bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting Nup358/RanBP2 by a viral protein disrupts stress granule formation
Authors: Sadasivan Jibin , Vlok Marli , Wang Xinying , Nayak Arabinda , Andino Raul , Jan Eric 
Published: May 2022

ABSTRACTViruses have evolved mechanisms to modulate cellular pathways to facilitate infection. One such pathway is the formation of stress granules (SG), which are ribonucleoprotein complexes that assemble during translation inhibition following cellular stress. Inhibition of SG assembly has been observed under numerous virus infections across species, suggesting a conserved fundamental viral strategy. However, the significance of SG modulation during virus infection is not fully understood. The 1A protein encoded by the model dicistrovirus, Cricket Paralysis Virus (CrPV), is a multifunctional protein that can bind to and degrade Ago-2 in an E3 ubiquitin ligase-dependent manner to block the antiviral RNA interference pathway and inhibit SG formation. Moreover, the R146 residue of 1A is necessary for SG inhibition and CrPV infection in both Drosophila S2 cells and adult flies. Here, we uncoupled CrPV-1A’s functions and provide insight into its underlying mechanism for SG inhibition. CrPV-1A mediated inhibition of SGs requires the E3 ubiquitin-ligase binding domain and the R146 residue, but not the Ago-2 binding domain. Wild-type but not mutant CrPV-1A R146A localizes to the nuclear membrane which correlates with nuclear enrichment of poly(A)+ RNA. Transcriptome changes in CrPV-infected cells are dependent on the R146 residue. Finally, Nup358/RanBP2 is targeted and degraded in CrPV-infected cells in an R146-dependent manner and the depletion of Nup358 blocks SG formation. We propose that CrPV utilizes a multiprong strategy whereby the CrPV-1A protein interferes with a nuclear event that contributes to SG inhibition in order to promote infection.AUTHOR SUMMARYViruses often inhibit a cellular stress response that leads to the accumulation of RNA and protein condensates called stress granules. How this occurs and why this would benefit virus infection are not fully understood. Here, we reveal a viral protein that can block stress granules and identify a key amino acid residue in the protein that inactivates this function. We demonstrate that this viral protein has multiple functions to modulate nuclear events including mRNA export and transcription to regulate stress granule formation. We identify a key host protein that is important for viral protein mediate stress granule inhibition, thus providing mechanistic insights. This study reveals a novel viral strategy in modulating stress granule formation to promote virus infection.
Associations between abstract working memory abilities and brain activity underlying long-term recognition of auditory sequences
Authors: Fernández Rubio G. , Carlomagno F. , Vuust P. , Kringelbach M. L. , Bonetti L. 
Published: May 2022

AbstractMemory is a complex cognitive process comprised by several subsystems, namely short- and long-term memory and working memory (WM). Previous research has shown that adequate interaction between subsystems is crucial for successful memory processes such as encoding, storage and manipulation of information. However, few studies have investigated the relationship between different subsystems at the behavioral and neural levels. Thus, here we assessed the relationship between individual WM abilities and brain activity underlying the recognition of previously memorized auditory sequences.First, recognition of previously memorized versus novel auditory sequences was associated with a widespread network of brain areas comprising the cingulate gyrus, hippocampus, insula, inferior temporal cortex, frontal operculum, and orbitofrontal cortex.Second, we observed positive correlations between brain activity underlying auditory sequence recognition and WM. We showed a sustained positive correlation in the medial cingulate gyrus, a brain area which was widely involved in the auditory sequence recognition. Remarkably, we also observed positive correlations in the inferior temporal, temporal-fusiform, and postcentral gyri, brain areas which were not strongly associated to auditory sequence recognition.In conclusion, we discovered positive correlations between WM abilities and brain activity underlying long-term recognition of auditory sequences, providing new evidence on the relationship between memory subsystems. Furthermore, we showed that high WM performers recruited a larger brain network including areas associated to visual processing (i.e., inferior temporal, temporal-fusiform and postcentral gyri) for successful auditory memory recognition.Significance statementMemory is a complex cognitive process dependent on the successful interaction between its multiple subsystems. Here, we assessed the relationship between individual WM abilities and brain activity underlying the recognition of previously memorized auditory sequences.We observed positive correlations between brain activity underlying auditory sequence recognition and WM, especially in the medial cingulate gyrus, inferior temporal, temporal-fusiform and postcentral gyri. In this study, we provided new evidence on the relationship between two memory subsystems: WM and long-term auditory recognition. Moreover, we showed that, to successfully complete memory recognition tasks, high WM performers recruited a larger brain network which comprised brain areas mainly associated to visual processing, such as inferior temporal, temporal-fusiform and postcentral gyri.
Programming the lymph node immune response with Amphiphile-CpG induces potent cellular and humoral immunity following COVID-19 subunit vaccination in mice and non-human primates
Authors: Seenappa Lochana M. , Jakubowski Aniela , Steinbuck Martin P. , Palmer Erica , Haqq Christopher M. , Carter Crystal , Fontenot Jane , Villinger Francois , McNeil Lisa K. , DeMuth Peter C. 
Published: May 2022

