Biology subjects

Albert, M.

Publications and source records attributed to Albert, M..

At least 19 recordsLinked to original sources

bioRxiv2026

Single-cell metabolomics reveals infection-specific metabolic reprogramming of human macrophages

During intracellular infection, host cells adopt different metabolic states that traditional bulk analyses cannot distinguish. Using single-cell spatial metabolomics of human macrophages infected with Legionella pneumophila, we show that bacterial uptake activates host metabolism, whereas the bacterial effectors secreted through the type IV secretion system counteract this response and promote a glycolytic shift. The activity of effectors also generates distinct metabolic states within the infected macrophage population.

microbiology↗

bioRxiv2026

Rapid repurposing of microvillar content drives a flagellate-to-amoeboid switch in the closest relative of animals

Animal cells extensively remodel their cytoskeleton during differentiation and can notably switch between two major motility modes: flagellum-based swimming and actin-based crawling. We previously showed that choanoflagellates, the closest living relatives of animals and classically viewed as obligate flagellated swimmers, can retract their collar complex and adopt an amoeboid form within seconds under spatial confinement, independently of regulated gene expression. Here, using live imaging, ultrastructural expansion microscopy, and cryo-electron tomography in Salpingoeca rosetta, we identify rapid, cell-wide cytoskeletal remodeling as the ultrastructural basis of this switch. Unconfined choanoflagellates lack a detectable actin cortex but display an apical flagellum and cortical microtubules, with F-actin being largely restricted to microvilli. Confinement triggers calcium release from intracellular stores, which induces microvillar retraction and absorption of microvillar material into the cell body, including actin, ezrin-radixin-moesin 1, and plasma membrane. Remodeling of the internalized F-actin and repurposing of associated proteins supports de novo actin cortex formation, which is necessary for amoeboid motility. In parallel, cortical microtubules are disassembled, and the reabsorbed microvillar plasma membrane increases the surface area of the cell body, allowing the cell to flatten under confinement. Cryo-electron tomography reveals stepwise actin reorganization from internalized microvillar bundles to a cortical contractile meshwork combining bundles and scattered filaments. This work reveals considerable ultrastructural plasticity in the cytoskeletal architecture of choanoflagellates and supports an ancestral role for microvilli as reservoirs of membrane and cytoskeleton to potentiate cell phenotypic transitions.

evolutionary biology↗

bioRxiv2026

Archaeogenomic and Bioinformatic Analysis of the Columbus Lineage: Evidence from the Counts of Gelves.

The geographical and familial origins of Christopher Columbus have remained a subject of intense historiographical debate for over five centuries. Despite numerous hypotheses, empirical genetic evidence capable of resolving his ancestral history or place of birth has been absent from the literature until now. This study presents the third stage of the first forensic genetic analysis performed on skeletal remains belonging to several direct descendants of Columbus, spanning the 16th to 18th centuries. By applying Massively Parallel Sequencing (MPS) to analyse autosomal, X- and Y- chromosome DNA markers, and integrating the results with multidisciplinary evidence from historical, genealogical, archaeological, and anthropological research implicated in this project, the identification of several individuals founded in the Crypt of Santa Maria de Gracia located in Gelves (Sevilla, Spain) has been achieved. The analysis of their biological relatedness enabled the reconstruction of kinship networks among the individuals interred in the crypt, which, when interpreted in the context of documented genealogical lineages, provides indirect but consistent evidence pointing toward the debated origin of the discoverer.

genetics↗

bioRxiv2026

Stress-responsive Mycobacterium tuberculosis subpopulations manipulate macrophage polarization and can be targeted to limit inflammation

