bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cold and distant: structural features of the nucleoprotein complex of a cold-adapted influenza A virus strain
Authors: Shvetsov A.V. , Lebedev D.V. , Zabrodskaya Y.A. , Shaldzhyan A.A. , Egorova M.A. , Vinogradova D.S. , Konevega A.L. , Gorshkov A.N. , Ramsay E.S. , Radulescu A. , Sergeeva M.V. , Plotnikova M.A. , Komissarov A.B. , Taraskin A.S. , Lebedev K.I. , Garmay Yu.P. , Kuznetsov V.V. , Isaev-Ivanov V.V. , Vasin A.V. , Tsybalova L.M. , Egorov V.V. 
Published: November 2019

AbstractTwo influenza A nucleoprotein variants (wt: G102R; and mutant: G102R and E292G) were studied with regard to macro-molecular interactions in oligomeric form (24-mers). The E292G mutation has been previously shown to provide cold adaptation. Molecular dynamics simulations of these complexes and trajectory analysis showed that the most significant difference between the obtained models was distance differences between nucleoprotein complex strands. Influenza virus nucleoprotein complexes were isolated from strains bearing the corresponding NP amino acid substitutions. The isolated complexes were characterized by transmission electron microscopy and differential scanning fluorimetry (DSF). Presence of the E292G substitution was shown by DSF to affect nucleoprotein complex melting temperature. In the filament interface peptide model, it was shown that the peptide corresponding in primary structure to the wild-type NP (SGYDFEREGYS, wild type peptide) is prone to temperature-dependent self-association, unlike the peptide carrying the substitution corresponding to E292G (SGYDFGREGYS, mutant peptide). It was also shown that the SGYDFEREGYS peptide (wt) is capable of interacting with a recombinant full-size monomeric nucleoprotein (with primary structure corresponding to wild type); this interaction’s equilibrium dissociation constant is five orders of magnitude lower than for the SGYDFGREGYS peptide. Using small-angle neutron scattering (SANS), the supramolecular structures of isolated complexes of these proteins was studied at temperatures of 15, 32, and 37°C. SANS data show that the structures of the studied complexes (mutant or normal proteins with RNA) at elevated temperature differ from the rod-like particle model and react differently to temperature changes. The data suggest that the mechanism behind cold adaptation with E292G is associated with a weakening of the interaction between strands of the ribonucleoprotein complex and, as a result, the appearance of inter-chain interface flexibility necessary for complex function at low temperature.
Gendered Fitness Interests: A Method Partitioning the Effects of Family Composition on Socio-Political Attitudes and Behaviors
Authors: Brooks Robert C. , Blake Khandis R. 
Published: November 2019

AbstractWhereas most people are biologically either male or female, their genetic interests are almost never aligned with just their own sex. Drawing on the evolutionary theory of inclusive fitness gained through relatives, we partition the effects of kin on fitness into those that derive from female versus male relatives. We argue that the balance of these female- and male-derived effects, which we call ‘Gendered Fitness Interests’ (GFI), might influence human behavior, especially the adoption of socio-political attitudes that have a gendered dimension. Our proposal builds on observations that individual socio-political views covary with the sex of their children or the numbers of relatives of each sex. Further, it is consistent with the relatively small average differences between women’s and men’s socio-political positions. We outline a method for partitioning GFI, and use simulation models to explore some of its properties. We then show that (1) the GFI component of women’s and men’s socio-political attitudes will converge, on average, with age. (2) The contributions of both descendent and non-descendent kin lead to considerable variation in GFI. (3) When men have longer average reproductive lifespans than women, GFI can show small male-biases. (4) Paternity uncertainty reduces the variation in GFI between individuals, and (5) Large family sizes are associated with more variation among individuals in GFI. Our proposal provides a framework for the study of the effects of kin on traits and attitudes with a gendered dimension. In this respect, it may prove generally useful in resolving the complex origins of gendered behavior.
Tissue Engineered Axon-Based “Living Scaffolds” Promote Survival of Spinal Cord Motor Neurons Following Peripheral Nerve Repair
Authors: Maggiore Joseph C. , Burrell Justin C. , Browne Kevin D. , Katiyar Kritika S. , Laimo Franco A. , Ali Zarina S. , Kaplan Hilton M. , Rosen Joseph M. , Cullen D. Kacy 
Published: November 2019

