bluuebunny/crossref_metadata_2025_split huggingface dataset:
Precipitation extremes and depth-duration-frequency under internal climate variability
Authors: Bhatia Udit , Ganguly Auroop Ratan 
Published: June 2019

AbstractNatural climate variability, captured through multiple initial condition ensembles, may be comparable to the variability caused by knowledge gaps in future emissions trajectories and in the physical science basis, especially at adaptation-relevant scales and projection horizons. The relations to chaos theory, including sensitivity to initial conditions, have caused the resulting variability in projections to be viewed as the irreducible uncertainty component of climate. The multiplier effect of ensembles from emissions-trajectories, multiple-models and initial-conditions contribute to the challenge. We show that ignoring this variability results in underestimation of precipitation extremes return periods leading to maladaptation. However, we show that concatenating initial-condition ensembles results in reduction of hydroclimate uncertainty. We show how this reduced uncertainty in precipitation extremes percolates to adaptation-relevant-Depth-Duration Frequency curves. Hence, generation of additional initial condition ensembles therefore no longer needs to be viewed as an uncertainty explosion problem but as a solution that can lead to uncertainty reduction in assessment of extremes.
Discovery of Biomarker Panels for Neural Dysfunction in Inborn Errors of Amino Acid Metabolism
Authors: Castells Alba-Aina , Gueraldi Daniela , Balada Rafel , Tristán-Noguero Alba , Cortès-Saladelafont Elisenda , Ramos Federico , Meavilla Silvia , De Los Santos Mariela , Garcia-Volpe Camila , Colomé Roser , Couce Maria Luz , Sierra Cristina , Ormazábal Aida , Batllori Marta , Artuch Rafael , Armstrong Judith , Alcántara Soledad , Garcia-Cazorla Àngels 
Published: June 2019

AbstractPatients with inborn errors of amino acid metabolism frequently show neuropsychiatric symptoms despite accurate metabolic control. This study aimed to gain insight into the underlying mechanisms of neural dysfunction. Here we analyzed the expression of brain-derived neurotrophic factor (BDNF) and 10 genes required for correct brain functioning in plasma and blood of patients with Urea Cycle Disorders (UCD), Maple Syrup Urine Disease (MSUD) and controls. Receiver-operating characteristic (ROC) analysis was used to evaluate sensitivity and specificity of potential biomarkers. CACNA2D2 (α2δ2 subunit of voltage-gated calcium channels) and MECP2 (methyl-CpG binding protein 2) mRNA and protein showed an excellent neural function biomarker signature (AUC ≥ 0,925) for recognition of MSUD. THBS3 (thrombospondin 3) mRNA and AABA gave a very good biomarker signature (AUC 0,911) for executive-attention deficits. THBS3, LIN28A mRNA, and alanine showed a perfect biomarker signature (AUC 1) for behavioral and mood disorders. Finally, a panel of BDNF protein and at least two large neural AAs showed a perfect biomarker signature (AUC 1) for recognition of psychomotor delay, pointing to excessive protein restriction as central causative of psychomotor delay. To conclude, our study has identified promising biomarker panels for neural function evaluation, providing a base for future studies with larger samples.
Blockade of microglial Cav1.2 Ca2+ channel exacerbates the symptoms in a Parkinson’s disease model
Authors: Wang Xinshuang , Saegusa Hironao , Huntula Soontaraporn , Tanabe Tsutomu 
Published: June 2019

AbstractCav1.2 channels are an L-type voltage-dependent Ca2+channel, which is specifically blocked by calcium antagonists. Voltage-dependent Ca2+channels are generally considered to be functional only in excitable cells like neurons and muscle cells, but recently they have been reported to also be functional in non-excitable cells like microglia, which are key players in the innate immune system and have been shown to be involved in the pathophysiology of Parkinson’s disease. Here, we show that Cav1.2 channels are expressed in microglia, and that calcium antagonists enhanced theneuroinflammatoryM1 transition and inhibitedneuroprotectiveM2 transition of microgliain vitro. Moreover, intensive degeneration of dopaminergic neurons and accompanying behavioural deficits were observed in microglia-specific Cav1.2 knockdown mice intoxicated with MPTP, a neurotoxin that induces Parkinson’s disease-like symptoms, suggesting detrimental effects of microglial Cav1.2 blockade on Parkinson’s disease. Therefore, microglial Cav1.2 channel may have neuroprotective roles under physiological conditions and may also contribute to recovery from disease conditions.
Weight Bearing Activities change the Pivot Position after Total Knee Arthroplasty
Authors: Moewis Philippe , Hommel Hagen , Trepczynski Adam , Krahl Leonie , von Roth Philipp , Duda Georg N. 
Published: June 2019

