Miracle-dz/UniFAR-FTUs huggingface dataset:
Lysophosphatidic acids are new substrates for the phosphatase domain of soluble epoxide hydrolase[S]

Soluble epoxide hydrolase (sEH) is a bifunctional enzyme that has a C-terminus epoxide hydrolase domain and an N-terminus phosphatase domain. The endogenous substrates of epoxide hydrolase are known to be epoxyeicosatrienoic acids, but the endogenous substrates of the phosphatase activity are not well understood. In this study, to explore the substrates of sEH, we investigated the inhibition of the phosphatase activity of sEH toward 4-methylumbelliferyl phosphate by using lecithin and its hydrolyzed products. Although lecithin itself did not inhibit the phosphatase activity, the hydrolyzed lecithin significantly inhibited it, suggesting that lysophospholipid or fatty acid can inhibit it. Next, we investigated the inhibition of phosphatase activity by lysophosphatidyl choline, palmitoyl lysophosphatidic acid, monopalmitoyl glycerol, and palmitic acid. Palmitoyl lysophosphatidic acid and fatty acid efficiently inhibited phosphatase activity, suggesting that lysophosphatidic acids (LPAs) are substrates for the phosphatase activity of sEH. As expected, palmitoyl, stearoyl, oleoyl, and arachidonoyl LPAs were efficiently dephosphorylated by sEH (Km, 3–7 μM; Vmax, 150–193 nmol/min/mg). These results suggest that LPAs are substrates of sEH, which may regulate physiological functions of cells via their metabolism.
Histological Observations of Early Gonadal Development to Form Asymmetrically in the Dwarf Gourami Colisa lalia

The asymmetrical and latitudinal formation of the gonads during early development in the dwarf gourami Colisa lalia was histologically observed using fish reared in laboratory. Hatching larvae obtained 33 hours after spawning possessed primordial germ cells (PGCs), which aggregated to the dorsal surface of the gut. In prolarvae on day 7, the gonadal anlagen were still situated on the dorsal surface of the gut, however, in those on day 10, the left gonadal anläge began to shift leftward, although the coelom did not develop sufficiently. In prolarvae on day 20, the right gonadal anlage also began to move leftward. During this period, the gut developed considerably in the right side of the coelom. On day 25, the developing gonads were located in the interspace of the developing spiral valve intestine. Sex differentiation of gonads appeared to begin by day 25. From those observations, we concluded that asymmetricity of gonads in C. lalia is caused by a limited space of the coelom opened on the left side of the body during the early phase of the formation of gonadal anlagen, which may be accurately determined by the position in which the gut develops.
Current challenges in understanding melanogenesis: bridging chemistry, biological control, morphology, and function

Melanin is a natural pigment produced within organelles, melanosomes, located in melanocytes. Biological functions of melanosomes are often attributed to the unique chemical properties of the melanins they contain; however, the molecular structure of melanins, the mechanism by which the pigment is produced, and how the pigment is organized within the melanosome remains to be fully understood. In this review, we examine the current understanding of the initial chemical steps in the melanogenesis. Most natural melanins are mixtures of eumelanin and pheomelanin, and so after presenting the current understanding of the individual pigments, we focus on the mixed melanin systems, with a critical eye towards understanding how studies on individual melanin do and do not provide insight in the molecular aspects of their structures. We conclude the review with a discussion of important issues that must be addressed in future research efforts to more fully understand the relationship between molecular and functional properties of this important class of natural pigments.
Antecedents and Consequences of Ecotourism Behavior: Independent and Interdependent Self-Construals, Ecological Belief, Willingness to Pay for Ecotourism Services and Satisfaction with Life

The purpose of this study is to investigate the antecedents related to why tourists engage in ecotourism and the consequences of ecotourism behavior. This study examined the concept of self-construal as a social aspect of self that influences different levels of ecological beliefs, which, in turn, affect ecotourism behavior. To address the unsatisfactory predictive power of the belief/attitude-behavior model, this study included the willingness to pay (WTP) for ecotourism between the ecological belief and ecotourism behavior relationships. Finally, this study examined the impact of ecotourism on tourists’ satisfaction with life as a result of ecotourism behavior. A structural equation model was constructed to test the proposed model. We found significant impacts of self-construals in explaining ecological beliefs. Significant relationships were found between ecological belief and WTP for ecotourism services which influenced ecotourism behavior, and between ecological belief and ecotourism behavior which affected satisfaction with life. The moderating effect of gender was only found on the path between WTP and ecotourism behavior. The findings of this study offer some implications for industry and policymakers to develop effective ecotourism programs.
Interactions of free and liposomal amphotericin B with renal proximal tubular cells in primary culture.

