bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chromosome-scale genome assembly of the brown anole (Anolis sagrei), a model species for evolution and ecology
Authors: Geneva Anthony J. , Park Sungdae , Bock Dan , de Mello Pietro , Sarigol Fatih , Tollis Marc , Donihue Colin , Reynolds R. Graham , Feiner Nathalie , Rasys Ashley M. , Lauderdale James D. , Minchey Sergio G. , Alcala Aaron J. , Infante Carlos R. , Kolbe Jason J. , Schluter Dolph , Menke Douglas B. , Losos Jonathan B. 
Published: September 2021

AbstractRapid technological improvements are democratizing access to high quality, chromosome-scale genome assemblies. No longer the domain of only the most highly studied model organisms, now non-traditional and emerging model species can be genome-enabled using a combination of sequencing technologies and assembly software. Consequently, old ideas built on sparse sampling across the tree of life have recently been amended in the face of genomic data drawn from a growing number of high-quality reference genomes. Arguably the most valuable are those long-studied species for which much is already known about their biology; what many term emerging model species. Here, we report a new, highly complete chromosome-scale genome assembly for the brown anole, Anolis sagrei – a lizard species widely studied across a variety of disciplines and for which a high-quality reference genome was long overdue.
Bcr4 is a Chaperone for the Inner Rod Protein in the Bordetella Type III Secretion System
Authors: Goto Masataka , Abe Akio , Hanawa Tomoko , Suzuki Masato , Kuwae Asaomi 
Published: September 2021

AbstractBordetella bronchiseptica injects virulence proteins called effectors into host cells via a type III secretion system (T3SS) conserved among many Gram-negative bacteria. Small proteins called chaperones are required for stabilizing some T3SS components or localizing them to the T3SS machinery. In a previous study, we identified a chaperone-like protein named Bcr4 that regulates T3SS activity in B. bronchiseptica. Bcr4 does not show strong sequence similarity to well-studied T3SS proteins of other bacteria, and its function remains to be elucidated. Here, we investigated the mechanism by which Bcr4 controls T3SS activity. A pull-down assay revealed that Bcr4 interacts with BscI, based on its homology to other bacterial proteins, to be an inner rod protein of the T3SS machinery. An additional pull-down assay using truncated Bcr4 derivatives and secretion profiles of B. bronchiseptica producing truncated Bcr4 derivatives showed that the Bcr4 C-terminal region is necessary for the interaction with BscI and activation of the T3SS. Moreover, the deletion of BscI abolished the secretion of type III secreted proteins from B. bronchiseptica and the translocation of a cytotoxic effector into cultured mammalian cells. Finally, we showed that BscI is unstable in the absence of Bcr4. These results suggest that Bcr4 supports the construction of the T3SS machinery by stabilizing BscI. This is the first demonstration of a chaperone for the T3SS inner rod protein among the virulence bacteria possessing the T3SS.ImportanceThe type III secretion system (T3SS) is a needle-like complex that projects outward from bacterial cells. Bordetella bronchiseptica uses the T3SS to inject virulence proteins into host cells. Our previous study reported that a protein named Bcr4 is essential for the secretion of virulence proteins from B. bronchiseptica bacterial cells and delivery through the T3SS. Because other bacteria lack a Bcr4 homologue, the function of Bcr4 has not been elucidated. In this study, we discovered that Bcr4 interacts with BscI, a component of the T3SS machinery. We showed that a B. bronchiseptica BscI-deficient strain was unable to secrete type III secreted proteins. Furthermore, in a B. bronchiseptica strain that overproduces T3SS component proteins, Bcr4 is required to maintain BscI in bacterial cells. These results suggest that Bcr4 stabilizes BscI to allow construction of the T3SS in B. bronchiseptica.
Spontaneous Clearance of Vertically Acquired Hepatitis C Infection: Implications for Testing and Treatment
Authors: Ades A E , Gordon Fabiana , Scott Karen , Collins Jeannie , Thorne Claire , Pembrey Lucy , Chappell Elizabeth , Mariné-Barjoan Eugènia , Butler Karina , Indolfi Giuseppe , Gibb Diana M , Judd Ali 
Published: September 2021

