bluuebunny/crossref_metadata_2025_split huggingface dataset:
BioBankRead: Data pre-processing in Python for UKBiobank clinical data
Authors: Schneider-Luftman D. , Crum W. R. 
Published: April 2019

AbstractMotivationUKBiobank collects health-related data from 500,000 volunteers and is widely used by medical researchers. However, the data is supplied in a custom compressed format and its preparation for analysis is cumbersome and time-consuming. This Python package automates the extraction of selected UKBiobank data, for easy integration in an analysis pipeline.FeaturesThe functions provided within this Python package reduce the number of steps, as well as human and computational time, required for extraction and preparation of the data for analysis. It is executable through command line, is easily installed on any platform and requires no prior knowledge of Python.ApplicationBiobankRead is used for an analysis of dietary lifestyles and cardio-vascular outcomes. A large range of dietary, phenotypical, lifestyle and vascular outcomes is extracted and pre-processed. Significant associations are found between non-meat-eating and lower blood pressure / reduced risk of hypertension.AvailabilityThe Python package BiobankRead is freely available under the GNU General Public License (version 3 or later). It can be downloaded from GitHub (https://github.com/saphir746/BiobankRead-Bash), where example scripts and detailed instructions are also available.
Connectal Coding: Discovering the Structures Linking Cognitive Phenotypes to Individual Histories
Authors: Vogelstein Joshua T. , Bridgeford Eric W. , Pedigo Benjamin D. , Chung Jaewon , Levin Keith , Mensh Brett , Priebe Carey E. 
Published: April 2019

AbstractCognitive phenotypes characterize our memories, beliefs, skills, and preferences, and arise from our ancestral, developmental, and experiential histories. These histories are written into our brain structure through the building and modification of various brain circuits. Connectal coding, by way of analogy with neural coding, is the art, study, and practice of identifying the network structures that link cognitive phenomena to individual histories. We propose a formal statistical framework for connectal coding and demonstrate its utility in several applications spanning experimental modalities and phylogeny.
Reducing malaria burden and accelerating elimination with long-lasting systemic insecticides: a modeling study of three potential use cases
Authors: Selvaraj Prashanth , Suresh Joshua , Wenger Edward A. , Bever Caitlin A. , Gerardin Jaline 
Published: April 2019

AbstractBackgroundWhile bednets and insecticide spraying have had significant impact on malaria burden in many endemic regions, outdoor vector feeding and insecticide resistance may ultimately limit their contribution to elimination and control campaigns. Complementary vector control methods such as endectocides or systemic insecticides are therefore generating much interest. Here we explore the conditions under which long-lasting systemic insecticides would have a substantial impact on transmission and burden.MethodsHypothetical long-lasting systemic insecticides with effective durations ranging from 14 days to 90 days are simulated using an individual-based mathematical model of malaria transmission. The impact of systemic insecticides when used to complement existing vector control and drug campaigns is evaluated in three settings – a highly seasonal high-transmission setting, a near-elimination setting with seasonal travel to a high-risk area, and a near-elimination setting in southern Africa.ResultsAt 60% coverage, a single round of long-lasting systemic insecticide with effective duration of at least 60 days, distributed at the start of the season alongside a seasonal malaria chemoprevention campaign in a high-transmission setting, results in further burden reduction of 30-90% depending on the sub-populations targeted. In a near-elimination setting where transmission is sustained by seasonal travel to a high-risk area, targeting high-risk travelers with systemic insecticide with effective duration of at least 30 days can result in likely elimination even if intervention coverage is as low as 50%. In near-elimination settings with robust vector control, the addition of a 14-day systemic insecticide alongside an antimalarial in mass drug administration (MDA) campaigns can decrease the necessary MDA coverage from about 85% to the more easily achievable 65%.ConclusionsWhile further research into the safety profile of systemic insecticides is necessary before deployment, we find that long-lasting systemic insecticides can play a critical role in reducing burden or eliminating malaria in a range of contexts with different target populations, existing malaria control methods, and transmission intensities.
Coordinated circadian timing through the integration of local inputs in Arabidopsis thaliana
Authors: Greenwood Mark , Domijan Mirela , Gould Peter D. , Hall Anthony J.W. , Locke James C.W. 
Published: April 2019

