bluuebunny/crossref_metadata_2025_split huggingface dataset:
Closing Gaps But Increasing Bias In North American Butterfly Inventory Completeness
Authors: Shirey Vaughn , Belitz Michael W. , Barve Vijay , Guralnick Robert 
Published: July 2020

AbstractAggregate biodiversity data from museum specimens and community observations have promise for macroscale ecological analyses. Despite this, many groups are under-sampled, and sampling is not homogeneous across space. Here we used butterflies, the best documented group of insects, to examine inventory completeness across North America. We separated digitally accessible butterfly records into those from natural history collections and burgeoning community science observations to determine if these data sources have differential spatio-taxonomic biases. When we combined all data, we found startling under-sampling in regions with the most dramatic trajectories of climate change and across biomes. We also found support for the hypothesis that community science observations are filling more gaps in sampling but are more biased towards areas with the highest human footprint. Finally, we found that both types of occurrences have familial-level taxonomic completeness biases, in contrast to the hypothesis of less taxonomic bias in natural history collections data. These results suggest that higher inventory completeness, driven by rapid growth of community science observations, is partially offset by higher spatio-taxonomic biases. We use the findings here to provide recommendations on how to alleviate some of these gaps in the context of prioritizing global change research.
Increased processing of SINE B2 non coding RNAs unveils a novel type of transcriptome de-regulation underlying amyloid beta neuro-pathology
Authors: Cheng Yubo , Gollen Babita , Saville Luke , Isaac Christopher , Mehla Jogender , Mohajerani Majid , Zovoilis Athanasios 
Published: July 2020

ABSTRACTMore than 97% of the mammalian genome is non-protein coding, and repetitive elements account for more than 50% of noncoding space. However, the functional importance of many non-coding RNAs generated by these elements and their connection with pathologic processes remains elusive. We have previously shown that B2 RNAs, a class of non-coding RNAs that belong to the B2 family of SINE repeats, mediate the transcriptional activation of stress response genes (SRGs) upon application of a stimulus. Notably, B2 RNAs bind RNA Polymerase II (RNA Pol II) and suppress SRG transcription during pro-stimulation state. Upon application of a stimulus, B2 RNAs are processed into fragments and degraded, which in turn releases RNA Pol II from suppression and upregulates SRGs. Here, we demonstrate a novel role for B2 RNAs in transcriptome response to amyloid beta toxicity and pathology in the mouse hippocampus. In healthy hippocampi, activation of SRGs is followed by a transient upregulation of pro-apoptotic factors, such as p53 and miRNA-34c, which target SRGs creating a negative feedback loop that facilitates transition to the pro-stimulation state. Using an integrative RNA genomics approach, we show that in mouse hippocampi of an amyloid precursor protein knock-in mouse model and in anin vitrocell culture model of amyloid beta toxicity, this regulatory loop is dysfunctional due to increased levels of B2 RNA processing, constitutively elevated SRG expression and high p53 levels. Evidence indicates that Hsf1, a master regulator of stress response, mediates B2 RNA processing in cells, and is upregulated during amyloid toxicity accelerating the processing of SINE RNAs and SRG hyper-activation. Our study reveals that in mouse, SINE RNAs constitute a novel pathway deregulated in amyloid beta pathology, with potential implications for similar cases in the human brain, such as Alzheimer’s disease (AD). This data attributes a role to SINE RNA processing in a pathological process as well as a new function to Hsf1 that is independent of its transcription factor activity.
Flight morphology and visual obstruction predict collision risk in birds
Authors: Jackson Erin K. , Elmore Jared A. , Loss Scott R. , Winger Benjamin M. , Dakin Roslyn 
Published: July 2020

ABSTRACTCollisions with buildings are a major source of mortality for wild birds, but these instantaneous events are difficult to observe. As a result, the mechanistic causes of collision mortality are poorly understood. Here, we evaluate whether sensory and biomechanical traits can explain why some species are more collision-prone than others. We first examined concordance of species vulnerability estimates across previous North American studies to determine whether these estimates are repeatable, and whether vulnerability is more similar among closely-related species. We found moderate concordance and phylogenetic signal, indicating that some bird species are consistently more collision-prone than others. We next tested whether morphological traits related to flight performance and sensory guidance explain these differences among species. Our comparative analysis shows that two traits primarily predict collision vulnerability within passerines: relative beak length and relative wing length. Small passerine species with relatively short wings and those with relatively long beaks are more collision-prone, suggesting that greater maneuverability and obstructed vision contribute to risk. Together, these findings can help inform mitigation strategies and predict which species will be most at risk in other regions.
Regulated assembly of the ER membrane protein complex
Authors: Pleiner Tino , Januszyk Kurt , Tomaleri Giovani Pinton , Oania Robert S. , Hazu Masami , Sweredoski Michael J. , Moradian Annie , Guna Alina , Voorhees Rebecca M. 
Published: July 2020

