bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cast away on Mindoro island: lack of space limits population growth of the endangered tamaraw (Bubalus mindorensis)
Authors: Bonenfant C. , Rutschmann A. , Burton J. , Boyles R. , García F. , Tilker A. , Schütz E. 
Published: May 2020

AbstractEndangered species, despite often living at low population densities, may undergo unexpected density-dependent feedbacks in the case of successful recovery or marked reduction in range. Because density-dependence dynamics can increase risk of extinction, these effects can hamper conservation efforts. In this study, we analyse the dynamics of the largest population of the tamaraw (Bubalus mindorensis), a critically endangered ungulate species endemic to Mindoro island, Philippines. The population is located within a < 3,000 ha area in Mounts Iglit-Baco Natural Park, with limited expansion possibilities. We took advantage of a 21 year time series of tamaraw counts to estimate annual population growth rate and possible density-dependence, accounting for sampling errors in the counts. The tamaraw population has been increasing at an average rate of +5% per year, as would be expected given its protected status by law. Population growth showed strong spatial structuring, with a population growth close to +10% in the core area of protection, and a reduction of abundance of −5% at the periphery of its range, inside the protected area. This range constriction is concerning because our best population dynamics model suggests significant negative density-dependence (Bayes factor = 0.9). The contraction of tamaraw range is likely caused by anthropogenic pressures forcing the species to live at relatively high densities in the core zone where protection is most effective, creating source-sink dynamics. Our study highlights the fact that, despite the continuous population growth over the last two decades, the long-term viability of the Mounts Iglit-Baco Natural Park tamaraw population remains uncertain.
Prevalence and phenology of mycorrhizal colonization across populations ofLycopodiella inundata
Authors: Kowal Jill , Arrigoni Elena , Serra Jordi , Bidartondo Martin 
Published: May 2020

AbstractMycorrhizal fungi are critical components of terrestrial habitats and agroecosystems. Recently, Mucoromycotina fine root endophyte (MucFRE) fungi were found to engage in nutritional mutualism with the rare plantLycopodiella inundata(‘marsh clubmoss’), one of the earliest vascular plant lineages known to associate with MucFRE. The extent to which this mutualism plays a role in resilient plant populations can only be understood by examining its occurrence rate and phenological patterns.To test for prevalence and seasonality in colonization, we examined 1,297 individualL. inundataroots collected during spring and autumn 2019 from 11 semi-natural heathlands in Britain and the Netherlands. We quantified presence/absence of MucFRE-like hyphae and vesicles and explored possible relationships between temperature and precipitation in the months immediately before sampling.MucFRE-like hyphae were the dominant mycorrhizal fungi observed in all of the examined heathlands. However, we found significant differences in colonization between the two seasons at every site. Overall, 14% ofL. inundataroots were colonised in spring (2.4% with vesicles) compared with 86% in autumn (7.6% with vesicles). Colonization levels between populations were also significantly different, and correlated with temperature and precipitation, suggesting some local environments may be more conducive to hyphal growth.These marked seasonal differences in host-plant colonization suggest that results about mycorrhizal status - typically drawn from single time point collections - should be carefully interpreted. Our findings are directly relevant to habitat restoration, species conservation plans, agricultural bio-inoculation nutrient enhancement treatments, microbial diversity and functional studies of host plants and symbionts.
Exploiting collateral sensitivity controls growth of mixed culture of sensitive and resistant cells and decreases selection for resistant cells
Authors: Kornél Grolmusz Vince , Chen Jinfeng , Emond Rena , Cosgrove Patrick A. , Pflieger Lance , Nath Aritro , Moos Philip J. , Bild Andrea H. 
Published: May 2020

