bluuebunny/crossref_metadata_2025_split huggingface dataset:
Emergence of a recurrent insertion in the N-terminal domain of the SARS-CoV-2 spike glycoprotein
Authors: Gerdol Marco , Dishnica Klevia , Giorgetti Alejandro 
Published: April 2021

AbstractTracking the evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through genomic surveillance programs is undoubtedly one of the key priorities in the current pandemic situation. Although the genome of SARS-CoV-2 acquires mutations at a slower rate compared with other RNA viruses, evolutionary pressures derived from the widespread circulation of SARS-CoV-2 in the human population have progressively favored the global emergence, though natural selection, of several variants of concern that carry multiple non-synonymous mutations in the spike glycoprotein. These are often placed in key sites within major antibody epitopes and may therefore confer resistance to neutralizing antibodies, leading to partial immune escape, or otherwise compensate infectivity deficits associated with other non-synonymous substitutions. As previously shown by other authors, several emerging variants carry recurrent deletion regions (RDRs) that display a partial overlap with antibody epitopes located in the spike N-terminal domain (NTD). Comparatively, very little attention has been directed towards spike insertion mutations prior to the emergence of the B.1.1.529 (omicron) lineage. This manuscript describes a single recurrent insertion region (RIR1) in the N-terminal domain of SARS-CoV-2 spike protein, characterized by at least 41 independent acquisitions of 1-8 additional codons between Val213 and Leu216 in different viral lineages. Even though RIR1 is unlikely to confer antibody escape, its association with two distinct formerly widespread lineages (A.2.5 and B.1.214.2), with the quickly spreading omicron and with other VOCs and VOIs warrants further investigation concerning its effects on spike structure and viral infectivity.
Sperm membrane proteins DCST1 and DCST2 are required for the sperm-egg fusion process in mice and fish
Authors: Noda Taichi , Blaha Andreas , Fujihara Yoshitaka , Gert Krista R. , Emori Chihiro , Deneke Victoria E. , Oura Seiya , Berent Sara , Kodani Mayo , Panser Karin , Cabrera-Quio Luis Enrique , Pauli Andrea , Ikawa Masahito 
Published: April 2021

AbstractThe process of sperm-egg fusion is critical for successful fertilization, yet the underlying mechanisms that regulate these steps have remained unclear in vertebrates. Here, we show that both mouse and zebrafish DCST1 and DCST2 are necessary in sperm to fertilize the egg, similar to their orthologs SPE-42 and SPE-49 inC. elegansand Sneaky inD. melanogaster. MouseDcst1andDcst2single knockout (KO) spermatozoa are able to undergo the acrosome reaction and show normal relocalization of IZUMO1, an essential factor for sperm-egg fusion, to the equatorial segment. While both single KO spermatozoa can bind to the oolemma, they rarely fuse with oocytes, resulting in male sterility. Similar to mice, zebrafishdcst1KO males are subfertile anddcst2anddcst1/2double KO males are sterile. Zebrafishdcst1/2KO spermatozoa are motile and can approach the egg, but rarely bind to the oolemma. These data demonstrate that DCST1/2 are essential for male fertility in two vertebrate species, highlighting their crucial role as conserved factors in fertilization.
Molecular relationships between SARS-CoV-2 Spike protein and LIFR, a pneumonia protective IL-6 family cytokine receptor
Authors: Ngara Mtakai , Siwo Geoffrey Henry 
Published: April 2021

