Biology subjects

Fischer, C.

Publications and source records attributed to Fischer, C..

At least 19 recordsLinked to original sources

bioRxiv2026

Targeting poorly differentiated thyroid cancer with bispecific antibodies and CAR T cells from the human anti-TSHR autoantibody repertoire

Background: Poorly differentiated thyroid carcinoma (PDTC) has no effective systemic treatment option once radioactive iodine and tyrosine kinase inhibitors fail. The thyroid-stimulating hormone receptor (TSHR) is highly tissue-restricted and the anti-TSHR autoantibody repertoire of thyroid autoimmunity offers sequence-defined, fully human binders. We asked whether this repertoire can be converted into an off-the-shelf T cell-redirecting therapy for PDTC. Methods: TSHR expression was profiled on a 151-case thyroid cancer tissue microarray (TMA), 50 healthy controls and on fresh tumor material. Eight anti-TSHR clones, four of human autoimmune origin (M22, K1-18, K1-70, 5C9) and four murine (IRI-SAb2, IRI-SAb3, 9D33, 1H7), were reformatted as CD3-engaging bispecific antibodies (bsAbs; anti-TSHR Fab x anti-CD3 scFv) and, for leading clones, as chimeric antigen receptor (CAR) T cells. Activity was compared in vitro, across graded and mixed antigen densities and in a CAL-62-Luc-TSHR xenograft model, using healthy-donor (HD) or thyroid cancer-patient T cells. Results: TSHR was retained on a substantial fraction of PDTC, including metastatic lesions. Both formats mediated potent, antigen-selective killing and the leading bsAbs suppressed xenograft growth in vivo. For CAR T cells, scFv heavy/light-chain orientation was decisive. Anti-TSHR bsAbs cleared mixed cultures far beyond the antigen-positive fraction matching mosunetuzumab and indicating a modality-intrinsic bystander effect. Patient-derived T cells obtained on or after oncological treatment retained full effector function. Conclusions: The anti-TSHR autoantibody repertoire provides a promising source of binders for off-the-shelf bispecific antibodies targeting TSHR-positive thyroid cancer, while CAR T cells offer an autologous alternative.

cancer biology↗

bioRxiv2026

Self-supervised representations reveal the genetic architecture of human cortical folding

Cortical folding emerges during fetal development, is under genetic control, and remains stable throughout life, offering a lasting window into early neurodevelopment. Conventional morphometric descriptors, however, only partially capture the shape variability of cortical folds. Here, we compare 56 regional self-supervised deep learning representations of cortical folds with classical sulcal morphometry via multivariate genome-wide association studies (GWAS) in 35,940 UK Biobank participants. The learned representations identified 567 independent genome-wide significant loci, versus 162 for classical morphometry, 87% of which were also detected by our approach. More than half of these associations replicated in the independent Adolescent Brain Cognitive Development (ABCD) cohort. Gene, gene-set, BrainSpan and single-cell expression enrichment converge on a shared prenatal window of neurogenesis and morphogenesis; spatial gene-association maps recapitulate known regional expression gradients, including for NR2F1. Together, these results establish self-supervised representations of cortical folding as a powerful phenotypic framework for the genetic study of neurodevelopment.

genomics↗

bioRxiv2026

Structural and chemical properties of insects' chitin-containing extracellular matrices

Insects body barriers rely on specialized extracellular matrices that protect against harmful environmental influences. The outer barrier is the cuticle, which is composed of chitin, cuticle proteins and lipids. The peritrophic matrix (PM) serves as an inner barrier lining the midgut epithelium. It is composed of chitin fibers that are organized by PM proteins. While cuticle and PM proteins have received considerable attention in the past, supramolecular organization and physicochemical properties of the chitin component - particularly of the PM - remain poorly understood. Here, we combine synchrotron-based X-ray diffraction data from the PMs of lepidopteran and coleopteran insects with RNA interference (RNAi), mass spectrometric and histochemical analyses of the PM from Tribolium castaneum to determine chitins allomorphic state and degree of acetylation. The chitin of the PM exhibits signatures characteristic of dihydrate {beta}-chitin along the entire midgut. In contrast, the cuticle is made of tightly packed -chitin nanofibrils. Mass spectrometry revealed that the PMs chitin is highly acetylated (>95%). RNAi silencing of gut-specific genes encoding chitin deacetylasesTcCDA6-9 further increases the degree of acetylation. Histochemical analyses staining chitin with different degrees of acetylation confirm the predominance of highly acetylated chitin in the PM. Notably, the larval cuticle has a layered organization with deacetylated chitin present in exo- and highly acetylated chitin in endocuticles. Depletion of both TcCDA1 or TcCDA2 impairs chitin deacetylation, which indicates that both proteins cooperate in their activity in the integument. These results establish fundamental principles of polysaccharide-based extracellular matrices, with broad implications for insect biology.