AbstractBackgroundCurrent guidelines recommend that infants born to women with hepatitis C (HCV) viremia are screened for HCV antibody at age 18 months, and if positive, referred for RNA testing at 3 years to confirm chronic infection. This policy is based in part on analyses suggesting 25%-40% of vertically acquired HCV infections clear spontaneously within 4-5 years.MethodsData on 179 infants with RNA and/or anti-HCV evidence of vertically acquired viraemia (single PCR+) or confirmed infection (2 PCR+ or anti-HCV beyond 18 months) in three prospective European cohorts were investigated. Ages at clearance of viremia and confirmed infection were estimated taking account of interval censoring and delayed entry. We also investigated clearance in infants in whom RNA was not detectable until after 6 weeks.ResultsClearance rates decline rapidly over the first 6 months. An estimated 90.6% (95%CrI: 83.5-95.9) of viremia cleared by 5 years, most within 3 months, and 65.9% (50.1-81.6) of confirmed infection cleared by 5 years, at a median 12.4 (7.1-18.9) months. If treatment began at age 6 months, 18 months or 3 years, at least 59.0% (42.0-76.9), 39.7 (17.9-65.9), and 20.9 (4.6-44.8) of those treated would clear without treatment. In seven (6.6%) confirmed infections, RNA was not detectable until after 6 weeks, and in 2 (1.9%) not until after 6 months. However, all such cases subsequently cleared.ConclusionsMost viraemia clears within 3 months, and most confirmed infection by 3 years. Delaying treatment avoids but does not eliminate over-treatment and should be balanced against loss to follow-up.Key pointsBased on a re-analysis of the largest purely prospective dataset assembled so far, 66% (50-82) of confirmed vertically acquired HCV clears spontaneously by age 5 years, rather than the 25-40% assumed in guidelines.
Intragenic proviral elements support transcription of defective HIV-1 proviruses
Authors: Kuniholm Jeffrey , Armstrong Elise , Bernabe Brandy , Coote Carolyn , Berenson Anna , Drinan Samantha D. , Olson Alex , He Xianbao , Lin Nina , Fuxman Bass Juan I. , Henderson Andrew J. 
Published: September 2021

ABSTRACTHIV-establishes a persistent proviral reservoir by integrating into the genome of infected host cells. Current antiretroviral treatments do not target this persistent population of proviruses which include latently infected cells that upon treatment interruption can be reactivated to contribute to HIV-1 rebound. Deep sequencing of persistent HIV proviruses has revealed that greater than 90% of integrated HIV genomes are defective and unable to produce infectious virions. We hypothesized that intragenic elements in the HIV genome support transcription of aberrant HIV-1 RNAs from defective proviruses that lack long terminal repeats (LTRs). Using an intact provirus detection assay, we observed that resting CD4+ T cells and monocyte-derived macrophages (MDMs) are biased towards generating defective HIV-1 proviruses. Multiplex reverse transcription digital drop PCR identified Env and Nef transcripts which lacked 5’ untranslated regions (UTR) in acutely infected CD4+ T cells and MDMs indicating transcripts are generated that do not utilize the promoter within the LTR. 5’UTR-deficient Env transcripts were also identified in a cohort of people living with HIV (PLWH) on ART, suggesting that these aberrant RNAs are produced in vivo. Using 5’ rapid amplification of cDNA ends (RACE), we mapped the start site of these transcripts within the Env gene. This region bound several cellular transcription factors and functioned as a transcriptional regulatory element that could support transcription and translation of downstream HIV-1 RNAs. These studies provide mechanistic insights into how defective HIV-1 proviruses are persistently expressed to potentially drive inflammation in PLWH.Author SummaryPeople living with HIV establish a persistent reservoir which includes latently infected cells that fuel viral rebound upon treatment interruption. However, the majority of HIV-1 genomes in these persistently infected cells are defective. Whether these defective HIV genomes are expressed and whether they contribute to HIV associated diseases including accelerated aging, neurodegenerative symptoms, and cardiovascular diseases are still outstanding questions. In this paper, we demonstrate that acute infection of macrophages and resting T cells is biased towards generating defective viruses which are expressed by DNA regulatory elements in the HIV genome. These studies describe an alternative mechanism for chronic expression of HIV genomes.
Enhancement of Chikungunya virus genome replication in mammalian cells at sub-physiological temperatures
Authors: Guo Jinchao , Harris Mark 
Published: September 2021