SummaryThe assembly of nascent proteins into multi-subunit complexes is tightly regulated to maintain cellular homeostasis. The ER membrane protein complex (EMC) is an essential insertase that requires seven membrane-spanning and two soluble subunits for function. Here we show that the kinase With no lysine 1 (WNK1), known for its role in hypertension and neuropathy, is required for assembly of the human EMC. WNK1 uses a conserved amphipathic helix to stabilize the soluble subunit, EMC2, by binding to the EMC2-8 interface. Shielding this hydrophobic surface prevents promiscuous interactions of unassembled EMC2 and precludes binding of ubiquitin ligases, permitting assembly. Using biochemical reconstitution, we show that after EMC2 reaches the membrane, its interaction partners within the EMC displace WNK1, and similarly shield its exposed hydrophobic surfaces. This work describes an unexpected role for WNK1 in protein biogenesis, and defines the general requirements of an assembly factor that will apply across the proteome.
Discovery of potential imaging and therapeutic targets for severe inflammation in COVID-19 patients
Authors: Lee Hyunjong , Im Hyung-Jun , Na Kwon Joong , Choi Hongyoon 
Published: July 2020

AbstractThe COVID-19 pandemic has caused more than 540,000 deaths globally. Hyperinflammation mediated by dysregulated monocyte/macrophage function is considered to be the key factor that triggers severe illness in COVID-19. However, no specific targeting molecule has been identified for detecting or treating hyperinflammation related to dysregulated macrophages in severe COVID-19. Herein, we suggest candidate targets for imaging and therapy in severe COVID-19 by analyzing single-cell RNA-sequencing data based on bronchoalveolar lavage fluid of COVID-19 patients. We found that expression ofSLC2A3, which can be imaged by [18F]fluorodeoxyglucose, was higher in macrophages from severe COVID-19 patients. Furthermore, by integrating the surface target database and drug-target binding database with RNA-sequencing data of severe COVID-19, we identifiedCCR1andFPR1as surface and druggable targets for drug delivery as well as molecular imaging. Our results provide a resource for candidate targets in the development of specific imaging and therapy for COVID-19-related hyperinflammation.
Central Nervous System Manifestations in COVID-19 Patients: A Systematic Review and Meta-analysis
Authors: Nazari Shahrzad , Jafari Amirhossein Azari , Mirmoeeni Seyyedmohammadsadeq , Sadeghian Saeid , Heidari Mohammad Eghbal , Sadeghian Siavash , Asarzadegan Farhad , Puormand Seyed Mahmoud , Alikhani Katayoun , Ebadi Hamid , Fathi Davood , Dalvand Sahar 
Published: July 2020

AbstractBackgroundAt the end of December 2019, a novel respiratory infection, initially reported in China, known as COVID-19 initially reported in China, and later known as COVID-19, led to a global pandemic. Despite many studies reporting respiratory infections as the primary manifestations of this illness, an increasing number of investigations have focused on the central nervous system (CNS) manifestations in COVID-19. In this study, we aimed to evaluate the CNS presentations in COVID-19 patients in an attempt to identify the common CNS features and provide a better overview to tackle this new pandemic.MethodsIn this systematic review and meta-analysis, we searched PubMed, Web of Science, Ovid, Embase, Scopus, and Google Scholar. Included studies were publications that reported the CNS features between January 1st, 2020, to April 20th, 2020. The data of selected studies were screened and extracted independently by four reviewers. Extracted data analyzed by using STATA statistical software. The study protocol registered with PROSPERO (CRD42020184456).ResultsOf 2353 retrieved studies, we selected 64 studies with 11282 patients after screening. Most of the studies were conducted in China (58 studies). The most common CNS symptom of COVID-19 were Headache (8.69%, 95%CI: 6.76%-10.82%), Dizziness (5.94%, 95%CI: 3.66%-8.22%), and Impaired consciousness (1.9%, 95%CI: 1%-2.79%).ConclusionsThe growing number of studies have reported COVID-19, CNS presentations as remarkable manifestations that happen. Hence, understanding the CNS characteristics of COVID-19 can help us for better diagnosis and ultimately prevention of worse outcomes.
Temporal dynamics of human respiratory and gut microbiomes during the course of COVID-19 in adults
Authors: Xu Rong , Lu Renfei , Zhang Tao , Wu Qunfu , Cai Weihua , Han Xudong , Wan Zhenzhou , Jin Xia , Zhang Zhigang , Zhang Chiyu 
Published: July 2020

