bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alfalfa vein mottling virus, a novel potyvirid infectingMedicago sativaL
Authors: Nemchinov Lev G. , Postnikova Olga A. , Wintermantel William M. , Palumbo John C. , Grinstead Sam 
Published: September 2023

AbstractWe have recently identified a novel virus detected in alfalfa seed material. The virus was tentatively named alfalfa-associated potyvirus 1, as its genomic fragments bore similarities with potyvirids. In this study, we obtained a complete genome sequence of the virus and classified it as a tentative species in the new genus, most closely related to the members of the genusIpomovirusin the familyPotyviridae. This assumption is based on the genome structure, phylogenetic relationships, transmission electron microscopy investigations and, in part, on serological cross-reactivity of the virus. We also demonstrated its mechanical transmission to the indicator plantNicotiana benthamianaand to the natural hostMedicago sativa, both of which developed characteristic symptoms therefore suggesting a pathogenic nature of the disease. Consistent with symptomatology, the virus was renamed to alfalfa vein mottling virus. A name Alvemovirus was proposed for the new genus in the familyPotyviridae, of which alfalfa vein mottling virus is a tentative member.
Heat Tolerance is Affected by the Gut Microbiota in a Vertebrate Ectotherm
Authors: Dallas Jason W. , Kazarina Anna , Lee Sonny T. M. , Warne Robin W. 
Published: September 2023

AbstractThe gut microbiota is known to influence and have regulatory effects in diverse physiological functions of host animals, but only recently has the relationship between host thermal biology and gut microbiota been explored. Here, we examined how early-life manipulations of the gut microbiota in larval amphibians influenced their critical thermal maximum (CTmax) at different acclimation temperatures. We removed the resident microbiome on the outside of wild-caught wood frog (Lithobates sylvaticus) egg masses via an antibiotic wash, and then either maintained eggs without a microbiota or inoculated eggs with pond water or the intestinal microbiota of another species, green frogs (L. clamitans), that have a wider thermal tolerance. We predicted that this cross-species transplant would improve the CTmaxof the recipient wood frog larvae relative to the other treatments. In line with this prediction, green frog-recipient larvae had the highest CTmaxwhile those with no inoculum had the lowest CTmax. Both the microbiome treatment and acclimation temperature significantly influenced the larval gut microbiota communities and alpha diversity indices. Green frog inoculated larvae were enriched in Rikenellaceae relative to the other treatments, which produce short-chain fatty acids and could contribute to greater energy availability and enhanced heat tolerance. Larvae that received no inoculation had higher relative abundances of potentially pathogenicAeromonasspp., which negatively affects host health and performance. Our results are the first to show that cross-species gut microbiota transplants alter heat tolerance in a predictive manner. This finding has repercussions for the conservation of species that are threatened by climate change and demonstrates a need to further explore the mechanisms by which the gut microbiota modulates host thermal tolerance.
Interferon induced circRNAs escape herpesvirus host shutoff and suppress lytic infection
Authors: Dremel Sarah E. , Tagawa Takanobu , Koparde Vishal N. , Arbuckle Jesse H. , Kristie Thomas M. , Krug Laurie T. , Ziegelbauer Joseph M. 
Published: September 2023

