bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mapping numerical perception and operations in relation to functional and anatomical landmarks of human parietal cortex
Authors: Castaldi Elisa , Vignaud Alexandre , Eger Evelyn 
Published: April 2019

AbstractHuman functional imaging has identified the middle part of the intraparietal sulcus (IPS) as an important brain substrate for different types of numerical tasks. This area is often equated with the macaque ventral intraparietal area (VIP) where neuronal selectivity for non-symbolic numbers is found. However, the low spatial resolution and whole-brain averaging analysis performed in most fMRI studies limit the extent to which an exact correspondence of activation in different numerical tasks with specific sub-regions of the IPS can be established. Here we disentangled the functional neuroanatomy of numerical perception and operations (comparison and calculation) by acquiring high-resolution 7T fMRI data in a group of human adults, and relating the activations in different numerical contrasts to anatomical and functional landmarks on the cortical surface. Our results reveal a functional heterogeneity within human intraparietal cortex where the visual field map representations in superior/medial parts of IPS and superior parietal gyrus are involved predominantly in numerosity perception, whereas numerical operations predominantly recruit lateral/inferior parts of IPS. Since calculation and comparison-related activity fell mainly outside the field map representations considered the functional equivalent of the monkey VIP/LIP complex, the areas most activated during such numerical operations in humans are likely different from VIP.
Fidelity of Prespacer Capture and Processing is Governed by the PAM Mediated Interaction of Cas1-2 Adaptation complex in Escherichia coli
Authors: Yoganand K.N.R. , Muralidharan Manasasri , Anand B. 
Published: April 2019

ABSTRACTDuring CRISPR adaptation, short sections of invader derived DNA of defined length are specifically integrated at the leader-repeat junction as spacers by Cas1-2 integrase complex. While several variants of CRISPR systems utilise Cas4 as an indispensible nuclease for processing the PAM containing prespacers to a defined length for integration– surprisingly– a few CRISPR systems such as type I-E are bereft of Cas4. Therefore, how the prespacers show impeccable conservation for length and PAM selection in type I-E remains intriguing. In Escherichia coli, we show that Cas1-2/I-E– via the type I-E specific extended C-terminal tail of Cas1 –displays intrinsic affinity for PAM containing prespacers of variable length and its binding protects the prespacer boundaries of defined length from the exonuclease action that ensues the pruning of aptly sized substrates for integration. This suggests that cooperation between Cas1-2 and cellular exonucleases drives the Cas4 independent prespacer capture and processing in type I-E.
Precise timing is ubiquitous, consistent and coordinated across a comprehensive, spike-resolved flight motor program
Authors: Putney Joy , Conn Rachel , Sponberg Simon 
Published: April 2019

Sequences of action potentials, or spikes, carry information in the number of spikes and their timing. Spike timing codes are critical in many sensory systems, but there is now growing evidence that millisecond-scale changes in timing also carry information in motor brain regions, descending decision-making circuits, and individual motor units. Across all the many signals that control a behavior how ubiquitous, consistent, and coordinated are spike timing codes? Assessing these open questions ideally involves recording across the whole motor program with spike-level resolution. To do this, we took advantage of the relatively few motor units controlling the wings of a hawk moth,Manduca sexta. We simultaneously recorded nearly every action potential from all major wing muscles and the resulting forces in tethered flight. We found that timing encodes more information about turning behavior than spike count in every motor unit, even though there is sufficient variation in count alone. Flight muscles vary broadly in function as well as in the number and timing of spikes. Nonetheless, each muscle with multiple spikes consistently blends spike timing and count information in a 3:1 ratio. Coding strategies are consistent. Finally, we assess the coordination of muscles using pairwise redundancy measured through interaction information. Surprisingly, not only are all muscle pairs coordinated, but all coordination is accomplished almost exclusively through spike timing, not spike count. Spike timing codes are ubiquitous, consistent, and essential for coordination.Significance StatementBrains can encode precise sensory stimuli and specific motor systems also appear to be precise, but how important are millisecond changes in timing of neural spikes across the whole motor program for a behavior? We record every spike that the hawk moth’s nervous system sends to its wing muscles. We show that all muscles convey the majority of their information in spike timing. The number of spikes does play a role, but not in a coordinated way across muscles. Instead, all coordination is done using in the millisecond timing of in spikes. The importance and prevalence of timing across the motor program pose new questions for how nervous systems create precise, coordinated motor commands.
Assessment and representation of variability in ecological niche model predictions
Authors: Cobos Marlon E. , Osorio-Olvera Luis , Peterson A. Townsend 
Published: April 2019