AbstractSARS-CoV-2 infects multiple organs including the respiratory tract and gut. Whether regional microbiomes are disturbed significantly to affect the disease progression of COVID-19 is largely unknown. To address this question, we performed cross-sectional and longitudinal analyses of throat and anal swabs from 35 COVID-19 adults and 15 controls by 16S rRNA gene sequencing. The results allowed a partitioning of patients into 3-4 categories (I-IV) with distinct microbial community types in both sites. Lower-diversity community types often appeared in the early phase of COVID-19, and synchronous fast restoration of both the respiratory and gut microbiomes from early dysbiosis towards late near-normal was observed in 6/8 mild COVID-19 adult patients despite they had a relatively slow clinical recovery. The synchronous shift of the community types was associated with significantly positive bacterial interactions between the respiratory tract and gut, possibly along the airway-gut axis. These findings reveal previously unknown interactions between respiratory and gut microbiomes, and suggest that modulations of regional microbiota might help to improve the recovery from COVID-19 in adult patients.
A geospatial examination of specialist care accessibility and impact on health outcomes for patients with acute traumatic spinal cord injury in NSW, Australia: a whole population record linkage study
Authors: Sharwood Lisa Nicole , Vaikuntam Bharat Phani , Cheng Christiana , Noonan Vanessa , Joseph Anthony , Ball Jonathon , Stanford Ralph , Kok Mei-Ruu , Whyatt David , Withers Samuel , Middleton James Walter 
Published: July 2020

ABSTRACTBackgroundTimely treatment is essential for achieving optimal outcomes after traumatic spinal cord injury (TSCI), and expeditious transfer to a specialist spinal cord injury unit (SCIU) is recommended within 24 hours from injury. Previous research in New South Wales (NSW) found only 57% of TSCI patients were admitted to SCIU for acute post-injury care; 73% transferred within 24 hours from injury.MethodsThis record linkage study included administrative pre-hospital, admissions and costs data for all patients aged ≥16 years with incident TSCI in NSW (2013-2016). Its aim was to examine potential geographical disparities in access to specialist care following TSCI using geospatial methods, and to better understand the impact of post-injury care pathways on patient outcomes.ResultsOf 316 cases with geospatial data, injury location analysis showed that over half (53%, n=168) of all patients were injured within 60 minutes road travel of a SCIU, yet only 28.6% (n=48) were directly transferred to a SCIU. Direct transfers received earlier operative intervention (median (IQR) 12.9(7.9) hours), compared with patients transferred indirectly to SCIU (median (IQR) 19.5(18.9) hours), and had lower risk of complications (OR 3.2 v 1.4, p<0.001).ConclusionsGetting patients with acute TSCI patients to the right place at the right time is dependent on numerous factors; some are still being triaged directly to non-trauma services which delays specialist and surgical care and increases complication risks. More stringent adherence to recommended guidelines would prioritise direct SCIU transfer for patients injured within 60 minutes radius, enabling the benefits of specialised care.
Spatial and temporal variability in the transmission potential of COVID-19 in South Korea including the second wave in the greater Seoul area, February to July 2020
Authors: Shim Eunha , Chowell Gerardo 
Published: July 2020

