Miracle-dz/UniFAR-FTUs huggingface dataset:
Potentiation of transient receptor potential V1 functions by the activation of metabotropic 5‐HT receptors in rat primary sensory neurons

5‐Hydroxytryptamine (5‐HT) is one of the major chemical mediators released in injured and inflamed tissue and is capable of inducing hyperalgesia in vivo. However, the cellular mechanisms of 5‐HT‐induced hyperalgesia remain unclear. Transient receptor potential V1 (TRPV1) plays a pivotal role in nociceptive receptors. In the present study, we determined whether 5‐HT changes TRPV1 functions in cultured dorsal root ganglion (DRG) neurons isolated from neonatal rats, using Ca2+ imaging and whole‐cell patch‐clamp techniques. In more than 70% of DRG neurons, 5‐HT potentiated the increases of [Ca2+]i induced by capsaicin, protons and noxious heat. Capsaicin‐induced current and depolarizing responses, and proton‐induced currents were also augmented by 5‐HT. RT‐PCR analysis revealed the expression of 5‐HT2A and 5‐HT7 receptors in rat DRG neurons. Agonists for 5‐HT2A and 5‐HT7 receptors mimicked the potentiating effect of 5‐HT, and their antagonists decreased it. In DRG ipsilateral to the complete Freund's adjuvant‐injected inflammation side, expression levels of 5‐HT2A and 5‐HT7 mRNAs increased, and the potentiating effect of 5‐HT was more prominent than in the contralateral control side. These results suggest that the PKC‐ and PKA‐mediated signalling pathways are involved in the potentiating effect of 5‐HT on TRPV1 functions through the activation of 5‐HT2A and 5‐HT7 receptors, respectively. Under inflammatory conditions, the increases of the biosynthesis of these 5‐HT receptors may lead to further potentiation of TRPV1 functions, resulting in the generation of inflammatory hyperalgesia in vivo.
Paradoxical Increase in Rate of Catabolism of Low-Density Lipoproteins after Hepatectomy

It has been suggested that the liver may be a major site for irreversible degradation of low-density lipoprotein (LDL). The disappearance of autologous 125I-labeled LDL from plasma was compared in intact and in hepatectomized swine. Contrary to expectations, the rate of irreversible removal of LDL from plasma was increased rather then decreased by hepatectomy. These studies suggest that the liver is not a major site for LDL removal. We propose further that the liver (or some function requiring an intact liver) may affect the metabolism of LDL in a manner that prolongs its lifetime in the plasma compartment.
Effect of calmodulin antagonists on calmodulin‐induced biphasic modulation of Ca2+‐induced Ca2+ release

1 Calmodulin (CaM) has a biphasic effect on Ca2+‐induced Ca2+ release (CICR) from the sarcoplasmic reticulum (SR): potentiation and inhibition at low (pCa > 6.0) and high (pCa 5) Ca2+ concentrations, respectively. To characterize the mode of action of CaM, we studied the effect of CaM antagonists on the CICR in skinned muscle fibres of the rabbit. Ca2+ release was measured by microfluorometry with Fura‐2. 2 A CaM antagonist, trifluoperazine (TFP), potentiated the CICR in a dose‐dependent manner (10–300 μm) at pCa 6, where a simple reversal of the CaM effect would be inhibition of the CICR. Furthermore, 100 μm TFP sensitized the CICR to Ca2+. A similar effect was produced by other CaM antagonists that were tested: chlorpromazine, W‐7, mastoparan, and peptide fragment of CaM‐binding residues of CaM‐dependent protein kinase II. 3 The biphasic effect of CaM on the CICR was observed even in the presence of high concentrations of CaM antagonists or CaM‐binding peptides. 4 From these results we suggest that CaM has a unique mode of action on the CICR which is quite different from the effect of CaM on known enzymes.
Quality of primary care for sexually transmitted diseases in Durban, South Africa: influences of patient, nurse, organizational and socioeconomic characteristics

