Natural variation reveals that intracellular distribution of ELF3 protein is associated with function in the circadian clock

Natural selection of variants within the Arabidopsis thaliana circadian clock can be attributed to adaptation to varying environments. To define a basis for such variation, we examined clock speed in a reporter-modified Bay-0 x Shakdara recombinant inbred line and localized heritable variation. Extensive variation led us to identify EARLY FLOWERING3 (ELF3) as a major quantitative trait locus (QTL). The causal nucleotide polymorphism caused a short-period phenotype under light and severely dampened rhythm generation in darkness, and entrainment alterations resulted. We found that ELF3-Sha protein failed to properly localize to the nucleus, and its ability to accumulate in darkness was compromised. Evidence was provided that the ELF3-Sha allele originated in Central Asia. Collectively we showed that ELF3 protein plays a vital role in defining its light-repressor action in the circadian clock and that its functional abilities are largely dependent on its cellular localization

Hybrid Machine Learning Technique for Forecasting Dhaka Stock Market Timing Decisions

Forecasting stock market has been a difficult job for applied researchers owing to nature of facts which is very noisy and time varying. However, this hypothesis has been featured by several empirical experiential studies and a number of researchers have efficiently applied machine learning techniques to forecast stock market. This paper studied stock prediction for the use of investors. It is always true that investors typically obtain loss because of uncertain investment purposes and unsighted assets. This paper proposes a rough set model, a neural network model, and a hybrid neural network and rough set model to find optimal buy and sell of a share on Dhaka stock exchange. Investigational findings demonstrate that our proposed hybrid model has higher precision than the single rough set model and the neural network model. We believe this paper findings will help stock investors to decide about optimal buy and/or sell time on Dhaka stock exchange

Left atrial pump strain predicts long-term survival after transcatheter aortic valve implantation

BACKGROUND This study aims at investigating left atrial (LA) deformation by left atrial reservoir (LARS) and pump strain (LAPS) and its implications for long-term survival in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). METHODS Speckle tracking echocardiography was performed in 198 patients with severe AS undergoing TAVI. Association of strain parameters with cardiovascular mortality was determined. RESULTS Over a follow-up time of 5 years, 49 patients (24.7%) died. LAPS was more impaired in non-survivors than survivors (P = 0.010), whereas no difference was found for LARS (P = 0.114), LA ejection fraction (P = 0.241), and LA volume index (P = 0.292). Kaplan-Meier analyses yielded a reduced survival probability according to the optimal threshold for LAPS (P = 0.002). A more impaired LAPS was associated with increased mortality risk (HR 1.12 [95% CI 1.02-1.22]; P = 0.014) independent of LVEF, LAVI, age, and sex. Addition of LAPS improved multivariable echocardiographic (LVEF, LAVI) and clinical (age, sex) models with potential incremental value for mortality prediction (P = 0.013 and P = 0.031, respectively). In contrast, LARS and LAVI were not associated with mortality. CONCLUSIONS In patients undergoing aortic valve replacement for severe AS, LAPS was impaired in patients dying during long-term follow-up after TAVI, differentiated survivors from non-survivors, was independently associated with long-term mortality, and yielded potential incremental value for survival prediction after TAVI. LAPS seems useful for risk stratification in severe AS and timely valve replacement

Glucose-6 Phosphate Dehydrogenase Deficiency in terms of hemolysis indicators and management

Background: Glucose-6 Phosphate Dehydrogenase (G6PD) Deficiency is one of the commonest inherited enzyme abnormalities in humans, caused by many mutations that reduce the stability of the enzyme and its level as red cells progress in age. Objectives: To determine the useful hematologic indicators of hemolysis, observe an early detection of G6PD enzyme deficiency (if any), and the available therapeutic measures. Patients and Methods: 123 patients with G6PD deficiency and hemolysis after exposure to fava beans whom visited AL-Elwiya Pediatric Teaching Hospital from the 1st of February 2016 till 31st of May 2016 were entered this study retrospectively. Hemolysis laboratory indicators were observed. Management supportive measures were put in consideration also. Results: We found that 10-20% levels of hematocrit and normochromic normocytic anemia were the most frequent on presentation, while a range of 15.1-20% of reticulocyte counts was the most common with lower rates in females group. Hyperbilirubinemia was seen with nil patients had abnormal renal function tests. About three quarters (76.4%) of the total number of involved cases had glucose-6-phosphate dehydrogenase (G6PD) deficiency. Only 4 patients required no blood transfusion, 102 patients (82.9%) needed transfusion once, and the rest 17 (13.8%) had more than one blood transfusion. Most of cases (91.1%) recovered within the first 3 days. However; all cases were recovered by the fourth day of admission. Conclusion: Hemoglobin and blood morphology with hyperbilirubinemia were useful hematologic indicators of hemolytic process, while blood transfusion was the most used therapeutic measure, and recovery was expected within 2-3 days

