bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drosophila immunity: The Drosocin gene encodes two host defence peptides with pathogen-specific roles
Authors: Hanson M.A. , Kondo S. , Lemaitre B. 
Published: May 2022

1.1AbstractAntimicrobial peptides (AMPs) are key players in innate defence against infection in plants and animals. In Drosophila, many host defence peptides are produced downstream of the Toll and Imd NF-κB pathways. Use of single and compound AMP mutations in Drosophila has revealed that AMPs can additively or synergistically contribute to combat pathogens in vivo. However, these studies also revealed a high degree of specificity, wherein just one AMP can play a major role in combatting a specific pathogen. We recently uncovered a specific importance of the antibacterial peptide Drosocin for defence against Enterobacter cloacae. Here, we show that the Drosocin locus (CG10816) is more complex than previously described. In addition to its namesake peptide “Drosocin”, it encodes a second peptide generated from a precursor via furin cleavage. We name this peptide “Buletin”, and show that it corresponds to the uncharacterized “Immune-induced Molecule 7” previously identified by MALDI-TOF. The existence of a naturally occurring polymorphism (Thr52Ala) in the CG10816 precursor protein masked the identification of this peptide previously. Using mutations differently affecting the production of these two CG10816 gene products, we show that Drosocin, but not Buletin, contributes to the CG10816-mediated defence against E. cloacae. Strikingly, we observed that Buletin, but not Drosocin, contributes to the CG10816-mediated defence against Providencia burhodogranariea. Moreover, the Thr52Ala polymorphism in Buletin affects survival to P. burhodogranariea, wherein the Alanine allele confers better defence than the Threonine allele. However, we found no activity of Buletin against either P. burhodogranariea or E. coli in vitro. Collectively, our study reveals that CG10816 encodes not one but two prominent host defence peptides with different specificity against different pathogens. This finding emphasizes the complexity of the Drosophila humoral response consisting of multiple host defence peptides with specific activities, and demonstrates how natural polymorphisms found in Drosophila populations can affect host susceptibility.
Rare CNVs and phenome-wide profiling: a tale of brain-structural divergence and phenotypical convergence
Authors: Kopal J. , Kumar K. , Saltoun K. , Modenato C. , Moreau C. A. , Martin-Brevet S. , Huguet G. , Jean-Louis M. , Martin C.O. , Saci Z. , Younis N. , Tamer P. , Douard E. , Maillard A. M. , Rodriguez-Herreros B. , Pain A. , Richetin S. ,   16p11.2 European Consortium,   Simons Searchlight Consortium, Kushan L. , Silva A. I. , van den Bree M. B. M. , Linden D. E. J. , Owen M. J. , Hall J. , Lippé S. , Draganski B. , Sønderby I. E. , Andreassen O. A. , Glahn D. C. , Thompson P. M. , Bearden C. E. , Jacquemont S. , Bzdok D. 
Published: May 2022

AbstractCopy number variations (CNVs) are rare genomic deletions and duplications that can exert profound effects on brain and behavior. Previous reports of pleiotropy in CNVs imply that they converge on shared mechanisms at some level of pathway cascades, from genes to large-scale neural circuits to the phenome. However, studies to date have primarily examined single CNV loci in small clinical cohorts. It remains unknown how distinct CNVs escalate the risk for the same developmental and psychiatric disorders. Here, we quantitatively dissect the impact on brain organization and behavioral differentiation across eight key CNVs. In 534 clinical CNV carriers from multiple sites, we explored CNV-specific brain morphology patterns. We extensively annotated these CNV-associated patterns with deep phenotyping assays through the UK Biobank resource. Although the eight CNVs cause disparate brain changes, they are tied to similar phenotypic profiles across ∼1000 lifestyle indicators. Our population-level investigation established brain structural divergences and phenotypical convergences of CNVs, with direct relevance to major brain disorders.
From the outer ear to the nerve: A complete computer model of the peripheral auditory system
Authors: Tichacek Ondrej , Mistrík Pavel , Jungwirth Pavel 
Published: May 2022

