bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Chromatin Remodeling Protein CHD-1 and the EFL-1/DPL-1 Transcription Factor Cooperatively Down Regulate CDK-2 to Control SAS-6 Levels and Centriole Number
Authors: Iyer Jyoti , Gentry Lindsey , Bergwell Mary , Smith Amy , Guargliardo Sarah , Kropp Peter A. , Sankaralingam Prabhu , Liu Yan , Spooner Eric , Bowerman Bruce , O’Connell Kevin F. 
Published: September 2021

AbstractCentrioles are submicron-scale, barrel-shaped organelles typically found in pairs, and play important roles in ciliogenesis and bipolar spindle assembly. In general, successful execution of centriole-dependent processes is highly reliant on the ability of the cell to stringently control centriole number. This in turn is mainly achieved through the precise duplication of centrioles during each S phase. Aberrations in centriole duplication disrupt spindle assembly and cilia based signaling and have been linked to cancer, primary microcephaly and a variety of growth disorders. Studies aimed at understanding how centriole duplication is controlled have mainly focused on the post-translational regulation of two key components of this pathway: the master regulatory kinase ZYG-1/Plk4 and the scaffold component SAS-6. In contrast, how transcriptional control mechanisms might contribute to this process have not been well explored. Here we show that the chromatin remodeling protein CHD-1 contributes to the regulation of centriole duplication in the C. elegans embryo. Specifically, we find that loss of CHD-1 or inactivation of its ATPase activity can restore embryonic viability and centriole duplication to a strain expressing insufficient ZYG-1 activity. Interestingly, loss of CHD-1 is associated with increases in the levels of two ZYG-1-binding partners: SPD-2, the centriole receptor for ZYG-1 and SAS-6. Finally, we explore transcriptional regulatory networks governing centriole duplication and find that CHD-1 and a second transcription factor, EFL-1/DPL-1 cooperate to down regulate expression of CDK-2, which in turn promotes SAS-6 protein levels. Disruption of this regulatory network results in the overexpression of SAS-6 and the production of extra centrioles.Author SummaryCentrioles are cellular constituents that play an important role in cell reproduction, signaling and movement. To properly function, centrioles must be present in the cell at precise numbers. Errors in maintaining centriole number result in cell division defects and diseases such as cancer and microcephaly. How the cell maintains proper centriole copy number is not entirely understood. Here we show that two transcription factors, EFL-1/DPL-1 and CHD-1 cooperate to reduce expression of CDK-2, a master regulator of the cell cycle. We find that CDK-2 in turn promotes expression of SAS-6, a major building block of centrioles. When EFL-1/DPL-1 and CHD-1 are inhibited, CDK-2 is overexpressed. This leads to increased levels of SAS-6 and excess centrioles. Our work thus demonstrates a novel mechanism for controlling centriole number and is thus relevant to those human diseases caused by defects in centriole copy number control.
Concomitant Pyroptotic and Apoptotic Cell Death Triggered in Monocytes Infected by Zika Virus
Authors: Wen Chunxia , Yu Yufeng , Gao Chengfeng , Qi Xian , Cardona Carol J. , Xing Zheng 
Published: September 2021

ABSTRACTZika virus (ZIKV) is a positive-sense RNA flavivirus and can cause serious neurological disorders including microcephaly in infected fetus. As a mosquito-borne arbovirus, ZIKV enters bloodstream and is transmitted into the fetus through the placenta in pregnant women. Monocytes are considered one of the earliest blood cell types to be infected by ZIKV. As a first line defence, monocytes are crucial components in innate immunity and host responses and may impact viral pathogenesis in humans. Previous studies have shown that ZIKV infection can activate inflammasomes and induce proinflammatory cytokines in monocytes. In this report, we showed that ZIKV carried out a productive infection, which lead to cell death in human and murine monocytic cells. In addition to the presence of cleaved caspase-3, indicating that apoptosis was involved, we identified the cleaved caspase-1 and gasdemin D (GSDMD) as well as increased secretion of IL-1β and IL-18, suggesting that the inflammasome was activated that may lead to pyroptosis in infected monocytes. The pyroptosis was NLRP3-dependent and could be suppressed in the monocytes treated with shRNA to target and knockdown caspase-1, or an inhibited for caspase-1, indicating that the pyroptosis was triggered via a canonical approach. Our findings in this study demonstrate a concomitant occurrence of apoptosis and pyroptosis in ZIKV-infected monocytes, with multiple mechanisms involved in the cell death, which may have potentially significant impacts on viral pathogenesis in humans.
WolbachiastrainwAu differs in cellular perturbation and virus inhibition profiles from previously characterisedWolbachiastrains
Authors: Rainey Stephanie M , Geoghegan Vincent , Lefteri Daniella A , Ant Thomas H , Martinez Julien , McNamara Cameron , Sinkins Steven P 
Published: September 2021

