bluuebunny/crossref_metadata_2025_split huggingface dataset:
SSEP in Therapeutic Hypothermia Era
Authors: Maciel Carolina B. , Morawo Adeolu O. , Tsao Ching Y. , Youn Teddy S. , Labar Douglas R. , Rubens Elayna O. , Greer David M. 
Published: May 2017

Purpose:The reliability of somatosensory evoked potentials (SSEPs) in predicting outcome in comatose survivors of cardiac arrest treated with therapeutic hypothermia (TH) has been questioned. We investigated whether the absence of cortical (N20) responses was a reliable predictor of a nonawakening in the setting of TH.Methods:A retrospective review was conducted in cardiac arrest survivors treated with TH admitted to a single tertiary care hospital from April, 2010 to March, 2013 who underwent SSEP testing at various time points after cardiac arrest. N20 responses were categorized as normal, present but abnormal, bilaterally absent, or inadequate for interpretation. Neurologic outcome was assessed at discharge by the Cerebral Performance Category Scale (CPC).Results:Ninety-three SSEP studies were performed in 73 patients. Fourteen patients had absent N20 responses; all had poor outcome (CPC 4–5). Eleven patients had absent N20 s during hypothermia, three of whom had follow-up SSEPs after rewarming and cortical responses remained absent. Fifty-seven patients had N20 peaks identified and had variable outcomes. Evaluation of 1 or more N20 peaks was limited or inadequate in 11.4% of SSEPs performed during the cooling because of artifact.Conclusions:Somatosensory evoked potentials remain a reliable prognostic indicator in patients undergoing TH. The limited sample size of patients who had SSEP performed during TH and repeated after normothermia added to the effect of self-fulfilling prophecy limit the interpretation of the reliability of this testing when performed during cooling. Further prospective, multicenter, large scale studies correlating cortical responses in SSEPs during and after TH are warranted. Technical challenges are commonplace during TH and caution is advised in the interpretation of suboptimal recordings.
Shared Genetic Architecture between Asthma and Allergic Diseases: A Genome-Wide Cross Trait Analysis of 112,000 Individuals from UK Biobank
Authors: Zhu Zhaozhong , Lee Phil H. , Chaffin Mark D. , Chung Wonil , Loh Po-Ru , Lu Quan , Christiani David C. , Liang Liming 
Published: May 2017

AbstractClinical and epidemiological data suggest that asthma and allergic diseases are associated. And may share a common genetic etiology. We analyzed genome-wide single-nucleotide polymorphism (SNP) data for asthma and allergic diseases in 35,783 cases and 76,768 controls of European ancestry from the UK Biobank. Two publicly available independent genome wide association studies (GWAS) were used for replication. We have found a strong genome-wide genetic correlation between asthma and allergic diseases (rg= 0.75,P= 6.84×10−62). Cross trait analysis identified 38 genome-wide significant loci, including novel loci such as D2HGDH and GAL2ST2. Computational analysis showed that shared genetic loci are enriched in immune/inflammatory systems and tissues with epithelium cells. Our work identifies common genetic architectures shared between asthma and allergy and will help to advance our understanding of the molecular mechanisms underlying co-morbid asthma and allergic diseases.
Thirty-five experimental fisheries reveal the mechanisms of selection
Authors: Nusslé Sébastien , Hendry Andrew P. , Knapp Roland A. , Bogan Michael T. , Sturrock Anna M. , Carlson Stephanie M. 
Published: May 2017