We studied in vitro the renal toxicity of amphotericin B (AMB) and liposomal AMB using primary cultures of rabbit proximal tubular cells grown to confluence in serum-free medium. Toxicity was assessed by changes 1) in the Na(+)-dependent uptakes of P1 and alpha-methylglucopyranoside (MGP), characteristic functions of proximal tubular cells; 2) K+ release into the supernatant, dependent upon membrane permeability; and 3) lactic dehydrogenase release as a marker for cellular death. Cells were exposed for 1 hr to AMB, alone or intercalated in small unilamellar vesicles prepared with one of the following phospholipids: dipalmitoylphosphatidyl choline, distearoylphosphatidyl choline or dimyristoylphosphatidyl choline. Although AMB concentrations of 20 microM or less did not increase lactic dehydrogenase release, P1 and MGP uptakes were significantly reduced (50% inhibition) by 2.5 and 5 microM AMB, respectively. AMB toxicity was dose-dependent, up to 20 microM. Analysis of P1 and MGP uptake kinetics, after treatment of the cells with 10 microM AMB, showed that inhibition occurred through a decrease in Vmax (66 and 57% inhibition for P1 and MGP, respectively) without affecting Km value. K+ release appeared for 2.5 microM AMB and increased with higher concentrations. Alteration of Na(+)-dependent uptakes by AMB, which parallels K+ release, may result from an alteration of the sodium gradient. Na(+)-dependent uptakes and K+ release were unaffected by liposomal AMB, even at the highest concentration tested (80 microM). The protective effect of liposomes was the same regardless of the phospholipid used. (ABSTRACT TRUNCATED AT 250 WORDS)
Defining the Interaction of HIV-1 with the Mucosal Barriers of the Female Reproductive Tract

ABSTRACT Worldwide, HIV-1 infects millions of people annually, the majority of whom are women. To establish infection in the female reproductive tract (FRT), HIV-1 in male ejaculate must overcome numerous innate and adaptive immune factors, traverse the genital epithelium, and establish infection in underlying CD4+ target cells. How the virus achieves this remains poorly defined. By utilizing a new technique, we define how HIV-1 interacts with different tissues of the FRT using human cervical explants and in vivo exposure in the rhesus macaque vaginal transmission model. Despite previous claims of the squamous epithelium being an efficient barrier to virus entry, we reveal that HIV-1 can penetrate both intact columnar and squamous epithelial barriers to depths where the virus can encounter potential target cells. In the squamous epithelium, we identify virus entry occurring through diffusive percolation, penetrating areas where cell junctions are absent. In the columnar epithelium, we illustrate that virus does not transverse barriers as well as previously thought due to mucus impediment. We also show a statistically significant correlation between the viral load of inocula and the ability of HIV-1 to pervade the squamous barrier. Overall, our results suggest a diffusive percolation mechanism for the initial events of HIV-1 entry. With these data, we also mathematically extrapolate the number of HIV-1 particles that penetrate the mucosa per coital act, providing a biological description of the mechanism for HIV-1 transmission during the acute and chronic stages of infection.
Inhibition of constitutively activated phosphoinositide 3‐kinase/AKT pathway enhances antitumor activity of chemotherapeutic agents in breast cancer susceptibility gene 1‐defective breast cancer cells

