bluuebunny/crossref_metadata_2025_split huggingface dataset:
Self-Assembling Peptide Hydrogels - PeptiGels®as a Platform for Hepatic Organoid Culture
Authors: Olayanju Adedamola , Miller Aline F , Ansari Tahera , Goldring Christopher E. 
Published: March 2021

AbstractA major challenge in advancing preclinical studies is the lack of robust in vitro culture systems that fully recapitulate thein vivoscenario together with limited clinical translational to humans. Organoids, as 3-dimensional (3D) self-replicating structures are increasingly being shown as powerful models forex vivoexperimentation in the field of regenerative medicine and drug discovery. Organoid formation requires the use of extracellular matrix (ECM) components to provide a 3D platform. However, the most commonly used ECM, essential for maintaining organoid growth is Matrigel and is derived from a tumorigenic source which limits its translational ability. PeptiGels®which are self-assembling peptide hydrogels present as alternatives to traditional ECM for use in 3D culture systems. Synthetic PeptiGels®are non-toxic, biocompatible, biodegradable and can be tuneable to simulate different tissue microenvironments. In this study, we validated the use of different types of PeptiGels®for porcine hepatic organoid growth. Hepatic organoids were assessed morphologically and using molecular techniques to determine the optimum PeptiGel®formulation. The outcome clearly demonstrated the ability of PeptiGel®to support organoid growth and offer themselves as a technological platform for 3D cultured physiologically and clinically relevant data.
A role for the immune system-released activating agent (ISRAA) in the ontogenetic development of brain astrocytes
Authors: Al-Awadi Aminah M. I. , AlJawder Abdulaziz Isa , Mousa Alyaa , Taha Safa , Bakhiet Moiz 
Published: March 2021

AbstractThe Immune System-Released Activating Agent (ISRAA) was discovered as a novel molecule that functions as a mediator between the nervous and immune systems in response to a nervous stimulus following an immune challenge. This research investigated the role of ISRAA) in promoting the ontogeny of the mouse brain astrocytes. Astrocyte cultures were prepared from two-month-old BALB/c mice. Recombinant ISRAA protein was used to stimulate astrocyte cultures. Immunohistochemistry and ELISA were utilized to measure ISRAA and IFN-γ levels, IFN-γR expression and STAT1 nuclear translocation. MTT-assay was used to evaluate cellular survival and proliferation. To assess astrocyte cell lysates and tyrosine-phosphorylated proteins, SDS-PAGE and western blot were used. ISRAA was highly expressed in mouse embryonic astrocytes, depending on cell age. Astrocytes aged seven days (E7) showed increased proliferation and diminished differentiation, while 21-day-old (E21) astrocytes depicted reversed effects. ISRAA stimulated the tyrosine phosphorylation of numerous cellular proteins and the nuclear translocation of STAT1. IFN-γ was involved in the ISRAA action as ISRAA induced IFN-γin both age groups, but only E21 astrocytes expressed IFN-γR. The results suggest that ISRAA is involved in mouse brain development through the cytokine network involving IFN-γ.
Derivation and Characterization of an inositol phosphate-independent HIV-1
Authors: Poston Daniel , Zang Trinity , Bieniasz Paul 
Published: March 2021