AbstractFisheries have been described as large-scale evolutionary experiments; yet such “experiments” tend to be poorly replicated and therefore lack the predictive power essential for designing appropriate management strategies to minimize the effects of fisheries-induced selection. Large-scale removal of non-native trout from 35 montane lakes in California provided repeated experimental fisheries that allowed us to explore how environmental parameters affect the three potential contributors to overall selection: the fitness-trait correlation, trait variability, and fitness variability. Our results demonstrate that fishing rapidly altered the size structure of harvested populations, and that the magnitude of change was primarily driven by the fitness-trait correlation (net selectivity). Fishing-induced selection was repeatable overall but was also influenced by environmental (lake size and quality) and demographic (size structure) parameters. Decomposing fishing-induced selection into its key components can improve the management of stocks experiencing fishing-induced selection by identifying the drivers of selection and therefore the appropriate target for management.
Rehabilitation promotes the recovery of functional and structural features of healthy neuronal networks after stroke
Authors: Allegra Mascaro Anna Letizia , Conti Emilia , Lai Stefano , Di Giovanna Antonino Paolo , Spalletti Cristina , Alia Claudia , Quarta Eros , Panarese Alessandro , Sacconi Leonardo , Micera Silvestro , Caleo Matteo , Pavone Francesco Saverio 
Published: May 2017

AbstractRehabilitation is the most effective treatment for promoting the recovery of motor deficits after stroke. Despite its importance, the processes associated with rehabilitative intervention are poorly understood. One of the most challenging experimental goals is to unambiguously link specific circuit changes induced by rehabilitation to improved behavior. Here, we investigate which facets of cortical remodeling are induced by rehabilitation by combining optical imaging and manipulation tools in a mouse model of stroke. We demonstrate the progressive restoration of cortical motor maps and of cortical activity in parallel with the reinforcement of inter-hemispheric connectivity after rehabilitation. Furthermore, we reveal that the increase in vascular density goes along with the stabilization of peri-infarct neural circuitry at synaptic level. The present work provides the first evidences that rehabilitation is sufficient to promote the combined recovery of distinct structural and functional features distinctive of healthy neuronal networks.
14-3-3 Negatively Regulates Actin Filament Formation in the Deep Branching EukaryoteGiardia lamblia
Authors: Krtková Jana , Xu Jennifer , Lalle Marco , Steele-Ogus Melissa , Alas Germain C. M. , Sept David , Paredez Alexander R. 
Published: May 2017

AbstractThe phosphoserine/phosphothreonine-binding protein 14-3-3 is known to regulate actin, this function has been previously attributed to sequestration of phosphorylated cofilin. The deep branching eukaryoteGiardia lamblialacks cofilin and all other canonical actin-binding proteins (ABPs), and 14-3-3 was identified as an actin-associated protein inGiardia, yet its role in actin regulation was unknown. Gl14-3-3 depletion resulted in an overall disruption of actin organization characterized by ectopically distributed short actin filaments. Using phosphatase and kinase inhibitors, we demonstrated that actin phosphorylation correlated with destabilization of the actin network and increased complex formation with 14-3-3, while blocking actin phosphorylation stabilized actin filaments and attenuated complex formation.Giardia'ssole Rho family GTPase, GlRac, modulates Gl14-3-3's association with actin, providing the first connection between GlRac and the actin cytoskeleton inGiardia.Giardiaactin contains two putative 14-3-3 binding motifs, one of which (S330) is conserved in mammalian actin. Mutation of these sites reduced, but did not completely disrupt, the association with 14-3-3. Native gels and overlay assays indicate that intermediate proteins are required to support complex formation between 14-3-3 and actin. Overall, our results support a role for 14-3-3 as a negative regulator of actin filament formation.ImportanceGiardialacks canonical actin binding proteins. 14-3-3 was identified as an actin interactor but the significance of this interaction was unknown. Loss of 14-3-3 results in ectopic short actin filaments, indicating that 14-3-3 is an important regulator of the actin cytoskeleton inGiardia. Drug studies indicate that 14-3-3 complex formation is in part phospho-regulated. We demonstrate that complex formation is downstream of Giardia’s sole Rho family GTPase, GlRac, this result provides the first mechanistic connection between GlRac and actin inGiardia. Native gels and overlay assays indicate intermediate proteins are required to support the interaction between 14-3-3 and actin suggesting that 14-3-3 is regulating multiple actin complexes. Overall, we find that 14-3-3 is a negative regulator of actin filament formation inGiardia.
Extensive tonotopic mapping across auditory cortex is recapitulated by spectrally-directed attention, and systematically related to cortical myeloarchitecture
Authors: Dick Frederic K. , Lehet Matt I. , Callaghan Martina F. , Keller Tim A. , Sereno Martin I. , Holt Lori L. 
Published: May 2017

