Zinc-binding properties of Junín virus nucleocapsid protein

The arenavirus nucleocapsid protein (N) is a highly basic 63 kDa protein with a dual function during the virus life-cycle. First, it is involved in essential steps of genome replication, promoting the synthesis of the full-length antigenomic copy of S RNA, and second it associates with the genomic RNA to form the nucleocapsid. We have expressed the N protein of Junín virus in E. coli and shown that it binds zinc in vitro. This property is in agreement with the presence in the carboxy-terminal region of the N protein of the CX2HX23CX4C sequence, which resembles a classical zinc-finger motif. The specificity for zinc binding was demonstrated by competition with other divalent metal ions. The ability of the predicted motif to bind zinc was established by analysis of a series of N mutants, including truncated variants and amino acid substitutions. In addition, alternative zinc-binding sites were found.Instituto de Biotecnologia y Biologia Molecula

APOE Gene Associated with Cholesterol-Related Traits in the Hispanic Population

Genetic variants in the apolipoprotein E (APOE) gene are associated with lipid metabolism and lipid-related traits in the non-Hispanic population. There have been limited studies regarding the association between the APOE gene and hypercholesterolemia in the Hispanic population; therefore, our aim for this study is to examine the APOE gene’s associations with cholesterol level and its related phenotypes. The APOE gene consists of three different alleles, ε2, ε3, and ε4, with ε4 being associated with dementia and cardiovascular diseases. A total of 1,382 subjects were collected from the Texas Alzheimer’s Research and Care Consortium (TARCC, N = 1320) and the Initial Study of Longevity and Dementia from the Rio Grande Valley (ISLD-RGV, N = 62). Questionnaires on demographics, medical history, and blood/saliva samples were collected and APOE genotypes were performed. We observed allele frequencies of the APOE ε3 (96.7%), ε4 (22.6%) and ε2 (6.8%) alleles, respectively. Multivariable logistic regression revealed a significant association between the APOE ε4 allele and hypercholesteremia (p = 1.8 × 10−4 ) in our studied Hispanic population. We prove for the first time, that the APOE ε4 allele increases the risk for hypercholesterol in Hispanics. Further research is needed to confirm and supports our current findings

Association Between the Use of a Mobile Health Strategy App and Biological Changes in Breast Cancer Survivors: Prospective Pre-Post Study

The objectives of this study were to: (1) check whether it is feasible to find changes in inflammation biomarkers through an mHealth strategy app as a delivery mechanism of an intervention to monitor energy balance; and (2) discover potential predictors of change of these markers in breast cancer survivors (BCSs). Analyzing changes in inflammatory biomarker concentrations after using the mHealth app, differences between preassessment CRP (4899.04 pg/ml; SD 1085.25) and IL-6 (87.15 pg/ml; SD 33.59) and postassessment CRP (4221.24 pg/ml; SD 911.55) and IL-6 (60.53 pg/ml; SD 36.31) showed a significant decrease in both markers, with a mean difference of –635.25 pg/ml (95% CI –935.65 to –334.85; P<.001) in CRP and –26.61 pg/ml (95% CI –42.51 to –10.71; P=.002) in IL-6. Stepwise regression analyses revealed that changes in global quality of life, as well as uMARS score and hormonal therapy, were possible predictors of change in CRP concentration after using the mHealth app. In the same way, the type of tumor removal surgery conducted, as well as changes in weight and pain score, were possible predictors of change in IL-6 concentration after using the app. In conclusion, through the results of this study, we hypothesize that there is a possible association between an mHealth energy balance monitoring strategy and biological changes in BCSs. These changes could be explained by different biopsychosocial parameters, such as the use of the application itself, quality of life, pain, type of tumor removal surgery, hormonal treatment or obesity.The study was funded by the Spanish Ministry of Economy and Competitiveness (Plan Estatal de I+D+I 2013-2016), Fondo de Investigación Sanitaria del Instituto de Salud Carlos III (PI14/01627), Fondos Estructurales de la Unión Europea (FEDER), and by the Spanish Ministry of Education (FPU14/01069 and FPU17/00939)

NLRP3-inflammasome inhibition prevents high fat and high sugar diets-induced heart damage through autophagy induction

