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Evidence Points (evidence + point)
Kinds of Evidence Points Selected AbstractsParasites in the food web: linking amphibian malformations and aquatic eutrophicationECOLOGY LETTERS, Issue 7 2004Pieter T. J. Johnson Abstract Emerging diseases are an ever-growing affliction of both humans and wildlife. By exploring recent increases in amphibian malformations (e.g. extra or missing limbs), we illustrate the importance of food web theory and community ecology for understanding and controlling emerging infections. Evidence points to a native parasite, Ribeiroia ondatrae, as the primary culprit of these malformations, but reasons for the increase have remained conjectural. We suggest that the increase is a consequence of complex changes to aquatic food webs resulting from anthropogenic disturbance. Our results implicate cultural eutrophication as a driver of elevated parasitic infection: (1) eutrophication causes a predator-mediated shift in snail species composition toward Planorbella spp., (2) Planorbella are the exclusive first intermediate hosts of R. ondatrae and (3) Ribeiroia infection is a strong predictor of amphibian malformation levels. Our study illustrates how the effects of anthropogenic disturbance on epidemic disease can be mediated through direct and indirect changes in food web structure. [source] Addressing the imbalance: empowering older people in disaster response and preparednessINTERNATIONAL JOURNAL OF OLDER PEOPLE NURSING, Issue 1 2010BSc(Hons), Nursing Adv Dip Ed., Pat Deeny RN Deeny P., Vitale C.T., Spelman R. & Duggan S. (2010) Addressing the imbalance: empowering older people in disaster response and preparedness. International Journal of Older People Nursing 5, 77,80 doi: 10.1111/j.1748-3743.2009.00204.x This paper explores the role of the nurse in empowering older people at all stages in the disaster cycle. Evidence points to the need to increase the level of consultation and inclusivity of older people on this topic. Caution is called for in relation to classifying older people as a vulnerable group in disasters without first recognising that older people are probably the richest resource within any culture when it comes to emergency planning and\or coping with disasters. Practical advice on how nurses can best assist older people is presented. [source] Urinary chemosignals in giant pandas (Ailuropoda melanoleuca): seasonal and developmental effects on signal discriminationJOURNAL OF ZOOLOGY, Issue 3 2004A. M. White Abstract As a solitary species, giant pandas Ailuropoda melanoleuca have a chemical communication system that allows for avoidance with conspecifics throughout most of the year and facilitates breeding during their brief reproductive period. To date, most studies have focused on adults during the breeding season, but much remains to be learned about developmental and seasonal effects on chemical communication. Here, using odour discrimination methodology, we examine these contextual influences on chemosignalling in giant pandas for the first time. During the breeding season both adult and subadult giant pandas overtly discriminated conspecific sex using chemical cues in urine. Male urine was consistently investigated more than female urine by pandas across all age-sex categories. This preference for male urine was observed for both adult and subadult urine donors, indicating that adult levels of reproductive hormones are not necessary for the production of sex-specific urinary odour cues. By contrast, giant pandas did not overtly discriminate sex during the non-breeding season. This finding underscores that negative results for discrimination studies need to be interpreted with caution, as many contextual factors may influence overt expression of this ability. Evidence points to seasonal changes in motivation, rather than in the availability of sex-specific chemical cues in urine, as the causal factor for changing odour discrimination patterns. These and other findings are discussed in the light of the potential role that discrimination of odour plays in the regulation of competitive and reproductive interactions in nature. [source] Promoter polymorphism of the IL-18 gene is associated with atopic asthma in Tunisian childrenINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 1 2008J. Lachheb Summary Several lines of evidence point to a relevant role of IL-18 in the process of asthma. Some studies suggest that the polymorphism in the gene of IL-18 can be involved in many inflammatory and atopic diseases such as asthma. The aim of our study is to estimate the frequency of the IL-18- 607 C/A (rs 1946518) promoter polymorphism in Tunisian children with asthma. We investigated whether the presence of this polymorphism -607 C/A was associated with asthma or atopy and whether this polymorphism influenced the severity of asthma in affected children. We examined also the relationship between the IL-18 gene polymorphism and the serum total IgE level. The IL-18/-607 C/A polymorphism was analysed by polymerase chain reaction and restriction fragment-length polymorphism (PCR-RFLP) analysis. A total of 105 asthma patients and 112 controls as part of the whole children population were studied in a case-control study. Among the 105 children with asthma, 40 were also studied for linkage analyses with their respective parents. We noted that the A allele was associated with statistically significant increases in the risk of asthma in the case-control study (odd ratio (OR) = 1.55, 95% confidence interval (CI) 1.03,2.33. Moreover, the A allele was also associated with atopic asthma (P = 0.008), but not with asthma severity. The transmission disequilibrium test (TDT) analysis in this family study did not suggest a