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Selected AbstractsPrevalence and correlates of traumatic brain injury among delinquent youthsCRIMINAL BEHAVIOUR AND MENTAL HEALTH, Issue 4 2008Brian E. Perron Background,Delinquent youth frequently exhibit high-risk behaviours that can result in serious injury. However, little is known about traumatic brain injuries (TBIs) and their correlates in this population. Aims,To examine the period prevalence and correlates of TBIs in delinquent youths. Method,Interviews were conducted with 720 (97.3%) residents of 27 Missouri Division of Youth Services rehabilitation facilities between March 1 and May 31, 2003. Participants [mean age (Mage) = 15.5, standard deviation (SD) = 1.2, 87% male] completed measures assessing TBI, substance use, psychiatric symptoms, and antisocial traits/behaviours. TBI was defined as ever having sustained a head injury causing unconsciousness for more than 20 minutes. Results,Nearly one-in-five youths (18.3%) reported a lifetime TBI. Youths with TBIs were significantly more likely than youths without to be male, have received a psychiatric diagnosis, report an earlier onset of criminal behaviour/substance use and more lifetime substance use problems and past-year criminal acts, evidence psychiatric symptoms, report lifetime suicidality, be impulsive, fearless, and external in locus of control and criminally victimized in the year preceding incarceration. Male gender and frequency of own criminal victimization were important predictors of TBI in multivariate analyses. Regression analyses adjusted for demographic factors, indicated that youths with TBIs were at significantly elevated risk for current depressive/anxious symptoms, antisocial behaviour, and substance abuse problems. Conclusions,TBI is common among delinquent youth and associated with wide ranging psychiatric dysfunction; however, the causal role of TBIs in the pathogenesis of co-morbid conditions remains unclear. Copyright © 2008 John Wiley & Sons, Ltd. [source] Matrix metalloproteinases mediate the dismantling of mesenchymal structures in the tadpole tail during thyroid hormone-induced tail resorptionDEVELOPMENTAL DYNAMICS, Issue 3 2002Jae-Chang Jung Abstract It has been suggested that a family of tissue remodelling enzymes called matrix metalloproteinases (MMPs) play a causal role in the process of tail resorption during thyroid hormone-induced metamorphosis of the anuran tadpole; however, this hypothesis has never been directly substantiated. We cloned two new Xenopus MMPs, gelatinase A (MMP-2) and MT3-MMP (MMP-16), and the MMP inhibitor TIMP-2. These clones were used along with several others to perform a comprehensive expression study. We show that all MMPs and TIMP-2 are dramatically induced in the resorbing tail during spontaneous metamorphosis and are spatially coexpressed, primarily in the remodelling mesenchymal tissues. By Northern blotting, we show that all the examined MMPs/TIMP-2 are also induced by treatment of organ-cultured tails with thyroid hormone (T3). Using the organ culture model, we provide the first direct evidence that MMPs are required for T3 -induced tail resorption by showing that a synthetic inhibitor of MMP activity/expression can specifically retard the resorption process. By gelatin zymography, we also show T3 induction of a fifth MMP, preliminarily identified as gelatinase B (GelB; MMP-9). Moreover, T3 not only induces MMP/TIMP expression but also MMP activation, and we provide evidence that TIMP-2 participates in the latter process. These findings suggest that MMPs and TIMPs act in concert to effect the dismantling of mesenchymal structures during T3 -induced metamorphic tadpole tail resorption. © 2002 Wiley-Liss, Inc. [source] Hyperphagia and obesity of OLETF rats lacking CCK1 receptors: Developmental aspectsDEVELOPMENTAL PSYCHOBIOLOGY, Issue 5 2006Timothy H. Moran Abstract Otsuka Long Evans Tokushima Fatty (OLETF) rats have a deletion in the gene encoding the cholecystokinin,1 (CCK1) receptor. This deletion prevents protein expression, making the OLETF rat a CCK1 receptor knockout model. Consistent with the absence of CCK1 receptors, OLETF rats do not reduce their food intake in response to exogenously administered CCK and consume larger than normal meals. This deficit in within-meal feedback signaling is evident in liquid as well as solid meals. Neonatal OLETF rats show similar differences in independent ingestion tests. Intake is higher and is reflected in greater licking behavior. Neonatal OLETF rats also have diminished latencies to consume and higher initial ingestion rats. Adult OLETF rats are hyperphagic and obese. Although arcuate nucleus peptide gene expression is apparently normal in OLETF rats, when obesity is prevented through pair-feeding to amounts consumed by control Long Evans Tokushima Otsuka (LETO) rats, dorsomedial hypothalamic NPY mRNA expression is significantly elevated in OLETF rats. NPY overexpression is also evident in preobese, juvenile OLETF rats suggesting a causal role for this overexpression in the hyperphagia and obesity. Running wheel exercise normalizes food intake and body weight in OLETF rats. When access to exercise is provided at a time when OLETF rats are obese, the effects are limited to the period of exercise. When running wheel access is available to younger, preobese OLETF rats, exercise results in long lasting reductions in food intake and body weight and improved glucose regulation. These lasting metabolic effects of exercise may be secondary to an exercise induced reduction in DMH NPY mRNA expression. © 2006 Wiley Periodicals, Inc. Dev Psychobiol 48: 360,367, 2006. [source] Developmental