AbstractThe knee joint center of rotation is altered in the absence of the anterior cruciate ligament, which leads to substantially higher variance in kinematic patterns. To overcome this, total knee arthroplasty (TKA) designs with a high congruency in the lateral compartment have been proposed. The purpose of this study was to analyze the influence of a lateral pivot TKA-design on in-vivo knee joint kinematics. Tibiofemoral motion was retrospectively addressed in 10 patients during unloaded flexion-extension and loaded lunge using single plane fluoroscopy. During the unloaded flexion-extension movement, the lateral condyle remained almost stationary with little rollback at maximum flexion. The medial condyle exhibited anterior translation during the whole flexion cycle. During the loaded lunge movement, a higher degree of rollback compared to the unloaded activity was observed on the lateral condyle, whereas the medial condyle remained almost stationary. The results showed a clear lateral pivot during the unloaded activity, reflective of the implant’s geometric characteristics, and a change to a medial pivot and a higher lateral rollback during the weight-bearing conditions, revealing the impact of load and muscle force. It remains unclear if the kinematics with a lateral TKA design could be considered as physiological, due to the limited knowledge available on native knee joint kinematics.
Genome-wide association study identifies loci for arterial stiffness index in 127,121 UK Biobank participants
Authors: Fung Kenneth , Ramírez Julia , Warren Helen R. , Aung Nay , Lee Aaron M. , Tzanis Evan , Petersen Steffen E. , Munroe Patricia B. 
Published: June 2019

AbstractArterial stiffness index (ASI) is a non-invasive measure of arterial stiffness using infra-red finger sensors (photoplethysmography). It is a well-suited measure for large populations as it is relatively inexpensive to perform, and data can be acquired within seconds. These features raise interest in using ASI as a tool to estimate cardiovascular disease risk as prior work demonstrates increased arterial stiffness is associated with elevated systolic blood pressure, and ASI is predictive of cardiovascular disease and mortality. We conducted genome-wide association studies (GWASs) for ASI in 127,121 UK Biobank participants of European-ancestry. Our primary analyses identified variants at four loci reaching genome-wide significance (P < 5 × 10−8): TEX41 (rs1006923; P = 5.3 × 10−12), FOXO1 (rs7331212; P = 2.2 × 10−11), C1orf21 (rs1930290, P = 1.1 × 10−8) and MRVI1 (rs10840457, P = 3.4 × 10−8). Gene-based testing revealed three significant genes, the most significant gene was COL4A2 (P = 1.41 × 10−8) encoding type IV collagen. Other candidate genes at associated loci were also involved in smooth muscle tone regulation. Our findings provide new information for understanding the development of arterial stiffness.
Characterization of metal binding of bifunctional kinase/phosphatase AceK and implication in activity modulation
Authors: Zhang Xiaoying , Shen Qingya , Lei Zhen , Wang Qianyi , Zheng Jimin , Jia Zongchao 
Published: June 2019

AbstractA unique bifunctional enzyme, isocitrate dehydrogenase kinase/phosphatase (AceK) regulates isocitrate dehydrogenase (IDH) by phosphorylation and dephosphorylation in response to nutrient availability. Herein we report the crystal structure of AceK in complex with ADP and Mn2+ ions. Although the overall structure is similar to the previously reported structures which contain only one Mg2+ ion, surprisingly, two Mn2+ ions are found in the catalytic center of the AceK-Mn2+ structure. Our enzymatic assays demonstrate that AceK-Mn2+ showed higher phosphatase activity than AceK-Mg2+, whereas the kinase activity was relatively unaffected. We created mutants of AceK for all metal-coordinating residues. The phosphatase activities of these mutants were significantly impaired, suggesting the pivotal role of the binuclear (M1-M2) core in AceK phosphatase catalysis. Moreover, we have studied the interactions of Mn2+ and Mg2+ with wild-type and mutant AceK and found that the number of metal ions bound to AceK is in full agreement with the crystal structures. Combined with the enzymatic results, we demonstrate that AceK exhibits phosphatase activity in the presence of two, but not one, Mn2+ ions, similar to PPM phosphatases. Taken together, we suggest that metal ions help AceK to balance and fine tune its kinase and phosphatase activities.
Recombinant production of human α2-macroglobulin variants and interaction studies with recombinant G-related α2-macroglobulin binding protein and latent transforming growth factor-β2
Authors: Marino-Puertas Laura , del Amo-Maestro Laura , Taulés Marta , Gomis-Rüth F. Xavier , Goulas Theodoros 
Published: June 2019