AbstractBackgroundCDK4/6 inhibitors such as ribociclib are becoming widely used targeted therapies in hormone-receptor-positive (HR+) human epidermal growth factor receptor 2-negative (HER2-) breast cancer. However, cancers can advance due to drug resistance, a problem in which tumor heterogeneity and evolution are key features.MethodsRibociclib-resistant HR+/HER2-CAMA-1 breast cancer cells were generated through long-term ribociclib treatment. Characterization of sensitive and resistant cells were performed using RNA sequencing and whole exome sequencing. Lentiviral labeling with different fluorescent proteins enabled us to track the proliferation of sensitive and resistant cells under different treatments in a heterogeneous, 3D spheroid coculture system using imaging microscopy and flow cytometry.ResultsTranscriptional profiling of sensitive and resistant cells revealed the downregulation of the G2/M checkpoint in the resistant cells. Exploiting this acquired vulnerability; resistant cells exhibited collateral sensitivity for the Wee-1 inhibitor, adavosertib (AZD1775). The combination of ribociclib and adavosertib achieved additional antiproliferative effect exclusively in the cocultures compared to monocultures, while decreasing the selection for resistant cells.ConclusionsOur results suggest that optimal antiproliferative effects in heterogeneous cancers can be achieved via an integrative therapeutic approach targeting sensitive and resistant cancer cell populations within a tumor, respectively.
No Evidence for a Difference in 2D:4D Ratio between Youth with Elevated Prenatal Androgen Exposure due to Congenital Adrenal Hyperplasia and Controls
Authors: Nave Gideon , Koppin Christina M. , Manfredi Dylan , Richards Gareth , Watson Steven J. , Geffner Mitchell E. , Yong Jillian E. , Kim Robert , Ross Heather M. , Serrano-Gonzalez Monica , Kim Mimi S. 
Published: May 2020

AbstractThe second-to-fourth digit ratio (2D:4D) has been associated with sexual dimorphism, with a lower 2D:4D in males. A large body of research has relied on the 2D:4D as a proxy for prenatal androgen exposure, and includes reports of relationships between 2D:4D and a wide range of human traits. Here, we examine the validity of the 2D:4D proxy by studying the association between 2D:4D and classical Congenital Adrenal Hyperplasia (CAH) due to 21-hydroxylase deficiency, a condition characterized by excessive prenatal exposure to androgens during most of the gestational period. To this end, we retrospectively examine 513 serial radiographs of the left hand obtained clinically in 90 youth with classical CAH (45 female) and 70 control youth (31 female). Replicating previous reports, we observe associations of the 2D:4D with sex (lower 2D:4D in males) and age (increase of 2D:4D through development). However, we find no evidence for differences in 2D:4D between CAH and controls (full sample: □ = -0.001 (−0.008, 0.006)]; females: □ = -0.004 [-0.015, 0.007]; males: □ = 0.001, [-0.008, 0.011]). Although our findings do not rule out a small association between the 2D:4D and CAH, they cast doubt on the usefulness of the 2D:4D as a biomarker for prenatal androgen exposure in behavioral research.
Genome-wide Studies Reveal the Essential and Opposite Roles of ARID1A in Controlling Human Cardiogenesis and Neurogenesis from Pluripotent Stem Cells
Authors: Liu Juli , Liu Sheng , Gao Hongyu , Han Lei , Chu Xiaona , Sheng Yi , Wang Yue , Shou Weinian , Liu Yunlong , Wan Jun , Yang Lei 
Published: May 2020

AbstractBackgroundEarly human heart and brain development simultaneously occur during embryogenesis. Notably, in human newborns, congenital heart defects strongly associate with neurodevelopmental abnormalities, suggesting a common gene/complex underlying both cardiogenesis and neurogenesis. However, due to lack ofin vivostudies, the molecular mechanisms that govern both early human heart and brain development remain elusive.ResultsHere, we report ARID1A, which is a DNA-binding-subunit of the SWI/SNF epigenetic complex, controls both neurogenesis and cardiogenesis from human embryonic stem cells (hESCs) via employing distinct mechanisms. Knockout of ARID1A (ARID1A-/-) led to spontaneous differentiation of neural cells together with globally enhanced expression of neurogenic genes in undifferentiated hESCs. Additionally, when compared with WT hESCs, cardiac differentiation from ARID1A-/-hESCs was prominently suppressed, whereas neural differentiation was significantly promoted. Whole genome-wide scRNA-seq, ATAC-seq, and ChIP-seq analyses revealed that ARID1A was required to open chromatin accessibility on promoters of essential cardiogenic genes, and temporally associated with key cardiogenic transcriptional factors T and MEF2C during early cardiac development. However, during early neural development, transcription of most essential neurogenic genes was dependent on ARID1A, which could interact with a known neural restrictive silencer factor REST/NRSF.ConclusionsWe uncovered the opposite roles by ARID1A to govern both early cardiac and neural development from pluripotent stem cells. Global chromatin accessibility on cardiogenic genes is dependent on ARID1A, whereas transcriptional activity of neurogenic genes is under control by ARID1A, possibly through ARID1A-REST/NRSF interaction.
Coarse-grained molecular simulations of the binding of the SARS-CoV-2 spike protein RBD to the ACE2 receptor
Authors: De Sancho David , Gavira José A. , Pérez-Jiménez Raul 
Published: May 2020

