bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lung, spleen and oesophagus tissue remains stable for scRNAseq in cold preservation
Authors: Madissoon E. , Wilbrey-Clark A. , Miragaia R.J. , Saeb-Parsy K. , Mahbubani K. , Georgakopoulos N. , Harding P. , Polanski K. , Nowicki-Osuch K. , Fitzgerald R.C. , Loudon K.W. , Ferdinand J.R. , Clatworthy M.R , Tsingene A. , Van Dongen S. , Dabrowska M. , Patel M. , Stubbington M.J.T. , Teichmann S. , Stegle O. , Meyer K.B. 
Published: September 2019

AbstractBackgroundThe Human Cell Atlas is a large international collaborative effort to map all cell types of the human body. Single cell RNA sequencing can generate high quality data for the delivery of such an atlas. However, delays between fresh sample collection and processing may lead to poor data and difficulties in experimental design. Despite this, there has not yet been a systematic assessment of the effect of cold storage time on the quality of scRNAseqResultsThis study assessed the effect of cold storage on fresh healthy spleen, oesophagus and lung from ≥5 donors over 72 hours. We collected 240,000 high quality single cell transcriptomes with detailed cell type annotations and whole genome sequences of donors, enabling future eQTL studies. Our data provide a valuable resource for the study of these three organs and will allow cross-organ comparison of cell types.We see little effect of cold ischaemic time on cell viability, yield, total number of reads per cell and other quality control metrics in any of the tissues within the first 24 hours. However, we observed higher percentage of mitochondrial reads, indicative of cellular stress, and increased contamination by background “ambient RNA” reads in the 72h samples in spleen, which is cell type specific.ConclusionsIn conclusion, we present robust protocols for tissue preservation for up to 24 hours prior to scRNAseq analysis. This greatly facilitates the logistics of sample collection for Human Cell Atlas or clinical studies since it increases the time frames for sample processing.
Visual acuity performance level is independent of locomotion
Authors: Swain Alex D. , Park Eunsol , Cheng Zhang Yu , Kowalewski Nina , Sun Angela , Allen Tessa , Kuhlman Sandra J. 
Published: September 2019

ABSTRACTLocomotion has a global impact on circuit function throughout the cortex, including regulation of spatiotemporal dynamics in primary visual cortex (V1). The mechanisms driving state-changes in V1 result in a 2-3 fold gain of responsiveness to visual stimuli. To determine whether locomotion-mediated increases in response gain improve the perception of spatial acuity we developed a head-fixed task in which mice were free to run or sit still during acuity testing. Spatial acuity, ranging from 0.1 to 0.7 cycles/°, was assessed before and after 3-4 weeks of reward-based training in adult mice. Training on vertical orientations once a day improved the average performance across mice by 22.5 ± 0.05%. Improvement transferred to non-trained orientations presented at 45°, indicating that the improvement in acuity generalized. Furthermore we designed a second closed-loop task in which acuity threshold could be directly assessed in a single session. Using this design, we established that acuity threshold matched the upper limit of the trained spatial frequency; in two mice spatial acuity threshold reached as high as 1.5 cycles/°. During the 3-4 weeks of training we collected a sufficient number of stimulus trials in which mice performed above chance but below 100% accuracy. Using this subset of stimulus trials, we found that perceptual acuity was not enhanced on trials in which mice were running compared to trials in which mice were still. Our results demonstrate that perception of spatial acuity is not improved by locomotion.
Dysfunctional and compensatory brain networks underlying math fluency
Authors: La Michelle AN , Saha Debjani , Berman Karen F , Tan Hao Yang 
Published: September 2019

