bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mathematical modeling of self-contained CRISPR gene drive reversal systems
Authors: Heffel Matthew G. , Finnigan Gregory C. 
Published: December 2019

AbstractThere is a critical need for further research into methods to control biological populations. Numerous challenges to agriculture, ecological systems, and human health could be mitigated by the targeted reduction and management of key species (e.g. pests, parasites, and vectors for pathogens). The discovery and adaptation of the CRISPR/Cas editing platform co-opted from bacteria has provided a mechanism for a means to alter an entire population. A CRISPR-based gene drive system can allow for the forced propagation of a genetic element that bypasses Mendelian inheritance which can be used to bias sex determination, install exogenous information, or remove endogenous DNA within an entire species. Laboratory studies have demonstrated the potency by which gene drives can operate within insects and other organisms. However, continued research and eventual application face serious opposition regarding issues of policy, biosafety, effectiveness, and reversal. Previous mathematical work has suggested the use of modified gene drive designs that are limited in spread such as daisy chain or underdominance drives. However, no system has yet been proposed that allows for an inducible reversal mechanism without requiring the introduction of additional individuals. Here, we study gene drive effectiveness, fitness, and inducible drive systems that could respond to external stimuli expanding from a previous frequency-based population model. We find that programmed modification during gene drive propagation could serve as a potent safeguard to either slow or completely reverse drive systems and allow for a return to the original wild-type population.
Statin treatment prevents the development of pulmonary arterial hypertension in a nonhuman primate model of HIV-associated PAH
Authors: Rabacal Whitney , Schweitzer Finja , Rayens Emily , Tarantelli Rebecca , Whang Patrick , Jimenez Viviana Cobos , Outwater Judy A. , Norris Karen A. 
Published: December 2019

AbstractPulmonary arterial hypertension (PAH) is a life-threatening disease characterized by pulmonary vascular remodeling, elevated pulmonary arterial pressure, and right heart failure. Human immunodeficiency virus (HIV)-infected individuals have a higher incidence of PAH than the non-HIV infected population and evidence suggests a role for systemic and pulmonary inflammation in the pathogenesis of HIV-associated PAH. Due to their pleiotropic effects, including immune-modulatory and anti-inflammatory effects, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have been considered for the treatment of PAH, with conflicting results. The effects of statins on HIV-associated PAH have not been specifically evaluated. We have developed a non-human primate (NHP) model of HIV-associated PAH that closely mimics HIV-PAH using simian immunodeficiency virus (SIV)-infected rhesus macaques (Macaca mulatta). We determined that treatment of healthy macaques with atorvastatin prior to and throughout SIV infection prevented the development of SIV-associated PAH. Additionally, SIV-infected macaques that initiated atorvastatin treatment during the early chronic disease stage had reduced incidence of PAH compared to untreated animals. Statin treatment reduced inflammatory mediators TGF-β, MIP-1α, and TNF-α and the numbers of CD14dimCD16+ non-classical monocytes, and CD14+CCR7−CD163−CD206+ alveolar macrophages previously shown to be associated with SIV-PAH. These results support the concept that statins reduce inflammatory processes that contribute to PAH and may provide a safe and effective prophylactic strategy for the prevention of PAH in HIV-infected individuals.
Identifying sequence variants contributing to hereditary breast and ovarian cancer in BRCA1 and BRCA2 negative breast and ovarian cancer patients
Authors: Jarhelle Elisabeth , Riise Stensland Hilde Monica Frostad , Hansen Geir Åsmund Myge , Skarsfjord Siri , Jonsrud Christoffer , Ingebrigtsen Monica , Strømsvik Nina , Van Ghelue Marijke 
Published: December 2019

AbstractFamilies with breast and ovarian cancer are often tested for disease associated sequence variants in BRCA1 and BRCA2. Pathogenic sequence variants (PVs) in these two genes are known to increase breast and ovarian cancer risks in females. However, in most families no PVs are detected in these two genes. Currently, several studies have identified other genes involved in hereditary breast and ovarian cancer (HBOC). To identify genetic risk factors for breast and ovarian cancer in a Norwegian HBOC cohort, 101 breast and/or ovarian cancer patients negative for PVs and variants of unknown clinical significance (VUS) in BRCA1/2 were screened for PVs in 94 genes using next-generation sequencing. Sixteen genes were closely scrutinized. Nine different deleterious germline PVs/likely pathogenic variants (LPVs) were identified in seven genes in 12 patients: three in ATM, and one in CHEK2, ERCC5, FANCM, RAD51C, TP53 and WRN. Additionally, 32 different VUSs were identified and these require further characterization. For carriers of PV/LPV in many of these genes, there are no national clinical management programs in Norway. The diversity of genetic risk factors possibly involved in cancer development show the necessity for more knowledge to improve the clinical follow-up of this genetically diverse patient group.
Envelope Dyadic Green’s Function for Uniaxial Metamaterials
Authors: Maslovski Stanislav I. , Mariji Hodjat 
Published: December 2019

