bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fractal Dimension of Cortical Functional Connectivity Networks Predicts Severity in Disorders of Consciousness
Authors: Varley TF. , Craig M. , Adapa R. , Finoia P. , Williams G. , Alanson J. , Pickard J. , Menon DK. , Stamatakis EA. 
Published: October 2019

AbstractRecent evidence suggests that the quantity and quality of conscious experience may be a function of the complexity of activity in the brain, and that consciousness emerges in a critical zone on the axes of order/randomness and integration/differentiation. We propose fractal shapes as a measure of proximity to this critical point, as fractal dimension encodes information about complexity beyond simple entropy or randomness, and fractal structures are known to emerge in systems nearing a critical point. To validate this, we tested the several measures of fractal dimension on the brain activity from healthy volunteers and patients with disorders of consciousness of varying severity. We used a Compact Box Burning algorithm to compute the fractal dimension of cortical functional connectivity networks as well as computing the fractal dimension of the associated adjacency matrices using a 2D box-counting algorithm. To test whether brain activity is fractal in time as well as space, we used the Higuchi temporal fractal dimension on BOLD time-series. We found significant decreases in the fractal dimension between healthy volunteers (n=15), patients in a minimally conscious state (n=10), and patients in a vegetative state (n=8), regardless of the mechanism of injury. We also found significant decreases in adjacency matrix fractal dimension and Higuchi temporal fractal dimension, which correlated with decreasing level of consciousness. These results suggest that cortical functional connectivity networks display fractal character and that this is predictive of level of consciousness in a clinically relevant population, with more fractal (i.e. more complex) networks being associated with higher levels of consciousness. This supports the hypothesis that level of consciousness and system complexity are positively associated, and is consistent with previous EEG, MEG, and fMRI studies.
HOX13-dependent chromatin accessibility modulates the target repertoires of the HOX factors
Authors: Desanlis Ines , Kherdjemil Yacine , Mayran Alexandre , Bouklouch Yasser , Gentile Claudia , Sheth Rushikesh , Zeller Rolf , Drouin Jacques , Kmita Marie 
Published: October 2019

ABSTRACTHox genes encode essential transcription factors that control patterning during embryonic development. Distinct combinations of nested Hox expression domains establish cell and tissue identities1–3. Consequently, spatial or temporal de-regulation of Hox genes can cause severe alterations of the body plan3. While HOX factors have very similar DNA binding motifs, their binding specificity is, in part, mediated by co-factors4–6. Yet, the interplay between HOX binding specificities and the cellular context remains largely elusive. To gain insight into this question, we took advantage of developing limbs for which the differential expression of Hox genes is well-characterized7. We show that the transcription factors HOXA13 and HOXD13 (hereafter referred as HOX13) allow another HOX factor, HOXA11, to bind loci initially assumed to be HOX13-specific. Importantly, HOXA11 is unable to bind these loci in distal limbs lacking HOX13 function indicating that HOX13 modulates HOXA11 target repertoire. In addition, we find that the HOX13 factors implement the distal limb developmental program by triggering chromatin opening, a defining property of pioneer factors8,9. Finally, single cell analysis of chromatin accessibility reveals that HOX13 factors pioneer chromatin opening in a lineage specific manner. Together, our data uncover a new mechanism underlying HOX binding specificity, whereby tissue-specific variations in the target repertoire of HOX factors rely, at least in part, on HOX13-dependent chromatin accessibility.
Varietal differences in physiological and biochemical responses to salinity stress in six finger millet plants
Authors: Mukami Asunta , Ng’etich Alex , Syombua Easter , Oduor Richard , Mbinda Wilton 
Published: October 2019