Tuberculosis is characterized by broad clinical heterogeneity that hinders infection control, with differences in lesion development, progression, and treatment outcomes. This complexity is likely associated with Mycobacterium tuberculosis inherent phenotypic variation and its capacity to diversify under host microenvironmental and antimicrobial stressors. Here, we analyze M. tuberculosis at the single-cell and subpopulation level using fluorescent reporters, imaging, transcriptomic, and functional assays. We identify RNA signatures specific to stress-responsive bacilli with translational potential. Focusing on the clinically validated chaperone GroEL2, we find that it correlates with M. tuberculosis growth rate and stress tolerance in vitro and intracellularly. Furthermore, GroEL2 phenotypic diversity influences innate responses in macrophages, which experience different polarization, in turn affecting GroEL2 expression. We also show that targeting GroEL2 impairs pathogen survival and dampens inflammation. This study provides a link between pathogen phenotypic variation and macrophage fates, with implications for early infection outcomes, local disease progression, and subpopulation-targeted interventions.

microbiology↗

bioRxiv2026

Automated Optimization of Bacterial Tracking Pipelines with TrackMate 8

Quantitative analysis of bacterial dynamics in time-lapse microscopy requires robust tracking pipelines, yet selecting and optimizing algorithms for specific experiments remains challenging. Indeed, Microbiologists are confronted with numerous algorithms that must be carefully chosen and parameterized to achieve optimal tracking for their experiments. We present an automated methodology to determine optimal tracking configurations for microbiological applications. It is based on TrackMate 8, a novel version of the TrackMate Fiji plugin extended with microbiology-specific tools. Our approach systematically evaluates algorithm-parameter combinations optimizing biologically relevant metrics (e.g., cell-cycle accuracy, bacteria morphology) and includes: (1) integration of deep-learning algorithms (Omnipose, YOLO, Trackastra) adequate for bacteria images in TrackMate, (2) a TrackMate-Helper extension for parameter optimization, and (3) a tracking and segmentation editor for tracking ground-truth generation. We demonstrate the effectiveness of the methodology on two use cases showing its adaptability to diverse experimental conditions. This methodology enables microbiologists with a widely applicable, automated framework to optimize tracking pipelines, facilitating quantitative analysis in bacterial imaging.

microbiology↗

bioRxiv2025

'Guess Who?': Forensic genetics and archaeology converge to identify Cristopher Columbus descendants.

The generation of DNA profiles from skeletal remains is a core challenge in forensic genetics, particularly for the identification of missing persons and the resolution of cold cases. Factors such as diagenesis, DNA fragmentation, and the presence of PCR inhibitors severely compromise traditional methodologies, limiting the potential for successful identification. Similarly, in many archaeological studies, the presence of multiple individuals within a single burial site presents a significant challenge for accurate identification. This study shows how the most innovative forensic genetic techniques can be integrated into archaeological research, enabling the identification of individuals through the establishment of familial relationships between remains recovered from an archaeological site. A large-scale SNP assay, Forenseq(R) Kintelligence HT, has been applied to a familial group dating back to the 16th-17th century, allowing robust kinship calculations and lineage studies, that, in a first stage, lead to the identification of four individuals spanning four generations within the same family.

genomics↗

bioRxiv2025

Poly(ADP-ribose) Polymerase 1 Deficiency Attenuates Amyloid Pathology, Neurodegeneration, and Cognitive Decline in a Familial Alzheimer Disease Model

