Biology subjects

Brandt, H.

Publications and source records attributed to Brandt, H..

4 recordsLinked to original sources

bioRxiv2024

T cell interaction partners of DHHC20

Reversible palmitoylation of proteins at cysteine residues represents a post-translational modification that can alter the cellular localization of proteins, change their distribution within lipid membranes or modulate their conformation and molecular interaction patterns. DHHC enzymes catalyze protein palmitoylation, while thioesterases or hydrolases can rapidly remove the acyl-chain. In human T cells, DHHC proteins have been shown to modify proteins that are involved in major signaling pathways such as Ca2+-signaling or kinase-dependent activation of transcription factors for cytokines. For DHHC20, a role in the palmitoylation of the Orai1 Ca2+-channel has been demonstrated, but otherwise its T cell interaction partners are largely unknown. Here, we show that recombinantly expressed DHHC20 robustly interacts with 28 proteins from Jurkat T cells, as shown by affinity enrichment combined with mass spectrometric analysis. We find a robust interaction between DHHC20 and the {beta}-subunit of the trimeric G protein Gs{beta}1{gamma}2, while the typically palmitoylated Ga subunit is not identified. Cross-linking mass spectrometry with purified DHHC20 and Gs{beta}1{gamma}2 then confirms a direct interaction between the {beta}1{gamma}2 domains and the enzyme, while rigid docking offers structural poses that are in agreement with the observed intermolecular cross-linking constraints. Thus, we suggest a model where the {beta}1{gamma}2 subunits of a trimeric G protein serve as a stable interaction partner of a DHHC enzyme, presumably acting as a landing platform for the G subunit that is subsequently palmitoylated by the enzyme.

biochemistry↗

bioRxiv2018

Co-occurrence of contrasting life-history strategies in a metapopulation inhabiting temporally variable and stable breeding sites

Life-history theory states that, during the lifetime of an individual, resources are allocated to either somatic maintenance or reproduction. Resource allocation trade-offs determine the evolution and ecology of life-history strategies and determine an organisms position along the fast-slow continuum. Theory predicts that environmental stochasticity is an important driver of resource allocation and therefore life-history evolution. Highly stochastic environments are expected to increase uncertainty in reproductive success and select for iteroparity and a slowing down of the life history. To date, most empirical studies have used comparisons among species to examine these theoretical predictions. By contrast, few have investigated how environmental stochasticity affects life-history strategies at the intraspecific level. In this study, we examined how variation in breeding site stochasticity (among-year variability in pond volume and hydroperiod) promotes the co-occurrence of different life-history strategies in a spatially structured population, and determines life-history position along the fast-slow continuum in the yellow-bellied toad (Bombina variegata). We collected mark-recapture data from a metapopulation and used multievent capture-recapture models to estimate survival, recruitment and breeding probabilities. We found higher survival and longer lifespans in populations inhabiting variable sites compared to those breeding in stable ones. In addition, probabilities of recruitment and skipping a breeding event were higher in variable sites. The temporal variance of survival and recruitment probabilities as well as the probability to skip breeding was higher in variable sites. Taken together, these findings indicate that populations breeding in variable sites experienced a slowing down of the life-history. Our study thus revealed similarities in the macroevolutionary and microevolutionary processes shaping life-history evolution.

ecology↗

bioRxiv2017

The Anorexia Nervosa Genetics Initiative: Overview and Methods

BackgroundGenetic factors contribute to anorexia nervosa (AN); and the first genome-wide significant locus has been identified. We describe methods and procedures for the Anorexia Nervosa Genetics Initiative (ANGI), an international collaboration designed to rapidly recruit 13000 individuals with AN as well as ancestrally matched controls. We present sample characteristics and the utility of an online eating disorder diagnostic questionnaire suitable for large-scale genetic and population research.\n\nMethodsANGI recruited from the United States (US), Australia/New Zealand (ANZ), Sweden (SE), and Denmark (DK). Recruitment was via national registers (SE, DK); treatment centers (US, ANZ, SE, DK); and social and traditional media (US, ANZ, SE). All cases had a lifetime AN diagnosis based on DSM-IV or ICD-10 criteria (excluding amenorrhea). Recruited controls had no lifetime history of disordered eating behaviors. To assess the positive and negative predictive validity of the online eating disorder questionnaire (ED100K-v1), 109 women also completed the Structured Clinical Interview for DSM-IV (SCID), Module H.\n\nResultsBlood samples and clinical information were collected from 13,364 individuals with lifetime AN and from controls. Online diagnostic phenotyping was effective and efficient; the validity of the questionnaire was acceptable.\n\nConclusionsOur multipronged recruitment approach was highly effective for rapid recruitment and can be used as a model for efforts by other groups. High online presence of individuals with AN rendered the Internet/social media a remarkably effective recruitment tool in some countries. ANGI has substantially augmented Psychiatric Genomics Consortium AN sample collection. ANGI is a registered clinical trial: clinicaltrials.gov NCT01916538; https://clinicaltrials.gov/ct2/show/NCT01916538?cond=Anorexia+Nervosa&draw=1&rank=3.

genetics↗

bioRxiv2016

Genome-Wide Association Study Reveals First Locus for Anorexia Nervosa and Metabolic Correlations

Anorexia nervosa (AN) is a serious eating disorder characterized by restriction of energy intake relative to requirements, resulting in abnormally low body weight. It has a lifetime prevalence of approximately 1%, disproportionately affects females1,2, and has no well replicated evidence of effective pharmacological or psychological treatments despite high morbidity and mortality2. Twin studies support a genetic basis for the observed aggregation of AN in families3, with heritability estimates of 48%-74%4. Although initial genome-wide association studies (GWASs) were underpowered5,6, evidence suggested that signals for AN would be detected with increased power5. We present a GWAS of 3,495 AN cases and 10,982 controls with one genome-wide significant locus (index variant rs4622308, p=4.3x10-9) in a region (chr12:56,372,585-56,482,185) which includes six genes. The SNP-chip heritability [Formula] of AN from these data is 0.20 (SE=0.02), suggesting that a substantial fraction of the twin-based heritability stems from common genetic variation. Using these GWAS results, we also find significant positive genetic correlations with schizophrenia, neuroticism, educational attainment, and HDL cholesterol, and significant negative genetic correlations with body mass, insulin, glucose, and lipid phenotypes. Our results support the reconceptualization of AN as a disorder with both psychiatric and metabolic components.

genomics↗