bluuebunny/crossref_metadata_2025 huggingface dataset:
Sumoylation E3 Ligase SIZ1 Modulates Plant Immunity Partly through the Immune Receptor Gene SNC1 in Arabidopsis
Authors: Gou Mingyue , Huang Quansheng , Qian Weiqiang , Zhang Zemin , Jia Zhenhua , Hua Jian
Published: April 2017

The small ubiqutin-like modifier E3 ligase SIZ1 regulates multiple processes in Arabidopsis, including salicylic-acid-dependent immune responses. However, the targets of SIZ1 in plant immunity are not known. Here, we provide evidence that the plant immune receptor nucleotide-binding leucine-rich repeat gene SNC1 partially mediates the regulation of plant immunity by SIZ1. The siz1 loss-of-function mutant has an autoimmune phenotype that is dependent on SNC1 and temperature. Overexpression of SIZ1 partially rescues autoimmune mutant phenotypes induced by activation or overaccumulation of SNC1, and the SNC1 protein amount is attenuated by SIZ1 overexpression. In addition, overexpression of the F-box protein CPR1 that degrades the SNC1 protein inhibits the growth defects and disease resistance of the siz1 mutant. Furthermore, we found that the SNC1 protein is sumoylated in planta. Although it remains to be determined whether SIZ1 primarily modulates the SNC1 protein via sumoylation or affects SNC1 transcript level, our data indicate that SNC1 is a major mediator of defense response modulated by SIZ1 and that SNC1 is a crucial target for fine-tuning plant defense responses.
Quaternary Ammonium Compounds as New Sanitizers for Reducing the Spread of the Olive Knot Pathogen on Orchard Equipment
Authors: Nguyen K. A. , Förster H. , Adaskaveg J. E.
Published: April 2017

Olive knot, caused by the wound pathogen Pseudomonas savastanoi pv. savastanoi, is a serious bacterial disease that can be disseminated by orchard equipment. Greenhouse studies confirmed that cutting tools contaminated during contact with olive knots are able to spread the pathogen to healthy olive tissue. Quaternary ammonium compounds (QACs) were assessed as sanitizing agents for contaminated equipment as a disease management strategy. In laboratory in vitro tests, QACs exhibited high toxicity against the bacterium over a broad pH range from 6 to 9 using short exposure periods (15 to 60 s) and low concentrations (5 µg/ml). QACs applied to contaminated hard surfaces in the presence of an organic load reduced bacterial recovery by ≥3.6 log10 CFU/ml. In field trials, sanitation of hedging equipment that was contaminated with the pathogen (2 × 107 CFU/ml) and used to prune olives, was successful and sometimes completely prevented new infections from occurring. Application of additional foliar spray treatments of copper or copper-kasugamycin mixtures after hedging significantly improved disease control. In laboratory and field studies, sodium hypochlorite was significantly less effective than QAC compounds in the presence of organic matter. A nonphenolic QAC formulation, however, was ineffective as a preventative treatment when applied prior to inoculation of olive wounds, whereas a copper hydroxide application was highly effective. Based on data from this research, a QAC formulation was registered for field use as a sanitizer for olive equipment in California in 2015.
Rare Pyrenophora teres Hybridization Events Revealed by Development of Sequence-Specific PCR Markers
Authors: Poudel Barsha , Ellwood Simon R. , Testa Alison C. , McLean Mark , Sutherland Mark W. , Martin Anke
Published: April 2017

Pyrenophora teres f. teres and P. teres f. maculata cause net form and spot form, respectively, of net blotch on barley (Hordeum vulgare). The two forms reproduce sexually, producing hybrids with genetic and pathogenic variability. Phenotypic identification of hybrids is challenging because lesions induced by hybrids on host plants resemble lesions induced by either P. teres f. teres or P. teres f. maculata. In this study, 12 sequence-specific polymerase chain reaction markers were developed based on expressed regions spread across the genome. The primers were validated using 210 P. teres isolates, 2 putative field hybrids (WAC10721 and SNB172), 50 laboratory-produced hybrids, and 7 isolates collected from barley grass (H. leporinum). The sequence-specific markers confirmed isolate WAC10721 as a hybrid. Only four P. teres f. teres markers amplified on DNA of barley grass isolates. Amplified fragment length polymorphism markers suggested that P. teres barley grass isolates are genetically different from P. teres barley isolates and that the second putative hybrid (SNB172) is a barley grass isolate. We developed a suite of markers which clearly distinguish the two forms of P. teres and enable unambiguous identification of hybrids.
Intraoperative Assessment of Syndesmotic Injury and How to Assess if the Syndesmosis is Reduced
Authors: Dowdle S. Blake , Duchman Kyle R. , Phisitkul Phinit , Amendola Annunziato
Published: April 2017