AbstractSome strains of the inherited bacteriumWolbachiahave been shown to be effective at reducing the transmission of dengue and other positive-sense RNA viruses byAedes aegyptiin both laboratory and field settings and are being deployed for dengue control. The degree of virus inhibition varies betweenWolbachiastrains; density and tissue tropism can contribute to these differences but there are also indications that this is not the only factor involved: for example, strainswAu andwAlbA are maintained at similar densities but onlywAu produces strong dengue inhibition. We previously reported perturbations in lipid transport dynamics, including sequestration of cholesterol in lipid droplets, with strainswMel /wMelPop inAe.aegypti. Here we show that strainwAu does not produce the same cholesterol sequestration phenotype despite displaying strong virus inhibition and moreover, in contrast towMel,wAu antiviral activity was not rescued by cyclodextrin treatment. To further investigate the cellular basis underlying these differences, proteomic analysis of midguts was carried out onAe.aegyptilines and revealed thatwAu-carrying midguts showed a distinct proteome when compared toWolbachia-free,wMel- orwAlbA-carrying midguts, in particular with respect to lipid transport and metabolism. The data suggest a possible role for perturbed RNA processing pathways inwAu virus inhibition. Together these results indicate thatwAu shows unique features in its inhibition of arboviruses compared to previously characterizedWolbachiastrains.Author SummaryWolbachiaendosymbionts can block transmission of dengue virus byAedes aegyptimosquitoes, andWolbachiarelease programs for dengue control are now being undertaken in several countries. Understanding the mechanisms ofWolbachia-mediated antiviral activity is important for maximizing the efficacy of this control approach. Using functional and proteomic analyses, this study indicates that different strains ofWolbachiaperturb cellular functions in diverse ways and display different antiviral profiles. These differences raise the possibility thatWolbachiastrain switching could be used to counteract viral escape mutations, should they arise and threaten the efficacy of dengue control programmes.
High lineage survivorship across the end-Devonian Mass Extinction suggested by a remarkable new Late Devonian actinopterygian
Authors: Giles Sam , Feilich Kara , Warnock Rachel , Pierce Stephanie E. , Friedman Matt 
Published: September 2021

AbstractA mass extinction at the end of the Devonian is thought to have had a major influence on the evolution of actinopterygians (ray-finned fishes), which comprise half of living vertebrates. This extinction appears to have acted as a bottleneck, paring the early diversity of the group to a handful of survivors. Coupled with increases in taxonomic and morphological diversity in the Carboniferous, this contributes to a model of explosive post-extinction radiation. However, most actinopterygians from within a ~20-million-year (Myr) window surrounding the extinction remain poorly known, contributing to uncertainty about these patterns. An exceptionally preserved fossil of a diminutive fish from 7 Myr before the extinction reveals unexpected anatomical features that suggest a very different story. This new fossil nests within a clade of post-Devonian species and, in an expanded phylogenetic analysis, draws multiple lineages of Carboniferous actinopterygians into the Devonian. This suggests cryptic but extensive lineage diversification in the latest Devonian, followed by more conspicuous feeding and locomotor structure diversification in the Carboniferous. Our revised model matches more complex patterns of divergence, survival, and diversification around the Devonian-Carboniferous boundary in other vertebrate clades. It also fundamentally recalibrates the onset of diversification early in the history of this major radiation.
ERM-1 phosphorylation and NRFL-1 redundantly control lumen formation in the C. elegans intestine
Authors: Sepers Jorian J. , Ramalho João J. , Kroll Jason R. , Schmidt Ruben , Boxem Mike 
Published: September 2021