molecular biology↗

bioRxiv2025

How big is enough? Movement-informed zoning for African swine fever mitigation

O_LIAfrican swine fever (ASF) poses a serious threat to domestic pigs and wild boar populations. Wild boar can disperse the virus, making effective containment crucial. One of the main control strategies involves establishing restricted zones around detected cases, i.e., areas with temporary restrictions on access and hunting; however, determining the appropriate size of these zones remains a major challenge. C_LIO_LITo inform the size of restricted zones, we analyzed GPS data from 527 wild boar across 46 European study sites using a two-step approach combining first-passage time analysis and survival modelling to quantify the risk of wild boar leaving areas of different radii (i.e., spatial scales). We investigated how the risk of leaving varied over time and across environmental gradients. To go further, we used our model findings to develop an online application that generates predictive maps of optimal buffer sizes for ASF management at the European scale, based on a given risk threshold (the maximum acceptable probability that a wild boar leaves the area). C_LIO_LIWe found that the relationship between radius and the risk of leaving is negative exponential, and the risk of leaving increased over time, with a more rapid increase for smaller radii. Landscape homogeneity, terrain ruggedness and human impact increased the risk of leaving, with stronger effects at small scales. Contrary to other predictors, agricultural cover exerted a strong effect on risk of leaving over large spatial scales, especially when it was abundant. C_LIO_LIAcross Europe, a buffer radius of [~]8 km is likely sufficient around high-risk infection zones in most areas (considering an infectious period of 14 days and a risk threshold of 5%); however, in certain areas, a radius of up to 20 km may be needed to effectively limit wild boar movement. C_LIO_LISynthesis and applications: Our results highlight the need for adaptive, context-specific restricted zones. Buffers of 8 km around ASF-affected areas can limit the risk of infected wild boar dispersal, but they may be reduced to 5 km in highly heterogeneous landscapes or high-human impacted areas. Larger buffers may be required in agricultural landscapes. We provide spatially explicit outputs (optimal buffer sizes) that can directly inform policy and wildlife disease response strategies. The approach can be adapted to any other infectious disease. C_LI

ecology↗

bioRxiv2025

circVDJ-seq for T cell clonotype detection in single-cell and spatial multi-omics

Monitoring T cell repertoires in human tissues provides important insights into immune response mechanisms in cancer, infectious diseases, and autoimmunity. However, retrieving VDJ information from single-cell and spatial transcriptomics workflows with 3-barcoding of cDNA remains resource-intensive or requires specialized sequencing equipment. Here, we introduce circVDJ-seq for simplified and cost-efficient T cell receptor (TCR) profiling from 3-directed workflows like single-cell or single-nucleus RNA sequencing, ATAC+RNA multi-omics, and spatial transcriptomics. Application of circVDJ-seq to freshly resected neuroblastomas and postmortem lymph nodes affected by pneumonia or COVID-19 reveals distinct immune microenvironments and T cell clonality patterns, highlighting broad utility across diverse clinical contexts.

genomics↗

bioRxiv2025

MIST-Explorer: The Comprehensive Toolkit for Spatial Omic Analysis and Visualization of Single-Cell MIST Array Data

