bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of JNK by compound C66 prevents pathological changes of the aorta in STZ‐induced diabetes
Authors: Liu Yucheng , Wang Yonggang , Miao Xiao , Zhou Shanshan , Tan Yi , Liang Guang , Zheng Yang , Liu Quan , Sun Jian , Cai Lu 
Published: April 2014

AbstractCardiovascular diseases as leading causes of the mortality world‐wide are related to diabetes. The present study was to explore the protective effect of curcumin analogue C66 on diabetes‐induced pathogenic changes of aortas. Diabetes was induced in male C57BL/6 mice with a single intraperitoneal injection of streptozotocin. Diabetic mice and age‐matched non‐diabetic mice were randomly treated with either vehicle (Control and Diabetes), C66 (C66 and Diabetes/C66) or c‐Jun N‐terminal kinase (JNK) inhibitor (sp600125, JNKi and Diabetes/JNKi). All three treatments were given by gavage at 5 mg/kg every other day for 3 months. Aortic inflammation, oxidative stress, fibrosis, cell apoptosis and proliferation, Nrf2 expression and transcription were assessed by immunohistochemical staining for the protein level and real‐time PCR method for mRNA level. Diabetes increased aortic wall thickness and structural derangement as well as JNK phosphorylation, all of which were attenuated by C66 treatment as JNKi did. Inhibition of JNK phosphorylation by C66 and JNKi also significantly prevented diabetes‐induced increases in inflammation, oxidative and nitrative stress, apoptosis, cell proliferation and fibrosis. Furthermore, inhibition of JNK phosphorylation by C66 and JNKi significantly increased aortic Nrf2 expression and transcription function (e.g. increased expression of Nrf2‐downstream genes) in normal and diabetic conditions. These results suggest that diabetes‐induced pathological changes in the aorta can be protected by C66 via inhibition of JNK function, accompanied by the up‐regulation of Nrf2 expression and function.
Isolation and characterization of a ranavirus from koi, Cyprinus carpio L., experiencing mass mortalities in India
Authors: George M R , John K R , Mansoor M M , Saravanakumar R , Sundar P , Pradeep V 
Published: April 2014

AbstractWe investigated mass mortalities of koi, Cyprinus carpio Linnaeus, 1758, experienced in South Indian fish farms by virus isolation, electron microscopy, PCR detection, sequencing of capsid protein gene and transmission studies. Samples of moribund koi brought to the laboratory suffered continuous mortality exhibiting swimming abnormalities, intermittent surfacing and skin darkening. Irido‐like virus was isolated from the infected fish in the indigenous snakehead kidney cell line (SNKD2a). Icosahedral virus particles of 100 to 120 nm were observed in the infected cell cultures, budding from the cell membrane. Virus transmission and pathogenicity studies revealed that horizontal transmission occurred associated with mortality. PCR analysis of infected fish and cell cultures confirmed the presence of Ranavirus capsid protein sequences. Sequence analysis of the major capsid protein gene showed an identity of 99.9% to that of largemouth bass virus isolated from North America. Detection and successful isolation of this viral agent becomes the first record of isolation of a virus resembling Santee–Cooper Ranavirus from a koi and from India. We propose the name koi ranavirus to this agent.
Rufy3, a protein specifically expressed in neurons, interacts with actin‐bundling protein Fascin to control the growth of axons
Authors: Wei Zhe , Sun Ming , Liu Xinyi , Zhang Jian , Jin Ying 
Published: April 2014

AbstractFor our nervous system to function properly, each neuron must generate a single axon and elongate the axon to reach its target. It is known that actin filaments and their dynamic interaction with microtubules within growth cones play important roles in inducing axon extension. However, it remains unclear how cytoskeletal dynamics is controlled in growth cones. In this study, we report that Rufy3, a RUN domain‐containing protein, is a neuron‐specific and actin filament‐relevant protein. We find that the appropriate expression of Rufy3 in mouse hippocampal neurons is required for the development of a single axon and axon growth. Our results show that Rufy3 specifically interacts with actin filament‐binding proteins, such as Fascin, and colocalizes with Fascin in growth cones. Knockdown of Rufy3 impairs the distribution of Fascin and actin filaments, accompanied by an increased proportion of neurons with multiple axons and a decrease in the axon length. Therefore, Rufy3 may be particularly important for neuronal axon elongation by interacting with Fascin to control actin filament organization in axonal growth cones.
image
We propose that Rufy3 may control mouse neuron axon development through its specific interaction with Fascin and Drebrin. Over‐expression of Rufy3 (Rufy3 OE) leads to longer axons and expands the distribution of Drebrin to almost the entire growth cone. In contrast, knockdown of Rufy3 (Rufy3 RNAi) results in shortened axons and enhanced the percentage of mutipolar neurons. Moreover, silencing of Rufy3 reduces and restricts the expression of Fascin and F‐actin to the edge of the growth cone. These findings provide new insights into the molecular regulation of axonal outgrowth and cell polarization in neurons.
Inflammation and tuberculosis: host‐directed therapies
Authors: Zumla A. , Rao M. , Parida S. K. , Keshavjee S. , Cassell G. , Wallis R. , Axelsson‐Robertsson R. , Doherty M. , Andersson J. , Maeurer M. 
Published: April 2014