AbstractA critical step in the HIV-1 replication cycle is the assembly of Gag proteins to form virions at the plasma membrane. Virion assembly and maturation is facilitated by the cellular polyanion inositol hexaphosphate (IP6), which is proposed to stabilize both the immature Gag lattice and the mature capsid lattice by binding to rings of primary amines at the center of Gag or capsid protein (CA) hexamers. The amino acids comprising these rings are critical for proper virion formation and their substitution results in assembly deficits or impaired infectiousness. To better understand the nature of the deficits that accompany IP6-deficiency, we passaged HIV-1 mutants that had substitutions in IP6-coordinating residues to select for compensatory mutations. We found a mutation, a threonine to isoleucine substitution at position 371 (T371I) in Gag, that restored replication competence to an IP6-binding-deficient HIV-1 mutant. Notably, unlike wild-type HIV-1, the assembly and infectiousness of resulting virus was not impaired when IP6 biosynthetic enzymes were genetically ablated. Surprisingly, we also found that the maturation inhibitor Bevirimat (BVM) could restore the assembly and replication of an IP6-binding deficient mutant. Moreover, using BVM-dependent mutants we were able to image the BVM-inducible assembly of individual HIV-1 particles assembly in living cells. Overall these results suggest that IP6-Gag and Gag-Gag contacts are finely tuned to generate a Gag lattice of optimal stability, and that under certain conditions BVM can functionally replace IP6.Author SummaryA key step in HIV-1 replication is the assembly of virions that are released from the infected cell. Previous work has suggested that a small molecule called IP6is critical role in this process, promoting both HIV-1 assembly and the stability of mature fully infectious virions. Since IP6is required for multiple steps in HIV-1 assembly and maturation, it is a candidate for the development of anti-retroviral therapies. Here, we identify an HIV-1 mutant that replicates independently of IP6, and show that a different small molecule can functionally substitute for IP6under certain conditions. These findings suggest that IP6regulates the stability of protein interactions during virion assembly and that the precise degree stability of these interactions is finely tuned and important for generating infectious virions. Finally, our work identifies an inducible virion assembly system that can be utilized to visualize HIV-1 assembly events using live cell microscopy.
Identify phage hosts from metaviromic short reads based on deep learning and Markov chain model
Authors: Tan Jie , Fang Zhencheng , Wu Shufang , Guo Qian , Jiang Xiaoqing , Zhu Huaiqiu 
Published: March 2021

AbstractPhages - viruses that infect bacteria and archaea - are dominant in the virosphere and play an important role in the microbial community. It is very important to identify the host of a given phage fragment from metavriome data for understanding the ecological impact of phage in a microbial community. State-of-the-art tools for host identification only present reliable results on long sequences within a narrow candidate host range, while there are a large number of short fragments in real metagenomic data and the taxonomic composition of a microbial community is often complicated. Here, we present a method, named HoPhage, to identify the host of a given phage fragment from metavirome data at the genus level. HoPhage integrates two modules using the deep learning algorithms and the Markov chain model, respectively. By testing on both the artificial benchmark dataset of phage contigs and the real virome data, HoPhage demonstrates a satisfactory performance on short fragments within a wide candidate host range at every taxonomic level. HoPhage is freely available athttp://cqb.pku.edu.cn/ZhuLab/HoPhage/.
Parvalbumin interneuron inhibition onto anterior insula neurons projecting to the basolateral amygdala orchestrates aversive taste memory retrieval
Authors: Yiannakas Adonis , Chandran Sailendrakumar Kolatt , Kayyal Haneen , Gould Nathaniel , Khamaisy Mohammad , Rosenblum Kobi 
Published: March 2021

AbstractMemory retrieval refers to the fundamental ability of organisms to make use of acquired, sometimes inconsistent, information about the world. While memory acquisition has been studied extensively, the neurobiological mechanisms underlying memory retrieval remain largely unknown. The anterior insula (aIC) is indispensable in the ability of mammals to retrieve associative information regarding tastants that have been previously linked with gastric malaise. Here, we show that aversive taste memory retrieval promotes cell-type-specific activation in the aIC. Aversive, but not appetitive taste memory retrieval, relies on specific changes in activity and connectivity at parvalbumin (PV) inhibitory synapses onto aIC pyramidal neurons projecting to the basolateral amygdala. PV aIC interneurons, coordinate aversive taste memory retrieval, and are necessary for its dominance when conflicting internal representations are encountered. This newly described interaction of PV and a subset of excitatory neurons can explain the coherency of aversive memory retrieval, an evolutionary pre-requisite for animal survival.Graphical AbstractRetrieval of Conditioned Taste Aversion (CTA) memories at the anterior insular cortex activates Parvalbumin (PV) interneurons and increases synaptic inhibition onto activated pyramidal neurons projecting to the basolateral amygdala (aIC-BLA).Unlike innately appetitive taste memory retrieval, CTA retrieval increases the amplitude and frequency of synaptic inhibition onto aIC-BLA projecting neurons, that is dependent on activity in aIC PV interneurons.Activation of aIC PV interneurons is necessary for the expression of learned taste avoidance, in both sexes, regardless of stimulus identity.Extinction of aversive taste memories suppresses the frequency, but not the amplitude of synaptic inhibition on aIC-BLA projecting neurons.The reinstatement of aversive taste memories following extinction is dependent upon activation of aIC PV interneurons and increases in the frequency of inhibition on aIC-BLA projecting neurons.
PRDM9 directs recombination hotspots to prevent competition with meiotic transcription
Authors: Schwarzkopf Enrique J. , Cornejo Omar E. 
Published: March 2021

