A robust method for measuring aminoacylation through tRNA-Seq.

Current methods to quantify the fraction of aminoacylated tRNAs, also known as the tRNA charge, are limited by issues with either low throughput, precision, and/or accuracy. Here, we present an optimized charge transfer RNA sequencing (tRNA-Seq) method that combines previous developments with newly described approaches to establish a protocol for precise and accurate tRNA charge measurements. We verify that this protocol provides robust quantification of tRNA aminoacylation and we provide an end-to-end method that scales to hundreds of samples including software for data processing.

An engineered biosensor enables dynamic aspartate measurements in living cells.

Intracellular levels of the amino acid aspartate are responsive to changes in metabolism in mammalian cells and can correspondingly alter cell function, highlighting the need for robust tools to measure aspartate abundance. However, comprehensive understanding of aspartate metabolism has been limited by the throughput, cost, and static nature of the mass spectrometry (MS)-based measurements that are typically employed to measure aspartate levels. To address these issues, we have developed a green fluorescent protein (GFP)-based sensor of aspartate (jAspSnFR3), where the fluorescence intensity corresponds to aspartate concentration.

Disinhibited attachment behavior among infants reared at home: Relations to maternal severe mental illness and personality disorder symptoms.

Disinhibited attachment behavior (DAB) among infants is persistent and associated with behavioral and relational problems throughout childhood and adolescence. Little is known about risk factors for DAB among infants reared at home, although studies have linked DAB with maternal psychiatric hospitalization and maternal borderline personality disorder. The aim of the current study was to further assess the association between DAB, maternal severe mental illness (SMI; schizophrenia, bipolar disorder, and depression), and maternal PD symptoms.

Hair cortisol concentrations in pregnant women with bipolar, depressive, or schizophrenic spectrum disorders.

Purpose: Maternal cortisol levels in pregnancy may support the growth of or adversely affect fetal organs, including the brain. While moderate cortisol levels are essential for fetal development, excessive or prolonged elevations may have negative health consequences for both the mother and the offspring. Little is known about predictors of altered hypothalamic-pituitary-adrenal (HPA) axis activity during pregnancy.

A robust method for measuring aminoacylation through tRNA-Seq.

Current methods to quantify the fraction of aminoacylated tRNAs, also known as the tRNA charge, are limited by issues with either low throughput, precision, and/or accuracy. Here, we present an optimized charge tRNA-Seq method that combines previous developments with newly described approaches to establish a protocol for precise and accurate tRNA charge measurements. We verify that this protocol provides robust quantification of tRNA aminoacylation and we provide an end-to-end method that scales to hundreds of samples including software for data processing.

The longitudinal association of combined regulatory problems in infancy and mental health outcome in early childhood: a systematic review.

Co-occurring regulatory problems in infancy, RPs, including excessive crying, feeding-eating and sleeping, have been found associated with mental health problems in school ages. Still, an overview is needed on trajectories of co-occurring or combined RPs, and mental health problems in early childhood. The aim of this review is to systematically review the literature on longitudinal community-based studies of combined RPs measuring mental health outcomes in early childhood.

An engineered biosensor enables dynamic aspartate measurements in living cells.

Intracellular levels of the amino acid aspartate are responsive to changes in metabolism in mammalian cells and can correspondingly alter cell function, highlighting the need for robust tools to measure aspartate abundance. However, comprehensive understanding of aspartate metabolism has been limited by the throughput, cost, and static nature of the mass spectrometry based measurements that are typically employed to measure aspartate levels. To address these issues, we have developed a GFP-based sensor of aspartate (jAspSnFR3), where the fluorescence intensity corresponds to aspartate concentration.

Life course partnership history and objectively measured physical functional ability in Danish middle-aged adults.

Background: Partnership break-up and living alone is associated with several negative health-related outcomes. Little is known about the association with physical functional ability in a life course perspective. The aim of this study is to investigate (1) the association between number of partnership break-ups and years living alone across 26 years of adult life respectively and objectively measured physical capability in midlife, (2) how the joint exposure of accumulated break-ups or years living alone respectively, and education relates to physical capability in midlife and (3) potential gender differences.

