bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ecological and evolutionary insights into pathogenic and non-pathogenic rice associatedXanthomonas
Authors: Bansal Kanika , Midha Samriti , Kumar Sanjeet , Kaur Amandeep , Sonti Ramesh V. , Patil Prabhu B. 
Published: October 2018

AbstractXanthomonas oryzaeis a devastating pathogen of rice worldwide, however,X. sontiiandX. maliensisare its non-pathogenic counterparts from the same host. So far, these non-pathogenic isolates were overlooked due to their less economic importance and lack of genomic information. We have carried out detailed ecological and evolutionary study focusing on diverse lifestyles of these strains. Phylogenomic analysis revealed two major lineages corresponding toX. sontii(ML-I) andX. oryzae(ML-II) species. Interestingly, one of the non-pathogenicXanthomonasstrains belonging toX. maliensisis intermediary to both the major lineages/species suggesting on-going diversification and selection. Accordingly, pangenome analysis revealed large number of lifestyle specific genes with atypical GC content indicating role of horizontal gene transfer in genome diversification. Our comprehensive comparative genomic investigation of major lineages has revealed that impact of recombination is more forX. sontiias compared toX. oryzae. Acquisition of type III secretion system and its effectome along with a type VI secretion system also seem to have played a major role in the pathogenic lineage. Other known key pathogenicity clusters or genes like biofilm forming cluster, cellobiohydrolase and non-fimbrial adhesin (yapH)are exclusive to pathogenic lineage. However, commonality of loci encoding exopolysacharide,rpfsignalling molecule, iron-uptake, xanthomonadin pigment, etc. suggests their essentiality in host adaptation. Overall, this study reveals evolutionary history of pathogenic and non-pathogenic strains and will further open up a new avenue for better management of pathogenic strains for sustainable cultivation of a major staple food crop.
Structure reveals mechanism of CRISPR RNA-guided nuclease recruitment and anti-CRISPR viral mimicry
Authors: Rollins MaryClare F. , Chowdhury Saikat , Carter Joshua , Golden Sarah M. , Miettinen Heini M. , Santiago-Frangos Andrew , Faith Dominick , Lawrence C. Martin , Lander Gabriel C. , Wiedenheft Blake 
Published: October 2018

AbstractBacteria and archaea have evolved sophisticated adaptive immune systems that rely on CRISPR RNA (crRNA)-guided detection and nuclease-mediated elimination of invading nucleic acids. Here we present the cryo-EM structure of the type I-F CRISPR RNA-guided surveillance complex (Csy complex) from Pseudomonas aeruginosa bound to a double-stranded DNA target. Comparison of this structure to previously determined structures of this complex reveals a Ȉ180-degree rotation of the C-terminal helical bundle on the “large” Cas8f subunit. We show that the dsDNA-induced conformational change in Cas8f exposes a Cas2/3 “nuclease recruitment helix” that is structurally homologous to a virally encoded anti-CRISPR protein (AcrIF3). Structural homology between Cas8f and AcrIF3 suggests that AcrIF3 is a mimic of the Cas8f “nuclease recruitment helix”, implying that cas genes may sometimes serve as genetic fodder for the evolution of anti-CRISPRs.
Highly Predictive Transdiagnostic Features Shared across Schizophrenia, Bipolar Disorder, and ADHD Identified Using a Machine Learning Based Approach
Authors: Liu Yuelu , Mellem Monika S. , Gonzalez Humberto , Kollada Matthew , Mahableshwarkar Atul R. , Madrid Annette , Martin William J. , Ahammad Parvez 
Published: October 2018