AbstractComputer models of the individual components of the peripheral auditory system – the outer, middle, and inner ears and the auditory nerve – have been developed in the past, with varying level of detail, breadth, and faithfulness of the underlying parameters. Building on previous work, we advance the modeling of the ear by presenting a complete, physiologically justified, bottom-up computer model based on up-to-date experimental data that integrates all of these parts together seamlessly. The detailed bottom-up design of the present model allows for the investigation of partial hearing mechanisms and their defects, including genetic, molecular, and microscopic factors. Also, thanks to the completeness of the model, one can study microscopic effects in the context of their implications on hearing as a whole, enabling the correlation with neural recordings and non-invasive psychoacoustic methods. Such a model is instrumental for advancing quantitative understanding of the mechanism of hearing, for investigating various forms of deafness, as well as for devising next generation hearing aids and cochlear implants.
EggVio: a user friendly and versatile pipeline for assembly and functional annotation of shallow depth sequenced samples
Authors: Bergk Pinto Benoit Marc , Vogel Timothy M , Larose Catherine 
Published: May 2022

1AbstractWe introduce a homemade pipeline allowing to improve the quality of the metagenomic annotations carried out when using shallow depth metagenomic datasets. The main motivation being to be able to quantify more precisely, with greater certainty, the genes involved in bacterial interactions. The limitation in our experimental design is that we use a sequencing technique with a low throughput (miSeq) compared to the metagenomic standard (hiSeq) because we carry out a fairly large sampling (almost a hundred samples) in time series. This methodological constraint from our study means that the assembly of the sequences is not very exhaustive (less than 50% of the sequences manage to be assembled). In this chapter, we will therefore present a new pipeline designed to specifically deal with such kind of data. We used co-assembly and a sequence annotation strategy in order to recover the sequences that could not be mapped on the assembled contigs. In addition, in order to avoid adding too much noise, when rescuing reads, we have built an algorithm to define a threshold of e-value based on the noise of the sequence annotation learned from sequences mapped in the assembly.We have selected several recent tools known to be effective for assembling, mapping and annotating these data. In addition, this pipeline was also built in order to be very user-friendly in terms of installation. In this idea of reproducibility, accessibility and transparency, we have designed an installation script to allow each user to install each tool required for the pipeline in a simple and reproducible way. Regarding the performances of this pipeline, we were able to show that the expected error rate (False discovery rate) for the annotation was close to 5%. Finally, we also used an actual dataset from a bioremediation site and showed that the representability of the samples seemed much better when we used our pipeline than when we used a classic metagenome assembly strategy.
Molecular and functional characterization of theDrosophila melanogasterconserved smORFome
Authors: Bosch Justin A. , Keith Nathan , Escobedo Felipe , Fisher William W. , LaGraff James Thai , Rabasco Jorden , Wan Kenneth H. , Weiszmann Richard , Hu Yanhui , Kondo Shu , Brown James B. , Perrimon Norbert , Celniker Susan E. 
Published: May 2022

SummaryShort polypeptides encoded by small open reading frames (smORFs) are ubiquitously found in eukaryotic genomes and are important regulators of physiology, development, and mitochondrial processes. Here, we focus on a subset of 298 smORFs that are evolutionarily conserved betweenDrosophila melanogasterand humans. Many of these smORFs are conserved broadly in the bilaterian lineage, with ∼182 conserved in plants. Within these conserved smORFs, we observed remarkably heterogenous spatial and temporal expression patterns – indicating wide-spread tissue-specific and stage-specific mitochondrial architectures. In addition, an analysis of annotated functional domains revealed a predicted enrichment of smORF polypeptides localizing to mitochondria. We conducted an embryonic ribosome profiling experiment finding support for translation of 137 of these smORFs during embryogenesis. We further embarked on functional characterization using CRISPR knockout/activation, RNAi knockdown, and cDNA overexpression, revealing diverse phenotypes. This study underscores the importance of identifying smORF function in disease and phenotypic diversity.
The salivary protein Saglin facilitates efficient midgut colonization of Anopheles mosquitoes by malaria parasites
Authors: Klug Dennis , Gautier Amandine , Calvo Eric , Marois Eric , Blandin Stéphanie A 
Published: May 2022