Quality of sexually transmitted disease (STD) primary care in South Africa varies widely but reasons for this are poorly understood. We investigated 37 randomly sampled clinics providing STD care, with simulated patients, and staff interviews and record review. Census data provided local socioeconomic indicators. Multiple regression identified independent predictors of quality. Of 271 simulated patient visits, 79% were correctly treated and 39% were correctly managed. Women received worse care, and care tended to be poorer in mainly African and mainly coloured (mixed race) areas. African and Indian nurses were more likely to provide correct treatment. Previous STD training was marginally associated with correct treatment. Quality assessments using simulated patients were not generally associated with assessments using staff interviews and record review. There were frequent missed opportunities for STD prevention and treatment, and evidence of racial but not socioeconomic inequalities.
Pollen diversity matters: revealing the neglected effect of pollen diversity on fitness in fragmented landscapes

Few studies have documented the impacts of habitat fragmentation on plant mating patterns together with fitness. Yet, these processes require urgent attention to better understand the impact of contemporary landscape change on biodiversity and for guiding native plant genetic resource management. We examined these relationships using the predominantly insect‐pollinated Eucalyptus socialis. Progeny were collected from trees located in three increasingly disturbed landscapes in southern Australia and were planted out in common garden experiments. We show that individual mating patterns were increasingly impacted by lower conspecific density caused by habitat fragmentation. We determined that reduced pollen diversity probably has effects over and above those of inbreeding on progeny fitness. This provides an alternative mechanistic explanation for the indirect density dependence often inferred between conspecific density and offspring fitness.
Cyclin-Dependent Kinase Inhibitors Sensitize Tumor Cells to Nutlin-Induced Apoptosis: a Potent Drug Combination

Current chemotherapy focuses on the use of genotoxic drugs that may induce general DNA damage in cancer cells but also high levels of toxicity in normal tissues. Nongenotoxic activation of p53 by targeting specific molecular pathways therefore provides an attractive therapeutic strategy in cancers with wild-type p53. Here, we explored the antitumor potential of cyclin-dependent kinase (CDK) inhibitors in combination with a small molecule inhibitor of p53-murine double minute 2 (MDM2) interaction. We show that low doses of CDK inhibitors roscovitine and DRB synergize with the MDM2 antagonist nutlin-3a in the induction of p53 activity and promote p53-dependent apoptosis in a dose- and time-dependent manner. Statistical measurement of the combination effects shows that the drug combination is additive on the reduction of cell viability and synergistic on inducing apoptosis, a critical end point of cytotoxic drugs. The degree of apoptosis observed 24 to 48 h after drug treatment correlated with the accumulation of p53 protein and concomitant induction of proapoptotic proteins Puma and PIG3. The antiproliferative and cytotoxic effects of this drug combination are validated in a range of tumor-derived cells including melanoma, colon carcinoma, breast adenocarcinoma, and hepatocarcinoma cells. Furthermore, this drug combination does not induce phosphorylation of Ser15 on p53 and does not induce genotoxic stress in the cell. Given that many cytotoxic drugs rely on their ability to induce apoptosis via DNA damage–mediated activation of p53, the data presented here may provide a new therapeutic approach for the use of CDK inhibitors and MDM2 antagonists in combinatorial drug therapy. (Mol Cancer Res 2007;5(11):1133–45)
Improving the power for disease locus detection in affected‐sib‐pair studies by using two‐locus analysis and multiple regression methods

In this paper we present a summary of an analysis of the simulated data (Problem 2) for GAW11. We used sib‐pair and affected‐sib‐pair (ASP) methods to evaluate linkage to the mild form of disease at markers across the genome, in data sets of realistic moderate size (containing between 100 and 300 families selected from the simulated replicates). The true ‘answers’ were known in advance. Although in most cases we were successful in detecting linkage to disease in the correct regions, it was often difficult to distinguish these results from false positives elsewhere in the genome. We used two‐locus methods to see whether the significance was improved by simultaneously modeling linkage to two disease loci, and found a modest increase in significance using two‐locus methods in several cases.
Seizure characteristics and control following resection in 332 patients with low-grade gliomas.