AbstractIn South Korea, 13,745 cases of COVID-19 have been reported as of 19 July, 2020. We used EpiEstim R package to investigate the time-varying reproduction numbers of the COVID-19 in the four most affected regions in South Korea: Seoul, Gyeonggi Province, Gyeongbuk Province, and Daegu. At the regional level, Seoul and Gyeonggi Province have experienced two waves with the first major peak of COVID-19 in early March, followed by the second wave in the first two weeks of June, with reproduction numbers in early May greater than 3.0.Gyeongbuk Province and Daegu are yet to experience a second wave of the disease, where the mean reproduction number reached values as high as 3.5-4.4. Our findings indicate that the loosening of the restrictions imposed by the government in May 2020 facilitated a second wave in the greater Seoul area.Article Summary LineThe loosening of the social distancing measures imposed by the Korean government in May 2020 has resulted in the second wave of COVID-19 in the greater Seoul area in the first two weeks of June, yielding reproduction numbers exceeding 3.0
Kv1.2 contributes to pattern separation by regulating the hippocampal CA3 neuronal ensemble size
Authors: Eom Kisang , Lee Hyoung Ro , Hyun Jung Ho , Ryu Hyun-Hee , Lee Yong-Seok , Lee Inah , Ho Won-Kyung , Lee Suk-Ho 
Published: July 2020

AbstractKv1.2 expression in rodent CA3 pyramidal cells (CA3-PC) is polarized to distal apical dendrites, and regulate the synaptic responses to perforant pathway (PP) inputs. Accordingly, Kv1.2 haploinsufficiency (Kcna2+/−) in CA3-PCs, but not Kv1.1 (Kcna1+/−), lowered the threshold for long-term potentiation at PP-CA3 synapses. TheKcna2+/− mice, but notKcna1+/−, displayed impairments in contextual fear discrimination task. The size and overlap of CA3 ensembles activated by the first visits to slightly different contexts were not different between wildtype andKcna2+/− mice, but these ensemble parameters diverged over training days between genotypes, suggesting abnormal plastic changes in the CA3 network ofKcna2+/− mice. Eventually, theKcna2+/− mice exhibited larger ensemble size and overlap upon retrieval of two contexts, compared to wildtype orKcna1+/− mice. These results suggest that Kv1.2 subunits prevent promiscuous plastic changes at PP-CA3 synapses, and contribute to sparse representation of memories and pattern separation in the CA3 network.
XGSEA: CROSS-species Gene Set Enrichment Analysis via domain adaptation
Authors: Cai Menglan , Nguyen Canh Hao , Mamitsuka Hiroshi , Li Limin 
Published: July 2020

AbstractGene set enrichment analysis (GSEA) has been widely used to identify gene sets with statistically significant difference between cases and controls against a large gene set. GSEA needs both phenotype labels and expression of genes. However, gene expression are assessed more often for model organisms than minor species. More importantly, gene expression could not be measured under specific conditions for human, due to high healthy risk of direct experiments, such as non-approved treatment or gene knockout, and then often substituted by mouse. Thus predicting enrichment significance (on a phenotype) of a given gene set of a species (target, say human), by using gene expression measured under the same phenotype of the other species (source, say mouse) is a vital and challenging problem, which we call CROSS-species Gene Set Enrichment Problem (XGSEP). For XGSEP, we propose XGSEA (Cross-species Gene Set Enrichment Analysis), with three steps of: 1) running GSEA for a source species to obtain enrichment scores andp-values of source gene sets; 2) representing the relation between source and target gene sets by domain adaptation; and 3) using regression to predictp-values of target gene sets, based on the representation in 2). We extensively validated XGSEA by using four real data sets under various settings, proving that XGSEA significantly outperformed three baseline methods. A case study of identifying important human pathways for T cell dysfunction and reprogramming from mouse ATAC-Seq data further confirmed the reliability of XGSEA. Source code is available throughhttps://github.com/LiminLi-xjtu/XGSEAAuthor summaryGene set enrichment analysis (GSEA) is a powerful tool in the gene sets differential analysis given a ranked gene list. GSEA requires complete data, gene expression with phenotype labels. However, gene expression could not be measured under specific conditions for human, due to high risk of direct experiments, such as non-approved treatment or gene knockout, and then often substituted by mouse. Thus no availability of gene expression leads to more challenging problem, CROSS-species Gene Set Enrichment Problem (XGSEP), in which enrichment significance (on a phenotype) of a given gene set of a species (target, say human) is predicted by using gene expression measured under the same phenotype of the other species (source, say mouse). In this work, we propose XGSEA (Cross-species Gene Set Enrichment Analysis) for XGSEP, with three steps of: 1) GSEA; 2) domain adaptation; and 3) regression. The results of four real data sets and a case study indicate that XGSEA significantly outperformed three baseline methods and confirmed the reliability of XGSEA.
Precise and programmable C:G to G:C base editing in genomic DNA
Authors: Chen Liwei , Park Jung Eun , Paa Peter , Rajakumar Priscilla D. , Chew Yi Ting , Manivannan Swathi N. , Chew Wei Leong 
Published: July 2020

