Miracle-dz/UniFAR-FTUs huggingface dataset:
Uncoupling Uncoating of Herpes Simplex Virus Genomes from Their Nuclear Import and Gene Expression

ABSTRACT Incoming capsids of herpes simplex virus type 1 (HSV-1) enter the cytosol by fusion of the viral envelopes with host cell membranes and use microtubules and microtubule motors for transport to the nucleus. Upon docking to the nuclear pores, capsids release their genomes into the nucleoplasm. Progeny genomes are replicated in the nucleoplasm and subsequently packaged into newly assembled capsids. The minor capsid protein pUL25 of alphaherpesviruses is required for capsid stabilization after genome packaging and for nuclear targeting of incoming genomes. Here, we show that HSV-1 pUL25 bound to mature capsids within the nucleus and remained capsid associated during assembly and nuclear targeting. Furthermore, we tested potential interactions between parental pUL25 bound to incoming HSV-1 capsids and host factors by competing for such interactions with an experimental excess of cytosolic pUL25. Overexpression of pUL25, GFPUL25, or UL25GFP prior to infection reduced gene expression of HSV-1. Electron microscopy and in situ hybridization studies revealed that an excess of GFPUL25 or UL25GFP prevented efficient nuclear import and/or transcription of parental HSV-1 genomes, but not nuclear targeting of capsids or the uncoating of the incoming genomes at the nuclear pore. Thus, the uncoating of HSV-1 genomes could be uncoupled from their nuclear import and gene expression. Most likely, surplus pUL25 competed with important interactions between the parental capsids, and possibly between authentic capsid-associated pUL25, and cytosolic or nuclear host factors required for functional interaction of the incoming genomes with the nuclear machinery.
Environmental performance, corruption and economic growth: global evidence using a new data set

ABSTRACT This study investigates the relationship between environmental performance, corruption and economic growth using panel data of 87 countries covering the period from 2002 to 2012. The Environmental Performance Index is used for the first time to evaluate the environmental quality on economic growth. By employing both ‘static’ and ‘dynamic’ panel models, we find that environmental performance is positively related to economic growth and is more significant in non-Organization for Economic Cooperation Development (OECD) countries. Moreover, when corruption is incorporated, the empirical estimation results indicate that although lower corruption helps economic growth in non-OECD countries, the negative coefficients of the three interactive terms show that the positive effect of environment performance on economic growth will drop, while greater environmental performance combined with natural resource abundance inevitably leads to inefficient bureaucracies and hence disadvantageous economic growth. As a result, policymakers in non-OECD countries should carefully ensure better government quality when they exhibit strong environmental performance so as to avoid any disadvantageous impact upon economic growth.
Work-Related Musculoskeletal Disorders Among Self Employed Sewing Machine Operators in Maiduguri, Nigeria

Background: Globally, studies on prevalence of WMSDs focused mainly on populations in organized industrial sectors and professions. Purpose: This study was therefore designed to determine the prevalence of WMSDs, risk factors and coping strategies for this disorder among self-employed sewing machine operators in Maiduguri, Nigeria. Method: Close-ended structured questionnaire, drafted and modified from the short version of the standardized Nordic Musculoskeletal Questionnaire (NMQ) for investigating work-related musculoskeletal symptoms in working populations was used for the study. Copies of this questionnaire were administered on willing and volunteer self-employed sewing machine operators in Maiduguri using a non-probability sampling of convenience technique. Results: Two hundred and nineteen copies of the questionnaire out of 247 administered were duly completed and retrieved. Ninety five out of the 219 respondents reported WMSDs, giving a prevalence of 43.4%. Mean and age range in years of the respondents were 30.03 ± 11.99 and 11-72 respectively. Majority (81.2%) of the respondents was in the age range of 11-40 years and males accounted for 63.9%. Weak significant association (p<0.05; p=0.042) in prevalence of WMSDs existed among the age groups. Lower back (41.7%) and neck (34.7%) were the most affected body parts. Conclusion: Majority of the respondents suffering from WMSDs were able to identify correctly the risk factors of this condition. This implies that this population may easily adjust to proper ergonomic measures if introduced to them.
Phosphorylation and protein–protein interactions in PXR-mediated CYP3A repression