AbstractTuberculosis (TB) is an airborne infectious disease that kills almost two million individuals every year. Multidrug‐resistant (MDR) TB is caused by strains of Mycobacterium tuberculosis (M. tb) resistant to isoniazid and rifampin, the backbone of first‐line antitubercular treatment. MDR TB affects an estimated 500 000 new patients annually. Genetic analysis of drug‐resistant MDR‐TB showed that airborne transmission of undetected and untreated strains played a major role in disease outbreaks. The need for new TB vaccines and faster diagnostics, as well as the development of new drugs, has recently been highlighted. The major problem in terms of current TB research and clinical demands is the increasing number of cases of extensively drug‐resistant and ‘treatment‐refractory’ TB. An emerging scenario of adjunct host‐directed therapies is intended to target pulmonary TB where inflammatory processes can be deleterious and lead to immune exhaustion. ‘Target‐organ‐saving’ strategies may be warranted to prevent damage to infected tissues and achieve focused, clinically relevant and long‐lasting anti‐M. tb cellular immune responses. Candidates for such interventions may be biological agents or already approved drugs that can be ‘re‐purposed’ to interfere with biologically relevant cellular checkpoints. Here, we review current concepts of inflammation in TB disease and discuss candidate pathways for host‐directed therapies to achieve better clinical outcomes.
Urine soluble urokinase‐type plasminogen activator receptor levels correlate with proteinuria in Puumala hantavirus infection
Authors: Outinen T. K. , Mäkelä S. , Huttunen R. , Mäenpää N. , Libraty D. , Vaheri A. , Mustonen J. , Aittoniemi J. 
Published: April 2014

AbstractObjectivesUrokinase‐type plasminogen activator receptor (uPAR) is upregulated during inflammation and known to bind to β3‐integrins, receptors used by pathogenic hantaviruses to enter endothelial cells. It has been proposed that soluble uPAR (suPAR) is a circulating factor that causes focal segmental glomerulosclerosis and proteinuria by activating β3‐integrin in kidney podocytes. Proteinuria is also a characteristic feature of hantavirus infections. The aim of this study was to evaluate the relation between urine suPAR levels and disease severity in acute Puumala hantavirus (PUUV) infection.DesignA single‐centre, prospective cohort study.Subjects and methodsUrinary suPAR levels were measured twice during the acute phase and once during convalescence in 36 patients with serologically confirmed PUUV infection. Fractional excretion of suPAR (FE suPAR) and of albumin (FE alb) was calculated.ResultsThe FE suPAR was significantly elevated during the acute phase of PUUV infection compared to the convalescent phase (median 3.2%, range 0.8–52.0%, vs. median 1.9%, range 1.0–5.8%, P = 0.005). Maximum FE suPAR was correlated markedly with maximum FE alb (r = 0.812, P < 0.001) and with several other variables that reflect disease severity. There was a positive correlation with the length of hospitalization (r = 0.455, P = 0.009) and maximum plasma creatinine level (r = 0.780, P < 0.001) and an inverse correlation with minimum urinary output (r = −0.411, P = 0.030). There was no correlation between FE suPAR and plasma suPAR (r = 0.180, P = 0.324).ConclusionUrinary suPAR is markedly increased during acute PUUV infection and is correlated with proteinuria. High urine suPAR level may reflect local production of suPAR in the kidney during the acute infection.
Association analysis between MTHFR genetic polymorphisms and the risk of congenital heart diseases in Chinese Han population
Authors: Zhang Quan , Zha Daogang , Dong Peikang , Zhang Ye , Zhang Wenjing , Liu Yili 
Published: April 2014

Abstract

Objectives
Congenital heart diseases (CHD) are common birth defects in the world. The methylenetetrahydrofolate reductase (MTHFR) gene is one of the most important candidate genes for the development of CHD. This case–control study aimed to evaluate the effect of MTHFR c.382A&gt;G and c.1129C&gt;T genetic polymorphisms as risk factors for the development of CHD.