FORMULATION AND CHARACTERIZATION OF FLUCONAZOLE LOADED OLIVE OIL NANOEMULSIONS

Present study was carried out to develop and evaluate olive oil based nano-emulsion for transdermal delivery of fluconazole, a bistriazole based antifungal agent with poor water solubility and lipophilicity. Olive oil, a natural non-irritating, non-toxic proposed permeation enhancer, is known to have some antifungal activity as well. Screening of common emulsifiers like Tweens (Tween 20, tween 60, tween 80), Spans (span 60, span 80), brij 35, puronic 127, and poloxamer 188 were done based on solubility of fluconazole in these surfactants followed by their efficiency to emulsify olive oil in water. Co-emulsifiers such as glycols (polyethylene glycol 200, polyethylene glycol 400, propylene glycol), and short chain alcohols (ethanol, propanol, butanol and octanol) were also screened similarly. Tween 80 and butanol were selected as emulsifier and co-emulsifier respectively to formulate nano-emulsion by aqueous titration method. However, separation was observed after 24 hours. Therefore, span 80 was added as an auxiliary emulsifier to improve emulsification efficiency. Finally, a blend of tween 80, span 80 and butanol was optimized as emulsifier (56 % wt/wt) to emulsify 9 % wt/wt of olive oil in 33 % wt/wt water. Pseudo-ternary phase diagram was employed to identify and optimize the components. Optimized formulation based on phase separation and thermokinetic stability was characterized for globule size, size distribution, zeta potential, viscosity, refractive index and pH. Globule size analysis by zetasizer nano ZS was further confirmed by transmission electron microscopy. Permeation flux of fluconazole from optimized formulation through artificial skin was approximately three fold higher than the control. In conclusion, developed olive oil based nano-emulsion of fluconazole demonstrated promising solubility, permeability and stability. Keywords: Fluconazole, olive oil, nano-emulsion, transdermal permeatio

EMBalance - validation of a decision support system in the early diagnostic evaluation and management plan formulation of balance disorders in primary care: study protocol of a feasibility randomised controlled trial

BACKGROUND: Balance problems are caused by multiple factors and often lead to falls and related fractures, bringing large socio-economic costs. The complexity of balance control mechanisms, the lack of medical expertise, and the absence of specialised equipment contribute to the delayed or incorrect diagnosis and management ofthese patients. Advances in computer science have allowed the development of computer systems that support clinical diagnosis and treatment decisions based on individualised patient data. The aim of the EMBalance decision support system (DSS) is to support doctors facing this clinical challenge, to make a definitive diagnosis and implement an effective management plan. The EMBalance study will determine the accuracy of this supportive tool when used by non-specialist doctors. This study is funded by the European Union's Seventh Framework Programme. METHODS/DESIGN: EMBalance is a proof-of-concept study designed as a non-commercial, international, multi-centre, single-blind, parallel-group randomised controlled trial to be carried out at four clinical sites in the United Kingdom, Germany, Greece and Belgium. The study is comprised of three stages: internal pilot, phase I (diagnosis) and stage II (management). For this purpose, 200 patients presenting with persistent dizziness (>3 months’ duration) to primary care services will be randomised to either the intervention group (diagnostic assessment with the DSS) or a control group (diagnostic assessment without the DSS). Patients allocated to the intervention group will be assessed by a doctor with the support of the EMBalance DSS, while patients allocated to the control group will receive a visit as per standard practice. Ultimately, all patients’ diagnoses and management plans will be certified by a consultant in neuro-otology. DISCUSSION: EMBalance is the first trial to test the accuracy of a DSS in both the diagnosis of and the management plan for vestibular disorders across the healthcare systems of four different countries. The EMBalance study is the result of a combined effort of engineers and physicians to develop an accurate tool to support non-specialist doctors, with no risk for the patient. This trial will provide reliable information about the benefits of implementing DSSs in primary care while supporting the feasibility of testing the EMBalance algorithms in further research. TRIAL REGISTRATION: ClinicalTrials.gov NCT02704819. Registered 29 February 2016

Effective generation of transgenic pigs and mice by linker based sperm-mediated gene transfer.

BACKGROUND: Transgenic animals have become valuable tools for both research and applied purposes. The current method of gene transfer, microinjection, which is widely used in transgenic mouse production, has only had limited success in producing transgenic animals of larger or higher species. Here, we report a linker based sperm-mediated gene transfer method (LB-SMGT) that greatly improves the production efficiency of large transgenic animals. RESULTS: The linker protein, a monoclonal antibody (mAb C), is reactive to a surface antigen on sperm of all tested species including pig, mouse, chicken, cow, goat, sheep, and human. mAb C is a basic protein that binds to DNA through ionic interaction allowing exogenous DNA to be linked specifically to sperm. After fertilization of the egg, the DNA is shown to be successfully integrated into the genome of viable pig and mouse offspring with germ-line transfer to the F1 generation at a highly efficient rate: 37.5% of pigs and 33% of mice. The integration is demonstrated again by FISH analysis and F2 transmission in pigs. Furthermore, expression of the transgene is demonstrated in 61% (35/57) of transgenic pigs (F0 generation). CONCLUSIONS: Our data suggests that LB-SMGT could be used to generate transgenic animals efficiently in many different species

