Miracle-dz/UniFAR-FTUs huggingface dataset:
Disruption of a mitochondrial MutS DNA repair enzyme homologue confers drug resistance in the parasite Toxoplasma gondii

MutS homologues (MSHs) are critical components of the eukaryotic mismatch repair machinery. In addition to repairing mismatched DNA, mismatch repair enzymes are known in higher eukaryotes to directly signal cell cycle arrest and apoptosis in response to DNA‐damaging agents. Accordingly, mammalian cells lacking certain MSHs are resistant to chemotherapeutic drugs. Interestingly, we have discovered that the disruption of TgMSH‐1, an MSH in the pathogenic parasite, Toxoplasma gondii, confers drug resistance. Through a genetic selection for T. gondii mutants resistant to the antiparasitic drug monensin, we have isolated a strain that is resistant not only to monensin but also to salinomycin and the alkylating agent, methylnitrosourea. We have shown that this phenotype is due to the disruption of TgMSH‐1 as the multidrug‐resistance phenotype is complemented by a wild‐type copy of TgMSH‐1 and is recapitulated by a directed disruption of this gene in a wild‐type strain. We have also shown that, unlike previously described MSHs involved in signalling, TgMSH‐1 localizes to the parasite mitochondrion. These results provide the first example of a mitochondrial MSH that is involved in drug sensitivity and implicate the induction of mitochondrial stress as a mode of action of the widely used drug, monensin.
Multiple approaches to understanding the taxonomic status of an enigmatic new scorpion species of the genus Tityus (Buthidae) from the biogeographic island of Paraje Tres Cerros (Argentina)

Tityus curupi n. sp. , belonging to the bolivianus complex, is described from the biogeographically distinct area of Paraje Tres Cerros in north-eastern Argentina. We also present a molecular species delimitation analysis between Tityus curupi n. sp. and its sister species Tityus uruguayensis Borelli 1901 to confirm species integrity. Furthermore, a cytogenetic analysis is presented for these two species which contain different multivalent associations in meiosis, as a consequence of chromosome rearrangements, and the highest chromosome numbers in the genus.
Measuring the Impact of Tourism Upon Urban Economies: A Review of Literature

Tourism is increasingly seen as a potential lever towards high economic growth, measured both in terms of income and employment. In recent years, interest in tourism has spread rapidly throughout many small and medium European cities, which previously have not considered themselves as tourist destinations. This paper reviews and summarises the existing literature on the economic assessment of tourism with the objectives of, firstly, identifying the main categories of impacts and, secondly, constructing an inventory of methodologies available to assess them. We will progress step by step, starting from the most simplistic approaches and relaxing assumptions as we proceed. Firstly, we assume a static setting, with spare capacity. In such a setting (partial equilibrium), prices do not respond to demand shocks: only quantities (production, income and jobs) adjust. Secondly, we relax this assumption and assume that there is no spare capacity: prices respond to increasing demand (general equilibrium), leading to reallocation of resources across sectors. We then move from a static to a dynamic setting and survey those contributions that look at the relationship between tourism specialisation and long-run growth.
Prevalence and impact of short sleep duration in redeployed OIF soldiers.