preferential transmission of the IL-18/ -607 C/A polymorphism to affected children. There is no correlation between the IgE level and the IL-18 - 607 C/A promoter polymorphism. Our data indicate that IL-18 - 607 C/A promoter polymorphism is associated with susceptibility to developing asthma in Tunisian population. [source] A double-blind, placebo-controlled study to assess the mitochondria-targeted antioxidant MitoQ as a disease-modifying therapy in Parkinson's diseaseMOVEMENT DISORDERS, Issue 11 2010Barry J. Snow MD Abstract Multiple lines of evidence point to mitochondrial oxidative stress as a potential pathogenic cause for Parkinson's disease (PD). MitoQ is a powerful mitochondrial antioxidant. It is absorbed orally and concentrates within mitochondria where it has been shown to protect against oxidative damage. We enrolled 128 newly diagnosed untreated patients with PD in a double-blind study of two doses of MitoQ compared with placebo to explore the hypothesis that, over 12 months, MitoQ would slow the progression of PD as measured by clinical scores, particularly the Unified Parkinson Disease Rating Scale. We showed no difference between MitoQ and placebo on any measure of PD progression. MitoQ does not slow the progression of PD, and this finding should be taken into account when considering the oxidative stress hypothesis for the pathogenesis of PD. © 2010 Movement Disorder Society [source] Contact in the Andes: Bioarchaeology of systemic stress in colonial Mórrope, PeruAMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, Issue 3 2009Haagen D. Klaus Abstract The biocultural interchange between the Eastern and Western Hemispheres beginning in the late fifteenth century initiated an unprecedented adaptive transition for Native Americans. This article presents findings from the initial population biological study of contact in the Central Andes of Peru using human skeletal remains. We test the hypothesis that as a consequence of Spanish colonization, the indigenous Mochica population of Mórrope on the north coast of Peru experienced elevated systemic biological stress. Using multivariate statistical methods, we examine childhood stress reflected in the prevalence of linear enamel hypoplasias and porotic hyperostosis, femoral growth velocity, and terminal adult stature. Nonspecific periosteal infection prevalence and D30+/D5+ ratio estimations of female fertility characterized adult systemic stress. Compared to the late pre-Hispanic population, statistically significant patterns of increased porotic hyperostosis and periosteal inflammation, subadult growth faltering, and depressed female fertility indicate elevated postcontact stress among both children and adults in Mórrope. Terminal adult stature was unchanged. A significant decrease in linear enamel hypoplasia prevalence may not indicate improved health, but reflect effects of high-mortality epidemic disease. Various lines of physiological, archaeological, and ethnohistoric evidence point to specific socioeconomic and microenvironmental factors that shaped these outcomes, but the effects of postcontact population aggregation in this colonial town likely played a fundamental role in increased morbidity. These results inform a model of postcontact coastal Andean health outcomes on local and regional scales and contribute to expanding understandings of the diversity of indigenous biological variation in the postcontact Western Hemisphere. Am J Phys Anthropol, 2009. © 2008 Wiley-Liss, Inc. [source] Your Money or Your Life: Changing Job Quality in OECD CountriesBRITISH JOURNAL OF INDUSTRIAL RELATIONS, Issue 3 2005Andrew E. Clark Job quality may usefully be thought of as depending on both job values (how much workers care about different job outcomes) and the job outcomes themselves. Here, both cross-section and panel data are used to examine changes in job quality in OECD countries during the 1990s. Despite rising wages and falling hours of work, overall job satisfaction is either stable or declining. These movements are neither due to changes in the type of workers nor because of changes in their job values. Some pieces of evidence point to stress and hard work as being strong candidates for what has gone wrong with employees' jobs. We find evidence of increasing inequality in a number of job outcomes. Some groups of workers have done better than others: the young and the highly educated have been insulated against downward movements in job quality, and there is tentative evidence that trade unions may have protected their members against adverse job outcomes. [source] Update on Atrial Fibrillation: Part ICLINICAL CARDIOLOGY, Issue 2 2008Irina Savelieva M.D. Abstract Atrial fibrillation (AF) is an epidemic, affecting 1% to 1.5% of the population in the developed world. Projected data from the population-based studies suggest that the prevalence of AF will grow at least 3-fold by 2050. The health and economic burden imposed by AF and AF-related morbidity is enormous. Atrial fibrillation has a multiplicity of causes ranging from genetic to degenerative, but hypertension and heart failure are the commonest and epidemiologically most prevalent conditions associated with AF as both have been shown to create an arrhythmogenic substrate. Several theories emerged regarding the mechanism of AF, which can be combined into two groups: the single focus hypothesis and the multiple sources hypothesis. Several lines of evidence point to the relevance of both hypotheses to the mechanism of AF, probably with a different degree of involvement depending on the variety of AF (paroxysmal or persistent). Sustained AF alters electrophysiological and structural properties of the atrial myocardium such that the atria become more susceptible to the