bluuebunny/crossref_metadata_2025_split huggingface dataset:
TaxonTableTools - A comprehensive, platform-independent graphical user interface software to explore and visualise DNA metabarcoding data
Authors: Macher Till-Hendrik , Beermann Arne J. , Leese Florian 
Published: August 2020

AbstractDNA metabarcoding is increasingly used in research and application to assess biodiversity. Powerful analysis software exists to process raw data. However, when it comes to the translation of sequence read data into biological information many end users with limited bioinformatic expertise struggle with the downstream analysis and explore data only to a minor extent. Thus, there is a growing need for easy-to-use, graphical user interface (GUI) analysis software to analyse and visualise DNA metabarcoding data. We here present TaxonTableTools (TTT), a new platform independent GUI software that aims to fill this gap by providing simple and reproducible analysis and visualisation workflows. TTT uses a so-called “TaXon table” as input. This format can easily be generated within TTT from two input files: a read table and a taxonomy table that can be obtained by various published metabarcoding pipelines. TTT analysis and visualisation modules include e.g. Venn diagrams to compare taxon overlap among replicates, samples or among different analysis methods. It analyses and visualises basic statistics such as read proportion per taxon as well as more sophisticated visualisation such as interactive Krona charts for taxonomic data exploration. Various ecological analyses such as alpha or beta diversity estimates, and rarefaction analysis ordination plots can be produced directly. Data can be explored also in formats required by traditional taxonomy-based analyses of regulatory bioassessment programs. TTT comes with a manual and tutorial, is free and publicly available through GitHub (https://github.com/TillMacher/TaxonTableTools) and the Python package index (https://pypi.org/project/taxontabletools/).
Versatile, Multivalent Nanobody Cocktails Efficiently Neutralize SARS-CoV-2
Authors: Xiang Yufei , Nambulli Sham , Xiao Zhengyun , Liu Heng , Sang Zhe , Duprex W. Paul , Schneidman-Duhovny Dina , Zhang Cheng , Shi Yi 
Published: August 2020

AbstractThe outbreak of COVID-19 has severely impacted global health and the economy. Cost-effective, highly efficacious therapeutics are urgently needed. Here, we used camelid immunization and proteomics to identify a large repertoire of highly potent neutralizing nanobodies (Nbs) to the SARS-CoV-2 spike (S) protein receptor-binding domain (RBD). We discovered multiple elite Nbs with picomolar to femtomolar affinities that inhibit viral infection at sub-ng/ml concentration, more potent than some of the best human neutralizing antibodies. We determined a crystal structure of such an elite neutralizing Nb in complex with RBD. Structural proteomics and integrative modeling revealed multiple distinct and non-overlapping epitopes and indicated an array of potential neutralization mechanisms. Structural characterization facilitated the bioengineering of novel multivalent Nb constructs into multi-epitope cocktails that achieved ultrahigh neutralization potency (IC50s as low as 0.058 ng/ml) and may prevent mutational escape. These thermostable Nbs can be rapidly produced in bulk from microbes and resist lyophilization, and aerosolization. These promising agents are readily translated into efficient, cost-effective, and convenient therapeutics to help end this once-in-a-century health crisis.
Mutation ofIDR1enhances drought tolerance by reducing ROS production and activating ROS scavenging in rice
Authors: Zu Xiaofeng , Lu Yanke , Wang Qianqian , La Yumei , Tan Feng , Niu Jiayu , Xia Huihui , Hong Xinyue , Wu Yufeng , Zhou Shaoxia , Li Kun , Chen Huhui , Qiang Sheng , Rui Qi , Wang Huaqi , La Honggui 
Published: August 2020