Mitochondrial redox adaptations enable alternative aspartate synthesis in SDH-deficient cells.

The oxidative tricarboxylic acid (TCA) cycle is a central mitochondrial pathway integrating catabolic conversions of NAD +to NADH and anabolic production of aspartate, a key amino acid for cell proliferation. Several TCA cycle components are implicated in tumorigenesis, including loss-of-function mutations in subunits of succinate dehydrogenase (SDH), also known as complex II of the electron transport chain (ETC), but mechanistic understanding of how proliferating cells tolerate the metabolic defects of SDH loss is still lacking. Here, we identify that SDH supports human cell proliferation through aspartate synthesis but, unlike other ETC impairments, the effects of SDH inhibition are not ameliorated by electron acceptor supplementation.

Proteomic Identification of Phosphorylation-Dependent Septin 7 Interactors that Drive Dendritic Spine Formation.

Septins are a family of cytoskeletal proteins that regulate several important aspects of neuronal development. Septin 7 (Sept7) is enriched at the base of dendritic spines in excitatory neurons and mediates both spine formation and spine and synapse maturation. Phosphorylation at a conserved C-terminal tail residue of Sept7 mediates its translocation into the dendritic spine head to allow spine and synapse maturation.

Prenatal and early childhood predictors of intelligence quotient (IQ) in 7-year-old Danish children from the Odense Child Cohort.

Background: Cognitive development measured as intelligence quotient can predict socioeconomic markers in adulthood. It is therefore of interest to determine predictors of childhood intelligence quotient.

Aim: To assess intelligence quotient scores based on standardised Danish age-appropriate scores and to evaluate potential predictors of intelligence quotient.

Do partnership dissolutions and living alone affect systemic chronic inflammation? A cohort study of Danish adults.

Background: Partnership breakups and living alone are associated with several adverse health outcomes. The aim of this study, carried out in Denmark, is to investigate whether accumulated numbers of divorces/partnership breakups or years lived alone across 26 years of adult life are associated with levels of inflammation, and if vulnerability with regards to gender or educational level can be identified.

Methods: 4835 participants from the Copenhagen Aging and Midlife Biobank (CAMB) aged 48-62 years were included.

Mental and pediatric disorders among children 0-6 years of parents with severe mental illness.

Objective: Parental severe mental illness (SMI) increases the lifetime risk of mental and pediatric disorders in the offspring but little is known about specific disorders during early childhood. The primary aim was to investigate the incidence of mental and pediatric disorders among children 0-6 years old exposed to parental SMI, and secondarily to investigate the distribution of disorders on specific child age.

Methods: A nationwide, register-based cohort study of 1,477,185 children born in Denmark between 1994.

Free Asparagine or Die: Cancer Cells Require Proteasomal Protein Breakdown to Survive Asparagine Depletion.

The chemotherapeutic enzyme asparaginase depletes systemic asparagine to kill cancers; however, its efficacy thus far is limited to a subset of leukemias. Hinze and colleagues identify that inhibiting proteasomal release of asparagine can sensitize colorectal cancers to asparagine depletion, providing a potential avenue to repurpose asparaginase for treatment of solid tumors..

Maternal prenatal stress and postnatal depressive symptoms: discrepancy between mother and teacher reports of toddler psychological problems.

Purpose: Maternal prenatal stress and postnatal depression are reported to increase the risk for early offspring psychological problems. We examined whether these two stressors predicted toddler emotional or behavioral problems based on the mother and teacher reports, respectively.

Methods: A longitudinal study within the Odense Child Cohort (OCC).

Parental mental illness, attendance at preventive child healthcare and dental caries in the offspring: a nation-wide population-based cohort study.

Purpose: Severe mental illness (SMI) may interfere with parental caregiving practices and offspring development. Adhering to preventive well-child visits and maintaining good oral hygiene during early childhood requires parental involvement. Whether these activities are affected by parental SMI is unclear.

Deep generative models for T cell receptor protein sequences.