ABSTRACTA first line of defense during infection is expression of interferon (IFN)-stimulated gene products which suppress viral lytic infection. To combat this, herpesviruses express endoribonucleases to deplete host RNAs. Here we demonstrate that IFN-induced circular RNAs (circRNAs) can escape viral-mediated degradation. We performed comparative circRNA expression profiling for representative alpha- (Herpes simplex virus-1, HSV-1), beta- (human cytomegalovirus, HCMV), and gamma-herpesviruses (Kaposi sarcoma herpesvirus, KSHV; murine gamma-herpesvirus 68, MHV68). Strikingly, we found that circRNAs are, as a population, resistant to host shutoff. This observation was confirmed by ectopic expression assays of human and murine herpesvirus endoribonucleases. During primary lytic infection, ten circRNAs were commonly regulated across all subfamilies of human herpesviruses, suggesting a common mechanism of regulation. We tested one such mechanism, namely how interferon-stimulation influences circRNA expression. 67 circRNAs were upregulated by either IFN-β or -γ treatment, with half of these also upregulated during lytic infection. Using gain and loss of function studies we found an interferon-stimulated circRNA, circRELL1, inhibited lytic HSV-1 infection. We have previously reported circRELL1 inhibits lytic KSHV infection, suggesting a pan-herpesvirus antiviral activity. We propose a two-pronged model in which interferon-stimulated genes may encode both mRNA and circRNA with antiviral activity. This is critical in cases of host shutoff, such as alpha- and gamma-herpesvirus infection, where the mRNA products are degraded but circRNAs escape.
One-shot entorhinal maps enable flexible navigation in novel environments
Authors: Wen John H. , Sorscher Ben , Ganguli Surya , Giocomo Lisa M 
Published: September 2023

AbstractAnimals face the substantial challenge of navigating novel environments to find food, shelter, or mates. In mammals, hexagonal grid cells in the medial entorhinal cortex create a map-like population representation of the external environment1–7. However, it remains unclear how the grid map can adapt to novel environmental features on a rapid, behaviorally relevant time scale. By recording over fifteen thousand grid cells in mice navigating virtual environments, we found grid cell activity was weakly anchored to landmark inputs through afixedcircuit relationship. A computational model based on this fixed circuit assumption accurately predicted grid spatial patterns in environments with novel landmark rearrangements. Finally, a medial entorhinal cortex-dependent task revealed that while grid cell firing patterns remain anchored to landmarks, behavior can adapt to changes in landmark location via a downstream region implementing behavioral time scale synaptic plasticity8. This fixed but weak anchoring of grid cells to landmarks endows the grid map with powerful computational properties. The fixed nature allows the generation of rapid stable maps for novel environments after asingleexposure. The weak nature allows these rapidly formed maps to incur only small distortions between distances traveled in real versus neural space. Overall, such rapid low distortion mapping can then mediate accurate navigational behavior in rapidly changing environments through downstream plasticity.
KSHV Terminal Repeat Regulates Inducible Lytic Gene Promoters
Authors: Izumiya Yoshihiro , Algalil Adhraa , Espera Jonna M. , Miura Hiroki , Inagaki Tomoki , Izumiya Chie , Kumar Ashish 
Published: September 2023

SummaryThe Kaposi’s sarcoma-associated herpesvirus (KSHV) genome consists of an approximately 140 kb unique coding region flanked by multiple copies of 0.8 kb terminal repeat (TR) sequence. While TR’s function in plasmid maintenance is well-established, TR’s transcription regulatory roles have not been fully explored. Here, we show KSHV TR is a large transcription regulatory domain.A series of Cleavage Under Targets & Release Using Nuclease demonstrated that TR fragments are occupied by histone modifying enzymes that are known to interact with LANA in naturally infected cells, and the TR possessed characteristic enhancer histone modifications. The H3K4me3 and H3K27Ac modifications were conserved in unique region of the KSHV genome among naturally infected cells, and the KSHV Origin of lytic replication (Ori-Lyt) showed similar protein and histone modification occupancies with TR’s. In the Ori-Lyt region, the LANA complex colocalizes with H3K27Ac-modified nucleosome along with paused RNA polymerase II, and two K-Rta recruitment sites frank the nucleosome. The isolated reporter assays demonstrated that neighboring TR fragments enhanced viral lytic gene promoter activity independent of orientation in KSHV-infected and non-infected 293FT cells. K-Rta transactivation function was drastically enhanced with TR, while LANA acquired promoter repression function with TR. KSHV TR is, therefore a regulatory domain for KSHV inducible genes. However, in contrast to cellular enhancers that are bound by multiple transcription factors, perhaps the KSHV enhancer is predominantly regulated by the LANA nuclear body with TR. KSHV evolved a clever mechanism to tightly control the latency-lytic switch with the TR/LANA complex.ImportanceEnhancers are a crucial regulator of differential gene expression programs. Enhancer is the cis-regulatory sequences that determine target genes’ spatiotemporal and quantitative expression. Here, we show that KSHV terminal repeats fulfill the enhancer definition for KSHV inducible gene promoters. KSHV enhancer is occupied by LANA and its interacting proteins, such as CHD4, and CHD4 is known to restrict enhancers to access promoters for activation. This study thus proposes a new latency-lytic switch model in which TR accessibility to the KSHV gene promoters regulates lytic gene transcription.
Children exhibit a developmental advantage in the offline processing of a learned motor sequence
Authors: Van Roy Anke , Albouy Geneviève , Burns Ryan D. , King Bradley R. 
Published: September 2023