Background: The expression of drug-metabolizing enzymes CYPs is controlled by pregnane X receptor (PXR), and, therefore, understanding how PXR modulates CYP expression is important to minimize adverse drug interactions, one type of preventable adverse drug reaction. Objective: We review the mechanisms of PXR-mediated repression of CYP expression. Methods: We discuss the clinical implications of CYP repression and the role of signal cross-talks, including protein–protein interactions and phosphorylation of PXR and coregulators, in inhibiting PXR and repressing CYP expression. Results/conclusion: Kinases such as cyclin-dependent kinase 2, protein kinase A, PKC and 70 kDa form of ribosomal protein S6 kinase repress CYP expression by phosphorylating and inhibiting PXR. Growth factor signaling represses CYP expression by phosphorylating and inhibiting forkhead in rhabdomyosarcoma, a co-activator of PXR. During inflammation, NF-κB represses both PXR and CYP expression through protein–protein interactions with the PXR pathway.
Robust Nonlinear Predictive Control Applied to a Solar Collector Field in a Solar Desalination Plant

This brief presents the application of a robust nonlinear predictive controller to the distributed collector field of a solar desalination plant. The main purpose of the controller is to manipulate the water flow rate to maintain the collector outlet-inlet temperature gradient constant in spite of disturbances. The controller uses a robust dead-time compensation structure and a nonlinear model predictive control to cope with time delay uncertainties and system nonlinearities, respectively. Simulation and real experimental results are shown to illustrate controller performance.
Extinction Risk and Conservation of the Earth's National Animal Symbols

Abstract Flagship species are commonly used as conservation tools, but to be effective, local public support is crucial. A country's national animal symbol is often selected for holding cultural and historical significance. Therefore, national animal symbols may serve as ideal flagships within their associated countries. Here, we evaluate the extinction risk and primary threats facing the world's national animal symbols and assess their levels of protection. Analysis of International Union for Conservation of Nature data revealed that 35% of symbols are threatened and 45% are exhibiting population declines. Two symbols are extinct, and four have been extirpated from their associated country. If population trends persist, over half of these symbols may face future extinction. The primary threats facing national animal symbols are exploitation, human‐wildlife conflict and habitat loss. Only 16% of these symbols are nationally protected, whereas 50% receive international trade restrictions. Given their significance to national identity, it may be relatively easy to garner support for national animal symbols as flagship species.
Possible predictive factors for ICSI? Molecular biology techniques in combination with therapeutic testicular biopsies

Summary. Applying intracytoplasmic sperm injection (ICSI), the selection of an unsuccessful spermatozoon results in great emotional consequences for the couple. Therefore, there is a need for a prognostic parameter to estimate their chances for successful fertility treatment. This review summarizes both the main reasons for spermatogenic impairment, and possible predictive factors for successful sperm retrieval applying testicular sperm extraction and outcome of ICSI. While basic sperm parameters, aetiology and type of spermatozoa, and serum follicle‐stimulating hormone and inhibin levels have been shown to be unrelated to the outcome of ICSI, Y‐chromosome microdeletions are known to have a negative influence on the fertilizing capacity of spermatozoa. Recently, a significant correlation has been reported between the protamine‐1 to protamine‐2 mRNA ratio in haploid spermatids of testicular biopsies and the ability of spermatozoa for successful fertilization of an oocyte. In future, both the outstanding role of the haploid spermatids and the involvement of molecular biological techniques will improve the role of therapeutic testicular biopsies.
Disruption of self‐organized actions in monkeys with progressive MPTP‐induced parkinsonism: II. Effects of reward preference

The motor and cognitive symptoms of Parkinson's disease (PD) are well documented, but little is known about the functionality of motivational processes mediated by the limbic circuits of basal ganglia. The aim of this study was to test the ability of motivational processes to direct and to urge behaviour, in four vervet monkeys (Cercopithecus aethiops) progressively intoxicated with systemic 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) injections (0.3–0.4 mg/kg every 4–7 days). In the food preference task, the monkeys had to retrieve two types of directly visible food, simultaneously available in the wells of a reward board. At all stages of MPTP‐induced parkinsonism, the monkeys continued to take their favourite food first. In the symbol discrimination task, the wells were covered with sliding plaques cued by symbols indicating the absence or presence of a reward, and the different types of food were blocked in separate sessions. Monkeys with mild or moderate parkinsonism made fewer attempts and took longer to retrieve non‐preferred compared with preferred rewards. These results indicate that motivational processes are still able to direct (food preference task) and to urge (symbol discrimination task) behaviour in MPTP‐lesioned monkeys. Such a functional preservation may be related to the relatively spared dopaminergic innervation of the limbic circuits that we found in our monkeys, in agreement with the literature on humans. Furthermore, the frequency of executive disorders (such as hesitations and freezing) appeared to be much lower with the preferred rewards. Thus, the preserved motivational processes may help to overcome executive dysfunction in the early stages of human PD.
The incidence of anorexia nervosa on Curaçao.

