bluuebunny/crossref_metadata_2025_split huggingface dataset:
Parallel genetic evolution and speciation from standing variation
Authors: Thompson Ken A. , Osmond Matthew M. , Schluter Dolph 
Published: March 2019

AbstractAdaptation often proceeds from standing variation, and natural selection acting on pairs of populations is a quantitative continuum ranging from parallel to divergent. Yet, it is unclear how the extent of parallel genetic evolution during adaptation from standing variation is affected by the difference in the direction of selection between populations. Nor is it clear whether the availability of standing variation for adaptation affects progress toward speciation in a manner that depends on the difference in the direction of selection. We conducted a theoretical study investigating these questions and have two primary findings. First, the extent of parallel genetic evolution between two populations rapidly declines as selection changes from fully parallel toward divergent, and this decline is steeper in organisms with more traits (i.e., greater dimensionality). This rapid decline happens because small differences in the direction of selection greatly reduce the fraction of alleles that are beneficial in both populations. For example, populations adapting to optima separated by an angle of 33° might have only 50% of potentially beneficial alleles in common. Second, relative to when adaptation is from only new mutation, adaptation from standing variation improves hybrid fitness under parallel selection and reduces hybrid fitness under divergent selection. Under parallel selection, genetic parallelism from standing variation reduces the phenotypic segregation variance in hybrids, thereby increasing mean fitness in the parental environment. Under divergent selection, larger pleiotropic effects of alleles fixed from standing variation cause maladaptive transgressive phenotypes when combined in hybrids. Adaptation from standing genetic variation therefore slows progress toward speciation under parallel selection and facilitates progress toward speciation under divergent selection.
A Galerkin finite element algorithm based on third‐order Runge‐Kutta temporal discretization along the uniform streamline for unsteady incompressible flows
Authors: Liao Shaokai , Zhang Yan , Chen Da 
Published: March 2019

SummaryIn this paper, for two‐dimensional unsteady incompressible flow, the Navier‐Stokes equations without convection term are derived by the coordinate transformation along the streamline characteristic. The third‐order Runge‐Kutta method along the streamline is introduced to discrete the alternative Navier‐Stokes equations in time, and spacial discretization is carried out by the Galerkin method, and then, the third‐order accuracy finite element method is obtained. Meanwhile, the streamline velocity is uniformly approximated by initial velocity in each time step in order to reduce update frequency of total element matrix and improve calculation efficiency. Finally, some classic unsteady flow examples are calculated and analyzed by different calculation methods, which further demonstrate that the present method has more advantages in stability, permissible time step, dissipation, computational cost, and accuracy. The code can be downloaded at https://doi.org/10.13140/RG.2.2.27706.44484.
Upregulation of PD‐L1 and PD‐L2 in neck node metastases of head and neck squamous cell carcinoma
Authors: Moratin Julius , Metzger Karl , Safaltin Ayse , Herpel Esther , Hoffmann Jürgen , Freier Kolja , Hess Jochen , Horn Dominik 
Published: March 2019

AbstractBackgroundThis study aimed on evaluating the expression levels of the immune checkpoint proteins, PD‐L1 and PD‐L2, in tissue specimens of 175 oral squamous cell carcinomas (OSCC) and 33 corresponding lymph node metastases (LNM).MethodsTissue microarrays of primary OSCC and matched LNM were investigated via immunohistochemistry regarding PD‐L1/PD‐L2 expression. Results were compared for primary tumors and corresponding metastases and correlated with clinicopathological data.ResultsPD‐L1 expression in cancer cells correlated significantly with tumor size, and the presence of regional metastases (P < 0.01). PD‐L1 expression was significantly higher in metastases as compared to primary OSCC (P < 0.05). Overall survival was significantly worse in patients with higher levels of PD‐L1 and PD‐L2 score (P < 0.05).ConclusionsThis is the first publication to compare PD‐L1 and PD‐L2 expression in primary OSCC and matched LNM. The results indicate that anti‐PD‐1 therapy may be of therapeutic use even in early stage OSCC to prevent further progression.
Importance of the immune system in head and neck cancer
Authors: Mirza Adal H. , Thomas Gareth , Ottensmeier Christian H. , King Emma V. 
Published: March 2019

