Biology subjects

Kaufmann, C.

Publications and source records attributed to Kaufmann, C..

5 recordsLinked to original sources

bioRxiv2025

Inhibitory control and error processing in Obsessive-Compulsive Disorder: A mega-analysis of task-based fMRI data by the ENIGMA-OCD consortium

ObjectiveObsessive-compulsive disorder (OCD) is a chronic condition in which impaired inhibitory control and excessive error monitoring may contribute to the maintenance of obsessions and compulsions. This mega-analysis investigates neural activation during response inhibition and error processing using adult and pediatric data from the ENIGMA-OCD consortium and the ABCD study. MethodsIndividual participant data was uniformly processed using HALFpipe to extract statistical maps for response inhibition and error processing contrasts. Bayesian multilevel models were used to assess regional and whole-brain effects of OCD, with additional analyses examining the association between the OCD clinical profile and task-related activation. ResultsAcross inhibitory control tasks, both individuals with OCD and control participants showed robust activation in regions implicated in response inhibition and error processing. During response inhibition, compared to controls, adults with OCD showed stronger somatomotor cortex activation, while children with OCD showed stronger occipital cortex activation. Children with likely OCD from the ABCD cohort showed reduced activity in the frontoparietal network in the anterior insula/frontal operculum region. During error processing, relative to controls, adults with OCD showed weaker activation in fronto-striatal regions, while children with OCD showed stronger activation in frontoparietal and attention networks. Greater OCD symptom severity was associated with weaker task-related activation in adults and stronger activation in children during response inhibition. ConclusionCase-control differences in brain activation during inhibitory control varied by age group and task contrast. Symptom severity emerged as the main clinical correlate of activation during inhibition, suggesting that inhibitory control deficits in OCD may be both state-dependent and developmentally specific.

neuroscience↗

bioRxiv2022

Primate Social Organization Evolved from a Flexible Pair-Living Ancestor

Explaining the evolution of primate social organization has been fundamental to understand human sociality and social evolution more broadly. It has often been suggested that the ancestor of all primates was solitary and that other forms of social organization evolved later. However, previous research included the assumption that many understudied primate species were solitary, then finding transitions to more complex social systems being driven by various life history traits and ecological factors. Here we show that when intra-specific variation is accounted for, the ancestral social organization of primates was variable, with the most common social organization being pair-living but with approximatively 15-20% of social units of the ancestral population deviating from this pattern by being solitary living. We built a detailed database from primary field studies quantifying the number of individuals (social units) expressing different social organizations in each population. We used Bayesian phylogenetic models to infer the probability of each social organization, conditional on several socio-ecological predictors, in ancestral populations. Body size and activity patterns had large effects on transitions between types of social organizations. Our results challenge the assumption that ancestral primates were solitary and that pair-living evolved afterwards. Moreover, our results emphasize the importance of focusing on field data and accounting for intra-specific variation. Pair-living is evolutionary ancient, likely caused by reproductive benefits such as access to partners and reduced intra-sexual competition, with more complex social structure (pair-bonding) and care systems (biparental and allo-parental care) evolving later. Significance StatementWas the ancestor of all primates a solitary-living species? Did more social forms of primate societies evolve from this basic and simple society? The dogma has been that the answer is yes. We used a modern statistical analysis, including variations within species, to show that the ancestral primate social organization was most likely variable. Most lived in pairs, and only 15-20% of individuals were solitary. Living in pairs was likely ancient and caused by reproductive benefits, like access to partners and reduced competition with the sexes. More complex social elaborations like pair-bonds, and biparental and allo-parental care, probably evolved later.

evolutionary biology↗

bioRxiv2021

TPST-dependent and -independent regulation of root development and signaling by PSK LRR receptor kinases in Arabidopsis