AbstractChikungunya virus (CHIKV) is an Alphavirus transmitted by Aedes mosquitoes, causing fever, rash and arthralgia. The function of the CHIKV non-structural protein 3 (nsP3) remains enigmatic. Building on previous studies (Gao et al, 2019), we generated a panel of mutants in a conserved and surface-exposed cluster in the nsP3 alphavirus unique domain (AUD) and tested their replication phenotype using a sub-genomic replicon (SGR) in mammalian and mosquito cells. Three mutants that replicated poorly in mammalian cells showed no defect in mosquito cells. These mutants were temperature-sensitive, rather than species-specific, as they exhibited no replication defect in mammalian cells at sub-physiological temperature (28°C). Similar effects were observed in the context of infectious CHIKV and the closely related O’Nyong Nyong virus. This analysis also revealed that the wildtype SGR replicated more efficiently at 28°C compared to 37°C. This was not due to either impaired interferon responses as the enhancement was observed in Vero cells, or to a defect in eIF2α phosphorylation as treatment with ISRIB, an inhibitor of global translation attenuation, did not compensate for replication defects at 37°C. The phenotype did correlate with enhanced recruitment of stress granule proteins (G3BP, eIF4G and TIA-1) into cytoplasmic sites of genome replication at 28°C. As cells in the periphery will be at sub-physiological temperatures, and will be the first cells infected in the mammalian host following a mosquito bite, we propose that alphaviruses such as CHIKV have evolved mechanisms to both promote viral genome replication and concomitantly limit antiviral responses in these cells.ImportanceChikungunya virus (CHIKV) is a re-emerging arbovirus, transmitted by Aedes mosquitos and posing epidemic threats. Arboviruses must be able to replicate efficiently in both the mosquito vector and the mammalian host, at different temperatures. Following a mosquito bite the first cells infected will be in the skin and at sub-physiological temperature (less than 37°C). We show that mutants in one of the CHIKV proteins (nsP3) could not replicate at 37°C, but replicated efficiently in mammalian cells at 28°C. We also showed that wildtype CHIKV replicated more efficiently at 28°C in comparison to 37°C in mammalian cells. We investigated the mechanism behind this observation and showed that at sub-physiological temperatures proteins present in cytoplasmic stress granules were more efficiently recruited to sites of virus replication. We propose that CHIKV has evolved mechanisms to promote their replication in mammalian cells at sub-physiological temperatures to facilitate infection of mammals via a mosquito bite.
Keap1 recognizes EIAV early accessory protein Rev to promote antiviral defense
Authors: Wang Yan , Ma Guanqin , Wang Xue-Feng , Na Lei , Guo Xing , Zhang Jiaqi , Liu Cong , Du Cheng , Lin Yuezhi , Wang Xiaojun 
Published: September 2021

AbstractThe Nrf2/Keap1 axis plays a complex role in viral susceptibility, virus-associated inflammation and immune regulation. However, whether or how the Nrf2/Keap1 axis is involved in the interactions between equine lentiviruses and their hosts remains unclear. Here, we demonstrate that the Nrf2/Keap1 axis was activated during EIAV infection. Mechanistically, EIAV-Rev competitively binds to Keap1 and releases Nrf2 from Keap1-mediated repression, leading to the accumulation of Nrf2 in the nucleus and promoting Nrf2 responsive genes transcription. Subsequently, we demonstrated that the Nrf2/Keap1 axis represses EIAV replication via two independent molecular mechanisms: directly increasing antioxidant enzymes to promote effective cellular resistance against EIAV infection, and repression of Rev-mediated RNA transport through direct interaction between Keap1 and Rev. Together, these data suggest that activation of the Nrf2/Keap1 axis mediates a passive defensive response to combat EIAV infection. The Nrf2/Keap1 axis could be a potential target for developing the strategies for combating EIAV infection.Author summaryHere we report that the Nrf2/Keap1 axis acts as an antiviral effector on EIAV replication through two-way regulation of Rev. On the one hand, EIAV-Rev activates the Nrf2/Keap1 axis by competitive interaction with Keap1, which promotes the transcription of cytoprotective genes implicated in the antiviral response. On the other hand, Keap1 restricts Rev/RRE-dependent RNA transport, leading to inhibition of viral protein synthesis and reduction in viral replication. This study highlights the importance of the Nrf2/Keap1 axis in controlling EIAV replication, and identifies this pathway as a potential new entry-point for treating lentivirus infection. Importantly, this report provides new insights into the regulation of viral replication by the Nrf2/Keap1 axis.
Single-cell transcriptomic analysis unveils spinal motor neuron subtype diversity underpinning the water-to-land transition in vertebrates
Authors: Liau Ee Shan , Jin Suoqin , Chen Yen-Chung , Liu Wei-Szu , Yong Luok Wen , Tsai Chang-Tai , Calon Maëliss , Yu Jr-Kai , Su Yi-Hsien , Nedelec Stéphane , Nie Qing , Chen Jun-An 
Published: September 2021