STUDY OBJECTIVES Short sleep duration (SSD) is common among deployed soldiers. The prevalence of SSD during redeployment, however, is unknown. DESIGN Cross-sectional study of a brigade combat team (n = 3152 US Army soldiers) surveyed 90-180 days after completing a 6-15 month deployment to Iraq as part of Operation Iraqi Freedom (OIF). Survey items targeted sleep habits and comorbid medical conditions. Multivariate logistic regression analyses were performed to calculate adjusted odds ratios of medical comorbidities associated with SSD. SETTING US Army Infantry Post. SUBJECTS All soldiers from a redeploying brigade combat team participated in a health assessment between 90 and 180 days upon return to Ft. Lewis from Iraq. INTERVENTIONS None. MEASUREMENTS AND RESULTS A total of 2738 (86.9%) soldiers answered questions regarding self-perceived sleep and were included in the analysis. Mean sleep duration was 5.8 ± 1.2 hours. Nineteen hundred fifty-nine (72%) slept ≤ 6 h, but only 16% reported a daytime nap or felt their job performance was affected due to lack of sleep. Short sleep was more common among soldiers who reported combat exposure. After controlling for combat exposure, short sleep duration (SSD) was associated with symptoms of depression, posttraumatic stress disorder, panic syndrome, and with high-risk health behaviors such as abuse of tobacco and alcohol products, and suicide attempts. CONCLUSIONS SSD is common among redeployed soldiers. Soldiers who experienced combat are at increased risk for persistent SSD and comorbidities associated with SSD. Efforts to reestablish good sleep habits and aggressive evaluation of soldiers with persistent SSD following deployment may aid in the prevention and management of associated medical conditions.
DISSEMINATED MYCOBACTERIOSIS IN A STRANDED LOGGERHEAD SEA TURTLE (CARETTA CARETTA)

Abstract: A loggerhead sea turtle (Caretta caretta) was found stranded alive along the Adriatic coast close to Ancona, Italy, displaying obtundation, tachypnea, and increased respiratory effort. It died a few hours after admission, and a postmortem examination was immediately performed. Miliary yellowish nodules were evident in the liver, and a lower number in the heart, stomach, and gut wall. Hundreds of whitish nodules were scattered in the lungs, with the majority of the pulmonary parenchyma being replaced by the lesions. Histologically, all nodular lesions consisted of a small central area of necrosis with acid-fast bacilli surrounded by epithelioid cells, macrophages, and lymphocytes. Giant cells were found in the spleen and the liver. Kidneys, lungs, liver, spleen, brain, and skin lesions were inoculated aseptically onto general isolation media and selective isolation media for mycobacteria. The isolate showed a restriction pattern identical to Mycobacterium chelonae by polymerase chain reaction–restriction fragment length polymorphism. To the best of the authors' knowledge, this is the first description of a disseminated infection caused by a potentially pathogenic mycobacteria in a stranded, free-ranging loggerhead sea turtle. Veterinary staff and biologists who handle sea turtles with suspected mycobacterial disease should protect themselves appropriately.
Higher Order Hybrid FEM-MoM Technique for Analysis of Antennas and Scatterers

A novel higher order large-domain hybrid computational electromagnetic technique based on the finite element method (FEM) and method of moments (MoM) is proposed for three-dimensional analysis of antennas and scatterers in the frequency domain. The geometry of the structure is modeled using generalized curved parametric hexahedral and quadrilateral elements of arbitrary geometrical orders. The fields and currents on elements are modeled using curl- and divergence-conforming hierarchical polynomial vector basis functions of arbitrary approximation orders, and the Galerkin method is used for testing. The elements can be as large as about two wavelengths in each dimension. As multiple MoM objects are possible in a global exterior region, the MoM part provides much greater modeling versatility and potential for applications, especially in antenna problems, than just as a boundary-integral closure to the FEM part. The examples demonstrate excellent accuracy, convergence, efficiency, and versatility of the new FEM-MoM technique, and very effective large-domain meshes that consist of a very small number of large flat and curved FEM and MoM elements, with p-refined field and current distributions of high approximation orders. The reduction in the number of unknowns is by two orders of magnitude when compared to available data for low-order FEM-MoM modeling.
Rediscovering Fire : Small Interventions , Large Effects

Unexpected findings are often the spark for new discoveries and theories. A puzzle emerged from a series of unanticipated findings over 3 decades, indicating that for problem drinkers (a) relatively brief interventions can trigger significant change, (b) increasing the intensity of treatment does not consistently improve outcome, (c) therapist empathy can be a potent predictor of client change, and (d) a single empathic counseling session can substantially enhance the outcome of subsequent treatment. These phenomena are considered in light of other findings in the addictions-treatment-outcome literature. There is, at present, no cogent explanation for the efficacy of brief interventions. An ancient construct is explored as one possible factor in how some brief encounters may exert large effects in human change.
p75 Neurotrophin Receptor Signaling Activates Sterol Regulatory Element-binding Protein-2 in Hepatocyte Cells via p38 Mitogen-activated Protein Kinase and Caspase-3*