Loss or decrease of wild type BRCA1 function, by either mutation or reduced expression, has a role in hereditary and sporadic human breast and ovarian cancers. We report here that the PI3K/AKT pathway is constitutively active in BRCA1‐defective human breast cancer cells. Levels of phospho‐AKT are sustained even after serum starvation in breast cancer cells carrying deleterious BRCA1 mutations. Knockdown of BRCA1 in MCF7 cells increases the amount of phospho‐AKT and sensitizes cells to small molecule protein kinase inhibitors (PKIs) targeting the PI3K/AKT pathway. Restoration of wild type BRCA1 inhibits the activated PI3K/AKT pathway and de‐sensitizes cells to PKIs targeting this pathway in BRCA1 mutant breast cancer cells, regardless of PTEN mutations. In addition, clinical PI3K/mTOR inhibitors, PI‐103, and BEZ235, showed anti‐proliferative effects on BRCA1 mutant breast cancer cell lines and synergism in combination with chemotherapeutic drugs, cisplatin, doxorubicin, topotecan, and gemcitabine. BEZ235 synergizes with the anti‐proliferative effects of gemcitabine by enhancing caspase‐3/7 activity. Our results suggest that the PI3K/AKT pathway can be an important signaling pathway for the survival of BRCA1‐defective breast cancer cells and pharmacological inhibition of this pathway is a plausible treatment for a subset of breast cancers. © 2012 Wiley Periodicals, Inc.
[Cone-beam computed tomography analysis of root canal configuration of 4 674 mandibular anterior teeth].

OBJECTIVE To investigate the root canal configuration of mandibular anterior teeth with cone-beam computed tomography (CBCT). METHODS The CBCT imaging data of 866 patients who visited Peking University School of Stomatology from October 2012 to July 2013 were inspected by an endodontist anda radiologists together. A total of 4 674 mandibular anterior teeth were involved. The number of root, root canals and root canal configuration were observed and analyzed statistically (Chi-squared test). RESULTS All the mandibular central incisors and lateral incisors were single root, and 0.7% (11/1 542) of canines were double roots. 6.7% (105/1 566) of central incisors, 17.4% (273/1 566) of lateral incisors and 3.0% (46/1 542) of canines had double root canals. The frequency of symmetry of double root canal was 58.7% (37/63) in central incisors, 76.1% (108/142) in lateral incisors and 29.6% (8/27) in canines. The highest frequency of double root canals in different ages was 9.8% (28/287, 31-40 years) in central incisors, 21.5% (61/284, 31-40 years) in lateral incisors and 9.2% (19/207, ≥51 years) in canines. Vertucci type III canal configurations were the most prevalent in mandibular anterior teeth. CONCLUSION The double root canals are most common in mandibular lateral incisors. The highest incidence of symmetry of double root canal is also observed in mandibular lateral incisors. Vertucci type III canal configurations are the most frequent type in mandibular anterior teeth.
Beyond Hopkinson's bar

In order to perform experimental identification of high strain rate material models, engineers have only a very limited toolbox based on test procedures developed decades ago. The best example is the so-called split Hopkinson pressure bar based on the bar concept introduced 100 years ago by Bertram Hopkinson to measure blast pulses. The recent advent of full-field deformation measurements using imaging techniques has allowed novel approaches to be developed and exciting new testing procedures to be imagined for the first time. One can use this full-field information in conjunction with efficient numerical inverse identification tools such as the virtual fields method (VFM) to identify material parameters at high rates. The underpinning novelty is to exploit the inertial effects developed in high strain rate loading. This paper presents results from a new inertial impact test to obtain stress–strain curves at high strain rates (here, up to 3000 s−1). A quasi-isotropic composite specimen is equipped with a grid and images are recorded with the new HPV-X camera from Shimadzu at 5 Mfps and the SIMX16 camera from Specialised Imaging at 1 Mfps. Deformation, strain and acceleration fields are then input into the VFM to identify the stiffness parameters with unprecedented quality.
Driving with Glaucoma: Task Performance and Gaze Movements

Purpose The aim of this pilot study was to assess the driving performance and the visual search behavior, that is, eye and head movements, of patients with glaucoma in comparison to healthy-sighted subjects during a simulated driving test. Methods Driving performance and gaze behavior of six glaucoma patients and eight healthy-sighted age- and sex-matched control subjects were compared in an advanced driving simulator. All subjects underwent a 40-minute driving test including nine hazardous situations on city and rural roads. Fitness to drive was assessed by a masked driving instructor according to the requirements of the official German driving test. Several driving performance measures were investigated: lane position, time to line crossing, and speed. Additionally, eye and head movements were tracked and analyzed. Results Three out of six glaucoma patients passed the driving test and their driving performance was indistinguishable from that of the control group. Patients who passed the test showed an increased visual exploration in comparison to patients who failed; that is, they showed increased number of head and gaze movements toward eccentric regions. Furthermore, patients who failed the test showed a rightward bias in average lane position, probably in an attempt to maximize the safety margin to oncoming traffic. Conclusions Our study suggests that a considerable subgroup of subjects with binocular glaucomatous visual field loss shows a safe driving behavior in a virtual reality environment, because they adapt their viewing behavior by increasing their visual scanning. Hence, binocular visual field loss does not necessarily influence driving safety. We recommend that more individualized driving assessments, which will take into account the patient’s ability to compensate, are required.
Neonatal Cholestasis - Single Centre Experience in Central India

