bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structures of ferroportin in complex with its specific inhibitor vamifeport
Authors: Lehmann Elena F. , Liziczai Márton , Drożdżyk Katarzyna , Altermatt Patrick , Manolova Vania , Sundstrom Hanna , Dürrenberger Franz , Dutzler Raimund , Manatschal Cristina 
Published: August 2022

AbstractA central regulatory mechanism of iron homeostasis in humans involves ferroportin (FPN), the sole cellular iron exporter, and the peptide hormone hepcidin, which inhibits Fe2+ transport and induces internalization and degradation of FPN. Dysregulation of the FPN/hepcidin axis leads to diverse pathological conditions, and consequently, pharmacological compounds that inhibit FPN-mediated iron transport are of high clinical interest. Here, we describe the cryo-EM structures of human FPN in complex with synthetic nanobodies and vamifeport (VIT-2763), the first clinical-stage oral FPN inhibitor. Vamifeport competes with hepcidin for FPN binding and is currently in clinical development for β-thalassemia and sickle cell disease. The structures display two distinct conformations of FPN, representing outward-facing and an occluded states of the transporter. The vamifeport site is located in the center of the protein, where the overlap with hepcidin interactions underlies the competitive relationship between the two molecules. The introduction of point mutations in the binding pocket of vamifeport reduces its affinity to FPN, emphasizing the relevance of the structural data. Together, our study reveals the conformational rearrangements of FPN on its transport cycle and it provides initial insight into the pharmacological targeting of this unique iron efflux transporter.
Comparing different computational approaches for detecting long-term vertical transmission in host-associated microbiota
Authors: Perez-Lamarque Benoît , Morlon Hélène 
Published: August 2022

AbstractLong-term vertical transmissions of gut bacteria are thought to be frequent and functionally important in mammals. Several phylogenetic-based approaches have been proposed to detect, among species-rich microbiota, the bacteria that have been vertically transmitted during a host clade radiation. Applied to mammal microbiota, these methods have sometimes led to conflicting results; in addition, how they cope with the slow evolution of markers typically used to characterize bacterial microbiota remains unclear. Here, we use simulations to test the statistical performances of two widely-used global-fit approaches (ParaFit and PACo) and two event-based approaches (ALE and HOME). We find that these approaches have different strengths and weaknesses depending on the amount of variation in the bacterial DNA sequences and are therefore complementary. In particular, we show that ALE performs better when there is a lot of variation in the bacterial DNA sequences, whereas HOME performs better when there is not. Global-fit approaches (ParaFit and PACo) have higher type-I error rates (false positives) but have the advantage to be very fast to run. We apply these methods to the gut microbiota of primates and our results suggest that only a small fraction of their gut bacteria is vertically transmitted.
A systematic scoping review of the ethics of contributor role ontologies and taxonomies
Authors: Hosseini Mohammad , Gordijn Bert , Wafford Q. Eileen , Holmes Kristi L. 
Published: August 2022

AbstractContributor Role Ontologies and Taxonomies (CROTs) provide a standard list of roles to specify individual contributions to publications. Due to the recent uptake of CROTs – the CRediT taxonomy in particular– researchers from different disciplinary backgrounds have anticipated a positive impact on ethical issues related to the attribution of credit and responsibilities. Yet, they have also voiced concerns about CROTs shortcomings and ways in which they could be misunderstood or misused and have provided suggestions to improve them. These discussions have never been collated and consolidated. To fill this gap, the current scoping review collates and explores published viewpoints about the ethics of CROTs. Ovid Medline, Scopus, Web of Science, and Google Scholar were searched. In total, 30 papers met the inclusion criteria and were subsequently analyzed using an inductive approach. We identified eight themes and 20 specific issues related to the ethics of CROTs and provided four recommendations for CROT developers: 1) Compile comprehensive instructions that explain how CROTs should be used and that note common pitfalls of employing them in practice; 2) Improve the coherence of used terms, 3) Provide translations of roles in languages other than English, and 4) Communicate a clear vision about future development plans.
Effects of human-wildlife Conflicts on Local People’s Livelihoods and Wildlife Conservation in and around Alitash National Park, Northwest Ethiopia
Authors: Ayalew Mekuriaw Zewdie , Melese Getahun Tassew 
Published: August 2022