Methods
A total of 230 CHD patients and 237 non-CHD controls were included in the present study. The genotyping of MTHFR c.382A&gt;G and c.1129C&gt;T genetic polymorphisms were detected by the polymerase chain reaction-restriction fragment length polymorphism and created restriction site-polymerase chain reaction methods, respectively.

Key findings
The alleles/genotypes distribution from these two genetic polymorphisms were statistically associated with the increased risk of CHD (for c.382A&gt;G, GG versus AA: odds ratio (OR) = 2.39, 95% confidence interval (CI), 1.27 to 4.52, P = 0.006; for c.1129C&gt;T, TT versus CC: OR = 2.73, 95% CI, 1.33 to 5.62, P = 0.005). The allele G and genotype GG of c.382A&gt;G and allele T and genotype TT of c.1129C&gt;T genetic polymorphisms might contribute to CHD susceptibility.

Conclusion
These preliminary findings indicate that these two MTHFR genetic polymorphisms are related with the risk of CHD in Chinese Han population, and might be potentially utilized as molecular markers.
Niche breadth of oligarchic species in Amazonian and Andean rain forests
Authors: Arellano Gabriel , Cala Victoria , Macía Manuel J. 
Published: April 2014

AbstractAimTo test the niche breadth hypothesis (NBH), which states that dominant species have broader environmental tolerances than rare species, focusing on oligarchic species distributions (1) along the gradients of edaphic and climatic individual variables, and (2) within the n‐dimensional environmental frame defined by all edaphic and climatic variability.LocationAmazonian and Andean tropical rain forests along a ca. 3000 m elevation gradient, covering an area of 200 × 200 km in northwestern Bolivia.MethodsAll woody plants with a DBH ≥2.5 cm were measured in 98 0.1‐ha plots. We analysed 18 chemical properties of the soils in each plot. Climatic and topographic variables were obtained from available open‐access databases. Three measures were calculated for each of the species found at each forest type: (1) regional‐scale dominance based on frequency and local abundance, (2) niche breadth along each of the environmental variables, and (3) total niche size within the whole environment.ResultsOligarchic species showed broader niche breadths than the other species that constituted the community assembly in both Amazonian and Andean rain forests. The niche breadth of any species tended to be positively correlated with its degree of dominance. The Amazonian forest showed a stronger oligarchic pattern than the Andean forest, and the Amazonian common species showed larger niches overall. However, this pattern differed for some particular variables: Amazonian oligarchies had narrower niches along the variables related to organic matter and most climatic variables, whereas Andean oligarchies had narrower niches along several micronutrient factors and temperature variables.ConclusionsThe results provide strong empirical support for the NBH in tropical rain forests. However, different patterns of dominance were found in the two habitats: oligarchic species ranged from narrow‐niched species to very broad generalist species. Broad‐niched oligarchic species have also been reported in other regions, suggesting an important role of niche size linking commonness at different scales. Oligarchic species exhibit relatively narrow niches with respect to soil factors if measured along wide gradients, regardless of the forest type studied. In contrast, the opposite pattern was found for many climatic variables, indicating higher sensitivity to climate in Amazonia compared to the Andes. Despite these differences, Amazonia has much larger total niche sizes for its common species than the Andes overall.
Recent speciation and secondary contact in endemic ants
Authors: Jowers Michael J. , Amor Fernando , Ortega Patrocinio , Lenoir Alain , Boulay Raphaël R. , Cerdá Xim , Galarza Juan A. 
Published: April 2014

AbstractGene flow is the main force opposing divergent selection, and its effects are greater in populations in close proximity. Thus, complete reproductive isolation between parapatric populations is not expected, particularly in the absence of ecological adaptation and sharp environmental differences. Here, we explore the biogeographical patterns of an endemic ant species, Cataglyphis floricola, for which two colour morphs (black and bicolour) coexist in parapatry throughout continuous sandy habitat in southern Spain. Discriminant analyses of six biometric measurements of male genitalia and 27 cuticular hydrocarbons reveal high differentiation between morphs. Furthermore, the low number of shared alleles derived from nuclear markers (microsatellites) between the morphs at their contact zone suggests the absence of recent gene flow. Mitochondrial DNA (COI) phylogenetic analysis and median‐joining networks show that the black morph is basal to the bicolour morph, with unique haplotypes recovered for each morph. Mismatch distribution analysis and Bayesian skyline plots suggest that they are undergoing different demographic changes, with the bicolour and black morphs at demographic equilibrium and expansion, respectively. Thus, our results show complete reproductive isolation between the two colour morphs as evidenced from genetic, chemical and morphological data. We suggest that these divergence events could be explained by historical vicariance during the Pleistocene, in which reproductive traits experienced strong divergent selection between the morphs initiating or culminating speciation.
Parameters of the Reproductive Tract, Spermatogenesis, Daily Sperm Production and Major Seminal Plasma Proteins of Tropically Adapted Morada Nova Rams
Authors: Sousa FML , Lobo CH , Menezes ESB , Rego JPA , Oliveira RV , Lima‐Souza AC , Fioramonte M , Gozzo FC , Pompeu RCFF , Cândido MJD , Oliveira JT , Moura AA 
Published: April 2014

