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van Gelder, C.

Publications and source records attributed to van Gelder, C..

3 recordsLinked to original sources

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↗

Characterization of apicomplexan amino acid transporters (ApiATs) in the malaria parasite Plasmodium falciparum

During the symptomatic human blood phase, malaria parasites replicate within red blood cells. Parasite proliferation relies on the uptake of nutrients, such as amino acids, from the host cell and the blood plasma, requiring transport across multiple membranes. Amino acids are delivered to the parasite through the parasite surrounding vacuolar compartment by specialized nutrient-permeable channels of the erythrocyte membrane and the parasitophorous vacuole membrane (PVM). However, further transport of amino acid across the parasite plasma membrane (PPM) is currently not well characterized. In this study, we focused on a family of Apicomplexan amino acid transporters (ApiATs) that comprises five members in Plasmodium falciparum. First, we localized four of the PfApiATs at the PPM using endogenous GFP-tagging. Next, we applied reverse genetic approaches to probe into their essentiality during asexual replication and gametocytogenesis. Upon inducible knockdown and targeted gene disruption a reduced asexual parasite proliferation was detected for PfApiAT2 and PfApiAT4. Functional inactivation of individual PfApiATs targeted in this study had no effect on gametocyte development. Our data suggest that individual PfApiATs are partially redundant during asexual in vitro proliferation and fully redundant during gametocytogenesis of P. falciparum parasites. IMPORTANCEMalaria parasites live and multiply inside cells. To facilitate their extremely fast intracellular proliferation they hijack and transform their host cells. This also requires the active uptake of nutrients, such as amino acids, from the host cell and the surrounding environment through various membranes that are the consequence of the parasites intracellular lifestyle. In this manuscript we focus on a family of putative amino acid transporters termed ApiAT. We show expression and localization of four transporters in the parasite plasma membrane of Plasmodium falciparum-infected erythrocytes that represent one interface of the pathogen to its host cell. We probed into the impact of functional inactivation of individual transporters on parasite growth in asexual and sexual blood stages of P. falciparum and reveal that only two of them show a modest but significant reduction in parasite proliferation but no impact on gametocytogenesis pointing towards redundancy within this transporter family.

molecular biology↗

Temporal quantitative proteomics of protein translation and phosphorylation in synaptic plasticity

At neuronal synapses, activation of metabotropic glutamate receptors (mGluR1/5) triggers a form of long-term depression (mGluR-LTD) that relies on new protein synthesis and the internalization of AMPA-type glutamate receptors. Dysregulation of these processes has been implicated in the development of mental disorders such as autism spectrum disorders and therefore merit a better understanding on a molecular level. Here, to study mGluR-LTD, we integrated quantitative high-resolution phosphoproteomics with the analyses of newly synthesized proteins via bio-orthogonal amino acids (azidohomoalanine) in a pulsed labeling strategy combined with tandem mass tag label-based quantification in cultured hippocampal neurons stimulated with DHPG. We identified several kinases with important roles in DHPG-mGluR-LTD, which we confirmed using small molecule kinase inhibitors. Furthermore, changes in the AMPA receptor endocytosis pathway in both protein synthesis and protein phosphorylation upon LTD were identified, whereby Intersectin-1 was validated as a vital player in this pathway. This study revealed several novel insights into the molecular mechanisms underlying mGluR-LTD and provides a broad view on its molecular basis, which serves as a rich resource for further analyses.

neuroscience↗