AbstractMalaria is caused by the unicelullar parasite Plasmodium which is transmitted to humans through the bite of infected female Anopheles mosquitoes. To initiate sexual reproduction and to infect the midgut of the mosquito, Plasmodium gametocytes are able to recognize the intestinal environment after being ingested during blood feeding. A shift in temperature, pH change and the presence of the insect-specific compound xanthurenic acid have been shown to be important stimuli perceived by gametocytes to become activated and proceed to sexual reproduction. Here we report that the salivary protein Saglin, previously proposed to be a receptor for the recognition of salivary glands by sporozoites, facilitates Plasmodium colonization of the mosquito midgut, but does not contribute to salivary gland invasion. In mosquito mutants lacking Saglin, Plasmodium infection of Anopheles females is greatly reduced, resulting in impaired transmission of sporozoites at low infection densities. Interestingly, our results suggest that Saglin, present in mosquito saliva, must be ingested with the blood meal to affect Plasmodium development, indicating a previously unknown host-pathogen interaction. Furthermore, we were able to show that saglin deletion has no fitness cost in laboratory conditions, suggesting this gene would be an interesting target for gene drive approaches.
Sensor NLR immune proteins activate oligomerization of their NRC helper
Authors: Contreras Mauricio P. , Pai Hsuan , Tumtas Yasin , Duggan Cian , Him Yuen Enoch Lok , Cruces Angel Vergara , Kourelis Jiorgos , Ahn Hee-Kyung , Wu Chih-Hang , Bozkurt Tolga O. , Derevnina Lida , Kamoun Sophien 
Published: May 2022

AbstractNucleotide-binding domain and leucine-rich repeat (NLR) immune receptors are important components of plant and metazoan innate immunity that can function as individual units or as pairs or networks. Upon activation, NLRs form multiprotein complexes termed resistosomes or inflammasomes. Whereas metazoan paired NLRs, such as NAIP/NLRC4, activate into hetero-complexes, the molecular mechanisms underpinning activation of plant paired NLRs, especially whether they associate in resistosome hetero-complexes is unknown. In asterid plant species, the NLR required for cell death (NRC) immune receptor network is composed of multiple resistance protein sensors and downstream helpers that confer immunity against diverse plant pathogens. Here, we show that pathogen effector-activation of the NLR proteins Rx (confers virus resistance) and Bs2 (confers bacterial resistance) leads to oligomerization of the helper NLR NRC2. Activated Rx does not oligomerize or enter into a stable complex with the NRC2 oligomer and remains cytoplasmic. In contrast, activated NRC2 oligomers accumulate in membrane-associated puncta. We propose an activation-and-release model for NLRs in the NRC immune receptor network. This points to a distinct activation model compared to mammalian paired NLRs.
Effector-dependent activation and oligomerization of NRC helper NLRs by Rpi-amr3 and Rpi-amr1
Authors: Ahn Hee-Kyung , Lin Xiao , Olave-Achury Andrea Carolina , Derevnina Lida , Contreras Mauricio P , Kourelis Jiorgos , Kamoun Sophien , Jones Jonathan D G 
Published: May 2022

AbstractPlant pathogens compromise crop yields. Plants have evolved robust innate immunity that depends in part on intracellular Nucleotide-binding, Leucine Rich-Repeat (NLR) immune receptors that activate defense responses upon detection of pathogen-derived effectors. Most “sensor” NLRs that detect effectors require the activity of “helper” NLRs, but how helper NLRs support sensor NLR function is poorly understood. Many Solanaceae NLRs require the NRC (NLR-Required for Cell death) class of helper NLRs. We show here that Rpi-amr3, a sensor NLR fromSolanum americanum, detects AVRamr3 from the potato late blight pathogen,Phytophthora infestans, and activates oligomerization of the helper NLR NRC2 into a high-molecular weight resistosome. The NRC2 resistosome also forms upon recognition ofP. infestanseffector AVRamr1 by another sensor NLR, Rpi-amr1. The ATP-binding motif of Rpi-amr3 is required for NRC2 resistosome formation, but not for interaction with the cognate effector. The NRC2 resistosome can be activated by AVRamr3 homologs from otherPhytophthoraspecies. Mechanistic understanding of NRC resistosome formation will underpin engineering crops with durable disease resistance.
Fear engrams and NPYergic circuit in the dorsal dentate gyrus determine remote fear memory generalization
Authors: Raza Syed Ahsan , Klinger Katharina , del Ángel Miguel , Demiray Yunus Emre , Çalışkan Gürsel , Kreutz Michael R. , Stork Oliver 
Published: May 2022