ContentsThis study describes the reproductive parameters of Morada Nova rams, a breed of hair sheep from Brazil and with unique adaption to tropical environments. At 42 weeks of age, 15 rams were subjected to semen collection and, 1 week later, animals were slaughtered for collection of testes, epididymis and accessory sex glands. We conducted 2‐D electrophoresis of seminal plasma proteins and major spots of stained gels were identified by LC‐MS/MS. Total RNA was isolated from testis, epididymis and vesicular glands and subjected to qPCR. At slaughter, scrotal circumference and testicular weight were 27.5 ± 0.5 cm and 109.5 ± 6.0 g, respectively. Seminiferous tubule (ST) diameter was 188.3 ± 4.0 μm and each testis contained 1.9 ± 0.1 Sertoli cells (×109). Each Sertoli cell supported 0.1 ± 0.01 A spermatogonia, 3.0 ± 0.2 pachytene spermatocytes and 7.7 ± 0.5 round spermatids/tubule cross section. Daily sperm production reached 5.6 × 106 cells/g of testis parenchyma. Testis size appeared as indicative of ST diameter and associated with epididymal measurements, as well as with the population of round spermatids and Sertoli cells/testis. Rams with heavier testes had greater daily sperm production and more Sertoli cells/testis. We detected 90.9 ± 9.6 spots per 2‐D gel of seminal plasma. Major seminal proteins were identified as ram seminal vesicle proteins at 14 and 22 kDa, representing 16.2% and 12.8% of the total intensity of valid spots in the gels, respectively. Expression of both genes was greater in the vesicular glands as compared to testis and epididymis. Pixel intensity for those proteins in the 2‐D gels was significantly correlated with seminal vesicle weight. This is the first description of the basic reproductive aspects of Morada Nova rams, including protein profiles of their seminal plasma. These findings will allow a better understanding of their reproductive physiology.
Towards Uniformly Efficient Trend Estimation Under Weak/Strong Correlation and Non‐stationary Volatility
Authors: Xu Ke‐Li , Yang Jui‐Chung 
Published: April 2014

AbstractIn this paper, we consider the deterministic trend model where the error process is allowed to be weakly or strongly correlated and subject to non‐stationary volatility. Extant estimators of the trend coefficient are analysed. We find that under heteroskedasticity, the Cochrane–Orcutt‐type estimator (with some initial condition) could be less efficient than Ordinary Least Squares (OLS) when the process is highly persistent, whereas it is asymptotically equivalent to OLS when the process is less persistent. An efficient non‐parametrically weighted Cochrane–Orcutt‐type estimator is then proposed. The efficiency is uniform over weak or strong serial correlation and non‐stationary volatility of unknown form. The feasible estimator relies on non‐parametric estimation of the volatility function, and the asymptotic theory is provided. We use the data‐dependent smoothing bandwidth that can automatically adjust for the strength of non‐stationarity in volatilities. The implementation does not require pretesting persistence of the process or specification of non‐stationary volatility. Finite‐sample evaluation via simulations and an empirical application demonstrates the good performance of proposed estimators.
Simple, Low-Cost Molecular Assays for TR
34
/L98H Mutations in the
cyp51A
Gene for Rapid Detection of Triazole-Resistant Aspergillus fumigatus Isolates
Authors: Ahmad Suhail , Khan Ziauddin , Hagen Ferry , Meis Jacques F. 
Published: April 2014