The NLRP3-inflammasome complex has emerged as an important component of inflammatory processes in metabolic dysfunction induced by high-caloric diets. In this study, we investigate the molecular mechanisms by which NLRP3 inhibition may attenuate diet-induced cardiac injury. Here we show the cardiac damage induced by high sugar diet (HSD), high fat diet (HFD) or high sugar/fat diet (HSFD) over 15 weeks. Genetic ablation of NLRP3 protected against this damage by autophagy induction and apoptotic control. Furthermore, NLRP3 inhibition by the selective small molecule MCC950 resulted in similar autophagy induction and apoptotic control in hearts after diets. These data were reproduced in THP-1 cells treated with MCC950 and cultured in media supplemented with serum from mice dosed with MCC950 and fed with diets. NLRP3 inhibition exerted beneficial metabolic, and autophagic adaptations in hearts from obesogenic diets. The inhibition of NLRP3 activation may hold promise in the treatment of metabolic and cardiovascular diseases.Junta de Andalucía CTS113Junta de Andalucia PI-0036-201

On the Bank Stocks Return and Volatility: Tale of a South Asian Economy

This paper examines Pakistani Banks stock return and volatility relationship with market, interest rate and foreign exchange rate. The study extensively applies different statistical approaches to model return and volatility relation. First, Ordinary Least Square (OLS) multiple regression model is applied for estimation of return relation. Further, Generalize Method of Movement (GMM) is applied to cater the endogeniety issue. Secondly, Due to presence of Conditional Heteroskedasticity, Weighted Least Square (WLS) and Generalize Auto Regression Conditional Heteroskedasticity - GARCH (1,1) estimation model is applied to estimate conditional return and volatility. Interest rate and foreign exchange rate have significant impact on unconditional and conditional bank stock returns under different model specifications. Market return is a determining factor in bank stock pricing. The results infer that bank volatility is significantly related with interest rate and foreign exchange rate risk. The volatility of bank stock returns is persistent with slower decay over time

Adaptations in energy metabolism and gene family expansions revealed by comparative transcriptomics of three Chagas disease triatomine vectors

Background: Chagas disease is a parasitic infection caused by Trypanosoma cruzi. It is an important public health problem affecting around seven to eight million people in the Americas. A large number of hematophagous triatomine insect species, occupying diverse natural and human-modified ecological niches transmit this disease. Triatomines are long-living hemipterans that have evolved to explode different habitats to associate with their vertebrate hosts. Understanding the molecular basis of the extreme physiological conditions including starvation tolerance and longevity could provide insights for developing novel control strategies. We describe the normalized cDNA, full body transcriptome analysis of three main vectors in North, Central and South America, Triatoma pallidipennis, T. dimidiata and T. infestans. Results: Two-thirds of the de novo assembled transcriptomes map to the Rhodnius prolixus genome and proteome. A Triatoma expansion of the calycin family and two types of protease inhibitors, pacifastins and cystatins were identified. A high number of transcriptionally active class I transposable elements was documented in T. infestans, compared with T. dimidiata and T. pallidipennis. Sequence identity in Triatoma-R. prolixus 1:1 orthologs revealed high sequence divergence in four enzymes participating in gluconeogenesis, glycogen synthesis and the pentose phosphate pathway, indicating high evolutionary rates of these genes. Also, molecular evidence suggesting positive selection was found for several genes of the oxidative phosphorylation I, III and V complexes. Conclusions: Protease inhibitors and calycin-coding gene expansions provide insights into rapidly evolving processes of protease regulation and haematophagy. Higher evolutionary rates in enzymes that exert metabolic flux control towards anabolism and evidence for positive selection in oxidative phosphorylation complexes might represent genetic adaptations, possibly related to prolonged starvation, oxidative stress tolerance, longevity, and hematophagy and flight reduction. Overall, this work generated novel hypothesis related to biological adaptations to extreme physiological conditions and diverse ecological niches that sustain Chagas disease transmission.Centro Regional de Estudios Genómico

Fragility Curves for Thin-Walled Cold-Formed Steel Wall Frames Affected by Ground Settlements Due to Land Subsidence

Land subsidence phenomenon due to ground water withdrawal is a current problem in many places around the world, particularly in the shallows of Mexico. This causes ground differential settlements that affect structures, mainly dwellings and buildings based on reinforced concrete and masonry. Eventually, these structural materials do not exhibit an adequate performance beyond a certain level of angular distortion. This work presents the results about a study regarding the performance of thin-walled cold-formed steel wall frames with different sheathing systems affected by angular distortions simulating ground differential settlements due to land subsidence. The wall frames are composed by vertical (studs) and horizontal elements (tracks), with different sheathing systems: polystyrene, OSB, gypsum and calcium silicate. By means of experimental testing of wall frames subjected to monotonic lateral loads, the rotational stiffness was obtained for the wall frames with polystyrene. Likewise the rotational stiffness of the other wall frame systems was calculated based on the data provided by other author’s publications. On the other hand, by means of numerical simulation, all the wall frame systems were modeled in structural analysis software, calibrating them based on the rotational stiffness. Also, the moment-rotation curves were calculated for the studs and tracks based on the direct strength method. A non-linear static pull down analysis was performed producing several degrees of angular distortion simulating ground settlements for all the wall frames sheathing systems. With the data acquired fragility curves were calculated according three levels of damage for the wall frames with different sheathing system