AbstractEvery plant cell has a genetic circuit, the circadian clock, that times key processes to the day-night cycle. These clocks are aligned to the day-night cycle by multiple environmental signals that vary across the plant. How does the plant integrate clock rhythms, both within and between organs, to ensure coordinated timing? To address this question, we examined the clock at the sub-tissue level across Arabidopsis thaliana seedlings under multiple environmental conditions and genetic backgrounds. Our results show that the clock runs at different speeds (periods) in each organ, which causes the clock to peak at different times across the plant in both constant environmental conditions and light-dark cycles. Closer examination reveals that spatial waves of clock gene expression propagate both within and between organs. Using a combination of modeling and experiment, we reveal that these spatial waves are the result of the period differences between organs and local coupling, rather than long distance signaling. With further experiments we show that the endogenous period differences, and thus the spatial waves, are caused by the organ specificity of inputs into the clock. We demonstrate this by modulating periods using light and metabolic signals, as well as with genetic perturbations. Our results reveal that plant clocks are set locally by organ specific inputs, but coordinated globally via spatial waves of clock gene expression.
Strong self-regulation and widespread facilitative interactions in phytoplankton communities
Authors: Picoche Coralie , Barraquand Frédéric 
Published: April 2019

AbstractThe persistence of phytoplanktonic diversity in spite of competition for basic resources has long been a source of wonder and inspiration to ecologists. To sort out, among the many coexistence mechanisms suggested by theory and experiments, which ones actually maintain diversity in natural ecosystems, long-term field studies are paramount.We analysed a large dataset of phytoplankton abundance time series using dynamic, multivariate autoregressive models. Phytoplankton was counted and identified down to the genus level, every two weeks over twenty years, at ten sites along the French coastline. Multivariate autoregressive models allowed to estimate biotic interaction networks, while also accounting for abiotic variables that may drive part of the phytoplankton fluctuations. We then analysed the ratio of intra-to inter-taxa interactions (measuring self-regulation, itself a measure of niche differentiation), the frequency of negative vs positive interactions, and how stability metrics (both at the network and genus level) relate to network complexity and genus self-regulation or abundance.We showed that a strong self-regulation, with competition strength within a taxon (genus) an order of magnitude higher than between taxa, was present in all phytoplanktonic interaction networks. This much stronger intragenus competition suggests that niche differentiation - rather than neutrality - is commonplace in phytoplankton. Furthermore, interaction networks were dominated by positive net effects between phytoplanktonic taxa (on average, more than 50% of interactions were positive). While network stability (sensuresilience) was unrelated to complexity measures, we unveiled links between self-regulation, intergenus interaction strengths and abundance. The less common taxa tend to be more strongly self-regulated and can therefore maintain in spite of competition with more abundant ones.Synthesis: We demonstrate that strong niche differentiation, widespread facilitation between phytoplanktonic taxa and stabilizing covariances between interaction strengths should be common features of coexisting phytoplankton communities in the field. These are structural properties that we can expect to emerge from plausible mechanistic models of phytoplankton communities. We discuss mechanisms, such as predation or restricted microscale movement, that are consistent with these findings, which paves the way for further research.
RST1 and RIPR connect the cytosolic RNA exosome to the Ski complex inArabidopsis
Authors: Lange Heike , Ndecky Simon Y. A. , Gomez-Diaz Carlos , Pflieger David , Butel Nicolas , Zumsteg Julie , Kuhn Lauriane , Piermaria Christina , Chicher Johana , Christie Michael , Karaaslan Ezgi S. , Lang Patricia L. M. , Weigel Detlef , Vaucheret Hervé , Hammann Philippe , Gagliardi Dominique 
Published: April 2019

