bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neurotransmitter regulation rather than cell-intrinsic properties shape the high-pass filtering properties of olfactory bulb glomeruli
Authors: Zak Joseph D. , Schoppa Nathan E. 
Published: September 2021

AbstractGABAergic periglomerular (PG) cells in the olfactory bulb are proposed to mediate an intraglomerular “high-pass” filter through inhibition targeted onto a glomerulus. With this mechanism, weak stimuli (e.g., an odor with a low affinity for an odorant receptor) mainly produce PG cell-driven inhibition but strong stimuli generate enough excitation to overcome inhibition. PG cells may be particularly susceptible to being activated by weak stimuli due to their intrinsically small size and high input resistance. Here, we used dual-cell patch-clamp recordings and imaging methods in bulb slices obtained from wild-type and transgenic rats with labeled GABAergic cells to test a number of predictions of the high-pass filtering model. We first directly compared the responsiveness of PG cells with that of external tufted cells (eTCs), which are a class of excitatory interneurons that reside in a parallel but opposing position in the glomerular circuitry. PG cells were in fact found to be no more responsive than eTCs at low levels of sensory neuron activity. While PG cells required smaller currents to be excited, this advantage was offset by the fact that a given level of sensory neuron activity produced much smaller synaptic currents. We did however identify other factors that shaped the excitation/inhibition balance in a manner that would support a high-pass filter, including glial glutamate transporters and presynaptic metabotropic glutamate receptors. We conclude that a single glomerulus may act as a high-pass filter to enhance the contrast between different olfactory stimuli through mechanisms that are largely independent cell intrinsic properties.Key Points SummaryGABAergic periglomerular (PG) cells in the olfactory bulb are proposed to mediate a “high-pass” filter at a single glomerulus that selectively blocks weak stimulus signals. Their efficacy may reflect their intrinsically small size and high input resistance, which allows them to be easily excited.We found that PG cells were in fact no more likely to be activated by weak stimuli than excitatory neurons. PG cells spiked more readily in response to a fixed current input, but this advantage for excitability was offset by small synaptic currents.Glomeruli nevertheless display an excitation/inhibition balance that can support a high pass filter, becoming much more favorable with increasing stimulus strength. Factors shaping the filter include glial glutamate transporters and presynaptic metabotropic glutamate receptors.We conclude that a single glomerulus may act as a high-pass filter to enhance stimulus contrast through mechanisms that are largely independent of cell-intrinsic properties.
Zika Virus Infection of Murine and Human Neutrophils and their Function as Trojan Horses to the Placenta
Authors: Zanluqui NG , Oliveira LG , Polonio CM , França TT , De Souza GP , Muraro SP , Amorim MR , Carregari VC , Brandão-Teles C , da Silva Patrick , de Oliveira MG , França RFO , Cunha MP , Nogueira ML , Martins-de-Souza D , Condino-Neto A , Proença-Modena JL , Peron JPS 
Published: September 2021

ABSTRACTZIKV is a 11Kb positive stranded flavivirus transmitted by infected Aedes aegypti and by sexual intercourse. After a short period of viremia of 5-7 days, the virus is cleared, and infection resolved in 80% of individuals. However, around 27% of the fetuses from pregnant infected mothers may develop several fetal brain and ocular pathology. Here we show that murine and peripheral blood human neutrophils support ZIKV infection and replication both in vitro and in vivo, which may correlate to the facilitation of vertical transmission. ZIKV did not interfere with cell viability, neither induced ROS production nor the release of NETs by infected neutrophils. Also, ZIKV infection of neutrophils did not trigger a pro-inflammatory profile, as evidenced by qPCR and proteomic analysis. Interestingly, ZIKV-infected neutrophils were isolated from the placenta were highly infected. The transference of in vitro ZIKV-infected neutrophils to pregnant female mice favored the transference of viral particles to the fetus. Conversely, neutrophil depletion with monoclonal antibodies reduced fetal viral loads whereas the treatment with recombinant G-CSF has the opposite effect. In summary, although it has already been shown that circulating monocytes harbor ZIKV, to our knowledge, this is the first report demonstrating the role of neutrophils during ZIKV infection, and most important, that it may act as a trojan horse to placental tissue directly impacting the pathogenesis of congenital syndrome.
An outbreak of Rift Valley fever among peri-urban dairy cattle in northern Tanzania, 2018
Authors: de Glanville William A. , Allan Kathryn J. , Nyarobi James M. , Thomas Kate. M. , Lankester Felix , Kibona Tito , Claxton John R. , Brennan Benjamin , Carter Ryan W. , Crump John A. , Halliday Jo E.B. , Ladbury Georgia , Mmbaga Blandina T. , Mramba Furaha , Nyasebwa Obed M. , Rubach Matthew P. , Rostal Melinda K. , Sanka Paul , Swai Emmanuel S. , Szemiel Agnieszka M. , Willett Brian J. , Cleaveland Sarah 
Published: September 2021