Recent advances in spatial proteomics have enabled high-dimensional protein analysis within tissue samples, yet few methods accurately detect low-abundance functional proteins. Spatial MIST (Multiplex In Situ Tagging) is one such technique, capable of profiling over 100 protein markers spatially at single-cell resolution on tissue sections and cultured cells. However, despite the availability of various open-source tools for image registration and visualization, no dedicated software exists to align the images and analyze spatial MIST data effectively. To address this gap, we present MIST-Explorer, a comprehensive, user-friendly toolkit for the visualization and analysis of single-cell spatial MIST array data. Developed in Python with a PyQt6-based graphical interface, MIST-Explorer streamlines the spatial omics workflow--from image preprocessing and registration to cell segmentation and protein quantification. The software supports two workflows: one for preprocessed datasets and another for raw image inputs, ensuring broad compatibility across experimental designs. Key features include tile-based image registration using Astroalign and PyStackReg, deep learning-based segmentation with StarDist, multi-channel visualization with layer controls, and an interactive analysis module offering ROI selection along with histograms, heatmaps, and UMAP plots. MIST-Explorer generates spatially resolved expression tables readily compatible with downstream single-cell analysis pipelines. By integrating all major steps into a single platform, MIST-Explorer empowers researchers to derive biological insights from complex spatial omics datasets without requiring extensive computational expertise. Availability and implementationFreely available at https://github.com/MIST-Explorer/MIST-Explorer.

bioinformatics↗

bioRxiv2025

CAR T cell engineering impacts antigen-independent activation and co-inhibition

Viral vectors have successfully modified T cells to express chimeric antigen receptors (CAR), leading to clinical approvals. However, their high cost and regulatory challenges hinder rapid and broad clinical translation. Here, we demonstrate that our lentivirally (LV) manufactured R110-CAR T cells, targeting a leukemia neoepitope, can also be engineered using non-viral Sleeping Beauty (SB) transposition with minimal-sized DNA vectors. Flow cytometry and single-cell sequencing was used to compare the two production modes using healthy donor and CLL patient-derived T cells and a CD19-CAR T cell control. SB products were shifted towards CD8+ subsets with expression of activation/co-inhibition markers (CD69, LAG-3, TIM-3) despite their naive-like phenotype and lack of antigenic challenge. The CAR binding moiety modulated these patterns with R110-CAR T cells showing more aberrant phenotypes. Moreover, SB engineering resulted in inflammatory signatures along with RIG-I-like and TOLL-like nucleotide sensing potentially resulting from the transfection procedure. Patient-derived products showed significantly fewer CAR-expressing cells, reduced proliferation clusters, and lower T cell diversity, particularly with SB manufacturing, pointing at potential challenges with this method when engineering CLL T cells. Together, our data suggest that the engineering mode may substantially influence T cell properties and that these are further modulated by the CAR binding moiety and the type of T cell donor.

immunology↗

bioRxiv2024

Assembling a true "Olympic Gel" from >16,000 combinatorial DNA rings

Olympic gels are an elusive form of soft matter, comprising a three-dimensional network of mechanically interlocked cyclic molecules. In the absence of defined network junctions, the high conformational freedom of the molecules was previously theorized to confer unique mechanical properties to Olympic gels, such as non-linear elasticity and unconventional swelling characteristics. However, the synthesis of an Olympic gel exhibiting these intriguing features is challenging, since unintended crosslinking and polymerization processes are often favored over cyclization. Here, we report the successful assembly of a true Olympic gel from a library of DNA rings comprising more than 16,000 distinct molecules. Each of these rings contains a unique sequence domain that can be enzymatically activated to produce reactive termini that favor intramolecular cyclization. We characterized the genetic, mechanical, and structural characteristics of the material by next-generation sequencing, oscillatory rheology, large-scale computational simulations, atomic force microscopy, and cryogenic electron microscopy. Our results confirm the formation of a stable Olympic gel, which exhibits unique swelling behavior and an elastic response that is exclusively determined by entanglements, yet persists on long time scales. By combining concepts from polymer physics, synthetic biology, and DNA nanotechnology, this new material class provides a flexible experimental platform for future studies into the effects of network topology on macroscopic material properties and its function as a carrier of genetic information in biological and biomimetic systems. This work moreover demonstrates that exotic material properties can emerge in systems with a high compositional complexity that is more reminiscent of biological than synthetic matter.