AbstractFinger millet is one of the most important cereals that are often grown in semiarid and arid regions of East-Africa. Salinity is known to be a major impediment for the crop growth and production. This study was aimed to understand the mechanisms of physiological and biochemical responses to salinity stress of Kenyan finger millet varieties (GBK043137, GBK043128, GBK043124, GBK043122, GBK043094, GBK043050) grown across different agroecological zones under NaCl-induced salinity stress. Seeds were germinated on the sterile soil and treated using various concentrations of NaCl (100, 200 and 300 mM) for two weeks. Again, the early-seedling stage of germinated plants was irrigated with the same salt concentrations for 60 days. Results indicated depression in germination percentage, shoot and root growth rate, leaf relative water content, chlorophyll content contents, leaf K+ concentration, and leaf K+/Na+ ratios increased salt levels. Contrary, proline and malonaldehyde (MDA) contents reduced sugar content and leaf total proteins. At the same time, the leaf Na+ and Cl− amounts of all plants increased substantially with rising stress levels. Clustering analysis revealed that GBK043094 and GBK043137 were placed together and identified as salt-tolerant varieties based on their performance under salt stress. Overall, our findings indicated a significant varietal variability for most of the parameters analysed. These superior varieties identified could be potentially used as promising genetic resources in future breeding programmes development directed towards salt-tolerant finger millet hybrids. Further analysis at genomic level need to be undertaken to better understand the genetic factors that promote salinity tolerance in finger millet.
Predicting Minimal Residual Disease in Acute Myeloid Leukemia through Stochastic Modeling of Clonality
Authors: Dinh Khanh , Jaksik Roman , Corey Seth J. , Kimmel Marek 
Published: October 2019

AbstractEvent-free and overall survival remains poor for acute myeloid leukemia (AML). Chemo-resistant clones contributing to relapse of the disease arise from minimal residual disease (MRD) rather than resulting from newly acquired mutations during or after chemotherapy. MRD is the presence of measurable leukemic cells using non-morphologic assays. It is considered a strong predictor of relapse. The dynamics of clones comprising MRD is poorly understood and is considered influenced by a form of Darwinian selection. We propose a stochastic model based on a multitype (multi-clone) age-dependent Markov branching process to study how random events in MRD contribute to the heterogeneity in response to treatment in a cohort of six patients from The Cancer Genome Atlas database with whole genome sequencing data at two time points. Our model offers a more accurate understanding of how relapse arises and which properties allow a leukemic clone to thrive in the Darwinian competition among leukemic and normal hematopoietic clones. The model suggests a quantitative relationship between MRD and time to relapse and therefore may aid clinicians in determining when and how to implement treatment changes to postpone or prevent the time to relapse.Author summaryRelapse affects about 50% of AML patients who achieved remission after treatment, and the prognosis of relapsed AML is poor. Current evidence has shown that in many patients, mutations giving rise to relapse are already present at diagnosis and remain in small numbers in remission, defined as the minimal residual disease (MRD). We propose a mathematical model to analyze how MRD develops into relapse, and how random events in MRD may affect the patient’s fate. This work may aid clinicians in predicting the range of outcomes of chemotherapy, given mutational data at diagnosis. This can help in choosing treatment strategies that reduce the risk of relapse.
Examination of zinc in the circadian system
Authors: Moshirpour Mahtab , Nakashima Amy S. , Sehn Nicole , Smith Victoria M. , Dyck Richard H. , Antle Michael C. 
Published: October 2019