Poly(ADP-ribose) (PAR) polymerase-1 (PARP1) has been implicated in DNA damage responses and neuroinflammation in Alzheimers disease (AD), yet its role in amyloid-{beta} (A{beta}) pathology remains unclear. Here, we show that PARP1 activation drives A{beta} pathology and neurodegeneration. Using a sensitive ELISA, we observed significantly elevated PAR levels in the cerebrospinal fluid (CSF) of patients with mild cognitive impairment (MCI) and AD compared to controls. In vitro, oligomeric A{beta}1-42 activated PARP1 and induced DNA damage, while genetic or pharmacological inhibition of PARP1 conferred neuroprotection. In vivo, PARP1 knockout in the 5XFAD mouse model of amyloidosis led to reduced amyloid plaque burden, preserved synaptic and neuronal integrity, attenuated glial activation and neuroinflammation, and rescued cognitive deficits. Mechanistically, PARP1 deficiency decreased amyloid precursor protein (APP) and BACE1 levels, altered {gamma}-secretase complex composition, and enhanced A{beta} degradation via neprilysin. These findings position PARP1 as a critical mediator of A{beta} toxicity and neurodegeneration, suggesting its inhibition as a promising therapeutic strategy for AD. Significance StatementOur study identifies poly(ADP-ribose) (PAR) as an elevated biomarker in the cerebrospinal fluid of patients with mild cognitive impairment and Alzheimers disease, correlating with established markers of amyloid pathology. We demonstrate that PARP1, the enzyme responsible for PAR synthesis, is activated by neurotoxic A{beta}1-42 and mediates neuronal death, amyloid plaque formation, neuroinflammation, and cognitive deficits in a mouse model of AD. Importantly, genetic ablation of PARP1 not only protects neurons from A{beta} toxicity but also reduces amyloid burden by suppressing A{beta} production and enhancing its degradation. These findings highlight PARP1 as a critical regulator of amyloid pathology and neurodegeneration, and suggest that PARP1 inhibition may offer a promising therapeutic avenue for Alzheimers disease by simultaneously targeting multiple pathogenic mechanisms.

neuroscience↗

bioRxiv2025

Human-specific morphoregulatory signatures in basal radial glia characterize neocortex evolution

As the seat of our cognition, the human neocortex is an object of immense fascination. Human neocortex expansion during evolution has been attributed to an increase in the proliferative capacity of neural progenitor cells during development, particularly basal radial glia (bRG). Despite their evolutionary relevance, the genomic changes driving human-specific bRG biology remain uncharacterized. We used comparative chromatin and transcriptional profiling of neural progenitor cells isolated from gorilla, chimpanzee and human cerebral organoids to identify cis-regulatory elements that have gained activity in humans. Focusing specifically on bRG, we discovered that morphoregulatory enhancer activity and gene expression signatures distinguish human bRG from other great apes. Functional analysis of the morphoregulatory genes FAM107A and CNGA3 in human organoids revealed that these genes are required for the morphological complexity of human bRG. Taken together, our interspecies comparison of basal radial glia suggests that human-specific morphoregulatory signatures characterize neocortex evolution.

neuroscience↗

bioRxiv2024

In toto analysis of multicellular arrangement reduces embryonic tissue diversity to two archetypes that require specific cadherin expression

Breakthroughs in transcriptomics are providing exciting new ways to characterise cellular diversity within organisms1-3. Yet, organisms are more than the sum of their differentiated cells, as the biological function of most cell types only emerges when they are organised into tissues with characteristic architectures4. The mechanisms that drive architectural diversification at the tissue level remain poorly understood, in part due to a general lack of methods for directly comparing different organisational patterns. Here we establish nuQLOUD, an efficient imaging and computational framework that reduces complex tissues to clouds of nuclear positions, enabling the extraction of cell-type agnostic architectural features. Applying nuQLOUD to whole developing zebrafish embryos reveals that global tissue diversity can be efficiently reduced to two primary archetypes, termed amorphous and crystalline. We investigate the molecular drivers of tissue archetypes by focussing on cadherin cell adhesion molecules and demonstrate that the expression domains of major cadherins segregate along tissue-archetypal lines. Further spatiotemporal analysis and targeted perturbation of cadherin expression in different organs identifies N-Cadherin as a general driver of the amorphous archetype. Thus, this systematic investigation of architectural diversity provides a new way to conceptualise embryonic organisation and understand drivers of tissue diversification within a standardised framework.