AbstractSince it was first observed, the COVID-19 pandemic has created a global emergency for national health systems due to millions of confirmed cases and hundreds of thousands of deaths. At a molecular level, the bottleneck for the infection is the binding of the receptor binding domain (RBD) of the viral spike protein to ACE2, an enzyme exposed on human cell membranes. Several experimental structures of the ACE2:RBD complex have been made available, however they offer only a static description of the arrangements of the molecules in either the free or bound states. In order to gain a dynamic description of the binding process that is key to infection, we use molecular simulations with a coarse grained model of the RBD and ACE2. We find that binding occurs in an all-or-none way, without intermediates, and that even in the bound state, the RBD exhibits a considerably dynamic behaviour. From short equilibrium simulations started in the unbound state we provide snapshots that result in a tentative mechanism of binding. Our findings may be important for the development of drug discovery strategies that target the RBD.
Development and validation of the COVID-19 severity index (CSI): a prognostic tool for early respiratory decompensation
Authors: Haimovich Adrian , Ravindra Neal G. , Stoytchev Stoytcho , Young H. Patrick , Wilson Francis Perry , van Dijk David , Schulz Wade L. , Taylor R. Andrew 
Published: May 2020

AbstractObjectiveThe goal of this study was to create a predictive model of early hospital respiratory decompensation among patients with COVID-19.DesignObservational, retrospective cohort study.SettingNine-hospital health system within the Northeastern United States.PopulationsAdult patients (≥ 18 years) admitted from the emergency department who tested positive for SARS-CoV-2 (COVID-19) up to 24 hours after initial presentation. Patients meeting criteria for respiratory critical illness within 4 hours of arrival were excluded.Main outcome and performance measuresWe used a composite endpoint of critical illness as defined by oxygen requirement (greater than 10 L/min by low-flow device, high-flow device, non-invasive, or invasive ventilation) or death within the first 24 hours of hospitalization. We developed models predicting our composite endpoint using patient demographic and clinical data available within the first four hours of arrival. Eight hospitals (n= 932) were used for model development and one hospital (n= 240) was held out for external validation. Area under receiver operating characteristic (AU-ROC), precision-recall curves (AU-PRC), and calibration metrics were used to compare predictive models to three illness scoring systems: Elixhauser comorbidity index, qSOFA, and CURB-65.ResultsDuring the study period from March 1, 2020 to April 27,2020, 1,792 patients were admitted with COVID-19. Six-hundred and twenty patients were excluded based on age or critical illness within the first 4 hours, yielding 1,172 patients in the final cohort. Of these patients, 144 (12.3%) met the composite endpoint within the first 24 hours. We first developed a bedside quick COVID-19 severity index (qCSI), a twelve-point scale using nasal cannula flow rate, respiratory rate, and minimum documented pulse oximetry. We then created a machine-learning gradient boosting model, the COVID-19 severity index (CSI), using twelve additional variables including inflammatory markers and liver chemistries. Both the qCSI (AU-ROC mean [95% CI]: 0.90 [0.85-0.96]) and CSI (AU-ROC: 0.91 [0.86-0.97]) outperformed the comparator models (qSOFA: 0.76 [0.69-0.85]; Elixhauser: 0.70 [0.62-0.80]; CURB-65: AU-ROC 0.66 [0.58-0.77]) on cross-validation and performed well on external validation (qCSI: 0.82, CSI: 0.76, CURB-65: 0.50, qSOFA: 0.59, Elixhauser: 0.61). We find that a qCSI score of 0-3 is associated with a less than 5% risk of critical respiratory illness, while a score of 9-12 is associated with a 57% risk of progression to critical illness.ConclusionsA significant proportion of admitted COVID-19 patients decompensate within 24 hours of hospital presentation and these events are accurately predicted using bedside respiratory exam findings within a simple scoring system.
The Leipzig Catalogue of Vascular Plants (LCVP) – An improved taxonomic reference list for all known vascular plants
Authors: Freiberg Martin , Winter Marten , Gentile Alessandro , Zizka Alexander , Muellner-Riehl Alexandra Nora , Weigelt Alexandra , Wirth Christian 
Published: May 2020