AbstractPeripheral nerve injury (PNI) impacts millions annually, often leaving debilitated patients with minimal repair options to improve functional recovery. Our group has previously developed tissue engineered nerve grafts (TENGs) featuring long, aligned axonal tracts from dorsal root ganglia (DRG) neurons that are fabricated in custom bioreactors using the process of axon “stretch-growth”. We have shown that TENGs effectively serve as “living scaffolds” to promote regeneration across segmental nerve defects by exploiting the newfound mechanism of axon-facilitated axon regeneration, or “AFAR”, by simultaneously providing haptic and neurotrophic support. To extend this work, the current study investigated the efficacy of living versus non-living regenerative scaffolds in preserving host sensory and motor neuronal health following nerve repair. Rats were assigned across five groups: naïve, or repair using autograft, nerve guidance tube (NGT) with collagen, NGT + non-aligned DRG populations in collagen, or TENGs. We found that TENG repairs yielded equivalent regenerative capacity as autograft repairs based on preserved health of host spinal cord motor neurons and acute axonal regeneration, whereas NGT repairs or DRG neurons within an NGT exhibited reduced motor neuron preservation and diminished regenerative capacity. These acute regenerative benefits ultimately resulted in enhanced levels of functional recovery in animals receiving TENGs, at levels matching those attained by autografts. Our findings indicate that TENGs may preserve host spinal cord motor neuron health and regenerative capacity without sacrificing an otherwise uninjured nerve (as in the case of the autograft), and therefore represent a promising alternative strategy for neurosurgical repair following PNI.HIGHLIGHTSTENGs preserve host spinal cord motor neuron health and regenerative capacity acutely following repair of segmental nerve defects, matching that of the clinical gold-standard autograft and exceeding commercially-available nerve guidance tubes.TENGs facilitated regeneration across segmental nerve defects, yielding similar degree of chronically surviving host spinal motor neurons and functional recovery as compared to autografts.Early surgical intervention for segmental nerve defect with living scaffolds, such as TENGs and autografts, preserves the host regenerative capacity, and likely increases the ceiling for total regeneration and functional recovery at chronic time points compared to (acellular) commercially-available nerve guidance tubes.TENGs preserve host neuronal health and regenerative capacity without sacrificing an otherwise uninjured nerve, and therefore represent a promising alternative strategy to autografts or nerve guidance tube repairs.
The contribution of lincRNAs at the interface between cell cycle regulation and cell state maintenance
Authors: Biasini Adriano , Thil Smith Adam Alexander , Abdulkarim Baroj , Tan Jennifer Yihong , da Silva Maria Ferreira , Marques Ana Claudia 
Published: November 2019

ABSTRACTCell cycle progression requires dynamic and tightly-regulated transitions between well-defined cell cycle stages. These transitions are controlled by the interplay of established cell cycle regulators. Changes in the activity of these regulators are thought to underpin differences in cell cycle kinetics between distinct cell types. Here, we investigate whether cell type-specific long intergenic noncoding RNAs (lincRNAs) contribute to embryonic stem cell adaptations, which have been shown to be essential for the maintenance of embryonic stem cell state.We used single cell RNA-sequencing data of mouse embryonic stem cells (mESC) staged as G1, S, or G2/M to identify genes differentially expressed between these phases. We found differentially expressed lincRNAs to be enriched amongst cell cycle regulated genes. These cell cycle associated lincRNAs (CC-lincRNAs) are co-expressed with protein-coding genes with established roles in cell cycle progression. Interestingly, 70% of CC-lincRNAs are differentially expressed between G1 and S, suggesting they may contribute to the maintenance of the short G1 phase that characterizes the embryonic stem cell cycle. Consistent with this hypothesis, the promoters of CC-lincRNAs are enriched in pluripotency transcription factor binding sites, and their transcripts are frequently co-regulated with genes involved in the maintenance of pluripotency. We tested the impact of 2 CC-lincRNA candidates and show that modulation of their expression is associated with impaired cell cycle progression, further underlining the contribution of mESC-specific lincRNAs to cell cycle modulation in these cells.
Oncologic therapy shapes the fitness landscape of clonal hematopoiesis
Authors: Bolton Kelly L , Ptashkin Ryan N , Gao Teng , Braunstein Lior , Devlin Sean M , Kelly Daniel , Patel Minal , Berthon Antonin , Syed Aijazuddin , Yabe Mariko , Coombs Catherine C. , Caltabellotta Nicole M. , Walsh Mike , Offit Kenneth , Stadler Zsofia , Mandelker Diana , Schulman Jessica , Patel Akshar , Philip John , Bernard Elsa , Gundem Gunes , Arango Juan E , Levine Max , Medina Juan S , Farnoud Noushin , Glodzik Dominik , Li Sonya , Robson Marc E , Lee Choonsik , Pharoah Paul D P , Stopsack Konrad , Spitzer Barbara , Mantha Simon , Fagin James , Boucai Laura , Gibson Christopher J , Ebert Benjamin L , Young Andrew , Druley Todd , Takahasi Koichi , Gillis Nancy , Ball Markus , Padron Eric , Hyman David M , Baselga Jose , Norton Larry , Gardos Stuart , Klimek Virginia M , Scher Howard , Bajorin Dean , Paraiso Eder , Benayed Ryma , Arcila Maria E , Ladanyi Marc , Solit David B , Berger Michael F , Tallman Martin , Garcia-Closas Montserrat , Chatterjee Nilanjan , Diaz Luis A , Levine Ross L , Morton Lindsay M , Zehir Ahmet , Papaemmanuil Elli 
Published: November 2019