Tyrosine-sulfated peptides are key regulators of plant growth and development. The disulfated pentapeptide phytosulfokine (PSK) mediates growth via leucine-rich repeat receptor-like kinases, PSKR1 and PSKR2. PSKRs are part of a response module at the plasma membrane that mediates short-term growth responses, but downstream signaling of transcriptional regulation remains unexplored. In Arabidopsis, tyrosine sulfation is catalyzed by a single-copy gene (TPST). We performed a microarray-based transcriptome analysis in the tpst-1 mutant background that lacks sulfated peptides to identify PSK-regulated genes and genes that are regulated by other sulfated peptides. Of the 160 PSK-regulated genes, several had functions in root growth and development in agreement with shorter roots and a higher lateral root density in tpst-1. Further, tpst-1 roots developed higher numbers of root hairs and PSK induced expression of WEREWOLF (WER), its paralog MYB DOMAIN PROTEIN 23 (MYB23) and At1g66800 that maintain non-hair cell fate. The tpst-1 pskr1-3 pskr2-1 mutant showed even shorter roots, and higher lateral root and root hair density than tpst-1 revealing unexpected synergistic effects of ligand and PSK receptor deficiencies. While residual activities may exist, overexpression of PSKR1 in the tpst-1 background induced root growth suggesting that PSKR1 may be active in the absence of sulfated ligands. HighlightPhytosulfokine (PSK) receptor signaling promotes root elongation, determines lateral root density and maintains non-hair cell fate partially independent of TPST responsible for the activating sulfation of PSK.

plant biology↗

bioRxiv2020

Haploid mouse germ cell precursors from embryonic stem cells reveal Xist activation from a single X chromosome

Mammalian haploid cells have applications for genetic screening and substituting gametic genomes. Here we characterize a culture system for obtaining haploid primordial germ cell-like cells (PCGLCs) from haploid mouse embryonic stem cells (ESCs). We find that a haploid genome is maintained in PGCLCs with a high frequency indicating a substantially lower rate of diploidization than somatic cells. Characterization of the differentiating haploid ESCs reveals that Xist is activated from the single X chromosome. This observation suggests that X chromosome inactivation is initiated in haploid cells consistent with a model where autosomal blocking factors set a threshold for X-linked activators. The germline segregates from the epiblast and differs from somatic lineages in gene expression and epigenetic mechanisms. The ability of primordial germ cells for repressing Xist might contribute to the maintenance of a haploid genome.

developmental biology↗

bioRxiv2019

White Matter Microstructure and its Relation to Clinical Features of Obsessive-Compulsive Disorder: Findings from the ENIGMA OCD Working Group

ImportanceMicrostructural alterations in cortico-subcortical connections are thought to be present in Obsessive-Compulsive Disorder (OCD). However, prior studies have yielded inconsistent findings, perhaps because small sample sizes provided insufficient power to detect subtle abnormalities. ObjectiveTo investigate microstructural white matter alterations and their relation to clinical features in the largest dataset of adult and pediatric OCD to date. Design, Setting, and ParticipantsIn this cross-sectional case-control magnetic resonance study, we investigated diffusion tensor imaging metrics from 700 adult patients and 645 adult controls, as well as 174 pediatric patients and 144 pediatric controls across 19 sites participating in the ENIGMA-OCD Working Group. Main Outcomes and MeasuresWe extracted measures of fractional anisotropy (FA) as main outcome, and mean diffusivity, radial diffusivity, and axial diffusivity as secondary outcomes for 25 white matter regions. We meta-analyzed patient-control group differences (Cohens d) across sites, after adjusting for age and sex, and investigated associations with clinical characteristics. ResultsAdult OCD patients showed significant FA reduction in the sagittal stratum (d=-0.21, z=-3.21, p=0.001) and posterior thalamic radiation (d=-0.26, z=-4.57, p<0.0001). In the sagittal stratum only, lower FA was associated with a younger age of onset (z=2.71, p=0.006), longer duration of illness (z=-2.086, p=0.036) and a higher percentage of medicated patients in the cohorts studied (z=-1.98, p=0.047). No significant association with symptom severity was found. Pediatric OCD patients did not show any detectable microstructural abnormalities compared to matched controls. Conclusions and RelevanceMicrostructural alterations in projection and association fibers to posterior brain regions were found in adult OCD, and related to disease course and medication status. Such results are relevant to models positing deficits in connectivity as a crucial mechanism in OCD. KEY POINTSO_ST_ABSQuestionC_ST_ABSDo patients with Obsessive-Compulsive Disorder (OCD) show white matter microstructural alterations, and are these alterations related to clinical features? FindingsData from 19 sites of the ENIGMA-OCD Consortium were included, involving 700 adult patients and 645 adult controls, 174 pediatric patients and 144 pediatric controls. Diffusion tensor imaging data were meta-analyzed using a harmonized data processing and analysis protocol. Adult, but not pediatric, patients showed alterations in the sagittal stratum and posterior thalamic radiation; sagittal stratum differences were associated with clinical features. MeaningMicrostructural abnormalities found in adult but not in the pediatric cohort, are related to illness duration and medication status.

neuroscience↗