bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of vaccinia virus L1 N-myristoylation by the host N-myristoyltransferase inhibitor IMP-1088 generates non-infectious virions defective in cell entry
Authors: Priyamvada Lalita , Kallemeijn Wouter W. , Faronato Monica , Wilkins Kimberly , Goldsmith Cynthia S. , Cotter Catherine A. , Ojeda Suany , Solari Roberto , Moss Bernard , Tate Edward W. , Satheshkumar Panayampalli Subbian 
Published: June 2022

ABSTRACTWe have recently shown that the replication of rhinovirus, poliovirus and foot-and-mouth disease virus requires the co-translational N-myristoylation of viral proteins by human host cell N-myristoyltransferases (NMTs), and is inhibited by treatment with IMP-1088, an ultrapotent small molecule NMT inhibitor. Here, we reveal the role of N-myristoylation during vaccinia virus (VACV) infection in human host cells and demonstrate the anti-poxviral effects of IMP-1088. N-myristoylated proteins from VACV and the host were metabolically labelled with myristic acid alkyne during infection using quantitative chemical proteomics. We identified VACV proteins A16, G9 and L1 to be N-myristoylated. Treatment with NMT inhibitor IMP-1088 potently abrogated VACV infection, while VACV gene expression, DNA replication, morphogenesis and EV formation remained unaffected. Importantly, we observed that loss of N-myristoylation resulted in greatly reduced infectivity of assembled mature virus particles, characterized by significantly reduced host cell entry and a decline in membrane fusion activity of progeny virus. While the N-myristoylation of VACV entry proteins L1, A16 and G9 was inhibited by IMP-1088, mutational and genetic studies demonstrated that the N-myristoylation of L1 was the most critical for VACV entry. Given the significant genetic identity between VACV, monkeypox virus and variola virus L1 homologs, our data provides a basis for further investigating the role of N-myristoylation in poxviral infections as well as the potential of selective NMT inhibitors like IMP-1088 as broad-spectrum poxvirus inhibitors.
Dynamic cybergenetic control of bacterial co-culture composition via optogenetic feedback
Authors: Gutiérrez Joaquín , Kumar Sant , Khammash Mustafa 
Published: June 2022

AbstractCommunities of microbes play important roles in natural environments and hold great potential for deploying division-of-labor strategies in synthetic biology and bioproduction. However, the difficulty of controlling the composition of microbial consortia over time hinders their optimal use in many applications. Here, we present a fully automated, high-throughput platform that combines real-time measurements and computer-controlled optogenetic modulation of bacterial growth to implement precise and robust compositional control of a two-strainE. colicommunity. Additionally, we develop a general framework for dynamic modeling of synthetic genetic circuits in the physiological context ofE. coliand use a host-aware model to determine the optimal control parameters of our closed-loop compositional control system. Our platform succeeds in stabilizing the strain ratio of multiple parallel co-cultures at arbitrary levels and in changing these targets over time, opening the door for the implementation of dynamic compositional programs in synthetic bacterial communities.
Extracellular appendages govern spatial dynamics and growth of Caulobacter crescentus on a prevalent biopolymer
Authors: Povolo Vanessa R , D’Souza Glen G , Kaczmarczyk Andreas , Stubbusch Astrid KM , Jenal Urs , Ackermann Martin 
Published: June 2022

ABSTRACTMicrobial breakdown of carbon polymers is an essential process in all ecosystems. Carbon polymers generally require extracellular breakdown by secreted exoenzymes. Exoenzymes and breakdown products can be lost through diffusion or flow. This diffusional loss is reduced when bacteria grow in surface-associated populations where they benefit from each other’s metabolic activities. The aquatic organism Caulobacter crescentus was recently shown to form clonal microcolonies on the carbon polymer xylan, but to grow solitary on the monosaccharide xylose. The underlying mechanisms of this substrate-mediated microcolony formation are unknown. In particular, the importance of extracellular appendages such as pili, adhesive holdfast, and flagellum in governing the spatial arrangement of surface-grown cells is unclear. Using microfluidics coupled to automated time-lapse microscopy and quantitative image analysis, we compared the temporal and spatial dynamics of C. crescentus wildtype and mutant strains grown on xylan, xylose, or glucose. We found that mutants lacking type IV pili or holdfast showed altered spatial patterns in microcolonies and were unable to maintain cell densities above a threshold required for maximal growth rates on the xylan polymer, whereas mutants lacking flagella showed increased cell densities that potentially lead to increased local competition. Our results demonstrate that extracellular appendages allow bacteria to reach local cell densities that maximize single-cell growth rates in response to their nutrient environment.
The human brain reactivates context-specific past information at event boundaries of naturalistic experiences
Authors: Hahamy Avital , Dubossarsky Haim , Behrens Timothy E. J. 
Published: June 2022