AbstractPRDM9 drives recombination hotspots in some mammals, including mice and apes. Non-functional orthologs of PRDM9 are present in a wide variety of vertebrates, but why it is functionally maintained in some lineages is not clear. One possible explanation is that PRDM9 plays a role in ensuring that meiosis is successful. During meiosis, available DNA may be a limiting resource given the tight packaging of chromosomes and could lead to competition between two key processes: meiotic transcription and recombination. Here we explore this potential competition and the role that PRDM9 might play in their interaction. Leveraging existing mouse genomic data, we use resampling schemes that simulate shuffled features along the genome and models that account for the rarity of features in the genome, to test if PRDM9 influences interactions between recombination hotspots and meiotic transcription in a whole genome framework. We also explored possible DNA sequence motifs associated to clusters of hotspots not tied to transcription or PRDM9. We find evidence of competition between meiotic transcription and recombination, with PRDM9 appearing to relocate recombination to avoid said conflict. We also find that retrotransposons may be playing a role in directing hotspots in the absence of other factors.
Approximate Hidden Semi-Markov Models for Dynamic Connectivity Analysis in Resting-State fMRI
Authors: Fiecas Mark B. , Coffman Christian , Xu Meng , Hendrickson Timothy J. , Mueller Bryon A. , Klimes-Dougan Bonnie , Cullen Kathryn R. 
Published: March 2021

AbstractMotivated by a study on adolescent mental health, we conduct a dynamic connectivity analysis using resting-state functional magnetic resonance imaging (fMRI) data. A dynamic connectivity analysis investigates how the interactions between different regions of the brain, represented by the different dimensions of a multivariate time series, change over time. Hidden Markov models (HMMs) and hidden semi-Markov models (HSMMs) are common analytic approaches for conducting dynamic connectivity analyses. However, existing approaches for HSMMs are limited in their ability to incorporate covariate information. In this work, we approximate an HSMM using an HMM for modeling multivariate time series data. The approximate HSMM model allows one to explicitly model dwell-time distributions that are available to HSMMs, while maintaining the theoretical and methodological advances that are available to HMMs. We conducted a simulation study to show the performance of the approximate HSMM relative to other approaches. Finally, we used the approximate HSMM to conduct a dynamic connectivity analysis, where we showed how dwell-time distributions vary across the severity of non-suicidal self-injury (NSSI) in female adolescents, and how those with moderate or severe NSSI have greater state-switching frequency.
An evolutionary genomic approach reveals both conserved and species-specific genetic elements related to human disease in closely relatedAspergillusfungi
Authors: Mead Matthew E. , Steenwyk Jacob L. , Silva Lilian P. , de Castro Patrícia A. , Saeed Nauman , Hillmann Falk , Goldman Gustavo H. , Rokas Antonis 
Published: March 2021

AbstractAspergillosis is an important opportunistic human disease caused by filamentous fungi in the genusAspergillus. Roughly 70% of infections are caused byAspergillus fumigatus, with the rest stemming from approximately a dozen otherAspergillusspecies. Several of these pathogens are closely related toA. fumigatusand belong in the same taxonomic section, sectionFumigati. Pathogenic species are frequently most closely related to non-pathogenic ones, suggestingAspergilluspathogenicity evolved multiple times independently. To understand the repeated evolution ofAspergilluspathogenicity, we performed comparative genomic analyses on 18 strains from 13 species, including 8 species in sectionFumigati, which aimed to identify genes, both ones previously connected to virulence as well as ones never before implicated, whose evolution differs between pathogens and non-pathogens. We found that most genes were present in all species, including approximately half of those previously connected to virulence, but a few genes were section- or species-specific. Evolutionary rate analyses identified hundreds of genes in pathogens that were faster-evolving than their orthologs in non-pathogens. For example, over 25% of all single-copy genes examined inA. fumigatuswere faster-evolving. Functional testing of deletion mutants of 17 transcription factor-encoding genes whose evolution differed between pathogens and non-pathogens identified eight genes that affect either fungal survival in a model of phagocytic killing, host survival in an animal model of fungal disease, or both. These results suggest that the evolution of pathogenicity inAspergillusinvolved both conserved and species-specific genetic elements, illustrating how an evolutionary genomic approach informs the study of fungal disease.
Analysis of Classic Tomato Mutants Reveals Influence of Leaf Vein Density on Fruit BRIX
Authors: Cheng Zizhang , Rowland S.D. , Czarnecki Karo , Zumstein Kristina , Nakayama Hokuto , Sinha Neelima R. 
Published: March 2021