AbstractPoor math fluency, or timed calculation (TC) performance, is a characteristic of dyscalculia, a common cause of poor educational and occupational outcomes. Here, we examined neural substrates of dysfunctional math fluency and potential compensatory mechanisms. We performed functional MRI scans of participants with divergent performance on an event-related TC paradigm (poor TC, <0.5 accuracy, n=34; vs. controls, accuracy>0.8, n=34). Individuals with poor TC had decreased intraparietal sulcus (IPS) engagement, and decreased IPS-striatal and IPS-prefrontal effective connectivity. We next examined an independent well-performing sample (TC accuracy>0.8, n=100), stratified according to relatively low-versus high-IPS activation during TC. Relatively reduced IPS engagement, or patterns of IPS-related effective connectivity similar to those with poor TC, appeared to be compensated for by increased engagement of effective connectivity involving fusiform gyrus, angular gyrus, inferior frontal gyrus and striatum. Neural connectivity involving high-level visual processing in fusiform gyrus and related ventral cortical networks may be relevant in compensatory function ameliorating aspects of dyscalculia and mathematical difficulty.
Computational Pan-genome Mapping and pairwise SNP-distance improve Detection of Mycobacterium tuberculosis Transmission Clusters
Authors: Jandrasits Christine , Kröger Stefan , Haas Walter , Renard Bernhard Y. 
Published: September 2019

AbstractNext-generation sequencing based base-by-base distance measures have become an integral complement to epidemiological investigation of infectious disease outbreaks. This study introduces PANPASCO, a computational pan-genome mapping based, pairwise distance method that is highly sensitive to differences between cases, even when located in regions of lineage specific reference genomes. We show that our approach is superior to previously published methods in several datasets and across different Mycobacterium tuberculosis lineages, as its characteristics allow the comparison of a high number of diverse samples in one analysis - a scenario that becomes more and more likely with the increased usage of whole-genome sequencing in transmission surveillance.Author summaryTuberculosis still is a threat to global health. It is essential to detect and interrupt transmissions to stop the spread of this infectious disease. With the rising use of next-generation sequencing methods, its application in the surveillance of Mycobacterium tuberculosis has become increasingly important in the last years. The main goal of molecular surveillance is the identification of patient-patient transmission and cluster detection. The mutation rate of M. tuberculosis is very low and stable. Therefore, many existing methods for comparative analysis of isolates provide inadequate results since their resolution is too limited. There is a need for a method that takes every detectable difference into account. We developed PANPASCO, a novel approach for comparing pairs of isolates using all genomic information available for each pair. We combine improved SNP-distance calculation with the use of a pan-genome incorporating more than 100 M. tuberculosis reference genomes for read mapping prior to variant detection. We thereby enable the collective analysis and comparison of similar and diverse isolates associated with different M. tuberculosis strains.
Neural representation of current and intended task sets during sequential judgements on human faces
Authors: Díaz-Gutiérrez Paloma , Gilbert Sam J. , Arco Juan E. , Sobrado Alberto , Ruz María 
Published: September 2019

AbstractEngaging in a demanding activity while holding in mind another task to be performed in the near future requires the maintenance of information about both the currently-active task set and the intended one. However, little is known about how the human brain implements such action plans. While some previous studies have examined the neural representation of current task sets and others have investigated delayed intentions, to date none has examined the representation of current and intended task sets within a single experimental paradigm. In this fMRI study, we examined the neural representation of current and intended task sets, employing sequential classification tasks on human faces. Multivariate decoding analyses showed that current task sets were represented in the orbitofrontal cortex (OFC) and fusiform gyrus (FG), while intended tasks could be decoded from lateral prefrontal cortex (lPFC). Importantly, a ventromedial region in PFC/OFC contained information about both current and delayed tasks, although cross-classification between the two types of information was not possible. These results help delineate the neural representations of current and intended task sets, and highlight the importance of ventromedial PFC/OFC for maintaining task-relevant information regardless of when it is needed.
Correlation of sympathetic and parasympathetic nervous system activity during rest and acute stress tasks
Authors: Weissman David G. , Mendes Wendy Berry 
Published: September 2019