AbstractReorganization of the plasma membrane and underlying actin cytoskeleton into specialized domains is essential for the functioning of most polarized cells in animals. Proteins of the ezrin-radixin-moesin (ERM) and Na+/H+ exchanger 3 regulating factor (NHERF) family are conserved regulators of cortical specialization. ERM proteins function as membrane-actin linkers and as molecular scaffolds that organize the distribution of proteins at the membrane. NHERF proteins are PDZ-domain containing adapters that can bind to ERM proteins and extend their scaffolding capability. Here, we investigate how ERM and NHERF proteins function in regulating intestinal lumen formation in the nematode Caenorhabditis elegans. C. elegans has single ERM and NHERF family proteins, termed ERM-1 and NRFL-1, and ERM-1 was previously shown to be critical for intestinal lumen formation. Using CRISPR/Cas9-generated nrfl-1 alleles we demonstrate that NRFL-1 localizes at the intestinal microvilli, and that this localization is depended on an interaction with ERM-1. However, nrfl-1 loss of function mutants are viable and do not show defect in intestinal development. Interestingly, combining nrfl-1 loss with erm-1 mutants that either block or mimic phosphorylation of a regulatory C-terminal threonine causes severe defects in intestinal lumen formation. These defects are not observed in the phosphorylation mutants alone, and resemble the effects of strong erm-1 loss of function. The loss of NRFL-1 did not affect the localization or activity of ERM-1. Together, these data indicate that ERM-1 and NRFL-1 function together in intestinal lumen formation in C. elegans. We postulate that the functioning of ERM-1 in this tissue involves actin-binding activities that are regulated by the C-terminal threonine residue and the organization of apical domain composition through NRFL-1.
Two Ubiquitin-Activating Systems Occur in Plants with One Playing a Major Role in Plant Immunity
Authors: Zhou Bangjun , Wang Chaofeng , Chen Xuanyang , Zhang Yi , Zeng Lirong 
Published: September 2021

AbstractMany plants possess two or more ubiquitin-activating enzymes (E1). However, it is unclear whether the E1s of a plant genome play equivalent roles in various pathways. Here we report that tomato and tobacco encode dual ubiquitin-activating systems (DUAS) in which the E1s UBA1 and UBA2 display differential specificities in charging four groups of E2s. The C-terminal ubiquitin-folding domain of the E1s play a major but not sole role in determining the differential specificities of charging the four groups E2s. The dual systems do not play equivalent roles in plant immunity, with silence of UBA2 only compromising host immunity. Among the differentially charged E2s, group IV members UBC32, UBC33 and UBC34 are shown to be essential for ER-associated protein degradation (ERAD) and plant immunity. Like tomato, Arabidopsis UBC32/33/34 E2 triplet are also differentially charged by its E1s and are essential for plant immunity. Loss of function in Arabidopsis UBC32, UBC33 and UBC34 does not affect flg22 and elf18-triggered inhibition of seedling growth but results in alteration of ER stress tolerance, which likely contribute to the diminished plant immunity in the mutants. Our results uncover DUAS in plants and a previously unknown E1–ERAD-associated E2 triplet module in the regulation of host immunity.One sentence summaryPlant dual ubiquitin E1 systems play distinct roles in plant immunity by differentially charging the ERAD-associated E2s for ER stress tolerance.
Coding of social odors in the hippocampal CA2 region as a substrate for social memory
Authors: Hassan Sami I. , Bigler Shivani , Siegelbaum Steven A. 
Published: September 2021

SummaryThe ability to encode and update information about individuals is critical for lasting social relationships. Although the hippocampus is important for social recognition memory, its underlying neural representations remain elusive. Here we investigate the neural codes mediating social recognition and learning by examining social odor recognition and associative odor-reward learning in mice. We performed high-resolution calcium imaging from the hippocampal CA2 region of awake head-fixed mice, as CA2 is necessary for social recognition memory. We find that CA2 encodes specific neural representations of novel social odors that are further refined during associative odor-reward learning. Optogenetic silencing of CA2 impairs the formation of reward associations. Furthermore, CA2 population activity represents odors in a geometry that enables abstract representations of social versus non-social odors. Thus, CA2 distinguishes multiple forms of olfactory stimuli to enhance the learning of social odors and associations, which are poised to serve as substrates of social memory.
Changes in antennal gene expression underlying sensory system maturation in Rhodnius prolixus
Authors: Latorre-Estivalis Jose Manuel , Große-Wilde Ewald , da Rocha Fernandes Gabriel , Hansson Bill S. , Lorenzo Marcelo Gustavo 
Published: September 2021