Injuries to the tibiofibular syndesmosis are common, both as isolated injuries and as a component of rotational ankle fractures. Recent evidence suggests a high incidence of tibiofibular syndesmosis malreduction with poor clinical outcomes associated with syndesmotic malreduction. Despite the notable clinical consequences of malreduction and heightened awareness surrounding the issue of syndesmotic malreduction, intraoperative methods to assess the adequacy of syndesmotic reduction remain imperfect. Although postoperative axial computed tomographic (CT) scans are often used to assess the adequacy of syndesmotic reduction postoperatively, the routine use of intraoperative CT is limited by the availability of technology as well as the limited ability to perform side-by-side comparison with the uninjured ankle intraoperatively. Although more readily available for intraoperative assessment, fluoroscopy has consistently demonstrated shortcomings with respect to assessment of syndesmotic reduction. Although the literature clearly suggests that there is no perfect method to consistently obtain anatomic reduction of the syndesmosis, several intraoperative methods to optimize syndesmotic malreduction, including the importance of anatomic fracture fixation, open visualization of syndesmotic reduction, posterior inferior tibiofibular ligament repair or anatomic posterior malleolar fracture fixation, and deep deltoid ligament repair, have been suggested. The following will include a review of these concepts as well as relevant recent literature to provide a basis for improving methods to assess the adequacy of syndesmotic reduction intraoperatively.
Parent-Reported Severity and Health/Educational Services Use Among US Children with Autism: Results from a National Survey
Authors: Zuckerman Katharine E. , Friedman Nora D. B. , Chavez Alison E. , Shui Amy M. , Kuhlthau Karen A.
Published: April 2017

Objective:

Little national data exist regarding service use patterns for children with autism spectrum disorder (ASD) of varying severity. This study aimed to assess the relationship between parent-reported severity and use of educational and health care services.

Methods:

Data from the 2011 Survey of Pathways to Diagnosis and Services were used to examine a nationally representative sample of 1420 US children aged 6 to 17 years with ASD, with or without developmental delay and intellectual disability. Weighted multivariable logistic regression assessed associations of parent-reported ASD severity and child sociodemographic characteristics with school-based therapy, non-school-based therapy, behavioral interventions, and specialty provider visits.

Results:

Higher parent-reported ASD severity was associated with increased likelihood of current use of school-based therapy (adjusted odds ratio [AOR] = 4.08, 95% confidence interval =1.85–8.98), non-school-based therapy (AOR = 3.60 [1.95–6.66]), and behavioral interventions (AOR = 2.30 [1.22–4.34]), as well as regular specialty provider visits (AOR = 2.99 [1.38–6.46]). Although rates of service use were generally highest among children with severe ASD, non-school-based therapy and behavioral interventions were only used by about half of children with severe ASD, and about 1 in 4 children with mild ASD were using none of the therapies asked about.

Conclusion:

Parent-reported severity is associated with increased therapy and specialty provider service use among children with ASD. However, substantial variability exists in service use across levels of severity.
Descemetorhexis Without Graft Placement for the Treatment of Fuchs Endothelial Dystrophy: Preliminary Results and Review of the Literature
Authors: Iovieno Alfonso , Neri Alberto , Soldani Anna Maria , Adani Chantal , Fontana Luigi
Published: April 2017

Purpose:

To report our preliminary experience with a central descemetorhexis without graft placement in Fuchs endothelial corneal dystrophy (FECD) and to review the existing literature on the topic.

Methods:

A 4-mm central descemetorhexis was performed in 5 patients (4 women, 1 man; mean age: 69.8 ± 8.6 yrs; range: 57–78 yrs) with FECD. All patients had central confluent guttae, undetectable central endothelial cell count, healthy peripheral corneal endothelium, no clinically evident bullous keratopathy, and no ocular comorbidities. In 3 patients, the procedure was combined with phacoemulsification and intraocular lens implantation.

Results:

All patients completed at least 6 months of postoperative follow-up (mean follow-up 9 ± 2.5 mo; 7–13 mo). Endothelial repopulation of the central stroma was completed in all patients by the third month. Corneal clarity was achieved in 4 of 5 patients. The patient with persistent edema and haze had the highest preoperative central pachymetry. A final improvement in corrected visual acuity was achieved in 4/5 patients. A reduction in preoperative central pachymetry was observed in all cases. All patients developed deep stromal opacities around the margin of the descemetorhexis, which did not resolve over the follow-up time. Abnormal corneal topography and irregular astigmatism developed in 3 of 5 patients; these patients achieved 20/20 corrected distance visual acuity with rigid gas-permeable contact lens fitting.

Conclusions:

In partial concordance with previous studies, preliminary outcomes of a central descemetorhexis in FECD performed without endothelial graft placement seemed rather unpredictable. Baring of central stroma may trigger a variable wound-healing response with subsequent posterior stromal scarring and topographical irregularity.
Effects of Tear Film Lipid Layer Thickness and Blinking Pattern on Tear Film Instability After Corneal Refractive Surgery
Authors: Chen Qingzhong , Li Min , Yuan Ying , Me Rao , Yu Yunjie , Shi Guangsen , Wang Xin , Ke Bilian
Published: April 2017

Purpose:

To investigate associations between changes in tear film instability and the lipid layer thickness (LLT) and blink pattern after corneal refractive surgery (CRS).

Methods:

Forty patients were enrolled in this study. The LLT and blink pattern were evaluated 1 week before and 30 days after CRS using a novel interferometer and an ocular surface disease index (OSDI) questionnaire, and other tear film stability markers were also evaluated.

Results:

Mean OSDI scores increased from 5.52 to 8.54 (P = 0.016), corneal fluorescence staining scores increased from 0.05 to 0.25 (P = 0.034), first noninvasive tear breakup time (NIBUT-F) decreased from 9.66 to 7.33 seconds (P = 0.014), and average noninvasive tear breakup time (NIBUT-Ave) decreased from 12.32 to 10.26 seconds (P = 0.047) 1 month after CRS. Meanwhile, mean total blink frequency in 20 seconds decreased significantly from 12.62 to 6.31 (P < 0.001); LLT did not change significantly (P = 0.447). The change in NIBUT-Ave was positively correlated with that in LLT (P = 0.003) and negatively correlated with that in the partial blink rate (P = 0.013). The changes in the OSDI questionnaire, NIBUT, LLT, and blink pattern were not different between the laser-assisted in situ keratomileusis and laser-assisted subepithelial keratomileusis groups.