ABSTRACTDespite the success of currently authorized vaccines for the reduction of severe COVID-19 disease risk, rapidly emerging viral variants continue to drive pandemic waves of infection, resulting in numerous global public health challenges. Progress will depend on future advances in prophylactic vaccine activity, including advancement of candidates capable of generating more potent induction of cross-reactive T cells and durable cross-reactive antibody responses. Here we evaluated an Amphiphile (AMP) adjuvant, AMP-CpG, admixed with SARS-CoV-2 Spike receptor binding domain (RBD) immunogen, as a lymph node-targeted protein subunit vaccine (ELI-005) in mice and non-human primates (NHPs). AMP-mediated targeting of CpG DNA to draining lymph nodes resulted in comprehensive local immune activation characterized by extensive transcriptional reprogramming, inflammatory proteomic milieu, and activation of innate immune cells as key orchestrators of antigen-directed adaptive immunity. Prime-boost immunization with AMP-CpG in mice induced potent and durable T cell responses in multiple anatomical sites critical for prophylactic efficacy and prevention of severe disease. Long-lived memory responses were rapidly expanded upon re-exposure to antigen. In parallel, RBD-specific antibodies were long-lived, and exhibited cross-reactive recognition of variant RBD. AMP-CpG-adjuvanted prime-boost immunization in NHPs was safe and well tolerated, while promoting multi-cytokine-producing circulating T cell responses cross-reactive across variants of concern (VOC). Expansion of RBD-specific germinal center (GC) B cells in lymph nodes correlated to rapid seroconversion with variant-specific neutralizing antibody responses exceeding those measured in convalescent human plasma. These results demonstrate the promise of lymph-node adjuvant-targeting to coordinate innate immunity and generate robust adaptive responses critical for vaccine efficacy.
Effects of netarsudil-family Rho kinase inhibitors on human trabecular meshwork cell contractility and actin remodeling using a bioengineered ECM hydrogel
Authors: Bagué Tyler , Singh Ayushi , Ghosh Rajanya , Yoo Hannah , Kelly Curtis , deLong Mitchell A. , Kopczynski Casey C. , Herberg Samuel 
Published: May 2022

