Structural Characterization of Peptide Antibodies.

The role of proteins as very effective immunogens for the generation of antibodies is indisputable. Nevertheless, cases in which protein usage for antibody production is not feasible or convenient compelled the creation of a powerful alternative consisting of synthetic peptides. Synthetic peptides can be modified to obtain desired properties or conformation, tagged for purification, isotopically labeled for protein quantitation or conjugated to immunogens for antibody production.

Can Machine Learning Models Predict Asparaginase-associated Pancreatitis in Childhood Acute Lymphoblastic Leukemia.

Asparaginase-associated pancreatitis (AAP) frequently affects children treated for acute lymphoblastic leukemia (ALL) causing severe acute and persisting complications. Known risk factors such as asparaginase dosing, older age and single nucleotide polymorphisms (SNPs) have insufficient odds ratios to allow personalized asparaginase therapy. In this study, we explored machine learning strategies for prediction of individual AAP risk.

Does rapid sequence divergence preclude RNA structure conservation in vertebrates?

Accelerated evolution of any portion of the genome is of significant interest, potentially signaling positive selection of phenotypic traits and adaptation. Accelerated evolution remains understudied for structured RNAs, despite the fact that an RNA's structure is often key to its function. RNA structures are typically characterized by compensatory (structure-preserving) basepair changes that are unexpected given the underlying sequence variation, i.

Processes Underlying Glycemic Deterioration in Type 2 Diabetes: An IMI DIRECT Study.

Objective: We investigated the processes underlying glycemic deterioration in type 2 diabetes (T2D).

Research Design And Methods: A total of 732 recently diagnosed patients with T2D from the Innovative Medicines Initiative Diabetes Research on Patient Stratification (IMI DIRECT) study were extensively phenotyped over 3 years, including measures of insulin sensitivity (OGIS), β-cell glucose sensitivity (GS), and insulin clearance (CLIm) from mixed meal tests, liver enzymes, lipid profiles, and baseline regional fat from MRI. The associations between the longitudinal metabolic patterns and HbA deterioration, adjusted for changes in BMI and in diabetes medications, were assessed via stepwise multivariable linear and logistic regression.

Changes in long-chain fatty acid composition of milk fat globule membrane and expression of mammary lipogenic genes in dairy cows fed sunflower seeds and rumen-protected choline.

The aim of this experiment was to investigate the effect of dietary supplementation of crushed high oleic sunflower seeds (HOS) and rumen-protected choline (RPC) on the fatty acid (FA) profile of phospholipids and sphingomyelin and mammary transcription of genes that are important for milk fat synthesis and de novo synthesis of sphingolipids. Twenty-four cows were divided into four groups that either received an unsupplemented diet (Control), the Control diet supplemented with 50 g RPC per day, a diet supplemented with HOS at 10% of dry matter, or RPC and HOS in combination (RPC + HOS). RPC supplementation had no effect on the FA composition of milk or sphingomyelin.

Predictive ability of host genetics and rumen microbiome for subclinical ketosis.

Subclinical metabolic disorders such as ketosis cause substantial economic losses for dairy farmers in addition to the serious welfare issues they pose for dairy cows. Major hurdles in genetic improvement against metabolic disorders such as ketosis include difficulties in large-scale phenotype recording and low heritability of traits. Milk concentrations of ketone bodies, such as acetone and β-hydroxybutyric acid (BHB), might be useful indicators to select cows for low susceptibility to ketosis.

Linking glycemic dysregulation in diabetes to symptoms, comorbidities, and genetics through EHR data mining.

Diabetes is a diverse and complex disease, with considerable variation in phenotypic manifestation and severity. This variation hampers the study of etiological differences and reduces the statistical power of analyses of associations to genetics, treatment outcomes, and complications. We address these issues through deep, fine-grained phenotypic stratification of a diabetes cohort.

Sharing Programming Resources Between Bio* Projects.

Open-source software encourages computer programmers to reuse software components written by others. In evolutionary bioinformatics, open-source software comes in a broad range of programming languages, including C/C++, Perl, Python, Ruby, Java, and R. To avoid writing the same functionality multiple times for different languages, it is possible to share components by bridging computer languages and Bio* projects, such as BioPerl, Biopython, BioRuby, BioJava, and R/Bioconductor.

Genetic studies of abdominal MRI data identify genes regulating hepcidin as major determinants of liver iron concentration.

Background & Aims: Excess liver iron content is common and is linked to the risk of hepatic and extrahepatic diseases. We aimed to identify genetic variants influencing liver iron content and use genetics to understand its link to other traits and diseases.

Methods: First, we performed a genome-wide association study (GWAS) in 8,289 individuals from UK Biobank, whose liver iron level had been quantified by magnetic resonance imaging, before validating our findings in an independent cohort (n = 1,513 from IMI DIRECT).

Impact of the rumen microbiome on milk fatty acid composition of Holstein cattle.

Background: Fatty acids (FA) in bovine milk derive through body mobilization, de novo synthesis or from the feed via the blood stream. To be able to digest feedstuff, the cow depends on its rumen microbiome. The relative abundance of the microbes has been shown to differ between cows.

Conflicting associations between dietary patterns and changes of anthropometric traits across subgroups of middle-aged women and men.

Background: Individuals respond differently to dietary intake leading to different associations between diet and traits. Most studies have investigated large cohorts without subgrouping them.

Objective: The purpose was to identify non-uniform associations between diets and anthropometric traits that appeared to be in conflict with one another across subgroups.

Dual roles of heparanase in human carotid plaque calcification.