Conclusions:

A decrease in tear film stability occurs 1 month after CRS, the change in the blink pattern and unchanged LLT preoperatively and postoperatively suggesting that these parameters play a role in maintaining tear film stability after CRS.
Use of Population Pharmacokinetics and Electronic Health Records to Assess Piperacillin–Tazobactam Safety in Infants
Authors: Salerno Sara , Hornik Christoph P. , Cohen-Wolkowiez Michael , Smith P. Brian , Ku Lawrence C. , Kelly Matthew S. , Clark Reese , Gonzalez Daniel
Published: April 2017

Background:

Piperacillin, in combination with tazobactam, is frequently used in infants for treating nosocomial infections, although safety data in this population are limited. Electronic health record (EHR) data can be used to evaluate drug safety in infants, but measures of drug exposure are lacking.

Methods:

To relate simulated piperacillin exposure with adverse events (AEs) in infants using EHR data, we identified infants discharged from 333 neonatal intensive care units managed by the Pediatrix Medical Group between 1997 and 2012. Using a previously published population pharmacokinetic model in the target population, we simulated piperacillin steady state area under the concentration versus time curve from zero to τ (AUCss,0-τ
) and steady state maximal drug concentration (Cmaxss). Next, we used multivariable logistic regression to evaluate the association between simulated AUCss,0-τ
and Cmaxss with clinical AEs (seizure and rash) and laboratory AEs controlling for gestational age. The odds ratios (95% confidence intervals) comparing the third versus the first tertiles for AUCss,0-τ
and Cmaxss were reported.

Results:

We identified 746 infants with a median (interquartile range) gestational age of 30 weeks (26–33) and postnatal age of 11 days (6–25). The median (interquartile range) piperacillin dose was 225 mg/kg/d (176–300). No significant associations were found between simulated piperacillin exposure (AUCss,0-τ
and Cmaxss) and clinical and laboratory AEs.

Conclusions:

We found no associations between predicted piperacillin exposures and the occurrence of AEs. This study confirms the feasibility of using population pharmacokinetics and EHR to relate drug exposure with safety.
HIV Transmission to Premature Very Low Birth Weight Infants
Authors: Levin Candyce , Le Roux David M. , Harrison Michael C. , Tooke Lloyd
Published: April 2017

There is sparse literature about HIV transmission in preterm infants. Eighty-two HIV-exposed preterm infants received birth polymerase chain reactions (PCRs). Five (6.1%) were HIV positive with all 5 mothers receiving inadequate antiretrovirals. Of the PCR-negative infants, 9 died and 87% of the survivors received further PCR testing which remained negative. With correct care, intrapartum transmission of HIV can virtually be eliminated.
Bayesian inference of cancer driver genes using signatures of positive selection
Authors: Zapata Luis , Susak Hana , Drechsel Oliver , Friedländer Marc R. , Estivill Xavier , Ossowski Stephan
Published: April 2017

Tumors are composed of an evolving population of cells subjected to tissue-specific selection, which fuels tumor heterogeneity and ultimately complicates cancer driver gene identification. Here, we integrate cancer cell fraction, population recurrence, and functional impact of somatic mutations as signatures of selection into a Bayesian inference model for driver prediction. In an in-depth benchmark, we demonstrate that our model, cDriver, outperforms competing methods when analyzing solid tumors, hematological malignancies, and pan-cancer datasets. Applying cDriver to exome sequencing data of 21 cancer types from 6,870 individuals revealed 98 unreported tumor type-driver gene connections. These novel connections are highly enriched for chromatin-modifying proteins, hinting at a universal role of chromatin regulation in cancer etiology. Although infrequently mutated as single genes, we show that chromatin modifiers are altered in a large fraction of cancer patients. In summary, we demonstrate that integration of evolutionary signatures is key for identifying mutational driver genes, thereby facilitating the discovery of novel therapeutic targets for cancer treatment.
Describing the Local Structure of Sequence Graphs
Authors: Rosen Yohei , Eizenga Jordan , Paten Benedict
Published: April 2017

Analysis of genetic variation using graph structures is an emerging paradigm of genomics. However, defining genetic sites on sequence graphs remains an open problem. Paten’s invention of theultra-bubbleandsnarl, special subgraphs of sequence graphs which can identified with efficient algorithms, represents important first step to segregating graphs into genetic sites. We extend the theory of ultrabubbles to a special subclass where every detail of the ultrabubble can be described in a series and parallel arrangement of genetic sites. We furthermore introduce the concept ofbundlestructures, which allows us to recognize the graph motifs created by additional combinations of variation in the graph, including but not limited to runs of abutting single nucleotide variants. We demonstrate linear-time identification of bundles in a bidirected graph. These two advances build on initial work on ultrabubbles in bidirected graphs, and define a more granular concept of genetic site.
Competition between histone and transcription factor binding regulates the onset of transcription in zebrafish embryos
Authors: Joseph Shai R. , Pálfy Máté , Hilbert Lennart , Kumar Mukesh , Karschau Jens , Zaburdaev Vasily , Shevchenko Andrej , Vastenhouw Nadine L.
Published: April 2017