AbstractUndetected Rift Valley fever (RVF) outbreaks are expected in endemic countries but little is known about their size or frequency. We describe a previously unreported RVF outbreak involving dairy cattle that appeared to be limited to the edge of the town of Moshi, Tanzania and occurred from May through August, 2018. The outbreak was detected retrospectively using samples collected as part of a cohort study investigating the causes of livestock abortion across northern Tanzania. A total of 14 RVF-associated cattle abortions were identified using a combination of serology and quantitative reverse transcription PCR (RT-qPCR). Milk samples from three (21%) of 14 cases were also RT-qPCR positive. Genotyping revealed circulation of RVF viruses from two lineages. The occurrence of an RVF outbreak among peri-urban dairy cattle, and evidence for RVF viral shedding in milk, highlights the potential for emerging zoonotic risks associated with the growth of urban and peri-urban livestock populations.
Seasonal temporal dynamics of marine protists communities in tidally mixed coastal waters
Authors: Caracciolo Mariarita , Rigaut-Jalabert Fabienne , Romac Sarah , Mahé Frédéric , Forsans Samuel , Gac Jean-Philippe , Arsenieff Laure , Manno Maxime , Chaffron Samuel , Cariou Thierry , Hoebeke Mark , Bozec Yann , Goberville Eric , Gall Florence Le , Guilloux Loïc , Baudoux Anne-Claire , de Vargas Colomban , Not Fabrice , Thiébaut Eric , Henry Nicolas , Simon Nathalie 
Published: September 2021

AbstractMajor seasonal community reorganizations and associated biomass variations are landmarks of plankton ecology. However, the processes determining marine species and community turnover rates have not been fully elucidated so far. Here, we analyse patterns of planktonic protist community succession in temperate latitudes, based on quantitative taxonomic data from both microscopy counts and ribosomal DNA metabarcoding from plankton samples collected biweekly over 8 years (2009-2016) at the SOMLIT-Astan station (Roscoff, Western English Channel). Considering the temporal structure of community dynamics (creating temporal correlation), we elucidated the recurrent seasonal pattern of the dominant species and OTUs (rDNA-derived taxa) that drive annual plankton successions. The use of morphological and molecular analyses in combination allowed us to assess absolute species abundance while improving taxonomic resolution, and revealed a greater diversity. Overall, our results underpinned a protist community characterised by a seasonal structure, which is supported by the dominant OTUs. We detected that some were partly benthic as a result of the intense tidal mixing typical of the French coasts in the English Channel. While the occurrence of these microorganisms is driven by the physical and biogeochemical conditions of the environment, internal community processes, such as the complex network of biotic interactions, also play a key role in shaping protist communities.
Tomato Prosystemin is much more than a simple Systemin precursor
Authors: Molisso Donata , Coppola Mariangela , Buonanno Martina , Di Lelio Ilaria , Monti Simona Maria , Melchiorre Chiara , Amoresano Angela , Corrado Giandomenico , Delano Frier John Paul , Becchimanzi Andrea , Pennacchio Francesco , Rao Rosa 
Published: September 2021