profiles for multiple object tracking and spatial memory: typically developing preschoolers and people with Williams syndromeDEVELOPMENTAL SCIENCE, Issue 3 2010Kirsten O'Hearn The ability to track moving objects, a crucial skill for mature performance on everyday spatial tasks, has been hypothesized to require a specialized mechanism that may be available in infancy (i.e. indexes). Consistent with the idea of specialization, our previous work showed that object tracking was more impaired than a matched spatial memory task in individuals with Williams syndrome (WS), a genetic disorder characterized by severe visuo-spatial impairment. We now ask whether this unusual pattern of performance is a reflection of general immaturity or of true abnormality, possibly reflecting the atypical brain development in WS. To examine these two possibilities, we tested typically developing 3- and 4-year-olds and people with WS on multiple object tracking (MOT) and memory for static spatial location. The maximum number of objects that could be correctly tracked or remembered (estimated from the k -statistic) showed similar developmental profiles in typically developing 3- and 4-year-old children, but the WS profile differed from either age group. People with WS could track more objects than 3-year-olds, and the same number as 4-year-olds, but they could remember the locations of more static objects than both 3- and 4-year-olds. Combining these data with those from our previous studies, we found that typically developing children show increases in the number of objects they can track or remember between the ages of 3 and 6, and these increases grow in parallel across the two tasks. In contrast, object tracking in older children and adults with WS remains at the level of 4-year-olds, whereas the ability to remember multiple locations of static objects develops further. As a whole, the evidence suggests that MOT and memory for static location develop in tandem typically, but not in WS. Atypical development of the parietal lobe in people with WS could play a causal role in the abnormal, uneven pattern of performance in WS. This interpretation is consistent with the idea that multiple object tracking engages different mechanisms from those involved in memory for static object location, and that the former can be particularly disrupted by atypical development. [source] The role of sensorimotor impairments in dyslexia: a multiple case study of dyslexic childrenDEVELOPMENTAL SCIENCE, Issue 3 2006Sarah White This study attempts to investigate the role of sensorimotor impairments in the reading disability that characterizes dyslexia. Twenty-three children with dyslexia were compared to 22 control children, matched for age and non-verbal intelligence, on tasks assessing literacy as well as phonological, visual, auditory and motor abilities. The dyslexic group as a whole were significantly impaired on phonological, but not sensorimotor, tasks. Analysis of individual data suggests that the most common impairments were on phonological and visual stress tasks and the vast majority of dyslexics had one of these two impairments. Furthermore, phonological skill was able to account for variation in literacy skill, to the exclusion of all sensorimotor factors, while neither auditory nor motor skill predicted any variance in phonological skill. Visual stress seems to account for a small proportion of dyslexics, independently of the commonly reported phonological deficit. However, there is little evidence for a causal role of auditory, motor or other visual impairments. [source] Oestrogen withdrawal associated psychosesACTA PSYCHIATRICA SCANDINAVICA, Issue 5 2001V. Mahé Objective: Oestrogen withdrawal has been hypothesized as playing a causal role in puerperal psychoses. However, oestrogen withdrawal exists in conditions others than puerperium. We searched the published case reports where a decrease in oestrogen levels not occurring during puerperium was associated with a psychotic disorder, in order to evaluate the relevance of this hypothesis. These cases were defined as oestrogen withdrawal associated psychoses. Method: A systematic research of the literature was conducted for the period 1960,2000. Results: We identified 26 observations reporting an association between a psychotic disorder and a phase of oestrogen withdrawal. Psychotic episodes were short and reversible with recurrences reported when oestrogen withdrawal recurred. Puerperal psychosis was frequently reported in the history of patients. Conclusion: The oestrogen withdrawal hypothesis can be extended to certain psychotic episodes not occurring during in puerperium. This provides an additional argument for the clinical relevance of oestrogen withdrawal in puerperal and related psychoses. [source] A Possible Role for Gap Junctions in Generation of Very Fast EEG Oscillations Preceding the Onset of, and Perhaps Initiating, SeizuresEPILEPSIA, Issue 2 2001Roger D. Traub Summary: ,Purpose: We propose an experimentally and clinically testable hypothesis, concerning the origin of very fast (>,70 Hz) EEG oscillations that sometimes precede the onset of focal seizures. These oscillations are important, as they may play a causal role in the initiation of seizures. Methods: Subdural EEG recordings were obtained from children with focal cortical dysplasias and intractable seizures. Intra- and extracellular recordings were performed in rat hippocampal slices, with induction of population activity, as follows: (a) bath-applied tetramethylamine (an intracellular alkalinizing agent, that opens gap junctions); (b) bath-applied carbachol, a cholinergic agonist; and (c) focal pressure ejection of