SummaryAlthough we perceive the world in a continuous manner, our experience is partitioned into discrete events. However, to make sense of these events, they must be stitched together into an overarching narrative – a model of unfolding events. It has been proposed that such a stitching process happens in offline neural reactivations when rodents build models of spatial environments. Here we show that, whilst understanding a natural narrative, humans reactivate neural representations of past events. Similar to offline replay, these reactivations occur in hippocampus and default mode network, where reactivations are selective to relevant past events. However, these reactivations occur, not during prolonged offline periods, but at the boundaries between ongoing narrative events. These results, replicated across two datasets, suggest reactivations as a candidate mechanism for binding temporally distant information into a coherent understanding of ongoing experience.
Brain and Organoid Manifold Alignment (BOMA), a machine learning framework for comparative gene expression analysis across brains and organoids
Authors: He Chenfeng , Kalafut Noah Cohen , Sandoval Soraya O. , Risgaard Ryan , Yang Chen , Khullar Saniya , Suzuki Marin , Chang Qiang , Zhao Xinyu , Sousa Andre M.M. , Wang Daifeng 
Published: June 2022

AbstractOrganoids have become valuable models for understanding cellular and molecular mechanisms in human development including brains. However, whether developmental gene expression programs are preserved between human organoids and brains, especially in specific cell types, remains unclear. Importantly, there is a lack of effective computational approaches for comparative data analyses between organoids and developing humans. To address this, by considering the public data availability and research significance, we developed a machine learning framework, Brain and Organoid Manifold Alignment (BOMA) for comparative gene expression analysis of brains and organoids, to identify conserved and specific developmental trajectories as well as developmentally expressed genes and functions, especially at cellular resolution. BOMA first performs a global alignment and then uses manifold learning to locally refine the alignment, revealing conserved developmental trajectories between brains and organoids. Using BOMA, we found that human cortical organoids better align with certain brain cortical regions than other non-cortical regions, implying organoid-preserved developmental gene expression programs specific to brain regions. Additionally, our alignment of non-human primate and human brains reveals highly conserved gene expression around birth. Also, we integrated and analyzed developmental scRNA-seq data of human brains and organoids, showing conserved and specific cell trajectories and clusters. Further identification of expressed genes of such clusters and enrichment analyses reveal brain- or organoid-specific developmental functions and pathways. Finally, we experimentally validated important specific expressed genes using immunofluorescence. BOMA is open-source available as a web tool for general community use.
A lysosomal surveillance response (LySR) that reduces proteotoxicity and extends healthspan
Authors: Li Terytty Yang , Gao Arwen W. , Li Xiaoxu , Liu Yasmine J. , Arey Rachel N. , Morales Kimberly , Lalou Amélia , Wang Qi , Lima Tanes , Auwerx Johan 
Published: June 2022