developmental biology↗

bioRxiv2024

THE FIRST COMPREHENSIVE FORENSIC GENETIC STUDY OF A MEMBER OF CHRISTOPHER COLUMBUS' FAMILY: HIS GREAT-GREAT-GRANDSON

The present study has successfully obtained genetic information that allow the identification from direct descendants of Christopher Columbus, dating from 1526 to 1734. This represents the first achievement of this unique objective. The results obtained from the analysed samples, characterized by their significant antiquity, yield exceptional insights into forensic genetics and its newest protocols and methodologies applied to the study of ancient skeletal remains. This work presents the preliminary results of the whole family study using massive parallel sequencing, focusing on the autosomal Single Nucleotide Polymorphism (SNP) and Short Tandem Repeats (STR) markers, including their flanking region sequences, as well as ancestry informative markers (AIMS) of the great-great-grandson of the discoverer. The results of this project pave the way towards the application of new sequencing technologies for the study of genetic evolution, biogeographical origins and forensic identification of historical characters.

genomics↗

bioRxiv2024

Epigenome profiling identifies H3K27me3 regulation of extra-cellular matrix composition in human corticogenesis

Epigenetic mechanisms regulate gene expression programs during neurogenesis, but the extent of epigenetic remodelling during human cortical development remains unknown. Here, we characterize the epigenetic landscape of the human developing neocortex by leveraging Epi-CyTOF, a mass cytometry-based approach for the simultaneous single cell analysis of more than 30 epigenetic marks. We identify H3K27me3, deposited by Polycomb Repressive Complex 2 (PRC2), as the modification with the strongest cell type-specific enrichment. Inhibition of PRC2 in human cortical organoids resulted in a shift of neural progenitor cell (NPC) proliferation towards differentiation. Cell type- specific profiling of H3K27me3 not only identified neuronal differentiation genes in the human neocortex, but also extra-cellular matrix (ECM) genes. PRC2 inhibition resulted in increased production of the proteoglycan Syndecan 1. Overall, this study comprehensively characterizes the epigenetic state of specific neural cell types and highlights a novel role for H3K27me3 in regulating the ECM composition in the human developing neocortex.

developmental biology↗

bioRxiv2024

TYPE THREE SECRETION SYSTEM-INDUCED MECHANOPORATION OF VACUOLAR MEMBRANES

SO_SCPLOWUMMARYC_SCPLOWEndomembrane breaching is a crucial strategy employed by intracellular pathogens enclosed within vacuoles to access the nutrient-rich cytosol for intracellular replication. While bacteria use various mechanisms to compromise host membranes, the specific processes and factors involved are often unknown. Shigella flexneri, a major human pathogen, accesses the cytosol relying on the Type Three Secretion System (T3SS) and secreted effectors. Using in-cell correlative light and electron microscopy, we tracked the sequential steps of Shigella host cell entry. Moreover, we captured the T3SS, which projects a needle from the bacterial surface, in the process of puncturing holes in the vacuolar membrane. This initial puncture ensures disruption of the vacuolar membrane. Together this introduces the concept of mechanoporation via a bacterial secretion system as a crucial process for bacterial pathogen-induced membrane damage. GO_SCPLOWRAPHICALC_SCPLOW AO_SCPLOWBSTRACTC_SCPLOW O_FIG O_LINKSMALLFIG WIDTH=199 HEIGHT=200 SRC="FIGDIR/small/613840v1_ufig1.gif" ALT="Figure 1"> View larger version (54K): org.highwire.dtl.DTLVardef@1669028org.highwire.dtl.DTLVardef@8259cborg.highwire.dtl.DTLVardef@1d522caorg.highwire.dtl.DTLVardef@1df0f2d_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2024

Canonical and non-canonical PRC1 differentially contribute to the regulation of neural stem cell fate