SummarySystemin (Sys) is an octadecapeptide which, upon wounding, is released from the carboxy terminus of its precursor, prosystemin(ProSys) to promote plant defenses. Recent findings on the disordered structure of ProSysprompted us to investigate a putative biological role of the whole precursor deprived of Sys peptide. We produced transgenic tomato plants expressing a truncatedProSysgene in which the exon coding for Sys was removed and compared their defense response with that induced by the exogenous application of the recombinant deleted ProSys[ProSys(1-178)].By combining protein structure analyses, transcriptomic analysis, gene expression profiling and bioassays with different pests we demonstrate that the truncated ProSys, that does not induce the endogenousProSysgene, promotes defense barriers in tomato plants through a hormone independent defense pathway, likely associated with the production of oligogalacturonides (OGs). Both transgenic and plants treated with the recombinant protein showed the modulation of the expression of genes linked with defense responses and resulted protected against the lepidopteran pestSpodoptera littoralisand the fungusBotrytis cinerea. Our results suggest that the overall function of the wild type prosystemin is more complex than previously shown as it might activate at least two tomato defense pathways: the well-known Sys-dependent pathway connected with the induction of JA biosynthesis and the successive activation of a set of defense-related genes and the ProSys(1-178)-dependent pathway associated with OGs production leading to the OGs mediate plant immunity.
Ecdysteroid kinase-like (EcKL) paralogs confer developmental tolerance to caffeine in Drosophila melanogaster
Authors: Scanlan Jack L. , Battlay Paul , Robin Charles 
Published: September 2021

AbstractA unique aspect of metabolic detoxification in insects compared to other animals is the presence of xenobiotic phosphorylation, about which little is currently understood. Our previous work raised the hypothesis that members of the taxonomically restricted ecdysteroid kinase-like (EcKL) gene family encode the enzymes responsible for xenobiotic phosphorylation in the model insect Drosophila melanogaster (Diptera: Ephydroidea)—however, candidate detoxification genes identified in the EcKL family have yet to be functionally validated. Here, we test the hypothesis that EcKL genes in the rapidly evolving Dro5 clade are involved in the detoxification of plant and fungal toxins in D. melanogaster. The mining and reanalysis of existing data indicated multiple Dro5 genes are transcriptionally induced by the plant alkaloid caffeine and that adult caffeine susceptibility is associated with a novel naturally occurring indel in CG31370 (Dro5-8) in the Drosophila Genetic Reference Panel (DGRP). CRISPR-Cas9 mutagenesis of five Dro5 EcKLs substantially decreased developmental tolerance of caffeine, while individual overexpression of two of these genes—CG31300 (Dro5-1) and CG13659 (Dro5-7)—in detoxification-related tissues increased developmental tolerance. In addition, we found Dro5 loss-of-function animals also have decreased developmental tolerance of the fungal secondary metabolite kojic acid. Taken together, this work provides the first compelling functional evidence that EcKLs encode detoxification enzymes and suggests that EcKLs in the Dro5 clade are involved in the metabolism of multiple ecologically relevant toxins in D. melanogaster. We also propose a biochemical hypothesis for EcKL involvement in caffeine detoxification and highlight the many unknown aspects of caffeine metabolism in D. melanogaster and other insects.HighlightsPhosphorylation is an under-characterised detoxification reaction in insectsDro5 EcKL genes are good detoxification candidate genes in Drosophila melanogasterKnockout and misexpression of some Dro5 genes modulated tolerance to caffeineDro5 genes may also confer tolerance to the fungal toxin kojic acidCaffeine tolerance could be adaptive for Drosophila associating with Citrus fruits
An Intersection between Iron Availability and Candida albicans Invasive Filamentation
Authors: Junier Ashlee , Weeks Anne , Alcaraz Ysabella , Kumamoto Carol A. 
Published: September 2021