initiation and maintenance of the arrhythmia, a process known as atrial remodeling. Angiotensin II has been recognized as a key element in atrial remodeling in association with AF opening the possibility of exploitation of "upstream" therapies to prevent or delay atrial remodeling. The clinical significance of AF lies predominantly in a 5-fold increased risk of stroke. The limitations of warfarin prompted the development of new antithrombotic drugs, which include anticoagulants, such as direct oral thrombin inhibitors (dabigatran) and factor Xa inhibitors (rivaroxaban, apixaban). Novel mechanical approaches for the prevention of cardioembolic stroke have recently been evaluated: percutaneous left atrial appendage occluders, minimally invasive surgical isolation of the left atrial appendage, and implantation of carotid filtering devices. Copyright © 2008 Wiley Periodicals, Inc. [source] ASSESSING THE EFFECTS OF MASS INCARCERATION ON INFORMAL SOCIAL CONTROL IN COMMUNITIESCRIMINOLOGY AND PUBLIC POLICY, Issue 2 2004JAMES P. LYNCH Research Summary: This paper reviews and evaluates the existing (and limited) evidence that increases in incarceration have affected the ability of residential neighborhoods to perform their traditional social control functions. It suggests that, although comparatively weak, the evidence points to the increases in the level and clustering in social and geographic space of incarceration as contributing to changes in the social organization of affected communities by weakening family formation, labor force attachments, and patterns of social interaction among residents. At the same time, however, the paper does find support for the contention that incarceration leads to reductions in crime in affected communities. Policy Implications: To the extent that mass incarceration disrupts patterns of social interaction, weakens community social organization, and decreases the stigma of imprisonment, its longer-run effects may be to reduce its effectiveness. [source] Increased right amygdala volume in lithium-treated patients with bipolar I disorderACTA PSYCHIATRICA SCANDINAVICA, Issue 2 2010J. Usher Usher J, Menzel P, Schneider-Axmann T, Kemmer C, Reith W, Falkai P, Gruber O, Scherk H. Increased right amygdala volume in lithium-treated patients with bipolar I disorder. Objective:, The amygdala plays a major role in processing emotional stimuli. Fourteen studies using structural magnetic resonance imaging (MRI) have examined the amygdala volume in paediatric and adult patients with bipolar disorder (BD) compared with healthy controls (HC) and reported inconsistent findings. Lithium has been found to increase grey matter volume, and first evidence points towards an effect on regional brain volume such as the amygdala. Method:, We examined the amygdala volume of euthymic patients with BD treated with lithium (n = 15), without lithium (n = 24) and HC (n = 41) using structural MRI. Results:, Patients treated with lithium exhibited in comparison to HC a larger right absolute (+17.9%, P = 0.015) and relative (+18%, P = 0.017) amygdala volume. There was no significant difference in amygdala volume between patients without lithium treatment and HC. Conclusion:, Lithium appears to have a sustained effect on a central core region of emotional processing and should therefore be considered in studies examining BD. [source] Interactions between microvascular and macrovascular disease in diabetes: pathophysiology and therapeutic implicationsDIABETES OBESITY & METABOLISM, Issue 6 2007Andrew J. Krentz Convention partitions the complications of diabetes into two main subtypes. First are the diabetes-specific microvascular complications of retinopathy, nephropathy and neuropathy; second are the atherothrombotic macrovascular complications that account for the majority of premature deaths. Pathological interactions between microvascular and macrovascular complications, for example, nephropathy and macrovascular disease, are common. Similar mechanisms and shared risk factors drive the development and progression of both small and large vessel disease. This concept has therapeutic implications. Mounting evidence points to the need for multifactorial strategies to prevent vascular complications in subjects with diabetes and/or the metabolic syndrome. We advocate a combined therapeutic approach that addresses small and large vessel disease. Preferential use should be made of drug regimens that (i) maximize vascular protection, (ii) reduce the risk of iatrogenic vascular damage and (iii) minimize the increasing problem of polypharmacy. [source] Seasonality and the dynamics of infectious diseasesECOLOGY LETTERS, Issue 4 2006Sonia Altizer Abstract Seasonal variations in temperature, rainfall and resource availability are ubiquitous and can exert strong pressures on population dynamics. Infectious diseases provide some of the best-studied examples of the role of seasonality in shaping population fluctuations. In this paper, we review examples from human and wildlife disease systems to illustrate the challenges inherent in understanding the mechanisms and impacts of seasonal environmental drivers. Empirical evidence points to several biologically distinct mechanisms by which seasonality can impact host,pathogen interactions, including seasonal changes in host social behaviour and contact rates, variation in encounters with infective stages in the environment, annual pulses of host births and deaths and changes in host immune defences. Mathematical models and field observations show that the strength and mechanisms of seasonality can alter the spread and persistence of infectious diseases, and that population-level responses can range from simple annual cycles to more complex multiyear fluctuations. From