ABSTRACTTomatobipinnate(bip) is a classic leaf mutant, with highly increased leaf complexity resulting from the loss of function of aBEL-LIKE HOMEODAMAIN(BELL) gene. Here, we analyzed severalbipmutants and their isogenic wildtype backgrounds for a suite of leaf morphology traits, ranging from leaf complexity, leaflet shape and size, to leaf vascular density to investigate how changes in leaf morphology influence fruit traits. Our analyses showed an unexpected relationship between leaf vein density and fruit sugar levels, where leaf vein density was negatively correlated with fruit BRIX. RNA-Seq analysis suggested variation inGlucose-6-phosphate translocator2(GPT2) gene expression caused correlated changes in leaf vein density and BRIX whenbipmutant and wildtype were compared, suggesting that the correlation between leaf vein density and fruit sugar may result from the genes regulating leaf vein development that are also involved in regulating leaf sugar biosynthesis. Our results provide a resource for further exploration of the genetic basis for the complex relationship between fruit quality and leaf traits in natural populations.
Two Types of Cinnamoyl-CoA Reductase Function Divergently in Tissue Lignification, Phenylpropanoids Flux Control, and Inter-pathway Cross-talk with Glucosinolates as Revealed inBrassica napus
Authors: Yin Nengwen , Li Bo , Liu Xue , Liang Ying , Lian Jianping , Xue Yufei , Qu Cunmin , Lu Kun , Wei Lijuan , Wang Rui , Li Jiana , Chai Yourong 
Published: March 2021

AbstractCinnamoyl-CoA reductase (CCR) is the entry point of lignin pathway and a crucial locus in dissection and manipulation of associated traits, but its functional dissection in Brassicaceae plants is largely lagged behind thoughArabidopsis thaliana CCR1has been characterized to certain extent. Here, 16CCRgenes are identified fromBrassica napusand its parental speciesB. rapaandB. oleracea. BrassicaceaeCCRgenes are divided intoCCR1subfamily andCCR2subfamily with divergent organ-specificity, yellow-seed trait participation and stresses responsiveness.CCR1is preferential in G- and H-lignins biosynthesis and vascular development, whileCCR2has a deviation to S-lignin biosynthesis and interfascicular fiber development.CCR1has stronger effects on lignification-related development, lodging resistance, phenylpropanoid flux control and seed coat pigmentation, whereasCCR2controls sinapates levels.CCR1upregulation could delay bolting and flowering time, whileCCR2upregulation weakens vascular system in leaf due to suppressed G lignin accumulation. Besides,CCR1andCCR2are deeply but almost oppositely linked with glucosinolates metabolism through inter-pathway crosstalk. Strangely, upregulation of bothCCR1andCCR2could not enhance resistance to UV-B andS. sclerotiorumthoughCCR2is sharply induced by them. These results provide systemic dissection onBrassica CCRs andCCR1-CCR2divergence in Brassicaceae.HighlightBrassicaceae contains two types of Cinnamoyl-CoA reductase. As revealed inBrassica napus, they are divergently involved in lignin monomer biosynthesis, tissue lignification, phenylpropanoid flux control, and inter-pathway crosstalk with glucosinolates.
Conformational changes in twitchin kinasein vivorevealed by FRET imaging of freely movingC. elegans
Authors: Porto Daniel , Matsunaga Yohei , Franke Barbara , Williams Rhys M. , Qadota Hiroshi , Mayans Olga , Benian Guy M. , Lu Hang 
Published: March 2021