AbstractAuditory selective attention is vital in natural soundscapes. But, it is unclear how attentional focus on the primary dimension of auditory representation - acoustic frequency - might modulate basic auditory functional topography during active listening. In contrast to visual selective attention, which is supported by motor-mediated optimization of input across saccades and pupil dilation, the primate auditory system has fewer means of differentially sampling the world. This makes spectrally-directed endogenous attention a particularly crucial aspect of auditory attention. Using a novel functional paradigm combined with quantitative MRI, we establish that human frequency-band-selective attention drives activation in both myeloarchitectonically-estimated auditory core, and across the majority of tonotopically-mapped non-primary auditory cortex. The attentionally-driven best-frequency maps show strong concordance with sensory-driven maps in the same subjects across much of the temporal plane, with poor concordance in non-auditory areas. There is significantly greater activation across most of auditory cortex when best frequency is attended, versus ignored. Moreover, the single frequency bands that evoke the least activation and the frequency bands that elicit the least activation when attention is directed to them also correspond closely. Finally, the results demonstrate that there is spatial correspondence between the degree of myelination and the strength of the tonotopic signal across a number of regions in auditory cortex. Strong frequency preferences across tonotopically-mapped auditory cortex spatially correlate with R1-estimated myeloarchitecture, indicating shared functional and anatomical organization that may underlie intrinsic auditory regionalization.SignificancePerception is an active process especially sensitive to attentional state. Listeners direct auditory attention to track a violin’s melody within an ensemble performance, or to follow a voice in a crowded cafe. Although diverse pathologies reduce quality of life by impacting such spectrally-directed auditory attention, its neurobiological bases are unclear. We demonstrate that human primary and non-primary auditory cortical activation is modulated by spectrally-directed attention in a manner that recapitulates its tonotopic sensory organization. Further, the graded activation profiles evoked by single frequency bands are correlated with attentionally-driven activation when these bands are presented in complex soundscapes. Finally, we observe a strong concordance in the degree of cortical myelination and the strength of tonotopic activation across several auditory cortical regions.
A multi-stage representation of cell proliferation as a Markov process
Authors: Yates Christian A. , Ford Matthew J. , Mort Richard L. 
Published: May 2017

AbstractThe stochastic simulation algorithm commonly known as Gillespie’s algorithm (originally derived for modelling well-mixed systems of chemical reactions) is now used ubiquitously in the modelling of biological processes in which stochastic effects play an important role. In well mixed scenarios at the sub-cellular level it is often reasonable to assume that times between successive reaction/interaction events are exponentially distributed and can be appropriately modelled as a Markov process and hence simulated by the Gillespie algorithm. However, Gillespie’s algorithm is routinely applied to model biological systems for which it was never intended. In particular, processes in which cell proliferation is important (e.g. embryonic development, cancer formation) should not be simulated naively using the Gillespie algorithm since the history-dependent nature of the cell cycle breaks the Markov process. The variance in experimentally measured cell cycle times is far less than in an exponential cell cycle time distribution with the same mean.Here we suggest a method of modelling the cell cycle that restores the memoryless property to the system and is therefore consistent with simulation via the Gillespie algorithm. By breaking the cell cycle into a number of independent exponentially distributed stages we can restore the Markov property at the same time as more accurately approximating the appropriate cell cycle time distributions. The consequences of our revised mathematical model are explored analytically as far as possible. We demonstrate the importance of employing the correct cell cycle time distribution by recapitulating the results from two models incorporating cellular proliferation (one spatial and one non-spatial) and demonstrating that changing the cell cycle time distribution makes quantitative and qualitative differences to the outcome of the models. Our adaptation will allow modellers and experimentalists alike to appropriately represent cellular proliferation - vital to the accurate modelling of many biological processes - whilst still being able to take advantage of the power and efficiency of the popular Gillespie algorithm.
HIV disrupts CD34+progenitors involved in T-cell differentiation
Authors: Tsukamoto Tetsuo 
Published: May 2017