AbstractThe Diagnostic and Statistical Manual of Mental Disorders (DSM) is the standard for diagnosing psychiatric disorders in the United States. However, evidence has suggested that symptoms in psychiatric disorders are not restricted to the boundaries between DSM categories, implying an underlying latent transdiagnostic structure of psychopathology. Here, we applied an importance-guided machine learning technique for model selection to item-level data from self-reported instruments contained within the Consortium for Neuropsychiatric Phenomics dataset. From 578 questionnaire items, we identified a set of features which consisted of 85 items that were shared across diagnoses of schizophrenia (SCZ), bipolar disorder (BD), and attention deficit/hyperactivity disorder (ADHD). A classifier trained on the transdiagnostic features reliably distinguished the patient group as a whole from healthy controls (classification AUC = 0.95) and only 10 items were needed to attain the performance level of AUC being 0.90. A sum score created from the items produced high separability between patients and healthy controls (Cohen’s d = 2.85), and it outperformed predefined sum scores and sub-scores within the instruments (Cohen’s d ranging between 0.13 and 1.21). The transdiagnostic features comprised both symptom domains (e.g. dysregulated mood, attention deficit, and anhedonia) and personality traits (e.g. neuroticism, impulsivity, and extraversion). Moreover, by comparing the features that were common across the three patient groups with those that were most predictive of a single patient category, we can describe the unique features for each patient group superimposed on the transdiagnostic feature structure. Overall, our results reveal a latent transdiagnostic symptom/behavioral phenotypic structure shared across SCZ, BD, and ADHD and present a new perspective to understand insights offered by self-report psychiatric instruments.
Are protein-ligand complexes robust structures?
Authors: Majewski Maciej , Ruiz-Carmona Sergio , Barril Xavier 
Published: October 2018

ABSTRACTThe predominant view in structure-based drug design is that small-molecule ligands, once bound to their target structures, display a well-defined binding mode. While this is convenient from a design perspective, it ignores the fact that structural stability (robustness) is not necessary for thermodynamic stability (binding affinity). In fact, any potential benefit of a rigid binding mode will have to be balanced against the entropic penalty that it entails. Surprisingly, little is known about the causes, consequences and real degree of robustness of protein-ligand complexes. Here we investigate two diverse sets of structures, comprising 79 drug-like and 27 fragment ligands, respectively. We focus on hydrogen bond interactions (469 in total), as they have been described as essential for structural stability. We find that 75% of complexes are anchored by at least one robust hydrogen bond, the remaining 25% either form loose complexes or are constrained by other interactions types. The first type of complexes generally combine a single anchoring point with looser regions, thus balancing order and disorder. Completely constricted protein-ligand complexes are rare and seem to fulfil a functional necessity. Structural stability analysis reveals a hidden layer of complexity in protein-ligand complexes that should be considered in ligand design.
Caribbean golden orbweaving spiders maintain gene flow with North America
Authors: Čandek Klemen , Agnarsson Ingi , Binford Greta J. , Kuntner Matjaž 
Published: October 2018

AbstractThe Caribbean archipelago offers one of the best natural arenas for testing biogeographic hypotheses. The intermediate dispersal model of biogeography (IDM) predicts variation in species richness among lineages on islands to relate to their dispersal potential. To test this model, one would need background knowledge of dispersal potential of lineages, which has been problematic as evidenced by our prior biogeographic work on the Caribbean tetragnathid spiders. In order to investigate the biogeographic imprint of an excellent disperser, we study the AmericanTrichonephila, a nephilid genus that contains globally distributed species known to overcome long, overwater distances. Our results reveal that the AmericanT. clavipesshows a phylogenetic and population genetic structure consistent with a single species over the Caribbean, but not over the entire Americas. Haplotype network suggests that populations maintain lively gene flow between the Caribbean and North America. Combined with prior evidence from spider genera of different dispersal ability, these patterns coming from an excellent disperser (Trichonephila) that is species poor and of a relatively homogenous genetic structure, support the IDM predictions.
Dendritic spikes expand the range of well-tolerated population noise structures
Authors: Poleg-Polsky Alon 
Published: October 2018