AbstractEcological niche models are popular tools used in fields such as ecology, biogeography, conservation biology, and epidemiology. These models are used commonly to produce representations of species’ potential distributions, which are then used to answer other research questions; for instance, where species richness is highest, where potential impacts of climate change can be anticipated, or where to expect spread of invasive species or disease vectors. Although these representations of potential distributions are variable which contributes to uncertainty in these predictions, model variability is neglected when presenting results of ecological niche model analyses. Here, we present examples of how to quantify and represent variability in models, particularly when models are transferred in space and time. To facilitate implementations of analyses of variability, we developed R functions and made them freely available. We demonstrate means of understanding how much variation exists and where this variation is manifested in geographic space. Representing model variability in geographic space gives a reference of the uncertainty in predictions, so analyzing this aspect of model outcomes must be a priority when policy is to be set or decisions taken based on these models. Our open access tools also facilitate post modeling process that otherwise could take days of manual work.
Pairing interactions between nucleobases and ligands in aptamer:ligand complexes of riboswitches: Crystal structure analysis, classification, optimal structures and accurate interaction energies
Authors: Prabhakar Preethi S. , Sharma Purshotam , Mitra Abhijit 
Published: April 2019

ABSTRACTIn the present work, sixty-seven crystal structures of the aptamer domains of RNA riboswitches, are chosen for analysis of the structure and strength of hydrogen bonding (pairing) interactions between nucleobases constituting the aptamer binding pockets and the bound ligands. A total of eighty unique base:ligand hydrogen-bonded pairs containing at least two hydrogen bonds were identified through visual inspection. Classification of these contacts in terms of the interacting edge of the aptamer nucleobase revealed that interactions involving the Watson-Crick edge are the most common, followed by the sugar edge of purines and the Hoogsteen edge of uracil. Alternatively, classification in terms of the chemical constitution of the ligand yields five unique classes of base:ligand pairs: base:base, base:amino acid, base:sugar, base:phosphate and base:other. Further, quantum mechanical (QM) geometry optimizations revealed that sixty seven out of eighty pairs exhibit stable geometries and optimal deviations from their macromolecular crystal occurrences. This indicates that these contacts are well-defined RNA aptamer:ligand interaction motifs. QM calculated interaction energies of base:ligand pairs reveal rich hydrogen bonding landscape, ranging from weak interactions (base:other, –3 kcal/mol) to strong (base:phosphate, –48 kcal/mol) contacts. The analysis was further extended to study the biological importance of base:ligand interactions in the binding pocket of the tetrahydrofolate riboswitch and thiamine pyrophosphate riboswitch. Overall, our study helps in understanding the structural and energetic features of base:ligand pairs in riboswitches, which could aid in developing meaningful hypotheses in context of RNA:ligand recognition. This can, in turn contribute towards current efforts to develop antimicrobials that target RNAs.
Evolution of Auxin Response Factors in plants characterized by phylogenomic synteny network analyses
Authors: Gao Bei , Wang Liuqiang , Oliver Melvin , Chen Moxian , Zhang Jianhua 
Published: April 2019