AbstractInteractions between trabecular meshwork (TM) cells and their extracellular matrix (ECM) are critical for normal outflow function in the healthy eye. Multifactorial dysregulation of the TM is the principal cause of elevated intraocular pressure that is strongly associated with glaucomatous vision loss. Key characteristics of the diseased TM are pathologic contraction and actin stress fiber assembly, contributing to overall tissue stiffening. Among first-line glaucoma medications, the Rho-associated kinase inhibitor (ROCKi) netarsudil is known to directly target the stiffened TM to improve outflow function via tissue relaxation involving focal adhesion and actin stress fiber disassembly. Yet, no in vitro studies have explored the effect of netarsudil on human TM (HTM) cell contractility and actin remodeling in a 3D ECM environment. Here, we use our bioengineered HTM cell-encapsulated ECM hydrogel to investigate the efficacy of different netarsudil-family ROCKi compounds on reversing pathologic contraction and actin stress fibers. Netarsudil and all related experimental ROCKi compounds exhibited significant ROCK1/2 inhibitory and focal adhesion disruption activities. Furthermore, all ROCKi compounds displayed potent contraction-reversing effects on HTM hydrogels upon glaucomatous induction in a dose-dependent manner, relatively consistent with their biochemical/cellular inhibitory activities. At their tailored EC50 levels, netarsudil-family ROCKi compounds exhibited distinct effect signatures of reversing pathologic HTM hydrogel contraction and actin stress fibers, independent of the cell strain used. Netarsudil outperformed the experimental ROCKi compounds in support of its clinical status. In contrast, at uniform EC50-levels using netarsudil as reference, all ROCKi compounds performed similarly. Collectively, our data suggest that netarsudil exhibits high potency to rescue HTM cell pathobiology in a tissue-mimetic 3D ECM microenvironment, solidifying the utility of our bioengineered hydrogel model as a viable screening platform to further our understanding of TM pathophysiology in glaucoma.
High Frequency of Dynamic Rearrangements In Crispr loci
Authors: Ou Yaqing , McInerney James O. 
Published: May 2022

AbstractCRISPR-Cas immunization of prokaryotes proceeds by the acquisition of short fragments of invading DNA and integrating them into specific positions within the host genome in a process called adaptation. Adaptation is thought to be polarised, which suggests that CRISPR array spacer order reflects the recentness of the infection. The detailed processes through which CRISPR loci arise, and how they evolve are not completely clear. In this study, we collected 12,461 prokaryotic genomes, and using a combination of four different approaches and a series of conservative filters, we identified CRISPR arrays in 82.7% of Archaea and 40.6% of Bacteria. To understand spacer evolution in these CRISPR loci we firstly tracked point mutations in CRISPR repeats, and secondly, we carried out a comparative analysis of arrays that share multiple similar spacers. Both results indicate that CRISPR arrays are frequently dynamically rearranged. These findings are at odds with a model that suggests that spacer order is likely to reflect the recentness of infection. We conclude that the order of spacers in a CRISPR array, as well as the spacer content of the array, is likely to arise from a combination of events, such as insertion in the middle of the array, recombination within or between arrays, or Horizontal transfer of all or part of an array. We suggest these rearrangements are favoured by natural selection in complex and dynamic environments.
Rdh54 stabilizes Rad51 at displacement loop intermediates to regulate genetic exchange between chromosomes
Authors: Keymakh Margaret , Dau Jennifer , Ferlez Bryan , Lisby Michael , Crickard J. Brooks 
Published: May 2022

AbstractHomologous recombination (HR) is a double-strand break DNA repair pathway that preserves chromosome structure. To repair the damaged recipient DNA, HR requires an intact donor DNA sequence located elsewhere in the genome. After the double-strand break is repaired, DNA sequence information can be transferred between donor and recipient DNA molecules through different mechanisms, including DNA crossovers that form between homologous chromosomes. Regulating this transfer of information is an important step in effectively completing HR and maintaining genome integrity. For example, mitotic exchange of information between homologous chromosomes can result in loss-of-heterozygosity (LOH) in diploid organisms, and in higher eukaryotes, the development of cancer. The DNA motor protein Rdh54 is a highly conserved DNA translocase that functions during HR but has a limited role in repairing DNA. Instead, several existing phenotypes inrdh54Δstrains suggest that Rdh54 may regulate the flow of information between donor and recipient DNA molecules post DNA repair. In our current study, we used a combination of biochemical and genetic techniques to dissect the role of Rdh54 on the exchange of genetic information after DNA repair. Our data indicates thatRDH54regulates DNA sequence exchange between chromosomes by limiting the disruption of Rad51 at an early HR intermediate called the displacement loop (D-loop). Rdh54 also protects Rad51 filaments, acting in opposition to Rad51 removal by the DNA motor protein Rad54. Furthermore, we find that expression of a catalytically inactivate allele of Rdh54,rdh54K318R, displays a different distribution of information exchange outcomes thanrdh54Δ cells. From these results, we propose a model for how Rdh54 may effectively regulate information transfer during homologous recombination.
Resolution doubling in light-sheet microscopy via oblique plane structured illumination
Authors: Chen Bingying , Chang Bo-Jui , Roudot Philippe , Zhou Felix , Sapoznik Etai , Marlar-Pavey Madeleine , Hayes James B. , Brown Peter T. , Zeng Chih-Wei , Lambert Talley , Friedman Jonathan R. , Zhang Chun-Li , Burnette Dylan T. , Shepherd Douglas P. , Dean Kevin M. , Fiolka Reto P. 
Published: May 2022