AbstractThe RNA exosome is a key 3’-5’ exoribonuclease with an evolutionarily conserved structure and function. Its cytosolic functions require the co-factors SKI7 and the Ski complex. Here we demonstrate by co-purification experiments that the ARM repeat protein RESURRECTION1 (RST1) and RST1 INTERACTING PROTEIN (RIPR) connect the cytosolicArabidopsisRNA exosome to the Ski complex.rst1andriprmutants accumulate RNA quality control siRNAs (rqc-siRNAs) produced by the post-transcriptional gene silencing (PTGS) machinery when mRNA degradation is compromised. The small RNA populations observed inrst1andriprmutants are also detected in mutants lacking the RRP45B/CER7 core exosome subunit. Thus, molecular and genetic evidence supports a physical and functional link between RST1, RIPR and the RNA exosome. Our data reveal the existence of additional cytosolic exosome co-factors besides the known SKI subunits. RST1 is not restricted to plants, as homologues with a similar domain architecture but unknown function exist in animals, including humans.
A neural system that represents the association of odors with rewarded outcomes and promotes behavioral engagement
Authors: Gadziola Marie A. , Stetzik Lucas A. , Wright Katherine N. , Milton Adrianna J. , Arakawa Keiko , del Mar Cortijo María , Wesson Daniel W. 
Published: April 2019

SummaryLearning strengthens the strong emotional and behavioral responses odors are well known for eliciting. Presumably subserving this, several brain regions display experience-dependent plasticity during odor learning, yet the specific cellular systems involved and the actual influence of these systems on odor-directed behavior are less understood. Here we investigated the transformation of odor information throughout the association of odors with rewards and also sought to link those neural systems with displays of reinforcement-based task engagement. First, we investigated the representation of odor-reward associations within two areas recipient of dense olfactory bulb input, the posterior piriform cortex (pPCX) and olfactory tubercle (OT), using simultaneous multi-site electrophysiological recordings from mice engaged in a reward-based olfactory learning task. As expected, neurons in both regions represented conditioned odors and did so with similar information content, yet both the proportion of neurons recruited by conditioned rewarded odors and the magnitudes and durations of their responses were greater in the OT. Using fiber photometry, we found that OT D1-type dopamine receptor expressing neurons flexibly represent odors based upon reward associations. In both the recordings and imaging, statistically meaningful changes in activity occurred soon after odor onset. Finally, using optogenetics we show that OT D1-receptor expressing neurons strongly influence behavior to promote task engagement. Together our results contribute to a model whereby OT D1 neurons support odor-guided motivated behaviors.
An open interface in the pre-80S ribosome coordinated by ribosome assembly factors Tsr1 and Dim1 enables temporal regulation of Fap7
Authors: Rai Jay , Parker Melissa D. , Huang Haina , Choy Stefan , Ghalei Homa , Johnson Matthew C. , Karbstein Katrin , Stroupe M. Elizabeth 
Published: April 2019

AbstractDuring their maturation, nascent 40S subunits enter a translation-like quality control cycle, where they are joined by mature 60S subunits to form 80S-like ribosomes. While these assembly intermediates are essential for maturation and quality control, how they form, and how their structure promotes quality control remains unknown. To address these questions, we determined the structure of an 80S-like ribosome assembly intermediate to an overall resolution of 3.4 Å. The structure, validated by biochemical data, resolves a large body of previously paradoxical data and illustrates how assembly and translation factors cooperate to promote the formation of an interface that lacks many mature subunit contacts but is stabilized by the universally conserved Dim1. We also show how Tsr1 enables this interface by blocking the canonical binding of eIF5B to 40S subunits, while maintaining its binding to 60S. The structure also shows how this interface leads to unfolding of the platform, which allows for temporal regulation of the ATPase Fap7, thus linking 40S maturation to quality-control during ribosome assembly.
A Large-scale Study Reveals 24 hour Operational Rhythms in Hospital Treatment
Authors: Ruben Marc D. , Francey Lauren J. , Guo Yuping , Wu Gang , Cooper Edward B. , Shah Amy S. , Hogenesch John B. , Smith David F. 
Published: April 2019