Abstractα2-Macroglobulins (α2Ms) regulate peptidases, hormones and cytokines. Mediated by peptidase cleavage, they transit between native, intact forms and activated, induced forms. α2Ms have been studied over decades using authentic material from primary sources, which was limited by sample heterogeneity and contaminants. Here, we developed high-yield expression systems based on transient transfection in Drosophila Schneider 2 and human Expi293F cells, which produced pure human α2M (hα2M) at ~1.0 and ~0.4 mg per liter of cell culture, respectively. In both cases, hα2M was mainly found in the induced form. Shorter hα2M variants encompassing N-/C-terminal parts were also expressed and yielded pure material at ~1.6/~1.3 and ~3.2/~4.6 mg per liter of insect or mammalian cell culture, respectively. We then analyzed the binding of recombinant and authentic hα2M to recombinant latent human transforming growth factor-β2 (pro-TGF-β2) and bacterial G-related α2M binding protein (GRAB) by surface plasmon resonance, multiple-angle laser light scattering, size-exclusion chromatography, fluorogenic labelling, gel electrophoresis and Western-blot analysis. Two GRAB molecules formed stable complexes of high affinity with native and induced authentic hα2M tetramers. The shorter recombinant hα2M variants interacted after preincubation only. In contrast, pro-TGF-β2 did not interact, probably owing to hindrance by the N-terminal latency-associated protein of the cytokine.
Current and future climatic regions favourable for a globally introduced wild carnivore, the raccoon Procyon lotor
Authors: Louppe Vivien , Leroy Boris , Herrel Anthony , Veron Géraldine 
Published: June 2019

AbstractInvasive species are considered as one of the major threats to biodiversity and represent a major challenge in the conservation of natural ecosystems, in preventing damage to agricultural production, and human health risks. Environmental Niche Modelling has emerged as a powerful tool to predict the patterns of range expansion of non-native species and to direct effective strategies for managing biological invasions. The raccoon,Procyon lotor, is a wild mesocarnivore presenting a high adaptability and showing successful introduced populations worldwide. Here, we modelled the current and future climatically favourable areas for the raccoon using two protocols, based on data sets filtrated in geographic and environmental spaces. Projections from these models show extensive current favourable geographical areas covering extensive regions of temperate biomes. Moreover, predictions for 2050 reveals extensive new favourable areas north of the current favourable regions. However, the results of the two modeling approaches differ in the extent of predicted favourable spaces. Protocols using geographically filtered data present more conservative forecasts, while protocol using environmental filtration presents forecasts across greater areas. Given the biological characteristics and the ecological requirements of a generalist carnivore such as the raccoon, the latter forecasts appears more relevant and should be privileged in the development of conservation plans for ecosystems.
Transcriptome Analysis of Long-lived Drosophila melanogaster E(z) Mutants Sheds Light on the Molecular Mechanisms of Longevity
Authors: Moskalev Alexey A. , Shaposhnikov Mikhail V. , Zemskaya Nadezhda V. , Koval Liubov А. , Schegoleva Eugenia V. , Guvatova Zulfiya G. , Krasnov George S. , Solovev Ilya A. , Sheptyakov Maksim A. , Zhavoronkov Alex , Kudryavtseva Anna V. 
Published: June 2019

AbstractThe E(z) histone methyltransferase heterozygous mutation in Drosophila is known to increase lifespan and stress resistance. However, the longevity mechanisms of E(z) mutants have not been revealed. Using genome-wide transcriptome analysis, we demonstrated that lifespan extension, increase of resistance to hyperthermia, oxidative stress and endoplasmic reticulum stress, and fecundity enhancement in E(z) heterozygous mutants are accompanied by changes in the expression level of 239 genes (p < 0.05). Our results demonstrated sex-specific effects of E(z) mutation on gene expression, which, however, did not lead to differences in lifespan extension in both sexes. We observed that a mutation in an E(z) gene leads to perturbations in gene expression, most of which participates in metabolism, such as Carbohydrate metabolism, Lipid metabolism, Drug metabolism, Nucleotide metabolism. Age-dependent changes in the expression of genes involved in pathways related to immune response, cell cycle, and ribosome biogenesis were found.
Revealing higher than expected diversity of Harpacticoida (Crustacea:Copepoda) in the North Sea using MALDI-TOF MS and molecular barcoding
Authors: Rossel S. , Martínez Arbizu P. 
Published: June 2019