Upon fertilization, the genome of animal embryos remains transcriptionally inactive until the maternal-to-zygotic transition. At this time, the embryo takes control of its development and transcription begins. How the onset of zygotic transcription is regulated remains unclear. Here, we show that a dynamic competition for DNA binding between nucleosome-forming histones and transcription factors regulates zebrafish genome activation. Taking a quantitative approach, we found that the concentration of non-DNA bound core histones sets the time for the onset of transcription. The reduction in nuclear histone concentration that coincides with genome activation does not affect nucleosome density on DNA, but allows transcription factors to compete successfully for DNA binding. In agreement with this, transcription factor binding is sensitive to histone levels and the concentration of transcription factors also affects the time of transcription. Our results demonstrate that the relative levels of histones and transcription factors regulate the onset of transcription in the embryo.
Genome-Wide Mechanisms of Lifespan Extension by Dietary Restriction in Yeast
Authors: Campos Sergio E. , Garay Erika , Avelar-Rivas J. Abraham , Juárez-Reyes Alejandro , DeLuna Alexander
Published: April 2017

Dietary restriction is arguably the most promising non-pharmacological intervention to extend human life and health span. Yet, only few genetic regulators mediating the cellular response to dietary restriction are known, and the question remains which other transcription factors and regulatory pathways are involved. To gain a comprehensive view of how lifespan extension under dietary restriction is elicited, we screened the chronological lifespan of most gene deletions ofSaccharomyces cerevisiaeunder two dietary regimens, restricted and non-restricted. We identified 472 mutants with enhanced or diminished extension of lifespan by dietary restriction. Functional analysis of such dietary-restriction genes revealed novel processes underlying longevity specifically by dietary restriction. Importantly, this set of genes allowed us to generate a prioritized catalogue of transcription factors orchestrating the dietary-restriction response, which underscored the relevance of cell-cycle arrest control as a key mechanism of chronological longevity in yeast. We show that the transcription factor Ste12 is needed for full lifespan extension and cell-cycle arrest in response to nutrient limitation; linking the pheromone/invasive growth pathway with cell survivorship. Strikingly,STE12overexpression was sufficient to extend chronological lifespan under non-restricted conditions. Our global picture of the genetic players of longevity by dietary restriction highlights intricate regulatory cross-talks in aging cells.
Limited contribution of rare, noncoding variation to autism spectrum disorder from sequencing of 2,076 genomes in quartet families
Authors: Werling Donna M. , Brand Harrison , An Joon-Yong , Stone Matthew R. , Glessner Joseph T. , Zhu Lingxue , Collins Ryan L. , Dong Shan , Layer Ryan M. , Markenscoff-Papadimitriou Eirene , Farrell Andrew , Schwartz Grace B. , Currall Benjamin B. , Dea Jeanselle , Duhn Clif , Erdman Carolyn , Gilson Michael , Handsaker Robert E. , Kashin Seva , Klei Lambertus , Mandell Jeffrey D. , Nowakowski Tomasz J. , Liu Yuwen , Pochareddy Sirisha , Smith Louw , Walker Michael F. , Wang Harold Z. , Waterman Mathew J. , He Xin , Kriegstein Arnold R. , Rubenstein John L. , Sestan Nenad , McCarroll Steven A. , Neale Ben M. , Coon Hilary , Willsey A. Jeremy , Buxbaum Joseph D. , Daly Mark J. , State Matthew W. , Quinlan Aaron , Marth Gabor T. , Roeder Kathryn , Devlin Bernie , Talkowski Michael E. , Sanders Stephan J.
Published: April 2017

Genomic studies to date in autism spectrum disorder (ASD) have largely focused on newly arising mutations that disrupt protein coding sequence and strongly influence risk. We evaluate the contribution of noncoding regulatory variation across the size and frequency spectrum through whole genome sequencing of 519 ASD cases, their unaffected sibling controls, and parents. Cases carry a small excess ofde novo(1.02-fold) noncoding variants, which is not significant after correcting for paternal age. Assessing 51,801 regulatory classes, no category is significantly associated with ASD after correction for multiple testing. The strongest signals are observed in coding regions, including structural variation not detected by previous technologies and missense variation. While rare noncoding variation likely contributes to risk in neurodevelopmental disorders, no category of variation has impact equivalent to loss-of-function mutations. Average effect sizes are likely to be smaller than that for coding variation, requiring substantially larger samples to quantify this risk.
Gamma oscillations in the rat ventral striatum originate in the piriform cortex
Authors: Carmichael James E. , Gmaz Jimmie M. , van der Meer Matthijs A. A.
Published: April 2017

Local field potentials (LFP) recorded from the human and rodent ventral striatum (vStr) exhibit prominent, behaviorally relevant gamma-band oscillations. These oscillations are related to local spiking activity and transiently synchronize with anatomically related areas, suggesting a possible role in organizing vStr activity. However, the origin of vStr gamma is unknown. We recorded vStr gamma oscillations across a 1.4mm2grid spanned by 64 recording electrodes as rats rested and foraged for rewards, revealing a highly consistent power gradient originating in the adjacent piriform cortex. Phase differences across the vStr were consistently small (<10°) and current source density analysis further confirmed the absence of local sink-source pairs in the vStr. Reversible occlusions of the ipsilateral (but not contralateral) nostril, known to abolish gamma oscillations in the piriform cortex, strongly reduced vStr gamma power and the occurrence of transient gamma-band events. These results imply that local circuitry is not a major contributor to gamma oscillations in the vStr LFP, and that piriform cortex is an important driver of gamma-band oscillations in the vStr and associated limbic areas.