ABSTRACTClonal hematopoiesis (CH) is frequent in cancer patients and associated with increased risk of therapy related myeloid neoplasms (tMN). To define the relationship between CH, oncologic therapy, and tMN progression, we studied 24,439 cancer patients. We show that previously treated patients have increased rates of CH, with enrichment of mutations in DNA Damage Response (DDR) genes (TP53, PPM1D, CHEK2). Exposure to radiation, platinum and topoisomerase II inhibitors have the strongest association with CH with evidence of dose-dependence and gene-treatment interactions. We validate these associations in serial sampling from 525 patients and show that exposure to cytotoxic and radiation therapy imparts a selective advantage specifically in hematopoietic cells with DDR mutations. In patients who progressed to tMN, the clone at CH demarcated the dominant clone at tMN diagnosis. CH mutational features predict risk of therapy-related myeloid neoplasm in solid tumor patients with clinical implications for early detection and treatment decisions.
Linking lysosomal enzyme targeting genes and energy metabolism with altered gray matter volume in children with persistent stuttering
Authors: Chow Ho Ming , Garnett Emily O. , Li Hua , Etchell Andrew , Sepulcre Jorge , Drayna Dennis , Chugani Diane C. , Chang Soo-Eun 
Published: November 2019

AbstractDevelopmental stuttering is a childhood onset neurodevelopmental disorder with an unclear etiology. Subtle changes in brain structure and function are present in both children and adults who stutter. It is a highly heritable disorder, and up to 12-20% of stuttering cases may carry a mutation in one of four genes involved in mannose-6-phosphate mediated protein intracellular trafficking. To better understand the relationship between genetic factors and brain structural changes, we used gene expression data from the Allen Institute for Brain Science (AIBS) and voxel-based morphometry (VBM) to investigate the spatial correspondence between gene expression patterns and differences in gray matter volume (GMV) between children with persistent stuttering (n=26, 87 scans) and their fluent peers (n=44, 139 scans). We found that expression patterns of two stuttering-related genes (GNPTGandNAGPA) in the brain exhibit a strong positive spatial correlation with the magnitude of GMV differences between groups. Further gene set enrichment analyses revealed that genes whose expression was highly correlated with the GMV differences were enriched for glycolysis and oxidative metabolism in mitochondria. Although the results are correlational and cannot inform us about underlying casual mechanisms, our results suggest a possibility that regions with high expression level of genes associated with stuttering may be particularly vulnerable to the effect of alterations in these genes. This effect may be further exacerbated by the relatively high energy utilization in those brain during the period of a sharp increase in brain energy utilization, which coincides with a period of rapid language development and the onset of stuttering during childhood.
Drought-induced mortality: stem diameter variation reveals a point of no return in lavender species
Authors: Lamacque Lia , Charrier Guillaume , Santos Farnese Fernanda dos , Lemaire Benjamin , Améglio Thierry , Herbette Stéphane 
Published: November 2019