Neocortex development is characterized by sequential phases of neural progenitor cell (NPC) expansion, neurogenesis and gliogenesis. Polycomb-mediated epigenetic mechanisms are known to play important roles in regulating the lineage potential of NPCs during development. The composition of Polycomb Repressive Complex 1 (PRC1) is highly diverse in mammals and was hypothesized to contribute to context-specific regulation of cell fate. Here, we have performed side-by-side comparison of the role of canonical PRC1.2/1.4 and non-canonical PRC1.3/1.5, all of which are expressed in the developing neocortex, in NSC proliferation and differentiation. We found that the deletion of Pcgf2/4 in NSCs led to a strong reduction in proliferation and to altered lineage fate, both during the neurogenic and gliogenic phase, whereas Pcgf3/5 played a minor role. Mechanistically, genes encoding stem cell and neurogenic factors were bound by PRC1 and differentially expressed upon Pcgf2/4 deletion. Thus, rather than different PRC1 sub-complexes contributing to different phases of neural development, we found that canonical PRC1 played a more significant role in NSC regulation during proliferative, neurogenic and gliogenic phases compared to non-canonical PRC1.

developmental biology↗

bioRxiv2024

A small RNA derived from the 5' end of the IS200 tnpA transcript regulates multiple virulence pathways in Salmonella Typhimurium

The insertion sequence IS200 is widely distributed in Eubacteria. Despite its wide-ranging occurrence, IS200 does not appear to be mobile and as such is considered an ancestral component of bacterial genomes. Previous work in Salmonella enterica revealed that the IS200 tnpA transcript is processed to form a small highly structured RNA (5tnpA) that participates in the post-transcriptional control of invF expression, encoding a key transcription factor in this enteropathogens invasion regulon. To further examine the scope of 5tnpA transcript integration into Salmonella gene expression networks, we performed comparative RNA-seq revealing the differential expression of over 200 genes in a Salmonella SL1344 5tnpA disruption strain. This includes the genes for the master regulators of both invasion and flagellar regulons (HilD and FlhDC, respectively), plus genes involved in cysteine biosynthesis (cysteine regulon) and an operon (phsABC) encoding a thiosulfate reductase complex. These expression changes were accompanied by an 80-fold increase in Salmonella invasion of HeLa cells. Likewise, a phsABC disruption strain was associated with an increased invasion specifically under anaerobic growth conditions. Based on these findings, we propose that early induction of invasion and motility regulons in the absence of 5tnpA causes a metabolic stress resulting in cysteine limitation and activation of CysB, which turns down expression of the phsABC operon to increase the flux of thiosulfate in the media towards cysteine production. Taken together, this study provides a powerful new example of bacterial transposon domestication that is based not on the production of a regulatory protein, but of a transposon-derived small RNA.

molecular biology↗

bioRxiv2024

HistoGWAS: An AI-enabled Framework for Automated Genetic Analysis of Tissue Phenotypes in Histology Cohorts

Understanding how genetic variation affects tissue structure and function is crucial for deciphering disease mechanisms, yet comprehensive methods for genetic analysis of tissue histology are lacking. We address this gap with HistoGWAS, a framework integrating AI tools for representation learning and image generation with fast variance component models to enable scalable and interpretable genome-wide association studies of histological traits. HistoGWAS employs histology foundation models for automated trait characterization and generative models to visually interpret the genetic influences on these traits. Applied to eleven tissue types from the GTEx cohort, HistoGWAS identifies four genome-wide significant loci, which we linked to specific tissue histological and gene expression changes. A power analysis confirms the effectiveness of HistoGWAS in analyses of large-scale histological data, underscoring its potential to transform imaging genetic studies.

genetics↗

bioRxiv2024

Sex, racial, and APOE-ϵ4 allele differences in longitudinal white matter microstructure in multiple cohorts of aging and Alzheimer's disease