an applied perspective, understanding the timing and causes of seasonality offers important insights into how parasite,host systems operate, how and when parasite control measures should be applied, and how disease risks will respond to anthropogenic climate change and altered patterns of seasonality. Finally, by focusing on well-studied examples of infectious diseases, we hope to highlight general insights that are relevant to other ecological interactions. [source] Carcinogenicity of acetaldehyde in alcoholic beverages: risk assessment outside ethanol metabolismADDICTION, Issue 4 2009Dirk W. Lachenmeier ABSTRACT Aims In addition to being produced in ethanol metabolism, acetaldehyde occurs naturally in alcoholic beverages. Limited epidemiological evidence points to acetaldehyde as an independent risk factor for cancer during alcohol consumption, in addition to the effects of ethanol. This study aims to estimate human exposure to acetaldehyde from alcoholic beverages and provide a quantitative risk assessment. Methods The human dietary intake of acetaldehyde via alcoholic beverages was estimated based on World Health Organization (WHO) consumption data and literature on the acetaldehyde contents of different beverage groups (beer, wine, spirits and unrecorded alcohol). The risk assessment was conducted using the European Food Safety Authority's margin of exposure (MOE) approach with benchmark doses obtained from dose,response modelling of animal experiments. Life-time cancer risk was calculated using the T25 dose descriptor. Results The average exposure to acetaldehyde from alcoholic beverages was estimated at 0.112 mg/kg body weight/day. The MOE was calculated to be 498, and the life-time cancer risk at 7.6 in 10 000. Higher risk may exist for people exposed to high acetaldehyde contaminations, as we have found in certain unrecorded alcohol beverages in Guatemala and Russia, for which we have demonstrated possible exposure scenarios, with risks in the range of 1 in 1000. Conclusions The life-time cancer risks for acetaldehyde from alcoholic beverages greatly exceed the usual limits for cancer risks from the environment set between 1 : 10 000 and 1 : 1 000 000. Alcohol consumption has thus been identified as a direct source of acetaldehyde exposure, which in conjunction with other sources (food flavourings, tobacco) results in a magnitude of risk requiring intervention. An initial public health measure could be to reduce the acetaldehyde content in alcoholic beverages as low as technologically possible, and to restrict its use as a food flavour additive. [source] Hypothalamic,endocrine aspects in Huntington's diseaseEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2006Ĺsa Petersén Abstract Huntington's disease (HD) is a hereditary and fatal disorder caused by an expanded CAG triplet repeat in the HD gene, resulting in a mutant form of the protein huntingtin. Wild-type and mutant huntingtin are expressed in most tissues of the body but the normal function of huntingtin is not fully known. In HD, the neuropathology is characterized by intranuclear and cytoplasmic inclusions of huntingtin aggregates, and cell death primarily in striatum and cerebral cortex. However, hypothalamic atrophy occurs at early stages of HD with loss of orexin- and somatostatin-containing cell populations. Several symptoms of HD such as sleep disturbances, alterations in circadian rhythm, and weight loss may be due to hypothalamic dysfunction. Endocrine changes including increased cortisol levels, reduced testosterone levels and increased prevalence of diabetes are found in HD patients. In HD mice, alterations in the hypothalamic,pituitary,adrenal axis occurs as well as pancreatic ,-cell and adipocyte dysfunction. Increasing evidence points towards important pathology of the hypothalamus and the endocrine system in HD. As many neuroendocrine factors are secreted into the cerebrospinal fluid, blood and urine, it is possible that their levels may reflect the disease state in the central nervous system. Investigating neuroendocrine changes in HD opens up the possibility of finding biomarkers to evaluate future therapies for HD, as well as of identifying novel targets for therapeutic interventions. [source] Differential targeting of components of the dystrophin complex to the postsynaptic membraneEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2001Sophie Marchand Abstract Accumulating evidence points to the participation of dystroglycan in the clustering of nicotinic acetylcholine receptors at the neuromuscular junction [Côtéet al.. (1999) Nature Genet., 3, 338,342]. Dystroglycan is part of a multimolecular complex, either associated with dystrophin (the dystrophin-associated protein complex) at the sarcolemma or with utrophin (the utrophin-associated protein complex) at the neuromuscular junction. Understanding the assembly of this complex at the developing synapse led us to investigate, in Torpedo electrocyte, the intracellular routing and the targeting of several of its components, including dystroglycan, syntrophin, dystrophin and dystrobrevin. We previously demonstrated that acetylcholine receptors and rapsyn, the 43-kDa receptor-associated protein at the synapse, are cotargeted to the postsynaptic membrane via the exocytic pathway [Marchand et al.. (2000) J. Neurosci., 20, 521,528]. Using cell fractionation, immunopurification and immuno-electron microscope techniques, we show that ,-dystroglycan, an integral glycoprotein that constitutes the core of the dystrophin-associated protein complex localized at the innervated membrane, is transported together with acetylcholine receptor and rapsyn in post-Golgi vesicles en route to the postsynaptic membrane. Syntrophin, a peripheral cytoplasmic protein