AbstractAutonomic nervous system (ANS) activity is a core and central component of emotion. The myriad social and cognitive challenges faced by humans require flexible modulation of ANS activity for different contexts. In this study, simultaneous activity of the parasympathetic and sympathetic nervous system was measured using respiratory sinus arrhythmia (RSA) and pre-ejection period (PEP), respectively. Samples combined four previous studies (N=325) in which RSA and PEP were collected continuously during a resting baseline and an acute stressor, the Trier Social Stress Task. The concurrent relation between RSA and PEP responses was modeled in order to determine the extent to which SNS and PNS activity is correlated across the task within and between participants, and whether this correlation was moderated by age, race, sex, or baseline RSA and PEP. Overall, RSA and PEP were reciprocally coupled, perhaps reflecting shared regulatory mechanisms in the brain. However, recovery from a stressor was characterized by coactivation. Individuals also vary in the extent to which their SNS and PNS are reciprocally coupled; women, younger adults, and individuals with higher baseline RSA showed more reciprocal coupling than men, older adults, and those with lower baseline RSA, respectively, reflecting greater coordination of physiological responding in the former group.
Adjusting ADJUST: Optimizing the ADJUST Algorithm for Pediatric Data Using Geodesic Nets
Authors: Leach Stephanie C. , Morales Santiago , Bowers Maureen E. , Buzzell George A. , Debnath Ranjan , Beall Daniel , Fox Nathan A. 
Published: September 2019

AbstractA major challenge for electroencephalograph (EEG) studies on pediatric populations is that large amounts of data are lost due to artifacts (e.g., movement and blinks). Independent component analysis (ICA) can separate artifactual and neural activity, allowing researchers to remove such artifactual activity and retain a greater percentage of EEG data for analyses. However, manual identification of artifactual components is time consuming and requires subjective judgment. Automated algorithms, like ADJUST and ICLabel, have been validated on adults using the international 10-20 system, but to our knowledge no such algorithms have been optimized for the geodesic sensor net, which is often used with infants and children. Therefore, in an attempt to automate artifact selection for pediatric data collected with geodesic nets, we modified ADJUST’s algorithm. Our “adjusted-ADJUST” algorithm was compared to the “original-ADJUST” algorithm and ICLabel in adults, children, and infants on three different performance measures: respective classification agreement with expert coders, the number of trials retained following artifact removal, and the reliability of the EEG signal after pre-processing with each algorithm. Overall, the adjusted-ADJUST algorithm performed better than the original-ADJUST algorithm and no ICA correction with adult and pediatric data. Moreover, it performed better than ICLabel for pediatric data. These results indicate that optimizing existing algorithms for data collected with a geodesic net improves artifact classification and retains more trials, potentially facilitating EEG studies with pediatric populations.
A key role for phosphorylation of PsbH in the biogenesis and repair of photosystem II in Chlamydomonas
Authors: Riché Alexis , Lefebvre-Legendre Linnka , Goldschmidt-Clermont Michel 
Published: September 2019

ABSTRACTPhosphorylation of the core subunits of photosystem II (PSII) is largely governed by a protein kinase and an antagonistic protein phosphatase. In plants the respective mutants show alterations in the architecture of thylakoid membranes and in the repair of PSII after photo-inhibition. However the protein kinase targets several subunits of PSII, as well as other proteins. To specifically investigate the role of phosphorylation of the different PSII subunits, we used site-directed mutagenesis and chloroplast transformation inChlamydomonas reinhardtii. Major, evolutionarily-conserved sites of phosphorylation in three components of PSII (CP43, D2 and PsbH) were mutated to replace the corresponding serine or threonine residues with alanine. The alanine substitution mutant of D2 had no apparent phenotype, while the mutant of CP43 presented a minor delay in recovery from photo-inhibition. Alanine substitutions of the phosphorylation sites in PsbH had significant effects on the accumulation of PSII or on its recovery from photo-inhibition. When mutations in two of the target subunits were combined through a second cycle of chloroplast transformation, the strongest phenotype was observed in the mutant lacking phosphorylation of both PsbH and CP43, which showed delayed recovery from photo-inhibition. Surprisingly this phenotype was reversed in the mutant defective for phosphorylation of all three subunits. Our analysis indicates a prominent role for the N-terminus of PsbH in the stable accumulation of PSII and of PsbH phosphorylation in its repair cycle.SIGNIFICANCE STATEMENTTo specifically investigate the role of PSII phosphorylation, alanine-substitution mutants of the major phospho-sites in the subunits of PSII were generated individually or in combinations using chloroplast transformation. PSII assembly was defective in some of the PsbH mutants. PSII repair after photo-inhibition was delayed most strongly in the mutant lacking phosphorylation of both PsbC (CP43) and PsbH.
Impact of peripheral mutations on the access channels of human cytochrome P450 1A2
Authors: Ying Beili , Zhong Yang , Wang Jingfang 
Published: September 2019

