bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatiotemporal Mapping of Cherry Blossom Blooming by Semi-Automatic Observation System with Street-Level Photos
Authors: Tsutsumida Narumasa , Funada Shuya 
Published: April 2023

AbstractThe importance of floral phenology as a critical indicator of regional climate change and ecosystem services is widely recognized. The annual blooming of cherry blossoms is a nationally celebrated event in Japan, and historical phenological records have been used to document regional climate change. The cultural ecosystem services provided by this phenomenon are important as they not only signal the arrival of spring but also offer a picturesque spring landscape. Despite its importance, constructing a spatiotemporal record of cherry blossom blooming is challenging due to the limited coverage of traditional stationary observations. To address this issue, citizen-based observation programs and remote sensing applications have been implemented; nevertheless, these strategies are still limited by infrequent and insufficient observations throughout space and time. To compensate, we developed a flower detection model for geographically and temporally dispersed street-level photos that may be used as the core component of a semi-automatic observation system. Specifically, we developed a customized YOLOv4 model for cherry blossom detection from street-level photos obtained through Mapillary, one of the social sensing data repositories. The detection model achieved an overall accuracy, recall, and precision of 86.7%, 70.3%, and 90.1%, respectively. By using observation coordinates and dates attached to Mapillary photos, we mapped the probability of cherry trees blooming in a spatial grid of dimensions 10 m x 10 m on a daily basis. With sufficient observations, start, peak, and end of blooming were estimated through time series analysis. A case study conducted at Saitama University’s main campus in 2022 confirmed the possibility of mapping the presence of cherry blossoms and their blooming timing automatically. Since our approach relies solely on geotagged street-level photos that can be taken by anyone with no prior knowledge of cherry tree species identification, we anticipate that it will be easier to build blooming records over space and time than conventional stationary observations or citizen-based observation programs. This novel approach also has potential applications for detecting other species as well.
Determination of the factors responsible for host tropism of SARS-CoV-2-related bat coronaviruses
Authors: Fujita Shigeru , Kosugi Yusuke , Kimura Izumi , Tokunaga Kenzo , Ito Jumpei , Sato Kei 
Published: April 2023

AbstractDifferences in host ACE2 genes may affect the host range of SARS-CoV-2-related coronaviruses (SC2r-CoVs) and further determine the tropism of host ACE2 for the infection receptor. However, the factor(s) responsible for determining the host tropism of SC2r-CoVs, which may in part be determined by the tropism of host ACE2 usage, remains unclear. Here, we use the pseudoviruses with the spike proteins of two Laotian SC2r-CoVs, BANAL-20-236 and BANAL-20-52, and the cells expressing ACE2 proteins of eight different Rhinolophus bat species, and show that these two spikes have different tropisms for Rhinolophus bat ACE2. Through structural analysis and cell culture experiments, we demonstrate that this tropism is determined by residue 493 of the spike and residues 31 and 35 of ACE2. Our results suggest that SC2r-CoVs exhibit differential ACE2 tropism, which may be driven by adaptation to different Rhinolophus bat ACE2 proteins.
Genome-wide association study stratified byMAPThaplotypes identifies potential novel loci in Parkinson’s disease
Authors: Senkevich Konstantin , Bandres-Ciga Sara , Cisterna-García Alejandro , Yu Eric , Bustos Bernabe I. , Krohn Lynne , Lubbe Steven J. , Botía Juan A. ,   the International Parkinson’s Disease Genomics Consortium (IPDGC), Gan-Or Ziv 
Published: April 2023