Background And Aims: Calcification is a hallmark of advanced atherosclerosis and an active process akin to bone remodeling. Heparanase (HPSE) is an endo-β-glucuronidase, which cleaves glycosaminoglycan chains of heparan sulfate proteoglycans. The role of HPSE is controversial in osteogenesis and bone remodeling while it is unexplored in vascular calcification.

New insights into the impact of primary lung adenocarcinoma location on metastatic sites and sequence: A multicenter cohort study.

Introduction: The presence of organ metastases is a major factor for unfavorable prognosis in lung adenocarcinoma (LADC). However, the influence of primary tumor location on metastatic sites and sequence has not been extensively analyzed.

Methods: We performed a multicenter cohort study, evaluating clinicopathological data of 1126 Caucasian LADC patients, focusing on the distinct location of primary tumors and metastatic sites during disease progression.

Trypsin-encoding variations influence the risk of asparaginase-associated pancreatitis in children with acute lymphoblastic leukemia: a Ponte di Legno toxicity working group report.

Asparaginase-associated pancreatitis is a life-threatening toxicity to childhood acute lymphoblastic leukemia treatment. To elucidate genetic predisposition and asparaginase-associated pancreatitis pathogenesis, ten trial groups contributed remission samples from patients aged 1.0-17.

Automated shape-based clustering of 3D immunoglobulin protein structures in chronic lymphocytic leukemia.

Background: Although the etiology of chronic lymphocytic leukemia (CLL), the most common type of adult leukemia, is still unclear, strong evidence implicates antigen involvement in disease ontogeny and evolution. Primary and 3D structure analysis has been utilised in order to discover indications of antigenic pressure. The latter has been mostly based on the 3D models of the clonotypic B cell receptor immunoglobulin (BcR IG) amino acid sequences.

Host genetics and the rumen microbiome jointly associate with methane emissions in dairy cows.

Cattle and other ruminants produce large quantities of methane (~110 million metric tonnes per annum), which is a potent greenhouse gas affecting global climate change. Methane (CH4) is a natural by-product of gastro-enteric microbial fermentation of feedstuffs in the rumen and contributes to 6% of total CH4 emissions from anthropogenic-related sources. The extent to which the host genome and rumen microbiome influence CH4 emission is not yet well known.

Protective role of the vulture facial skin and gut microbiomes aid adaptation to scavenging.

Background: Vultures have adapted the remarkable ability to feed on carcasses that may contain microorganisms that would be pathogenic to most other animals. The holobiont concept suggests that the genetic basis of such adaptation may not only lie within their genomes, but additionally in their associated microbes. To explore this, we generated shotgun DNA sequencing datasets of the facial skin and large intestine microbiomes of the black vulture (Coragyps atratus) and the turkey vulture (Cathartes aura).

The governance structure for data access in the DIRECT consortium: an innovative medicines initiative (IMI) project.

Biomedical research projects involving multiple partners from public and private sectors require coherent internal governance mechanisms to engender good working relationships. The DIRECT project is an example of such a venture, funded by the Innovative Medicines Initiative Joint Undertaking (IMI JU). This paper describes the data access policy that was developed within DIRECT to support data access and sharing, via the establishment of a 3-tiered Data Access Committee.

Pharmacometabolomics Informs About Pharmacokinetic Profile of Methylphenidate.

Carboxylesterase 1 (CES1) metabolizes methylphenidate and other drugs. CES1 gene variation only partially explains pharmacokinetic (PK) variability. Biomarkers predicting the PKs of drugs metabolized by CES1 are needed.

Computational Analysis of LOX1 Inhibition Identifies Descriptors Responsible for Binding Selectivity.

Lipoxygenases are a family of cytosolic, peripheral membrane enzymes, which catalyze the hydroperoxidation of polyunsaturated fatty acids and are implicated in the pathogenesis of major human diseases. Over the years, a substantial number of scientific reports have introduced inhibitors active against one or another subtype of the enzyme, but the selectivity issue has proved to be a major challenge for drug design. In the present work, we assembled a dataset of 317 structurally diverse molecules hitherto reported as active against 15S-LOX1, 12S-LOX1, and 15S-LOX2 and identified, using supervised machine learning, a set of structural descriptors responsible for the binding selectivity toward the enzyme 15S-LOX1.

High-fat feeding induces mobilization of vitamin C in obese prone rats.

In obesity and dyslipidemia, hydrolysis of triacylglycerol (TAG) into non-esterified fatty acids (NEFAs) may contribute to insulin resistance, and production of oxygenated, bioactive polyunsaturated fatty acids may increase oxidative stress. Here we show that after six weeks of high-fat feeding of obese prone rats (Crl:OP(CD), vitamin C was increased both in liver (P < 0.01) and plasma (P < 0.

Benchmarking the HLA typing performance of Polysolver and Optitype in 50 Danish parental trios.

Background: The adaptive immune response intrinsically depends on hypervariable human leukocyte antigen (HLA) genes. Concomitantly, correct HLA phenotyping is crucial for successful donor-patient matching in organ transplantation. The cost and technical limitations of current laboratory techniques, together with advances in next-generation sequencing (NGS) methodologies, have increased the need for precise computational typing methods.

Bioinformatics Tools for the Prediction of T-Cell Epitopes.

T-cell responses are activated by specific peptides, called epitopes, presented on the cell surface by MHC molecules. Binding of peptides to the MHC is the most selective step in T-cell antigen presentation and therefore an essential factor in the selection of potential epitopes. Several in-vitro methods have been developed for the determination of peptide binding to MHC molecules, but these are all costly and time-consuming.