AbstractCandida albicans filamentation, the ability to convert from oval yeast cells to elongated hyphal cells, is a key factor in its pathogenesis. Previous work has shown that the integral membrane protein Dfi1 is required for filamentation in cells grown in contact with a semi-solid surface. Investigations into the downstream targets of the Dfi1 pathway revealed potential links to two transcription factors – Sef1 and Czf1. Sef1 regulates iron uptake and iron utilization genes in low iron conditions, leading us to hypothesize that there exists a link between iron availability and contact-dependent invasive filamentation. Here, we showed that Sef1 was not required for contact dependent filamentation, but it was required for WT expression levels of a number of genes during growth in contact conditions. Czf1 is required for contact-dependent filamentation and for WT levels of expression of several genes. Constitutive expression and activation of either Sef1 or Czf1 individually in a dfi1 null strain resulted in a complete rescue of the dfi1 null filamentation defect. Because Sef1 is normally activated in low-iron environments, we embedded WT and dfi1 null cells in iron-free agar medium supplemented with various concentrations of Ferrous Ammonium Sulfate (FAS). dfi1 null cells embedded in media with a low concentration of iron (20uM FAS) showed increased filamentation in comparison to mutant cells embedded in higher concentrations of iron (50-500uM). WT cells produced filamentous colonies in all concentrations. Together, this data indicates that Dfi1, Czf1, Sef1, and environmental iron regulate C. albicans contact-dependent filamentation.ImportanceCandida albicans is an opportunistic pathogen responsible for a larger proportion of candidiasis and candidemia cases than any other Candida species (CDC). The ability of C. albicans cells to invade and cause disease is linked to their ability to filament and form hyphae. Despite this, there are gaps in our knowledge of the environmental cues and intracellular signaling that triggers the switch from commensal organism to filamentous pathogen. Here we identified a link between contact-dependent filamentation and iron availability. Over the course of tissue invasion, C. albicans cells encounter a number of different iron microenvironments, from the iron-rich gut to iron-poor tissues. Increased expression of Sef1-depndent iron uptake genes as a result of contact-dependent signaling will promote the adaptation of C. albicans cells to a low iron availability environment.
Isolation and characterization of a highly specific monoclonal antibody targeting the botulinum neurotoxin type E exposed SNAP-25 neoepitope
Authors: Mechaly Adva , Diamant Eran , Alcalay Ron , Ben-David Alon , Dor Eyal , Torgeman Amram , Barnea Ada , Girshengorn Meni , Levin Lilach , Epstein Eyal , Tennenhouse Ariel , Fleishman Sarel J. , Zichel Ran , Mazor Ohad 
Published: September 2021

AbstractBotulinum neurotoxin type E (BoNT/E), the fastest acting toxin of all BoNTs, cleaves the 25 kDa synaptosomal associated protein (SNAP-25) in motor neurons, leading to flaccid paralysis. Specific detection and quantification of BoNT/E-cleaved SNAP-25 neoepitope is essential for diagnosis of BoNT/E intoxication as well as for characterization of anti-BoNT/E antibody preparations. In order to isolate highly specific monoclonal antibodies suitable for in vitro immuno-detection of the exposed neoepitope, mice and rabbits were immunized with an eight amino acid peptide composed of the C-terminus of the cleaved SNAP-25. Immunized rabbits developed a specific and robust polyclonal antibody response, whereas immunized mice mostly demonstrated a weak antibody response that could not discriminate between the two forms of SNAP-25. An immune scFv phage-display library was constructed from the immunized rabbits and a panel of antibodies was isolated. Sequence alignment of the isolated clones revealed high similarity between both heavy and light chains, with exceptionally short HCDR3 sequences. A chimeric scFv-Fc antibody was further expressed and characterized, exhibiting a selective, ultra-high affinity (pM) towards the SNAP-25 neoepitope. Moreover, this antibody enabled sensitive detection of the cleaved SNAP-25 in BoNT/E treated SiMa cells with no cross reactivity with the intact SNAP-25. This novel antibody can be further used to develop an in vitro cell-based assay to diagnose BoNT/E intoxication and to characterize antitoxin preparations, thus eliminating the use of animals in the standard mouse bioassay.
Surface marker expression in small and medium/large mesenchymal stromal cell-derived extracellular vesicles in naïve or apoptotic condition using orthogonal techniques
Authors: Skovronova Renata , Grange Cristina , Dimuccio Veronica , Deregibus Maria Chiara , Camussi Giovanni , Bussolati Benedetta 
Published: September 2021