AbstractObjectiveTo identify genetic factors that may modify the effects of theMAPTlocus in Parkinson’s disease (PD).MethodsWe used data from the International Parkinson’s Disease Genomics Consortium (IPDGC) and the UK biobank (UKBB). We stratified the IPDGC cohort for carriers of the H1/H1 genotype (PD patients n=8,492 and controls n=6,765) and carriers of the H2 haplotype (with either H1/H2 or H2/H2 genotypes, patients n=4,779 and controls n=4,849) to perform genome-wide association studies (GWASs). Then, we performed replication analyses in the UKBB data. To study the association of rare variants in the new nominated genes, we performed burden analyses in two cohorts (Accelerating Medicines Partnership – Parkinson Disease and UKBB) with a total sample size PD patients n=2,943 and controls n=18,486.ResultsWe identified a novel locus associated with PD amongMAPTH1/H1 carriers nearEMP1(rs56312722, OR=0.88, 95%CI= 0.84-0.92, p= 1.80E-08), and a novel locus associated with PD amongMAPTH2 carriers nearVANGL1(rs11590278, OR=1.69 95%CI=1.40-2.03, p= 2.72E-08). Similar analysis of the UKBB data did not replicate these results and rs11590278 nearVANGL1did have similar effect size and direction in carriers of H2 haplotype, albeit not statistically significant (OR= 1.32, 95%CI= 0.94-1.86, p=0.17). RareEMP1variants with high CADD scores were associated with PD in theMAPTH2 stratified analysis (p=9.46E-05), mainly driven by the p.V11G variant.InterpretationWe identified several loci potentially associated with PD stratified byMAPThaplotype and larger replication studies are required to confirm these associations.
Cross-cohort mixture analysis: a data integration approach with applications on gestational age and DNA-methylation-derived gestational age acceleration metrics
Authors: Colicino Elena , Ascari Roberto , Saddiki Hachem , Merced-Nieves Francheska , Pedretti Nicolo Foppa , Huddleston Kathi , Wright Robert O , Wright Rosalind J , Outcomes Child Health 
Published: April 2023

ABSTRACTBackgroundData integration of multiple epidemiologic studies can provide enhanced exposure contrast and statistical power to examine associations between environmental exposure mixtures and health outcomes. Extant studies have combined population studies and identified an overall mixture-outcome association, without accounting for differences across studies.ObjectiveTo extend the novel Bayesian Weighted Quantile Sum (BWQS) regression to a hierarchical framework to analyze mixtures across multiple cohorts of different sample sizes.MethodsWe implemented a hierarchical BWQS (HBWQS) approach that (i) aggregates sample size of multiple cohorts to calculate an overall mixture index, thereby identifying the most harmful exposure(s) across cohorts; and (ii) provides cohort-specific associations between the overall mixture index and the outcome. We showed results from six simulated scenarios including four mixture components in five and ten populations, and two real case-examples on the association between prenatal metal mixture exposure—comprising arsenic, cadmium and lead—and both gestational age and gestational age acceleration metrics.ResultsResults from simulated scenarios showed good empirical coverage and little bias for all parameters estimated with HBWQS. The Watanabe-Akaike information criterion (WAIC) for the HBWQS regression showed a better average performance across scenarios than the BWQS regression. HBWQS results incorporating cohorts within the national Environmental influences on Child Health Outcomes (ECHO) program from three different sites (Boston, New York City (NYC), and Virginia) showed that the environmental mixture—composed of low levels of arsenic, cadmium, and lead—was negatively associated with gestational age in NYC..ConclusionsThis novel statistical approach facilitates the combination of multiple cohorts and accounts for individual cohort differences in mixture analyses. Findings from this approach can be used to develop regulations, policies, and interventions regarding multiple co-occurring environmental exposures and it will maximize use of extant publicly available data.
Loss of Mitochondrial Enoyl CoA Reductase causes elevated ceramide levels and impairs iron metabolism
Authors: Dutta Debdeep , Kanca Oguz , Byeon Seul Kee , Marcogliese Paul C. , Zuo Zhongyuan , Shridharan Rishi V. , Park Jun Hyoung ,   Undiagnosed Diseases Network, Lin Guang , Ge Ming , Heimer Gali , Kohler Jennefer N. , Wheeler Matthew T. , Kaipparettu Benny A. , Pandey Akhilesh , Bellen Hugo J. 
Published: April 2023

AbstractIn most eukaryotic cells fatty acid synthesis occurs in the cytoplasm as well as in mitochondria. However, the relative contribution of mitochondrial fatty acid synthesis (mtFAS) to the cellular lipidome of metazoans is ill-defined. Hence, we studied the function of the fly Mitochondria enoyl CoA reductase (Mecr), the enzyme required for the last step of mtFAS. Loss ofmecrcauses lethality while neuronal loss leads to progressive neurological defects. We observe an elevated level of ceramides, a defect in Fe-S cluster biogenesis and increased iron levels inmecrmutants. Reducing the levels of either iron or ceramide suppresses the neurodegenerative phenotypes indicating that increased ceramides and iron metabolism are interrelated and play an important role in the pathogenesis. Mutations in humanMECRcause pediatric-onset neurodegeneration and patient-derived fibroblasts display similar elevated ceramide levels and impaired iron homeostasis. In summary, this study shows an as-yet-unidentified role ofmecr/MECRin ceramide and iron metabolism providing a mechanistic link between mtFAS and neurodegeneration.
Grazing hinders seed dispersal during crop failure in a declining oak woodland
Authors: Vaz Pedro G. , Bugalho Miguel N. , Fedriani Jose M. 
Published: April 2023