ABSTRACT

Simple, low-cost PCR/PCR-restriction fragment length polymorphism (RFLP) assays targeting
cyp51A
promoter and codon 98 regions were developed for the detection of triazole-resistant
Aspergillus fumigatus
strains carrying TR
34
/L98H mutations. The assays were evaluated using 40 itraconazole-susceptible isolates and 35 itraconazole-resistant isolates. The prevalence of TR
34
/L98H mutations in clinical/environmental
A. fumigatus
isolates may now be determined easily from resource-poor settings.
Multicenter Evaluation of the New Vitek 2 Yeast Susceptibility Test Using New CLSI Clinical Breakpoints for Fluconazole
Authors: Pfaller M. A. , Diekema D. J. , Procop G. W. , Wiederhold N. P. 
Published: April 2014

ABSTRACTA fully automated antifungal susceptibility test system recently updated to reflect the new species-specific clinical breakpoints (CBPs) of fluconazole forCandida(Vitek 2 AF03 yeast susceptibility test; bioMérieux, Inc., Durham, NC) was compared in three different laboratories with the Clinical and Laboratory Standards Institute (CLSI) reference broth microdilution (BMD) method by testing 2 quality control strains, 10 reproducibility strains (4Candidaspecies and 6Cryptococcus neoformansstrains), and 746 isolates ofCandidaspecies (702 isolates, 13 species) and 44 isolates ofC. neoformansagainst fluconazole. Excellent essential agreement (EA) (within 2 dilutions) between the reference and Vitek 2 MICs was observed for fluconazole andCandidaspecies (94.0%). The EA was lower for fluconazole andC. neoformansat 86.4%. The mean times to a result with the Vitek 2 test were 9.1 h forCandidaspecies and 12.1 h forC. neoformans. Categorical agreement (CA) between the two methods was assessed by using the new species-specific CBPs. For less common species without fluconazole CBPs, the epidemiological cutoff values (ECVs) were used to differentiate wild-type (WT; MIC, ≤ECV) from non-WT (MIC, >ECV) strains. The CAs between the two methods were 92.0% forCandidaspecies (0.3% very major errors [VME] and 2.6% major errors [ME]) and 84.1% forC. neoformans(4.5% VME and 11.4% ME). The updated Vitek 2 AF03 IUO yeast susceptibility system is comparable to the CLSI BMD reference method for testing the susceptibility of clinically important yeasts to fluconazole when using the new (lower) CBPs and ECVs.
Development of a High-Yield Live Attenuated H7N9 Influenza Virus Vaccine That Provides Protection against Homologous and Heterologous H7 Wild-Type Viruses in Ferrets
Authors: Chen Zhongying , Baz Mariana , Lu Janine , Paskel Myeisha , Santos Celia , Subbarao Kanta , Jin Hong , Matsuoka Yumiko 
Published: April 2014

ABSTRACT

Live attenuated H7N9 influenza vaccine viruses that possess the hemagglutinin (HA) and neuraminidase (NA) gene segments from the newly emerged wild-type (wt) A/Anhui/1/2013 (H7N9) and six internal protein gene segments from the cold-adapted influenza virus A/Ann Arbor/6/60 (AA
ca
) were generated by reverse genetics. The reassortant virus containing the original wt A/Anhui/1/2013 HA and NA sequences replicated poorly in eggs. Multiple variants with amino acid substitutions in the HA head domain that improved viral growth were identified by viral passage in eggs and MDCK cells. The selected vaccine virus containing two amino acid changes (N133D/G198E) in the HA improved viral titer by more than 10-fold (reached a titer of 10
8.6
fluorescent focus units/ml) without affecting viral antigenicity. Introduction of these amino acid changes into an H7N9 PR8 reassortant virus also significantly improved viral titers and HA protein yield in eggs. The H7N9
ca
vaccine virus was immunogenic in ferrets. A single dose of vaccine conferred complete protection of ferrets from homologous wt A/Anhui/1/2013 (H7N9) and nearly complete protection from heterologous wt A/Netherlands/219/2003 (H7N7) challenge infection. Therefore, this H7N9 live attenuated influenza vaccine (LAIV) candidate has been selected for vaccine manufacture and clinical evaluation to protect humans from wt H7N9 virus infection.

IMPORTANCE
In response to the recent avian H7N9 influenza virus infection in humans, we developed a live attenuated H7N9 influenza vaccine (LAIV) with two amino acid substitutions in the viral HA protein that improved vaccine yield by 10-fold in chicken embryonated eggs, the substrate for vaccine manufacture. The two amino acids also improved the antigen yield for inactivated H7N9 vaccines, demonstrating that this finding could great facilitate the efficiency of H7N9 vaccine manufacture. The candidate H7N9 LAIV was immunogenic and protected ferrets against homologous and heterologous wild-type H7 virus challenge, making it suitable for use in protecting humans from H7 infection.