hypertonic K+ solution. Detailed network simulations were performed, the better to understand the cellular mechanisms underlying oscillations. A major feature of the simulations was inclusion of axon,axon gap junctions between principal neurons, as supported by recent experimental data. Results: Very fast oscillations were found in children before seizure onset, but also superimposed on bursts during the seizure, and on interictal bursts. In slice experiments, very fast oscillations had previously been seen on interictal-like bursts; we now show such oscillations before, between, and after epileptiform bursts. Very fast oscillations were also seen superimposed on gamma (30,70 Hz) oscillations induced by carbachol or hypertonic K+, and in the latter case, very fast oscillations became continuous when chemical synapses were blocked. Simulations replicate these data, when axonal gap junctions are included. Conclusions: Electrical coupling between principal neurons, perhaps via axonal gap junctions, could underlie very fast population oscillations, in seizure-prone brain, but possibly also in normal brain. The anticonvulsant potential of gap-junction blockers such as carbenoxolone, now in clinical use for treatment of ulcer disease, should be considered. [source] Functional specificity of human premotor,motor cortical interactions during action selectionEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2007Jacinta O'Shea Abstract Functional connections between dorsal premotor cortex (PMd) and primary motor cortex (M1) have been revealed by paired-pulse transcranial magnetic stimulation (TMS). We tested if such connections would be modulated during a cognitive process (response selection) known to rely on those circuits. PMd,M1 TMS applied 75 ms after a cue to select a manual response facilitated motor-evoked potentials (MEPs). MEPs were facilitated at 50 ms in a control task of response execution, suggesting that PMd,M1 interactions at 75 ms are functionally specific to the process of response selection. At 100 ms, PMd,M1 TMS delayed choice reaction time (RT). Importantly, the MEP (at 75 ms) and the RT (at 100 ms) effects were correlated in a way that was hand-specific. When the response was made with the M1-contralateral hand, MEPs correlated with slower RTs. When the response was made with the M1-ipsilateral hand, MEPs correlated with faster RTs. Paired-pulse TMS confined to M1 did not produce these effects, confirming the causal influence of PMd inputs. This study shows that a response selection signal evolves in PMd early during the reaction period (75,100 ms), impacts on M1 and affects behaviour. Such interactions are temporally, anatomically and functionally specific, and have a causal role in choosing which movement to make. [source] Is there more assimilation in Catalonia than in the Basque Country?EUROPEAN JOURNAL OF POLITICAL RESEARCH, Issue 6 2008Analysing dynamics of assimilation in nationalist contexts This article builds on recent attempts in political science to illuminate the ,micro-level' mechanisms of identity formation. It analyses the dynamics of assimilation in two similar contexts with extremely salient regional-nationalist movements: Catalonia and the Basque Country. It poses the question: In which of the two regions has there been more assimilation of demographically significant, internal-immigrant segments of the population? It tests whether there has been more assimilation in Catalonia , a result expected from the allegedly more ,civic' nature of the nationalist movement there. To do so, it draws on and goes beyond the tools provided by David Laitin for operationalising assimilation. It uses existing public opinion surveys to construct and present assimilation indices for both regions. The authors show that though rates of ,linguistic adaptation' are higher in Catalonia, such adaptation correlates weakly with assimilation into feelings of subjective identification and the espousal of nationalist views and aspirations more generally. The article goes on to demonstrate that rates of assimilation, when measured using several more robust proxies for the feeling of national identity, are actually lower in Catalonia. The authors then proceed to provide a theoretical explanation for their surprising empirical results. The explanation stresses the causal role of institutional pressures , themselves the product of nationalist coalition-building strategies , in accounting for patterns of linguistic adaptation and of cultural assimilation. Furthermore, it emphasises the relevance of ,cultural demography', particularly among natives/insiders, in accounting for the different nationalist strategies and the different intensity as well as different types of institutional pressures faced by immigrants/outsiders in the two regions. [source] THE CONTRIBUTION OF AN HOURGLASS TIMER TO THE EVOLUTION OF PHOTOPERIODIC RESPONSE IN THE PITCHER-PLANT MOSQUITO, WYEOMYIA SMITHIIEVOLUTION, Issue 10 2003W. E. Bradshaw Abstract Photoperiodism, the ability to assess the length of day or night, enables a diverse array of plants, birds, mammals, and arthropods to organize their development and reproduction in concert with the changing seasons in temperate climatic zones. For more than 60 years, the mechanism controlling photoperiodic response has been debated. Photoperiodism may be a simple interval timer, that is, an hourglasslike mechanism that literally measures the length of day or night or, alternatively, may be an overt expression of an underlying circadian oscillator. Herein, we test experimentally whether the rhythmic response in Wyeomyia smithii indicates a causal, necessary relationship between circadian