AbstractThe fine-tuned control of immune responses is attained by pairs of activating and inhibitory signaling receptors which modulate the quality and magnitude of immune responses. Some viruses exploit these pathways to enter host cells as well as interfere with immune responses. Here, we report that the SARS-CoV-1/2 Spike proteins (S) contain a potential inhibitory tyrosine- based immunoreceptor motif (ITIM) with the D614G variant occurring within this motif. Through anin silicoscreen of ITIM-containing human proteins, we find that the S-located ITIM is closely related to a previously reported ITIM in the cytoplasmic tail of the human Leukemia Inhibitory Factor Receptor (LIFR), a pneumonia protective IL-6 family cytokine receptor. To infer potential functional interactions between SARS-CoV-2 infection and LIFR expression, we performed single-cell transcriptome analysis of public datasets of lung tissues from healthy individuals and COVID-19 patients. We show that transcripts ofLIFRand its ligandLIFare highly expressed in SARS-CoV-2 susceptible lung cells from mild and severe COVID-19 patients but not in healthy individuals. In addition, the human endogenous retroviral envelope gene (ERVW-1) encoding a fusogenic protein of the same functional class as the S protein, is induced in SARS-CoV-2 susceptible cell subpopulations in COVID-19 patients with no detectable expression in healthy individuals. We also report that pulmonary epithelial cells express transcripts of several immunoreceptors including the ITIM-containing antibody receptorFCGR2Bwhich is detectable in healthy and severe COVID-19 cases but not in mild cases. These results suggest that molecular dysregulation of ITIM-mediated inhibitory signaling by the SARS-CoV-2 S protein may play a role in COVID-19 immunopathology.
Anophelesspp. distribution and climatological niche modeling to predict malaria potential along bioclimatic envelope gradients in South Coast of West Java landscape
Authors: Wibowo Andri 
Published: April 2021

AbstractMalaria remains a major public health problem mainly in particular South East Asian countries. As malaria transmission andAnophelesspp. continues to spread, control interventions should emphasize on the ability to define potential areas that can favorAnophelesspp. distribution. Then there is an urgent need to use novel approach capable to predict potential spatial patterns ofAnophelesspp. and delineate malaria potential hotspots for better environmental health planning and management. Here, this study modeledAnophelesspp. potential distribution as a function of 15 bioclimatic variables using Species Distribution Modeling (SDM) in South Coast of West Java Province spans over 20 km from West to East. Findings of this study show that bioclimatic variables and SDM can be used to predictAnophelesspp. habitat suitability, suggesting the possibility of developing models for malaria early warning based on habitat suitability model. The resulting model shows that the potential distributions ofAnophelesspp. encompassed areas from West to Central parts of the coasts, with Central parts were the most potential prevalence areas ofAnophelesspp. considering this area has higher precipitation. The less potential prevalence areas ofAnophelesspp. were observed in the East parts of the coast. The model also shows that inland areas adjacent to the settlements were more potential in comparison to the areas near coast and in the beach. Land cover conditions dominated by cropland, herbaceous wetland, and inundated land were also influencing theAnophelesspp. potential distribution.
Punctual ecological changes rather than global factors drive species diversification and the evolution of wing phenotypes inMorphobutterflies
Authors: Chazot Nicolas , Blandin Patrick , Debat Vincent , Elias Marianne , Condamine Fabien L. 
Published: April 2021

AbstractAssessing the relative importance of geographical and ecological drivers of evolution is paramount to understand the diversification of species and traits at the macroevolutionary scale. Here, we use an integrative approach, combining phylogenetics, biogeography, ecology, and quantified phenotypes to investigate the drivers of both species and phenotypic diversification of the iconic Neotropical butterfly genusMorpho. We generated a time-calibrated phylogeny for all known species and inferred historical biogeography. We fitted models of time-dependent (accounting for rate heterogeneity across the phylogeny) and paleoenvironment-dependent diversification (accounting for global effect on the phylogeny). We used geometric morphometrics to assess variation of wing size and shape across the tree, and investigated their dynamics of evolution. We found that the diversification ofMorphois best explained when considering multiple independent diversification dynamics across the tree, possibly associated with lineages occupying different microhabitat conditions. First, a shift from understory to canopy was characterized by an increased speciation rate partially coupled with an increasing rate of wing shape evolution. Second, the occupation of dense bamboo thickets accompanying a major host-plant shift from dicotyledons towards monocotyledons was associated with a simultaneous diversification rate shift and an evolutionary “jump” of wing size. Our study points to a diversification pattern driven by punctual ecological changes instead of a global driver or biogeographic history.
Alpha variant versus D614G strain in the Syrian hamster model
Authors: Cochin Maxime , Luciani Léa , Touret Franck , Driouich Jean-Sélim , Petit Paul-Rémi , Moureau Grégory , Baronti Cécile , Laprie Caroline , Thirion Laurence , Maes Piet , Boudewijns Robbert , Neyts Johan , de Lamballerie Xavier , Nougairède Antoine 
Published: April 2021