AbstractTo discover new mutant alleles conferring enhanced tolerance to drought stress, we screened a mutagenized rice population (cv. IAPAR9) and identified a mutant, namedidr1-1(for increased drought resistance 1-1), with obviously increased drought tolerance under upland field conditions. Theidr1-1mutant possessed a significantly enhanced ability to tolerate high-drought stress in different trials. Map-based cloning revealed that the gene LOC_Os05g26890 (corresponding toD1orRGA1gene), residing in the mapping region ofIDR1locus, carried a single-base deletion in theidr1-1mutant, which caused a frameshift and premature translation termination. Complementation tests indicated that such a mutation was indeed responsible for the elevated drought tolerance inidr1-1mutant. IDR1 protein was localized in nucleus and to plasma membrane or cell periphery. Further investigations indicated that the significantly increased drought tolerance inidr1-1mutant stemmed from a range of physiological and morphological changes occurring in such a mutant, including greater leaf potentials, increased proline contents, heightened leaf thickness, and upregulation of antioxidant-synthesizing and drought-induced genes, etc., under drought-stressed conditions. Especially, ROS production from NADPH oxidases and chloroplasts might be remarkably impaired, while ROS-scavenging ability appeared to be markedly enhanced as a result of significantly elevated expression of a dozen ROS-scavenging enzyme genes inidr1-1mutant under drought-stressed conditions. Besides, IDR1 physically interacted with TUD1, andidr1-1mutant showed impaired EBR responsiveness. Altogether, these results suggest that mutation of IDR1 leads to alterations of multiple layers of regulations, which ultimately confers obviously enhanced drought tolerance to theidr1-1mutant.One-sentence summaryMutation ofIDR1significantly enhances drought tolerance in an upland cultivar IAPAR9 by decreasing apoplastic and chloroplastic ROS production and increasing ROS-scavenging ability
Leptin signaling regulates physiological damage and host-pathogen cooperation
Authors: Sanchez Karina K. , Troha Katia , Stengel Sarah , Ayres Janelle S. 
Published: August 2020

ABSTRACTTo combat infections, hosts employ a combination of antagonistic and cooperative defense strategies. The former refers to pathogen killing mediated by resistance mechanisms, while the latter refers to physiological defense mechanisms that promote host health during infection independent of pathogen killing, leading to an apparent cooperation between the host and the pathogen. Previous work has shown that leptin, a pleiotropic hormone that plays a central role in regulating appetite and energy metabolism, is indispensable for resistance mechanisms, while a role for leptin signaling in cooperative host-pathogen interactions remains unknown. Using a mouse model ofYersinia pseudotuberculosis(Yptb) infection, the causative agent of Far East scarlet-like fever, we unexpectedly found that genetic inhibition of leptin signaling conferred protection fromYptbinfection due to increased host-pathogen cooperation rather than greater resistance defenses. The protection againstYptbinfection was not due to differences in food consumption, lipolysis or fat mass. Furthermore, we found that the survival advantage was associated with increased liver damage and dysfunction. Our work reveals an additional level of complexity for the role of leptin in infection defense and suggests that in some contexts, in addition to tolerating the pathogen, tolerating organ damage and dysfunction is more beneficial for survival than preventing the damage.
A functional chromogen geneCfrom wild rice is involved in a different anthocyanin biosynthesis pathway inindicaandjaponica
Authors: Qiao Weihua , Wang Yanyan , Xu Rui , Yang Ziyi , Sun Yan , Su Long , Zhang Lizhen , Wang Junrui , Huang Jingfen , Zheng Xiaoming , Liu Shijia , Tian Yunlu , Chen Liangming , Liu Xi , Lan Jinhao , Yang Qingwen 
Published: August 2020

AbstractAccumulation of anthocyanin is a desirable trait to be selected in rice domestication, but the molecular mechanism of anthocyanin biosynthesis in rice remains largely unknown. In this study, a novel allele of chromogen geneC,OrC1, fromOryza rufipongonwas cloned and identified as a determinant regulator of anthocyanin biosynthesis. AlthoughOrC1functions in purple apiculus, leaf sheath and stigma inindicabackground, it only promotes purple apiculus injaponica. Transcriptome analysis revealed thatOrC1regulates flavonoid biosynthesis pathway and activates a few bHLH and WD40 genes of ternary MYB-bHLH-WD40 complex inindica. Differentially expressed genes and metabolites were found in theindicaandjaponicabackgrounds, indicating thatOrC1activated the anthocyanin biosynthetic genesOsCHI,OsF3H,OsANS,OsINSandOsANRand produced six metabolites independently. Artificial selection and domestication ofC1gene in rice occurred on the coding region in the two subspecies independently. Our results reveal the regulatory system and domestication ofC1, provide new insights into MYB transcript factor involved in anthocyanin biosynthesis, and show the potential of engineering anthocyanin biosynthesis in rice.Author summaryAccumulation of anthocyanin is a selection trait in rice domestication, whereas the mechanisms regulating the anthocyanin biosynthetic pathway in rice remain unresolved. Here, a novel allele of chromogen gene C from wild rice (Oryza rufipongon) was identified as a determinant regulator of anthocyanin biosynthesis. A key question is to what extent the involvement of the C1 gene can explain coloration variability of cultivated rice, where anthocyanin accumulation has been eliminated by artificial selection. Our results reveal the functional chromogen gene C from wild rice causes different coloration phenotypes, regulates various anthocyanin biosynthetic genes and produces different metabolites inindicaandjaponica. Artificial selection and domestication of the C1 gene in rice only occurs within the coding region of the two subspecies independently.
Dipeptidyl peptidase 9 triggers BRCA2 degradation by the N-degron pathway to promote DNA-damage repair
Authors: Silva-Garcia Maria , Bolgi Oguz , Ross Breyan , Pilla Esther , Kari Vijayalakshmi , Killisch Markus , Stark Nadine , Lenz Christof , Spitzner Melanie , Gorrell Mark D. , Grade Marian , Urlaub Henning , Dobbelstein Matthias , Huber Robert , Geiss-Friedlander Ruth 
Published: August 2020