SUMMARYLysosomes are cytoplasmic organelles central for the degradation of macromolecules to maintain cellular homeostasis and health. Here, we discovered an adaptive lysosomal transcriptional response that we termed the Lysosomal Surveillance Response (LySR). Typified by the induction of a large group of transcripts involved in lysosomal function and proteolysis, the LySR can be triggered by silencing of specific vacuolar H+-ATPase subunits in Caenorhabditis elegans. Notably, LySR activation enhances the clearance of protein aggregates in worm models of Alzheimer’s and Huntington’s disease and amyotrophic lateral sclerosis, thereby boosting fitness and extending lifespan. The GATA transcription factor, ELT-2, regulates the LySR program as well as its associated beneficial effects. In mammalian cells, overexpression of GATA4/GATA6, the mammalian orthologs of ELT-2, is sufficient to induce the expression of multiple lysosome-specific proteases and alleviate proteotoxicity. Activating the LySR pathway may therefore represent an attractive mechanism to reduce proteotoxicity and, as such, potentially extend healthspan.HighlightsRNAi of specific v-ATPase subunits extends C. elegans lifespan and activates LySRGATA transcription factor ELT-2 regulates LySR and LySR-associated lifespan extensionLySR activation reduces protein aggregates and extends worm healthspanOverexpression of GATA4/GATA6 alleviates amyloid-β proteotoxicity in mammalian cells
Cas12a2 elicits abortive infection via RNA-triggered destruction of double-stranded DNA
Authors: Dmytrenko Oleg , Neumann Gina C. , Hallmark Thomson , Keiser Dylan J. , Crowley Valerie M. , Vialetto Elena , Mougiakos Ioannis , Wandera Katharina G. , Domgaard Hannah , Weber Johannes , Metcalf Josie , Begemann Matthew B. , Gray Benjamin N. , Jackson Ryan N. , Beisel Chase L. 
Published: June 2022

ABSTRACTBacterial abortive infection systems limit the spread of foreign invaders by shutting down or killing infected cells before the invaders can replicate1, 2. Several RNA-targeting CRISPR-Cas systems (e.g., types III and VI) cause Abi phenotypes by activating indiscriminate RNases3–5. However, a CRISPR-mediated abortive mechanism that relies on indiscriminate DNase activity has yet to be observed. Here we report that RNA targeting by the type V Cas12a2 nuclease drives abortive infection through non-specific cleavage of double-stranded (ds)DNA. Upon recognition of an RNA target with an activating protospacer-flanking sequence, Cas12a2 efficiently degrades single-stranded (ss)RNA, ssDNA, and dsDNA. Within cells, the dsDNase activity induces an SOS response and impairs growth, stemming the infection. Finally, we harnessed the collateral activity of Cas12a2 for direct RNA detection, demonstrating that Cas12a2 can be repurposed as an RNA-guided, RNA-targeting tool. These findings expand the known defensive capabilities of CRISPR-Cas systems and create additional opportunities for CRISPR technologies.
Dissociating the contributions of sensorimotor striatum to automatic and visually-guided motor sequences
Authors: Mizes Kevin G. C. , Lindsey Jack , Escola G. Sean , Ölveczky Bence P. 
Published: June 2022

AbstractThe ability to sequence movements in response to new task demands enables rich and adaptive behavior. Such flexibility, however, is computationally costly and can result in halting performances. Practicing the same motor sequence repeatedly can render its execution precise, fast, and effortless, i.e., ‘automatic’. The basal ganglia are thought to underlie both modes of sequence execution, yet whether and how their contributions differ is unclear. We parse this in rats trained to perform the same motor sequence in response to cues and in an overtrained, or ‘automatic’, condition. Neural recordings in the sensorimotor striatum revealed a kinematic code independent of execution mode. While lesions affected the detailed kinematics similarly across modes, they disrupted high-level sequence structure for automatic, but not visually-guided, behaviors. These results suggest that the basal ganglia contribute to learned movement kinematics and are essential for ‘automatic’ motor skills but can be dispensable for sensory-guided motor sequences.
Disruption of CFAP418 interaction with lipids causes abnormal membrane-associated cellular processes in retinal degenerations
Authors: Clark Anna M. , Yu Dongmei , Neiswanger Grace , Zhu Daniel , Maschek J. Alan , Burgoyne Thomas , Yang Jun 
Published: June 2022

