Biology subjects

Camara, A.

Publications and source records attributed to Camara, A..

9 recordsLinked to original sources

bioRxiv2026

Booster vaccination improves the durability of antibody-secreting plasma cells

Booster vaccination can restore antibody titres and protection, but whether it improves long-term durability by expanding plasma cell (PC) numbers or also by shifting PC fate toward intrinsically longer-lived states remains unclear. Here we established longitudinal in vivo ground truth for PC persistence by combining PC-specific genetic timestamping, clonal tracking, and multi-timepoint single-cell profiling across spleen and bone marrow. We resolved PC longevity as a layered, non-binary architecture comprising short-, intermediate-, and long-lived programs, and showed that program identity is specified early in secondary lymphoid tissues and largely maintained as PCs populate bone marrow niches. Primary vaccine responses initiated from naive B-cells generated a prominent intermediate-lived wave, whereas memory B-cell recall during boosting redistributed output toward long-lived programs rather than recreating the intermediate-lived compartment characteristic of priming. Conserved longevity signatures projected onto early circulating PCs provide a cross-species framework to infer durability programs, supporting benchmarking of vaccine regimens by predicted persistence rather than peak titres. HighlightsO_LIGenetic timestamping resolves short-, intermediate-, and long-lived PC programs C_LIO_LILongevity programs are imprinted early and maintained from lymphoid organs to bone marrow C_LIO_LICross-species signatures stratify human blood and bone marrow PCs by persistence C_LIO_LIBoosting via MBC recall enriches long-lived PC and contracts the intermediate-lived tier C_LI

immunology↗

bioRxiv2026

Emergence of mpox in Guinea: sporadic clade IIa cases and a clade IIb upsurge

BackgroundMpox virus (MPXV) has caused recurrent outbreaks in West Africa. However, Guinea had not previously reported laboratory-confirmed cases or MPXV genomic data. MethodsSuspected cases were identified in the NZerekore region as well as in the Conakry (Sept 2024- Dec 2025) and confirmed by real-time PCR in regional and central laboratories, respectively. Whole-genome sequencing using nanopore technology was performed in-country, followed by phylogenetic and time-scaled evolutionary analyses. FindingsThe first mpox case was clinically diagnosed in September 2024 in the NZerekore region and laboratory-confirmed by the prefectural laboratory in Gueckedou. In total, seven cases were confirmed in Forest Guinea, of which five complete or almost complete MPXV genomes were recovered. All belonged to MPXV clade IIa. Genomic divergence, ancestral dating, and low APOBEC3-associated mutation frequencies were consistent with multiple independent zoonotic spillover events. In June 2025, one of the first mpox cases of an unfolding outbreak was confirmed in Conakry. Whole genome sequencing revealed MPXV clade IIb lineage G.1. By December 2025, the number of laboratory-confirmed mpox cases nationwide increased to 2,151. A total of nine outbreak strains were sequenced, all belonging to Clade IIb. The genomes clustered with contemporaneous genomes from Sierra Leone and showed high APOBEC3-associated mutation frequencies, suggesting sustained human-to-human transmission in the region. InterpretationThese data demonstrate simultaneous circulation of MPXV clade IIa and IIb strains in Guinea, likely resulting from zoonotic spillover and human-to-human transmission, respectively. Decentralised diagnostics and in-country sequencing facilitated rapid case confirmation and genomic surveillance, highlighting the importance of these critical capacities for outbreak preparedness and response. FundingGerman Federal Ministry of Health and the German Center for Infection Research (DZIF).

genomics↗

bioRxiv2025

Phospho-signalling deregulation of the mTOR pathway in fibroblasts from LRRK2 Parkinson s patients

Activating mutations at the leucine-rich repeat kinase 2 (LRRK2) gene are the most frequent genetic cause of Parkinsons Disease (PD). Using in-depth mass-spectrometry, here we analysed the impact of LRRK2 mutations on the proteome and phospho-proteome of skin fibroblasts from a large LRRK2 clinical cohort from Spain. The cohort encompassed G2019S LRRK2-associated PD (L2PD) (n=15), G2019S LRRK2 non-manifesting carriers (L2NMCs) (n=13), idiopathic PD (iPD) (n=12), and control subjects (n=14) (total n=54). The proteome analysis revealed 89 differential proteins in G2019S L2PD (58 down/ 31 up) and 168 in G2019S L2NMCs (127 down / 41 up) compared to controls. Most of these proteome changes involved deficits in proteins related to mitochondrial energy and ribosomal protein synthesis. At the phospho-proteome level, we identified 394 differential phospho-sites in G2019S L2PD (188 hyper / 206 hypo), 367 in G2019S L2NMCs (215 hyper / 152 hypo), and 428 in iPD (214 hyper / 214 hypo) compared with controls. These phospho-proteomic changes included hyper-phosphorylated proteins associated with the mTOR and Rho GTPase pathways. Notably, the top hyper-phosphorylated hit in G2019S carriers was pThr37/46 4E-BP1, a key effector of the mTOR pathway controlling protein synthesis, and this protein was also deregulated in iPD. In summary, our study uncovers peripheral deregulation of mTOR phospho-signalling associated with LRRK2 mutations, which is related to deficits in mitochondrial and ribosomal proteins, and affects converging pathways altered in iPD.