AbstractGeneralization is a critical feature of aversive memories and significantly contributes to post-traumatic stress disorder (PTSD) pathogenesis. While fear memories over time tend to generalize across differences in the contextual background and even to novel contextual settings, this effect can be counteracted by exposure to controlled reminder sessions even at remote time points. Using Pavlovian fear conditioning in mice, we show that generalization to a novel context of remote memory is associated with a loss of cellular engram activation in the dorsal dentate gyrus (dDG) and can be effectively counteracted by a preceding contextual reminder session. In addition to engram cells activation in response to a novel context, the reminder session also leads to a recovery of neuropeptide Y (NPY) function in the dDG and dDG-CA3 neurotransmission. In line with a proposed role of NPY as a resilience factor, we found that chronic viral knockdown of NPY in the dDG and blockage of its activity-dependent expression in NPYergic dDG interneurons with dominant-negative CREBS133A both increase remote memory generalization. With chemogenetic silencing of these interneurons, we could localize their critical involvement to a time window during and immediately following the fear memory acquisition. Together, these findings suggest that NPYergic interneurons of the dDG, shaping the memory engram during fear learning and early consolidation, determine fear generalization.
Imitation performance in primary school children
Authors: Ottoboni Giovanni , Toraldo Alessio , Proietti Riccardo , Cangelosi Angelo , Tessari Alessia 
Published: May 2022

AbstractWe studied the development of imitation ability in a cohort of 6-11-year-old children (N=174) with specific attention to error types and their cognitive interpretation. Participants imitated meaningless actions as if they were in front of a mirror (specularly). Actions varied across three levels of complexity (movements of a single limb, arm and leg of the same body side, or arm and leg of opposite sides). Overall performance improved with age. Among the most frequent error categories, ‘side’ errors (movement imitated with the left instead of the right limb or vice-versa) paradoxically increased with age (from 9 years). Still, their sensitivity to complexity decreased with age. Thus, encoding two opposite body sides has high cognitive costs in younger children and smaller or null costs in older children. We interpreted these results in terms of the enhancement of Working Memory (WM) and body knowledge with age. When WM increases, it paradoxically drives older children to apply their superior body knowledge and imitate ‘anatomically’, producing side errors. Younger children are free from such interference because they still lack the necessary body knowledge and WM capacity. In conclusion, this study suggests that anatomical imitation becomes available in children’s cognitive repertoire from age nine due to increased body knowledge and WM capacity.Research HighlightsThe analysis of error types uncovers/illustrates the role of working memory and body knowledge in imitation.As an effect of little working memory capacity, younger children pay a cognitive cost to encode opposite body sides and make “side errors”.Imitation performance improves with age, but side errors paradoxically increase in frequency due to greater ability to master body knowledge bringing to anatomical imitation.Anatomical imitation is available in childrens’ cognitive repertoire from age 9, as an effect of the development of body knowledge and working memory capacity.
Estimation of the reference lead (Pb) concentration levels affecting immune cells in the blood of Black-headed Gulls (Chroicocephalus ridibundus, Laridae)
Authors: Ushine Nana , Kurata Osamu , Tanaka Yoshikazu , Nakayama Shouta M M , Ishizuka Mayumi , Kato Takuya , Hayama Shin-ichi 
Published: May 2022