bioengineering↗

bioRxiv2024

A direct neural signature of serial dependence in working memory

Serial dependence describes the phenomenon that current object representations are attracted to previously encoded and reported representations. While attractive biases have been observed reliably in behavior, a direct neural correlate has not been established. Previous studies have either shown a reactivation of past information without observing a neural signal related to the bias of the current information, or a repulsive distortion of current neural representations contrasting the behavioral bias. The present study recorded neural signals with magnetoencephalography during a working memory task to identify neural correlates of serial dependence. Participants encoded and memorized two sequentially presented motion directions per trial, one of which was later retro-cued for report. Multivariate analyses provided reliable reconstructions of both motion directions. Importantly, the reconstructed directions in the current trial were attractively shifted towards the target direction of the previous trial. This neural bias mirrored the behavioral attractive bias, thus reflecting a direct neural signature of serial dependence. The use of a retro-cue task in combination with magnetoencephalography allowed us to determine that this neural bias emerged at later, post-encoding time points. This timing suggests that serial dependence in working memory affects memorized information during read-out and reactivation processes that happen after the initial encoding. Impact StatementMagnetoencephalographic recordings revealed a direct neural signature of serial dependence, i.e., an attractive bias of current towards previous representations, which emerged at late, post-encoding stages of processing in working memory.

neuroscience↗

bioRxiv2024

Electrophysiological correlates of lucid dreaming

Lucid dreaming (LD) is a state of conscious awareness of the current dream state, predominantly associated with REM sleep. Research progress in uncovering the neurobiological basis of LD has been hindered by low sample sizes, diverse EEG setups, and specific artifact issues like saccadic eye movements and signal non-stationarity. To address these matters, we developed a multi-stage preprocessing pipeline that integrates standardized early-stage preprocessing, artifact subspace reconstruction, and signal-space projection. This approach enhanced data quality by precisely removing saccadic potential effects even in setups with minimal channels. To robustly identify the electrophysiological correlates of LD, we applied this methodology to LD data collected across laboratories (pooled N = 44) and explored sensor-and source-level markers hypothesized to underlie LD. Compared to non-lucid REM sleep, we observed few robust differences on the EEG sensor level, which is in line with recent findings. In contrast, on the source level, gamma1 power (30-36 Hz) showed increases during LD in left-hemispheric temporal areas, which might reflect verbal insight processes. Gamma1 power also increased around the onset of LD eye signaling in right temporo-occipital regions including the right precuneus, in line with its involvement in self-referential thinking. Reductions in beta power (12-30 Hz) during LD in right central and parietal areas including the temporo-parietal junction are potentially associated with a conscious reassessment of the veridicality of the currently perceived reality. Notably, functional connectivity in alpha band (8-12 Hz) increased during LD, in contrast to the reductions typically seen in psychedelic states, highlighting enhanced self-awareness. Taken together, these findings illuminate the electrophysiological correlates of LD state, and may serve as a basis to uncover neural mechanisms at the time point of lucid dream insight.

neuroscience↗

bioRxiv2023

Dopamine-iron homeostasis interaction rescues mitochondrial fitness in Parkinson's disease

Imbalances of iron and dopamine metabolism along with mitochondrial dysfunction have been linked to the pathogenesis of Parkinsons disease (PD). We have previously suggested a direct link between iron homeostasis and dopamine metabolism, as dopamine can increase cellular uptake of iron into macrophages thereby promoting oxidative stress responses. In this study, we investigated the interplay between iron, dopamine, and mitochondrial activity in neuroblastoma SH-SY5Y cells and human induced pluripotent stem cell (hiPSC)-derived dopaminergic neurons differentiated from a healthy control and a PD patient with a mutation in the -synuclein (SNCA) gene. In SH-SY5Y cells, dopamine treatment affected the expression of transmembrane iron transporters and cellular iron accumulation. Furthermore, dopamine supplementation led to decreased mitochondrial respiration and reduced mitochondrial fitness, including reduced mtDNA copy number and citrate synthase activity, increased oxidative stress and impaired aconitase activity. In dopaminergic neurons derived from a healthy control individual, dopamine showed comparable effects as observed in SH-SY5Y cells. The hiPSC-derived PD neurons harboring an endogenous SNCA mutation demonstrated altered mitochondrial iron homeostasis, reduced mitochondrial capacity along with increased oxidative stress and alterations of tricarboxylic acid cycle linked metabolic pathways compared with control neurons. Importantly, dopamine treatment of these PD neurons promoted a rescue effect by increasing mitochondrial respiration, activating antioxidant stress response, and normalizing altered metabolite levels linked to mitochondrial function. These observations provide evidence that dopamine affects iron homeostasis, intracellular stress responses and mitochondrial function in healthy cells, while dopamine supplementation can restore this disturbed regulatory network in PD cells.