neuroscience↗

bioRxiv2025

A SHERLOCK toolbox for the eco-epidemiological surveillance of animal African trypanosomosis reveals a similar parasite diversity in domestic pigs in two ancient sleeping sickness foci in Western Africa.

Animal African trypanosomosis (AAT), caused by protist parasites of the genus Trypanosoma, puts upward of a million head of livestock at risk across 37 countries in Africa. The economic impact of AAT and the presence of human-infectious trypanosomes in animals place a clear importance on improving diagnostics for animal trypanosomes to map the distribution of the veterinary parasites and identify reservoirs of human-infectious trypanosomes. We have adapted the CRISPR-based detection toolkit SHERLOCK (Specific High-sensitivity Enzymatic Reporter unLOCKing) for trypanosomatid parasites responsible for AAT (SHERLOCK4AAT) including Pan- trypanosomatid, Trypanozoon, T. vivax, T. congolense, T. theileri, T. simiae and T. suis assays. To test the applicability of this technique in the field, we analysed dried blood spots collected from 200 farm and 224 free-ranging pigs in endemic and historical human African trypanosomiasis foci in Guinea and Cote dIvoire, respectively. The results revealed that SHERLOCK4AAT can detect and discriminate between trypanosome species involved in multiple infections with a high sensitivity. 62.7 % [58.1, 67.3] of pigs were found infected with at least one trypanosome species. T. brucei gambiense, a human-infectious trypanosome, was found in one animal at both sites, highlighting the risk that these animals may act as persistent reservoirs. These data suggest that, due to their proximity to humans and their attractiveness to tsetse flies, pigs could act as sentinels to monitor T. b. gambiense circulation using the SHERLOCK4AAT toolbox.

microbiology↗

bioRxiv2023

Regulation of BCR-mediated Ca2+ mobilization by MIZ1-TIMBIM4 safeguards IgG1+ GC B cell positive selection

The transition from IgM to affinity-matured IgG antibodies is vital for effective humoral immunity. This is facilitated by germinal centers (GCs) through affinity maturation and preferential accumulation of IgG+ B cells over IgM+ B cells. However, it is not known whether the positive selection of the different immunoglobulin isotypes within GCs varies in its dependency on specific transcriptional mechanisms. Here, we identified IgG1+ GC B cell transcription factor dependency using CRISPR-Cas9 and conditional mouse genetics. We found that MIZ1 was specifically required for IgG1+ GC B cell survival during positive selection, whereas IgM+ GC B cells were largely independent. Mechanistically, MIZ1 induced TMBIM4, an ancestral anti-apoptotic protein that regulated inositol trisphosphate receptor mediated Ca2+ mobilization downstream of IgG1. The MIZ1-TMBIM4 axis prevented mitochondrial dysfunction-induced IgG1+ GC cell death caused by excessive Ca2+ accumulation. This study uncovers a unique immunoglobulin isotype-specific dependency, on a hitherto unidentified mechanism in GC positive selection.

immunology↗

bioRxiv2022

Actin cytoskeleton dynamics affect replication of Human Metapneumovirus

Human Metapneumovirus (hMPV) is responsible for viral respiratory infection with clinical and epidemiological relevance in pediatric, immunocompromised, and elderly populations. Little is known about hMPV in vitro replication processes and their relationship with cellular structures such as the cytoskeleton. Our goal was to evaluate the role of the actin cytoskeleton in hMPV replication at different stages of viral growth. hMPV was isolated in Vero cells from a clinical sample and identified as A2 genotype. The cytopathic effect was detected by the appearance of cell rounding and refractory cell clusters. The growth curve showed that viral replication maximum level was between 48 and 72 hpi. The highest percentage of infected cells and intracellular hMPV-protein were detected at the early stages of the replication cycle. Disruption of actin microfilaments with Cytochalasin D during the early events provoked an increase in both intracellular and extracellular viruses. We demonstrate that the early phase of the hMPV curve is crucial for viral replication; and the disruption of microfilaments during this time increments both viral protein expression and release of viruses to the extracellular space. This study contributes to elucidate wild-type hMPV growth kinetics, providing new insights on the actin cytoskeleton role in viral replication mechanisms.