ABSTRACTHospitals operate 24 hours a day, and it is assumed that critical decisions occur continuously around the clock. However, many aspects of hospital operation occur at particular times of day, including medical team rounding and shift changes. It is unclear if this impacts patient care, as an empirical account of 24 h treatment patterns is lacking. We analyzed the daily distribution of ~120K doses of 12 separate drugs in 1,486 inpatients at a major children’s hospital in the U.S. Treatment orders and administration were strongly time-of-day-dependent, marked by distinct morning time surges and overnight lulls. These 24 h rhythms in treatment were remarkably consistent across drugs, diagnoses, and hospital units. In sum, nearly one-third of all 116,975 orders for treatment were placed between 8 AM and 12 PM. This rhythm in hospital medicine coincided with medical team rounding time, not necessarily immediate medical need. Lastly, we show that the clinical response to hydralazine, an acute antihypertensive, is dosing time-dependent and greatest at night, when the fewest doses were administered. The prevailing dogma is that hospital treatment is administered as needed regardless of time of day. Our findings challenge this notion and reveal a potential operational barrier to best clinical care.SIGNIFICANCE STATEMENTThe order and administration of hospital treatment was characterized by morning time surges and overnight lulls, regardless of drug type, diagnosis or care unit. As the first large-scale account of 24 h rhythms in hospital medicine, this study identifies a potential operational barrier to best clinical care. Critical clinical decisions should be made around the clock; pain, infection, hypertensive crisis, and other conditions do not occur selectively in the morning. Systemic bias in the timing of medicine is also at odds with circadian biology, which can influence when certain treatments are most effective or safe. Prevailing dogma is that hospital treatment is administered as needed regardless of time of day. Our findings challenge this notion and suggest that time of day in hospital operations deserves further consideration.
Loss of function in the autism and learning disabilities associated gene Nf1 disrupts corticocortical and corticostriatal functional connectivity in human and mouse
Authors: Shofty Ben , Bergmann Eyal , Zur Gil , Asleh Jad , Bosak Noam , Kavushansky Alexandra , Castellanos F. Xavier , Ben-Sira Liat , Packer Roger J. , Vezina Gilbert L. , Constantini Shlomi , Acosta Maria T. , Kahn Itamar 
Published: April 2019

ABSTRACTChildren with the autosomal dominant single gene disorder, neurofibromatosis type 1 (NF1), display multiple structural and functional changes in the central nervous system, resulting in neuropsychological cognitive abnormalities. Here we assessed the pathological functional organization that may underlie the behavioral impairments in NF1 using resting-state functional connectivity MRI. Coherent spontaneous fluctuations in the fMRI signal across the entire brain were used to interrogate the pattern of functional organization of corticocortical and corticostriatal networks in both NF1 pediatric patients and mice with a heterozygous mutation in the Nf1 gene (Nf1+/-). Children with NF1 demonstrated abnormal organization of cortical association networks and altered posterior-anterior functional connectivity in the default network. Examining the contribution of the striatum revealed that corticostriatal functional connectivity was altered. NF1 children demonstrated reduced functional connectivity between striatum and the frontoparietal network and increased striatal functional connectivity with the limbic network. Awake passive mouse functional connectivity MRI in Nf1+/- mice similarly revealed reduced posterior-anterior connectivity along the cingulate cortex as well as disrupted corticostriatal connectivity. The striatum of Nf1+/- mice showed increased functional connectivity to somatomotor and frontal cortices and decreased functional connectivity to the auditory cortex. Collectively, these results demonstrate similar alterations across species, suggesting that NF1 pathogenesis is linked to striatal dysfunction and disrupted corticocortical connectivity in the default network.
Multifactorial pathways facilitate resilience among kindergarteners at risk for dyslexia: A longitudinal behavioral and neuroimaging study
Authors: Zuk Jennifer , Dunstan Jade , Norton Elizabeth , Yu Xi , Ozernov-Palchik Ola , Wang Yingying , Hogan Tiffany P. , Gabrieli John D. E. , Gaab Nadine 
Published: April 2019