AbstractHIV-1 causes the loss of CD4+T cells via depletion or impairment of their production. The latter involves infection of thymocytes, but the involvement of other cells including haematopoietic CD34+cells remains unclear even though HIV-positive patients frequently manifest myelosuppression. This study utilised the OP9-DL1 coculture system, which supports in vitro T-lineage differentiation of human haematopoietic stem/progenitor cells. Cord-derived CD34+cells were infected with CXCR4-tropic HIV-1NL4-3and cocultured. HIV-infected cocultures exhibited sustained viral replication for 5 weeks, as well as reduced CD4+T-cell growth at weeks 3–5. It was further revealed that CD34+CD7+CXCR4+cells can be quickly depleted as early as in 1 week after infection of the subset, and this was accompanied by the emergence of CD34+CD7+CD4+cells. These results indicate that CXCR4-tropic HIV-1 strains may disrupt CD34+CD7+lymphoid progenitor cell pools, presumably leading to impaired T-cell production potential.
Marginal Returns and Levels of Research Grant Support among Scientists Supported by the National Institutes of Health
Authors: Lauer Michael , Roychowdhury Deepshikha , Patel Katie , Walsh Rachael , Pearson Katrina 
Published: May 2017

AbstractThe current era of worsening hypercompetition in biomedical research has drawn attention to the possibility of decreasing marginal returns from research funding. Recent work has described decreasing marginal returns as a function of annual dollars granted to individual scientists. However, different fields of research incur varying cost structures. Therefore, we developed a Grant Support Index (GSI) that focuses on grant activity code, as opposed to field of study or cost. In a cohort of over 71,000 unique scientists funded by NIH between 1996 and 2014 we analyzed the association of grant support (as measured by annual GSI) with 3 bibliometric outcomes, maximum Relative Citation Ratio (which arguably reflects a scientist’s most influential work), median Relative Citation Ratio, and annual weighted Relative Citation Ratio (which is more dependent on publication counts). We found that for all 3 measures marginal returns decline as annual GSI increases. Thus, we confirm prior findings of decreasing marginal returns with higher levels of research funding support.
Mutations in Membrin/GOSR2reveal stringent secretory pathway demands of dendritic growth and synaptic integrity
Authors: Praschberger Roman , Lowe Simon A. , Malintan Nancy T. , Houlden Henry , Kullmann Dimitri M. , Usowicz Maria M. , Krishnakumar Shyam S. , Hodge James J.L. , Rothman James E. , Jepson James E.C. 
Published: May 2017

AbstractMutations in the Golgi SNARE protein Membrin (encoded by theGOSR2gene) cause progressive myoclonus epilepsy (PME). Membrin is a ubiquitously important protein mediating ER-to-Golgi membrane fusion, and hence it is unclear how these mutations result in a disorder restricted to the nervous system. Here we use a multi-layered strategy to elucidate the consequences of Membrin mutations from protein to neuron. We show that the pathogenic mutations cause partial reductions in SNARE-mediated membrane fusion. Importantly, these alterations were sufficient to profoundly impair dendritic growth in novelDrosophilamodels ofGOSR2-PME. We also observed axonal trafficking abnormalities in this model, as well as synaptic malformations, trans-synaptic instability and hyperactive synaptic transmission. Our study highlights how dendritic growth is vulnerable even to subtle secretory pathway deficits, uncovers a previously uncharacterized role for Membrin in synaptic function, and provides a comprehensive explanatory basis for genotype-phenotype relationships inGOSR2-PME.
A sequencer coming of age:de novogenome assembly using MinION reads
Authors: de Lannoy Carlos , de Ridder Dick , Risse Judith 
Published: May 2017