AbstractThe biological effects of lead (Pb) contamination have been reported in various species. There are no restrictions on the use of Pb products, including bullets, in the areas south of Hokkaido, Japan. Local governments have announced the presence of some Pb in the soil sediments of water bodies. Previous studies have confirmed the relationship between blood Pb level (BLL) and immune cells. This study was performed with the aim of clarifying the effect of Pb contamination on immune cells. In total, 170 Black-headed Gulls (Chroicocephalus ridibundus) were captured, including a population in Tokyo Bay between November 2018 and April 2021 and a population in Mikawa Bay between January 2019 and April 2021. Linear regression analysis was performed with the white blood cell count (WBC), proportion of heterophils (Het), proportion of lymphocytes (Lym), ratio of heterophils and lymphocytes (H/L ratio), copy number of CD4 messenger RNA, and copy number of CD8α messenger RNA as the objective variables, and the BLL as the explanatory variable. The group with BLL < 1.0 μg/dL had a significantly lower Het and higher Lym than that with BLL > 3.5 μg/dL (P < 0.05). In addition, the group with BLL < 1.0 μg/dL had a significantly lower H/L ratio than that with BLL > 3.5 μg/dL. CD8α and WBC were higher in the group with the group with BLL range, from 1.0 to 3.5 μg/dL than those in the group with BLL < 1.0 μg/dL. This study suggests that the effect of Pb pollution on the immune cells of Black-headed Gulls is lower than some previous criteria values.
Polyphyly of theNiphargus stygiusspecies group (Crustacea, Amphipoda, Niphargidae) in the Southern Limestone Alps
Authors: Stoch Fabio , Salussolia Alice , Flot Jean-François 
Published: May 2022

AbstractTheNiphargus stygiusspecies complex is a groundwater group of large-sized, sexually dimorphic species inhabiting mainly caves and, less frequently, wells and springs. According to the taxonomists of the last century, this species complex was supposed to be present in the whole Southern Limestone Alps of Italy as well as in peninsular Italy, Slovenia, and Croatia. Considering the large, presumed distribution area, we tested the contrasting hypotheses of monophyly versus paraphyly of this subterranean species complex, taking in account the presence of putative cryptic species. For this reason, we sampled the type localities of all the described species in the complex present in the Italian Southern Limestone Alps and neighbouring areas, and used nuclear rDNA (28S, ITS region) and mtDNA (COI) markers to assess the phylogenetic relationships and species richness. Phylogenetic analysis confirmed that theNiphargus stygiuscomplex in the Southern Limestone Alps is polyphyletic comprising an eastern clade (theN. juliusclade, present in NW Italy, northern Slovenia, and southern Austria) and two western clades (theN. brixianusandN. montellianusclades). These two clades are not closely related to the eastern one but rather form a monophyletic group together with a widely distributed Apennine clade (N. speziaeclade). None of these clades is closely related to typicalN. stygius. Three different molecular species delimitation methods applied to COI and rDNA sequences recognized slighlty different numbers of putative species, suggesting that each clade is a species complex. Bayesian time-calibrated phylogeny revealed that most clades began to split up during Miocene and Pliocene, ruling out the effect of Pleistocene glaciations, evidenced only by the COI marker, in explaining their speciation process and justifying the presence of several putative cryptic or pseudocryptic species.
Tau seeds translocate across the cell membrane to initiate aggregation
Authors: Dodd Dana A. , LaCroix Michael , Valdez Clarissa , Knox Gregory M. , Vega Anthony R. , Kumar Ashwani , Xing Chao , White Charles L. , Diamond Marc I. 
Published: May 2022

ABSTRACTNeurodegenerative tauopathies, including Alzheimer’s disease and related disorders, are caused by intracellular aggregation of tau protein in ordered assemblies. Experimental evidence suggests that tau assemblies propagate pathology across brain networks. Tau seeds enter cells through endocytosis but must access the cytoplasm to serve as templates for their own replication. The mechanism by which this occurs is unknown. To study tau uptake, we began with a whole-genome CRISPR knockout screen, which indicated a requirement vacuolar H+ ATPase (v-ATPase) components. Treatment with Bafilomycin A1, an inhibitor of the v-ATPase, also reduced tau entry. We next tested direct modifiers of endolysosomal trafficking. Dominant-negative Rab5a expression uniquely decreased tau uptake, as did temporary cold temperature during tau exposure, consistent with a primary role of endocytosis in tau uptake. However, despite reducing tau uptake, these interventions all paradoxically increased intracellular seeding. Consequently, we generated giant plasma membrane vesicles (GPMVs), which cannot undergo endocytosis, and observed that tau fibrils and monomer translocated into the vesicles, in addition to TAT peptide, whereas transferrin and albumin did not. In every case, tau required binding to heparan sulfate proteoglycans (HSPGs) for cell uptake, seeding, or GPMV entry. These findings are most consistent with direct translocation of tau seeds across the lipid bilayer, a novel mechanism of entry into the cytoplasm.