SummaryDipeptidyl peptidase 9(DPP9) is a serine protease cleaving N-terminal dipeptides preferentially post-proline with (patho)physiological roles in the immune system and cancer. Only few DPP9 substrates are known. Here we identify an association of human DPP9 with the tumour suppressor BRCA2, a key player in repair of DNA double-strand breaks that promotes the formation of RAD51 filaments. This interaction is triggered by DNA-damage and requires access to the DPP9 active-site. We present crystallographic structures documenting the N-terminal Met1-Pro2of a BRCA21-40peptide captured in the DPP9 active-site. Mechanistically, DPP9 targets BRCA2 for degradation by the N-degron pathway, and promotes RAD51 foci formation. Both processes are phenocopied by BRCA2 N-terminal truncation mutants, indicating that DPP9 regulates both stability and the cellular stoichiometric interactome of BRCA2. Consistently, DPP9-deprived cells are hypersensitive to DNA-damage. Together, we identify DPP9 as a regulator of BRCA2, providing a possible explanation for DPP9 involvement in cancer development.
Contextual Prediction Errors Reorganize Episodic Memories in Time
Authors: Yazin Fahd , Das Moumita , Banerjee Arpan , Roy Dipanjan 
Published: August 2020

AbstractEpisodic memories are contextual experiences ordered in time. This is underpinned by associative binding between events within the same contexts. The role of prediction errors in strengthening declarative memory is well established but has not been investigated in the time dimension of complex episodic memories. Here we used 3-day movie viewing paradigm to test the hypothesis that contextual prediction errors leads to temporal organization of sequential memory processing. Our main findings uncover that prediction errors lead to changes in temporal organization of events, secondly, new unexpected sequences show as high accuracy as control sequences viewed repeatedly, and these effects are specifically due to prediction errors, and not novel associations. A drift-diffusion modelling further revealed a lower decision threshold for the newer, unexpected sequences compared to older sequences reflected by their faster recall leads to reorganization of episodes in time. Moreover, we found individual decision threshold could significantly predict their relative speed of sequence memory recall. Taking together our results suggest a temporally distinct role for prediction errors in ordering sequences of events in episodic memory.
A Connectome-Based Approach to Assess Motor Outcome after Neonatal Arterial Ischemic Stroke
Authors: Harrach Mariam Al , Pretzel Pablo , Groeschel Samuel , Rousseau François , Dhollander Thijs , Hertz-Pannier Lucie , Lefevre Julien , Chabrier Stéphane , Dinomais Mickael ,   on behalf of the AVCnn study group
Published: August 2020