neuroscience↗

bioRxiv2023

Linking modulation of bio-molecular phase behaviour with collective interactions

Bio-molecular condensates formed in the cytoplasm of cells are increasingly recognised as key spatiotemporal organisers of living matter, and are implicated in a wide range of functional or pathological processes. This discovery opens up a new avenue for condensate-based applications and a crucial step in controlling this process is to understand the underlying interactions driving condensate formation or dissolution. However, these condensates are highly multi-component assemblies and many inter-component interactions are present, rendering it difficult to identify key promoters of phase separation. In this work, we extend the recently formulated dominance analysis to modulations of condensate formation. By carrying out dilute phase concentration measurements of a single target solute, the theoretical framework allows one to deduce whether the modulator acts on the target solute or another unspecified, auxiliary solute, as well as the attractive/repulsive nature of the added interaction. This serve as a general guide towards deducing possible modulation mechanisms on the molecular level, which can be complemented by orthogonal measurements. As a case study, we investigate the modulation of G3BP1/RNA condensates by the small molecule suramin, and the dominance measurements point towards a dissolution mechanism where suramin acts on G3BP1 to disrupt G3BP1/RNA interactions, as confirmed by a diffusional sizing assay. Our approach and the dominance framework have a high degree of adaptability and can be applied in many other condensate-forming systems.

biophysics↗

bioRxiv2022

Coronary vessel assembly involves patterned endocardial sprouting and tip-cell-to artery specification

The coronary vasculature comprises superficial coronary veins and deeper coronary arteries and capillaries that critically support the high metabolic activity of the beating heart. Understanding how different endothelial progenitor sources jointly shape and remodel the coronary vasculature into its adult pattern has recently attracted great research interest, and spurred much debate. Here, using lineage tracing tools in combination with three-dimensional imaging, live-imaging in explants and single-cell transcriptional profiling, we demonstrate that sprouting angiogenesis drives both sinus venosus and endocardial contribution to coronary plexus. Whereas previous studies limit endocardial contribution to coronary vessels to the interventricular septum and ventral aspect of the heart, our study demonstrates extensive endocardial sprouting angiogenesis in the free ventricular walls. In particular, we identify a distinct subpopulation of endocardial cells that express future coronary markers and reside in both the embryonic and adult ventricular wall endocardium. Most importantly, we provide evidence for sprouting angiogenesis from both endocardium and subepicardial plexus towards the inner myocardial wall to determine pre-arterial specification. Additionally, sprouting from the endocardium leads to the establishment of perfused connections to the advancing coronary plexus, also followed by transitioning to the pre-arterial cell state. Distinct molecular profiles characterize sprouting populations in the intramyocardial and subepicardial layers that shape the prospective coronary arteries and veins, respectively. Harnessing the endocardial progenitors and targeting the distinct sprouting populations may in the future serve to tailor cardiac vascular adaptations for therapeutic purposes.

developmental biology↗

bioRxiv2022

Disturbed trophoblast transition links preeclampsia progression from placenta to the maternal syndrome