microbiology↗

bioRxiv2019

The genetic architecture of Parkinson disease in Spain: characterizing population-specific risk, differential haplotype structures, and providing etiologic insight

BackgroundThe Iberian Peninsula stands out as having variable levels of population admixture and isolation, making Spain an interesting setting for studying the genetic architecture of neurodegenerative diseases.\n\nObjectivesTo perform the largest Parkinson disease (PD) genome-wide association study (GWAS) restricted to a single country.\n\nMethodsWe performed a GWAS for both risk of PD and age-at-onset (AAO) in 7,849 Spanish individuals. Further analyses included population-specific risk haplotype assessments, polygenic risk scoring through machine learning, Mendelian randomization of expression and methylation data to gain insight into disease-associated loci, heritability estimates, genetic correlations and burden analyses.\n\nResultsWe identified a novel population-specific GWAS signal at PARK2 associated with AAO. We replicated four genome-wide independent signals associated with PD risk, including SNCA, LRRK2, KANSL1/MAPT and HLA-DQB1. A significant trend for smaller risk haplotypes at known loci was found compared to similar studies of non-Spanish origin. Seventeen PD-related genes showed functional consequence via two-sample Mendelian randomization in expression and methylation datasets. Long runs of homozygosity at 28 known genes/loci were found to be enriched in cases versus controls.\n\nConclusionsOur data demonstrate the utility of the Spanish risk haplotype substructure for future fine-mapping efforts, showing how leveraging unique and diverse population histories can benefit genetic studies of complex diseases. The present study points to PARK2 as a major hallmark of PD etiology in Spain.

neuroscience↗

bioRxiv2019

Alpha-Synuclein is a Target of Fic-mediated Adenylylation/AMPylation: Implications for Parkinson’s Disease

During disease, cells experience various stresses that manifest as an accumulation of misfolded proteins and eventually lead to cell death. To combat this stress, cells activate a pathway called UPR (Unfolded Protein Response) that functions to maintain ER (endoplasmic reticulum) homeostasis and determines cell fate. We recently reported a hitherto unknown mechanism of regulating ER stress via a novel post-translational modification (PTM) called Fic-mediated Adenylylation/AMPylation. Specifically, we showed that the human Fic (filamentation induced by cAMP) protein, HYPE/FicD, catalyzes the addition of an AMP (adenosine monophosphate) to the ER chaperone, BiP, to alter the cells UPR-mediated response to misfolded proteins. Here, we report that we have now identified a second target for HYPE - alpha-Synuclein (Syn), a presynaptic protein involved in Parkinsons disease (PD). Aggregated Syn has been shown to induce ER stress and elicit neurotoxicity in PD models. We show that HYPE adenylylates Syn and reduces phenotypes associated with Syn aggregation in vitro, suggesting a possible mechanism by which cells cope with Syn toxicity.\n\nHIGHLIGHTSO_LIAggregated forms of the presynaptic protein Syn cause neurotoxicity and induce ER stress in cellular and animal models of Parkinsons disease.\nC_LIO_LIWe have identified Syn as a novel target for the human Fic protein, HYPE, a key regulator of ER homeostasis.\nC_LIO_LIHYPE adenylylates Syn and reduces the aggregation of recombinant Syn\nC_LIO_LIFic-mediated adenylylation/AMPylation is a possible mechanism by which cells cope with Syn toxicity.\nC_LI\n\nGraphic Abstract O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

biochemistry↗

bioRxiv2018

N-linked glycosylation of the antagonist Short gastrulation increases the functional complexity of BMP signals

Disorders of N-linked glycosylation are increasingly reported in the literature. However, targets responsible for the associated developmental and physiological defects are largely unknown. Bone Morphogenetic Proteins (BMPs) act as highly dynamic complexes to regulate several functions during development. The range and strength of BMP activity depend on interactions with glycosylated protein complexes in the extracellular milieu. Here we investigate the role of glycosylation for the function of the conserved extracellular BMP antagonist Short gastrulation (Sog). We identify conserved N-glycosylated sites and describe the effect of mutating these residues on BMP pathway activity in Drosophila. Functional analysis reveals that loss of individual Sog glycosylation sites enhances BMP antagonism and/or increases the spatial range of Sog effects in the tissue. Mechanistically, we provide evidence that N-terminal and stem glycosylation controls extracellular Sog levels and distribution. The identification of similar residues in vertebrate Chordin proteins suggests that N-glycosylation may be an evolutionarily conserved process that adds complexity to the regulation of BMP activity.\n\nSummary StatementN-glycosylation restricts the function of Short gastrulation during Drosophila development by controlling the amount of extracellular protein. This adds another layer of complexity to regulation of Bone Morphogenetic Protein signals.

developmental biology↗