AbstractThe lack of comprehensive and standardized taxonomic reference information is an impediment for robust plant research, e.g. in systematics, biogeography or macroecology. Here we provide an updated and much improved reference list of 1,315,479 scientific plant taxa names for all described vascular plant taxa names globally. The Leipzig Catalogue of Vascular Plants (LCVP; version 1.0.2) contains 351.176 accepted species (plus 6.160 natural hybrids), within 13.422 genera, 561 families and 84 orders. The LCVP a) contains more information on the taxonomic status of global plant names than any other similar resource and b) significantly improves the reliability of our knowledge by e.g. resolving the taxonomic status of ∼184.000 taxa names compared to The Plant List, the up to date most commonly used plant name resource. We used ∼4500 publications, existing relevant databases and available studies on molecular phylogenetics to construct a robust reference backbone. For easy access and integration into automated data processing pipelines, we provide an ‘R’-package (lcvplants) with the LCVP.
Efficacy of a novel iodine complex solution, CupriDyne, in inactivating SARS-CoV-2
Authors: Mantlo Emily , Evans Alex , Patterson-Fortin Laura , Boutros Jenny , Smith Richard , Paessler Slobodan 
Published: May 2020

AbstractThe coronavirus known as SARS-CoV-2, which causes COVID-19 disease, is presently responsible for a global pandemic wherein more than 3.5 million people have been infected and more than 250,000 killed to-date. There is currently no vaccine for COVID-19, leaving governments and public health agencies with little defense against the virus aside from advising or enforcing best practices for virus transmission prevention, which include hand-washing, physical distancing, use of face covers, and use of effective disinfectants. In this study, a novel iodine complex called CupriDyne®was assessed for its ability to inactivate SARS-CoV-2. CupriDyne was shown to be effective in inactivating the virus in a time-dependent manner, reducing virus titers by 99% (2 logs) after 30 minutes, and reducing virus titers to below the detection limit after 60 minutes. The novel iodine complex tested herein offers a safe and gentle alternative to conventional disinfectants for use on indoor and outdoor surfaces.
YTHDF1 drives intestinal immune response against bacterial infection
Authors: Zong Xin , Xiao Xiao , Shen Bin , Jiang Qin , Wang Hong , Lu Zeqing , Wang Fengqin , Jing Minliang , Wang Yizhen 
Published: May 2020

AbstractInvasion of pathogenic bacteria is a serious threat to intestinal health. Recent emerging evidence has demonstrated that N6-methyladenosine (m6A) is closely associated with innate immunity; however, the underlying mechanism remains unclear. Herein, we aim to explore the function and mechanism of m6A modification in the regulation of innate immune responses against bacterial pathogens in the intestine. Ribo-seq and m6A-seq data have demonstrated that YTHDF1, an m6A reader, directs the translation of tumor necrosis factor receptor-associated factor 6 (TRAF6) mRNA to regulate immune responses via modulation of m6A methylation near stop codon. Furthermore, we have identified a unique mechanism that the interaction between YTHDF1 and the host factor DDX60 are critical in regulating intestinal immune response against bacterial infection by recognizing TRAF6 target transcripts. Additionally, our results provide novel insights as to why YTHDF1 could recognize its unique targets using the same domain as other YTHDF proteins. This work identifies YTHDF1 as a key driver of intestinal immune responses and provides an avenue for development of novel strategies to modulate intestinal immune response against bacterial infection.
Whole Genome Sequences ofAedes aegypti(Linn.) Field Isolates from Southern India
Authors: Bernard Venitha , Moudgalya Sanjana , Reegan Daniel , Sreekanthreddy Peddagangannagari , Mohan Abhilash , Subramanya Hosahalli S , Vembar Shruthi Sridhar , Ghosh Sanjay 
Published: May 2020