AbstractSyndromic ciliopathies and retinal degenerations are large heterogeneous groups of genetic diseases. CFAP418 is a causative gene of both disorders, and its protein sequence is evolutionarily conserved. However, the pathogenic mechanism caused by CFAP418 mutations is largely unknown. Here, we employed affinity purification coupled with mass spectrometry and quantitative lipidomic, proteomic, and phosphoproteomic approaches to address the molecular function of CFAP418 in mouse retinas. We showed that CFAP418 bound to lipid metabolism precursor phosphatidic acid (PA) and mitochondrion-specific lipid cardiolipin but did not form a tight and static complex with proteins. Loss of Cfap418 led to membrane lipid imbalance and protein-membrane association alteration, which subsequently caused mitochondrial defects and membrane remodeling abnormalities in multiple vesicular trafficking pathways. Loss of Cfap418 also increased the activity of PA-binding protein kinase Cα. Our results indicate that membrane lipid imbalance is a new pathological mechanism underlying syndromic ciliopathies and retinal degenerations, which is associated with other known causative genes for these diseases, such as RAB28 and BBS genes.
Connexin43 Overexpression Promotes Bone Regeneration by Osteogenesis and Angiogenesis in Rat Glucocorticoid-Induced Osteonecrosis of the Femoral Head
Authors: Zhao Xin , Chen Changjun , Luo Yue , Li Donghai , Wang Qiuru , Fang Yuying , Kang Pengde 
Published: June 2022

AbstractGlucocorticoids induced osteonecrosis of the femoral head (GIONFH) is a devastating orthopedic disease. Previous studies suggested that connexin43 (Cx43) is involved in the process of osteogenesis and angiogenesis. However, the role of Cx43 potentiates in the osteogenesis and angiogenesis of bone marrow-derived stromal stem cells (BMSCs) in GIONFH is still not investigated. In this study, BMSCs were isolated and transfected with green fluorescent protein (GFP) or the fusion gene encoding GFP and Cx43. The osteogenic differentiation of BMSCs were detected after transfected with Cx43. In addition, the migration abilities and angiogenesis of human umbilical vein endothelial cells (HUVECs) were been detected after induced by transfected BMSCs supernatants in vitro. Our results showed that Cx43 overexpression in BMSCs promoted osteogenic differentiation and angiogenesis in vitro. Finally, we established GC-ONFH rat model, then, a certain amount of transfected or controlled BMSCs were injected into the tibia of the rats. Immunohistological staining and micro-CT scanning results showed that the transplanted experiment group had significantly promoted more bone regeneration, vessel volume and the expressions of Runx2, ALP, COL I, VEGF and CD31 when compared with the effects of the negative or control groups. This study demonstrated for the first time that the Cx43 overexpression in BMSCs could promote bone regeneration as seen in the osteogenesis and angiogenesis process, suggesting that Cx43 may serve as a therapeutic gene target for GIONFH treatment.
Chimpanzee play sequences are structured hierarchically as games
Authors: Mielke Alexander , Carvalho Susana 
Published: June 2022

AbstractSocial play is ubiquitous in the development of many animal species and involves players adapting actions flexibly to their own previous actions and partner responses. Play differs from other behavioural contexts for which fine-scale analyses of action sequences are available, such as tool use and communication, in that its form is not defined by its functions, making it potentially more unpredictable. In humans, play is often organised in games, where players know context-appropriate actions but string them together unpredictably. Here, we use the sequential nature of play elements to explore whether play elements in chimpanzees are structured hierarchically and follow predictable game-like patterns. Based on 5711 play elements from 143 bouts, we extracted individual-level play sequences of 11 Western chimpanzees (Pan troglodytes verus) of different ages from the Bossou community. We detected transition probabilities between play elements that exceeded expected levels and show that play elements form hierarchically clustered and interchangeable groups, indicative of at least six ‘games’ that can be identified from transition networks, some with different roles for different players. We also show that increased information about preceding play elements improved predictability of subsequent elements, further indicating that play elements are not strung together randomly but that flexible action rules underlie their usage. Thus, chimpanzee play is hierarchically structured in short ‘games’ which limit acceptable play elements and allow players to predict and adapt to partners’ actions. This ‘grammar of action’ approach to social interactions can be valuable in understanding cognitive and communicative abilities within and across species.
Developing generation Z employees: a two-stage mediation model
Authors: Bhushan Balram 
Published: June 2022

Purpose
The entry of generation Z employees into workforce poses new challenges for managers in designing learning and development interventions as they are better informed and well-equipped to access the available information. This paper investigates how training comprehensiveness serves their unique developmental needs.