AbstractObjectivestudies of motor outcome after Neonatal Arterial Ischemic Stroke (NAIS) often rely on lesion mapping using MRI. However, clinical measurements indicate that motor deficit can be different than what would solely be anticipated by the lesion extent and location. Because this may be explained by the cortical disconnections between motor areas due to necrosis following the stroke, the investigation of the motor network can help in the understanding of visual inspection and outcome discrepancy. In this study, we propose to examine the structural connectivity between motor areas in NAIS patients compared to healthy controls in order to define the cortical and subcortical connections that can reflect the motor outcomeMethods30 healthy controls and 32 NAIS patients with and without Cerebral Palsy (CP) underwent MRI acquisition and manual assessment. The connectome of all participants was obtained from T1-weighted and diffusion-weighted imaging.Resultssignificant disconnections in the lesioned and contra-lesioned hemispheres of patients were found. Furthermore, significant correlations were detected between the structural connectivity metric of specific motor areas and manuality assessed by the Box and Block Test (BBT) scores in patients.Interpretationusing the connectivity measures of these links the BBT score can be estimated using a multiple linear regression model. In addition, the presence or not of CP can also be predicted using the KNN classification algorithm. According to our results, the structural connectome can be an asset in the estimation of gross manual dexterity and can help uncover structural changes between brain regions related to NAIS.
Improved genetic prediction of complex traits from individual-level data or summary statistics
Authors: Zhang Qianqian , Privé Florian , Vilhjálmsson Bjarni , Speed Doug 
Published: August 2020

ABSTRACTMost existing tools for constructing genetic prediction models begin with the assumption that all genetic variants contribute equally towards the phenotype. However, this represents a suboptimal model for how heritability is distributed across the genome. Therefore, we develop prediction tools that allow the user to specify the heritability model. We compare individual-level data prediction tools using 14 UK Biobank phenotypes; our new tool LDAK-Bolt-Predict outperforms the existing tools Lasso, BLUP, Bolt-LMM and BayesR for all 14 phenotypes. We compare summary statistic prediction tools using 225 UK Biobank phenotypes; our new tool LDAK-BayesR-SS outperforms the existing tools lassosum, sBLUP, LDpred and SBayesR for 223 of the 225 phenotypes. The increase in prediction accuracy from improving the heritability model tends to be substantial. For example, when using LDAK-Bolt-Predict, the proportion of phenotypic variance explained increased by on average 14% (range 5-29%), equivalent to increasing the sample size by a quarter.
Acquired deficiency of the peroxisomal enzyme enoyl-CoA hydratase/3-hydroxyacyl CoA dehydrogenase is a metabolic vulnerability in hepatoblastoma
Authors: Wang Huabo , Chen Xiaoguang , Schwalbe Marie , Gorka Joanna E. , Mandel Jordan A. , Wang Jinglin , Lu Jie , Goetzman Eric S. , Dobrowolski Steven , Prochownik Edward V. 
Published: August 2020

AbstractMetabolic reprogramming provides transformed cells with proliferative and/or survival advantages. However, capitalizing on this therapeutically has been only moderately successful due to the relatively small magnitude of these differences and because cancers may re-program their metabolism to evade metabolic pathway inhibition. Mice lacking the peroxisomal bi-functional enzyme enoyl-CoA hydratase/3-hydroxyacyl CoA dehydrogenase (Ehhadh) and supplemented with the 12-carbon fatty acid lauric acid (C12) accumulate dodecanedioic acid (DDDA), a toxic C12 metabolite that causes hepatocyte necrosis and acute liver failure. In a murine model of pediatric hepatoblastoma (HB), down-regulation of Ehhadh also occurs in combination with a more general suppression of mitochondrial β- and peroxisomal ω-fatty acid oxidation (FAO) pathways. HB-bearing mice provided with C12 and/or DDDA-supplemented diets survived significantly longer than those on standard diets. The tumors also developed massive necrosis in response to short-term DDDA supplementation. Reduced Ehhadh was noted in murine hepatocellular carcinomas (HCCs) and in substantial subsets of human cancers, including HCCs. Acquired DDDA resistance was not associated with Ehhadh re-expression but was associated with 129 transcript differences ~90% of which were down-regulated in DDDA-resistant tumors and ~two-thirds of which correlated with survival in several human cancers. These transcripts often encoded components of the extracellular matrix suggesting that DDDA resistance arises from its reduced intracellular transport. Our results demonstrate the feasibility of a metabolic intervention that is non-toxic, inexpensive and likely compatible with traditional therapies. C12 and/or DDDA-containing diets could potentially be used to supplement other treatments or as alternative therapeutic choices.
Mu Opioid Receptor Gene Dosage Influences Reciprocal Social Behaviors and Nucleus Accumbens Microcircuitry
Authors: Toddes Carlee , Lefevre Emilia M. , Brandner Dieter D. , Zugschwert Lauryn , Rothwell Patrick E. 
Published: August 2020