SUMMARYAuxin response factors (ARFs) have long been a research focus and represent a class of key regulators of plant growth and development. Previous studies focusing genes from limited number of species were unable to uncover the evolutionary trajectory of this family. Here, more than 3,500 ARFs collected from plant genomes and transcriptomes covering major streptophyte lineages were used to reconstruct the broad-scale family phylogeny, where the early origin and diversification ofARFin charophytes was delineated. Based on the family phylogeny, we proposed a unified six-group classification system for angiosperm ARFs. Phylogenomic synteny network analyses revealed the deeply conserved genomic syntenies within each of the six ARF groups and the interlocking syntenic relationships connecting distinct groups. Recurrent duplication events, such as those that occurred in seed plant, angiosperms, core eudicots and grasses contributed the expansion of ARF genes which facilitated functional diversification. Ancestral transposition activities in important plant families, including crucifers, legumes and grasses, were unveiled by synteny network analyses. Ancestral gene duplications along with transpositions have profound evolutionary significance which may have accelerated the functional diversification process of paralogues. Our study provides insights into the evolution of ARFs which will enhance our current understandings for this important transcription factor family.
Nuisance effects in inter-scan functional connectivity estimates before and after nuisance regression
Authors: Nalci Alican , Luo Wenjing , Liu Thomas T. 
Published: April 2019

AbstractIn resting-state functional MRI, the correlation between blood-oxygenation-level-dependent (BOLD) signals across brain regions is used to estimate the functional connectivity (FC) of the brain. FC estimates are prone to the influence of nuisance factors including scanner-related artifacts and physiological modulations of the BOLD signal. Nuisance regression is widely performed to reduce the effect of nuisance factors on FC estimates on a per-scan basis. However, a dedicated analysis of nuisance effects on the variability of FC metrics across a collection of scans has been lacking. This work investigates the effects of nuisance factors on the variability of FC estimates across a collection of scans both before and after nuisance regression. Inter-scan variations in FC estimates are shown to be significantly correlated with the geometric norms of various nuisance terms, including head motion measurements, signals derived from white-matter and cerebrospinal regions, and the whole-brain global signal (GS) both before and after nuisance regression. In addition, it is shown that GS regression (GSR) can introduce GS norm-related fluctuations that are negatively correlated with inter-scan FC estimates. The empirical results are shown to be largely consistent with the predictions of a theoretical framework previously developed for the characterization of dynamic FC measures. This work shows that caution must be exercised when interpreting inter-scan FC measures across scans both before and after nuisance regression.
Positional dynamics and glycosomal recruitment of developmental regulators during trypanosome differentiation
Authors: Szöőr Balázs , Simon Dorina V. , Rojas Federico , Young Julie , Robinson Derrick R. , Krüger Timothy , Engstler Markus , Matthews Keith R. 
Published: April 2019

AbstractGlycosomes are peroxisome-related organelles that compartmentalise the glycolytic enzymes in kinetoplastid parasites. These organelles are developmentally regulated in their number and composition, allowing metabolic adaptation to the parasite’s needs in the blood of mammalian hosts or within their arthropod vector. A protein phosphatase cascade regulates differentiation between parasite developmental forms, comprising a tyrosine phosphatase, TbPTP1, that dephosphorylates and inhibits a serine threonine phosphatase TbPIP39 that promotes differentiation. When TbPTP1 is inactivated, TbPIP39 is activated and during differentiation becomes located in glycosomes. Here we have tracked TbPIP39 recruitment to glycosomes during differentiation from bloodstream stumpy forms to procyclic forms. Detailed microscopy and live cell imaging during the synchronous transition between life cycle stages revealed that in stumpy forms, TbPIP39 is located at a periflagellar pocket site closely associated with TbVAP, that defines the flagellar pocket endoplasmic reticulum. TbPTP1 is also located at the same site in stumpy forms, as is REG9.1, a regulator of stumpy-enriched mRNAs. This site provides a molecular node for the interaction between TbPTP1 and TbPIP39. Within 30 minutes of the initiation of differentiation TbPIP39 relocates to glycosomes whereas TbPTP1 disperses to the cytosol. Overall, the study identifies a ‘stumpy regulatory nexus’ (STuRN) that co-ordinates the molecular components of life cycle signalling and glycosomal development during transmission ofTrypanosoma brucei.ImportanceAfrican trypanosomes are parasites of sub-Saharan Africa responsible for both human and animal disease. The parasites are transmitted by tsetse flies and completion of their life cycle involves progression through several development steps. The initiation of differentiation between blood and tsetse forms is signalled by a phosphatase cascade, ultimately trafficked into peroxisome-related organelles called glycosomes that are unique to this group of organisms. Glycosomes undergo substantial remodelling of their composition and function during the differentiation step but how this is regulated is not understood. Here we identify a cytological site where the signalling molecules controlling differentiation converge before the dispersal of one of them into glycosomes. This coincides with a specialised ER site that may contribute to glycosome developmental biogenesis or regeneration. In combination, the study provides the first insight into the spatial co-ordination of signalling pathway components in trypanosomes as they undergo cell-type differentiation.
DNA barcoding reveals that injected transgenes are predominantly processed by homologous recombination in mouse zygote
Authors: Smirnov Alexander , Yunusova Anastasia , Korablev Alexey , Serova Irina , Fishman Veniamin , Battulin Nariman 
Published: April 2019