of the complex, associates initially with these exocytic vesicles. Conversely, dystrophin and dystrobrevin were absent from these post-Golgi vesicles and associate directly with the postsynaptic membrane. This study provides the first evidence for a separate targeting of the various components of the dystrophin-associated protein complex and a step-by-step assembly at the postsynaptic membrane. [source] THE MACROEVOLUTIONARY DYNAMICS OF ANT DIVERSIFICATIONEVOLUTION, Issue 11 2009Marcio R. Pie The availability of increasingly comprehensive phylogenies has provided unprecedented opportunities to assess macroevolutionary patterns, yet studies on invertebrate diversification are few. In particular, despite the ecological and evolutionary importance of ants, little is known about their tempo and mode of diversification. Recent advances in ant phylogenetics can now provide a basis for rigorous analyses of the diversification of ant lineages. The goals of the present study are threefold. First, we demonstrate that a hypothesized disproportionate increase in ant diversification during the angiosperm radiation is largely artifactual. Rather, current evidence points to a fairly constant rate of lineage growth during its history. Moreover, an analysis of diversification patterns across the ant phylogeny indicates considerable rate heterogeneity among lineages. Indeed, and contrary to the expectation if lineages had experienced a single rate of lineage increase, we found no correspondence between genus age and diversity. Finally, we demonstrate a statistically significant phylogenetic signal in ant diversification: closely related genera have diversities that are more similar to one another than one would expect by chance. This suggests that the capacity for diversification may be itself a biological trait that evolved during the radiation of the family Formicidae. [source] MBSJ MCC Young Scientist Award 2009 REVIEW: Selective autophagy regulates various cellular functionsGENES TO CELLS, Issue 9 2010Masaaki Komatsu Autophagy is a self-eating system conserved among eukaryotes, in which cellular components including organelles are entrapped into a double membrane structure called the autophagosome and then degraded by lysosomal hydrolases. In addition to its role in supplying amino acids in response to nutrient starvation, autophagy is involved in quality control to maintain cell health. Thus, inactivation of autophagy causes the formation of cytoplasmic protein inclusions, which comprise misfolded proteins and the accumulation of many degenerated organelles, resulting in liver injury, diabetes, myopathy and neurodegeneration. Furthermore, although autophagy has been considered nonselective, increasing evidence points to the selectivity of autophagy in sorting vacuolar enzymes and removal of aggregate-prone proteins and unwanted organelles. Such selectivity allows diverse cellular regulation, similar to the ubiquitin proteasome pathway. In this review, we discuss the physiological roles of selective autophagy and their molecular mechanisms. [source] Employer responses to union organising: patterns and effectsHUMAN RESOURCE MANAGEMENT JOURNAL, Issue 1 2010Edmund Heery This article presents original research on employer responses to trade union organising campaigns in the United Kingdom. The evidence indicates that there is no single response, with employers in some cases seeking to block and in others support union activity. These different patterns are strongly path dependent and reflect the prior degree of exposure to trade unionism of workplaces targeted for organising. Another finding is that employer responses co-vary with union approaches to organising, such that when the employer adopts adversarial tactics so does the union. The militancy of both parties, it seems, is mutually reinforcing. Finally, the evidence points to substantial influence of employer responses over the outcomes of organising. When employers are supportive then campaigns tend to be more successful, measured on a range of criteria. When the employer is hostile unions find it difficult to make progress and encounter particular difficulties in securing recognition. [source] Estradiol levels in prepubertal boys and girls , analytical challengesINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 5 2004Katrine Bay Summary Increasing evidence points at an important function of low concentrations of estradiol (E2) in prepubertal boys and girls. E2 serum levels in prepubertal children are, however, often immeasurable in conventional E2 assays. This strongly hampers further investigation of the physiological relevance of E2 in children. In addition, there is an increasing concern of the potential effect of exposure to endocrine disrupters with estrogenic or antiandrogenic activity on pubertal development. A requirement of assessing the instance for this concern, adds further to the demands for applicable methodologies for the evaluation of the sensitivity of the organism to low E2 concentrations. Traditionally, E2 is measured by use of the radioimmunoassay (RIA). As an ultrasensitive alternative to the RIA, a recombinant cell bioassay has been developed. In this review, methodological aspects for these methods of analysis are examined and their applicability for evaluation of low E2 serum concentrations in children is estimated. Furthermore, available data on E2 levels in prepubertal boys and girls are evaluated and discussed, taking into consideration the limitations of the methods of analysis. In conclusion, there is a pronounced demand for new and improved methods of analysis for accurate and sensitive evaluation of low concentrations of E2. [source] Recent evidence on the development and maintenance of constructive staff,family