Nerve growth factor (NGF) influences the survival and differentiation of a specific population of neurons during development, but its role in non-neuronal cells has been less studied. We observed here that NGF and its pro-form, pro-NGF, are elevated in fatty livers from leptin-deficient mice compared with controls, concomitant with an increase in low density lipoprotein receptors (LDLRs). Stimulation of mouse primary hepatocytes with NGF or pro-NGF increased LDLR expression through the p75 neurotrophin receptor (p75NTR). Studies using Huh7 human hepatocyte cells showed that the neurotrophins activate the sterol regulatory element-binding protein-2 (SREBP2) that regulates genes involved in lipid metabolism. The mechanisms for this were related to stimulation of p38 mitogen-activated protein kinase (p38 MAPK) and activation of caspase-3 and SREBP2 cleavage following NGF and pro-NGF stimulations. Cell fractionation experiments showed that caspase-3 activity was increased particularly in the membrane fraction that harbors SREBP2 and caspase-2. Experiments showed further that caspase-2 interacts with pro-caspase-3 and that p38 MAPK reduced this interaction and caused caspase-3 activation. Because of the increased caspase-3 activity, the cells did not undergo cell death following p75NTR stimulation, possibly due to concomitant activation of nuclear factor-κB (NF-κB) pathway by the neurotrophins. These results identify a novel signaling pathway triggered by ligand-activated p75NTR that via p38 MAPK and caspase-3 mediate the activation of SREBP2. This pathway may regulate LDLRs and lipid uptake particularly after injury or during tissue inflammation accompanied by an increased production of growth factors, including NGF and pro-NGF.
Antimicrobial properties of green tea extract against cariogenic microflora: an in vivo study.

The aim of the present study was to test in vivo the effectiveness of an experimental green tea extract in reducing levels of mutans streptococci and lactobacilli in saliva by means of selective culture medium. Sixty-six healthy patients ranging in age from 12 to 18 years were recruited and randomly divided into two groups: Group A (n=33) and group B (n=33). Group A subjects were asked to rinse their mouths with 40 mL of an experimental green tea extract, for 1 minute, three times a day for a week, whereas Group B subjects were asked to rinse with 40 mL of a placebo mouth rinse. Saliva samples were obtained at baseline, 4 days, and 7 days. The counts of mutans streptococci and lactobacilli were investigated by chair-side kits. Data were statistically processed. A regression binary logistic analysis was done. The statistical significance level was established at P<. 05. The experimental group showed a statistically significant reduction in colony counts of mutans streptococci and lactobacilli relative to the control group. These findings showed the efficacy of a green tea extract against cariogenic oral flora, opening a promising avenue of clinical applications in the preparation of specific and natural anticariogenic remedies.
Traditional versus Open Office Design

Research in open office design has shown that it is negatively related to workers’ satisfaction with their physical environment and perceived productivity. A longitudinal study was conducted within a large private organization to investigatethe effects of relocating employees from traditional offices to open offices. A measure was constructed that assessed employees’satisfaction with the physical environment, physical stress, coworker relations, perceived job performance, and the use of open office protocols. The sample consisted of 21 employees who completed the surveys at all three measurement intervals: prior to the move, 4 weeks after the move, and 6 months after the move. Results indicated decreased employee satisfaction with all of the dependent measures following the relocation. Moreover, the employees’dissatisfaction did not abate, even after an adjustment period. Reasons for these findings are discussed and recommendations are presented.
Achieving Cultural Appropriateness in Health Promotion Programs: Targeted and Tailored Approaches