AbstractIn the context of climate changes, water availability is expected to severely decline. Consequently, there is a need to predict mortality of woody species, especially to find a physiological threshold to drought-induced mortality. Lavender species (Lavandula angustifoliaandLavandula x intermedia) which are important crops of the Mediterranean region are affected by a decline, notably caused by successive intense drought events. Lavender response to extreme drought events was monitored using continuous stem diameter measurements. Water potential, stomatal conductance, loss of xylem hydraulic conductivity and electrolyte leakage were also measured during desiccation, and recovery was evaluated after rewatering. Two parameters computed from stem diameter variations were related to stress intensity and resilience to stress: PLD (Percentage Loss of Diameter) and stem PLRC (Percentage Loss of Rehydration Capacity of the stem), respectively. We showed that plants did not recover when the PLD reached its maximal value (PLDmax) which was 21.27 ± 0.57% in both lavender species and whatever the growing conditions. This point of no return was associated with a high level of cell lysis evaluated by electrolyte leakage, and occurred far after the xylem hydraulic failure. We discussed the relevance of PLDmaxas a threshold for drought-induced mortality and its physiological significance, in relation to the mortality mechanisms.One-sentence summaryUnder extreme drought, lavender death occurs when the water storage of the elastic compartment of the stem is exhausted.
Investigation of anLPAKIV-2 nonsense mutation in 11,000 individuals: the importance of linkage disequilibrium structure inLPAgenetics
Authors: Di Maio Silvia , Streiter Gertraud , Grüneis Rebecca , Lamina Claudia , Maglione Manuel , Öfner Dietmar , Thorand Barbara , Peters Annette , Eckardt Kai-Uwe , Köttgen Anna , Kronenberg Florian , Coassin Stefan 
Published: November 2019

AbstractObjectiveElevated Lp(a) plasma concentrations are determined mainly genetically by theLPAgene locus, but up to 70% of the coding sequence is located in the so-called “kringle IV type 2” (KIV-2) copy number variation. This region is not resolved by common genotyping technologies and large epidemiological studies on this region are therefore missing. The Arg21Ter variant (R21X, variant frequency ≈2%) is a functional variant in this region, but it has never been analyzed in large cohorts and is it unknown whether it is captured by genome-wide association studies.Approach and ResultsWe developed a highly sensitive allele-specific qPCR assay and genotyped R21X in 10,910 individuals from three populations (GCKD, KORA F3, KORA F4). R21X carriers showed significantly lower mean Lp(a) concentrations (−11.7 mg/dL [−15.5;−7.82], p=3.39e-32). Of particular note, virtually all R21X carriers also carried the splice mutation rs41272114 (D’=0.957, R2=0.275), as confirmed by pulsed-field gel electrophoresis and long-range haplotyping. This proposes that the R21X mutation arose on the background of the rs41272114 splice variant.ConclusionsWe performed the largest epidemiological study on anLPAKIV-2 variant so far. Interestingly, R21X is located on the same haplotype as the splice mutation rs41272114, creating “double-null”LPAalleles that are inactivated by two independent mutations. The effect of the R21X nonsense mutation can thus not be discerned from the effect of rs41272114 splice site mutation. This emphasizes the importance of assessing the complex LD structure withinLPAeven for functional variants.
Do genetic differences in growth thermal reaction norms maintain genetic variation in timing of diapause induction?
Authors: Fossen Erlend I. F. , Raeymaekers Joost A. M. , Einum Sigurd 
Published: November 2019

AbstractAn optimal timing for diapause induction through the sexual production of dormant propagules is expected in populations of annual organisms. Yet, experimental work typically finds high within-population genetic variation in the sexual production of such propagules. Thus, high genetic variation in timing for diapause induction should be a common feature of annual organisms.Here, we hypothesize that genetic variation in the propensity to produce diapause propagules, Pd, is maintained by a genotype-by-environment interaction in growth performance, where fast-growing genotypes within an environment should delay diapause relative to slow-growing genotypes. From this, we derive two predictions. First, if there is ecological crossover in growth performance, the genetic correlation of Pd between environments should be negative. Second, the correlation between absolute plasticities of growth and Pd should be negative.We tested these predictions by quantifying ephippia production in genotypes of a population of the facultative sexual cladoceran Daphnia magna at two temperatures. The population biomass at the onset of ephippia production was used as a measure of Pd, whereas somatic growth rate was used to quantify growth. Plasticity for both measurements was derived from thermal reaction norms.Our results did not support either prediction, as neither the genetic correlation of Pd between environments, nor the correlation between absolute plasticity of growth and Pd were found to be significant.Our results suggest that genetic variation in the timing of diapause is not maintained by genetic differences in thermal growth reaction norms. We propose as an alternative hypothesis that if there is across year variation in how stochastically the environment deteriorates, fluctuating selection may favor genotypes with different Pd between years.
Genetic deletion of Autotaxin from CD11b+ cells decreases the severity of experimental autoimmune encephalomyelitis
Authors: Ninou Ioanna , Sevastou Ioanna , Magkrioti Christiana , Kaffe Eleanna , Stamatakis George , Thivaios Spyros , Panayotou George , Aoki Junken , Kollias George , Aidinis Vassilis 
Published: November 2019