AbstractSpinal motor neurons (MNs) integrate sensory stimuli and brain commands to generate motor movements in vertebrates. Distinct MN populations and their diversity has long been hypothesized to co-evolve with motor circuit to provide the neural basis from undulatory to ambulatory locomotion during aquatic-to-terrestrial transition of vertebrates. However, how these subtypes are evolved remains largely enigmatic. Using single-cell transcriptomics, we investigate heterogeneity in mouse MNs and discover novel segment-specific subtypes. Among limb-innervating MNs, we reveal a diverse neuropeptide code for delineating putative motor pool identities. We further uncovered that axial MNs are subdivided by three conserved and molecularly distinct subpopulations, defined by Satb2, Nr2f2 or Bcl11b expression. Although axial MNs are conserved from cephalochordates to humans, subtype diversity becomes prominent in land animals and appears to continue evolving in humans. Overall, our study provides a unified classification system for spinal MNs and paves the way towards deciphering how neuronal subtypes are evolved.
Biochemical and structural characterization of the fused Bacteroides fragilis NFeoAB domain reveals a role for FeoA
Authors: Sestok Alex E. , Brown Janae B. , Obi Juliet O. , O’Sullivan Sean M. , Garcin Elsa D. , Deredge Daniel J. , Smith Aaron T. 
Published: September 2021

ABSTRACTIron is an essential element for nearly all organisms, and under anoxic and/or reducing conditions, Fe2+ is the dominant form of iron available to bacteria. The ferrous iron transport (Feo) system has been identified as the primary prokaryotic Fe2+ import machinery, and two proteins (FeoA and FeoB) are conserved across most bacterial species. However, how FeoA and FeoB function relative to one another remained enigmatic. In this work we explored the distribution of feoAB operons predicted to encode for a fusion of FeoA tethered to the soluble N-terminal, G-protein domain of FeoB via a connecting linker region. We hypothesized that this fusion might poise FeoA to interact with FeoB in order to affect function. To test this hypothesis, we cloned, expressed, purified, and biochemically characterized the soluble NFeoAB fusion protein from Bacteroides fragilis, a commensal organism implicated in drug-resistant peritoneal infections. Using X-ray crystallography, we determined to 1.50 Å resolution the structure of BfFeoA, which adopts an SH3-like fold implicated in protein-protein interactions. In combination with structural modeling, small-angle X-ray scattering, and hydrogen-deuterium exchange mass spectrometry, we show that FeoA and NFeoB indeed interact in a nucleotide-dependent manner, and we have mapped the protein-protein interaction interface. Finally, using GTP hydrolysis assays, we demonstrate that BfNFeoAB exhibits one of the slowest known rates of Feo-mediated GTP hydrolysis and is not potassium-stimulated, indicating that FeoA-NFeoB interactions may function to stabilize the GTP-bound form of FeoB. Our work thus reveals a role for FeoA function in the fused FeoAB systems and suggests a broader role for FeoA function amongst prokaryotes.
De novo variants in Chinese ASD trios reveal genetic basis underlying autism without developmental delay and intellectual disabilities
Authors: Wang Jincheng , Yu Juehua , Wang Mengdi , Zhang Lingli , Yang Kan , Du Xiujuan , Wu Jinyu , Wang Xiaoqun , Li Fei , Qiu Zilong 
Published: September 2021