AbstractAs an important member of cytochrome P450 (CYP) enzymes, human CYP1A2 is associated with the metabolism of caffeine and melatonin and the activation of precarcinogens. Besides, this CYP protein also involves in metabolizing 5-10% of clinical medicines. Some peripheral mutations in CYP1A2 (P42R, I386F, R431W, and R456H) significantly decrease the enzyme activities, resulting in a vital reduction in substrate metabolisms. To explore the effects of these peripheral mutations, we constructed a membrane-binding model for the full-length human CYP1A2 and studied their dynamic behaviors on lipid membranes. Free energy calculations indicate that the peripheral mutations donot influence substrate binding. P42R is located in the N-terminal anchor, and its positive charged sidechain is adverse to membrane binding. I386F enhances the van der Waals contacts of the water channel bottleneck and R456H breaks the hydrogen bonding interactions that function to position the BC loop, both of which result in a significant inhibition on the water channel. R431W causes a sidechain conformational rearrangement for aromatic residues around the substrate channel, making it in a closed state in most cases. Our computational simulations demonstrate that pi-pi stacking interactions are essential for substrate binding and channel opening. We hope that these findings may be of general relevance to the mutation-induced activity changes for CYP proteins, providing useful information for understanding the CYP-mediated drug metabolism.
Three-dimensional chromatin interactions remain stable upon CAG/CTG repeat expansion
Authors: Buendía Gustavo A. Ruiz , Leleu Marion , Marzetta Flavia , Vanzan Ludovica , Tan Jennifer Y. , Marques Ana C. , Baubec Tuncay , Murr Rabih , Xenarios Ioannis , Dion Vincent 
Published: September 2019

AbstractExpanded CAG/CTG repeats underlie thirteen neurological disorders, including myotonic dystrophy (DM1) and Huntington’s disease (HD). Upon expansion, CAG/CTG repeat loci acquire heterochromatic characteristics. This observation raises the hypothesis that repeat expansion provokes changes to higher order chromatin folding and thereby affects both gene expression in cis and the genetic instability of the repeat tract. Here we tested this hypothesis directly by performing 4C sequencing at the DMPK and HTT loci from DM1 and HD patient-derived cells. Surprisingly, chromatin contacts remain unchanged upon repeat expansion at both loci. This was true for loci with different DNA methylation levels and CTCF binding. Repeat sizes ranging from 15 to 1,700 displayed strikingly similar chromatin interaction profiles. Our findings argue that extensive changes in heterochromatic properties are not enough to alter chromatin folding at expanded CAG/CTG repeat loci. Moreover, the ectopic insertion of an expanded repeat tract did not change three-dimensional chromatin contacts. We conclude that expanded CAG/CTG repeats have little to no effect on chromatin conformation.
Insights into the dynamic control of breathing revealed through cell-type-specific responses to substance P
Authors: Baertsch Nathan A , Ramirez Jan-Marino 
Published: September 2019