Probabilistic models of adaptive immune repertoire sequence distributions can be used to infer the expansion of immune cells in response to stimulus, differentiate genetic from environmental factors that determine repertoire sharing, and evaluate the suitability of various target immune sequences for stimulation via vaccination. Classically, these models are defined in terms of a probabilistic V(D)J recombination model which is sometimes combined with a selection model. In this paper we take a different approach, fitting variational autoencoder (VAE) models parameterized by deep neural networks to T cell receptor (TCR) repertoires.

COMBINES-CID: An Efficient Method for De Novo Engineering of Highly Specific Chemically Induced Protein Dimerization Systems.

Chemically induced dimerization (CID) systems, in which two proteins dimerize only in the presence of a small molecule ligand, offer versatile tools for small molecule sensing and actuation. However, only a handful of CID systems exist and creating one with the desired sensitivity and specificity for any given ligand is an unsolved problem. Here, we developed a binatorial ders-nabled election of CID (COMBINES-CID) method broadly applicable to different ligands.

Morbidity and Mortality in the Children and Young Adult Offspring of Parents With Schizophrenia or Affective Disorders-A Nationwide Register-Based Cohort Study in 2 Million Individuals.

Background: The offspring of parents with severe mental illness (SMI) are at higher risk of mortality and of developing certain somatic diseases. However, across the full spectrum of somatic illness, there remains a gap in knowledge regarding morbidity.

Methods: We conducted a register-based nationwide cohort study of all 2 000 694 individuals born in Denmark between 1982 and 2012.

Antenatal caregiving representations among expectant mothers with severe mental illness: a cross-sectional study.

: The study explores predictors of antenatal caregiving representations among mothers with a history of severe mental illness (SMI). : Attachment research has demonstrated that multifactorial assessment of antenatal caregiving representations predicts later maternal behaviour and child attachment. However, the field lacks research among clinical groups.

Hair cortisol in the perinatal period mediates associations between maternal adversity and disrupted maternal interaction in early infancy.

Existing literature points to the possibility that cortisol could be one link between maternal adversity and poorer parenting quality, but most studies have examined salivary cortisol concentrations rather than hair cortisol concentrations. The current study examined hair cortisol concentration (HCC) during the third trimester of pregnancy as a mediator between maternal adversity indicators (childhood abuse, severe mental illness, symptomatic functioning) and maternal caregiving behavior at 4 months postpartum. Forty-four women participated in the study: 30 with severe mental disorders, and 14 nonclinical controls.

BioReader: a text mining tool for performing classification of biomedical literature.

Background: Scientific data and research results are being published at an unprecedented rate. Many database curators and researchers utilize data and information from the primary literature to populate databases, form hypotheses, or as the basis for analyses or validation of results. These efforts largely rely on manual literature surveys for collection of these data, and while querying the vast amounts of literature using keywords is enabled by repositories such as PubMed, filtering relevant articles from such query results can be a non-trivial and highly time consuming task.

Benchmarking Tree and Ancestral Sequence Inference for B Cell Receptor Sequences.

B cell receptor sequences evolve during affinity maturation according to a Darwinian process of mutation and selection. Phylogenetic tools are used extensively to reconstruct ancestral sequences and phylogenetic trees from affinity-matured sequences. In addition to using general-purpose phylogenetic methods, researchers have developed new tools to accommodate the special features of B cell sequence evolution.

Predicting B cell receptor substitution profiles using public repertoire data.

B cells develop high affinity receptors during the course of affinity maturation, a cyclic process of mutation and selection. At the end of affinity maturation, a number of cells sharing the same ancestor (i.e.

Antibody Cross-Reactivity in Antivenom Research.

Antivenom cross-reactivity has been investigated for decades to determine which antivenoms can be used to treat snakebite envenomings from different snake species. Traditionally, the methods used for analyzing cross-reactivity have been immunodiffusion, immunoblotting, enzyme-linked immunosorbent assay (ELISA), enzymatic assays, and in vivo neutralization studies. In recent years, new methods for determination of cross-reactivity have emerged, including surface plasmon resonance, antivenomics, and high-density peptide microarray technology.