relationships in the care of older people , a report on a systematic review updateINTERNATIONAL JOURNAL OF EVIDENCE BASED HEALTHCARE, Issue 2 2010Emily Haesler BN PgradDipAdvNsg Abstract Aim, This paper is an update to a systematic review that presents the best available evidence on the factors that are most effective in promoting constructive staff,family relationships in the care of older people in the institutional healthcare setting. Methods, Systematic review. Results, The updated review supports findings from the earlier review. Additional evidence points to the importance of monitoring care, family involvement in decision-making, staff upholding the uniqueness of the older person, trust, the involvement of the multidisciplinary care team and family dynamics as factors underpinning effective staff,family relationships. Conclusion, A number of factors critical to the development and maintenance of positive staff,family relationships in the institutional setting have been identified. The delivery of quality care is predicated on staff having an understanding of these factors. [source] Steroid and thyroid hormone receptors in mitochondriaIUBMB LIFE, Issue 4 2008Anna-Maria G. Psarra Abstract Receptors for glucocorticoids, estrogens, androgens, and thyroid hormones have been detected in mitochondria of various cell types by Western blotting, immunofluorescence labeling, confocal microscopy, and immunogold electron microscopy. A role of these receptors in mitochondrial transcription, OXPHOS biosynthesis, and apoptosis is now being revealed. Steroid and thyroid hormones regulate energy production, inducing nuclear and mitochondrial OXPHOS genes by way of cognate receptors. In addition to the action of the nuclearly localized receptors on nuclear OXPHOS gene transcription, a parallel direct action of the mitochondrially localized receptors on mitochondrial transcription has been demonstrated. The coordination of transcription activation in nuclei and mitochondria by the respective receptors is in part realized by their binding to common trans acting elements in the two genomes. Recent evidence points to a role of the mitochondrial receptors in cell survival and apoptosis, exerted by genomic and nongenomic mechanisms. The identification of additional receptors of the superfamily of nuclear receptors and of other nuclear transcription factors in mitochondria increases their arsenal of regulatory molecules and further underlines the central role of these organelles in the integration of growth, metabolic, and cell survival signals. © 2008 IUBMB IUBMB Life, 60(4): 210,223, 2008 [source] Analysis of the vitamin D system in cutaneous squamous cell carcinomasJOURNAL OF CUTANEOUS PATHOLOGY, Issue 3 2004Jörg Reichrath Background:, Increasing evidence points at an important function of vitamin D metabolites for growth regulation in various tissues, and new vitamin D analogs are interesting candidates for the treatment of malignancies, including squamous cell carcinomas (SCC). Methods:, We have analyzed expression of vitamin D receptor (VDR), vitamin D-25-hydroxylase (25-OHase), 25-hydroxyvitamin D-1,-hydroxylase (1,-OHase), and 1,25-dihydroxyvitamin D-24-hydroxylase (24-OHase) in SCC. Results:, Intensity of VDR immunoreactivity was increased in SCCs as compared to normal human skin. VDR staining did not correlate with histological type or grading, nor with markers for proliferation, differentiation, or apoptotic cells. Incubation of SCC cell lines (SCL-1, SCL-2) with calcitriol resulted in a dose-dependent suppression of cell proliferation (approximately up to 30%) in vitro, as measured by a tetrazolium salt (WST-1)-based colorimetric assay. RNA levels for VDR, 25-OHase, 1,-OHase, and 24-OHase were significantly elevated in SCCs as compared to HS, as measured by real-time polymerase chain reaction. Conclusions:, Our findings demonstrate that modulation of VDR expression and local synthesis or metabolism of vitamin D metabolites may be of importance for growth regulation of SCCs. Additionally, SCCs represent potential targets for therapy with new vitamin D analogs that exert little calcemic side effects or for pharmacological modulation of calcitriol synthesis/metabolism in these tumors. [source] Bacterial flora in irritable bowel syndrome: role in pathophysiology, implications for managementJOURNAL OF DIGESTIVE DISEASES, Issue 1 2007Eamonn M M QUIGLEY Irritable bowel syndrome (IBS) may, in part at least, result from a dysfunctional interaction between the indigenous flora and the intestinal mucosa which, in turn, leads to immune activation in the colonic mucosa. Some propose a role for bacterial overgrowth as a common causative factor in the pathogenesis of symptoms in IBS; other evidence points to more subtle qualitative changes in the colonic flora; both hypotheses remain to be confirmed but the likelihood that bacterial overgrowth will prove to be a major factor in IBS now seems remote. Nevertheless, short-term therapy with either antibiotics or probiotics does seem to reduce symptoms among IBS patients. It seems most likely that the benefits of antibiotic therapy are mediated through subtle and, perhaps, localized, quantitative and/or qualitative changes in the colonic flora. How probiotics exert their effects remain to be defined but an anti-inflammatory effect seems likely. While this approach to the management of IBS is in its infancy, it is evident that manipulation of the flora, whether through the administration of antibiotics or probiotics, deserves further attention in IBS. [source] Vegetation dynamics of predator-free land-bridge islandsJOURNAL OF ECOLOGY, Issue 2 2006JOHN TERBORGH Summary 1We tested the ,green world' hypothesis of Hairston, Smith and Slobodkin by monitoring vegetation change on recently created predator-free land-bridge islands in a huge hydroelectric impoundment, Lago Guri, in the State of Bolivar, Venezuela. 