AbstractMasting, the synchronized production of variable quantities of seeds, occurs in many grazed systems and can be interspersed with years of extreme crop failure, whose frequency and unpredictability are increasing with climate change. Yet, the combined impact of crop failure and grazing on seed dispersal and seed-to-seedling transition remains poorly understood. To address this concern, we investigated rodent-mediated cork-oak (Quercus suber) acorn predation, dispersal, and seedling emergence in cattle grazed and non-grazed areas in central Portugal during years with contrasting masting seasons. We found that extreme crop failure led to six times longer and faster acorn dispersal, with 83% more dispersal events than during a year of reproductive success. The percentage of predated acorns also increased by 84%. However, the higher acorn predation was offset by a 2.4-fold higher percentage of unpredated dispersed acorns recruiting into seedlings. Both years ended up recruiting a similar number of seedlings. Acorns emerged seedlings 3.4 times farther in the crop failure year than in the crop success year. Cattle grazing was the main constraint on seed dispersal distance, reducing it by 51% during the extreme crop failure year, while having no noticeable effect during the successful crop year. Our study provides empirical evidence that cattle grazing modulates how an extreme crop failure year can surprisingly be an opportunity for trees remaining fecund to have seedlings established farther apart than in a crop success year. If we are to better manage and preserve the high conservation and socio-economic value of Mediterranean cork oak woodlands in the face of climate change, we must prioritize fecund trees and carefully manage seed dispersal factors such as cattle grazing, particularly during years of crop failure.
Myosin inhibitor reverses hypertrophic cardiomyopathy in pediatric iPSC-cardiomyocytes to mirror variant correction
Authors: Kinnear Caroline , Said Abdelrahman , Meng Guoliang , Zhao Yimu , Wang Erika Y , Parmar Neha , Wei Wei , Billia Filio , Simmons Craig A , Radisic Milica , Ellis James , Mital Seema 
Published: April 2023

SUMMARYHypertrophic cardiomyopathy (HCM) is mainly caused by sarcomere gene variants in MYH7 and MYBPC3. Targeted drugs like myosin ATPase inhibitors have shown efficacy in adult HCM but have not been evaluated in children. We generated iPSC-cardiomyocytes (CMs) from four children with HCM harboring variants inMYH7(V606M; R453C)orMYBPC3 (G148R; P955fs and TNNI3_A157P), variant-corrected controls, and a healthy individual. All CMs showed hypertrophy and sarcomere disorganization. All 3 single variant CMs showed higher contractility, slower relaxation, higher calcium transients and higher ATPase activity. OnlyMYH7variant CMs showed stronger myosin-actinin binding. Targeted myosin ATPase inhibitor showed complete rescue of the phenotype in affected CMs and in cardiac Biowires to mirror isogenic controls. The response was stronger compared to verapamil or metoprolol, highlighting the need for clinical trials of myosin targeted therapy in pediatric HCM patients. The phenotype and response to drug therapy are influenced by the underlying genotype.
Reprogramming a high robustGeobacillus thermoglucosidasiusfor efficient synthesis of polymer-grade lactic acid under extremely high temperature (60°C)
Authors: Liu Jiongqin , Han Xiao , Tao Fei , Xu Ping 
Published: April 2023