ABSTRACTHuman-wildlife conflict becomes one of the fundamental aspects of wildlife management because it threatens both wildlife and human. People injured, abused, and killed wildlife in response to the perceived and/or actual damages from wildlife. Such negative interaction between humans and wildlife exists everywhere but more intense and costly in adjacent protected areas. This study aimed to assess the effects of human-wildlife conflicts on local people’s livelihood and wildlife conservation in and around Alitash National Park. The primary data were collected using multi-stage sampling techniques by employing a combination of social survey methods involving participatory techniques (focus group discussions and key informant interviews) and structured household interviewers. The survey questionnaire consisted of both open-ended and fixed-response questions designed to solicit information mainly for wildlife-caused damages and other costs to the local community along with human-induced wildlife decline and perceptions towards wildlife conservation. The results revealed that 59.6% of the respondents encountered at least a single type of damage. More than half (54%) of respondents encountered crop damage, of which 34.4% lost up to 25% of their crop fields whereas the amount of loss to the remaining (18.7%) was to 75% of the crop fields. The livestock loss during the last five years of the period prior to the survey administration was 287.89 tropical livestock units which were shared by 47.5% of the respondents. Wildlife attacks on humans were rare but eighteen attacks were caused by Panther leo, Crocuta crocuta and Panthera pardus were encountered when the victims cross the habitats of the species. The responses of the victims to the wildlife imposed the damage was negative and full of anger and resentment. This has been undermining conservation efforts and the socio-economic welfare of the local people around Alitash National Park. Providing alternative livelihood opportunities and creating a context-based conservation scheme along with continuous conservation education would help to reduce the negative effect of human-wildlife conflicts on both wildlife and people in the study area.
The claudin-like apicomplexan microneme protein is required for gliding motility and infectivity of Plasmodium sporozoites
Authors: Loubens Manon , Marinach Carine , Paquereau Clara-Eva , Hamada Soumia , Hoareau-Coudert Bénédicte , Akbar David , Franetich Jean-François , Silvie Olivier 
Published: August 2022

AbstractInvasion of host cells by apicomplexan parasites such as Toxoplasma and Plasmodium spp requires the sequential secretion of the parasite apical organelles, the micronemes and the rhoptries. The claudin-like apicomplexan microneme protein (CLAMP) is a conserved protein that plays an essential role during invasion in Toxoplasma gondii tachyzoites and Plasmodium falciparum merozoites. CLAMP is also expressed in Plasmodium sporozoites, the mosquito-transmitted forms of the malaria parasite, but its role in this stage is still unknown. CLAMP is essential for Plasmodium blood stage growth and is refractory to conventional gene deletion. To circumvent this obstacle and study the function of CLAMP in sporozoites, we used a conditional genome editing strategy based on the dimerisable Cre recombinase in the rodent malaria model parasite P. berghei. We successfully deleted clamp gene in P. berghei transmission stages and analyzed the functional consequences on sporozoite infectivity. In mosquitoes, sporozoite development and egress from oocysts was not affected in conditional mutants. However, invasion of the mosquito salivary glands was dramatically reduced upon deletion of clamp gene. In addition, CLAMP-deficient sporozoites were impaired in cell traversal and productive invasion of mammalian hepatocytes. This severe phenotype was associated with major defects in gliding motility and with reduced shedding of the sporozoite adhesin TRAP. These results demonstrate that CLAMP is essential across invasive stages of the malaria parasite, and strongly suggest that the protein acts upstream of host cell invasion, possibly by regulating the secretion or function of adhesins in Plasmodium sporozoites.Author summaryPlasmodium parasites, the causative agents of malaria, are transmitted during the bite of an infected mosquito. Infectious parasite stages known as sporozoites are released from the insect salivary glands and injected into the host skin. Sporozoites rapidly migrate to the host liver, invade hepatocytes and differentiate into the next invasive forms, the merozoites, which invade and replicate inside red blood cells. Sporozoite motility and host cell invasion rely on the secretion of apical organelles called micronemes and rhoptries. Here we characterize the function of a microneme protein expressed both in merozoites and sporozoites, the claudin-like protein CLAMP. We used a conditional genome editing strategy in a rodent malaria model to generate CLAMP-deficient sporozoites. In the absence of CLAMP, sporozoites failed to invade mosquito salivary glands and mammalian hepatocytes, and showed defects in gliding motility and microneme secretion. Our data establish that CLAMP plays an essential role across Plasmodium invasive stages, and might represent a potential target for transmission-blocking antimalarial strategies.
Antimicrobial activity of cationic antimicrobial peptides against stationary phase bacteria
Authors: Rodríguez-Rojas Alexandro , Rolff Jens 
Published: August 2022