2Our results affirm the green world hypothesis and expose the operation of a strong top-down trophic cascade that negatively impacted nearly every plant species present, implying that community stability is maintained through the action of predators. 3To test the hypothesis, we monitored vegetation on nine predator-free islands and compared demographic parameters to those observed at control sites supporting complete or nearly complete suites of predators. 4Herbivore abundance was high on ,small' (, 0.5, < 2 ha) islands, moderate on ,medium' islands (> 3, < 15 ha) and low on the ,large' landmasses that served for reference. 5Small sapling densities on small islands were only 37% of controls in 1997 (after 11 years of isolation), and when recensused in 2002, had fallen to 25% of controls. High mortality and, especially, low recruitment contributed to the decline in sapling cohorts. 6Sapling decline occurred earlier on small islands, although recruitment failure had become equally pronounced on medium islands by the end of the monitoring period. 7Several mechanisms could potentially account for suppressed sapling recruitment, but the weight of evidence points to herbivory on seedlings and small saplings by leaf-cutter ants (Atta spp. and Acromyrmex sp.). Exposure to prevailing trade winds (windward vs. leeward slopes of islands) had no detectable effect on the density or diversity of seedlings or saplings. [source] Causes and consequences of proteinuria: the kidney filtration barrier and progressive renal failureJOURNAL OF INTERNAL MEDICINE, Issue 3 2003K. Tryggvason Abstract., Tryggvason K, Pettersson E (Karolinska Institute, Stockholm, Sweden). Causes and consequences of proteinuria: the kidney filtration barrier and progressive renal failure (Review). J Intern Med 2003; 254: 216,224. The past few years have witnessed a major breakthrough in the understanding of the molecular mechanisms and ultrastructural changes behind the development of proteinuria. The discovery of several proteins in the glomerular podocyte and slit diaphragm, where mutations lead to disease, has revealed the importance of this cell with its diaphragm as the major filtration barrier as opposed to the glomerular basement membrane (GBM) previously ascribed this function. Furthermore, accumulating clinical as well as experimental evidence points to the harmful effects of proteinuria, irrespective of the original damage. The purpose of this review is to shed light on what we know today about the two sides of this ,coin', the causes and the consequences of proteinuria. [source] High-pressure granulites: formation, recovery of peak conditions and implications for tectonicsJOURNAL OF METAMORPHIC GEOLOGY, Issue 1 2003P. J. O'Brien Abstract High-pressure granulites are characterised by the key associations garnet-clinopyroxene-plagioclase-quartz (in basic rocks) and kyanite-K-feldspar (metapelites and felsic rocks) and are typically orthopyroxene-free in both basic and felsic bulk compositions. In regional metamorphic areas, two essential varieties exist: a high- to ultrahigh-temperature group and a group representing overprinted eclogites. The high- to ultrahigh-temperature type formerly contained high-temperature ternary feldspar (now mesoperthite) coexisting with kyanite, is associated with garnet peridotites, and formed at conditions above 900 °C and 1.5 GPa. Clinopyroxene in subordinate basic rocks is Al-rich and textural evidence points to a high-pressure,high-temperature melting history. The second variety contains symplectite-like or poikilitic clinopyroxene-plagioclase intergrowths indicating former plagioclase-free, i.e. eclogite facies assemblages. This type of rock formed at conditions straddling the high-pressure amphibolite/high-pressure granulite field at around 700,850 °C, 1.0,1.4 GPa. Importantly, in the majority of high-pressure granulites, orthopyroxene is secondary and is a product of reactions at pressures lower than the peak recorded pressure. In contrast to low- and medium-pressure granulites, which form at conditions attainable in the mid to lower levels of normal continental crust, high-pressure granulites (of nonxenolith origin) mostly represent rocks formed as a result of short-lived tectonic events that led to crustal thickening or subduction of the crust into the mantle. Short times at high-temperature conditions are reflected in the preservation of prograde zoning in garnet and pyroxene. High-pressure granulites of both regional types, although rare, are known from both old and young metamorphic terranes (e.g. c. 45 Ma, Namche Barwa, E Himalaya; 400,340 Ma, European Variscides; 1.8 Ga Hengshan, China; 1.9 Ga, Snowbird, Saskatchewan and 2.5 Ga Jianping, China). This spread of ages supports proposals suggesting that thermal and tectonic processes in the lithosphere have not changed significantly since at least the end of the Archean. [source] The Quaternary is here to stay,JOURNAL OF QUATERNARY SCIENCE, Issue 1 2007D. Q. Bowen Abstract The proposals to drop the name Quaternary, to extend the Neogene Period to the present day, and to confirm the base of the Pleistocene at 1.8,Ma are reviewed. It is concluded that there is no scientific case for dropping the name Quaternary and that an overwhelming volume of evidence points to 2.6,Ma as the most appropriate base for the Quaternary/Pleistocene, when extensive Northern Hemisphere mid-latitude glaciation occurred under what were essentially similar physical boundary conditions of continents, oceans, seaways and mountain ranges that characterise, and are unique to, the Quaternary. It is desirable that