AbstractOptically pure lactic acid is an important precursor for the synthesis of biodegradable plastic polylactic acid.Geobacillus thermoglucosidasiusis a thermophilic bacterial chassis with industrial potential. In this study, we reprogrammed this chassis to efficiently produce polymer-grade lactic acid by combining rational and semi-rational design strategies. We obtained optically pure L-lactic acid- and D-lactic acid-producing strains, GTD17 and GTD7, respectively, via rational strategies: constructing a lactic acid synthesis module, deleting by-product synthesis, and enhancing lactic acid production. At an extremely high temperature (60°C), the engineered strain GTD17 produced 94.2 g L−1of L-lactic acid with an overall yield and productivity of 91.5% and 2.0 g L−1h−1, respectively, and the optical purity of L-lactic acid was 99.5%. We then performed semi-rational adaptive evolution on the engineered strain GTD7 to obtain an optically pure D-lactic acid-producing strain GTD7-144; at the extremely high temperature (60°C), it produced 153.1 g L−1of D-lactic acid with an overall yield and productivity of 93.0% and 3.2 g L−1h−1, respectively. The optical purity of the D-lactic acid was 99.6%. Genome resequencing and analysis of the strain GTD7-144 revealed potential genetic targets that may improve production performance. This study represents an advancement in the high-temperature production of polymer-grade lactic acid byG. thermoglucosidasius.
Osmolar modulation drives reversible cell cycle exit and human pluripotent cell differentiation via NF-κВ and WNT signaling
Authors: Chui Jonathan Sai-Hong , Izuel-Idoype Teresa , Qualizza Alessandra , Pires de Almeida Rita , van der Veer Bernard K. , Vanmarcke Gert , Athanasouli Paraskevi , Boon Ruben , Vriens Joris , Koh Kian Peng , Grunsven Leo van , Verfaillie Catherine M. , Lluis Frederic 
Published: April 2023

ABSTRACTTerminally differentiated cells are regarded as the most stable and common cell state in adult organisms as they reside in growth arrest and carry out their cellular function. Improving our understanding of the mechanisms involved in promoting cell cycle exit would facilitate our ability to manipulate pluripotent cells into mature tissues for both pharmacological and therapeutic use. Here, we demonstrated that a hyperosmolar environment enforced a protective p53-independent quiescent state in dedifferentiated hepatoma cells and pluripotent stem cells (PSCs)-derived models of human hepatocytes and endothelial cells, representing the endodermal and mesodermal lineages. Prolonged culture in hyperosmolar conditions stimulated transcriptional and functional cell maturation. Interestingly, hyperosmolar conditions did not only trigger cell cycle exit and cellular maturation but were also necessary to maintain this maturated state, as switching back to plasma osmolarity caused the loss of maturation markers and the gain of proliferative markers. Transcriptome analysis revealed activation of NF-κВ and repression of WNT signaling as the two main pathways downstream of osmolarity-regulated growth arrest and cell maturation, respectively. This study revealed that increased osmolarity serves as a biochemical signal to promote long-term growth arrest, transcriptional changes, and maturation into different lineages, serving as a practical method to generate differentiated hiPSCs that resemble their mature counterpart more closely.
Never judge a bird by its feathers: genetics unveils the true target of trafficking in morphologically similarCopsychusspecies
Authors: Cavill Emily L. , Hernández-Alonso Germán , Ogden Rob , Gilbert M. Thomas. P. 
Published: April 2023

AbstractTrends in wildlife crime continue to rise and contribute to the ongoing decline of our planet’s biodiversity. We applied a genetic approach to ascertain the geographic origin of a suspected Seychelles Magpie-robin confiscated in Singapore during international transit, and to confirm illegal trade of this species. However, mitochondrial analyses revealed this individual to be a subspecies of Oriental Magpie-robin, endemic to the island of Borneo, and bearing similar morphology to the Seychelles species. We thus consider the implications of correct species identification on captive care and repatriation in cases of wildlife confiscation, and emphasise the value of using genetics in wildlife crime investigation.
Fast and flexible joint fine-mapping of multiple traits via the Sum of Single Effects model
Authors: Zou Yuxin , Carbonetto Peter , Xie Dongyue , Wang Gao , Stephens Matthew 
Published: April 2023

AbstractWe introduce mvSuSiE, a multi-trait fine-mapping method for identifying putative causal variants from genetic association data (individual-level or summary data). mvSuSiE learns patterns of shared genetic effects from data, and exploits these patterns to improve power to identify causal SNPs. Comparisons on simulated data show that mvSuSiE is competitive in speed, power and precision with existing multi-trait methods, and uniformly improves on single-trait fine-mapping (SuSiE) in each trait separately. We applied mvSuSiE to jointly fine-map 16 blood cell traits using data from the UK Biobank. By jointly analyzing the traits and modeling heterogeneous effect sharing patterns, we discovered a much larger number of causal SNPs (>3,000) compared with single-trait fine-mapping, and with narrower credible sets. mvSuSiE also more comprehensively characterized the ways in which the genetic variants affect one or more blood cell traits; 68% of causal SNPs showed significant effects in more than one blood cell type.
SINGLE CELL RESOLUTION OF THE ADULT ZEBRAFISH INTESTINE UNDER CONVENTIONAL CONDITIONS, AND IN RESPONSE TO AN ACUTEVIBRIO CHOLERAEINFECTION
Authors: Jones Lena O. , Willms Reegan J. , Eklund Mckenna , Graham Ralph Derrick V. , Xu Xinyue , Shin Minjeong , Foley Edan 
Published: April 2023