rhythmicity and the evolutionary modification of photoperiodic response over the climatic gradient of North America, or may be explained by a simple interval timer. We show that a day-interval timer is sufficient to predict the photoperiodic response of W. smithii over this broad geographic range and conclude that rhythmic responses observed in classical circadian-based experiments alone cannot be used to infer a causal role for circadian rhythmicity in the evolution of photoperiodic time measurement. More importantly, we argue that the pursuit of circadian rhyth-micity as the central mechanism that measures the duration of night or day has distracted researchers from consideration of the interval-timing processes that may actually be the target of natural selection linking internal photoperiodic time measurement to the external seasonal environment. [source] CD4+CD25hi regulatory T-cell frequency correlates with persistence of human papillomavirus type 16 and T helper cell responses in patients with cervical intraepithelial neoplasiaINTERNATIONAL JOURNAL OF CANCER, Issue 8 2007Johan W. Molling Abstract CD4+CD25hiCTLA4+FoxP3+ regulatory T cells (Treg) have been shown to maintain immune tolerance against self antigens and increased circulating frequencies have been reported in various types of cancers. Circulating invariant natural killer T-cells (iNKT) are reduced in cancer patients and low iNKT frequency is related to poor prognosis. It is not yet clear whether high Treg numbers and low iNKT cell numbers pose an increased risk for the progression of premalignant lesions or whether Treg and iNKT cell numbers are influenced by dysplasia. We therefore studied prospectively the relation between iNKT cell and Treg frequencies and the natural course of human papillomavirus type 16 (HPV16) induced pre-malignant cervical dysplasia in 82 patients who participated in a nonintervention cohort study of women with abnormal cytology. Treg frequencies were significantly increased in women who had persistent HPV16 infection. Within the HPV16 persistence group there was no difference in Treg frequencies among patients who developed a CIN3 lesion and patients who did not progress to CIN3. Furthermore, Treg frequencies were increased in patients who had detectable HPV16 E7 specific IL-2 producing T-helper cells, which suggests a causal role of HPV infection in Treg development in parallel with HPV16 specific T helper cells. No evidence was found for a role for iNKT cells in persistence of HPV16 and progression of HPV16 induced CIN lesions. However, HPV-persistence-associated Tregs may explain the inefficacy of concomitant persistence associated immunity and may contribute to subsequent progression to neoplasia. © 2007 Wiley-Liss, Inc. [source] Identification of antigenic targets of paraproteins by expression cloning does not support a causal role of chronic antigenic stimulation in the pathogenesis of multiple myeloma and MGUSINTERNATIONAL JOURNAL OF CANCER, Issue 2 2007Klaus-Dieter Preuss Abstract Antigenic targets of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) paraproteins have been suggested to play an important role as growth stimulators in the pathogenesis of these neoplasms. To identify such targets, we screened cDNA libraries from human testis, lung and breast cancer, bovine and porcine muscle and wheat germ for reactivity with paraproteins in the sera from 115 patients with MGUS and MM. Of >6 × 108 paraprotein,antigen interactions screened, an IgA paraprotein from a female patient bound to sperm-specific cylicin-2, and 3 IgG paraproteins bound to tripeptidyl-peptidase-II (TPP-2), insulin-like growth-factor binding-protein-2 (IGFBP-2) and porcine kinesin. Specificity was confirmed by reverse Western blots using recombinant antigens. The broad spectrum of auto-, allo- and heteroantigens as targets of human paraproteins in patients without signs of chronic antigenic stimulation renders a causal role of the antigenic stimulus in the pathogenesis of MGUS and MM unlikely. © 2007 Wiley-Liss, Inc. [source] Loss of intercellular adhesion activates a transition from low- to high-grade human squamous cell carcinomaINTERNATIONAL JOURNAL OF CANCER, Issue 4 2006Alexander Margulis Abstract The relationship between loss of intercellular adhesion and the biologic properties of human squamous cell carcinoma is not well understood. We investigated how abrogation of E-cadherin-mediated adhesion influenced the behavior and phenotype of squamous cell carcinoma in 3D human tissues. Cell-cell adhesion was disrupted in early-stage epithelial tumor cells (HaCaT-II-4) through expression of a dominant-negative form of E-cadherin (H-2Kd -Ecad). Three-dimensional human tissue constructs harboring either H-2Kd -Ecad-expressing or control II-4 cells (pBabe, H-2Kd -Ecad,C25) were cultured at an air-liquid interface for 8 days and transplanted to nude mice; tumor phenotype was analyzed 2 days and 2 and 4 weeks later. H-2Kd -Ecad-expressing tumors demonstrated a switch to a high-grade aggressive tumor phenotype characterized by poorly differentiated tumor cells that infiltrated throughout the stroma. This high-grade carcinoma revealed elevated cell proliferation in a random pattern, loss of keratin 1 and diffuse deposition of laminin 5 ,2 chain. When II-4 cell variants were seeded into type I collagen gels as an in vitro assay for cell migration, we found that only E-cadherin-deficient cells detached, migrated as single cells and expressed N-cadherin. Function-blocking studies demonstrated that this migration was matrix metalloproteinase-dependent, as GM-6001 and TIMP-2, but not TIMP-1, could block migration. Gene expression profiles