OBJECTIVE Although anorexia nervosa was once thought to occur only in affluent societies, cases have now been documented across the globe. To examine whether anorexia nervosa emerges in societies undergoing socioeconomic transition, the authors studied the incidence of anorexia nervosa on the Caribbean island of Curaçao. METHOD The authors contacted the full range of community health and service providers on Curaçao, including dietitians, school counselors, and all 82 general practitioners. They also studied inpatient records for 84,420 admissions to Curaçao General Hospital and two private hospitals in 1995-1998. Probable-incident subjects were interviewed. RESULTS The incidence rates in 1995-1998 per 100,000 person-years for anorexia nervosa on Curaçao were 1.82 (95% confidence interval [CI]=0.74-2.89) for the total population and 17.48 (95% CI=4.13-30.43) for the high-risk group of 15-24-year-old females. No cases were found among the majority black population. For the Curaçao mixed and white population, the incidence rate per 100,000 person-years for anorexia nervosa was 9.08 (95% CI=3.71-14.45). CONCLUSIONS The overall incidence of anorexia nervosa on Curaçao is much lower than in the affluent societies of the United States and Western Europe. Within Curaçao, sociocultural factors appear to be associated with differential incidence rates of anorexia nervosa. The incidence of anorexia nervosa among the majority black population is nil, while the incidence among the minority mixed and white population on Curaçao is similar to that of the United States and the Netherlands.
Brachial-ankle pulse wave velocity as an index of central arterial stiffness.

AIM Stiffness of the central arteries plays an important role in the pathophysiology of cardiovascular disease, and pulse wave velocity (PWV) of the aorta has been used as the standard measure of central arterial stiffness. An automated device for brachial-ankle (ba) PWV is available, although information is limited whether baPWV reflects the stiffness of central or peripheral arteries. We therefore addressed this question in the present study. METHODS The subjects were 2,806 consecutive participants in our non-invasive vascular laboratory, excluding those with an ankle-brachial index (ABI) lower than 0.95. PWV measurements were simultaneously performed using an automated device for the ba, heart-femoral (hf, aorta), heart-carotid (hc), heart-brachial (hb), and femoral-ankle (fa) segments. Correlational analyses were performed (1) among these PWV values, (2) between PWV and individual risk factors, and (3) between PWV and the Framingham risk score (FRS), a surrogate index for integrated cardiovascular risk. RESULTS The correlation of baPWV was the highest with hfPWV (r=0.796) and the lowest with hcPWV (r=0.541). Among the known factors preferentially affecting central arterial stiffness, higher age, diabetes mellitus, and chronic kidney disease (CKD) were also closely associated with increased baPWV. Finally, FRS was more closely correlated with hfPWV (r=0.613) and baPWV (r=0.609) than with hbPWV (r=0.523), hcPWV (r=0.509), and faPWV (r=0.393). CONCLUSION These results indicate that baPWV is an index of arterial stiffness showing similar characteristics to those of aortic PWV.
CSF cyclic nucleotides and somatostatin in Parkinson's disease

Concentrations of cyclic adenosine 3',5' monophosphate (cAMP) were significantly lower in parkinsonian patients than in controls, but concentrations of guanosine 3',5' monophosphate (cGMP) were not altered. Both cAMP and cGMP levels were lower in patients with more severe symptoms on the left side of the body. Somatostatin-like immunoreactivity (SLI) was similar in parkinsonian patients and controls. Both cAMP and SLI were significantly related to acetylcholinesterase activity.
ATP-dependent release of glucocorticoid receptors from the nuclear matrix