Significance Statement

The ventral striatum is an area of anatomical convergence in circuits underlying motivated behavior, but it remains unclear how its inputs from different sources interact. One of the major proposals of how neural circuits may dynamically switch between convergent inputs is through temporal organization reflected in local field potential (LFP) oscillations. Our results show that in the rat, the mechanisms controlling vStr gamma oscillations are primarily located in the in the adjacent piriform cortex, rather than vStr itself. This provides a novel interpretation of previous rodent work on gamma oscillations in the vStr and related circuits, and an important consideration for future work seeking to use oscillations in these areas as biomarkers in rodent models of human behavioral and neurological disorders.
Comparison of NMR and crystal structures of membrane proteins and computational refinement to improve model quality
Authors: Leman Julia Koehler , D’Avino Andrew R. , Bhatnagar Yash , Gray Jeffrey J.
Published: April 2017

Membrane proteins are challenging to study and restraints for structure determination are typically sparse or of low resolution because the membrane environment that surrounds them leads to a variety of experimental challenges. When membrane protein structures are determined by different techniques in different environments, a natural question is “which structure is most biologically relevant?” Towards answering this question, we compiled a dataset of membrane proteins with known structures determined by both solution NMR and X-ray crystallography. By investigating differences between the structures, we found that RMSDs between crystal and NMR structures are below 5 Å in the membrane region, NMR ensembles have a higher convergence in the membrane region, crystal structures typically have a straighter transmembrane region, have higher stereo-chemical correctness, and are more tightly packed. After quantifying these differences, we used high-resolution refinement of the NMR structures to mitigate them, which paves the way for identifying and improving the structural quality of membrane proteins.
The Unique Protein-To-Protein Carotenoid Transfer Mechanism
Authors: Maksimov Eugene G. , Sluchanko Nikolai N. , Slonimskiy Yury B. , Mironov Kirill S. , Klementiev Konstantin E. , Moldenhauer Marcus , Friedrich Thomas , Los Dmitry A. , Paschenko Vladimir Z. , Rubin Andrew B.
Published: April 2017

Orange Carotenoid Protein (OCP) is known to be an effector and regulator of cyanobacterial photoprotection. This 35 kDa water-soluble protein provides specific environment for keto-carotenoids, the excitation of which induced by the absorption of blue-green light causes dramatic but fully reversible rearrangements of the OCP structure, including carotenoid translocation and separation of C- and N-terminal domains upon transition from the basic orange to photoactivated red OCP form. While recent studies significantly improved our understanding of the OCP photocycle and interaction with phycobilisomes and the fluorescence recovery protein, the mechanism of OCP assembly remains unclear. Apparently, this process requires targeted delivery and incorporation of a highly hydrophobic carotenoid molecule into the water-soluble apoprotein of OCP. Recently, we introduced a novel carotenoid carrier protein, COCP, which consists of dimerized C-domain(s) of OCP and can combine with the isolated N-domain to form transient OCP-like species. Here, we demonstrate that in vitro COCP efficiently transfers otherwise tightly bound carotenoid to the full-length OCP apoprotein, resulting in formation of the photoactive OCP from completely photoinactive species. We accurately analyze peculiarities of this carotenoid transfer process which, to the best of our knowledge, seems unique, previously uncharacterized protein-to-protein carotenoid transfer process. We hypothesize that a similar OCP assembly can occur in vivo, substantiating specific roles of the COCP carotenoid carrier in cyanobacterial photoprotection.
A Collection of 2,280 Public Domain (CC0) Curated Human Genotypes
Authors: Shaw Richard J. , Corpas Manuel
Published: April 2017

Cheap sequencing has driven the proliferation of big human genome data aggregation consortiums, providing extensive reference datasets for genome research. These datasets, however, may come with restrictive terms of use, conditioned by the consent frameworks within which individuals donate their data. Having an aggregated genome dataset with unrestricted use, analogous to public domain licensing, is therefore unusually rare. Yet public domain data is tremendously useful because it allows freedom to perform research with it. This comes with the price of donors surrendering their privacy and accepting the associated risks derived from publishing personal data. Using the Repositive platform (https://repositive.io/?23andMe), an indexing service for human genome datasets, we aggregated all deposited files in public data sources under a CC0 license from 23andMe, a leading Direct-to-Consumer genetic testing service. After downloading 3,137 genotypes, we filtered out those that were incomplete, corrupt or duplicated, ending up with a dataset of 2,280 curated files, each one corresponding to a unique individual. Although the size of this dataset is modest compared to current major genome data aggregation projects, its full access and licensing terms, which allows free reuse without attribution, make it a useful reference pool for validation purposes and control experiments.
Ras/MAPK modifier loci revealed by eQTL inC. elegans
Authors: Sterken Mark G. , van Bemmelen van der Plaat Linda , Riksen Joost A. G. , Rodriguez Miriam , Schmid Tobias , Hajnal Alex , Kammenga Jan E. , Snoek Basten L.
Published: April 2017