AbstractWe introduce the concept of the envelope dyadic Green’s function (EDGF) and present a formalism to study the propagation of electromagnetic fields with slowly varying amplitude (EMFSVA) in dispersive anisotropic media with two dyadic constitutive parameters: the dielectric permittivity and the magnetic permeability. We find the matrix elements of the EDGFs by applying the formalism for uniaxial anisotropic metamaterials. We present the relations for the velocity of the EMFSVA envelopes which agree with the known definition of the group velocity in dispersive media. We consider examples of propagation of the EMFSVA passing through active and passive media with the Lorentz and the Drude type dispersions, demonstrating beam focusing in hyperbolic media and superluminal propagation in media with inverted population. The results of this paper are applicable to the propagation of modulated electromagnetic fields and slowly varying amplitude fluctuations of such fields through frequency dispersive and dissipative (or active) anisotropic metamaterials. The developed approach can be also used for the analysis of metamaterial-based waveguides, filters, and delay lines.
Behavioral evolution contributes to hindbrain diversification among Lake Malawi cichlid fish
Authors: York Ryan A. , Byrne Allie , Abdilleh Kawther , Patil Chinar , Streelman Todd , Finger Thomas E. , Fernald Russell D. 
Published: December 2019

AbstractThe evolutionary diversification of animal behavior is often associated with changes in the structure and function of nervous systems. Such evolutionary changes arise either through alterations of individual neural components (“mosaically”) or through scaling of the whole brain (“concertedly”). Here we show that the evolution of a courtship behavior in Malawi cichlid fish is associated with rapid, extensive, and specific diversification of orosensory, gustatory centers in the hindbrain. We find that hindbrain volume varies significantly between species that build pit (depression) compared to castle (mound) type bowers and that this trait is evolving rapidly among castle-building species. Molecular analyses of neural activity via immediate early gene expression indicate a functional role for hindbrain structures during bower building. Finally, comparisons of bower building species in neighboring Lake Tanganyika suggest parallel patterns of neural diversification to those in Lake Malawi. Our results suggest that mosaic brain evolution via alterations to individual brain structures is more extensive and predictable than previously appreciated.
Untargeted LC-HRMS-based metabolomics to identify novel biomarkers of metastatic colorectal cancer
Authors: Martín-Blázquez Ariadna , Díaz Caridad , González-Flores Encarnación , Franco-Rivas Daniel , Jiménez-Luna Cristina , Melguizo Consolación , Prados José , Genilloud Olga , Vicente Francisca , Caba Octavio , Pérez del Palacio José 
Published: December 2019

AbstractColorectal cancer is one of the main causes of cancer death worldwide, and novel biomarkers are urgently needed for its early diagnosis and treatment. The utilization of metabolomics to identify and quantify metabolites in body fluids may allow the detection of changes in their concentrations that could serve as diagnostic markers for colorectal cancer and may also represent new therapeutic targets. Metabolomics generates a pathophysiological ‘fingerprint’ that is unique to each individual. The purpose of our study was to identify a differential metabolomic signature for metastatic colorectal cancer. Serum samples from 60 healthy controls and 65 patients with metastatic colorectal cancer were studied by liquid chromatography coupled to high-resolution mass spectrometry in an untargeted metabolomic approach. Multivariate analysis revealed a separation between patients with metastatic colorectal cancer and healthy controls, who significantly differed in serum concentrations of one endocannabinoid, two glycerophospholipids, and two sphingolipids. These findings demonstrate that metabolomics using liquid-chromatography coupled to high-resolution mass spectrometry offers a potent diagnostic tool for metastatic colorectal cancer.
The oldest freshwater crabs: claws on dinosaur bones
Authors: Robin Ninon , van Bakel Barry W. M. , Hyžný Matúš , Cincotta Aude , Garcia Géraldine , Charbonnier Sylvain , Godefroit Pascal , Valentin Xavier 
Published: December 2019