AbstractThe rhythm generating network for breathing must continuously adjust to changing metabolic and behavioral demands. Here, we examine network-based mechanisms in the mouse preBӧtzinger complex using substance P, a potent excitatory modulator of breathing frequency and stability, as a tool to dissect network properties that underlie dynamic breathing. We find that substance P does not alter the balance of excitation and inhibition during breaths or the duration of the resulting refractory period. Instead, mechanisms of recurrent excitation between breaths are enhanced such that the rate that excitation percolates through the network is increased. Based on our results, we propose a conceptual framework in which three distinct phases, the inspiratory phase, refractory phase, and percolation phase, can be differentially modulated to influence breathing dynamics and stability. Unravelling mechanisms that support this dynamic control may improve our understanding of nervous system disorders that destabilize breathing, many of which are associated with changes in brainstem neuromodulatory systems.
High photosynthesis rate in the selected wild rice is driven by leaf anatomy mediating high Rubisco activity and electron transport rate
Authors: Mathan Jyotirmaya , Singh Anuradha , Jathar Vikram , Ranjan Aashish 
Published: September 2019

AbstractThe importance of increasing photosynthetic efficiency for sustainable crop yield increases to feed the growing world population is well recognized. The natural genetic variation for leaf photosynthesis in crop plants is largely unexploited for increasing genetic yield potential. The genus Oryza, including cultivated rice and wild relatives, offers tremendous genetic variability to explore photosynthetic differences, and underlying biochemical, photochemical, and developmental bases. We quantified leaf photosynthesis and related physiological parameters for six cultivated and three wild rice genotypes, and identified photosynthetically efficient wild rice accessions. Fitting A/Ci curves and biochemical analyses showed that the leaf photosynthesis in cultivated rice varieties, IR64 and Nipponbare, was limited due to leaf nitrogen content, Rubisco activity, and electron transport rate compared to photosynthetically efficient accessions of wild rice Oryza australiensis and Oryza latifolia. The selected wild rice accessions with high leaf photosynthesis per unit area had striking anatomical features, such as larger mesophyll cells with more chloroplasts, fewer mesophyll cells between two consecutive veins, and higher mesophyll cell and chloroplast surface area exposed to intercellular space. Our results show the existence of desirable variations in Rubisco activity, electron transport rate, and leaf anatomical features in the rice system itself that could be targeted for increasing the photosynthetic efficiency of cultivated rice varieties.HighlightDistinct leaf biochemical, photochemical, and developmental features contribute to efficient photosynthesis in the selected wild rice accessions that could potentially be exploited to increase rice leaf photosynthesis.
Concomitant phytonutrient and transcriptome analysis of mature fruit and leaf tissues of tomato (Solanum lycopersicum L. cv. Oregon Spring) grown using organic and conventional fertilizer
Authors: Sharpe Richard M , Gustafson Luke , Hewitt Seanna , Kilian Benjamin , Crabb James , Hendrickson Christopher , Jiwan Derick , Andrews Preston , Dhingra Amit 
Published: September 2019

ABSTRACTEnhanced levels of antioxidants, phenolic compounds, carotenoids and vitamin C have been reported for several crops grown under organic fertilizer, albeit with yield penalties. As organic agricultural practices continue to grow and find favor it is critical to gain an understanding of the molecular underpinnings of the factors that limit the yields in organically farmed crops. Concomitant phytochemical and transcriptomic analysis was performed on mature fruit and leaf tissues derived from Solanum lycopersicum L. ‘Oregon Spring’ grown under organic and conventional fertilizer conditions to evaluate the following hypotheses. 1. Organic soil fertilizer management results in greater allocation of photosynthetically derived resources to the synthesis of secondary metabolites than to plant growth, and 2. Genes involved in changes in the accumulation of phytonutrients under organic fertilizer regime will exhibit differential expression, and that the growth under different fertilizer treatments will elicit a differential response from the tomato genome. Both these hypotheses were supported, suggesting an adjustment of the metabolic and genomic activity of the plant in response to different fertilizers. Organic fertilizer treatment showed an activation of photoinhibitory processes through differential activation of nitrogen transport and assimilation genes resulting in higher accumulation of phytonutrients. This information can be used to identify alleles for breeding crops that allow for efficient utilization of organic inputs.Significance statementOrganic fertilizer changes the expression of the tomato genome, induces photosynthetic stress which elicits higher production of secondary metabolites.