Characterization of seed oils from different varieties of watermelon [<i>Citrullus lanatus</i> (Thunb.)] from Pakistan

This paper reports the physicochemical characteristics of the seed oils from different varieties of watermelon (<i>Citrullus lanatus</i>) cultivated in Pakistan, namely Sugar Baby, Q-F-12, D-W-H-21 and Red Circle-1885. The oil and crude protein contents from watermelon seeds, within the range of 28.25 to 35.65% and 20.50 to 35.00%, respectively, varied significantly (<i>p</i> < 0.05) among the varieties tested. The levels of moisture, ash, and crude fiber in the seeds tested were found to be 2.16-3.24%, 1.95-3.42% and 4.29-6.60%, respectively. The physicohemical characteristics of the extracted oils were: free fatty acid contents (1.17-2.10% as oleic acid), iodine value (97.10-116.32 g of I2 100g^-1 of oil), saponification index (190.20-205.57 mg KOH g^-1 of oil), unsaponifiable matter (0.54-0.82%) and color (1.12-4.30 R + 12.20-33.40 Y). The oils revealed a reasonable oxidative parameter range as depicted by the determinations of specific extinction at 232 and 270 nm (2.90-4.40 and 2.05- 3.09, respectively), <i>p</i>-anisidine value (5.60-7.70) and peroxide value (2.90-5.06 meqO₂ kg^-1 of oil). Linoleic acid was the major fatty acid found in all the seed oils with contributions of 45.30-51.80% of the total fatty acids (FA). Other fatty acids detected were known to be oleic acid (20.2- 23.5%), palmitic acid (15.1-16.9%) and stearic acid (11.5- 14.4%). The contents of α- and δ-tocopherol in the oils accounted for 120.6-195.6 and 9.1-58.3 mg kg^-1, respectively. The physicochemical attributes of the watermelon seed oils showed a wider variation among the varieties tested. The results of the present study indicate that the seeds of the tested watermelon varieties from Pakistan are a potential source of high-linoleic oil and thus can be explored for commercial use and value addition.<br><br>Se presentan las características físico-químicas de aceites de diferentes variedades de semillas de sandías (Citrullus lanatus) cultivadas en Pakistán: Sugar Baby, QF-12, DWH-21 y Círculo rojo-1885. El aceite y el contenido de proteína cruda de las semillas de sandía están dentro de los rangos: 28,25-35,65% y 20,50-35,00%, respectivamente y varian significativamente (p < 0,05) entre las variedades ensayadas. Los niveles de humedad, fibra cruda y cenizas en las semillas se encontró entre 2.16-3.24%, 1.95-3.42% y 4.29-6.60%, respectivamente. Las características fisico-químicas estudiadas de los aceites extraídos fueron: contenido de ácidos grasos libres (1.17-2.10% de ácido oleico), índice de yodo (97,10-116,32 g de I2 100 g^-1 de aceite), índice de saponificación (190,20-205,57 mg de KOH g^-1 de aceite), insaponificable (0,54-0.82%) y color (1.12-4.30 de I + 12.20- 33.40 y). Los aceites presentaron unos rangos de los parámetros de oxidación razonables, como se muestra en las determinaciones de la extinción específica a 232 y 270 nm (2.90-4.40 y 2.05-3.09 respectivamente), valores de <i>p</i>-anisidina (5.60-7.70) e índice de peróxidos (2,90-5,06 meqO₂ kg^-1 de aceite). El ácido linoleico es el principal ácido graso que se encuentra en todos los aceites de las semillas, con una contribución del 45.30-51.80% del total de ácidos grasos. Otros ácidos grasos determinados fueron oleico, 20,2-23,5%, palmítico, 15,1-16,9%) y esteárico, 11,5-14,4%. El contenido de α- y δ-tocoferol en los aceites fué de 120,6-195,6 y 9,1- 58,3 mg kg^-1, respectivamente. Los atributos físico-químicos de los aceites de semillas de sandía variaron significativamente entre las variedades ensayadas. Los resultados del presente estudio indican que las semillas de las variedades de sandía ensayadas procedentes de Pakistán son una fuente potencial aceites con alto contenido en ácido linoleico y, por lo tanto, se puede explorar para usos comerciales y productos con valor añadido

Adventitial transplantation of blood outgrowth endothelial cells in porcine haemodialysis grafts alleviates hypoxia and decreases neointimal proliferation through a matrix metalloproteinase-9-mediated pathway—a pilot study

Purpose. We hypothesized that adventitial transplantation of blood outgrowth endothelial cells (BOEC) to the vein-to-graft anastomosis of polytetrafluoroethylene grafts will reduce neointimal hyperplasia by reducing hypoxia inducible factor-1α (HIF-1α), by increasing angiogenesis in a porcine model of chronic renal insufficiency with haemodialysis polytetrafluoroethylene grafts. Because matrix metalloproteinases (MMPs) have been shown to be involved with angiogenesis, the expression of MMPs and their inhibitors was determined