AbstractWith approximately 1,500 extant species, freshwater crabs (Decapoda: Brachyura) are among the most diverse decapod crustaceans. Nevertheless, their fossil record is extremely limited: only Potamidae, Potamonautidae and Trichodactylidae are reported up to the Eocene of the Neotropics so far. This work documents unusually large decapod claws from the Upper Cretaceous (Campanian) continental deposits of Velaux and vicinity (southern France), in close association with large vertebrate remains. In addition to (1) the systematic assignment of these claws, the study addresses (2) the salinity trends in the deposit environment from its faunal assemblage and the elementary chemical patterns of fossils, and (3) the likely scenario for their auto/allochthony in the Velaux fluvial system. These claws belong to a new taxon,Dinocarcinus velauciensisn. gen. n. sp., referred to as Portunoidea sensu lato, a group of “true” crabs nowadays linked to marine systems. However, the faunal assemblage, the claw taphonomy and the carbonates Y/Ho signatures support their ancient freshwater/terrestrial ecology, making them the oldest reported continental brachyurans and extending the presence of crabs in freshwater environments by 40 Ma. Either as primary or as secondary freshwater crabs, the occurrence of these portunoids in Velaux is an evidence for the independent colonizations of continental environments by multiple brachyuran clades over time, as early as the Campanian.
mTORC1 and mTORC2 Differentially Regulate Cell Fate Programs to Coordinate Osteoblastic Differentiation in Mesenchymal Stromal Cells
Authors: Schaub Theres , Gürgen Dennis , Maus Deborah , Lange Claudia , Tarabykin Victor , Dragun Duska , Hegner Björn 
Published: December 2019

AbstractVascular regeneration depends on intact function of progenitors of vascular smooth muscle cells such as pericytes and their circulating counterparts, mesenchymal stromal cells (MSC). Deregulated MSC differentiation and maladaptive cell fate programs associated with age and metabolic diseases may exacerbate arteriosclerosis due to excessive transformation to osteoblast-like calcifying cells. Targeting mTOR, a central controller of differentiation and cell fates, could offer novel therapeutic perspectives. In a cell culture model for osteoblastic differentiation of pluripotent human MSC we found distinct roles for mTORC1 and mTORC2 in the regulation of differentiation towards calcifying osteoblasts via cell fate programs in a temporally-controlled sequence. Activation of mTORC1 with induction of cellular senescence and apoptosis were hallmarks of transition to a calcifying phenotype. Inhibition of mTORC1 with Rapamycin elicited reciprocal activation of mTORC2, enhanced autophagy and recruited anti-apoptotic signals, conferring protection from calcification. Pharmacologic and genetic negative interference with mTORC2 function or autophagy both abolished regenerative programs but induced cellular senescence, apoptosis, and calcification. Overexpression of the mTORC2 constituent rictor revealed that enhanced mTORC2 signaling without altered mTORC1 function was sufficient to inhibit calcification. Studies in mice reproduced the in vitro effects of mTOR modulation with Rapamycin on cell fates in vascular cells in vivo. Amplification of mTORC2 signaling promotes protective cell fates including autophagy to counteract osteoblast differentiation and calcification of MSC, representing a novel mTORC2 function. Regenerative approaches aimed at modulating mTOR network activation patterns hold promise for delaying age-related vascular diseases and treatment of accelerated arteriosclerosis in chronic metabolic conditions.
Spin polarization in the phase diagram of a Li–Fe–S system
Authors: Takami Tsuyoshi , Takeuchi Tomonari , Fukunaga Toshiharu 
Published: December 2019

AbstractDivalent and trivalent states of Fe ions are known to be stable in inorganic compounds. We focus a novel LixFeS5 cathode, in which the Li content (x) changes from 2 to 10 by an electrochemical technique. As x increases from 2, a Pauli paramagnetic conductive Li2FeS5 phase changes into a superparamagnetic insulating Li10FeS5 phase. Density functional theory calculations suggest that Fe+ ions in a high-x phase are responsible for ferromagnetic spin polarization. Reaching the monovalent Fe ion is significant for understanding microscopic chemistry behind operation as Li-ion batteries and the original physical properties resulting from the unique local structure.
High resolution structural and functional analysis of a hemopexin motif protein from Dolichos
Authors: Sharma Sarita Chandan , Kumar Ashish , Vashisht Sharad , Salunke Dinakar M. 
Published: December 2019

