between stimuli within a category, is an efficient manner of classification. The current study examined the development of categorical perception of emotional stimuli in infancy. We used morphed facial images to investigate whether infants find contrasts between emotional facial images that cross categorical boundaries to be more salient than those that do not, while matching the degree of differences in the two contrasts.

Development of a human milk concentrate with human milk lyophilizate for feeding very low birth weight preterm infants: A preclinical experimental study.

Breast milk is considered the gold standard nutritional resource for very low birth weight (VLBW) infants in terms of nutrients and protective factors. If mother's milk is not available, the second choice is donated and fortified human milk (HM) from the Human Milk Bank (HMB). This study hypothesized that HM could be lyophilized and used as an additive to increase the levels of macronutrients and micronutrients available to VLBW infants.

Pre-fractionation Extends but also Creates a Bias in the Detectable HLA Class Ι Ligandome.

HLA class Ι molecules can communicate a range of cellular alterations (mutations, changes in protein copy number, aberrant post-translational modifications, or pathogen proteins) to CD8+ T lymphocytes in the form of HLA peptide ligands. At any given moment, tens of thousands of different self and foreign HLA class Ι peptides may be presented on the cell surface by HLA class Ι complexes. Due to the enormous biochemical diversity and low abundance of each of these peptides, HLA ligandome analysis presents unique challenges.

Proteomic Profiling of Mouse Helper T Cell Differentiation.

Helper T cell differentiation is a key process in the regulation of adaptive immune responses. Here, mouse Th1 and Th2 cells are profiled using high-throughput proteomics to increase the understanding of the molecular biology of Th differentiation to support the design of prophylactic and therapeutic intervention strategies for (infectious) diseases. Protein profiling of Th1/Th2 differentiated cells results in the quantification of almost 6000 proteins of which 41 are differentially expressed at FDR < 0.

Toward an efficient workflow for the analysis of the human milk peptidome.

There is a growing interest for investigating endogenous peptides from human biofluids which may provide yet unknown functional benefits or provide an early indication of disease states as potential biomarkers. A major technical bottleneck in the investigation of endogenous peptides from body fluids, e.g.

PaDuA: A Python Library for High-Throughput (Phospho)proteomics Data Analysis.

The increased speed and sensitivity in mass spectrometry-based proteomics has encouraged its use in biomedical research in recent years. Large-scale detection of proteins in cells, tissues, and whole organisms yields highly complex quantitative data, the analysis of which poses significant challenges. Standardized proteomic workflows are necessary to ensure automated, sharable, and reproducible proteomics analysis.

Discovery and Quantification of Nonhuman Proteins in Human Milk.

The question whether and which nonhuman peptides or proteins are present in human milk was raised many decades ago. However, due to cross-reactivity or nonspecific antibody recognition, the accuracy of detection by immunochemical methods has been a concern. Additionally, the relative low-abundance of nonhuman peptides/proteins in the complex milk sample makes them a challenging target to detect.

Sequences encoding C2H2 zinc fingers inhibit polyadenylation and mRNA export in human cells.

The large C2H2-Zinc Finger (C2H2-ZNF) gene family has rapidly expanded in primates through gene duplication. There is consequently considerable sequence homology between family members at both the nucleotide and amino acid level, allowing for coordinated regulation and shared functions. Here we show that multiple C2H2-ZNF mRNAs experience differential polyadenylation resulting in populations with short and long poly(A) tails.

Parathyroid hormone independent hypercalcemia in adults.

Parathyroid independent hypercalcemia is characterized by suppressed parathyroid hormone (PTH) in the presence of hypercalcemia. Well known causes and mechanisms are redistribution of calcium from the skeleton, by malignant diseases; inadequately increased intestinal calcium uptake mediated by increased vitamin D activity, and reduced renal elimination due to medications. Frequent and infrequent causes are discussed, and more recent mechanistic models presented in this review.

Efficient and robust proteome-wide approaches for cross-linking mass spectrometry.

Cross-linking mass spectrometry (XL-MS) has received considerable interest, owing to its potential to investigate protein-protein interactions (PPIs) in an unbiased fashion in complex protein mixtures. Recent developments have enabled the detection of thousands of PPIs from a single experiment. A unique strength of XL-MS, in comparison with other methods for determining PPIs, is that it provides direct spatial information for the detected interactions.

Label-free targeted LC-ESI-MS analysis of human milk oligosaccharides (HMOS) and related human milk groups with enhanced structural selectivity.

Human milk (HM) supports the healthy development of neonates and exerts many of its beneficial effects via contained free human milk oligosaccharides (HMOS). These HMOS exhibit a complexity and structural diversity that pose a significant analytical challenge. A detailed characterization of HMOS is essential as every individual structure may have a different function/activity.

The effect of surgery on fat mass, lipid and glucose metabolism in mild primary hyperparathyroidism.

Context: Mild primary hyperparathyroidism has been associated with increased body fat mass and unfavorable cardiovascular risk factors.

Objective: To assess the effect of parathyroidectomy on fat mass, glucose and lipid metabolism.

Design, Patients, Interventions, Main Outcome Measures: 119 patients previously randomized to observation (OBS; n = 58) or parathyroidectomy (PTX; n = 61) within the Scandinavian Investigation of Primary Hyperparathyroidism (SIPH) trial, an open randomized multicenter study, were included.

Targeted Analysis of Lysosomal Directed Proteins and Their Sites of Mannose-6-phosphate Modification.

Mannose-6-phosphate (M6P) is a distinctive post-translational modification critical for trafficking of lysosomal acid hydrolases into the lysosome. Improper trafficking into the lysosome, and/or lack of certain hydrolases, results in a toxic accumulation of their substrates within the lysosomes. To gain insight into the enzymes destined to the lysosome these glycoproteins can be distinctively enriched and studied using their unique M6P tag.

A New Tool to Reveal Bacterial Signaling Mechanisms in Antibiotic Treatment and Resistance.

The rapid emergence of antimicrobial resistance is a major threat to human health. Antibiotics modulate a wide range of biological processes in bacteria and as such, the study of bacterial cellular signaling could aid the development of urgently needed new antibiotic agents. Due to the advances in bacterial phosphoproteomics, such a systemwide analysis of bacterial signaling in response to antibiotics has recently become feasible.