AbstractThe brain operates surprisingly well despite the noisy nature of individual neurons. The central mechanism for noise mitigation in the nervous system is thought to involve averaging over multiple noise-corrupted inputs. Subsequently, there has been considerable interest recently to identify noise structures that can be integrated linearly in a way that preserves reliable signal encoding. By analyzing realistic synaptic integration in biophysically accurate neuronal models, I report a complementary de-noising approach that is mediated by focal dendritic spikes. Dendritic spikes might seem to be unlikely candidates for noise reduction due to their miniscule integration compartments and poor averaging abilities. Nonetheless, the extra thresholding step introduced by dendritic spike generation increases neuronal performance for a broad category of computational tasks, including analog and binary discrimination, as well as for a range of correlated and uncorrelated noise structures, some of which cannot be adequately resolved with averaging. This property of active dendrites compensates for compartment size constraints and expands the repertoire of brain states and presynaptic population activity dynamics can be reliably de-noised by biologically-realistic neurons.Significance StatementNoise, or random variability, is a prominent feature of the neuronal code and poses a fundamental challenge for information processing. To reconcile the surprisingly accurate output of the brain with the inherent noisiness of biological systems, previous work examined signal integration in idealized neurons. The notion that emerged from this body of work is that accurate signal representation relies largely on input averaging in neuronal dendrites. In contrast to the prevailing view, I show that de-noising in simulated neurons with realistic morphology and biophysical properties follows a different strategy: dendritic spikes act as classifiers that assist in extracting information from a variety of noise structures that have been considered before to be particularly disruptive for reliable brain function.
Cell-autonomous transcriptional mechanism for enhancement of translation capacity in secretory cells
Authors: Khetchoumian Konstantin , Balsalobre Aurélio , Mayran Alexandre , Christian Helen , Chénard Valérie , St-Pierre Julie , Drouin Jacques 
Published: October 2018

AbstractTranslation is a basic cellular process and its capacity is adapted to cell function. In particular, secretory cells achieve high protein synthesis levels without triggering the protein stress response. It is unknown how and when translation capacity is increased during differentiation. Here, we show that the transcription factor Creb3l2 is a scaling factor for translation capacity in secretory cells and that it directly binds ~75% of regulatory and effector genes for translation. In parallel with this cell-autonomous mechanism, implementation of the physiological UPR pathway prevents triggering the protein stress response. The pituitary differentiation factor Tpit activates Creb3l2 expression, the Creb3l2-dependent regulatory network as well as the physiological UPR pathway. Thus, Creb3l2 implements high basal translation levels through direct targeting of translation effector genes acting downstream of signaling pathways that otherwise regulate protein synthesis. Expression of Creb3l2 may be a useful means to enhance production of therapeutic proteins.
PS membrane asymmetry influences the folding and insertion of a transmembrane helix
Authors: Scott Haden L. , Heberle Frederick A. , Katsaras John , Barrera Francisco N. 
Published: October 2018

AbstractThe plasma membrane (PM) contains an asymmetric distribution of lipids between the inner and outer leaflets of its bilayer. A lipid of special interest in eukaryotic cells is the negatively charged phosphatidylserine (PS). In healthy cells, PS is actively sequestered to the inner leaflet of the PM but can redistribute to the outer leaflet when the cell is damaged or at the onset of apoptosis. The influence of PS asymmetry and its loss on membrane protein structure and organization have not been widely addressed. Marginally hydrophobic membrane proteins contain acidic residues in their transmembrane sequence, which can enable topological transitions after membrane association. The pH low insertion peptide (pHLIP), which undergoes a topological reorientation and inserts into the membrane at acidic pH – as its name implies, is a useful and well-characterized model for studying these transitions. Although it is known that the inclusion of PS in symmetric vesicles affects the membrane insertion process of pHLIP by lowering the pH midpoint of insertion, it is unclear how PS asymmetry influences these topological transitions. Here, we studied pHLIP’s topology using freely-floating asymmetric phosphatidylcholine (PC)/PS vesicles with PS enriched in the inner leaflet. We developed a modified protocol to create asymmetric vesicles containing PS and employed Annexin V labeled with an Alexa 568 fluorophore as a new probe to quantifying PS asymmetry. For pHLIP, membrane insertion was affected by the surface charge difference between bilayer leaflets caused by the asymmetric distribution of charged lipids between the leaflets. We thus conclude that lipid asymmetry can have consequences for the behavior of membrane-associated proteins. A corollary is that model studies using symmetric bilayers to mimic the PM may fail to capture important aspects of protein-membrane interactions.
fruitlessfunctions downstream ofdoublesexto promote sexual dimorphism of the gonad stem cell niche
Authors: Zhou Hong , Whitworth Cale , Pozmanter Caitlin , Neville Megan C. , Van Doren Mark 
Published: October 2018