Background: Neonatal cholestasis syndrome (NCS) is a major cause of morbidity and mortality in infants. The disorder has rarely been studied in centers from Central India. Objectives: To study the prevalence, clinical presentation and etiology of NCS at a tertiary referral center in Central India. Materials and Methods: The study was carried out at a tertiary referral center in Central India. The study is a descriptive study. The records of all patients with suspected NCS treated in the Department of Pediatrics from 2007-2012 were analyzed. Results: One hundred and sixty-eight children had a provisional diagnosis of NCS. The complete records of 100 children were available for the study. The median age of presentation was 78 days (range 15-270 days). The male: female ratio was 1.17:1. The clinical features noted were- jaundice (100/100,100%), failure to thrive (73,73%), organomegaly (68, 68%), acholic stools (38,38%), abdominal distention (52,52%) and poor feeding (29, 29%). The etiology as confirmed by investigations is as follows- neonatal hepatitis (20,20%), idiopathic neonatal hepatitis (18,18%), biliary atresia (41,41%), sepsis (14,14%) and others (7,7%). Conclusions: The proportion of NCS in our group of patients was 1.2 per 1000 patients. Jaundice, organomegaly and failure to thrive are the common presentations. Biliary atresia, neonatal hepatitis and idiopathic neonatal hepatitis were the common etiological factors at our center.
Omega-3 fatty acids lower blood pressure by directly activating large-conductance Ca2+-dependent K+ channels

Long-chain polyunsaturated omega-3 fatty acids such as docosahexaenoic acid (DHA), found abundantly in oily fish, may have diverse health-promoting effects, potentially protecting the immune, nervous, and cardiovascular systems. However, the mechanisms underlying the purported health-promoting effects of DHA remain largely unclear, in part because molecular signaling pathways and effectors of DHA are only beginning to be revealed. In vascular smooth muscle cells, large-conductance Ca2+- and voltage-activated K+ (BK) channels provide a critical vasodilatory influence. We report here that DHA with an EC50 of ∼500 nM rapidly and reversibly activates BK channels composed of the pore-forming Slo1 subunit and the auxiliary subunit β1, increasing currents by up to ∼20-fold. The DHA action is observed in cell-free patches and does not require voltage-sensor activation or Ca2+ binding but involves destabilization of the closed conformation of the ion conduction gate. DHA lowers blood pressure in anesthetized wild-type but not in Slo1 knockout mice. DHA ethyl ester, contained in dietary supplements, fails to activate BK channels and antagonizes the stimulatory effect of DHA. Slo1 BK channels are thus receptors for long-chain omega-3 fatty acids, and these fatty acids—unlike their ethyl ester derivatives—activate the channels and lower blood pressure. This finding has practical implications for the use of omega-3 fatty acids as nutraceuticals for the general public and also for the critically ill receiving omega-3–enriched formulas.
Labor Drops: Experimental Evidence on the Return to Additional Labor in Microenterprises

A field experiment in Sri Lanka provided wage subsidies to randomly chosen microenterprises to test whether hiring additional labor benefits such firms and whether a short-term subsidy can have a lasting impact on firm employment. Using 12 rounds of surveys to track dynamics 4 years after treatment, we find that firms increased employment during the subsidy period. Treated firms were more likely to survive, but there was no lasting impact on employment and no effect on profitability or sales either during or after the subsidy period. There is some heterogeneity in effects; the subsidies have a more durable effect on manufacturers. (JEL C93, J22, J24, J31, J38, O14, O15)
[Proteomic screening of postsynaptic density proteins related with temporal lobe epilepsy].