AbstractHead and neck squamous cell carcinoma (HNSCC) are a heterogeneous group of tumors, mainly caused by exposure to cigarette smoke and/or alcohol. In recent years, a virally driven subset of cancers driven by human papillomavirus subtype 16 [HPV‐16]) has emerged. Our own data and data from other groups have demonstrated the favorable clinical outcome of HPV‐driven oropharyngeal tumors and in both HPV+ and HPV− cancers the importance of a high density of tumor‐associated lymphocytes for survival. These data underpin manipulation and activation of the patients' immune system by treatment, and as a result immunotherapy is rapidly taking its place in the management of HNSCC. Here we review the role the immune system in relation to HNSCC and consider the implications these have for HNSCC immunotherapy. Studies to quantify survival benefits and treatment‐associated toxicities are ongoing.
Halloysite nanotubes as tools to improve the actual challenge of fixed doses combinations in tuberculosis treatment
Authors: Carazo Esperanza , Sandri Giuseppina , Cerezo Pilar , Lanni Cristina , Ferrari Franca , Bonferoni Cristina , Viseras Cesar , Aguzzi Carola 
Published: March 2019

AbstractHalloysite nanotubes (HLNTs) were used as nanocarriers of the tuberculostatic agent isoniazid (INH), a BCS (Biopharmaceutics Classification System) class III drug. Self‐assembling nanohybrids (INH‐loaded HLNTs) with an average outer diameter of 90 nm and polydispersity index of 0.7 approximately, were obtained by spontaneous adsorption of INH molecules to HLNTs powder in aqueous medium. The nanohybrids were aimed to improve oral drug bioavailability and reduce physicochemical incompatibility of INH with other concomitantly administered tuberculostatic agents. In vitro drug release from INH‐loaded HLNTs was successfully fitted to a diffusive kinetic law founded on the adsorption–desorption equilibrium between drug molecules in solution and solid inorganic excipients. INH‐loaded HLNTs showed good in vitro biocompatibility toward Caco‐2 cells at the concentrations studied (up to 1233 μg/mL), with improved cell proliferation. Permeability tests showed that INH transport across Caco‐2 cellular membranes was greatly enhanced and fluorescent microscopy confirmed that the drug encapsulated into nanohybrid was effectively internalized by the cells. INH‐loaded HLNTs enhanced stability of the drug in presence of other tuberculostatic agents, both in binary and quaternary combinations. It has been demonstrated that simple interaction between INH with HLNTs leads to drug permeability and stability improvements that could greatly facilitate the design of multiple drug dosage forms, an actual challenge in oral treatment of tuberculosis. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2019.
Controlled in vitro degradation behavior of highly oriented long‐chain‐branched poly(lactic acid) produced by solid‐phase die drawing
Authors: Li Ruiguang , Li Jiafeng , Zhao Xiaowen , Ye Lin , Coates Phil , Caton‐Rose Fin 
Published: March 2019

AbstractHighly oriented long‐chain‐branched poly(lactic acid) (LCB‐PLA) was fabricated through solid‐phase die drawing technology, and the in vitro degradation behavior of the oriented samples in phosphate‐buffered saline (PBS) was studied. During degradation, the weight retention and molecular weight for both PLA and LCB‐PLA increased with the increase of draw ratio. Moreover, the degradation autocatalytic effect was delayed, and the deterioration of mechanical strength was reduced by orientation, which was beneficial for controlling the degradation degree and decay rate of strength for PLA as bone fixation materials. The influence mechanism of orientation on the in vitro degradation of PLA was explored. The degradation of PLA in PBS was ascribed to the hydrolytic degradation of ester bonds on the molecular chain. By orientation, a dense microfibrillar crystalline structure formed both on the surface and inside of PLA samples, limiting the diffusion and absorption of PBS molecules into the PLA matrix effectively, inhibiting the hydrolytic degradation of ester bonds, and thus delaying the deterioration of mechanical properties of PLA. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2019.
Upregulation of miRNA‐223‐3p ameliorates RIP3‐mediated necroptosis and inflammatory responses via targeting RIP3 after spinal cord injury
Authors: Wang Yang , Jiao Jianhang , Ren Pengfei , Wu Minfei 
Published: March 2019