AbstractAntimicrobial peptides (AMPs) are ancient antimicrobial weapons used by multicellular organisms as components of their innate immune defences. Because of the antibiotic crisis, AMPs have also become candidates for developing new drugs. Here, we show that five different AMPs of different classes are effective against non-dividing E. coli and S. aureus. By comparison, three conventional antibiotics from the main three classes of antibiotics poorly kill non-dividing bacteria at clinically relevant doses. The killing of fast-growing bacteria by AMPs is faster than that of slow-dividing bacteria and, in some cases, without any difference. Still, non-dividing bacteria are effectively killed over time. Our results point to a general property of AMPs, which might explain why selection has favoured AMPs in the evolution of metazoan immune systems. The ability to kill non-dividing cells is another reason that makes AMPs exciting candidates for drug development.
Stable isotopomers of myo-inositol to uncover the complex MINPP1-dependent inositol phosphate network
Authors: Trung Minh Nguyen , Kieninger Stefanie , Fandi Zeinab , Qiu Danye , Liu Guizhen , Saiardi Adolfo , Jessen Henning , Keller Bettina , Fiedler Dorothea 
Published: August 2022

AbstractThe water-soluble inositol phosphates (InsPs) represent a functionally diverse group of small-molecule messengers central to a myriad of cellular processes. However, we have an incomplete understanding of InsP metabolism because the available analytical toolset for inositol phosphates is rather limited. Here, we have synthesized and utilized fully and unsymmetrically 13C-labeled myo-inositol and inositol phosphates. These probes were applied in combination with nuclear magnetic resonance spectroscopy (NMR) and capillary electrophoresis mass spectrometry (CE-MS) to further annotate central aspects of InsP metabolism in human cells. The labeling strategy provided detailed structural information via NMR – down to individual enantiomers – which overcomes a crucial blind spot in the analysis of InsPs. We uncovered a novel branch of InsP dephosphorylation in human cells which is dependent on MINPP1, a phytase-like enzyme, that contributes to cellular homeostasis. Full characterization of MINPP1 activity in vitro and in cells, provided a clear picture of this multifunctional phosphatase. Metabolic labeling with stable isotopomers thus constitutes a powerful tool for investigating InsP networks in a variety of different biological contexts.
Sequential And Directional Insulation By Conserved CTCF Sites Underlies The Hox Timer In Pseudo-Embryos
Authors: Rekaik Hocine , Lopez-Delisle Lucille , Hintermann Aurélie , Mascrez Bénédicte , Bochaton Célia , Duboule Denis 
Published: August 2022