AbstractStructured illumination microscopy (SIM) doubles the spatial resolution of a fluorescence microscope without requiring high laser powers or specialized fluorophores. However, the excitation of out-of-focus fluorescence can accelerate photobleaching and phototoxicity. In contrast, light-sheet fluorescence microscopy (LSFM) largely avoids exciting out-of-focus fluorescence, thereby enabling volumetric imaging with low photo-bleaching and intrinsic optical sectioning. Combining SIM with LSFM would enable gentle 3D imaging at doubled resolution. However, multiple orientations of the illumination pattern, which are needed for isotropic resolution doubling in SIM, are challenging to implement in a light-sheet format. Here we show that multidirectional structured illumination can be implemented in oblique plane microscopy, a LSFM technique that uses a single objective for excitation and detection, in a straightforward manner. We demonstrate isotropic lateral resolution below 150nm, combined with lower photo-toxicity compared to traditional SIM systems and volumetric acquisition speed exceeding 1Hz.
Self-organized canals enable long range directed material transport in bacterial communities
Authors: Li Ye , Liu Shiqi , Zhang Yingdan , Seng Zi Jing , Xu Haoran , Yang Liang , Wu Yilin 
Published: May 2022

AbstractLong-range material transport is essential to maintain the physiological functions of multicellular organisms such as animals and plants. By contrast, material transport in bacteria is often short-ranged and limited by diffusion. Here we report a unique form of actively regulated long-range directed material transport in structured bacterial communities. UsingPseudomonas aeruginosacolonies as a model system, we discover that a large-scale and temporally evolving open channel system spontaneously develops in the colony via shear-induced banding. Fluid flows in the open channels support high-speed (up to 450 µm/s) transport of cells and outer membrane vesicles over centimeters, and help to eradicate colonies of a competing speciesStaphylococcus aureus. The open channels are reminiscent of human-made canals for cargo transport, and the channel flows are driven by interfacial tension mediated by cell-secreted biosurfactants. The spatial-temporal dynamics of fluid flows in the open channels are qualitatively described by flow profile measurement and mathematical modeling. Our findings demonstrate that mechanochemical coupling between interfacial force and biosurfactant kinetics can coordinate large-scale material transport in primitive life forms, suggesting a new principle to engineer self-organized microbial communities.
Confident Clustering via PCA Compression Ratio and Its Application to Single-cell RNA-seq Analysis
Authors: Li Yingcong , Mukherjee Chandra Sekhar , Zhang Jiapeng 
Published: May 2022

AbstractUnsupervised clustering algorithms for vectors has been widely used in the area of machine learning. Many applications, including the biological data we studied in this paper, contain some boundary datapoints which show combination properties of two underlying clusters and could lower the performance of the traditional clustering algorithms. We develop a confident clustering method aiming to diminish the influence of these datapoints and improve the clustering results. Concretely, for a list of datapoints, we give two clustering results. The first-round clustering attempts to classify only pure vectors with high confidence. Based on it, we classify more vectors with less confidence in the second round. We validate our algorithm on single-cell RNA-seq data, which is a powerful and widely used tool in biology area. Our confident clustering shows a high accuracy on our tested datasets. In addition, unlike traditional clustering methods in single-cell analysis, the confident clustering shows high stability under different choices of parameters.
Shaping health and well-being in a COVID era: the role of design
Authors: Asojo Abimbola , Vo Hoa , Fisher Thomas , Singh Virajita 
Published: May 2022