AbstractResearch that examines changes in a specific behavior across the lifespan frequently reports an inverted-U trajectory. That is, young adults exhibit optimal performance, children are conceptualized as developing systems progressing towards this ideal state, and older adulthood is characterized by performance decrements. However, not all behaviors follow this trajectory, as there are instances in which children outperform young adults. This study aimed to reveal instances of childhood advantage in the domain of motor learning and memory consolidation. Using a visually cued serial reaction time task, data were acquired from 7-35 and >55-year-old participants (n=238 datasets) across two experiments that assessed initial encoding as well as memory consolidation over 5-hour and 24-hour offline periods. Results revealed comparable initial learning dynamics among age groups, but 7- to 12-year-old children exhibited smaller sequence-specific learning relative to adolescents (13-17 year-olds), young adults (18-35 year-olds) and older adults (> 55 years). Interestingly, children demonstrated the greatest performance gains in the 5-hour and 24-hour delayed retests, reflecting enhanced motor memory consolidation. These results suggest that children exhibit an advantage in the offline processing of recently learned motor sequences.
Long-read RNA sequencing redefines the clear cell renal cell carcinoma transcriptome and reveals novel genes and transcripts associated with disease recurrence and immune evasion
Authors: Lee Joshua , Snell Elizabeth A. , Brown Joanne , Banks Rosamonde E. , Turner Daniel J. , Vasudev Naveen S. , Lagos Dimitris 
Published: September 2023

AbstractBackgroundLong-read direct RNA sequencing (DRS) and PCR cDNA sequencing (PCS) of tumour samples could lead to discovery of novel transcript isoforms, novel genes, and transcriptomic co-dependencies missed by conventional short-read sequencing. However, only a handful of reports using DRS or PCS in cancer exist with no direct comparison between the two methods. Clear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer. Following primary tumour resection approximately 30% of patients experience disease recurrence. Long-read RNA sequencing has not been applied to kidney cancer.Methods12 primary ccRCC archival tumours (discovery cohort), 6 from patients who went on to relapse, were analysed by Oxford Nanopore DRS and PCS. Results were validated in an independent cohort of 20 patients and compared to DRS analysis of RCC4 cells.ResultsDRS and PCS were successfully performed achieving high read length, with PCS achieving higher sequencing depth. Differentially expressed gene sets in patients who went on to relapse were determined with good overlap between DRS and PCS. Deconvolution analysis showed a loss of immune infiltrate in primary tumours of patients who relapse and revealed the CD8+T cell exhaustion markerTOXas a novel recurrence-associated gene. Notably, novel transcript analysis revealed more than 10,000 uncharacterised candidate novel transcripts detected by both methods and in a ccRCC cell linein vitro. This allowed the definition of the full exonic structure of ccRCC-associated splice variants, including variants ofMVKandHPCAL1. Remarkably, this also revealed a novel sPD-L1transcript encoding for the soluble version of the protein with a longer 3’UTR and lower stability in ccRCC cells than the annotated transcript. Levels ofsPD-L1transcripts are unchanged in primary tumours that go on to relapse, whereas membranePD-L1shows a trend towards down-regulation. Finally, both methods identified 414 novel genes, also detected in ccRCC cellsin vitro, including a novel non-coding gene over-expressed in patients who relapse.ConclusionsPCS and DRS can be used in tumour samples to uncover substantial yet unmapped features underpinning the plasticity and instability of cancer transcriptomes which are linked to disease progression and immune evasion.
Endogenous oncogenic KRAS expression increases cell proliferation and motility in near-diploid hTERT RPE-1 cells
Authors: Hindul Naushin L. , Abbott Lauren R. , Adan Sumaya M.D. , Straatman Kornelis R. , Fry Andrew M. , Hirota Kouji , Tanaka Kayoko 
Published: September 2023