ABSTRACTDuring development, Hox genes are activated in a time sequence following their relative positions on their clusters, leading to the proper identities of structures along the rostral to caudal axis. To understand the mechanism operating this Hox timer, we used ES-cells derived stembryos and show that the core of the process involves the start of transcription at the 3’ part of the cluster, following Wnt signaling, and the concomitant loading of cohesin complexes on the transcribed DNA segments, i.e., with an asymmetric distribution along the gene cluster. Chromatin extrusion then occurs with successively more posterior CTCF sites acting as transient insulators, thus generating a progressive time-delay in the activation of more 5’-located genes due to long-range contacts with a flanking TAD. Mutant stembryos support this model and reveal that the iterated presence of evolutionary conserved and regularly spaced intergenic CTCF sites control the precision and the pace of this temporal mechanism.
Persistent virus-specific and clonally expanded antibody secreting cells respond to induced self antigen in the CNS
Authors: Agrafiotis Andreas , Dizerens Raphael , Vincenti Ilena , Wagner Ingrid , Kuhn Raphael , Shlesinger Danielle , Manero-Carranza Marcos , Cotet Tudor-Stefan , Hong Kai-Lin , Page Nicolas , Fonta Nicolas , Shammas Ghazal , Mariotte Alexandre , Piccinno Margot , Kreutzfeldt Mario , Gruntz Benedikt , Ehling Roy , Genovese Alessandro , Pedrioli Alessandro , Dounas Andreas , Franzenburg Sören , Kavaka Vladyslav , Gerdes Lisa Ann , Dornmair Klaus , Beltrán Eduardo , Oxenius Annette , Reddy Sai T. , Merkler Doron , Yermanos Alexander 
Published: August 2022

AbstractB cells contribute to the pathogenesis of both cellular- and humoral-mediated central nervous system (CNS) inflammatory diseases through a variety of mechanisms. In such conditions, B cells may enter the CNS parenchyma and contribute to local tissue destruction. It remains unexplored, however, how infection and autoimmunity drive transcriptional phenotypes, repertoire features, and antibody functionality. Here, we profiled B cells from the CNS of murine models of intracranial (i.c.) viral infections and autoimmunity. We identified a population of clonally expanded, antibody secreting cells (ASCs) that had undergone class-switch recombination and extensive somatic hypermutation following i.c. infection with attenuated lymphocytic choriomeningitis virus (rLCMV). Recombinant expression and characterisation of these antibodies revealed specificity to viral antigens (LCMV glycoprotein GP), correlating with ASC persistence in the brain weeks after resolved infection. Furthermore, these virus-specific ASCs upregulated proliferation and expansion programs in response to the conditional and transient induction of the LCMV GP as a neo-self antigen by astrocytes. This class-switched, clonally expanded, and mutated population persisted and was even more pronounced when peripheral B cells were depleted prior to autoantigen induction in the CNS. In contrast, the most expanded B cell clones in mice with persistent expression of LCMV GP in the CNS did not exhibit neo-self antigen specificity, potentially a consequence of local tolerance induction. Finally, a comparable population of clonally expanded, class-switched, proliferating ASCs was detected in the cerebrospinal fluid of multiple sclerosis patients. Taken together, our findings support the existence of B cells that populate the CNS and are capable of responding to locally encountered autoantigens.Graphical abstract
Statistical modelling of aquatic size spectra: integrating data from multiple taxa and sampling methods
Authors: Giacomini Henrique Corrêa , de Kerckhove Derrick T. , Kopf Victoria , Chu Cindy 
Published: August 2022