AbstractSpinal cord injury (SCI) has been a major burden on the society because of the high rate of disability. Receptor‐interacting protein 3 (RIP3)‐mediated necroptosis is a newly discovered pathway of programmed cell death and is involved in multiple pathologies of various human diseases. Micro RNAs (miRNAs) have been shown to be a potential target for therapeutic interventions after SCI. The aim of the present study is to explore the potential role of miR‐223‐3p and possible mechanism in SCI. We found that miR‐223‐3p was significantly downregulated in spinal neurons after H2O
2‐induced damage, while RIP3‐mediated necroptosis was elevated. Accordingly, RIP3‐mediated necroptosis and the inflammatory factor secretion could be significantly inhibited by Nec‐1 treatment. In adittion, overexpression of miR‐223‐3p in spinal neurons protected against H
2O
2‐induced necroptosis, and ablation of miR‐223‐3p exhibited the opposite effect. We found that miR‐223‐3p bound to the 3′‐untranslated region of RIP3 mRNA to negatively regulate the expression of RIP3. Moreover, the activated RIP3 reversed the inhibition of RIP3 and MLKL expression and the levels of TNF‐α, IL‐1β, and lactate dehydrogenase, which were induced by transfection with miR‐223‐3p in a H
2O
2‐induced model. Finally, these results indicate that miR‐223‐3p negatively regulates the RIP3 necroptotic signaling cascades and inflammatory factor secretion, which significantly relieves injury of spinal neurons. The miR‐223‐3p/RIP3 pathway offers a novel therapeutic target for the protection of spinal neurons after SCI.
An examination of grit in black men who have sex with men and associations with health and social outcomes
Authors: Winiker Abigail K. , Tobin Karin E. , Davey‐Rothwell Melissa , Latkin Carl 
Published: March 2019

AbstractAimsThis study sought to examine the prevalence and correlates of grit in a sample of Black men who have sex with men (BMSM) in Baltimore, Maryland.MethodsA trained research assistant administered the Short‐Grit and Center for Epidemiological Studies Depression (CES‐D) scales and surveyed participants of a community‐based behavioral health intervention for demographic, health, and sexual behaviors.ResultsOf 239 participants, two‐thirds scored in the high grit category. A greater proportion of men with high grit demonstrated higher educational attainment, were employed in the prior 6 months, reported very good/excellent health, were human immunodeficiency virus‐positive, scored < 16 on the CES‐D, and had more friends who were gay. After controlling for other variables, high grit was associated with higher odds of having more friends who are gay and lower odds of alcohol use, unemployment, and a high CES‐D score.ConclusionsThese findings demonstrate that grit could be an important mechanism upon which to focus health and behavioral interventions for BMSM.
Potential candidate biomarkers associated with osteoarthritis: Evidence from a comprehensive network and pathway analysis
Authors: Zhang Rongqiang , Guo Hao , Yang Xiaoli , Li Zhaofang , Zhang Dandan , Li Baorong , Zhang Di , Li Qiang , Xiong Yongmin 
Published: March 2019

AbstractOsteoarthritis (OA) is one of the most common forms of arthritis world widely. Some key genes and diagnostic markers have been reported due to the development of modern molecular biology technologies. However, the etiology and pathogenesis of OA remains unknown. In this study, an integrated network and pathway analysis towards the biological function of OA‐associated genes was conducted to provide valuable information to further explore the etiology and pathogenesis of OA. A total of 2,548 genes which reported a statistically significant association with OA were screened. An integrated network and pathway analysis was performed to identify the pathways and genes most associated to OA. Moreover, OA‐specific protein–protein interaction (PPI) network was constructed by cytocluster based on the Molecular Complex Detection Algorithm (MCODE) to screen its candidate biomarkers. Quantitative real‐time polymerase chain reaction was used to confirm the expression levels and to validate the results of MCODE cluster analysis by six genes. The pathway networks suggested that extracellular matrix (ECM) organization, collagen degradation and collagen formation showed important associations with OA. In top two PPI clusters, 61 of the OA‐associated genes were included in the OA‐specific PPI network, which also included 23 candidate genes that are likely to be highly associated with OA based on MCODE clusters. Analysis of mRNA showed that the expression levels of COL9A1, COL9A2, ITGA3, COL9A3, ITGA2, and LAMA1 in the peripheral blood mononuclear cells of OA patients were significantly lower than those of the normal controls (p<0.005). To our knowledge, this is the first comprehensive and systematic report based on OA‐related genes demonstrating that the functional destruction of collagen in cartilage may be a very important contributing factor to OA. Quantitative detection of collagen synthesis may be of great help in early identification and prediction of OA. Maintaining the quality and quantity of collagen can be a potential target for clinical treatment of OA in the future practice.
TRIM72 contributes to cardiac fibrosis via regulating STAT3/Notch‐1 signaling
Authors: Chen Xu , Su Jie , Feng Jianyu , Cheng Liang , Li Qing , Qiu Chen , Zheng Qijun 
Published: March 2019