ABSTRACTVibrio choleraeis an aquatic bacterium that primarily infects the gastrointestinal tract, causing the severe and potentially deadly diarrheal disease, cholera. Despite the impact ofVibrioon global health, our understanding of host mucosal responses to the pathogen at the site of infection remains limited, highlighting a critical knowledge gap that must be addressed to develop more effective prevention and treatment strategies. Using a natural infection model, we combined physiological and single-cell transcriptomic studies to characterize adult zebrafish guts raised under conventional conditions and after a challenge withVibrio. We discovered thatVibriocauses a mild mucosal immune response characterized by T cell activation and enhanced antigen capture in the epithelium. Additionally, we discovered thatVibriosuppresses host interferon signaling, and that ectopic activation of interferon significantly alters the course of infection. Notably, we also found that the adult zebrafish gut shares many similarities with mammalian counterparts, including the presence of previously undescribed Best4+ cells, tuft cells, and a population of basal cycling cells. These discoveries provide important insights into host-pathogen interactions and emphasize the utility of zebrafish as a natural model ofVibrioinfection.
Ribosomal L12 stalks recruit elongation factors to speed protein synthesis inEscherichia coli
Authors: Hofmann Jennifer L. , Yang Theodore S. , Sunol Alp M. , Zia Roseanna N. 
Published: April 2023

ABSTRACTActively translating ribosomes must wait after each elongation step for a new ternary complex (EF-Tu·aa-tRNA·GTP) to be delivered, facilitating rapid codon recognition testing and continued elongation. We recently showed that this wait time rate-limits elongation inEscherichia colidue to a competitive combinatoric search through crowded cytoplasm by thousands ofE. coli’s 42 unique ternary complexes. Here, we investigate whether L12 subunits on ribosomes’ surfaces pool translation molecules to reduce this wait time. To do so, we mimic elongation transport and reactions in a physiologically accurate, physics-based model of crowdedE. colicytoplasm. We find that L12 pre-loading as much as doubles translation rate by optimizing sampling of novel ternary complexes. But more L12 is not always better: faster-growing bacteria tend to have fewer L12. We resolve this paradox by demonstrating a tradeoff between binding and novel sampling as a function of copy number inE. coli. Variable L12 copy numbers may thus have evolved for fast or slow bacterial growth as complementary survival strategies.
Abundance of Oligoflexales bacteria is associated with algal symbiont density independent of thermal stress in Aiptasia anemones
Authors: Aguirre Emily G. , Fine Marissa J. , Kenkel Carly D. 
Published: April 2023

ABSTRACTMany multicellular organisms, such as humans, plants, and invertebrates, depend on symbioses with microbes for metabolic cooperation and exchange. Reef-building corals, an ecologically important order of invertebrates, are particularly vulnerable to environmental stress in part because of their nutritive symbiosis with dinoflagellate algae, and yet also benefit from these and other microbial associations. While coral microbiomes remain difficult to study because of their complexity, the anemone Aiptasia is emerging as a simplified model. Research has demonstrated co-occurrences between microbiome composition and the abundance and type of algal symbionts in cnidarians. However, whether these patterns are the result of general stress-induced shifts or depletions of algal-associated bacteria remains unclear. Our study aimed to distinguish the effect of changes in symbiont density and thermal stress on the microbiome of symbiotic Aiptasia strain CC7 by comparing them with aposymbiotic anemones, depleted of their native symbiont,Symbiodinium linucheae. Our analysis indicated that overall, thermal stress had the greatest impact on disrupting the microbiome. We found that three bacterial classes made up most of the relative abundance (60-85 %) in all samples, but the rare microbiome fluctuated between symbiotic states and following thermal stress. We also observed thatS. linucheaedensity correlated with abundance of Oligoflexales, suggesting these bacteria may be primary symbionts of the dinoflagellate algae. The findings of this study help expand knowledge on prospective multipartite symbioses in the cnidarian holobiont and how they respond to environmental disturbance.