AbstractLate 2020, SARS-CoV-2 Alpha variant from lineage B.1.1.7 emerged in United Kingdom and gradually replaced the G614 strains initially involved in the global spread of the pandemic. In this study, we used a Syrian hamster model to compare a clinical strain of Alpha variant with an ancestral G614 strain. The Alpha variant succeeded to infect animals and to induce a pathology that mimics COVID-19. However, both strains replicated to almost the same level and induced a comparable disease and immune response. A slight fitness advantage was noted for the G614 strain during competition and transmission experiments. These data do not corroborate the epidemiological situation observed during the first half of 2021 in humans nor reports that showed a more rapid replication of Alpha variant in human reconstituted bronchial epithelium.
A simulation study of the age‐structured spatially explicit dynamic N‐mixture model
Authors: Zhao Qing 
Published: April 2021

AbstractKnowledge of age‐specific movement and vital rates is important for understanding metapopulation dynamics yet difficult to obtain without capturing/marking individual animals. The development of dynamic N‐mixture models allows for the inference of recruitment and apparent survival while accounting for imperfect detection in count data of unmarked populations. Recent studies have further developed dynamic N‐mixture models to account for age structures or movement among local populations; however, there has yet to be a dynamic N‐mixture model that simultaneously accounts for both age structure and movement despite the fact that natural populations are composed of individuals of different ages with different movement and vital rates. In this study, I developed a dynamic N‐mixture model that allows different movement and vital rates between age classes while accounting for imperfect detection in age‐structured count data. I then conducted a simulation study to evaluate the inferential performance of the model while considering different local abundances, number of sites, and detection probabilities. The simulation study showed that the model could provide unbiased estimates of adult‐related parameters under a high detection probability, but bias was found for young‐related parameters regardless of detection probability. The bias in young‐related parameters also tended to be lower when local abundance was lower, probably due to more frequent extinction‐recolonization events in these populations. Overall, the results indicated that cautions should be taken when using dynamic N‐mixture models alone. However, these models may be useful sub‐models under integrated modeling frameworks, and thus improve our understanding of metapopulation dynamics.
Patients' experiences and perspectives of a mobile phone text messaging intervention to improve dietary behaviours in haemodialysis
Authors: Dawson Jessica , Tong Allison , Matus Gonzalez Andrea , Campbell Katrina L. , Craig Jonathan C. , Lee Vincent W. 
Published: April 2021

AbstractAimDietary requirements for people on haemodialysis are complex and often poorly adhered to. Mobile phone text messaging offers a simple strategy to enhance current nutritional care. KIDNEYTEXT was a 6‐month pilot randomised controlled trial that evaluated the feasibility and impact of mobile phone text messages to alter participants' dietary behaviours. The aim of this study was to elicit the perspectives of people on haemodialysis regarding acceptability of mobile phone text messages targeting dietary behaviours.MethodsSemi‐structured interviews were conducted with participants in the intervention arm of the KIDNEYTEXT study. Participants were purposively sampled and interviews were conducted in‐person or over the phone. Transcripts were thematically analysed using principles of grounded theory.ResultsInterviews were conducted with 25 participants. Four major themes were identified: building awareness (reinforcement of information, simple and comprehensible, guiding choices, accessible information enhancing motivation, gaining skills in management), valuing care (boosting self‐esteem, in‐person care bolstered by reminders), activating change (adjusting lifestyle, gaining control of electrolytes and fluid, striving to improve overall health), waning attention and motivation (lack of personalisation limiting change, maintaining the status quo, reverting back to old habits).ConclusionsParticipants perceived that the KIDNEYTEXT intervention enabled participants to build on their knowledge through the dissemination of simple and actionable content. Participants appreciated frequent reminders of how to improve their diet and felt that this increased contact motivated them to alter some dietary behaviours. Future trials should consider strategies to enhance personalisation to further motivate dietary change.
Screening of pepino (Solanum muricatum) and wild relatives against four major tomato diseases threatening its expansion in the Mediterranean region
Authors: Pacheco Juan , Soler Salvador , Figàs Maria R. , San Bautista Alberto , Prohens Jaime , Gramazio Pietro 
Published: April 2021