AbstractBackgroundTriatomine bugs are the blood feeding insect vectors transmitting Chagas disease to humans, a neglected tropical disease that affects over 8 million people, mainly in Latin America. The behavioral responses to host cues and bug signals in Rhodnius prolixus are state dependent, i.e., they vary as a function of post-ecdysis age. At the molecular level, these changes in behavior are probably due to a modulation of peripheral and central processes. In the present study, we report a significant modulation of the expression of a large set of sensory-related genes. Results were generated by means of antennal transcriptomes of 5th instar larvae along the first week (days 0, 2, 4, 6 and 8) after ecdysis sequenced using the Illumina platform.ResultsAge induced significant changes in transcript abundance were established in more than 6,120 genes (54,7 % of 11,186 genes expressed) in the R. prolixus antenna. This was especially true between the first two days after ecdysis when more than 2,500 genes had their expression significantly altered. In contrast, expression profiles were almost identical between day 6 and 8, with only a few genes showing significant modulation of their expression. A total of 86 sensory receptors, odorant carriers and odorant degrading enzymes were significantly modulated across age points and clustered into three distinct expression profiles.ConclusionsThe set of sensory genes whose expression increased with age (profile 3) may include candidates underlying the increased responsiveness to host cues shown by R. prolixus during the first days after molting. For the first time, we describe the maturation process undergone at the molecular level by the peripheral sensory system is described in an hemimetabolous insect.
Green synthesis of silver nanoparticles using psychrotolerant strains of Tulasnella albida from South Orkney Islands (Antarctica)
Authors: Kobashigawa Jesica M. , Robles Carolina A. , Gaiser Rocío F. , Schinca Daniel C. , Scaffardi Lucía B. , Carmarán Cecilia C. 
Published: September 2021

AbstractNanoparticles are widely studied due to their possible uses in biological and technological systems. Four psychrotolerant strains of Tulasnella albida isolated from Antarctica were tested and compared in their ability to synthesize silver nanoparticles. The four strains were capable of synthesizing silver nanoparticles with the addition of AgNO3 (final concentration of 0.5 mM), showing similar results under the same conditions: 28°C, 200 rpm, pH 9. Additionally, we registered the synthesis of nanoparticles at 6°C using biomass generated at the same temperature. For the characterization of synthesized nanoparticles, TEM and SEM microscopy analyses were performed. The images obtained showed the existence of spherically shaped silver nanoparticles with a log-normal size distribution centered at 2 nm diameter for 28°C. The largest ones showed a capping shell around them, appearing associated with the formation of small silver nanoparticles. Theoretical calculations of optical absorption based on core-shell Ag-Ag2O nanoparticles were used to characterize the experimental absorption spectra of silver nanoparticles colloids. This work contributes to expanding the studies and possible technological applications of psychrotolerant organisms in the industry, particularly in the green synthesis of nanoparticles at suboptimal conditions.
Mechanism of innate immune reprogramming by a fungal meningitis pathogen
Authors: Dang Eric V. , Lei Susan , Radkov Atanas , Madhani Hiten D. 
Published: September 2021

AbstractHow deadly fungal pathogens overcome mammalian innate immunity is largely unknown. Cryptococcus neoformans, the most common cause of fungal meningitis, induces a pathogenic type 2 response characterized by pulmonary eosinophilia and alternatively activated macrophages. Using forward genetics, we identified a fungal secreted protein, Cpl1, necessary and sufficient to enhance alternative activation of primary macrophages in vitro. Cpl1-enhanced polarization requires Toll-like receptor 4, a known mediator of allergen-induced type 2 responses. Cpl1 is essential for virulence, drives polarization of interstitial macrophages in vivo, and requires type 2 cytokine signaling for its impact on infectivity. C. neoformans selectively associates with polarized interstitial macrophages during infection, supporting a direct hostpathogen interaction. This work identifies a secreted effector produced by a human fungal pathogen that reprograms innate immunity to enable tissue infection.One sentence summaryIdentification of a secreted fungal effector that promotes virulence by enhancing type 2 inflammation
Uip4p modulates nuclear pore complex function in Saccharomyces cerevisiae
Authors: Deolal Pallavi , Jamir Imlitoshi , Mishra Krishnaveni 
Published: September 2021