The oncogenic Ras/MAPK pathway is evolutionarily conserved across metazoans. Yet, almost all our knowledge on this pathway comes from studies using single genetic backgrounds, whereas mutational effects can be highly background dependent. Therefore, we lack insight in the interplay between genetic backgrounds and the Ras/MAPK-signaling pathway. Here, we used aCaenorhabditis elegansRIL population containing a gain-of-function mutation in the Ras/MAPK pathway genelet-60and measured how gene expression regulation is affected by this mutation. We mapped eQTL and found that the majority (~73%) of the 1516 detectedcis-eQTL were not specific for thelet-60mutation, whereas most (~76%) of the 898 detectedtrans-eQTL were associated with thelet-60mutation. We detected 6 eQTLtrans-bands specific for the interaction between the genetic background and the mutation, one of which co-localized with the polymorphic Ras/MAPK modifieramx-2. Comparison between transgenic lines expressing allelic variants ofamx-2showed the involvement ofamx-2in 79% of thetrans-eQTL for genes mapping to thistrans-band. Together, our results have revealed loci hidden loci affecting Ras/MAPK signaling using sensitized backgrounds inC. elegans. These loci harbor putative polymorphic modifier genes that would not have been detected using mutant screens in single genetic backgrounds.
Just above chance: is it harder to decode information from human prefrontal cortex BOLD signals?
Authors: Bhandari Apoorva , Gagne Christopher , Badre David
Published: April 2017

Understanding the nature and form of prefrontal cortex representations that support flexible behavior is an important open problem in cognitive neuroscience. In humans, multi-voxel pattern analysis (MVPA) of fMRI BOLD measurements has emerged as an important approach for studying neural representations. An implicit, untested assumption underlying many PFC MVPA studies is that the base rate of decoding information from PFC BOLD activity patterns is similar to that of other brain regions. Here we estimate these base rates from a meta-analysis of published MVPA studies and show that the PFC has a significantly lower base rate for decoding than visual sensory cortex. Our results have implications for the design and interpretation of MVPA studies of prefrontal cortex, and raise important questions about its functional organization.
Volumetric grey matter alterations in adolescents and adults born very preterm suggest accelerated brain maturation
Authors: Karolis Vyacheslav R. , Froudist-Walsh Sean , Kroll Jasmin , Brittain Philip J. , Tseng Chieh-En Jane , Nam Kie-Woo , Reinders Antje A. T. S. , Murray Robin M. , Williams Steven C. R. , Thompson Paul M. , Nosarti Chiara
Published: April 2017

Previous research investigating structural neurodevelopmental alterations in individuals who were born very preterm demonstrated a complex pattern of grey matter changes that defy straightforward summary. Here we addressed this problem by characterising volumetric brain alterations in individuals who were born very preterm from adolescence to adulthood at three hierarchically related levels - global, modular and regional. We demarcated structural components that were either particularly resilient or vulnerable to the impact of very preterm birth. We showed that individuals who were born very preterm had smaller global grey matter volume compared to controls, with subcortical and medial temporal regions being particularly affected. Conversely, frontal and lateral parieto-temporal cortices were relatively resilient to the effects of very preterm birth, possibly indicating compensatory mechanisms. Exploratory analyses supported this hypothesis by showing a stronger association of lateral parieto-temporal volume with IQ in the very preterm group compared to controls. We then related these alterations to brain maturation processes. Very preterm individuals exhibited a higher maturation index compared to controls, indicating accelerated brain ageing and this was specifically associated with younger gestational age. We discuss how the findings of accelerated maturation might be reconciled with evidence of delayed maturation at earlier stages of development.
Extending the spectrum of DNA sequences retrieved from ancient bones and teeth
Authors: Glocke Isabelle , Meyer Matthias
Published: April 2017

The number of DNA fragments surviving in ancient bones and teeth is known to decrease with fragment length. Recent genetic analyses of Middle Pleistocene remains have shown that the recovery of extremely short fragments can prove critical for successful retrieval of sequence information from particularly degraded ancient biological material. Current sample preparation techniques, however, are not optimized to recover DNA sequences from fragments shorter than ∼35 base pairs (bp). Here, we show that much shorter DNA fragments are present in ancient skeletal remains but lost during DNA extraction. We present a refined silica-based DNA extraction method that not only enables efficient recovery of molecules as short as 25 bp but also doubles the yield of sequences from longer fragments due to improved recovery of molecules with single-strand breaks. Furthermore, we present strategies for monitoring inefficiencies in library preparation that may result from co-extraction of inhibitory substances during DNA extraction. The combination of DNA extraction and library preparation techniques described here substantially increases the yield of DNA sequences from ancient remains and provides access to a yet unexploited source of highly degraded DNA fragments. Our work may thus open the door for genetic analyses on even older material.
Metabolic Profile of Obeticholic Acid and Endogenous Bile Acids in Rats with Decompensated Liver Cirrhosis
Authors: Roda A , Aldini R , Camborata C , Spinozzi S , Franco P , Cont M , D'Errico A , Vasuri F , Degiovanni A , Maroni L , Adorini L
Published: April 2017

Obeticholic acid (OCA) is a semisynthetic bile acid (BA) analog and potent farnesoid X receptor agonist approved to treat cholestasis. We evaluated the biodistribution and metabolism of OCA administered to carbon tetrachloride‐induced cirrhotic rats. This was to ascertain if plasma and hepatic concentrations of OCA are potentially more harmful than those of endogenous BAs. After administration of OCA (30 mg/kg), we used liquid chromatography–mass spectrometry to measure OCA, its metabolites, and BAs at different timepoints in various organs and fluids. Plasma and hepatic concentrations of OCA and BAs were higher in cirrhotic rats than in controls. OCA and endogenous BAs had similar metabolic pathways in cirrhotic rats, although OCA hepatic and intestinal clearance were lower than in controls. BAs' qualitative and quantitative compositions were not modified by a single administration of OCA. In all the matrices studied, OCA concentrations were significantly lower than those of endogenous BAs, potentially much more cytotoxic.
Comparison of equine platelet function and survival in whole blood collected in acid‐citrate‐dextrose solution or citrate‐phosphate‐dextrose‐adenine solution
Authors: Bozorgmanesh Rana , Sutton‐Burges Julie W. , Tablin Fern
Published: April 2017

Background

Equine whole blood collection and storage methods have been evaluated to assess red blood cell viability; however, platelet (PLT) viability has not been comprehensively assessed.