ABSTRACTThe mu opioid receptor regulates reward derived from both drug use and natural experiences, including social interaction. Homozygous genetic knockout of the mu opioid receptor (Oprm1−/−) causes social deficits in mice, whereas partial dysregulation of mu opioid signaling has been documented in several neuropsychiatric disorders. Here, we investigated the social behavior of male and female mice with heterozygous genetic knockout of the mu opioid receptor (Oprm1+/−), modeling partial reduction of mu opioid signaling. Reciprocal social interaction and social conditioned place preference were diminished in Oprm1+/− and Oprm1−/− mutants of both sexes. Interaction with Oprm1 mutants also altered the social behavior of genotypical test partners. We corroborated this latter result using a social preference task, in which genotypical mice preferred interactions with another typical mouse over Oprm1 mutants. We also analyzed inhibitory synapses in the nucleus accumbens, a key brain region for mu opioid regulation of social behavior, using methods that differentiate between medium spiny neurons (MSNs) expressing the D1 or D2 dopamine receptor. Inhibitory synaptic transmission was increased in D2-MSNs of male mutants, but not female mutants, while the density of inhibitory synaptic puncta at the cell body of D2-MSNs was increased in both male and female mutants. These changes in nucleus accumbens microcircuitry were more robust in Oprm1+/− mutants than Oprm1−/− mutants, demonstrating that partial reductions of mu opioid signaling can have large effects on brain function and behavior. Our results support a role for partial dysregulation of mu opioid signaling in social deficits associated with neuropsychiatric conditions.
An Easy-to-Fabricate Cell Stretcher Reveals Density-Dependent Mechanical Regulation of Collective Cell Movements in Epithelia
Authors: Hart Kevin C. , Sim Joo Yong , Hopcroft Matthew A. , Cohen Daniel J. , Tan Jiongyi , Nelson W. James , Pruitt Beth L. 
Published: August 2020

AbstractIntroductionMechanical forces regulate many facets of cell and tissue biology. Studying the effects of forces on cells requires real-time observations of single- and multi-cell dynamics in tissue models during controlled external mechanical input. Many of the existing devices used to conduct these studies are costly and complicated to fabricate, which reduces the availability of these devices to many laboratories.MethodsWe show how to fabricate a simple, low-cost, uniaxial stretching device, with readily available materials and instruments that is compatible with high-resolution time-lapse microscopy of adherent cell monolayers. In addition, we show how to construct a pressure controller that induces a repeatable degree of stretch in monolayers, as well as a custom MATLAB code to quantify individual cell strains.ResultsAs an application note using this device, we show that uniaxial stretch slows down cellular movements in a mammalian epithelial monolayer in a cell density-dependent manner. We demonstrate that the effect on cell movement involves the relocalization of myosin downstream of Rho-associated protein kinase (ROCK).ConclusionsThis mechanical device provides a platform for broader involvement of engineers and biologists in this important area of cell and tissue biology. We used this device to demonstrate the mechanical regulation of collective cell movements in epithelia.
Sex-specific effects of developmental density on life history and age-dependent flight traits
Authors: Sanghvi Krish , Zajitschek Felix , Iglesias-Carrasco Maider , Head Megan L. 
Published: August 2020

AbstractThe environment organisms experience during development can have effects which carry over into their adult lives. These developmental environments may not only affect adult traits at a given point in time, but also how these traits change with age. Generally, stressful developmental environments can lead to sub-optimal adult fitness traits and a faster deterioration of these traits with age. But whether these environments affect how performance traits change with age or whether they affect males and females differently lacks evidence. Here, we test the sex-specific effects of crowding during development on life history traits such as lifespan, fecundity, age-dependent survival, and reproductive senescence, as well as flight performance traits, in the seed beetle-Callosobruchus maculatus. We show that although developmental crowding has no effect on flight performance of either sex, on male adult lifespan, or on female age-dependant survival, it is detrimental to female lifespan and fecundity, as well as female age-dependent reproduction. Additionally, we show that flight traits can change with age and differ between males and females, which may be reflective of sex-specific life-histories and behaviour. Our study has implications for understanding how developmental environments affect life history and behavioural strategies of both males and females.