ABSTRACTZinc is a trace element that is essential for a large number of biological and biochemical processes in the body. In the nervous system zinc is packaged into synaptic vesicles by the ZnT3 transporter, and synaptic release of zinc can influence the activity of postsynaptic cells, either directly though its own cognate receptors, or indirectly by modulating activation of receptors for other neurotransmitters. Here, we explore the anatomical and functional aspects of zinc in the circadian system. Melanopsin-containing retinal ganglion cells in the mouse retina were found to colocalize ZnT3, indicating that they can release zinc at their synaptic targets. While the master circadian clock in the hamster suprachiasmatic nucleus (SCN) was found to contain, at best, sparse zincergic input, the intergeniculate leaflet (IGL) was found to have prominent zincergic input. Levels of zinc in these areas were not affected by time of day. Additionally, IGL zinc staining persisted following enucleation, indicating other prominent sources of zinc instead of, or in addition to, the retina. Neither enhancement nor chelation of free zinc at either the SCN or IGL altered circadian responses to phase-shifting light in hamsters. Finally, entrainment, free-running, and circadian responses to light were explored in mice lacking the ZnT3 gene. In every aspect explored, the ZnT3-KO mice were not significantly different from their wildtype counterparts. These findings highlight the presence of zinc in areas critical for circadian functioning but have yet to identify a role for zinc in these areas.HighlightsThe synaptic zinc transporter ZnT3 is found in melanopsin-containing retinal ganglion cells.While zinc input to the hamster SCN was found to be sparse at best, prominent zincergic staining was found throughout the IGL.Zinc levels in the SCN and IGL did not change between the night and day.Neither increasing nor decreasing zinc levels in either the SCN or IGL had an influence on circadian responses to light.Mice lacking the ZnT3 transporter did not differ from wildtype mice on a wide variety of circadian measures.
Cotranslational Folding Stimulates Programmed Ribosomal Frameshifting in the Alphavirus Structural Polyprotein
Authors: Harrington Haley R. , Zimmer Matthew H. , Chamness Laura M. , Nash Veronica , Penn Wesley D. , Miller Thomas F. , Mukhopadhyay Suchetana , Schlebach Jonathan P. 
Published: October 2019

ABSTRACTViruses maximize their genetic coding capacity through a variety of biochemical mechanisms including programmed ribosomal frameshifting (PRF), which facilitates the production of multiple proteins from a single transcript. PRF is typically stimulated by structural elements within the mRNA that generate mechanical tension between the transcript and ribosome. However, in this work we show that the forces generated by the cotranslational folding of the nascent polypeptide chain can also enhance PRF. Using an array of biochemical, cellular, and computational techniques, we first demonstrate that the Sindbis virus structural polyprotein forms two competing topological isomers during biosynthesis at the ribosome-translocon complex. We then show that the formation of one of these topological isomers is linked to PRF. Coarse-grained molecular dynamic simulations reveal that the translocon-mediated membrane integration of a transmembrane domain upstream from the ribosomal slip-site generates a force on the nascent polypeptide chain that scales with observed frameshifting. Together, our results demonstrate that cotranslational folding of this protein generates a tension that stimulates PRF. To our knowledge, this constitutes the first example in which the conformational state of the nascent chain has been linked to PRF. These findings raise the possibility that, in addition to RNA-mediated translational recoding, a variety of cotranslational folding and/ or binding events may also stimulate PRF.
Temporal regulation of nicotinic acetylcholine receptor subunits supports central cholinergic synapse development
Authors: Rosenthal Justin S. , Yin Jun , Long Caixia , Spillman Emma , Sheng Chengyu , Yuan Quan 
Published: October 2019

AbstractConstruction and maturation of the postsynaptic apparatus are crucial for synapse and dendrite development. The fundamental mechanisms underlying these processes are most often studied in glutamatergic central synapses in vertebrates. Whether the same principles apply to excitatory cholinergic synapses in the insect central nervous system (CNS) is not known. To address this question, we investigated Drosophila ventral lateral neurons (LNvs) and identified nAchRα1 (Dα1) and nAchRα6 (Dα6) as the main functional nicotinic acetylcholine receptor (nAchR) subunits in these cells. With morphological and calcium imaging studies, we demonstrated their distinct roles in supporting dendrite morphogenesis and synaptic transmission. Furthermore, our analyses revealed a transcriptional upregulation of Dα1 and downregulation of Dα6 during larval development, indicating a close association between the temporal regulation of nAchR subunits and synapse maturation. Together, our findings show transcriptional regulation of nAchR composition is a core element of developmental and activity-dependent regulation of central cholinergic synapses.
COMT Val158Met polymorphism associated with greater susceptibility to framing effects in healthy older adults
Authors: Quinn Carson M. , Borzello Mia , Zahir Ali , Kramer Joel H. , Chiong Winston 
Published: October 2019