OBJECTIVE To explore the postsynaptic density (PSD) proteins related with the development of temporal lobe epilepsy (TLE). METHODS Five SD rats were injected intra-peritoneally with lithium chloride and then pilocarpine twice to establish epilepsy models. At last 24 rats developed TLE, and 12 developed non-TLE. Then rats underwent intraperitoneal injection of normal saline (Norm group). Thirty days after the appearance of epilepticus the rats were decapitated with their brains taken out. The PSD proteins were extracted and purified by using sucrose gradient centrifugation and membrane sequence extraction, isolated by using two-dimensional gel electrophoresis. PDQuest software was used to screen the specifically and differentially expressed protein spots. Partial differentially expressed PSD protein spots were selected and identified by MALDI-TOF-MS. Several identified proteins were detected in the PSD fraction by Western blotting. RESULTS Compared with the non-TLE and Norm groups, there were 40 differential protein spots in the TLE group. The expression levels of heat shock protein-27 (HSP-27), fructose-bisphosphate aldolase A (FBA), creatine kinase (CK), thyroid receptor-interacting protein 6 (TRIP6), myelin basic protein S (MBP), and LIM domain were up-regulated, but the expression levels of tubulin, actin, internexin-alpha, peptidyl-prolyl cis-trans isomerase (PPIase), sorting nexin 3 (SNX3), aconitate hydratase (ACO), glyceradehydea-3-phosphate dehydrogenase (GADPH), and succinate-coenzyme A ligase (SCOAL) were down-regulated in the TLE group. The HSP27, tubulin-alpha, and SNX3 were in the PSD gels were immunostaining positive in the 3 groups. CONCLUSION The differential expression of PSD proteins in TLE may be due to injury induced neural plasticity. But the degree thereof may contribute to the development of TLE. These identified proteins can be regarded as important candidates for or against the development of TLE.
Physiological changes with periodized resistance training in women tennis players.

PURPOSE To compare the physiological and performance adaptations between periodized and nonperiodized resistance training in women collegiate tennis athletes. METHODS Thirty women (19 +/- 1 yr) were assigned to either a periodized resistance training group (P), nonperiodized training group (NV), or a control group (C). Assessments for body composition, anaerobic power, VO2(max), speed, agility, maximal strength, jump height, tennis-service velocity, and resting serum hormonal concentrations were performed before and after 4, 6, and 9 months of resistance training performed 2-3 d.wk (-1). RESULTS Nine months of resistance training resulted in significant increases in fat-free mass; anaerobic power; grip strength; jump height; one-repetition maximum (1-RM) leg press, bench press, and shoulder press; serve, forehand, and backhand ball velocities; and resting serum insulin-like growth factor-1, testosterone, and cortisol concentrations. Percent body fat and VO2(max) decreased significantly in the P and NV groups after training. During the first 6 months, periodized resistance training elicited significantly greater increases in 1-RM leg press (9 +/- 2 vs 4.5 +/- 2%), bench press (22 +/- 5 vs 11 +/- 8%), and shoulder press (24 +/- 7 vs 18 +/- 6%) than the NV group. The absolute 1-RM leg press and shoulder press values in the P group were greater than the NV group after 9 months. Periodized resistance training also resulted in significantly greater improvements in jump height (50 +/- 9 vs 37 +/- 7%) and serve (29 +/- 5 vs 16 +/- 4%), forehand (22 +/- 3 vs 17 +/- 3%), and backhand ball velocities (36 +/- 4 vs 14 +/- 4%) as compared with nonperiodized training after 9 months. CONCLUSIONS These data demonstrated that periodization of resistance training over 9 months was superior for enhancing strength and motor performance in collegiate women tennis players.
Uncovering hidden information and relations in time series data with wavelet analysis: three case studies in finance

This paper examines the ability of GARCH models to forecast stock return volatility under a range of forecast metrics, including both statistical and economic evaluation. Our particular interest is whether wavelet de-noising of the data prior to estimation affects the ability of the models to provide accurate forecasts. To de-noise the data, we use soft thresholding and Stein’s Unbiased Risk Estimator in order to obtain the decomposition level-based threshold limit. Our key results demonstrate that de-noising returns improves the accuracy of volatility forecasts regardless of whether we use statistical metrics or tests of equal predictive accuracy. Moreover, in terms of a particular volatility model, the asymmetric GARCH approach tends to be preferred although this result is not universal. Indeed, the central result from our analysis is that the process of de-noising is more important than the specific model. When considering VaR forecasting, wavelet de-noising is found to be more accurate at the key 99% level but less so at the 95% level.