Design of New Dispersants Using Machine Learning and Visual Analytics

Artificial intelligence (AI) is an emerging technology that is revolutionizing the discovery of new materials. One key application of AI is virtual screening of chemical libraries, which enables the accelerated discovery of materials with desired properties. In this study, we developed computational models to predict the dispersancy efficiency of oil and lubricant additives, a critical property in their design that can be estimated through a quantity named blotter spot. We propose a comprehensive approach that combines machine learning techniques with visual analytics strategies in an interactive tool that supports domain experts’ decision-making. We evaluated the proposed models quantitatively and illustrated their benefits through a case study. Specifically, we analyzed a series of virtual polyisobutylene succinimide (PIBSI) molecules derived from a known reference substrate. Our best-performing probabilistic model was Bayesian Additive Regression Trees (BART), which achieved a mean absolute error of (Formula presented.) and a root mean square error of (Formula presented.), as estimated through 5-fold cross-validation. To facilitate future research, we have made the dataset, including the potential dispersants used for modeling, publicly available. Our approach can help accelerate the discovery of new oil and lubricant additives, and our interactive tool can aid domain experts in making informed decisions based on blotter spot and other key propertie

Dielectric 5-Branes and Giant Gravitons in ABJM

We construct a supersymmetric NS5-brane wrapped on a twisted 5-sphere expanding in the $CP^3$ in $AdS_4\times CP^3$, with D0-brane charge. This configuration provides a realization of the stringy exclusion principle in terms of giant D0-branes. In the maximal case the twisted 5-sphere reduces to a $CP^2$ and its energy can be accounted for both by a bound state of $k$ D4-branes wrapping the $CP^2$ and a bound state of $N$ D0-branes, a realization on the gravity side of the symmetry of Young diagrams with $N$ rows and $k$ columns. We discuss some generalizations of this configuration in M-theory carrying angular momentum, some of them with an interpretation as giant gravitons. We provide the microscopical description that allows to explore the region of finite 't Hooft coupling.Comment: 26 pages, reference adde

A risk prediction model for the assessment and triage of women with hypertensive disorders of pregnancy in low-resourced settings: the miniPIERS (Pre-eclampsia Integrated Estimate of RiSk) multi-country prospective cohort study.

BACKGROUND: Pre-eclampsia/eclampsia are leading causes of maternal mortality and morbidity, particularly in low- and middle- income countries (LMICs). We developed the miniPIERS risk prediction model to provide a simple, evidence-based tool to identify pregnant women in LMICs at increased risk of death or major hypertensive-related complications. METHODS AND FINDINGS: From 1 July 2008 to 31 March 2012, in five LMICs, data were collected prospectively on 2,081 women with any hypertensive disorder of pregnancy admitted to a participating centre. Candidate predictors collected within 24 hours of admission were entered into a step-wise backward elimination logistic regression model to predict a composite adverse maternal outcome within 48 hours of admission. Model internal validation was accomplished by bootstrapping and external validation was completed using data from 1,300 women in the Pre-eclampsia Integrated Estimate of RiSk (fullPIERS) dataset. Predictive performance was assessed for calibration, discrimination, and stratification capacity. The final miniPIERS model included: parity (nulliparous versus multiparous); gestational age on admission; headache/visual disturbances; chest pain/dyspnoea; vaginal bleeding with abdominal pain; systolic blood pressure; and dipstick proteinuria. The miniPIERS model was well-calibrated and had an area under the receiver operating characteristic curve (AUC ROC) of 0.768 (95% CI 0.735-0.801) with an average optimism of 0.037. External validation AUC ROC was 0.713 (95% CI 0.658-0.768). A predicted probability ≥25% to define a positive test classified women with 85.5% accuracy. Limitations of this study include the composite outcome and the broad inclusion criteria of any hypertensive disorder of pregnancy. This broad approach was used to optimize model generalizability. CONCLUSIONS: The miniPIERS model shows reasonable ability to identify women at increased risk of adverse maternal outcomes associated with the hypertensive disorders of pregnancy. It could be used in LMICs to identify women who would benefit most from interventions such as magnesium sulphate, antihypertensives, or transportation to a higher level of care