It is a truism of health education that programs and interventions will be more effective when they are culturally appropriate for the populations they serve. In practice, however, the strategies used to achieve cultural appropriateness vary widely. This article briefly describes five strategies commonly used to target programs to culturally defined groups. It then explains how a sixth approach, cultural tailoring, might extend these strategies and enhance our ability to develop effective programs for cultural groups. The authors illustrate this new approach with an example of cultural tailoring for cancer prevention in a population of lower income urban African American women.
Overexpression of the Na+/K+/Cl− cotransporter gene induces cell proliferation and phenotypic transformation in mouse fibroblasts

Na+/K+/Cl− cotransporter activity is stimulated in early G1 phase of the cell cycle and this stimulation was shown to be an essential event in fibroblast cell proliferation. In order to elucidate further the role of the Na+/K+/Cl− cotransporter in cell proliferation, we overexpressed the gene encoding the Na+/K+/Cl− cotransporter in mouse fibroblasts, and analyzed cellular phenotypic changes. Mouse Balb/c 3T3 cells were stably transfected with the cDNA of the shark rectal gland Na+/K+/Cl− cotransporter gene (NKCC1), and expressed in a mammalian vector under the cytomegalovirus promoter (Balb/c‐NKCC1 cells). The transfected cells exhibited up to 10‐fold greater bumetanide‐sensitive Rb+ influx compared to the control cells. The Balb/c‐NKCC1 cells have acquired a typical transformation phenotype indicated by: (1) Loss of contact inhibition exhibited by growth to a higher cell density in confluent cultures, and formation of cell foci; (2) proliferation in low serum concentrations; and (3) formation of cell colonies in soft agar. The control cells transfected with the NKCC1 gene inserted in the opposite orientation in the vector retained their normal phenotype. Furthermore, the two specific inhibitors of the Na+/K+/Cl− cotransporter activity; bumetanide and furosemide inhibited the clonogenic efficiency in the NKCC1 transfected cells. These control experiments indicate that the apparent transformation phenotype acquired by the Balb/c‐NKCC1 cells was not merely associated with the process of transfection and selecting for the neomycin‐resistant clones, but rather with the overexpression of the Na+/K+/Cl− cotransporter gene. In order to ascertain that the regulated and normal expression of the Na+/K+/Cl− cotransporter control cell proliferation, the effect of bumetanide a specific inhibitor of the cotransporter, was tested on Balb/c 3T3 cell proliferation, induced by fibroblasts growth factor (FGF) and fetal calf serum (FCS). Bumetanide inhibited synchronized Balb/c 3T3 cell exit from the G0/G1 arrest and entering S‐phase. The inhibition was reversible, as removal of bumetanide completely released cell proliferation. Taken together, these results propose that the NKCC1 gene is involved in the control of normal cell proliferation, while its overexpression results in apparent cell transformation, in a manner similar to some protooncogenes. J. Cell. Physiol. 182:109–118, 2000. © 2000 Wiley‐Liss, Inc.
How do you know you have a drug problem? The role of knowledge of negative consequences in explaining drug choice in humans and rats

Choice models of addiction raise a stark puzzle. Why, if addicts are able to control their consumption and choose to abstain in many circumstances, do they routinely choose to continue to use despite negative consequences? We delineate four options available to a choice theorist to explain this puzzle with respect to human addicts; describe recent experiments with addicted rats which determine the conditions under which they do and do not choose alternative goods over cocaine and heroin respectively; and consider how this animal research bears on our understanding of the nature of addiction. We conclude by arguing for the importance to addiction research of the popular notion of ‘denial’ which, paradoxically, we can begin to theorize by appeal to animal models: for the puzzle dissolves if addicts do not know that the choice to use is the cause of negative consequences, as rats, given their cognitive limitations, cannot.
Transport limits in high-speed quantum-well lasers: experiment and theory