AbstractIt is increasingly evident that seed proteins exhibit specific functions in plant physiology. However, many proteins remain yet to be functionally characterized. We have screened the seed proteome of Dolichos which lead to identification and purification of a protein, DC25. The protein was monomeric and highly thermostable in extreme conditions of pH and salt. It was crystallized and structure determined at 1.28 Å resolution using x-ray crystallography. The high-resolution structure of the protein revealed a four-bladed β-propeller hemopexin-type fold containing pseudo four-fold molecular symmetry at the central channel. While the structure exhibited homology with 2S albumins, variations in the loops connecting the outermost strands and the differences in surface-charge distribution may be relevant for distinct functions. Comparative study of the protein with other seed hemopexins revealed the presence of four conserved water molecules in between the blades which cross-link them and maintain the tertiary structure. The protein exhibited intrinsic peroxidase activity, which could be inhibited by binding of a heme analog. The identification of redox-sensitive cysteine and inhibition of peroxidase activity by iodoacetamide facilitated characterization of the possible active site. The determined peroxidase activity of DC25 may be responsible for rescuing germinating seeds from oxidative stress.
Lattice disorder effect on magnetic ordering of iron arsenides
Authors: Sefat Athena S. , Wang Xiaoping P. , Liu Yaohua , Zou Qiang , Fu Mimgming , Gai Zheng , Ganesan Kalaiselvan , Vohra Yogesh , Li Li , Parker David S. 
Published: December 2019

AbstractThis study investigates magnetic ordering temperature in nano- and mesoscale structural features in an iron arsenide. Although magnetic ground states in quantum materials can be theoretically predicted from known crystal structures and chemical compositions, the ordering temperature is harder to pinpoint due to potential local lattice variations that calculations may not account for. In this work we find surprisingly that a locally disordered material can exhibit a significantly larger Néel temperature (TN) than an ordered material of precisely the same chemical stoichiometry. Here, a EuFe2As2 crystal, which is a ‘122’ parent of iron arsenide superconductors, is found through synthesis to have ordering below TN = 195 K (for the locally disordered crystal) or TN = 175 K (for the ordered crystal). In the higher TN crystals, there are shorter planar Fe-Fe bonds [2.7692(2) Å vs. 2.7745(3) Å], a randomized in-plane defect structure, and diffuse scattering along the [00 L] crystallographic direction that manifests as a rather broad specific heat peak. For the lower TN crystals, the a-lattice parameter is larger and the in-plane microscopic structure shows defect ordering along the antiphase boundaries, giving a larger TN and a higher superconducting temperature (Tc) upon the application of pressure. First-principles calculations find a strong interaction between c-axis strain and interlayer magnetic coupling, but little impact of planar strain on the magnetic order. Neutron single-crystal diffraction shows that the low-temperature magnetic phase transition due to localized Eu moments is not lattice or disorder sensitive, unlike the higher-temperature Fe sublattice ordering. This study demonstrates a higher magnetic ordering point arising from local disorder in 122.
RETRACTED ARTICLE: High diversity of Morchella and a novel lineage of the Esculenta clade from the north Qinling Mountains revealed by GCPSR-based study
Authors: Phanpadith Phonepaserd , Yu Zhongdong , Li Tao 
Published: December 2019

AbstractChina is a mainland country rich in natural morel recourses, having records of half of the worldwide 61 morel phylospecies. In this study, 31 collections of ascocarps from the north Qinling Mountains, 4 collections of commercial cultivars from the south Qinling Mountains, and 3Morchellamycelium clones from commercial cultivars were investigated using the genealogical concordance phylogenetic species recognition (GCPSR) method. Maximum-likelihood was employed for the construction of phylogenetic trees. A total of five phylogenetic species were found among the 38 collections, namelyMorchellasp. Mes-8, Mes-9, Mes-13, and Mes-25, andMorchella chensiensis(IF556780), in addition to the false morel (Verpa bohemica). The identification of cultivatedMorchellasp. Mel-2, Mel-6, Mel-10, and Mel-12 coincided with that of the commercial farms. A total of 80% (4/5) of yellow morels were new records for the Qinling region, except Mes-19; moreover, a novel monophyletic lineage,Morchella chensiensis, was found to be distinct from the previously reported phylospecies by single gene and combined genes analysis, thus being herein proposed as a new phylospecies. All collections from this study showed continental endemism, and all Qinling Mountains collections were grouped together in rDNA phylogenetic trees. The study provided insights on biodiversities in this key region of China.
A simple analytic model for predicting the wicking velocity in micropillar arrays
Authors: Krishnan Siva Rama , Bal John , Putnam Shawn A. 
Published: December 2019