ABSTRACTRecent efforts have focused on screening methods to identify children at risk for dyslexia as early as preschool/kindergarten. Unfortunately, while low sensitivity leads to under-identification of at-risk children, low specificity can lead to over-identification, resulting in inaccurate allocation of limited educational resources. The present study focused on children identified as at-risk in kindergarten who donotsubsequently develop dyslexia to specify factors associated with better reading outcomes among at-risk children. Early screening was conducted in kindergarten and a subset of children was tracked longitudinally until second grade. Potential protective factors were evaluated at cognitive-linguistic, environmental, and neural levels. Relative to at-risk kindergarteners who subsequently developed dyslexia, those who did not were characterized by significantly higher socioeconomic status (SES), speech production accuracy, and microstructure of the posterior right-hemispheric superior longitudinal fasciculus (SLF). A positive association between microstructure of the right SLF and subsequent decoding skills was found to be specific to at-risk children and not observed among typical controls. Among at-risk children, several kindergarten-age factors were found to significantly contribute to the prediction of subsequent decoding skills: microstructure of the posterior right SLF, age, gender, SES, and phonological awareness. These findings suggest that putative compensatory mechanisms are already present by the start of kindergarten. The right SLF, in conjunction with the cognitive-linguistic and socioeconomic factors identified, may play an important role in facilitating reading development among at-risk children. This study has important implications for approaches to early screening, and assessment strategies for at-risk children.
Complexity and ultrastructure of infectious extracellular vesicles from cells infected by non-enveloped virus
Authors: Yang Jie E. , Rossignol Evan D. , Chang Deborah , Zaia Joseph , Forrester Isaac , Saulsbery Holly , Nicastro Daniela , Jackson William T. , Bullitt Esther 
Published: April 2019

AbstractEnteroviruses support cell-to-cell viral transmission prior to their canonical lytic spread of virus. Poliovirus (PV), a prototype for human pathogenic positive-sense RNA enteroviruses, and picornaviruses in general, transport multiple virionsen blocvia infectious extracellular vesicles secreted from host cells. Using biochemical and biophysical methods we identify multiple components in these secreted vesicles, including PV virions; positive and negative-sense viral RNA; essential viral replication proteins; ribosomal and regulatory cellular RNAs; and numerous host cell proteins, such as regulators of cellular metabolism and structural remodeling. Using cryo-electron tomography, we visualize the near-native three-dimensional architecture of secreted infectious extracellular vesicles containing both virions and a unique mat-like structure. Based on our biochemical data (western blot, RNA-Seq, and mass spectrometry), these mat-like structures are expected to be comprised of unencapsidated RNA and proteins. Our data show that, prior to cell lysis, non-enveloped viruses are secreted within infectious vesicles that also transport viral and host RNAs and proteins.ImportanceThe family of picornaviridae is comprised of small positive-sense RNA viruses, many of which are significant human pathogens. Picornaviruses exploit secreted extracellular vesicles for cell-to-cell viral transmission without cell lysis, and poliovirus serves as a model system for picornaviruses that are not protected by a surrounding membrane (non-enveloped viruses). The structure and contents of these vesicles secreted by virus-infected cells are described here. In addition to mature virions, these vesicles carry negative-sense, ‘template’ viral RNA and essential replication proteins, as well as cellular resources from the host. Their complex contents may comprise an enhanced virulence factor for propagation of infection, and understanding their structure and function is helping elucidate the mechanism by which extracellular vesicles contribute to the spread of non-enveloped virus infection.