ABSTRACTAedes spp. mosquitoes are a major health concern as they transmit several viral pathogens resulting in millions of deaths annually around the world. This is compounded by the emergence of insecticide-resistant strains and global warming, which could expose more than half of the world's population to Aedes-borne diseases in the future. Therefore, a comprehensive understanding of vector biology and the genomic basis of phenotypes such as insecticide resistance in natural populations are of paramount importance. Here, we sequenced the genome of Aedes aegypti mosquitos sampled from dengue-endemic areas and investigated the genetic variations between the previously reported laboratory-reared strain and our field isolates. The mosquito genomic DNA was used for paired-end sequencing using the Illumina platform. The reads were used for template-based assembly and mapped to the Aedes aegypti reference genome. Stringent parameters and multiple variant calling methods were used to identify unique single nucleotide variants (SNVs) and insertions-deletions (indels) and mapped to the Aedes chromosomes to create a draft consensus genome. Gene Ontology analyses was performed on the variant-enriched genes while two gene families involved in insecticide resistance were used for comparative sequence and phylogenetic analyses. Comparative sequence variant analyses showed that the majority of the high-quality variants in our samples mapped to non-coding regions of the genome, while gene ontology analyses of genic variants revealed enrichment of terms relevant to drug binding and insecticide resistance. Importantly, one mutation implicated in pyrethroid resistance was found in one Aedes sample. This is the first report of genome sequences of A. aegypti field isolates from India which reveals variants specific to the wild population. This is a useful resource which will facilitate development of robust integrated vector control strategies for management of Aedes-borne diseases through genetic manipulation of local mosquito populations.
The non-typeableHaemophilus influenzaemajor adhesin Hia is a dual function lectin that binds to human-specific respiratory tract sialic acid glycan receptors
Authors: Atack John M , Day Christopher J , Poole Jessica , Brockman Kenneth L. , Timms Jamie R L , Winter Linda E. , Haselhorst Thomas , Bakaletz Lauren O , Barenkamp Stephen J , Jennings Michael P 
Published: May 2020

AbstractNTHi is a human-adapted pathogen that colonises the human respiratory tract. Strains of NTHi express multiple adhesins, however there is a unique, mutually exclusive relationship between the major adhesins Hia and HMW1/2. Approximately 25% of NTHi strains express Hia, a phase-variable autotransporter protein, and which has a critical role in colonisation of the host nasopharynx. The remaining 75% of strains express HMW1/2. Previous work has shown that the HMW1 and HMW2 proteins mediate binding to 2,3- and 2,6-linked sialic acid glycans found in the human respiratory tract. Here we show that that the high affinity binding domain of Hia, binding domain 1 (BD1) is responsible for binding to α2,6-sialyllactosamine glycans. BD1 is highly specific for glycans that incorporate the form of sialic acid expressed by humans,N-acetylneuraminic acid (Neu5Ac). We further show that Hia has lower affinity binding activity for 2,3-linked sialic acid and that this binding activity is mediated via a distinct domain. Thus, Hia with its dual binding activities functionally mimics the combined activities of the HMW1 and 2 adhesins. In addition, we show that Hia has a role in biofilm formation by strains of NTHi that express the adhesin. Knowledge of the binding affinity of a major NTHi adhesin, and putative vaccine candidate, will direct and inform development of future vaccines and therapeutic strategies for this important pathogen.ImportanceHost-adapted bacterial pathogens like NTHi have evolved specific mechanisms to colonize their restricted host niche. Relatively few of the adhesins expressed by NTHi have been characterized as regards their binding affinity at the molecular level. In this work we show that the major NTHi adhesin, Hia, preferentially binds to Neu5Ac-α2,6-sialyllactosamine, the form of sialic acid expressed in humans. The receptors targeted by Hia in the human airway mirror those targeted by influenza A virus and indicates the broad importance of sialic acid glycans as receptors for airway pathogens.