AbstractHemiwicking is the phenomena where a liquid wets a textured surface beyond its intrinsic wetting length due to capillary action and imbibition. In this work, we derive a simple analytical model for hemiwicking in micropillar arrays. The model is based on the combined effects of capillary action dictated by interfacial and intermolecular pressures gradients within the curved liquid meniscus and fluid drag from the pillars at ultra-low Reynolds numbers $${\boldsymbol{(}}{{\bf{10}}}^{{\boldsymbol{-}}{\bf{7}}}{\boldsymbol{\lesssim }}{\bf{Re}}{\boldsymbol{\lesssim }}{{\bf{10}}}^{{\boldsymbol{-}}{\bf{3}}}{\boldsymbol{)}}$$(10−7≲Re≲10−3). Fluid drag is conceptualized via a critical Reynolds number: $${\bf{Re}}{\boldsymbol{=}}\frac{{{\bf{v}}}_{{\bf{0}}}{{\bf{x}}}_{{\bf{0}}}}{{\boldsymbol{\nu }}}$$Re=v0x0ν, where v0 corresponds to the maximum wetting speed on a flat, dry surface and x0 is the extension length of the liquid meniscus that drives the bulk fluid toward the adsorbed thin-film region. The model is validated with wicking experiments on different hemiwicking surfaces in conjunction with v0 and x0 measurements using Water $${\boldsymbol{(}}{{\bf{v}}}_{{\bf{0}}}{\boldsymbol{\approx }}{\bf{2}}\,{\bf{m}}{\boldsymbol{/}}{\bf{s}}{\boldsymbol{,}}\,{\bf{25}}\,{\boldsymbol{\mu }}{\bf{m}}{\boldsymbol{\lesssim }}{{\bf{x}}}_{{\bf{0}}}{\boldsymbol{\lesssim }}{\bf{28}}\,{\boldsymbol{\mu }}{\bf{m}}{\boldsymbol{)}}$$(v0≈2m/s,25µm≲x0≲28µm), viscous FC-70 $${\boldsymbol{(}}{{\boldsymbol{v}}}_{{\bf{0}}}{\boldsymbol{\approx }}{\bf{0.3}}\,{\bf{m}}{\boldsymbol{/}}{\bf{s}}{\boldsymbol{,}}\,{\bf{18.6}}\,{\boldsymbol{\mu }}{\bf{m}}{\boldsymbol{\lesssim }}{{\boldsymbol{x}}}_{{\bf{0}}}{\boldsymbol{\lesssim }}{\bf{38.6}}\,{\boldsymbol{\mu }}{\bf{m}}{\boldsymbol{)}}$$(v0≈0.3m/s,18.6µm≲x0≲38.6µm) and lower viscosity Ethanol $${\boldsymbol{(}}{{\boldsymbol{v}}}_{{\bf{0}}}{\boldsymbol{\approx }}{\bf{1.2}}\,{\bf{m}}{\boldsymbol{/}}{\bf{s}}{\boldsymbol{,}}\,{\bf{11.8}}\,{\boldsymbol{\mu }}{\bf{m}}{\boldsymbol{\lesssim }}{{\bf{x}}}_{{\bf{0}}}{\boldsymbol{\lesssim }}{\bf{33.3}}\,{\boldsymbol{\mu }}{\bf{m}}{\boldsymbol{)}}$$(v0≈1.2m/s,11.8µm≲x0≲33.3µm).
Characterization of a five-microRNA signature as a prognostic biomarker for esophageal squamous cell carcinoma
Authors: Yu Jun , Zhu Ming , Lv Min , Wu Xiaoliu , Zhang Xiaomei , Zhang Yuanying , Li Jintian , Zhang Qin 
Published: December 2019

AbstractThis study aims to identify a miRNAs signature for predicting overall survival (OS) in esophageal squamous cell carcinoma (ESCC) patients. MiRNA expression profiles and corresponding clinical information of 119 ESCC patients were obtained from NCBI GEO and used as the training set. Differentially expressed miRNAs (DEmiRNAs) were screened between early-stage and late-stage samples. Cox regression analysis, recursive feature elimination (RFE)-support vector machine (SVM) algorithm, and LASSO Cox regression model were used to identify prognostic miRNAs and consequently build a prognostic scoring model. Moreover, promising target genes of these prognostic miRNAs were predicted followed by construction of miRNA-target gene networks. Functional relevance of predicted target genes of these prognostic miRNAs in ESCC was analyzed by performing function enrichment analyses. There were 46 DEmiRNAs between early-stage and late-stage samples in the training set. A risk score model based on five miRNAs was built. The five-miRNA risk score could classify the training set into a high-risk group and a low-risk group with significantly different OS time. Risk stratification ability of the five-miRNA risk score was successfully validated on an independent set from the Cancer Genome Atlas (TCGA). Various biological processes and pathways were identified to be related to these miRNAs, such as Wnt signaling pathway, inflammatory mediator regulation of TRP channels pathway, and estrogen signaling pathway. The present study suggests a pathological stage-related five-miRNA signature that may have clinical implications in predicting prognosis of ESCC patients.