revealed that E-cadherin-deficient II-4 cells demonstrated increased expression of proteases and cell-cell and cell-matrix proteins. These findings showed that loss of E-cadherin-mediated adhesion plays a causal role in the transition from low- to high-grade squamous cell carcinomas and that the absence of E-cadherin is an important prognostic marker in the progression of this disease. © 2005 Wiley-Liss, Inc. [source] Renal damage in rats induced by myocardial ischemia/reperfusion: Role of nitric oxideINTERNATIONAL JOURNAL OF UROLOGY, Issue 10 2006HAKAN PARLAKPINAR Background: It has been demonstrated that myocardial ischemia/reperfusion (MI/R) causes renal damage. However, the mechanism underlying this damage in kidneys during revascularization of myocardium is unclear. Direct renal ischemia/reperfusion has been implicated in the induction of inducible nitric oxide synthase (iNOS) that leads to increase production of nitric oxide (NO). Recently, excessive production of NO has been found to be involved in causing renal injury by formatting peroxinitrite (ONOO,). The aim of this study was to investigate whether NO has a role in this damage, using aminoguanidine (AMG), a known iNOS inhibitor and an antioxidant, in rats undergoing MI/R. Methods: Male Wistar rats were used for the experiments (n = 7 each group). In the MI/R group, the left coronary artery was occluded for 30 min and then reperfused for 120 min; the same procedure was used for the AMG group, with the additional step of AMG (200 mg/kg) administered 10 min prior to ischemia. A control group underwent sham operation. At the end of the reperfusion period, all rats were killed and their kidneys removed for biochemical determination and histopathological analysis. Results: Myocardial ischemia/reperfusion in the rat kidney was accompanied by a significant increase in malondialdehyde and NO production, and a decrease in glutathione content. Administration of AMG reduced malondialdehyde and NO production and prevented depletion of glutathione content. These beneficial changes in the biochemical parameters were also associated with parallel changes in histopathological appearance. Conclusion: These findings suggest that MI/R plays a causal role in kidney injury and AMG exerts renal-protective effects, probably by inhibiting NO production and antioxidant activities. [source] Sex Hormones and Sexual DesireJOURNAL FOR THE THEORY OF SOCIAL BEHAVIOUR, Issue 1 2008JAMES GILES ABSTRACT Some scholars attempt to explain sexual desire biologically by claiming that sex hormones play a necessary causal role in sexual desire. This can be claimed even if sexual desire is seen to be an experience. Yet the evidence for such biological essentialism is inadequate. With males the loss of sexual desire following hormonal changes can easily be explained in terms of social stigmas that are attached to the physiological situation. Concerning females, the relevance of sex hormones here is even more unclear. Although some women seem to have fluctuations in sexual desire during hormonal changes, other women do not. Even where there are such fluctuations these can be explained by responses to other physiological changes or the meanings that are attached to the situation. Research with non-human primates supports this view of the non-essential relation of sex hormones to sexual desire. A phenomenology of sex hormones is given that shows a possible non-essential relation between sex hormones and sexual desire. Here hormone induced excitations in the genitals may or may not lead to sexual desire depending on the meaning they are given within awareness. This suggests that sexual desire has its origin in the meanings we give our biology and not in our biology itself. [source] Density effects on life-history traits in a wild population of the great tit Parus major: analyses of long-term data with GIS techniquesJOURNAL OF ANIMAL ECOLOGY, Issue 2 2006TEDDY A. WILKIN Summary 1Population density often has strong effects on the population dynamics and reproductive processes of territorial animals. However, most estimates of density-dependent effects use the number of breeding pairs per unit area in a given season and look for correlations across seasons, a technique that assigns the same density score to each breeding pair, irrespective of local spatial variation. 2In this study, we employed GIS techniques to estimate individual breeding densities for great tits breeding in Wytham Woods UK, between 1965 and 1996. We then used linear mixed modelling to analyse the effect of density on reproductive processes. 3The areas of Thiessen polygons formed around occupied nestboxes were used to approximate territory size (necessarily inverse of breeding density). There were significant, independent and positive relationships between clutch size, fledging mass and the number of offspring recruited to the population, and territory size (all P < 0·001), but no effect of territory size on lay-date or egg mass. 4Thiessen polygons are contiguous and cover all of the available area. Therefore, at low nest densities territory polygons were excessively oversized. Using a novel procedure to address this limitation, territory sizes were systematically capped through a range of maxima, with the greatest effect in the models when territories were capped at 0·9,2·3 ha. This figure approximates to the maximum effective territory size in our population and is in close agreement with several field-based studies. This capping refinement also revealed a significant negative relationship between lay-date and territory size capped at 0·9 ha (P < 0·001). 