OBJECT Seizures play an important role in the clinical presentation and postoperative quality of life of patients who undergo surgical resection of low-grade gliomas (LGGs). The aim of this study was to identify factors that influenced perioperative seizure characteristics and postoperative seizure control. METHODS The authors performed a retrospective chart review of all cases involving adult patients who underwent initial surgery for LGGs at the University of California, San Francisco between 1997 and 2003. RESULTS Three hundred and thirty-two cases were included for analysis; 269 (81%) of the 332 patients presented with >or=1 seizures (generalized alone, 33%; complex partial alone, 16%; simple partial alone, 22%; and combination, 29%). Cortical location and oligodendroglioma and oligoastrocytoma subtypes were significantly more likely to be associated with seizures compared with deeper midline locations and astrocytoma, respectively (p=0.017 and 0.001, respectively; multivariate analysis). Of the 269 patients with seizures, 132 (49%) had pharmacoresistant seizures before surgery. In these patients, seizures were more likely to be simple partial and to involve the temporal lobe, and the period from seizure onset to surgery was likely to have been longer (p=0.0005, 0.0089, and 0.006, respectively; multivariate analysis). For the cohort of patients that presented with seizures, 12-month outcome after surgery (Engel class) was as follows: seizure free (I), 67%; rare seizures (II), 17%; meaningful seizure improvement (III), 8%; and no improvement or worsening (IV), 9%. Poor seizure control was more common in patients with longer seizure history (p<0.001) and simple partial seizures (p=0.004). With respect to treatment-related variables, seizure control was far more likely to be achieved after gross-total resection than after subtotal resection/biopsy alone (odds ratio 16, 95% confidence interval 2.2-124, p=0.0064). Seizure recurrence after initial postoperative seizure control was associated with tumor progression (p=0.001). CONCLUSIONS The majority of patients with LGG present with seizures; in approximately half of these patients, the seizures are pharmacoresistant before surgery. Postoperatively, >90% of these patients are seizure free or have meaningful improvement. A shorter history of seizures and gross-total resection appear to be associated with a favorable prognosis for seizure control.
Determinant of life insurance demand in Ethiopia

Life Insurance plays an important role to insure against lifetime uncertainty resulting for the mortality risk of individual. Even though the performance of insurance industry contributes to smooth operation of the nation’s economy, the industry in general and life insurance in particular is at its low level of development in Ethiopian context. This study therefore, is aimed at investigating the determinants of life insurance demand in Ethiopia. The study used balanced panel data model to examine the determinants of life insurance demand usingdata collected from four insurance companies for sixteen years, from 2001-2016. Random effect model was usedto analyze the data using STATA version 13 software. The study used life insurance density as dependent variable and seven independent variables that are income, inflation, real interest rate, life expectance, age dependence ratio, price of insurance and urbanization. The regression result show that real interest rate, life expectancies, age dependency ratio, urbanization and inflation show positive and significant effect at 1% and 5% significance level on life insurance demand in Ethiopia, whereas GDP per capita and price of insurance has insignificant effect on life insurance demand in Ethiopia.Urbanization is the most important factor that influences demand for life insurance followed by life expectance, age dependency ratio and Inflation. Real interest rate is the least important factor in influence demand for life insurance. The concerned insurance companies are recommended to consider these factors in marketing their life insurance products.
Healthy Convenience: Nudging Students to Make Healthier Choices in the Lunchroom

Many students cite lack of time as one of the major constraints determining what they eat for lunch at school. In some schools, students receive as little as 15–20 minutes to purchase and eat their lunch which may encourage students to take the more convenient and often less healthy options such as a hot dog or chicken patty. The goal of this study was to encourage students to eat healthier by making the healthier foods more convenient. Food sales, consumption and food waste were measured for 6 weeks before the intervention in a cafeteria where there were two identical serving lines and both healthier and less healthy items were available on both lines. Then, one of the lines was converted into an express line that only offered healthy options such as sub sandwiches, salad, yogurt and fruit. The other line remained the same offering all items. Sales, consumption and food waste were measured for 6 weeks. Results show a 21% increase in the number of healthy items purchased and an 8% increase in unhealthy items purchased after the introduction of the express line. Although there was a slight increase in unhealthy items purchased, total consumption of these items decreased by 38%. This study indicates that changing the convenience of existing food options can drastically change purchasing behavior and consumption of foods available in the school lunchroom.
Reality effects of conflict avoidance in rewilding and ecotourism practices – the case of Western Iberia