SUMMARYBackgrounddoublesex(dsx) andfruitless(fru) are the two downstream transcription factors that actuateDrosophilasex determination. Whiledsxassistsfruto regulate sex-specific behavior, whetherfrucollaborates withdsxin regulating other aspects of sexual dimorphism remains unknown. One important aspect of sexual dimorphism is found in the gonad stem cell (GSC) niches, where male and female GSCs are regulated to create large numbers of sperm and eggs.ResultsHere we report that Fru is expressed male-specifically in the GSC niche and plays important roles in the development and maintenance of these cells. Unlike previously studied regulation of sex-specific Fru expression, which is regulated by alternative splicing by Transformer (Tra), we show that male-specific expression offruis regulated downstream ofdsx, and is independent of Tra. Regulation offrubydsxalso occurs in the nervous system.frugenetically interacts withdsxto support maintenance of the hub throughout development. Ectopic expression offruinhibited female niche formation and partially masculinized the ovary.fruis also required autonomously for cyst stem cell maintenance and cyst cell survival. Finally, we identified a conserved Dsx binding site upstream offrupromoter P4 that regulatesfruexpression in the hub, indicating thatfruis likely a direct target for transcriptional regulation by Dsx.ConclusionsThese findings demonstrate thatfruacts outside the nervous system to influence sexual dimorphism and reveal a new mechanism for regulating sex-specific expression offruthat is regulated at the transcriptional level by Dsx, rather than by alternative splicing by Tra.
Identifying Emerging Phenomenon in Plant Long Temporal Phenotyping Experiments
Authors: Peng Jiajie , Lu Junya , Hoh Donghee , Dina Ayesha S , Shang Xuequn , Kramer David M , Chen Jin 
Published: October 2018

AbstractThe rapid improvement of phenotyping capability, accuracy, and throughput have greatly increased the volume and diversity of phenomics data. A remaining challenge is an efficient way to identify phenotypic patterns to improve our understanding of the quantitative variation of complex phenotypes, and to attribute gene functions. To address this challenge, we developed a new algorithm to identify emerging phenomena from large-scale temporal plant phenotyping experiments. An emerging phenomenon is defined as a group of genotypes who exhibit a coherent phenotype pattern during a relatively short time. Emerging phenomena are highly transient and diverse, and are dependent in complex ways on both environmental conditions and development. Identifying emerging phenomena may help biologists to examine potential relationships among phenotypes and genotypes in a genetically diverse population and to associate such relationships with the change of environments or development. We present an emerging phenomenon identification tool called Temporal Emerging Phenomenon Finder (TEP-Finder). Using large-scale longitudinal phenomics data as input, TEP-Finder first encodes the complicated phenotypic patterns into a dynamic phenotype network. Then, emerging phenomena in different temporal scales are identified from dynamic phenotype network using a maximal clique based approach. Meanwhile, a directed acyclic network of emerging phenomena is composed to model the relationships among the emerging phenomena. The experiment that compares TEP-Finder with two state-of-art algorithms shows that the emerging phenomena identified by TEP-Finder are more functionally specific, robust, and biologically significant. The source code, manual, and sample data of TEP-Finder are all available at:http://phenomics.uky.edu/TEP-Finder/.
Why do a PhD in geography? A sympathetic response to ‘the career aspirations and expectations of geography students’
Authors: Sigler Thomas , Lieske Scott N. , Charles‐Edwards Elin , Corcoran Jonathan 
Published: October 2018