AbstractSize spectra are used to assess the status and functioning of marine and freshwater ecosystems worldwide. Its use is underpinned by theory linking the dynamics of trophic interactions to a power-law decline of abundance with body size in ecological communities. Recent papers on empirical size spectrum estimation have argued for Maximum Likelihood Estimation (MLE) of power-law probability distributions as a more accurate alternative to traditional linear regression approaches. One major limitation of currently used size spectrum estimators from MLE is that they cannot account for the use of multiple sampling protocols, nor the distortions caused by gear size selectivity, and therefore they become restricted to a relatively narrow taxonomic group and size range. Further progress in the field requires new methods that are flexible enough to combine multiple trophic groups and sampling gears into a single size spectrum estimate, while taking advantage of more accurate distributional approaches. The method we propose in this paper fills this gap by deriving the distribution of observed sizes explicitly from the underlying power-law spectrum and gear selectivity functions. It specifies likelihoods as a product of two components: (i) the probability of belonging to a given group and (ii) the probability distribution within the group. Using Bayesian estimation, we applied the method to surveys of phytoplankton, zooplankton, and fishes in lakes of Quetico Provincial Park, northwestern Ontario, using Van Dorn samplers, zooplankton nets, gillnets, and hydroacoustics. The results show that the spectra estimated from subsets of trophic groups or gears are weak predictors of more complete spectra, highlighting the importance of using more inclusive community data. The two-component partitioning of likelihoods also helped demonstrating the existence of between-group spectrum slopes that were overall steeper than within-group slopes, indicating that heterogeneity of trophic transfers across the size spectrum is an important factor structuring these ecosystems.
«Application of RT-LAMP-CRISPR-Cas13a technology to the detection of OXA-48 producing Klebsiella pneumoniae»
Authors: Ortiz-Cartagena Concha , Blasco Lucia , Fernández-García Laura , Pacios Olga , Bleriot Ines , López María , Fernández-Cuenca Felipe , Cantón Rafael , Tomás María 
Published: August 2022

AbstractCarbapenem-resistant pathogens have been recognized as a health concern because of their ability to cause severe infections and because they are difficult to detect in laboratories. Researchers are making great efforts to develop a diagnostic technique with high levels of sensitivity and specificity, as accurate, early diagnosis is required to prevent the spread of these microorganisms and improve the prognosis of patients. In this context, CRISPR-Cas systems are proposed as promising tools for the development of diagnostic techniques due to their high specificity: Cas13 endonuclease discriminates single nucleotide changes and displays collateral activity against single-stranded RNA molecules. This technology is usually combined with isothermal pre-amplification reactions in order to increase the sensitivity of diagnosis. We have developed an RT-LAMP-CRISPR-Cas13a-based assay for the detection of Klebsiella pneumoniae OXA-48 producer strains in clinical samples without the need for RNA extraction. The assay exhibited 100 % specificity, sensitivity, positive predictive value and negative predictive value.
Proteomics unveil a central role for peroxisomes in butyrate assimilation of the heterotrophic Chlorophyte alga Polytomella sp
Authors: Lacroux J. , Atteia A. , Brugière S. , Couté Y. , Vallon O. , Steyer J.-P. , van Lis R. 
Published: August 2022

AbstractVolatile fatty acids found in effluents of the dark fermentation of biowastes can be used for mixotrophic growth of microalgae, improving productivity and reducing the cost of the feedstock. Microalgae can use the acetate in the effluents very well, but butyrate is poorly assimilated and can inhibit growth above 1 gC.L-1. The non-photosynthetic chlorophyte alga Polytomella sp. SAG 198.80 was found to be able to assimilate butyrate fast. To decipher the metabolic pathways implicated in butyrate assimilation, quantitative proteomics study was developed comparing Polytomella sp. cells grown on acetate and butyrate at 1 gC.L-1. After statistical analysis, a total of 1772 proteins were retained, of which 119 proteins were found to be overaccumulated on butyrate vs. only 46 on acetate, indicating that butyrate assimilation necessitates additional metabolic steps. The data show that butyrate assimilation occurs in the peroxisome via the β-oxidation pathway to produce acetyl-CoA and further tri/dicarboxylic acids in the glyoxylate cycle. Concomitantly, reactive oxygen species defense enzymes as well as the branched amino acid degradation pathway were strongly induced.Although no clear dedicated butyrate transport mechanism could be inferred, several membrane transporters induced on butyrate are identified as potential condidates. Metabolic responses correspond globally to the increased needs for central cofactors NAD, ATP and CoA, especially in the peroxisome and the cytosol.