AbstractThe force-induced unfolding and refolding of proteins is speculated to be a key mechanism in the sensing and transduction of mechanical signals in the living cell. Yet, little evidence has been gathered for its existencein vivo. Prominently, stretch-induced unfolding is postulated to be the activation mechanism of the twitchin/titin family of autoinhibited sarcomeric kinases linked to the mechanical stress response of muscle. To test the occurrence of mechanical kinase activation in living working muscle, we generated transgenicC. elegansexpressing twitchin containing FRET moieties flanking the kinase domain and developed a quantitative technique for extracting FRET signals in freely movingC. elegans, using tracking and simultaneous imaging of animals in three channels (donor fluorescence, acceptor fluorescence, and transmitted light). Computer vision algorithms were used to extract fluorescence signals and muscle contraction states in each frame, in order to obtain fluorescence and body curvature measurements with spatial and temporal precisionin vivo. The data revealed statistically significant periodic changes in FRET signals during muscle activity, consistent with a periodic change in the conformation of twitchin kinase. We conclude that stretch-unfolding of twitchin kinase occurs in the active muscle, whereby mechanical activity titrates the signalling pathway of this cytoskeletal kinase. We anticipate that the methods we have developed here could be applied to obtainingin vivoevidence for force-induced conformational changes or elastic behavior of other proteins not only inC. elegansbut in other animals in which there is optical transparency (e.g zebrafish).
A ciliopathy complex builds distal appendages to initiate ciliogenesis
Authors: Kumar Dhivya , Rains Addison , Herranz-Pérez Vicente , Lu Quanlong , Shi Xiaoyu , Swaney Danielle L. , Stevenson Erica , Krogan Nevan J. , Huang Bo , Westlake Christopher , Garcia-Verdugo Jose Manuel , Yoder Bradley , Reiter Jeremy F. 
Published: March 2021

ABSTRACTCells inherit two centrioles, the older of which is uniquely capable of generating a cilium. Using proteomics and super-resolved imaging, we identified a module which we term DISCO (DIStal centriole COmplex). DISCO components CEP90, MNR and OFD1 underlie human ciliopathies. This complex localized to both distal centrioles and centriolar satellites, proteinaceous granules surrounding centrioles. Cells and mice lacking CEP90 or MNR did not generate cilia, failed to assemble distal appendages, and did not transduce Hedgehog signals. Disrupting the satellite pools did not affect distal appendage assembly, indicating that it is the centriolar populations of MNR and CEP90 that are critical for ciliogenesis. CEP90 recruited the most proximal known distal appendage component, CEP83, to root distal appendages formation, an early step in ciliogenesis. In addition, MNR, but not CEP90, restricted centriolar length by recruiting OFD1. We conclude that DISCO acts at the distal centriole to support ciliogenesis by restraining centriole length and assembling distal appendages, defects in which cause human ciliopathies.eTOC summaryKumar et al. identifies a multi-protein complex called DISCO (DIStal centriole COmplex) required to nucleate distal appendages and restrain centriole elongation, essential for the initiation of cilium assembly. Without DISCO, cells fail to ciliate and transduce Hedgehog signals, critical for mammalian development.
Circular RNA repertoires are associated with evolutionarily young transposable elements
Authors: Gruhl Franziska , Janich Peggy , Kaessmann Henrik , Gatfield David 
Published: March 2021

AbstractCircular RNAs (circRNAs) are found across eukaryotes and can function in post-transcriptional gene regulation. Their biogenesis through a circle-forming backsplicing reaction is facilitated by reverse-complementary repetitive sequences promoting pre-mRNA folding. Orthologous genes from which circRNAs arise, overall contain more strongly conserved splice sites and exons than other genes, yet it remains unclear to what extent this conservation reflects purifying selection acting on the circRNAs themselves. Our analyses of circRNA repertoires from five species representing three mammalian lineages (marsupials, eutherians: rodents, primates) reveal that surprisingly few circRNAs arise from orthologous exonic loci across all species. Even the circRNAs from orthologous loci are associated with young, recently active and species-specific transposable elements, rather than with common, ancient transposon integration events. These observations suggest that many circRNAs emerged convergently during evolution – as a byproduct of splicing in orthologs prone to transposon insertion. Overall, our findings argue against widespread functional circRNA conservation.