Objectives

The purpose of the study was to compare viability of PLTs collected in whole blood into 2 different anticoagulants.

Methods

Whole blood from 6 healthy adult Thoroughbred horses was collected into citrate‐phosphate‐dextrose‐adenine (CPDA) or acid‐citrate‐dextrose (ACD). Platelet count, pH, and concentrations of glucose, lactate, carbon dioxide, oxygen, bicarbonate, sodium, potassium, and chloride were measured within 10 minutes of collection and then again one hour later at which time PLT aggregometry was performed to assess PLT function.

Results

Aggregometry mean amplitudes were significantly higher in CPDA compared to ACD. Blood glucose, pH, bicarbonate, sodium, and lactate concentrations were significantly higher in CPDA compared to ACD. Lactate concentration was higher following one hour in either anticoagulant. Potassium, oxygen, and carbon dioxide concentrations were significantly higher in ACD compared to CPDA at collection.

Conclusions

Platelet aggregometry results suggest that CPDA is superior to ACD for maintaining PLT viability following whole blood collection. This may be associated with the higher, more neutral pH as well as an increase in glucose available for metabolism. Although lactate was increased in the CPDA samples it was not high enough to decrease pH and therefore may not have been high enough to cause morphologic lesions and loss of PLT viability.
Pupils’ Perceptions of Attainment in Music at the Start of Secondary School in England: A Descriptive Analysis
Authors: Kokotsaki Dimitra
Published: April 2017

The provision of constructive feedback gives meaning to educational assessment and is an important requirement in every good educational system. In addition to the value of summative and formative judgements about a learner’s progress, when pupils are given opportunities to assess their own work, they can develop a sense of ownership and responsibility towards their work that can help promote a proactive and critical learning attitude. The present study aims to explore the issue of self-assessment in music learning and to contribute to the discussion about the importance of pupils’ involvement in evaluating their musical skills. It particularly looks at pupils’ views on their musical progress during their first year in secondary school (N=530). The findings suggest that equal attention needs to be given to pupils’ development in all areas of musical achievement. Furthermore, pupils’ sense of musical progress seems to be related to their overall enjoyment of music.
Review Article: Dynamics of methane dissociation on transition metals
Authors: Luntz Alan C. , Beck Rainer D.
Published: April 2017

One of the many contributions of Harold Winters to surface science was his pioneering ultrahigh vacuum study on the kinetics of the technologically important dissociation of CH4 on transition metals in the 1970s. He observed a dramatic activation of the dissociation with surface temperature alone and a huge isotope effect and suggested a simple dynamical model to rationalize his results. Since that time, our general understanding of the dynamics of gas-surface dissociations has exploded due to experimental advances (e.g., molecular beam and eigenstate resolved studies) and theoretical advances (quantum or classical dynamics on ab initio potential energy surfaces). This review tries to highlight how our understanding of the dynamics of CH4 dissociation on transition metals has matured since Harold's pioneering experiments and original model.
Sensorimotor adaptation affects perceptual compensation for coarticulation
Authors: Schuerman William L. , Nagarajan Srikantan , McQueen James M. , Houde John
Published: April 2017

A given speech sound will be realized differently depending on the context in which it is produced. Listeners have been found to compensate perceptually for these coarticulatory effects, yet it is unclear to what extent this effect depends on actual production experience. In this study, whether changes in motor-to-sound mappings induced by adaptation to altered auditory feedback can affect perceptual compensation for coarticulation is investigated. Specifically, whether altering how the vowel [i] is produced can affect the categorization of a stimulus continuum between an alveolar and a palatal fricative whose interpretation is dependent on vocalic context is tested. It was found that participants could be sorted into three groups based on whether they tended to oppose the direction of the shifted auditory feedback, to follow it, or a mixture of the two, and that these articulatory responses, not the shifted feedback the participants heard, correlated with changes in perception. These results indicate that sensorimotor adaptation to altered feedback can affect the perception of unaltered yet coarticulatorily-dependent speech sounds, suggesting a modulatory role of sensorimotor experience on speech perception.
Acoustic generation of underwater cavities—Comparing modeled and measured acoustic signals generated by seismic air gun arrays
Authors: Khodabandeloo Babak , Landrø Martin , Hanssen Alfred
Published: April 2017

Underwater vapor cavities can be generated by acoustic stimulation. When the acoustic signals from several air guns are reflected from the sea surface, the pressure drop at some locations is sufficient for cavity growth and subsequent collapse. In this paper the generation of multiple water vapor cavities and their collapses are numerically modeled and the results are validated by comparing with field data from a seismic air gun array test. In a first modeling attempt where cavity interaction is neglected, a correspondence between measured and modeled data is found. Then, this correspondence is improved by assuming that the acoustic signal generated by the other cavities changes the hydrostatic pressure surrounding each cavity. This modeling can be used to estimate the amount and strength of high frequency signals generated by typical marine air gun arrays, given that a calibration step is performed prior to the modeling.
Quantifying the negative impact of brain drain on the integration of European science
Authors: Doria Arrieta Omar A. , Pammolli Fabio , Petersen Alexander M.
Published: April 2017