AbstractThe pepino (Solanum muricatum) is an Andean vegetable crop closely related to tomato. In the last decades, it has been introduced in the Mediterranean region and other parts of the world as a potential new crop. However, several tomato major pathogens may threaten the expansion of pepino cultivation. We identified Fusarium oxysporum f. sp. lycopersici (FOL), Verticillium dahliae (VE), pepino mosaic virus (PepMV) and tomato mosaic virus (ToMV) as four of the most likely pathogens to cause damage to pepino crops in Mediterranean climates. In order to evaluate the response of the pepino genepool against these pathogens, as well as to identify sources of tolerance, we inoculated six accessions of cultivated pepino, nine accessions of seven pepino wild relatives, and one interspecific hybrid with FOL, VE, PepMV and ToMV and followed its symptomatology for 30 days (FOL and VE) or 60 days (PepMV and ToMV). ELISA tests were also performed for PepMV and ToMV. Susceptible tomato materials were used as controls. The pepino genepool displayed fewer symptoms than susceptible tomato controls after inoculation with FOL, with most accessions being tolerant or resistant. Regarding VE, a wide variation of values for the symptoms index (SI) was observed, with three cultivated pepino accessions displaying tolerance. For PepMV a wide variation for SI was also observed, with one accession of S. caripense being resistant, and several accessions of pepino and other wild relatives displaying different degrees of tolerance. PepMV absorbance values obtained by ELISA tests followed a pattern similar to that of SI. For ToMV no resistances were found, although two wild accessions and the interspecific hybrid displayed low values for the SI and were considered as moderately tolerant. ELISA tests against ToMV revealed that the virus replicated well in all materials. None of the accessions evaluated displayed resistance or high levels of tolerance to the four pathogens, but some of them were complementary for resistance or high levels of tolerance. Although the interspecific hybrid tested was not resistant to any of the pathogens, it was tolerant to FOL and PepMV and moderately tolerant to VE and ToMV. A multivariate hierarchical clustering revealed similar patterns among accessions in the response to the two fungal diseases (FOL and VE) on one side and to the two viral ones (PepMV and ToMV) on the other. The information generated in this study has allowed identifying materials within the pepino genepool for the development of multi‐resistant pepino cultivars to major diseases threatening its expansion in the Mediterranean region.
Social Capital and Firm Innovation: Evidence from Cooperative Banking in Korea*
Authors: Oh Frederick Dongchuhl , Yoon Heejin 
Published: April 2021

AbstractThis study investigates the link between social capital and firm innovation by examining the cooperative banking channel in Korea. Social capital has a positive impact on the activities of cooperative banks, thus fostering innovation in regional firms. We first confirm a positive association between social capital and firm innovation in Korea and find that firms located in provinces with higher social capital innovate more. We then show that social capital positively influences firm innovation mainly through the cooperative banking channel. Further, we demonstrate that the cooperative banking channel is more pronounced in regions where cooperative banks are riskier, human capital is less, and commercial banking is less developed.
How is surgery included in the Strategic Health Plans of the Pacific, Papua New Guinea and Timor‐Leste?
Authors: Nagra Sonal , Singh Sheetal , Kaur Balbindar , McCaig Eddie , Tangi Viliame , Guest Glenn , Watters David A. 
Published: April 2021