AbstractAutism spectrum disorder (ASD) is a complex neurodevelopmental disorder that causes a range of social communication and behavioral impairments. ASD typically manifests in young children, often with developmental delay or intellectual disabilities (DD/ID) as comorbidities. Accruing evidence indicates that ASD is highly heritable and genomewide studies on ASD cohorts have defined numerous genetic contributors. Notably, most of these studies have been performed with individuals of European and Hispanic ancestry and thus there is a paucity of genetic analyses of ASD in the East Asian population. Here, we performed whole-exome sequencing on 772 ASD trios from China, combining with a previous study of 369 Chinese ASD trios, to identify de novo variants in a total of 1141 ASD trios. We found that ASD probands without DD/ID carried less disruptive de novo variants, including protein-truncating and missense variants, than ASD with DD/ID. Surprisingly, we showed that expression of genes with de novo variants found in ASD probands without DD/ID were enriched in a specific group of neural progenitor cells, suggesting a potential mechanism underlying high-functioning autism. Importantly, some ASD risk genes from this study are not present in the current ASD gene database, suggesting that there are novel genetic contributors to ASD in East Asian populations. We validated one such novel ASD risk gene – SLC35G1 by showing that mice harboring heterozygous deletion of Slc35g1 exhibited defects in social interaction behaviors. Together, this work nominates novel ASD risk genes and indicates that ASD genetic studies in different geographic populations are essential to reveal the comprehensive genetic architecture of ASD.
Why and how informatics and applied computing can still create structural changes and competitive advantage
Authors: Mitropoulos Sarandis , Douligeris Christos 
Published: September 2021

Purpose
In the new digital age, enterprises are facing an increasing global competition. In this paper, we first examine how Information Technology (IT) can play an important role in giving significant competitive advantage in the modern enterprises. The business value of IT is examined, as well as the limitations and the trade-offs that its applicability faces. Next, we present the basic principles for a successful IT strategy, considering the development of a long-term IT renovation plan, the strategic alignment of IT with the business strategy, and the adoption of an integrated, distributed, and interoperable IT platform. Finally, we examine how a highly functional and efficient IT organization can be developed.

Design/methodology/approach
Our methodological approach was based to the answers of the following questions: 1. Does IT still matter? 2. What is the business value created by IT along with the corresponding limitations and trade-offs? 3. How could a successful IT Strategy be build up? 4. How could an effective? T planning aligned with the business strategy be build up? 5. How could a homogenized and distributed corporate IT platform be developed? and finally, 6. How could a high-performance IT-enabled enterprise be build up?

Findings
The enterprises in order to succeed in the new digital area need to: 1. synchronize their IT strategy with their business strategy, 2. formulate a long-term IT strategy, 3. adopt IT systems and solutions that are implemented with elasticity, interoperability, distribution, and service-orientation. 4. keep a strategic direction towards the creation of an exceptional organization based on IT.

Originality/value
This paper is original with respect to the integrated approach the overall problem is examined. There is a prototype combined investigation of all perspectives for an effective enforcement of IT in a way that causes acceleration in competitive advantage when conducting business.
Governance and sustainability in Southeast Asia
Authors: Tran Mi , Beddewela Eshani , Ntim Collins G. 
Published: September 2021

PurposeThis paper aims to examine the relationship between a diverse set of corporate governance (CG) mechanisms and corporate sustainability disclosure (CSD) in Southeast Asian countries under national stakeholder reform.Design/methodology/approachData analysis is based on 171 of the largest companies across six Southeast Asian countries using a 30-item CSD measure.FindingsThe authors find that there are wide variations in the levels of CSD across the countries. The findings indicate that board size, board gender diversity, block ownership and the presence of a sustainability committee are significant determinants of CSD. Additionally, whilst more stringent stakeholder governance reform motivates firms to publish more sustainability information, it fails to influence the effectiveness of the board of directors in promoting CSD.Practical implicationsFindings of this study highlight the essential role internal governance structure plays in monitoring corporate actions and enabling corporations to reduce their legitimacy gap. The findings further encourage regulators and policymakers to question, with utmost importance, the effectiveness of stakeholder reform in making significant organisational changes.Originality/valueThere is a dearth of studies that examine the CG-CSD nexus in relation to specific institutional characteristics. Existing studies mainly focus on a single country with similar institutional environments and thus limiting the ability to understand the “context specificity” of sustainability content development. This paper provides an overview of stakeholder reform in Southeast Asian countries and empirically substantiates the relationship between CG and CSD across six countries undergoing such reforms in the region.