AbstractExtracellular vesicles released by mesenchymal stromal cells (MSC EVs) are a promising resource for regenerative medicine. In particular, small MSC EVs represent the active EV fraction for therapeutic applications. A bulk analysis is applied to characterize MSC EVs identity and purity, coupled with the assessment of single EV morphology, size and integrity using electron microscopy. We here applied different orthogonal methods to provide a quantitative analysis of size and surface marker expression in medium/large and small fractions, namely 10k and 100k fractions, of MSC EVs obtained by sequential ultracentrifugations. Bone marrow, adipose tissue, and umbilical cord MSC EVs were compared, in naïve and apoptotic conditions. The 100k EV size <100 nm, as detected by electron microscopy, was confirmed by super-resolution microscopy and ExoView. Quantitative single-vesicle imaging using super-resolution microscopy revealed heterogeneous patterns of tetraspanin expressions, being all MSC EV fractions single, double and triple positive, in variable proportions, for CD63, CD81 and CD9. Moreover, ExoView analysis allowed a comparative multiplex screening of single MSC EV tetraspanin and mesenchymal marker levels. Finally, a semiquantitative bead based cytofluorimetric analysis showed the segregation of immunological and pro-coagulative markers on the 10k MSC EV fraction. Apoptotic MSC EVs were released in higher number, without significant differences from the naïve fractions in surface marker expression. These results indicate that a consistent profile of MSC EV fractions among the different MSC sources, and a safer profile of the 100k MSC EV population for clinical application. Finally, our study identified suitable applications for different EV analytical techniques.
Paving the way towards understanding the inflammatory pathways triggered by giant viruses in mammalian cells: effect of mimivirus-cell interactions on IκBα degradation
Authors: Oliveira Juliana dos Santos , Oliveira Dahienne Ferreira , Essus Victor Alejandro , Nunes Gabriel Henrique Pereira , Honorato Leandro , Oliveira Leandro , Nimrichter Leonardo , Peralta José Mauro , Guimaraes Allan Jefferson , Foguel Debora , Cortines Juliana Reis 
Published: September 2021

AbstractEven after two decades since the identification of the first giant virus, the Acanthamoeba polyphaga mimivirus (APMV), it still elude scientists. Their gigantic size and genome are unique in the whole virosphere, and many aspects of their biology are still unknown, including their possible hosts. They are cultivated in laboratories using Acanthamoeba cells as hosts, but little is known about the infectivity of these giant viruses in vertebrate cells. However, there is evidence of the possible involvement of APMV in pneumonia and activation of inflammatory pathways. Among the hundreds of prospected giant viruses members is Tupanvirus, isolated in Brazil. Its particles have a characteristically large size varying between 1.2 to 2 μm and are covered by fibrils. In the present work, we aim to study the consequences of the incubation of APMV and Tupanvirus with mammalian cells. These cells express Toll-like receptors (TLR) that are capable of recognizing lipopolysaccharides, favoring the internalization of the antigen and activation of the inflammatory system. We used a lineage of human lung adenocarcinoma cells (A549) to evaluate possible effects of TLR activation by the giant viruses and if we could detect the probable cause of the said giant-virus dependent pneumonia. Our results show that APMV and Tupanvirus (TPV) activate cellular receptors related to the Toll-like 4 type-induced inflammatory response and that the A549 cells are capable of internalizing the latter virus. Therefore, this study brings new insights into the possible interactions established between mimiviruses (here represented by APMV and Tupanvirus) and members of the innate cellular immune response.
MyD88 Mediates Colitis- and RANKL-induced Microfold Cell Differentiation
Authors: Li Yang , Yang Shanshan , Huang Xin , Yang Ning , Wang Caiying , Zhao Jing , Jing Zhizhong , Willems Luc , Liu Guangliang 
Published: September 2021

AbstractIntestinal microfold (M) cells are critical for sampling antigen in the gut and initiating the intestinal mucosal immune response. In this study, we found that the differentiation efficiency of M cells was closely related to the colitis severity. The expression levels of M cells differentiation-related genes were synchronized with the kinetics of pro-inflammatory cytokines expression originated from dextran sulfate sodium (DSS) induction and Salmonella infection. Compared with wild-type (WT) mice, MyD88-/- mice exhibited significantly lower expression levels of M cells differentiation-related genes. However, DSS could induce colitis in MyD88-/- mice but failed to promote M cells differentiation. Furthermore, the receptor activator of the Nuclear Factor-κB ligand (RANKL) induced M cells differentiation in murine intestinal organoids prepared from both WT and MyD88-/- mice. However, less M cells differentiation were found in MyD88-/- mice as compared with WT mice. Hence, we concluded that myeloid differentiation factor 88 (MyD88) is an essential molecule for colitis- and RANKL-related M cells differentiation.