It is shown experimentally that the modulation bandwidth of quantum well lasers can be reduced by a factor of six due to carrier transport across undoped layers of the laser as in the separate confinement heterostructure (SCH). Analytical expressions are given for the modulation response function, resonance frequency, damping rate and K factor to include carrier transport, and it is shown that carrier transport is responsible for a low-frequency rolloff which limits the modulation response of quantum-well lasers. It also shown that carrier transport leads to a reduction in the effective differential gain, while the gain compression factor remains largely unaffected by it. <<ETX>>
Inequity Aversion and Individual Behavior in Public Good Games: An Experimental Investigation

We present a simple two-steps procedure for a within-subject test of the inequity aversion model of Fehr and Schmidt (1999). In the first step, subjects played modified ultimatum and dictator games and were classified according to their preferences. In the second step, subjects with specific preferences according to the Fehr and Schmidt model were matched into pairs and interacted with each other in a standard public good game and a public good game with punishment possibility. Our results show that the specific composition of groups significantly influences the subjects' performance in the public good games. We identify the aversion against advantageous inequity and the information about the coplayer's type as the main influencing factors for the behavior of subjects.
Functional MR imaging using a visually guided saccade paradigm for comparing activation patterns in patients with probable Alzheimer's disease and in cognitively able elderly volunteers.

BACKGROUND AND PURPOSE Alzheimer's disease is associated with progressive visuospatial dysfunction. This study used functional MR (fMR) imaging with an eye movement paradigm to investigate differences in visuospatial cognition between patients with probable Alzheimer's disease (pAD) and cognitively able elderly volunteers. METHODS Using established, although imperfect, clinical criteria, patients with pAD (n = 18) and cognitively able elderly volunteers (n = 10) were selected for study. All patients underwent echo-planar fMR imaging at 1.5 T. The visually guided saccade paradigm consisted of alternating periods (30 s) of central fixation and visually guided saccades to a target appearing randomly along the horizontal meridian. Activation maps were derived using a voxelwise t test, comparing the signal intensities between the two steady-state conditions. The activation patterns were characterized by Talairach coordinates, activation volumes, and laterality ratios (LRs). RESULTS Statistically significant differences existed between the activation patterns of the patients with pAD and those of the volunteers. In contrast to the control group, a left-dominant parietal activation pattern and enhanced prefrontal cortical activation were observed in most patients with pAD. CONCLUSION Within the limitations of the imperfect clinical standard of reference, the reduction in right parietal activation producing the left-dominant LR for the intraparietal sulcus may reflect the progressive dysfunction in spatial attention associated with Alzheimer's disease, considering the known parietal lobe involvement in this function and the disease. The high specificity of a positive intraparietal sulcal LR measured by fMR imaging may have a role in detecting and monitoring Alzheimer's disease.
Diamond Blackfan anemia 2008–2009: broadening the scope of ribosome biogenesis disorders

Purpose of review Diamond Blackfan anemia (DBA) is an inherited bone marrow failure syndrome characterized by erythroid failure, congenital anomalies and predisposition to cancer. Recently, the notion of DBA as a disorder of ribosome biogenesis has been clarified. Correlations between molecular underpinnings and disease pathophysiology, while elusive, are beginning to emerge. Advances in these areas will be explored in this review. Recent findings All known genes mutated in DBA encode ribosomal proteins associated with either the small (RPS) or large (RPL) subunit and in these cases ribosomal protein haploinsufficiency gives rise to the disease. The number of genes affected, their potential interactions with the environment and modifier genes, and the myriad of potential signaling pathways linking abortive ribosome synthesis to cell-cycle regulators may all contribute to disease heterogeneity. Genotype/phenotype relationships emerging over the past year promise to shed light on these complex interrelationships and their role in DBA pathophysiology. Summary The nosology of DBA has recently expanded to include two distinct disease categories: a classical inherited bone marrow failure syndrome and a ‘ribosomopathy’. The description of DBA as a ribosomopathy has provided a context for scientific inquiry analogous to the description of Fanconi anemia as a disorder of DNA repair.