AbstractMechanisms that ensure repair of double-stranded DNA breaks play a key role in the integration of foreign DNA into the genome of transgenic organisms. After pronuclear microinjection, exogenous DNA is usually found in the form of concatemer consisting of multiple co-integrated transgene copies. Here we investigated contribution of various DSB repair pathways to the concatemer formation. We injected a pool of linear DNA molecules carrying unique barcodes at both ends into mouse zygotes and obtained 10 transgenic embryos with transgene copy number ranging from 1 to 300 copies. Sequencing of the barcodes allowed us to assign relative positions to the copies in concatemers and to detect recombination events that happened during integration. Cumulative analysis of approximately 1000 integrated copies revealed that more than 80% of copies underwent recombination when their linear ends were processed by SDSA or DSBR. We also observed evidence of double Holliday junction (dHJ) formation and crossing-over during the formation of concatemers. Additionally, sequencing of indels between copies showed that at least 10% of the DNA molecules introduced into the zygote are ligated by non-homologous end joining (NHEJ). Our barcoding approach documents high activity of homologous recombination after exogenous DNA injection in mouse zygote.
Intraspecific variation in Artiodactyla social organisation: A Bayesian phylogenetic multilevel analysis of detailed population-level data
Authors: Miles M.I. , Jaeggi A.V. , Festa-Bianchet M. , Schradin C. , Hayes L.D. 
Published: April 2019

AbstractUnderstandinginter-specific variation in social systems is a major goal of behavioural ecology. Previous comparative studies of mammalian social organisation produced inconsistent results, possibly because they ignoredintra-specific variation in social organisation (IVSO). The Artiodactyla have been the focus of many comparative studies as they occupy a wide diversity of habitats and exhibit large variation in life history patterns as well as other potential correlates of social organisation. Here we present the first systematic data on IVSO among Artiodactyla, infer their ancestral social organisation, and test whether habitat, sexual dimorphism, seasonal breeding, and body size predict inter- and intraspecific variation in social organisation. We found data on social organisation for 110 of 226 artiodactyl species, of which 74.5% showed IVSO. Using Bayesian phylogenetic multilevel models, the ancestral artiodactyl population was predicted to have a variable social organisation with significantly higher probability (0.77, 95% CI 0.29-1.00) than any non-variable form (i.e. solitary, pair-living, group-living). Greater sexual dimorphism and smaller body size both predicted more IVSO; smaller body size also predicted a higher likelihood of pair-living. Our results challenge the long-held assumption that ancestral Artiodactyla were pair-living and strongly imply that taking IVSO into account is crucial for understanding mammalian social evolution.
Crowder-induced Conformational Ensemble Shift inEscherichia ColiProlyl-tRNA Synthetase
Authors: Adams L. M. , Andrews R. J. , Hu Q. H. , Schmit H. L. , Hati S. , Bhattacharyya S. 
Published: April 2019