5These density-dependent effects were also detected when analyses were restricted to changes within individual females, suggesting that density effects do not merely result from either increased proportions of low-quality individuals, or increased occupation of poor sites, when population density is high. 6Overall, these results suggest that, in the current population, great tits with territories smaller than c. 2 ha independently lay smaller and later clutches, have lighter fledglings, and recruit fewer offspring to the breeding population. These analyses thus suggest a pervasive and causal role of local population density in explaining individual reproductive processes. [source] Concentration of aluminium in breast cyst fluids collected from women affected by gross cystic breast diseaseJOURNAL OF APPLIED TOXICOLOGY, Issue 1 2009Ferdinando Mannello Abstract Gross cystic breast disease (GCBD) is the most common benign breast disorder, but the molecular basis of cyst formation remains to be identified. If the use of aluminium-based antiperspirant salts is involved in the etiology of gross breast cyst formation, it might be expected that aluminium would be at elevated levels in human breast cyst fluid (BCF). Aluminium was measured by ICP-MS in 48 samples of BCF, 30 samples of human blood serum and 45 samples of human breast milk at different stages of lactation (colostrum, intermediate, mature). The median level of aluminium in apocrine type I BCF (n = 27, 150 µg l,1) was significantly higher than in transudative type II BCF (n = 21, 32 µg l,1; P <0.0001). By comparison, aluminium measurements gave a median concentration of 6 µg l,1 in human serum and 25 µg l,1 in human breast milk, with no difference between colostrum, intermediate and mature milk. Levels of aluminium were significantly higher in both types of BCF than in human serum (P <0.0001). However when compared with human breast milk, aluminium levels were only significantly higher in apocrine type I BCF (P <0.0001) and not in transudative type II BCF (P = 0.152). It remains to be identified why such high levels of aluminium were found in the apocrine type I BCF and from where the aluminium originated. However, if aluminium-based antiperspirants are found to be the source and to play any causal role in development of breast cysts, then it might become possible to prevent this common breast disorder. Copyright © 2008 John Wiley & Sons, Ltd. [source] Long-Term Leisure Time Physical Activity and Properties of Bone: A Twin Study,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2009Hongqiang Ma Abstract Effects of physical activity on bone properties, when controlled for genetic effects, are not fully understood. We aimed to study the association between long-term leisure time physical activity (LTPA) and bone properties using twin pairs known to be discordant for leisure time physical activity for at least 30 yr. Volumetric BMD and geometric properties were measured at the tibia shaft and distal end using pQCT in 16 middle-aged (50,74 yr) same-sex twin pairs (seven monozygotic [MZ] and nine dizygotic [DZ] pairs) selected from a population-based cohort. Paired differences between active and inactive co-twins were studied. Active members of MZ twin pairs had larger cortical bone cross-sectional area (intrapair difference: 8%, p = 0.006), thicker cortex (12%, p = 0.003), and greater moment of inertia (Imax, 20%, p = 0.024) at the tibia shaft than their inactive co-twins. At the distal tibia, trabecular BMD (12%, p = 0.050) and compressive strength index (18%, p = 0.038) were also higher in physically active MZ pair members than their inactive co-twins. The trends were similar, but less consistently so, in DZ pairs as in MZ pairs. Our genetically controlled study design shows that LTPA during adulthood strengthens bones in a site-specific manner, that is, the long bone shaft has a thicker cortex, and thus higher bending strength, whereas the distal bone has higher trabecular density and compressive strength. These results suggest that LTPA has a potential causal role in decreasing the long-term risk of osteoporosis and thus preventing osteoporotic fractures. [source] Downregulation of miR-122 in the rodent and human hepatocellular carcinomasJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 3 2006Huban Kutay Abstract MicroRNAs (miRs) are conserved small non-coding RNAs that negatively regulate gene expression. The miR profiles are markedly altered in cancers and some of them have a causal role in tumorigenesis. Here, we report changes in miR expression profile in hepatocellular carcinomas (HCCs) developed in male Fisher rats-fed folic acid, methionine, and choline-deficient (FMD) diet. Comparison of the miR profile by microarray analysis showed altered expression of some miRs in hepatomas compared to the livers from age-matched rats on the normal diet. While let-7a, miR-21, miR-23, miR-130, miR-190, and miR-17-92 family of genes was upregulated, miR-122, an abundant liver-specific miR, was downregulated in the tumors. The decrease in hepatic miR-122 was a tumor-specific event because it did not occur in the rats switched to the folate and methyl-adequate diet after 36 weeks on deficient diet, which did not lead to hepatocarcinogenesis. miR-122 was also silent in a transplanted rat hepatoma. Extrapolation of this study to human primary HCCs revealed that miR-122 expression was significantly (P,=,0.013) reduced in 10 out of 20 tumors compared to the pair-matched control tissues. These findings suggest that the downregulation of miR-122 is associated with hepatocarcinogenesis and could be a potential biomarker for liver cancers. J. Cell. Biochem. 