AbstractMany genetic diseases are caused by single-nucleotide polymorphisms (SNPs). Base editors can correct SNPs at single-nucleotide resolution, but until recently, only allowed for C:G to T:A and A:T to G:C transition edits, addressing four out of twelve possible DNA base substitutions. Here we developed a novel class of C:G to G:C Base Editors (CGBEs) to create single-base genomic transversions in human cells. Our CGBEs consist of a nickase CRISPR-Cas9 (nCas9) fused to a cytosine deaminase and base excision repair (BER) proteins. Characterization of >30 CGBE candidates and 27 guide RNAs (gRNAs) revealed that CGBEs predominantly perform C:G to G:C editing (up to 90% purity), with rAPOBEC-nCas9-rXRCC1 being the most efficient (mean C:G to G:C edits at 15% and up to 37%). CGBEs target cytosine in WCW, ACC or GCT sequence contexts and within a precise two-nucleotide window of the target protospacer. We further targeted genes linked to dyslipidemia, hypertrophic cardiomyopathy, and deafness, showing the therapeutic potential of CGBE in interrogating and correcting human genetic diseases.
Implications of the COVID-19 lockdown on dengue transmission in Malaysia
Authors: Ong Song-Quan , Ahmad Hamdan , Ngesom Ahmad Mohiddin Mohd 
Published: July 2020

AbstractThe impact of movement restrictions during the COVID-19 lockdown on the existing endemic infectious disease dengue fever has generated considerable research interest. We compared the Malaysia weekly epidemiological records of dengue incidences during the period of lockdown to the trend of previous years (2015 to 2019) and a simulation at the corresponding period that expected no movement restrictions. We found that the dengue incidence declined significantly with a greater magnitude at phase 1 of lockdown, with a negative gradient of 3.2-fold steeper than the trend observed in previous years and 6.5-fold steeper than the simulation, indicating that the control of population movement did reduce dengue transmission. However, starting from phase 2 of lockdown, the dengue incidences demonstrated an elevation and earlier rebound by at least 4 weeks and grew with an exponential pattern compared to the simulation and previous years. Together with our data onAedesmosquitoes from a district of Penang, Malaysia, we revealed thatAedes albopictusis the predominant species for both indoor and outdoor environments. The abundance of the mosquito was increasing steadily during the period of lockdown, and demonstrated strong correlation with the locally reported dengue incidences; therefore, we proposed the possible diffusive effect of vector that led to a higher acceleration of incidence rate. These findings would help authorities review the direction and efforts of the vector control strategy.
Cre/LoxP-HBV plasmids generating recombinant covalently closed circular DNA genome upon transfection
Authors: Kruse Robert L. , Legras Xavier , Barzi Mercedes 
Published: July 2020

AbstractNew therapies against hepatitis B virus (HBV) require the elimination of covalently closed circular DNA (cccDNA), the episomal HBV genome. HBV plasmids containing an overlength 1.3-mer genome and bacterial backbone (pHBV1.3) are used in many different models, but do not replicate the unique features of cccDNA. Since the stable cccDNA pool is a barrier to HBV eradication in patients, we developed a recombinant circular HBV genome (rcccDNA) to mimic the cccDNA using Cre/LoxP technology. We validated four LoxP insertion sites into the HBV genome using hydrodynamic tail vein injection into murine liver, demonstrating high levels of HBV surface antigen (HBsAg) and HBV DNA expression with rcccDNA formation. HBsAg expression from rcccDNA was >30,000 ng/mL over 78 days, while HBsAg-expression from pHBV1.3 plasmid DNA declined from 2,753 ng/mL to 131 ng/mL over that time in immunodeficient mice (P<0.001), reflective of plasmid DNA silencing. We then cloned Cre-recombinase in cis on the LoxP-HBV plasmids, achieving plasmid stability in bacteria with intron insertion into Cre and demonstrating rcccDNA formation after transfectionin vitroandin vivo. These cis-Cre/LoxP-HBV plasmids were then used to create HBx-mutant and GFP reporter plasmids to further probe cccDNA biology and antiviral strategies against cccDNA. Overall, we believe these auto-generating rcccDNA plasmids will be of great value to model cccDNA for testing new therapies against HBV infection.