ABSTRACT This paper explores the performative role of conflict avoidance in enabling rewilding and ecotourism visions in Western Iberia, one of the first European rewilding pilots situated in Northeast Portugal. Conflict avoidance is delineated here as a process based on expectations of potentially enduring, mutually contradicting and heated communications. In line with and contributing to a Social Systems Theory of conflicts, various examples of conflict avoidance are described as either a form of proactive anticipation to conflicts as risks or as a reactive adaptation to conflicts as dangers. The findings illustrate various forms of conflict avoidance in terms of silence, materialisation, co-optation, and ad hoc manoeuvring. These forms are subject to different goal dependencies of rewilding and ecotourism visions. Furthermore, these findings support a more critical discussion of the highly co-productive role of latent conflict processes in evolving rewilding and ecotourism practices in places like Western Iberia.
Control of Fetal Growth and Neonatal Survival by the RasGAP-Associated Endoribonuclease G3BP

ABSTRACT The regulation of mRNA stability plays a major role in the control of gene expression during cell proliferation, differentiation, and development. Here, we show that inactivation of the RasGAP-associated endoribonuclease (G3BP)-encoding gene leads to embryonic lethality and growth retardation. G3BP − / − mice that survived to term exhibited increased apoptotic cell death in the central nervous system and neonatal lethality. Both in mouse embryonic fibroblasts and during development, the absence of G3BP altered the expression of essential growth factors, among which imprinted gene products and growth arrest-specific mRNAs were outstanding. The results demonstrate that G3BP is essential for proper embryonic growth and development by mediating the coordinate expression of multiple imprinted growth-regulatory transcripts.
Preferential Costimulation by CD80 Results in IL-10-Dependent TGF-β1+-Adaptive Regulatory T Cell Generation1

Costimulatory ligands CD80 and CD86 have different binding preferences and affinities to their receptors, CD28 and CTLA-4. Earlier, we demonstrated that CD80 binds to CTLA-4 with higher affinity and has a role in suppressing T cell response. The current study demonstrates that not only did blockade of CD86 upon Ag presentation by bone marrow-derived dendritic cells (DC) to OVA-specific T cells result in induction of hyporesponsive T cells but also that these T cells could suppress the proliferative response of effector T cells. These T cells showed TGF-β1 on their surface and secreted TGF-β1 and IL-10 upon restimulation. Although blockade of CTLA-4 and neutralization of IL-10 profoundly inhibited the induction of these TGF-β1+ T cells, their ability to suppress the effector T cell proliferation was abrogated by neutralization of TGF-β1 alone. Induction of TGF-β1+ and IL-10+ T cells was found to be independent of natural CD4+CD25+ regulatory T cells, demonstrating that preferential ligation of CTLA-4 by CD80 induced IL-10 production by effector T cells, which in turn promoted the secretion of TGF-β1. Treatment of prediabetic NOD mice with islet β cell Ag-pulsed CD86−/− DCs, but not CD80−/− DCs, resulted in the induction of TGF-β1- and IL-10-producing cells, significant suppression of insulitis, and delay of the onset of hyperglycemia. These observations demonstrate not only that CD80 preferentially binds to CTLA-4 but also that interaction during Ag presentation can result in IL-10-dependent TGF-β1+ regulatory T cell induction, reinstating the potential of approaches to preferentially engage CTLA-4 through CD80 during self-Ag presentation in suppressing autoimmunity.
Paired Basic/Furin-like Proprotein Convertase Cleavage of Pro-BMP-1 in the trans-Golgi Network*