ABSTRACTThe effect of macromolecular crowding on the structure and function ofEscherichia coliprolyl-tRNA synthetase (Ec ProRS) has been investigated using a combined experimental and theoretical method. Ec ProRS is a multi-domain enzyme; coupled-domain dynamics is essential for efficient catalysis. To gain an insight into the mechanistic detail of the crowding effect, kinetic studies were conducted with varying concentrations and sizes of crowders. In parallel, spectroscopic and quantum chemical studies were employed to probe the “soft-interactions” between crowders and protein side chains. Finally, the dynamics of the dimeric protein was examined in the presence of crowders using a long-duration (70 ns) classical molecular dynamic simulations. The results of the simulations revealed a significant shift in the conformational ensemble, which is consistent with the “soft-interactions” model of the crowding effect and explained the observed alteration in kinetic parameters. Collectively, the present study demonstrated that the effects of molecular crowding on both conformational dynamics and catalytic function, are correlated. This is the first report where molecular crowding has been found to impact the conformational ensemble in the multi-domain Ec ProRS, a member of aminoacyl-tRNA synthetase family, which is central to protein synthesis in all living cells. The present study affirmed that the effect of crowders should be considered while investigating the structure-dynamics-function relationship in modular enzymes.
Measuring and Mitigating PCR Bias in Microbiome Data
Authors: Silverman Justin D. , Bloom Rachael J. , Jiang Sharon , Durand Heather K. , Mukherjee Sayan , David Lawrence A. 
Published: April 2019

AbstractPCR amplification plays a central role in the measurement of mixed microbial communities via high-throughput sequencing. Yet PCR is also known to be a common source of bias in microbiome data. Here we present a paired modeling and experimental approach to characterize and mitigate PCR bias in microbiome studies. We use experimental data from mock bacterial communities to validate our approach and human gut microbiota samples to characterize PCR bias under real-world conditions. Our results suggest that PCR can bias estimates of microbial relative abundances by a factor of 2-4 but that this bias can be mitigated using simple Bayesian multinomial logistic-normal linear models.Author summaryHigh-throughput sequencing is often used to profile host-associated microbial communities. Many processing steps are required to transform a community of bacteria into a pool of DNA suitable for sequencing. One important step is amplification where, to create enough DNA for sequencing, DNA from many different bacteria are repeatedly copied using a technique called Polymerase Chain Reaction (PCR). However, PCR is known to introduce bias as DNA from some bacteria are more efficiently copied than others. Here we introduce an experimental procedure that allows this bias to be measured and computational techniques that allow this bias to be mitigated in sequencing data.
The Parkinson’s Disease Mendelian Randomization Research Portal
Authors: Noyce Alastair J , Bandres-Ciga Sara , Kim Jonggeol , Heilbron Karl , Kia Demis , Hemani Gibran , Xue Angli , Lawlor Debbie A , Smith George Davey , Duran Raquel , Gan-Or Ziv , Blauwendraat Cornelis , Gibbs J Raphael ,   23andMe Research Team,   International Parkinson’s Disease Genomics Consortium (IPDGC), Hinds David A , Yang Jian , Visscher Peter , Cuzick Jack , Morris Huw , Hardy John , Wood Nicholas W , Nalls Mike A , Singleton Andrew B 
Published: April 2019

ABSTRACTBackgroundMendelian randomization (MR) is a method for exploring observational associations to find evidence of causality.ObjectiveTo apply MR between multiple risk factors/phenotypic traits (exposures) and Parkinson’s disease (PD) in a large, unbiased manner, and to create a public resource for research.MethodsWe used two-sample MR in which the summary statistics relating to SNPs from genome wide association studies (GWASes) of 5,839 exposures curated on MR Base were used to assess causal relationships with PD. We selected the highest quality exposure GWASes for this report (n=401). For the disease outcome, summary statistics from the largest published PD GWAS were used. For each exposure, the causal effect on PD was assessed using the inverse variance weighted (IVW) method, followed by a range of sensitivity analyses. We used a false discovery rate (FDR) corrected p-value of <0.05 from the IVW analysis to prioritize traits of interest.ResultsWe observed evidence for causal associations between twelve exposures and risk of PD. Of these, nine were causal effects related to increasing adiposity and decreasing risk of PD. The remaining top exposures that affected PD risk were tea drinking, time spent watching television and forced vital capacity, but the latter two appeared to be biased by violations of underlying MR assumptions.DiscussionWe present a new platform which offers MR analyses for a total of 5,839 GWASes versus the largest PD GWASes available (https://pdgenetics.shinyapps.io/pdgenetics/). Alongside, we report further evidence to support a causal role for adiposity on lowering the risk of PD.