AbstractNanopore technology provides a novel approach to DNA sequencing that yields long, label-free reads of constant quality. The first commercial implementation of this approach, the MinION, has shown promise in various sequencing applications. The presented literature review gives an up-to-date overview of the MinION’s utility as ade novosequencing device. It is argued that the MinION may allow for portable and affordablede novosequencing of even complex genomes in the near future, despite the currently error-prone nature of its reads. Through continuous updates to the MinION hardware and the development of new assembly pipelines, both sequencing accuracy and assembly quality have already risen rapidly. However, this fast pace of development has also lead to a lack of oversight in the expanding landscape of analysis tools, as performance evaluations are outdated quickly. Now that the MinION is approaching a state of maturity, a thorough comparative benchmarking effort ofde novoassembly pipelines may be at place.
Wireless implantable sensor for non-invasive, longitudinal quantification of axial strain across rodent long bone defects
Authors: Klosterhoff Brett S. , Ong Keat Ghee , Krishnan Laxminarayanan , Hetzendorfer Kevin M. , Chang Young-Hui , Allen Mark G. , Guldberg Robert E. , Willett Nick J. 
Published: May 2017

AbstractBone development, maintenance, and regeneration are remarkably sensitive to mechanical cues. Consequently, mechanical stimulation has long been sought as a putative target to promote endogenous healing after fracture. Given the transient nature of bone repair, tissue-level mechanical cues evolve rapidly over time after injury and are challenging to measure non-invasively. The objective of this work was to develop and characterize an implantable strain sensor for non-invasive monitoring of axial strain across a rodent femoral defect during functional activity. Herein, we present the design, characterization, andin vivodemonstration of the device’s capabilities for quantitatively interrogating physiological dynamic strains during bone regeneration.Ex vivoexperimental characterization of the device showed that it exceeded the technical requirements for sensitivity, signal resolution, and electromechanical stability. The digital telemetry minimized power consumption, enabling long-term intermittent data collection. Devices were implanted in a rat 6 mm femoral segmental defect model and after three days, data were acquired wirelessly during ambulation and synchronized to corresponding radiographic videos, validating the ability of the sensor to non-invasively measure strain in real-time. Lastly,in vivostrain measurements were utilized in a finite element model to estimate the strain distribution within the defect region. Together, these data indicate the sensor is a promising technology to quantify local tissue mechanics in a specimen specific manner, facilitating more detailed investigations into the role of the mechanical environment in dynamic skeletal healing and remodeling.
Quantitative analysis shows that repair of Cas9-induced double-strand DNA breaks is slow and error-prone
Authors: Brinkman Eva K. , Chen Tao , Haas Marcel de , Holland Hanna A. , Akhtar Waseem , Steensel Bas van 
Published: May 2017

SummaryThe RNA-guided DNA endonuclease Cas9 is a powerful tool for genome editing. Little is known about the kinetics and fidelity of the double-strand break (DSB) repair process that follows a Cas9 cutting event in living cells. Here, we developed a strategy to measure the kinetics of DSB repair for single loci in human cells. Quantitative modeling of repaired DNA in time series after Cas9 activation reveals a relatively slow repair rate (~6h). Furthermore, the double strand break is predominantly repaired in an error-prone fashion (at least 70%). Both classical and microhomology-mediated end-joining pathways are active and contribute to the repair in a stochastic manner. However, the balance between these two pathways changes over time and can be altered by chemical inhibition of DNAPKcs or additional ionizing radiation. Our strategy is generally applicable to study DSB repair kinetics and fidelity in single loci, and demonstrates that Cas9-induced DSBs are repaired in an unusual manner.
Genetically engineered orange petunias on the market
Authors: Bashandy Hany , Teeri Teemu H. 
Published: May 2017

AbstractGenetic engineering of petunia was shown to lead to novel flower color some twenty years ago. Here we show that petunia lines with orange flowers, generated for scientific purposes, apparently found their way to petunia breeding programmes, intentionally or unintentionally. Today they are widely available, but have not been registered for commerce.