AbstractAbout 18% of all human cancers carry a mutation in theKRASgene making it among the most sought-after anti-cancer targets. However, mutant KRas protein has proved remarkably undruggable. The recent approval of the first generation of RAS inhibitors therefore marks a seminal milestone in the history of cancer research. Inevitably though, it also raises the predictable challenges of limited drug efficacies and acquired resistance. Hence, new approaches that improve our understanding of the tumorigenic mechanisms of oncogenic RAS within more physiological settings continue to be essential. Here, we have employed the near-diploid human hTERT RPE-1 cells to generate isogenic cell lines in which one of the endogenousKRASalleles carries an oncogenicKRASmutation at glycine 12. Cells with aKRASG12V/+,KRASG12C/+, orKRASG12D/+genotype, together with wild-typeKRASG12G(WT)/+cells, reveal that oncogenicKRAS.G12Xmutations increase cell proliferation rate, while further analyses showed thatKRASG12V/+cells had increased cell motility and reduced focal adhesions. EGF-induced ERK phosphorylation was marginally increased inKRASG12V/+cells, while EGF-induced AKT phosphorylation was comparable betweenKRASG12V/+andKRASG12G(WT)/+cells. Interestingly, theKRASG12V/+cells were more sensitive to hydroxyurea and a MEK inhibitor, U0126, but more resistant to a PI3K inhibitor, PIK-90, than theKRASG12G(WT)/+cells. A combination of low doses of hydroxyurea and U0126 showed an additive inhibition on growth rate that was greater inKRASG12V/+than wild-type cells. Collectively, these cell lines will be a valuable resource for studying oncogenic RAS signalling and developing effective anti-KRAS reagents with minimum cytotoxicity on wild-type cells.
Modeling trade openness–unemployment nexus in sub-Saharan Africa: the role of asymmetries
Authors: Abdul-Mumuni Abdallah , Amakye Kwaku , Abukari Abdul-Lateef , Insaidoo Michael 
Published: September 2023

PurposeWhile several existing panel studies have focused on the linear specifications of the nexus between trade openness and unemployment, nonlinear panel studies on this subject remain less explored. This paper examines the asymmetric nexus between trade openness and unemployment in 34 selected sub-Saharan Africa (SSA) countries for the period spanning from 1991 to 2020.Design/methodology/approachThe Pedroni and Westerlund panel cointegration tests were conducted to ascertain a long run relationship among the studied variables, while the panel nonlinear autoregressive distributed lag approach was applied to account for asymmetries.FindingsThe study revealed among other things that trade openness asymmetrically influences unemployment in the selected panel of SSA countries. In the long run, the positive shock in trade openness on unemployment is greater as compared to the negative shock.Research limitations/implicationsThe implications of this study include the need to (1) ensure the effective monitoring and supervision of trade flows in the sub-region so that their full benefits are maximized in terms of job creation and (2) ensure that a positive trade balance is maintained in the selected SSA countries.Originality/valueThe positive and negative shocks in trade openness are examined to determine their asymmetric effects on unemployment.
Enhancing the employee experience: exploring a global positive climate to influence key employee outcomes
Authors: McCallum Sarah , Haar Jarrod , Myers Barbara 
Published: September 2023