Glucocorticoid receptors (GRs) have the capacity to shuttle between the nuclear and cytoplasmic compartments, sharing that trait with other steroid receptors and unrelated nuclear proteins of diverse function. Although nuclear import of steroid receptors, like that of nearly all other karyophilic proteins examined to date, requires ATP, there appear to be different energetic requirements for export of proteins, including steroid receptors, from nuclei. In an attempt to reveal which steps, if any, in the nuclear export pathway utilized by steroid receptors require ATP, we have used indirect immunofluorescence to visualize GRs within cells subjected to a reversible ATP depletion. Under conditions which lead to >95% depletion of cellular ATP levels within 90 min, GRs remain localized within nuclei and do not efflux into the cytoplasm. Under analogous conditions of ATP depletion, transfected progesterone receptors are also retained within nuclei. Importantly, GRs which accumulate within nuclei of ATP-depleted cells are distinguished from nuclear receptors in metabolically active cells by their resistance to in situ extraction with a hypotonic, detergent-containing buffer. GRs in ATP-depleted cells are not permanently trapped in this nuclear compartment, as nuclear receptors rapidly regain their capacity to be extracted upon restoration of cellular ATP, even in the absence of de novo protein synthesis. More extensive extraction of cells with high salt and detergent, coupled with DNase I digestion, established that a significant fraction of GRs in ATP-depleted cells are associated with an RNA-containing nuclear matrix. Quantitative Western blot (immunoblot) analysis confirmed the dramatic increase in GR binding to the nuclear matrix of ATP-depleted cells, while confocal microscopy revealed that GRs are bound to the matrix throughout all planes of the nucleus. ATP depletion does not lead to wholesale collapse of nuclear proteins onto the matrix, as the interaction of a subpopulation of simian virus 40 large tumor antigen with the nuclear matrix is not quantitatively altered in ATP-depleted Cos-1 cells. Nuclear GRs which are not bound to the nuclear matrix of metabolically active cells (i.e., a DNA-binding domain deletion mutant and a beta-galactosidase chimera possessing the GR nuclear localization signal sequence) are not recruited to the matrix upon depletion of cellular ATP. Thus, it appears that ATP depletion does not expose the GR to nuclear matrix interactions which are not normally encountered in cells but merely alters the dynamics of such interactions. The dynamic association of steroid receptors with the nuclear matrix may provide a mechanism which is utilized by these regulable transcription factors to facilitate their efficient scanning of the genome.
Prevention of secondary hyperparathyroidism in hemodialysis patients: The key role of native vitamin D supplementation

Secondary hyperparathyroidism (SHPT) is a frequent complication in chronic kidney disease, especially in hemodialysis (HD) patients. Treatments for SHPT include calcitriol analogues (CA), phosphate binders, cinacalcet (CC), and surgical parathyroidectomy (PTX). This study aimed to assess the incidence and prevalence of SHPT in a single center during the period when native vitamin D (N‐VitD) supplementation and CC treatment became available. All incident and prevalent HD patients were prospectively recorded and compared using 3 periods from 2004 to 2005 (period 1), 2006 to 2007 (period 2), and 2008 to 2009 (period 3). SHPT was diagnosed with serum parathyroid hormone (PTH) levels >300 pg/mL or the need for CA, CC, or PTX. Between periods 1 and 3, in incident patients (n=120 and 101), N‐VitD prescription increased from 11% to 68% (P<0.0001), CA prescription remained stable (40%), and patients with PTH>300 pg/mL decreased from 40% to 12% (P<0.0001). In prevalent HD patients (n=235), N‐VitD treatment increased from 55% to 91% (P<0.0001), whereas treatment with CA decreased from 67% to 17% (P<0.0001). Patients with serum PTH>300 pg/mL decreased from 38% to 13% (P<0.001), whereas patients with PTH<150 pg/mL remained stable (<30%). New CC prescriptions decreased from 45 to 3 (P<0.0001). Since 2004, SHPT has decreased drastically in incident and prevalent HD patients. The preventive role of N‐VitD supplementation appears to be obvious and represents one more argument for its general recommendation in CKD patients.
Influence of Platelet-Rich Fibrin on Alveolar Ridge Preservation