Pre-eclampsia (PE) is a syndrome that affects multiple organ systems and is the most severe hypertensive disorder in pregnancy. It frequently leads to preterm delivery, maternal and fetal morbidity and mortality and life-long complications1. We currently lack efficient screening tools2, 3 and early therapies4, 5 to address PE. To investigate the early stages of early onset PE, and identify candidate markers and pathways, we performed spatio-temporal multi-omics profiling of human PE placentae and healthy controls and validated targets in early gestation in a longitudinal clinical cohort. We used a single-nuclei RNA-seq approach combined with spatial proteo- and transcriptomics and mechanistic in vitro signalling analyses to bridge the gap from late pregnancy disease to early pregnancy pathomechanisms. We discovered a key disruption in villous trophoblast differentiation, which is driven by the increase of transcriptional coactivator p300, that ultimately ends with a senescence-associated secretory phenotype (SASP) of trophoblasts. We found a significant increase in the senescence marker activin A in preeclamptic maternal serum in early gestation, before the development of clinical symptoms, indicating a translation of the placental syndrome to the maternal side. Our work describes a new disease progression, starting with a disturbed transition in villous trophoblast differentiation. Our study identifies potential pathophysiology-relevant biomarkers for the early diagnosis of the disease as well as possible targets for interventions, which would be crucial steps toward protecting the mother and child from gestational mortality and morbidity and an increased risk of cardiovascular disease later in life.

systems biology↗

bioRxiv2022

Clarifying space use concepts in ecology: range vs. occurrence distributions

Quantifying animal movements is necessary for answering a wide array of research questions in ecology and conservation biology. Consequently, ecologists have made considerable efforts to identify the best way to estimate an animals home range, and many methods of estimating home ranges have arisen over the past half century. Most of these methods fall into two distinct categories of estimators that have only recently been described in statistical detail: those that measure range distributions (methods such as Kernel Density Estimation that quantify the long-run behavior of a movement process that features restricted space use) and those that measure occurrence distributions (methods such as Brownian Bridge Movement Models and the Correlated Random Walk Library that quantify uncertainty in an animal movement path during a specific period of observation). In this paper, we use theory, simulations, and empirical analysis to demonstrate the importance of applying these two classes of space use estimators appropriately and distinctly. Conflating range and occurrence distributions can have serious consequences for ecological inference and conservation practice. For example, in most situations, home-range estimates quantified using occurrence estimators are too small, and this problem is exacerbated by ongoing improvements in tracking technology that enable more frequent and more accurate data on animal movements. We encourage researchers to use range estimators to estimate the area of home ranges and occurrence estimators to answer other questions in movement ecology, such as when and where an animal crosses a linear feature, visits a location of interest, or interacts with other animals. Open Research StatementTracking data on Aepyceros melampus, Beatragus hunteri, Bycanistes bucinator, Cerdocyon thous, Eulemur rufifrons, Glyptemys insculpta, Gyps coprotheres, Madoqua guentheri, Ovis canadensis, Propithecus verreauxi, Sus scrofa, and Ursus arctos are publicly archived in the Dryad repository (Noonan et al. 2018; https://doi.org/10.5061/dryad.v5051j2), as are data from Procapra gutturosa (Fleming et al. 2014a; https://doi.org/10.5061/dryad.45157). Data on Panthera onca were taken from (Morato et al. 2018). Additional data are publicly archived in the Movebank repository under the following identifiers: Canis latrans, 8159699; Canis lupus, 8159399; Chrysocyon brachyurus, 18156143; Felis silvestris, 40386102; Gyps africanus, 2919708; Lepus europaeus, 25727477; Martes pennanti, 2964494; Panthera leo, 220229; Papio cynocephalus, 222027; Syncerus caffer, 1764627; Tapirus terrestris, 443607536; Torgos tracheliotus, 2919708; and Ursus americanus, 8170674.

ecology↗

bioRxiv2022

Cell Atlas at Single-Nuclei Resolution of the Adult Human Adrenal Gland and Adrenocortical Adenomas