AbstractThe North Sea is one of the most extensively studied marine regions of the world. Hence, large amounts of molecular data for species identification are available in public repositories, and expectations to find numerous new species in this well-known region are rather low. However, molecular reference data for harpacticoid copepods from this area in particular but also for this group in general is scarce. By assessing COI barcodes and MALDI-TOF mass spectra for this group of small crustaceans, it was discovered that there is a huge unknown diversity in this area. In total, COI sequences for 548 specimens from 115 species of harpacticoid copepods are presented. Over 19% of these were new to science and ten MOTUs were found to be part of cryptic species complexes. MALDI-TOF mass spectra were assessed for 622 specimens from 75 species. Because results were in concordance with species delimitation by COI barcoding and also enabled recognition of possible cryptic species, the discriminative power of this technique for biodiversity assessments is highlighted. Findings imply, species diversity in this group may be largely underestimated and total species number can be expected to be much higher than previously assumed.
Methodical inaccuracy of the Z-scan method for few-cycle terahertz pulses
Authors: Melnik Maksim , Vorontsova Irina , Putilin Sergey , Tcypkin Anton , Kozlov Sergei 
Published: June 2019

AbstractModern sources of THz radiation generate high-intensity pulses allowing to observe nonlinear effects in this spectral range. To describe many nonlinear effects theoretically, it is necessary to know the nonlinear refractive index coefficient of optical materials. The work studies the applicability of the Z-scan method to determine the nonlinear refractive index coefficient in the THz frequency range for few-cycle pulses. We have discussed the correctness of the known Z-scan method for calculating the nonlinear refractive index coefficient for broadband THz radiation regarding number of cycles pulses have. We have demonstrated that the error in determining the nonlinear refractive index coefficient is always greater than 70% for true single-cycle pulses. With the increase in the number of oscillations to the measurement error shows strong dependence on the sample thickness and can vary from 2% to 90% regarding the parameters chosen. The fact that such radiation dispersion length is commensurate with the nonlinear length or even less than the latter results in the discrepancy mentioned. It is demonstrated that the decrease in the sample thickness leads to the reduction of the nonlinear refractive index coefficient determination error, and this error is <2% when the ratio between the sample thickness and the pulse longitudinal spatial size is ≤1. This can relate to the fact that the nonlinear effects in such a thin sample occur faster than the dispersion ones.
Phenotypic and molecular cytogenetic variability in calendula (Calendula officinalis L.) cultivars and mutant lines obtained via chemical mutagenesis
Authors: Samatadze Tatiana E. , Zoshchuk Svyatoslav A. , Hazieva Firdaus M. , Yurkevich Olga Yu , Svistunova Natalya Yu , Morozov Alexander I. , Amosova Alexandra V. , Muravenko Olga V. 
Published: June 2019

AbstractThe morphological, meiotic and chromosomal variability were studied in two cultivars of Calendula officinalis L. and their mutant lines obtained though chemical mutagenesis using diethyl sulphate (DES) (0.04%, 0.08%) and dimethyl sulphate (DMS) (0.025%, 0.05%). The studied cultivars displayed different sensitivity to DMS and DES mutagens. More M1 plants with morphological changes were observed in C. officinalis cv. ‘Zolotoe more’ than in cv. ‘Rajskij sad’. DMS and DES at low concentrations had positive effects on main agro-metrical traits in both cultivars including plant height, inflorescence diameter and number of inflorescences per plant. Dose-dependent increase in number of various meiotic abnormalities was revealed in both mutant lines. Comparative karyotype analysis and FISH-based visualization of 45S and 5S rDNA indicated a high level of karyotype stability in M1 and M2 plants. Seed treatments with DMS and DES at certain concentrations resulted in higher yields of inflorescences in M1 plants compared to the control. In M2 generation, dose-dependent reduction in the yields of inflorescences was observed. Our findings demonstrate that DMS and DES at low concentrations have great potential in calendula mutation breeding.
Lysophosphatidic acids and their substrate lysophospholipids in cerebrospinal fluid as objective biomarkers for evaluating the severity of lumbar spinal stenosis
Authors: Hayakawa Kentaro , Kurano Makoto , Ohya Junichi , Oichi Takeshi , Kano Kuniyuki , Nishikawa Masako , Uranbileg Baasanjav , Kuwajima Ken , Sumitani Masahiko , Tanaka Sakae , Aoki Junken , Yatomi Yutaka , Chikuda Hirotaka 
Published: June 2019