Counterintuitively, by joining the European Union, scientific collaboration in entrant countries became less international.
Decarboxylative borylation
Authors: Li Chao , Wang Jie , Barton Lisa M. , Yu Shan , Tian Maoqun , Peters David S. , Kumar Manoj , Yu Antony W. , Johnson Kristen A. , Chatterjee Arnab K. , Yan Ming , Baran Phil S.
Published: April 2017

Swapping boron acids for carbon acids

Carbon-bound boronic acids and their esters are widely used as coupling partners to make carbon-carbon bonds. More recently, these chemicals have garnered pharmaceutical interest in their own right. Li
et al.
report a versatile nickel-catalyzed process to replace carboxylic acids with boronate esters by using a phthalimide activator. The reaction is well suited to late-stage modification of complex molecules. The authors used the approach to produce a potent in vitro inhibitor of human neutrophil elastase, a target of interest in treating inflammatory lung diseases.

Science
, this issue p.
eaam7355
Water harvesting from air with metal-organic frameworks powered by natural sunlight
Authors: Kim Hyunho , Yang Sungwoo , Rao Sameer R. , Narayanan Shankar , Kapustin Eugene A. , Furukawa Hiroyasu , Umans Ari S. , Yaghi Omar M. , Wang Evelyn N.
Published: April 2017

Solar heat helps harvest humidity

Atmospheric humidity and droplets constitute a huge freshwater resource, especially at the low relative humidity (RH) levels typical of arid environments. Water can be adsorbed by microporous materials such as zeolites, but often, making these materials release the water requires too much energy to be practical. Kim
et al.
used a metal-organic framework (MOF) material that has a steep increase in water uptake over a narrow RH range to harvest water, using only ambient sunlight to heat the material. They obtained 2.8 liters of water per kilogram of MOF daily at 20% RH.

Science
, this issue p.
430
Permanent Draft Genome Sequence of Desulfurococcus amylolyticus Strain Z-533
T
, a Peptide and Starch Degrader Isolated from Thermal Springs in the Kamchatka Peninsula and Kunashir Island, Russia
Authors: Susanti Dwi , Johnson Eric F. , Lapidus Alla , Han James , Reddy T. B. K. , Mukherjee Supratim , Pillay Manoj , Perevalova Anna A. , Ivanova Natalia N. , Woyke Tanja , Kyrpides Nikos C. , Mukhopadhyay Biswarup
Published: April 2017

Desulfurococcus amylolyticus
Z-533
T
, a hyperthermophilic crenarcheon, ferments peptide and starch, generating acetate, isobutyrate, isovalerate, CO
2
, and hydrogen. Unlike
D. amylolyticus
Z-1312, it cannot use cellulose and is inhibited by hydrogen. The reported draft genome sequence of
D. amylolyticus
Z-533
T
will help to understand the molecular basis for these differences.
Draft Genome Sequences of 13 Colombian Helicobacter pylori Strains Isolated from Pacific Coast and Andean Residents
Authors: Pazos Alvaro , Kodaman Nuri , Piazuelo M. Blanca , Romero-Gallo Judith , Sobota Rafal S. , Israel Dawn A. , Bravo Luis E. , Morgan Douglas R. , Wilson Keith T. , Correa Pelayo , Peek Richard M. , Williams Scott M. , Schneider Barbara G.
Published: April 2017

We present here the draft genomes of 13
Helicobacter pylori
strains isolated from Colombian residents on the Pacific coast (
n
= 6) and in the Andes mountains (
n
= 7), locations that differ in gastric cancer risk. These 13 strains were obtained from individuals with diagnosed gastric lesions.
Complete Genome Sequence of
Mycobacterium
sp. MS1601, a Bacterium Performing Selective Oxidation of Polyols
Authors: Sayed Mahmoud , Sayed Waiel F. , Hatti-Kaul Rajni , Pyo Sang-Hyun
Published: April 2017

Corynebacterium
sp. (ATCC 21245) is reclassified here as
Mycobacterium
sp. MS1601 based on 16S rRNA gene and complete-genome sequence analysis. It is able to oxidize branched polyols to corresponding hydroxycarboxylic acids. The total size of the genome sequence was 6,829,132 bp, including one circular chromosome of 6,407,860 bp.
Complete Genome Sequence of Human Norovirus GII.Pe-GII.4 Sydney from the United States
Authors: Yang Zhihui , Vinjé Jan , Kulka Michael
Published: April 2017

We report here the first near-complete genome sequence (7,551 nucleotides) of a human norovirus GII.Pe-GII.4 Sydney variant, detected in a stool sample from an outbreak on a cruise ship in 2013.
Complete Genome Sequence of Komagataeibacter hansenii Strain SC-3B
Authors: Pfeffer Sarah , Santos Richard , Ebels Marcus , Bordbar Darius , Brown R. Malcolm
Published: April 2017

This study reports the release of the complete nucleotide sequence of
Komagataeibacter hansenii
SC-3B, a new efficient producer of cellulose. Elucidation of the genome may provide more information to aid in understanding the genes necessary for cellulose biosynthesis.
Draft Genome Sequence of Multidrug-Resistant Abortive Campylobacter jejuni from Northern California
Authors: Weis Allison M. , Clothier Kristin A. , Huang Bihua C. , Kong Nguyet , Weimer Bart C.
Published: April 2017

Campylobacter jejuni
is an enteric bacterium that can cause abortion in livestock. This is the release of a multidrug-resistant
Campylobacter jejuni
genome from an isolate that caused an abortion in a cow in northern California. This isolate is part of the 100K Pathogen Genome Project.