AbstractCardiac fibrosis is a pathophysiological process characterized by excessive deposition of extracellular matrix. We developed a cardiac hypertrophy model using transverse aortic constriction (TAC) to uncover mechanisms relevant to excessive deposition of extracellular matrix in mouse myocardial cells. TAC caused upregulation of Tripartite motif protein 72 (TRIM72), a tripartite motif‐containing protein that is critical for proliferation and migration. Importantly, in vivo silencing of TRIM72 reversed TAC‐induced cardiac fibrosis, as indicated by markedly increased left ventricular systolic pressure and decreased left ventricular end‐diastolic pressure. TRIM72 knockdown also attenuated deposition of fibrosis marker collagen type I and α‐smooth muscle actin (α‐SMA). In an in vitro study, TRIM72 was similarly upregulated in cardiac fibroblasts. Knockdown of TRIM72 markedly suppressed collagen type I and α‐SMA expression and significantly decreased the proliferation and migration of cardiac fibroblasts. However, TRIM72 overexpression markedly increased collagen type I and α‐SMA expression and increased the proliferation and migration of cardiac fibroblasts. Further study demonstrated that TRIM72 increased phosphorylated STAT3 in cardiac fibroblasts. TRIM72 knockdown in cardiac fibroblasts resulted in increased expression of Notch ligand Jagged‐1 and its downstream gene and Notch‐1 intracellular domain. Inhibition of Notch‐1 abrogated sh‐TRIM72‐induced cardiac fibrosis. Together, our results support a novel role for TRIM72 in maintaining fibroblast‐to‐myofibroblast transition and suppressing fibroblast growth by regulating the STAT3/Notch‐1 pathway.
Inhibition of miR‐148b ameliorates myocardial ischemia/reperfusion injury via regulation of Wnt/β‐catenin signaling pathway
Authors: Yang Mei , Kong De‐Yan , Chen Jian‐Chang 
Published: March 2019

AbstractOur work aims to elucidate the effect how microRNA‐148b (miR‐148b) participated in myocardial ischemia/reperfusion (I/R) injury via regulation of Wnt/β‐catenin signaling pathway. The in vivo myocardial I/R models of SD rats and in vitro hypoxia/reoxygenation (H/R) models of H9C2 cells were established. The heart function and infarction area of rats and lactic dehydrogenase (LDH), creatine kinase (CK), malondialdehyde (MDA), and superoxide dismutase (SOD) levels were evaluated. Myocardial cell viability was measured using positron emission tomography combined with computer tomography and (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) assay, and the apoptosis was assessed by terminal deoxynucleotidyl transferase‐mediated nick‐end labeling method and flow cytometry; quantitative reverse‐transcription polymerase chain reaction and western blot were used to detect the related molecules expressions. The myocardial infarction area of rats was significantly increased with reductions in LVSP, + dp/dtmax, − dp/dtmax, LVFS%, LVEF% and standardized uptake value and elevation in left ventricular developed pressure after ischemia/reperfusion (I/R), and the LDH, CK, and MDA levels were enhanced with the decreased SOD. The apoptotic rates were higher in I/R rats and H/R H9C2 cells with upregulated miR‐148b and cleaved caspase‐3, but decreased Bcl‐2/Bax ratio; and meanwhile, the Wnt/β‐catenin pathway was inhibited. Additionally, the H/R‐induced H9C2 cells also exhibited decreased cell viability. MiR‐148b overexpression further aggravated I/R injury of rats, whereas inhibition of miR‐148b reduced I/R and H/R injury through activation of Wnt/β‐catenin pathway. In addition, Wnt‐1 small interfering RNA exposure abolished the effect of miR‐148b inhibitor on H/R injury of H9C2 cells. Inhibition of miR‐148b improved the antioxidative ability and myocardial cell survival to suppress its apoptosis by activating Wnt/β‐catenin signaling pathway, thus ameliorating the myocardial I/R injury.
Ultrasound‐guided needle biopsy of large thyroid nodules: Core needle biopsy yields more reliable results than fine needle aspiration
Authors: Lee Hyeon Jin , Kim Young Joong , Han Hye Yeon , Seo Jae Young , Hwang Cheol Mog , Kim KeumWon 
Published: March 2019