AbstractLysophospholipids (LPLs) are known to have potentially important roles in the initiation and maintenance of neuropathic pain in animal models. This study investigated the association between the clinical severity of lumbar spinal stenosis (LSS) and the cerebrospinal fluid (CSF) levels of LPLs, using human samples. We prospectively identified twenty-eight patients with LSS and fifteen controls with idiopathic scoliosis or bladder cancer without neurological symptoms. We quantified LPLs from CSF using liquid chromatography-tandem mass spectrometry. We assessed clinical outcome measures of LSS (Neuropathic Pain Symptom Inventory (NPSI) and Zurich Claudication Questionnaire (ZCQ)) and categorized patients into two groups according to their severity. Five species of lysophosphatidic acid (LPA), nine species of lysophosphatidylcholine (LPC), and one species of lysophosphatidylinositol (LPI) were detected. The CSF levels of all species of LPLs were significantly higher in LSS patients than controls. Patients in the severe NPSI group had significantly higher LPL levels (three species of LPA and nine species of LPC) than the mild group. Patients in the severe ZCQ group also had significantly higher LPL levels (four species of LPA and nine species of LPC). This investigation demonstrates a positive correlation between the CSF levels of LPLs and the clinical severity of LSS. LPLs are potential biomarkers for evaluating the severity of LSS.
Genome wide identification and comparative analysis of glutathione transferases (GST) family genes in Brassica napus
Authors: Wei Lijuan , Zhu Yan , Liu Ruiying , Zhang Aoxiang , Zhu Meicheng , Xu Wen , Lin Ai , Lu Kun , Li Jiana 
Published: June 2019

AbstractGlutathione transferases (GSTs) are multifunctional enzymes that play important roles in plant development and responses to biotic and abiotic stress. However, a systematic analysis of GST family members in Brassica napus has not yet been reported. In this study, we identified 179 full-length GST genes in B. napus, 44.2% of which are clustered on various chromosomes. In addition, we identified 141 duplicated GST gene pairs in B. napus. Molecular evolutionary analysis showed that speciation and whole-genome triplication played important roles in the divergence of the B. napus GST duplicated genes. Transcriptome analysis of 21 tissues at different developmental stages showed that 47.6% of duplicated GST gene pairs have divergent expression patterns, perhaps due to structural divergence. We constructed a GST gene coexpression network with genes encoding various transcription factors (NAC, MYB, WRKY and bZIP) and identified six modules, including genes expressed during late seed development (after 40 days; BnGSTU19, BnGSTU20 and BnGSTZ1) and in the seed coat (BnGSTF6 and BnGSTF12), stamen and anther (BnGSTF8), root and stem (BnGSTU21), leaves and funiculus, as well as during the late stage of pericarp development (after 40 days; BnGSTU12 and BnGSTF2) and in the radicle during seed germination (BnGSTF14, BnGSTU1, BnGSTU28, and BnGSTZ1). These findings lay the foundation for elucidating the roles of GSTs in B. napus.
Patterns of genetic structure and adaptive positive selection in the Lithuanian population from high-density SNP data
Authors: Urnikyte A. , Flores-Bello A. , Mondal M. , Molyte A. , Comas D. , Calafell F. , Bosch E. , Kučinskas V. 
Published: June 2019

AbstractThe analysis of geographically specific regions and the characterization of fine-scale patterns of genetic diversity may facilitate a much better understanding of the microevolutionary processes affecting local human populations. Here we generated genome-wide high-density SNP genotype data in 425 individuals from six geographical regions in Lithuania and combined our dataset with available ancient and modern data to explore genetic population structure, ancestry components and signatures of natural positive selection in the Lithuanian population. Our results show that Lithuanians are a homogenous population, genetically differentiated from neighbouring populations but within the general expected European context. Moreover, we not only confirm that Lithuanians preserve one of the highest proportions of western, Scandinavian and eastern hunter-gather ancestry components found in European populations but also that of an steppe Early to Middle Bronze Age pastoralists, which together configure the genetic distinctiveness of the Lithuanian population. Finally, among the top signatures of positive selection detected in Lithuanians, we identified several candidate genes related with diet (PNLIP, PPARD), pigmentation (SLC24A5, TYRP1 and PPARD) and the immune response (BRD2, HLA-DOA, IL26 and IL22).