99: 671,678, 2006. © 2006 Wiley-Liss, Inc. [source] Explaining adult homelessness in the US by stratification or situationJOURNAL OF COMMUNITY & APPLIED SOCIAL PSYCHOLOGY, Issue 2 2003Michael R. Sosin Abstract In the US, the most widely accepted individual-level explanations of homelessness suggest that adults lose their dwellings when they cannot compete in the marketplace for the monetary resources needed to pay for housing, and cannot compete in a non-market struggle for compensatory resources. Such resource problems allegedly typically reflect myriad lifetime and current personal problems or deficits. However, the causal role of the problems and deficits is now known to be complex, and evidence about transitions in and out of homelessness suggests that key events occur somewhat independently of easily measured individual problems or deficits. This article, therefore, provides an alternative explanatory approach that directly focuses on aspects of the probabilistic situations that spur, or fail to reverse homelessness. The events and resource issues are posited to give rise to episodes of homelessness that vary in length, that are indirectly affected by many commonly mentioned individual traits, and that can be matched to targeted policies. Copyright © 2003 John Wiley & Sons, Ltd. [source] DNA damage response and cellular senescence in tissues of aging miceAGING CELL, Issue 3 2009Chunfang Wang Summary The impact of cellular senescence onto aging of organisms is not fully clear, not at least because of the scarcity of reliable data on the mere frequency of senescent cells in aging tissues. Activation of a DNA damage response including formation of DNA damage foci containing activated H2A.X (,-H2A.X) at either uncapped telomeres or persistent DNA strand breaks is the major trigger of cell senescence. Therefore, ,-H2A.X immunohistochemistry (IHC) was established by us as a reliable quantitative indicator of senescence in fibroblasts in vitro and in hepatocytes in vivo and the age dependency of DNA damage foci accumulation in ten organs of C57Bl6 mice was analysed over an age range from 12 to 42 months. There were significant increases with age in the frequency of foci-containing cells in lung, spleen, dermis, liver and gut epithelium. In liver, foci-positive cells were preferentially found in the centrilobular area, which is exposed to higher levels of oxidative stress. Foci formation in the intestine was restricted to the crypts. It was not associated with either apoptosis or hyperproliferation. That telomeres shortened with age in both crypt and villus enterocytes, but telomeres in the crypt epithelium were longer than those in villi at all ages were confirmed by us. Still, there was no more than random co-localization between ,-H2A.X foci and telomeres even in crypts from very old mice, indicating that senescence in the crypt enterocytes is telomere independent. The results suggest that stress-dependent cell senescence could play a causal role for aging of mice. [source] Life events as a risk factor for psychological problems in individuals with intellectual disabilities: a critical reviewJOURNAL OF INTELLECTUAL DISABILITY RESEARCH, Issue 11 2008L. Hulbert-Williams Abstract Background Stressful life events such as bereavement, moving house and changing jobs have repeatedly been implicated as risk factors for mental and physical ill health. Since the 1940s, researchers have demonstrated the negative effects of stressful life events, refined methods of recording such events and investigated the relative impact of different types of event. These investigations have generally not extended to include people with intellectual disabilities. Methods We conducted a narrative review of research on life events as they occur to people with intellectual disabilities and critically assessed the evidence that life events function as a risk factor for psychological problems. Evidence was reviewed for an association between life events and a range of outcome variables, including affective disorders, challenging behaviour, psychosis and psychological problems more generally. We also critiqued the methodology behind the current evidence base and discussed a number of methodological advances that would help to strengthen it. Conclusions There is reasonable evidence that life events are associated with psychological problems, and that there is some tentative evidence that life events play a causal role, although to date, no relationship with psychosis in people with intellectual disabilities has been demonstrated. Life events are likely to be pertinent in clinical work with people with intellectual disabilities. [source] The Well-Being of Children Born to Teen MothersJOURNAL OF MARRIAGE AND FAMILY, Issue 1 2007Judith A. Levine Children born to early child bearers are more likely than other children to display problem behaviors or poor academic performance, but it is unclear whether early childbearing plays a causal role in these outcomes. Using multiple techniques to control for background factors, we analyze 2,908 young children and 1,736 adolescents and young adults in the National Longitudinal Survey of Youth (NLSY79) and the NLSY79 Children and Young Adults (CNLSY79) data sets to examine whether early childbearing causes children's outcomes. We find evidence that teen childbearing plays no causal role in children's test scores and in some behavioral outcomes of adolescents. For other behavioral outcomes, we find that different methodologies produce differing results. We thus suggest caution in drawing conclusions about early parenthood's overarching effect. [source] The Influence of In-Laws on Change in Marital SuccessJOURNAL OF MARRIAGE AND FAMILY, Issue 3 2001Chalandra M. Bryant This