The human adrenal gland is a complex endocrine tissue. Developmental studies on this tissue have been limited to animal models or human foetus. Here, we present a cell atlas analysis of the adult human normal adrenal gland, combining single-nuclei RNA sequencing and spatial transcriptome data to reconstruct adrenal gland development and tumourigenesis. We identified two populations of potential progenitor cells resident within the adrenal cortex: adrenocortical progenitors NR2F2+-ID1+ cells, located within and underneath the capsule, and medullary progenitors SYT1+-CHGA- cells, located in islets in the subcapsular region. Using pseudotime analyses, we provided evidence of the centripetal nature of adrenocortical cell development and of the essential role played by the Wnt/{beta}-catenin pathway in the adrenocortical self-renewal. By comparing transcriptional profiles of cells of normal adrenal glands and adrenocortical adenomas we revealed a high heterogeneity with six adenoma-specific clusters. Overall, our results give insights into adrenal plasticity and mechanisms underlying adrenocortical tumourigenesis.

physiology↗

bioRxiv2022

Recombination between heterologous human acrocentric chromosomes

The short arms of the human acrocentric chromosomes 13, 14, 15, 21, and 22 share large homologous regions, including the ribosomal DNA repeats and extended segmental duplications (Floutsakou et al. 2013; van Sluis et al. 2019). While the complete assembly of these regions in the Telomere-to-Telomere consortiums CHM13 provided a model of their homology (Nurk et al. 2022), it remained unclear if these patterns were ancestral or maintained by ongoing recombination exchange. Here, we show that acrocentric chromosomes contain pseudo-homologous regions (PHRs) indicative of recombination between non-homologs. Considering an all-to-all comparison of the high-quality human pangenome from the Human Pangenome Reference Consortium (HPRC) (Liao et al. 2022), we find that contigs from all of the acrocentric short arms form a community similar to those formed by single chromosomes or the sex chromosome pair. A variation graph (Garrison et al. 2018) constructed from centromere-spanning acrocentric contigs indicates the presence of regions where most contigs appear nearly identical between heterologous CHM13 acrocentrics. Except on chromosome 15, we observe faster decay of linkage disequilibrium in the PHRs than in the corresponding short and long arms, indicating higher rates of recombination (N. Li and Stephens 2003; Huttley et al. 1999). The PHRs include sequences previously shown to lie at the breakpoint of Robertsonian translocations (Jarmuz-Szymczak et al. 2014), and we show that their arrangement is compatible with crossover in inverted duplications on chromosomes 13, 14, and 21. The ubiquity of signals of recombination between heterologous chromosomes seen in the HPRC draft pangenomes acrocentric assemblies suggests that these shared sequences form the basis for recurrent Robertsonian translocations, providing sequence and population-based confirmation of hypotheses first developed cytogenetically fifty years ago (Hamerton et al. 1975).

genomics↗

bioRxiv2022

Exploring the emergence of morphological asymmetries around the brain's Sylvian fissure: a longitudinal study of shape variability in preterm infants.

Brain folding patterns vary within the human species, but some folding properties are common across individuals, including the Sylvian fissures inter-hemispheric asymmetry. Contrarily to the other brain folds (sulci), the Sylvian fissure develops through the process of opercularization, with the frontal, parietal and temporal lobes growing over the insular lobe. Its asymmetry may be related to the leftward functional lateralization for language processing, but the time-course of these asymmetries development is still poorly understood. In this study, we investigated refined shape features of the Sylvian fissure and their longitudinal development in 71 infants born extremely preterm (mean gestational age at birth: 26.5 weeks) and imaged once before and once at term-equivalent age (TEA). We additionally assessed asymmetrical sulcal patterns at TEA in the perisylvian and inferior frontal regions, neighbor to the Sylvian fissure. While reproducing renown strong asymmetries in the Sylvian fissure, we captured an early encoding of its main asymmetrical shape features, and we observed global asymmetrical shape features representative of a more pronounced opercularization in the left-hemisphere, contrasting with the previously reported right-hemisphere advance in sulcation around birth. This added novel insights about the processes governing early-life brain folding mechanisms, potentially linked to the development of language-related capacities. Highlights- Shape features can be isolated to describe quantitatively the development of the Sylvian fissure - Strong asymmetries are encoded as soon as 30 weeks of post-menstrual age - The process of opercularization is more pronounced in the left hemisphere

neuroscience↗