Structured AbstractO_ST_ABSINTRODUCTIONC_ST_ABSThe effects of sex, race, and Apolipoprotein E (APOE) - Alzheimers disease (AD) risk factors - on white matter integrity are not well characterized. METHODSDiffusion MRI data from nine well-established longitudinal cohorts of aging were free-water (FW)-corrected and harmonized. This dataset included 4,702 participants (age=73.06 {+/-} 9.75) with 9,671 imaging sessions over time. FW and FW-corrected fractional anisotropy (FAFWcorr) were used to assess differences in white matter microstructure by sex, race, and APOE-{varepsilon}4 carrier status. RESULTSSex differences in FAFWcorr in association and projection tracts, racial differences in FAFWcorr in projection tracts, and APOE-{varepsilon}4 differences in FW limbic and occipital transcallosal tracts were most pronounced. DISCUSSIONThere are prominent differences in white matter microstructure by sex, race, and APOE- {varepsilon}4 carrier status. This work adds to our understanding of disparities in AD. Additional work to understand the etiology of these differences is warranted. HighlightsO_LISex, race, and APOE-{varepsilon}4 carrier status relate to white matter microstructural integrity C_LIO_LIFemales generally have lower FAFWcorr compared to males C_LIO_LINon-Hispanic Black adults generally have lower FAFWcorr than non-Hispanic White adults C_LIO_LIAPOE-{varepsilon}4 carriers tended to have higher FW than non-carriers C_LI Research in Context Systematic ReviewThe authors used PubMed and Google Scholar to review literature that used conventional and free-water (FW)-corrected microstructural metrics to evaluate sex, race, and APOE-{varepsilon}4 differences in white matter microstructure. While studies have previously explored differences by sex and APOE-{varepsilon}4 status, less is known about racial differences and no large-scale FW-corrected analysis has been performed. InterpretationSex and race were more associated with FAFWcorr while APOE-{varepsilon}4 status was associated with FW metrics. Association, projection, limbic, and occipital transcallosal tracts showed the greatest differences. Future DirectionFuture studies to determine the biological and social pathways that lead to sex, racial, and APOE-{varepsilon}4 differences are warranted. Consent StatementAll participants provided informed consent in their respective cohort studies.

neuroscience↗

bioRxiv2024

Molecular Signatures of Normal Pressure Hydrocephalus: A Large-scale Proteomic Analysis of Cerebrospinal Fluid

Given the persistent challenge of differentiating idiopathic Normal Pressure Hydrocephalus (iNPH) from similar clinical entities, we conducted an in-depth proteomic study of cerebrospinal fluid (CSF) in 28 shunt-responsive iNPH patients, 38 Mild Cognitive Impairment (MCI) due to Alzheimers disease, and 49 healthy controls. Utilizing the Olink Explore 3072 panel, we identified distinct proteomic profiles in iNPH that highlight significant downregulation of synaptic markers and cell-cell adhesion proteins. Alongside vimentin and inflammatory markers upregulation, these results suggest ependymal layer and transependymal flow dysfunction. Moreover, downregulation of multiple proteins associated with congenital hydrocephalus (e.g., L1CAM, PCDH9, ISLR2, ADAMTSL2, and B4GAT1) points to a possible shared molecular foundation between congenital hydrocephalus and iNPH. Through orthogonal partial least squares discriminant analysis (OPLS-DA), a panel comprising 13 proteins has been identified as potential diagnostic biomarkers of iNPH, pending external validation. These findings offer novel insights into the pathophysiology of iNPH, with implications for improved diagnosis.

neuroscience↗

bioRxiv2023

Primate-expressed EPIREGULIN promotes basal progenitor proliferation in the developing neocortex

Neocortex expansion during evolution is linked to higher numbers of neurons thought to result from increased proliferative capacity and neurogenic potential of basal progenitor cells (BPs) during development. Here we show that EREG, encoding the growth factor EPIREGULIN, is expressed in the human developing neocortex and in gorilla organoids, but not in the mouse neocortex. Addition of EPIREGULIN to the mouse neocortex increases proliferation of BPs via EGFR-mediated signaling, whereas ablation of EREG in human cortical organoids reduces BP proliferation. Addition of EPIREGULIN to cortical organoids promotes a further increase in proliferation of gorilla but not human BPs. Finally, we identify putative cis-regulatory elements that may contribute to inter-species differences in EREG expression. Overall, our results suggest that species-specific expression of EPIREGULIN may contribute to increased neocortex size in primates by providing a pro-proliferative signal to BPs in the subventricular zone progenitor niche.

developmental biology↗