AbstractAge-related neural changes may compromise older adults’ decision-making, increasing their risk of fraud and financial abuse. One manifestation of nonrational influences on decision-making is susceptibility to “framing effects,” in which decisions are biased by irrelevant contextual features of how choice information is presented. We investigated whether polymorphisms in genes related to dopamine neurotransmission (COMT) and neurodegeneration (ApoE) influence the susceptibility of older adults to framing effects. We administered an online test of susceptibility to framing effects to a cohort of 113 healthy older adults who had undergone genetic testing for COMT and ApoE genotype. The task required the participant to choose a risky or safe option in pairs of situations that were monetarily equivalent but differed in whether the choice was framed in terms of gains or losses. A general linear model was used to test for associations between inconsistency in choice across the set of choice pairs and these genotypes, controlling for age, education, gender and traditional measures of executive function. While no association to framing effects was found for ApoE, the Valine allele of COMT Val158Met was significantly associated with greater susceptibility to framing, although the association was no longer significant after adjustment for demographic covariates. Our results suggest that greater frontal dopamine concentrations associated with the COMT Met allele are protective against less consistent decision making in older adults. When compared to previous findings in young adults, our findings provide additional support for an inverted-U shaped model of prefrontal dopamine function.
Non-conservation of folding rates in the thioredoxin family reveals degradation of ancestral unassisted-folding
Authors: Gamiz-Arco Gloria , Risso Valeria A. , Candel Adela M. , Inglés-Prieto Alvaro , Romero-Romero Maria L. , Gaucher Eric A. , Gavira Jose A. , Ibarra-Molero Beatriz , Sanchez-Ruiz Jose M. 
Published: October 2019

AbstractEvolution involves not only adaptation, but also the degradation of superfluous features. Many examples of degradation at the morphological level are known (vestigial organs, for instance). However, the impact of degradation on molecular evolution has been rarely addressed. Thioredoxins serve as general oxidoreductases in all cells. Here, we report extensive mutational analyses on the folding of modern and resurrected ancestral bacterial thioredoxins. Contrary to claims from recent literature,in vitrofolding rates in the thioredoxin family are not evolutionary conserved, but span at least a ∼100-fold range. Furthermore, modern thioredoxin folding is often substantially slower than ancestral thioredoxin folding. Unassisted folding, as probedin vitro, thus emerges as an ancestral vestigial feature that underwent degradation, plausibly upon the evolutionary emergence of efficient cellular folding-assistance. More generally, our results provide evidence that degradation of ancestral features shapes, not only morphological evolution, but also the evolution of individual proteins.
Population genetic analysis of 12 X-STRs in a Bahraini population sample (Allele and haplotype frequencies of 12 X-STRs in Bahraini population)
Authors: Al-Snan Noora R. , Messaoudi Safia A. , Bakhiet Moiz , Mansoor Latifa A. 
Published: October 2019

AbstractTo date, there are very limited genetic studies conducted on the Kingdom of Bahrain and this is one of the first studies conducted to evaluate the 12 X-STRs included in the Investigator X-12 QS kit. Bahrain is a small archipelago located in the Arabian Gulf. X-STRs are very informative in population genetics studies, human identification and complex kinship analysis. One hundred and fifty-six (156) buccal swabs were collected using cotton from non-relatives’ Bahraini males from four different regions of Bahrain. DNA was processed using QIAsymphony SP instrument following quantification with Investigator Quantiplex HYres Kit in the 7500 Real-Time PCR System and detected in ABI 3500xl Genetic Analyzer. Analysis was done using different statistical softwares to obtain allele frequencies and haplotype frequencies-based upon the available four clusters of Linkage Groups (LGs)- and the forensic parameters.. Results indicated the diversity of the Bahraini population in terms of high Power of Discrimination (PD) and Probability of Match (PM) values obtained. The combined values of each forensic parameter such as cPDM, Mean exclusion chance (CMEC) Krüger, CMEC Kishida, and CMEC Desmarais as well as CMEC Desmarais Duo, were 0.9999983, 9999979, 0.9999939, 0.9999996 and 0.9999514 respectively based on the allele and haplotype frequencies. No shared profiles were observed. Number of non-standard alleles and null samples were obtained with more profoundly in locus DXS10148. We have conducted phylogenetic tree as well as multidimensional scale to analyze the Interpopulation diversity between Bahraini population and nine other populations and found out they reflect the geographical and social background of the region. Overall, the results confirm the importance of X-STRs in discriminating between individuals among Bahraini population and in establishing DNA databases for forensic and kinship studies.
Influenza B viruses exhibit lower within-host diversity than influenza A viruses in human hosts
Authors: Valesano Andrew L. , Fitzsimmons William J. , McCrone John T. , Petrie Joshua G. , Monto Arnold S. , Martin Emily T. , Lauring Adam S. 
Published: October 2019