AbstractA double membrane bilayer perforated by nuclear pore complexes (NPCs) governs the shape of the nucleus, the prominent distinguishing organelle of a eukaryotic cell. Despite the absence of lamins in yeasts, the nuclear morphology is stably maintained and shape changes occur in a regulated fashion. In a quest to identify factors that contribute to regulation of nuclear shape and function in Saccharomyces cerevisiae, we used a fluorescence imaging based approach. Here we report the identification of a novel protein, Uip4p, that is required for regulation of nuclear morphology. Loss of Uip4 compromises NPC function and loss of nuclear envelope (NE) integrity. Our localisation studies show that Uip4 localizes to the NE and endoplasmic reticulum (ER) network. Furthermore, we demonstrate that the localization and expression of Uip4 is regulated during growth, which is crucial for NPC distribution.
Category-specific representational patterns in left inferior frontal and temporal cortex reflect similarities and differences in the sensorimotor and distributional properties of concepts
Authors: Carota Francesca , Kriegeskorte Nikolaus , Nili Hamed , Pulvermüller Friedemann 
Published: September 2021

AbstractNeuronal populations code similar concepts by similar activity patterns across the human brain’s networks supporting language comprehension. However, it is unclear to what extent such meaning-to-symbol mapping reflects statistical distributions of symbol meanings in language use, as quantified by word co-occurrence frequencies, or, rather, experiential information thought to be necessary for grounding symbols in sensorimotor knowledge. Here we asked whether integrating distributional semantics with human judgments of grounded sensorimotor semantics better approximates the representational similarity of conceptual categories in the brain, as compared with each of these methods used separately. We examined the similarity structure of activation patterns elicited by action- and object-related concepts using multivariate representational similarity analysis (RSA) of fMRI data. The results suggested that a semantic vector integrating both sensorimotor and distributional information yields best category discrimination on the cognitive-linguistic level, and explains the corresponding activation patterns in left posterior inferior temporal cortex. In turn, semantic vectors based on detailed visual and motor information uncovered category-specific similarity patterns in fusiform and angular gyrus for object-related concepts, and in motor cortex, left inferior frontal cortex (BA 44), and supramarginal gyrus for action-related concepts.
Characterization of SARS-CoV-2 variants B.1.617.1 (Kappa), B.1.617.2 (Delta) and B.1.618 on cell entry, host range, and sensitivity to convalescent plasma and ACE2 decoy receptor
Authors: Ren Wenlin , Ju Xiaohui , Gong Mingli , Lan Jun , Yu Yanying , Long Quanxin , Zhang Yu , Zhong Jin , Zhong Guocai , Wang Xinquan , Huang Ailong , Zhang Rong , Ding Qiang 
Published: September 2021

ABSTRACTRecently, highly transmissible SARS-CoV-2 variants B.1.617.1 (Kappa), B.1.617.2 (Delta) and B.1.618 were identified in India with mutations within the spike proteins. The spike protein of Kappa contains four mutations E154K, L452R, E484Q and P681R, and Delta contains L452R, T478K and P681R, while B.1.618 spike harbors mutations Δ145-146 and E484K. However, it remains unknown whether these variants have altered in their entry efficiency, host tropism, and sensitivity to neutralizing antibodies as well as entry inhibitors. In this study, we found that Kappa, Delta or B.1.618 spike uses human ACE2 with no or slightly increased efficiency, while gains a significantly increased binding affinity with mouse, marmoset and koala ACE2 orthologs, which exhibits limited binding with WT spike. Furthermore, the P618R mutation leads to enhanced spike cleavage, which could facilitate viral entry. In addition, Kappa, Delta and B.1.618 exhibits a reduced sensitivity to neutralization by convalescent sera owning to the mutation of E484Q, T478K, Δ145-146 or E484K, but remains sensitive to entry inhibitors-ACE2-lg decoy receptor. Collectively, our study revealed that enhanced human and mouse ACE2 receptor engagement, increased spike cleavage and reduced sensitivity to neutralization antibodies of Kappa, Delta and B.1.618 may contribute to the rapid spread of these variants and expanded host range. Furthermore, our result also highlighted that ACE2-lg could be developed as broad-spectrum antiviral strategy against SARS-CoV-2 variants.