AbstractAutotaxin (ATX) is a secreted lysophospholipase D catalyzing the extracellular production of lysophosphatidic acid (LPA), a growth factor-like signaling lysophospholipid. ATX and LPA signaling have been incriminated in the pathogenesis of different chronic inflammatory diseases and various types of cancer. In this report, deregulated ATX and LPA levels were detected in the spinal cord and plasma of mice during the development of experimental autoimmune encephalomyelitis (EAE). Among the different sources of ATX expression in the inflamed spinal cord, F4/80+CD11b+ cells, mostly activated macrophages and microglia, were found to express ATX, further suggesting an autocrine role for ATX/LPA in their activation, an EAE hallmark. Accordingly, ATX genetic deletion from CD11b+ cells attenuated the severity of EAE, thus proposing a pathogenic role for the ATX/LPA axis in neuroinflammatory disorders.
Mechanisms of high-intensity sound exposure on inhibiting hippocampal long-term potentiation: role of brain-derived neurotrophic factor
Authors: de Deus Júnia L. , Amorim Mateus R. , Ribeiro Aline B. , Barcellos-Filho Procópio C. G. , Ceballos César C. , Branco Luiz Guilherme S. , Cunha Alexandra O.S. , Leão Ricardo M. 
Published: November 2019

AbstractExposure to humans and experimental animals to loud noises produce cognitive and emotional disorders and recent studies have shown that hippocampal neuronal function is affected by auditory stimulation or deprivation. We have found previously that in the hippocampus of rats exposed to high-intensity sound (110 dB) for one-minute the Schaffer-CA1 long-term potentiation (LTP) is strongly inhibited. Here we investigated possible mechanisms involved in this effect. We found, using c-fos expression, that exposure to 110 dB sound-activated neurons in the CA1 and CA3 hippocampal region. Using electrophysiological recordings in hippocampal slices, we found that both GABAergic and glutamatergic neurotransmission were unaffected by high-intensity sound stimulation. However, hippocampal brain-derived neurotrophic factor (BDNF), which is involved in promoting hippocampal synaptic plasticity, presented decreased levels in sound-stimulated animals. Perfusion of slices with BDNF revert the inhibition of LTP after a single sound stimulus in comparison to sham-stimulated rats. Furthermore, the perfusion with LM 22A4, a TrkB receptor agonist also rescued LTP from sound-stimulated animals. Our results strongly suggest that the exposure to high-intensity sound inhibits the BDNF production in the hippocampus, which could be a possible mechanism of the inhibition of LTP by high-intensity sound exposure.
Arsenic, cadmium, and lead contents of rice imported into Qatar-impact on intake
Authors: Elobeid Tahra , Ganji Vijay , Moustafa Khloud , Mohammed Fatima , El-Ouzi Loujain , Attieh Grace 
Published: November 2019

Purpose
The purpose of this paper is to determine arsenic, cadmium and lead contents of rice imports and to estimate their impact on these heavy metal intakes in Qatar.

Design/methodology/approach
In total, 30 rice samples imported from various countries (Vietnam, Thailand, India, Pakistan, the USA, Australia, the UK and Lebanon) were analyzed for arsenic, cadmium and lead contents with plasma optical spectrometer. These heavy metal intakes from rice were estimated for Qatar population based on the per capita consumption of rice as per 2018 rice consumption data.

Findings
In all rice samples, mean concentrations of arsenic, cadmium and lead were 1.11 mg/kg, 19.7 µg/kg and 131.3 µg/kg, respectively. Average arsenic, cadmium and lead contents were the highest in rice imported from Thailand (1.25 mg/kg), Vietnam (30 µg/kg) and India (178.3 µg/kg), respectively. Estimated arsenic, cadmium and lead intakes through rice consumption by Qatari population were 225.7, 4 and 26.7 µg/day, respectively.

Originality/value
In all rice imports, arsenic content is approximately 5.5 times higher than the maximum allowable concentration (MAC), whereas the cadmium and lead levels are within the MAC. Because these heavy metals are linked to health, all Middle Eastern countries that import rice from Thailand, Vietnam and India should monitor the metal contents in their food supply on a regular basis.