Bone morphogenetic protein (BMP)-1 is a zinc-dependent metalloproteinase that cleaves a variety of extracellular matrix substrates, including type I procollagen. Little is known about the site of action of BMP-1, although the extracellular matrix seems likely to be it. BMP-1 is synthesized with an N-terminal prodomain. The removal of the prodomain presumably activates the proteinase. In this study we show that the prodomain is cleaved in thetrans-Golgi network (TGN) and by furin-like/paired basic proprotein convertases. Inhibitors of furin resulted in the secretion of pro-BMP-1, which could not cleave procollagen. Recombinant furin cleaved the prodomain from pro-BMP-1. Site-directed mutagenesis of the prodomain cleavage site (RSRR) to RSAA resulted in efficient secretion of pro-BMP-1. Therefore, prodomain cleavage was not required for secretion. Using peptide N-glycosidase and neuraminidase digestion to determine the post-translational status of pro-BMP-1 during its conversion to BMP-1, we showed that BMP-1 first appears in the TGN during sialylation of the molecule. Furthermore, immunofluorescence studies using an antibody to the nascent N terminus of BMP-1 showed localization to the TGN and plasma membrane. The observation that BMP-1 occurs inside the cell raises the possibility that BMP-1 might begin to cleave its substrates prior to secretion to the extracellular matrix.
Board independence and internal control quality in Egypt: does CEO duality matter?

Purpose This paper aims to examine the relationship between board independence and internal control quality (ICQ) in Egypt and investigate whether CEO duality moderates such an association. Design/methodology/approach A survey among external auditors is used to assess ICQ among Egyptian listed firms over the period of 2007-2010. Findings Findings show that board independence does not have a significant positive effect on ICQ. However, when testing for the moderating effect of CEO duality on such a relationship, the authors document that the association becomes positive and significant under combined board leadership structure, whereas it is negative under separated leadership structure. Originality/value The authors’ results demonstrate that CEO duality plays a governance role in weak legal environment like Egypt by strengthening board independence role in increasing ICQ.
Are they still viable? Physical conditions and abundance of Daphnia pulicaria resting eggs in sediment cores from lakes in the Tatra Mountains

All species of Daphnia (Cladocera) produce, at some stage in their life cycle, diapausing eggs, which can remain viable for decades or centuries forming a “seed bank” in lake sediments. Because of their often good preservation in lake sediment, they are useful in paleolimnology and microevolutionary studies. The focus of this study was the analysis of cladoceran resting eggs stored in the sediment in order to examine the ephippial eggs bank of Daphnia pulicaria Forbes in six mountain lakes in the High Tatra Mountains, the Western Carpathians (northern Slovakia and southern Poland). Firstly, we analyzed distribution, abundance and physical condition of resting eggs in the sediment for their later used in historical reconstruction of Daphnia populations by genetic methods. To assess changes in the genetic composition of the population through time, we used two microsatellite markers. Although DNA from resting eggs preserved in the High Tatra Mountain lake sediments was extracted by various protocols modified for small amounts of ancient DNA, DNA from eggs was not of sufficient quality for microsatellite analyses. Distribution curves of resting eggs from sediment cores correspond to the environmental changes that have occurred in the High Tatra Mountains area during last two centuries (atmospheric acid deposition, fish introduction) and demonstrate their influence on natural populations. Evaluation of ephippia physical condition (the most common category was empty ephippial covers) suggests that the majority of resting eggs hatched to produce a new generation of Daphnia or may be due to failed deposition of resting eggs by Daphnia to the chitinous case. In conclusion, age, low quantity and poor physical condition of resting eggs from these Tatra lake sediments proved to be unsuitable not just for use in genetic analyses, but also the possibilities of autogenous restoration of Daphnia populations from the resting egg banks in the Tatra sediments are negligible.
Antimicrobial susceptibilities of Listeria monocytogenes strains isolated from 1958 to 1982 in Sweden

Antibiotic susceptibility was studied in 175 clinical isolates of Listeria monocytogenes. There were no major changes in the susceptibility of strains between 1958 and 1982. Benzylpenicillin and ampicillin had MICs for 90% of the strains (MIC90) of 0.5 micrograms/ml. Gentamicin also had good activity against L. monocytogenes, with an MIC90 of 1.0 microgram/ml. All the new beta-lactamase-stable cephalosporins tested had relatively poor activity against L. monocytogenes. Of the bacteriostatic antibiotics, trimethoprim had by far the lowest MIC90 (0.06 microgram/ml), and in combination with sulfamethoxazole (co-trimoxazole), it had an MIC90 of 0.5 microgram/ml. Both erythromycin and doxycycline had low MIC90s (0.25 microgram/ml).