AbstractThis article provides commentary on the changing nature of the geography PhD. Taking as a point of departure Rae Dufty‐Jones's article on the career aspirations and expectations of geography doctoral students published in this journal earlier this year, we frame the paper around a series of propositions that prospective higher degree candidates may find useful. We buttress Dufty‐Jones's argument with numerical evidence that the “supply” of Australian PhDs outstrips “demand” by any reasonable measure. This evidence brings to light the question of whether a PhD in geography is meant to serve its traditional function as a threshold for an academic career and whether those pursuing non‐academic pathways should invest their time and effort in what may have become a “gladiatorial” pursuit. While the challenges facing PhD candidates are not insurmountable, they are not trivial. To optimise the experience and outcomes of a PhD, the needs and aspirations of candidates must be balanced, therefore, against the levels of support provided by universities. Candidates thus need to understand how such professional and personal aspirations fit in the contemporary higher education landscape and to appreciate what value a PhD holds—both to the individual and to society more broadly. We suggest two solutions to the pessimism of neoliberalisation and “massification”: greater emphasis on a terminal master's degree in geography and insistence that geographers promote disciplinary visibility to the greatest extent possible, with the hope that geographical approaches to problem‐solving are increasingly recognised across industry and government.
Unsafe drinking water quality in remote Western Australian Aboriginal communities
Authors: Rajapakse Jay , Rainer‐Smith Semone , Millar Graeme J. , Grace Peter , Hutton Allison , Hoy Wendy , Jeffries‐Stokes Christine , Hudson Brian 
Published: October 2018

AbstractChronic kidney disease (CKD) is important in the fields of public health and health geography because of its heavy burden on the health system and high cost of treatment in its advanced stages. The causes of CKD are associated with diabetes and hypertension, but in some parts of the world, the disease occurs in the absence of these factors. Researchers identify this condition as CKD of “unknown” causes (CKDu). CKDu is a multi‐factored health problem and one suspected causal factor is contaminated drinking water. The disease occurs globally but is found in particularly high concentrations among people of certain ethnic and disadvantaged social groups living in very different locations around the world. CKD has become endemic in Western Australia where hospital admissions for Aboriginal people requiring renal dialysis or treatment for diabetes are much higher than for the general population. The possible proportions of CKDu cases among the CKD patients are unknown. This study examines the drinking water quality among communities such as these. Water chemistry analysis in these areas indicates that the nitrate and uranium content greatly exceed officially recommended levels. Most of these communities rely on raw groundwater to supply their domestic needs, and it is very likely that the people are unwittingly ingesting high levels of nitrates and uranium, probably including uranyl nitrates. Very few such remote communities have access to treated drinking water, and cost‐effective water treatment systems are required to provide potable water at the local scale.
The effect of dexmedetomidine on delirium and agitation in patients in intensive care: systematic review and meta‐analysis with trial sequential analysis
Authors: Ng K. T. , Shubash C. J. , Chong J. S. 
Published: October 2018

SummaryDelirium is common in intensive care patients. Dexmedetomidine is increasingly used for sedation in this setting, but its effect on delirium remains unclear. The primary aim of this review was to examine whether dexmedetomidine reduces the incidence of delirium and agitation in intensive care patients. We sought randomised clinical trials in MEDLINE, EMBASE, PubMed and CENTRAL from their inception until June 2018. Observational studies, case reports, case series and non‐systematic reviews were excluded. Twenty‐five trials including 3240 patients were eligible for inclusion in the data synthesis. In the patients who received dexmedetomidine (eight trials, 1425 patients), delirium was reduced, odds ratio (95%CI) 0.36 (0.26–0.51), p < 0.001 and high quality of evidence. The use of dexmedetomidine was associated with a reduced incidence of agitation, OR (95%CI) 0.34 (0.20–0.59), p < 0.001, moderate quality of evidence. Patients who were randomly assigned to dexmedetomidine had a significantly higher incidence of bradycardia, OR (95%CI) 2.18 (1.46–3.24), p < 0.001, moderate quality of evidence; and hypotension, OR (95%CI) 1.89 (1.48–2.41), p < 0.001, high quality of evidence. We found no evidence of an effect on mortality, OR (95%CI) 0.86 (0.66–1.10), p = 0.23, moderate quality of evidence. The trial sequential analyses for the incidence of delirium, bradycardia and hypotension was conclusive but not for the incidence of agitation and mortality. In summary, this meta‐analysis suggests that dexmedetomidine reduces the incidence of delirium and agitation in intensive care patients. The general quality of evidence ranged from moderate to high.