Design/methodology/approach
Employees responded to the online survey on training comprehensiveness, person-job fit, and task significance while the data on task performance was collected from their supervisors. In total, 215 complete and valid responses were received. Gender, age, education level and industry type were used as control variables and the statistical analysis was performed using SPSS and RStudio.

Findings
Findings indicate that generation Z employees aim for person-job fit as a proximal outcome and task performance as distal outcome of training. Also, task-significance mediates the relationship between person-job fit and task performance. Apart from the indirect path which involves mediation of person-job fit and task significance, the direct impact of training on task performance is also noticed. Interestingly, the older colleagues do not display such behavior

Originality/value
This is the first empirical study that investigates the developmental needs of generation Z employees and integrates the elements of task design and training needs together. With their better skills to access increasing job opportunities, generation Z employees use training to meet the job demands. Thus, person-job fit, and task significance are found to be better performance drivers than training for generation Z, but training adds to their performance through person-job fit as well.
Effects of in-game brand congruity on esports consumers' implicit and explicit memory
Authors: Hwang Yongjin , Watanabe Nicholas Masafumi , Nagel Mark 
Published: June 2022

PurposeThis study aims to examine the impacts of brand congruity of in-game brand placement on esports consumers' implicit and explicit memory.Design/methodology/approachA 2 × 2 × 2 experimental design (N = 224) was used with an automobile racing game, NASCAR Heat 5. A series of statistical analyses, including MANOVA and logistic regressions, was conducted to test the proposed hypotheses.FindingsThe results revealed that ads on virtual billboards in the video game primed participants to create an implicit memory. Also, incongruent brands that were not very familiar to gamers provided greater impact than congruent brands.Originality/valueThis research is the first to test both implicit and explicit memory and provide practical evidence for the possibility of implicit memory building in the esports context. In addition, the current study also examined the impact of congruity to answer the previously inconsistent results.
Supporting teacher candidates to become collaborative teaching professionals: developing professional capital through a collaborative inquiry-based community of practice
Authors: Osmond-Johnson Pamela , Fuhrmann Lucrécia Raquel 
Published: June 2022

PurposeThis paper draws on data from a research project that examined the impact of a community of practice (CoP) model of teaching practicum that engaged teacher candidates in collaborative inquiry projects based on self-identified problems of practice that emerged during their practicum experiences.Design/methodology/approachA qualitative approach was adopted to better understand the ways in which the CoP served as a support mechanism for teacher candidates to develop social capital during internship. Data collection included anecdotal observation notes, student postings in online discussion forums, and a one-hour post-project focus group. Data analysis was rooted in phenomenology (Lin, 2013) and was guided by the four pronged coding process outlined by Bicudo (2000).FindingsAs the paper illustrates, the CoP created rich opportunities for teacher candidates to cultivate social capital, which positively impacted their human and decisional capital. Relatedly, teacher candidates demonstrated an enhanced sense of collective efficacy and an understanding of the significance of collaborative professional cultures on their continued growth as members of the teaching profession.Originality/valueWhile a number of studies have considered various factors impacting the professional capital of practicing teachers, the development of professional capital amongst interning teachers remains as an under-explored area in the research literature.
Collective compass to unit performance: linking transformational leadership climate, trust and engagement
Authors: Gabel Shemueli Rachel , Tzafrir Shay , Rodriguez Perez Berlan , Bahamonde Danae , Enosh Guy 
Published: June 2022

PurposeThe purpose of the study is to examine how shared perceptions of collective behaviors, such as transformational leadership climate (TLC), collective trust and collective engagement, affect unit performance.Design/methodology/approachThe sample consisted of 450 employees in 74 agencies of a financial organization, using measurements at the collective team level. Multiple structural equation modeling analyses were used to test the hypotheses.FindingsThe relationship between TLC and unit performance was sequentially mediated by collective trust and collective engagement.Originality/valueThis study highlights how employees' shared perceptions of different team characteristics can affect the overall functioning and performance of an organization.