PurposeIn this study, an interdisciplinary research team at a Midwest US University collaborated with a local county to co-envision interior design strategies for five county buildings: three libraries and two government buildings to reduce in-person contact in response to the COVID-19 pandemic.Design/methodology/approachThe authors' interdisciplinary team used a community-based participatory design process which focused on creating consensus, while seeking out divergent perspectives among stakeholders to serve the needs of diverse users. The design process involved meetings with stakeholders remotely and analyzing survey results from the target occupants collected by the county.FindingsThe county with a population of 550,321 is the second most populous and diverse county in the state. The authors' collaborative efforts resulted in short-and long-term recommendations for the interior space planning to promote health, safety, and well-being for the county's diverse user groups of young children, adults, elderly and vulnerable populations. The short-term recommendations focus on service redesigns that can be implemented as the state shifts out of the stay-at-home order and the community returns to the county's public-facing buildings. The long-term recommendations focus on experiences and design strategies that can be carried forward to future-proof buildings in a post-COVID era and provide models for other counties.Research limitations/implicationsOne limitation is the dynamic nature of how rapidly our team responded to a critical need in the community to develop tangible interior design solutions during the initial stages of the COVID-19 pandemic for the county. The solutions we proposed were based on the scientific evidence available earlier on during that phase of the pandemic. The authors hope to conduct further studies in the future and conduct assessments of our rapid design responses.Practical implicationsThis paper documents a dynamic experience during a once in a lifetime pandemic and thus contributes to further the body of knowledge about the role of interior design in shaping health and well-being during the COVID-19 pandemic.Originality/valueThe article presents a timely interdisciplinary response to the COVID-19 pandemic to promote community safety inside public buildings at the county. The interior design solutions reflected intensive literature reviews, critical space planning, innovative use of lighting, and thoughtful furniture/material selections.
Effect of AIS on planning process effectiveness: a case of SMEs in a less developed nation
Authors: Al-Hattami Hamood Mohammed , Abdullah Abdulwahid Abdullah Ahmed Hashed , Kabra Jawahar D. , Alsoufi Maged A.Z. , Gaber Mohammed M.A. , Shuraim Abdullah M.A. 
Published: May 2022

Purpose
This paper aims to examine the influence of accounting information system (AIS) success on planning process effectiveness (PPE) in small- and medium-sized enterprises (SMEs) of Yemen, a less developed nation (LDN).

Design/methodology/approach
This study developed a theoretical model based on IS success model (DMISS2003). The model’s components were tested using structural equation modeling via SmartPLS on a sample of 325 SMEs.

Findings
The empirical results imply that AIS success positively affects PPE if SMEs focus on AIS information quality, system quality, user satisfaction and usage.

Research limitations/implications
This study focused on SMEs in Yemen. Thus, it can be expanded to include different other countries.

Practical implications
The results of this study could be considered by owners and managers of SMEs, policymakers and AIS designers/vendors. This study could provide them insight into the role of AIS success in promoting PPE in SMEs. This study could assist policymakers in analyzing the work of SMEs and assessing their success, referring to AIS. Moreover, knowing the most critical determinants of AIS success could direct designers’/vendors’ efforts toward upgrading and improving the present AIS.

Social implications
Government policymakers in LDNs considering how to motivate SME development in their nation should be aware of the significance of AIS success and implementation among SMEs and its role in the nation’s economic development.

Originality/value
This research is one of the first that investigates the impact of AIS success on PPE in SMEs. Current literature largely lacks the investigation of such an impact, especially among SMEs in LDNs such as Yemen. Most AIS’s prior research focused on SMEs in developed nations, which may not fully apply to LDNs such as Yemen. Indeed, no existing literature is available where AIS success impacts PPE in SMEs of LDNs. In this respect, this study claims its uniqueness.