AbstractInfluenza B virus undergoes seasonal antigenic drift more slowly than influenza A, but the reasons for this difference are unclear. While the evolutionary dynamics of influenza viruses play out globally, they are fundamentally driven by mutation, reassortment, drift, and selection within individual hosts. These processes have recently been described for influenza A virus, but little is known about the evolutionary dynamics of influenza B virus (IBV) at the level of individual infections and transmission events. Here we define the within-host evolutionary dynamics of influenza B virus by sequencing virus populations from naturally-infected individuals enrolled in a prospective, community-based cohort over 8176 person-seasons of observation. Through analysis of high depth-of-coverage sequencing data from samples from 91 individuals with influenza B, we find that influenza B virus accumulates lower genetic diversity than previously observed for influenza A virus during acute infections. Consistent with studies of influenza A viruses, the within-host evolution of influenza B viruses is characterized by purifying selection and the general absence of widespread positive selection of within-host variants. Analysis of shared genetic diversity across 15 sequence-validated transmission pairs suggests that IBV experiences a tight transmission bottleneck similar to that of influenza A virus. These patterns of local-scale evolution are consistent with influenza B virus’ slower global evolutionary rate.ImportanceThe evolution of influenza virus is a significant public health problem and necessitates the annual evaluation of influenza vaccine formulation to keep pace with viral escape from herd immunity. Influenza B virus is a serious health concern for children, in particular, yet remains understudied compared to influenza A virus. Influenza B virus evolves more slowly than influenza A, but the factors underlying this are not completely understood. We studied how the within-host diversity of influenza B virus relates to its global evolution by sequencing viruses from a community-based cohort. We found that influenza B virus populations have lower within-host genetic diversity than influenza A virus and experience a tight genetic bottleneck during transmission. Our work provides insights into the varying dynamics of influenza viruses in human infection.
Sex and pedagogy influences in physics learning-related reorganization of brain activation
Authors: Bartley Jessica E. , Riedel Michael C. , Salo Taylor , Bottenhorn Katherine L. , Boeving Emily R. , Laird Robert W. , Sutherland Matthew T. , Pruden Shannon M. , Brewe Eric , Laird Angela R. 
Published: October 2019

ABSTRACTPhysics is a challenging academic pursuit in which university students regularly struggle to achieve success. Female students tend to perform negatively on introductory physics conceptual assessments compared to their male peers; however, active-learning classroom curricula are known to broadly improve performance on these tests. Here, we used fMRI to delineate physics-related brain activity in 107 students and probed for changes following a semester of active-learning or lecture-based physics instruction. Large-scale reorganization of brain activity accompanying learning occurred in a mixed frontoparietal and default mode network. Sex differences were observed in frontoparietal, default mode, and primary visual areas before and after instruction. Regions showing significant pedagogy, sex, and time interactions were revealed during physics retrieval, suggesting the type of class students complete may influence sex differences in how students retrieve information. These results reveal potentially elucidating sex and pedagogy differences underlying the neural mechanisms supporting physics learning.