AbstractBackgroundPapua New Guinea, Pacific Island nations, and Timor‐Leste represent a range of island nations with populations ranging from a few thousand to 8 million. They perform on average about 25% of the Lancet Commission of Global Surgery's target 5000 per 100 000 population and their health workforce have significant deficits of trained surgeons and anaesthetists. This study was conducted to determine how the current national health plans of these nations have included surgery and anaesthesia.MethodsThe most recent (as of December 2018) published national health plans of 10 Pacific Island nations (Cook Islands, Fiji, Nauru, Federated States of Micronesia, Kiribati, Samoa, Solomon Islands, Tonga, Tuvalu and Vanuatu), Papua New Guinea and Timor‐Leste were reviewed for content and process, searching for key words and identifying themes related to surgery and anaesthesia.ResultsThere were 12 national health plans with a combined total of 478 pages. There was limited surgical and/or anaesthesia input within the planning process. Injuries, blindness, cancer and non‐communicable diseases were included themes, but the potential role of surgical care in addressing these conditions was not well documented. The need for better information and registries was noted by several nations but possible surgical care delivery or outcome metrics were not included.ConclusionThere is limited mention of surgical and anaesthesia care planning within current health plans in the Pacific, PNG and TL. There is a need for greater surgical and anaesthesia engagement in future plans with performance measured against World Health Organization core surgical indicators.
Stratified Cox models with time‐varying effects for national kidney transplant patients: A new blockwise steepest ascent method
Authors: He Kevin , Zhu Ji , Kang Jian , Li Yi 
Published: April 2021

AbstractAnalyzing the national transplant database, which contains about 300,000 kidney transplant patients treated in over 290 transplant centers, may guide the disease management and inform the policy of kidney transplantation. Cox models stratified by centers provide a convenient means to account for the clustered data structure, while studying more than 160 predictors with effects that may vary over time. As fitting a time‐varying effect model with such a large sample size may defy any existing software, we propose a blockwise steepest ascent procedure by leveraging the block structure of parameters inherent from the basis expansions for each coefficient function. The algorithm iteratively updates the optimal blockwise search direction, along which the increment of the partial likelihood is maximized. The proposed method can be interpreted from the perspective of the minorization‐maximization algorithm and increases the partial likelihood until convergence. We further propose a Wald statistic to test whether the effects are indeed time varying. We evaluate the utility of the proposed method via simulations. Finally, we apply the method to analyze the national kidney transplant data and detect the time‐varying nature of the effects of various risk factors.
The T‐type calcium channel antagonist, Z944, reduces spinal excitability and pain hypersensitivity
Authors: Harding Erika K. , Dedek Annemarie , Bonin Robert P. , Salter Michael W. , Snutch Terrance P. , Hildebrand Michael E. 
Published: April 2021

Background and PurposeT‐type voltage‐gated calcium channels are an emerging therapeutic target for neurological disorders including epilepsy and pain. Inhibition of T‐type channels reduces the excitability of peripheral nociceptive sensory neurons and reverses pain hypersensitivity in male rodent pain models. However, administration of peripherally restricted T‐type antagonists failed to show efficacy in multiple clinical and preclinical pain trials, suggesting that inhibition of peripheral T‐type channels alone may be insufficient for pain relief.Experimental ApproachWe utilized the selective and CNS‐penetrant T‐type channel antagonist, Z944, in electrophysiological, calcium imaging and behavioural paradigms to determine its effect on lamina I neuron excitability and inflammatory pain behaviours.Key ResultsVoltage‐clamp recordings from lamina I spinal neurons of adult rats revealed that approximately 80% of neurons possess a low threshold T‐type current, which was blocked by Z944. Due to this highly prevalent T‐type current, Z944 potently blocked action‐potential evoked somatic and dendritic calcium transients in lamina I neurons. Moreover, application of Z944 to spinal cord slices attenuated action potential firing rates in over half of laminae I/II neurons. Finally, we found that intraperitoneal injection of Z944 (1–10 mg·kg−1) dose‐dependently reversed mechanical allodynia in the complete Freund's adjuvant model of persistent inflammatory pain, with a similar magnitude and time course of analgesic effects between male and female rats.Conclusion and ImplicationsT‐type calcium channels critically shape the excitability of lamina I pain processing neurons and inhibition of these channels by the clinical stage antagonist Z944 potently reverses pain hypersensitivity across sexes.