AimThe aim of this study was to investigate the influence of platelet-rich fibrin (PRF) on early wound healing and preservation of the alveolar ridge shape following tooth extraction. MethodsIn this clinical trial, 20 symmetrical, premolar extraction sockets using split-mouth design were randomly selected with PRF or blood clot. The evaluations of wound healing, alveolar ridge contour changes, and crestal bone resorption were performed in dental casts and periapical radiographs (T0, initial; T1, 1 week; T2, 2 weeks; T4, 4 weeks; T6, 6 weeks; T8, 8 weeks). ResultsPlatelet-rich fibrin clinically showed early healing of soft tissue covering socket orifices in the first 4 weeks. At the first week, the horizontal resorption on buccal aspect of PRF (1.07 ± 0.31 mm) was significantly less than that of the control (1.81 ± 0.88 mm). Platelet-rich fibrin demonstrated the tendency to enter the steady stage after the fourth week following tooth extraction, whereas in the control group the progression of buccal contour contraction was still detected through the eighth week. Radiographically, the overall resorption of marginal bone levels at mesial and distal to the extraction site in PRF (0.70, 1.23 mm) was comparable to that of the control (1.33, 1.14 mm). Although the PRF group demonstrated faster bone healing compared with the control, no statistically significant difference was detected. ConclusionsThis preliminary result demonstrated neither better alveolar ridge preservation nor enhanced bone formation of PRF in the extraction socket. The use of PRF revealed limited effectiveness by accelerated soft-tissue healing on the first 4 weeks.
Effects of Itopride Hydrochloride on Plasma Gut-Regulatory Peptide and Stress-Related Hormone Levels in Healthy Human Subjects

Itopride hydrochloride (itopride), a gastrokinetic drug, has recently been evaluated for its clinical usefulness in functional dyspepsia. We investigated effects of itopride on human plasma gastrin-, somatostatin-, motilin-, and cholecystokinin (CCK)-like immunoreactive substances (IS); adrenocorticotropic hormone (ACTH)-immunoreactive substances (IS), and cortisol under stress conditions in healthy subjects. A single administration of itopride caused significant increases in plasma somatostatin- and motilin-IS levels compared to placebo. Itopride significantly decreased plasma CCK-IS, and suppressed the ACTH-IS level compared to placebo. We hypothesize that itopride may have an accelerating gastric emptying effect, and a modulatory effect on the hypothalamo-pituitary-adrenal axis and autonomic nervous functions. These effects might be beneficial in stress-related diseases, suggesting that itopride has clinicopharmacological activities.
Hepatobiliary damage and changes in hepatic gene expression caused by the antitumor drug ecteinascidin-743 (ET-743) in the female rat.

Ecteinascidin-743 (ET-743) is a novel marine-derived anticancer drug with clinical activity in soft tissue sarcoma and ovarian cancer. Reversible transaminitis and subclinical cholangitis have frequently been described in patients who receive ET-743. To facilitate understanding of this adverse effect and help design suitable therapeutic rescue strategies, we characterized the hepatic effects of ET-743 in rats. Female rats received ET-743 (single dose, 40 microg/kg) i.v. , and liver changes were assessed from 6 h up to 3 months after dosing by histopathology, immunohistochemistry, electron microscopy, hepatic and plasma biochemistry, and DNA microarray analysis. At 24 h posttreatment and beyond, livers displayed degeneration and patchy focal necrosis of bile duct epithelial cells associated with mild inflammation followed by fibrosis. Sporadic and focal zones of hepatic necrosis and hemorrhage were observed from day 2 onward, although the majority of hepatocytes appeared normal as judged by electron microscopy. Pathological alterations persisted up to 3 months after dosing. Plasma levels of total bilirubin were elevated up to 7-fold over those in untreated rats from day 2 onward and returned to control values by day 24. Activities of alkaline phosphatase and aspartate aminotransferase in plasma were elevated for 2 and 3 months, respectively. Activities of the hepatic microsomal drug-metabolizing enzymes cytochrome P-450 A1/2, CYP2E1, and CYP3A2 were decreased. DNA microarray analysis of livers from ET-743-treated animals showed a dramatic increase in the expression of ATP binding cassette transport genes Abcb1a and Abcb1b, which impart resistance to anticancer drugs, and of Cdc2a and Ccnd1, the rodent homologues of human cell cycle genes CDC2 and cyclin D1, respectively. The cell cycle gene expression changes mirrored ET-743-induced increases in liver weight and Ki-67 labeling of liver nuclei. The results suggest that the toxicity exerted by ET-743 in the rat liver is a consequence of biliary rather than hepatocellular damage and that it is accompanied by a wave of mitogenic activity, which may be driven by the transcriptional increase in Cdc2a expression.