PurposeOrganizational climates reflect employee perceptions of the way organizational culture is actualized and most studies explore one or two climates only. The present study uses a positive organizational behavior approach and conservation of resources theory to explore a global positive climate (GPC) encompassing five climates: perceive organizational support, psychosocial safety climate, organizational mindfulness, worthy work and inclusion climate. The GPC is used to predict employee engagement and job satisfaction, with psychological capital as a mediator. Beyond this, high performance work systems (HPWS) are included as a moderator of GPC to test the potential way HR practices might interact with positive climates to achieve superior outcomes.Design/methodology/approachA large sample (n = 1,007) of New Zealand workers across a wide range of occupations and industries. Confirmatory factor analysis (CFA) of the data was used and moderated mediation tests were conducted.FindingsGPC is significantly related to psychological capital, employee engagement and job satisfaction, and while psychological capital also predicts the outcomes, and has some mediation effects on GPC influence, GPC remains significant. HPWS is significantly related to psychological capital only and interacts with GPC leading to the highest psychological capital and employee engagement. Significant moderated mediation effects are found, with the indirect effect of GPC increasing as HPWS increase.Research limitations/implicationsThis research is important because it provides empirical evidence around a GPC and shows how organizations and HRM managers can enhance key employee attitudes through building a strong climate and providing important HR practices.Originality/valueBeyond unique effects from GPC, the findings provide useful theoretical insights toward conservation of resources theory.
Adapting and implementing the new normal: an Islamic university perspective
Authors: Basir Khairul Hidayatullah , Haji Sismat Muhamad Alif , Ahmad Siti Sara 
Published: September 2023

PurposeThis paper explores the experiences and strategies that have emerged from an Islamic university in Brunei Darussalam in its efforts to adapt to the new normal. It aims to provide a comprehensive post COVID-19 teaching and learning strategies framework and understand how the principles of Islam can be harmonised with modern practices, offering valuable lessons for educational institutions worldwide.Design/methodology/approachThe study employed a three-fold methodology. Initially, the authors conducted a comprehensive review of the post-COVID-19 experiences within Islamic universities. Subsequently, they administered a structured questionnaire to academic staff and students at an Islamic university in Brunei, utilising Google survey forms. Based on the insights from the data analysis, strategies were carefully formulated. Ultimately, this informed the development of a framework grounded in the established strategies.FindingsThe significant findings from this study include the adoption of “e-Talaqqi” and how this can be related to Maqasid Shariah to produce a conceptual framework of post-COVID-19 strategies adaptable for Islamic Higher Education Institutions (HEIs) and how that can be related to Maqasid Shariah in line with the values of Islamic-based universities.Research limitations/implicationsThe applicability of the framework developed from data gathered at an Islamic university in Brunei might have certain limitations when extended to other Islamic HEIs. Future research should aim to cover more Islamic HEIs across various countries, thereby strengthening a broader applicability of the framework. Moreover, it is advisable that the developed framework undergoes statistical validation to fortify it.Practical implicationsThe study's implications encompass theory, researchers, educators, policymakers, and all stakeholders concerned with the past, present, and future of HEIs, particularly in facilitating the adaptation of post-COVID-19 norms within Islamic HEIs.Social implicationsThis paper holds the potential to significantly benefit society by providing invaluable insights to educators and various sectors, aiding them in enhancing their learning pedagogies.Originality/valueThis study has developed a conceptual framework that offers strategies tailored for Islamic HEIs in the post-COVID-19 era, harmonising with the principles of Islamic-based universities, in alignment with Maqasid Shariah. Consequently, this research serves as a significant contribution to the evolution of new theoretical paradigms because of COVID-19.