AbstractPurposeThe objective of this study was to compare the false negative rate, sensitivity and false positive rate of ultrasound (US)‐guided fine needle aspiration (FNA) with those of US‐guided core needle biopsy (CNB) for large thyroid nodules ≥2.0 cm, which reportedly have an increased risk of thyroid malignancy.MethodsWe retrospectively studied surgically confirmed thyroid nodules that had preoperative US‐guided FNA or CNB between March 2005 and December 2013. We reviewed nodule size, sonographic features, cytohistologic results, and final surgical pathology. We assessed false negative rates, sensitivity, and false positive rates by biopsy method and nodule size for diagnosis of thyroid malignancy. We assessed complications for procedures.ResultsUS‐guided CNB showed better diagnostic performance, in terms of lower false negative rates and greater sensitivity, than US‐guided FNA in large thyroid nodules. There was no significant difference in false positive rate according to biopsy methods in large thyroid nodules. The false negative rates of large thyroid nodules (≥2.0 cm) were higher than those of small nodules (<2.0 cm). There were no major complications, and no significant differences in complication according to biopsy methods.ConclusionUS‐guided CNB improved the false negative rate and sensitivity for large nodules. Therefore, US‐guided CNB can be considered a useful diagnostic method for large thyroid nodules that might reduce the risk of unnecessary diagnostic surgery.
Class I myosins: Highly versatile proteins with specific functions in the immune system
Authors: Girón-Pérez Daniel Alberto , Piedra-Quintero Zayda Lizbeth , Santos-Argumedo Leopoldo 
Published: March 2019

AbstractConnections established between cytoskeleton and plasma membrane are essential in cellular processes such as cell migration, vesicular trafficking, and cytokinesis. Class I myosins are motor proteins linking the actin-cytoskeleton with membrane phospholipids. Previous studies have implicated these molecules in cell functions including endocytosis, exocytosis, release of extracellular vesicles and the regulation of cell shape and membrane elasticity. In immune cells, those proteins also are involved in the formation and maintenance of immunological synapse-related signaling. Thus, these proteins are master regulators of actin cytoskeleton dynamics in different scenarios. Although the localization of class I myosins has been described in vertebrates, their functions, regulation, and mechanical properties are not very well understood. In this review, we focused on and summarized the current understanding of class I myosins in vertebrates with particular emphasis in leukocytes.
Sunflower Acid Oil‐Based Production of Rhamnolipid Using Pseudomonas aeruginosa and Its Application in Liquid Detergents
Authors: Jadhav Jagruti V. , Anbu Padmini , Yadav Sneha , Pratap Amit P. , Kale Sandeep B. 
Published: March 2019

AbstractUtilization of industrial waste as substrates for the rhamnolipid synthesis by Pseudomonas aeruginosa is a worthy alternative for conventionally used vegetable oils and fatty acids to reduce the production cost of rhamnolipid. Sunflower acid oil (SAO), a by‐product of the oil industry, contains 70% 18:0 fatty acid, with oleic acid as a major component. In this scope, production and analysis of rhamnolipid was successfully demonstrated using SAO as a new substrate. Pseudomonas aeruginosa produced rhamnolipid (a glycolipid biosurfactant) at a maximum concentration of 4.9 g L−1 with 60 g L−1 of SAO in the medium. Structural properties of rhamnolipid biosurfactant are confirmed using thin layer chromatography (TLC), high performance liquid chromatography (HPLC), and fourier transformed infrared spectroscopy (FTIR) analysis. Further surface‐active properties of the crude rhamnolipid were evaluated by measuring surface tension and emulsification properties. The synthesized rhamnolipid reduced the surface tension of water to 30.12 mN m−1 and interfacial tension (against heptane) to 0.52 mN m−1. Moreover, rhamnolipid shows the highest emulsification index (above 80%) for vegetable oils. This study confirms the use of SAO as a potential substrate for rhamnolipid production. The synthesized rhamnolipid was incorporated in liquid detergent formulation along with alpha olefin sulfonate (AOS) and sodium lauryl ether sulfate (SLES). The performance properties including foaming and cleaning efficiency of liquid detergent were compared.