all stratigraphical and geochronological evidence is tied rigorously into the Global Stratigraphic Timescale. Copyright © 2007 John Wiley & Sons, Ltd. [source] Acute Ethanol Exposure Combined With Burn Injury Enhances IL-6 Levels in the Murine IleumALCOHOLISM, Issue 10 2007Michael T. Scalfani Background:, Recent studies suggest that ethanol use imposes a greater risk of trauma-associated intestinal injury than trauma alone. The initiating and regulatory factors for multiple organ dysfunction syndromes are not well defined, yet evidence points to the gut as a possible trigger of the systemic inflammatory cascade as well as a potential source of cytokines. In the current study, we hypothesized that ethanol administration would alter cytokine levels and intestinal infiltration by neutrophils within the ileum of mice exposed to burn injury (15% total body surface of dorsal skin). Methods:, Ileal samples were collected for histological assessment, myeloperoxidase quantitation and the protein presence of tumor necrosis factor alpha (TNF,), interleukin (IL-) 6, macrophage inflammatory protein-2 (MIP-2; CXCL2) and the anti-inflammatory cytokine, IL-10. Additional ileal tissue samples were examined for localization of the IL-6 immunoreactivity. Results:, We did not detect statistically significant cytokine/chemokine differences (MIP-2 and IL-10) between sham control and treatment conditions at either 2 or 24 hours. However, there was a significant decrease in TNF, at 24 hours in both burn injury alone and in combination with ethanol treatment conditions (p < 0.05). In addition, there was an increase in IL-6 levels at 24 hours in intestinal tissue obtained from mice subjected to a combination of acute ethanol and burn injury, compared to the mice receiving burn or sham injury (p < 0.001). Ileal homogenate increases in IL-6 at 24 hours were concurrent with decreased villus height in the ileum, but no discernable changes in neutrophil infiltration (myeloperoxidase activity levels) at either 2 or 24 hours. Additional immunocytochemical localization studies of ileal tissue revealed that there was a substantial increase of IL-6 in intestinal enterocytes subjected to both burn injury alone, or in combination with acute ethanol exposure. Conclusions:, The present study suggests that acute ethanol exposure combined with burn injury enhances levels of IL-6 protein in the ileum. The enhanced levels of ileal IL-6 are likely due to enterocyte production of the cytokine. [source] Antioxidant Protection Mechanisms And Arachidonic Acid Synthesis Are Altered In Schwann Cells Grown In Elevated GlucoseJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 3 2000C Miinea Accumulating evidence points to oxidative stress as an important factor in the onset of diabetic neuropathy. We have investigated the status of antioxidant protection mechanisms in immortalized rat Schwann cells cultured in high (30 and 50 mM) concentrations of glucose. As compared to growth in 5 mM glucose, the cells contained 40% less reduced glutathione (n =8, p < 0.01). Total superoxide dismutase activity was diminished by more than 50% (n=3; p < 0.001), whereas catalase activity was unchanged. The cellular NADH/NAD+ ratio was progressively increased with increasing medium glucose concentrations. Our previous findings have established that upon exposure of cultured cells to elevated glucose, the proportions of arachidonic acid-containing molecular species (ACMS) in phospholipids are decreased in a pattern similar to alterations exhibited by diabetic nerve. To examine whether biosynthesis of arachidonic acid might be perturbed, confluent cells maintained in either high or low glucose were incubated with either [14C]linoleic acid (18:2) or [14C]dihomo-,-linolenic acid (20:3) and radioactivity incorporated into molecular species of major phospholipid classes was measured. The incorporation of 18:2 either as unchanged fatty acid or into ACMS did not differ as a function of glucose concentration. Negligible labeled 18:3 or 20:3 molecular species were detected. In contrast, the uptake of 20:3 into 18:1/20:4 and 16:0/20:4 phosphatidylcholine and 18:1/20:4 phosphatidylethanolamine, but not into 20:3-containing molecular species, was significantly reduced in cells cultured in 30 mM glucose. These data imply that ,5 desaturase activity is decreased in cells exposed to elevated glucose. This reduced enzyme activity could adversely affect polyunsaturated fatty acid metabolism and might arise as a consequence of impaired scavenging of reactive oxygen species. (Supported by NIH grant DK30577) [source] The ,3 integrin cytoplasmic tail: protein scaffold and control freakJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 2009S. J. SHATTIL Summary., Platelet integrin ,IIb,3 plays an essential role in thrombus formation through interactions with adhesive ligands. Successful parenteral blockade of these interactions has validated ,IIb,3 as a therapeutic target in cardiovascular medicine. However, oral ,IIb,3 antagonists have not been successful and there is an unmet need for more effective anti-platelet drugs. Growing evidence points to the cytoplasmic tails of ,IIb and ,3, and the ,3 tail in particular, as scaffolds for intracellular proteins that mediate inside-out signaling and regulate ,IIb,3 affinity for ligands. Intracellular protein interactions with the integrin cytoplasmic tails also regulate outside-in signals to the actin cytoskeleton. Here we focus on recent studies that illustrate the relevance of the ,3 cytoplasmic tail as a regulatory scaffold in vivo. We speculate that this scaffold or its interacting proteins may serve as therapeutic targets for the development of future anti-thrombotic drugs. [source] | ||||||||||||||||||||||||||||||||||