study prospectively examines the association between discord with in-laws and the long-term relationship success of husbands and wives who had been married for an average of almost 2 decades. We hypothesized that the quality of spouses' relationships with their parents-in-law would predict spouses' marital success. In addition, this study underscores the causal role of in-laws by examining the influence of marital success on relationships with in-laws. For wives, discord with mothers- and fathers-in-law predicted own perceptions of marital success at a later time period. Results were slightly different for husbands' discord with fathers-in-law. The reverse (marital success predicting less discord with in-laws) was only true for husbands. The study also explored the influence of spouses' discord with in-laws on partners' perceptions of marital success. These are among the first prospective, longitudinal findings demonstrating that, even in long-term marriages, conflicts in extended family relations will erode marital stability, satisfaction, and commitment over time. [source] Depressive Symptoms in Early Adolescence: Their Relations with Classroom Problem Behavior and Peer StatusJOURNAL OF RESEARCH ON ADOLESCENCE, Issue 4 2002Jeff Kiesner It has been suggested that early antisocial behavior plays a causal role in the development of depression during childhood and adolescence through pervasive failures in social competence and social acceptance (Patterson & Capaldi, 1990). The present study was conducted to test this hypothesis by examining longitudinal data from a sample of 215 Italian middle school students. Analyses revealed that Time 1 (T1) problem behavior predicted both Time 2 (T2) peer status and T2 depressive symptoms, even after controlling for T1 peer status and depressive symptoms, respectively. Moreover, T1 peer status predicted depressive symptoms at T2, even after controlling for prior levels of depressive symptoms. However, analyses did not support the hypothesis that peer rejection mediates the effects of problem behavior on depression. [source] Emerging role of mitogen-activated protein kinases in peripheral neuropathiesJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 3 2007Guido Cavaletti Abstract Among the different families of intracellular molecules that can be modulated during cell damage and repair, mitogen-activated protein kinases (MAPKs) are particularly interesting because they are involved in several intracellular pathways activated by injury and regeneration signals. Despite most of the studies have been performed in non-neurological models, recently a causal role for MAPKs has been postulated in central nervous system disorders. However, also in some peripheral neuropathies, MAPK changes can occur and these modifications might be relevant in the pathogenesis of the damage as well as during regeneration and repair. In this review, the current knowledge on the role of MAPKs in peripheral neuropathies will be discussed. [source] Genetic variants and haplotypes of lipoprotein associated phospholipase A2 and their influence on cardiovascular disease (The Ludwigshafen Risk and Cardiovascular Health Study)JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 1 2009M. M. HOFFMANN Summary.,Background:, There is increasing evidence that lipoprotein-associated phospholipase A2 (LpPLA2) is associated with cardiovascular disease. However, it is still unclear whether LpPLA2 is simply a marker or has a causal role as either a pro- or anti-atherogenic factor. Methods:, We analyzed the association of five polymorphisms (,1357G>A, ,403T>C, Arg92His, Ile198Thr, Ala379Val) and related haplotypes at the PLA2G7 locus with angiographic coronary artery disease (CAD), plasma LpPLA2 activity, and long-term survival in 3234 patients scheduled for coronary angiography. Results:, The promoter variant ,403C and His92 were associated with a decrease and Val379 with an increase in plasma LpPLA2 activity. Both coding variants revealed a clear gene-dose effect. Interestingly, the rare Thr198 allele, which was not associated with any change in plasma LpPLA2 activity, was more frequent in subjects without CAD (P = 0.009), with an adjusted odds ratio for CAD of 0.69 (95% CI: 0.49,0.96; P = 0.029). None of the analyzed variants showed any robust association with all-cause or cardiovascular mortality. Conclusion:, Irrespective of the significant association between some variants with plasma LpPLA2 activity, it is still unclear whether these polymorphisms or haplotypes are associated with the risk and outcome of cardiovascular disease in Caucasians. [source] The Causal Inefficacy of ContentMIND & LANGUAGE, Issue 1 2009GABRIEL M. A. SEGAL It then articulates a familiar apparent problem concerning the causal role of psychological properties. If they do not reduce to physical properties, then either they must be epiphenomenal or any effects they cause must also be caused by physical properties, and hence be overdetermined. It then argues that both epiphenomenalism and over-determinationism are prima facie perfectly reasonable and relatively unproblematic views. The paper proceeds to argue against Kim's (Kim, 2000, 2005) attempt to articulate a plausible version of reductionism. It is then argued that psychological properties, along with paradigmatically causally efficacious macro-properties, such as toughness, are causally inefficacious in respect of their possessor's typical effects, because they are insufficiently distinct from those effects. It is finally suggested that the distinction between epiphenomenalism and overdeterminationism may be more terminological than real. [source] What's the Role of Spatial Awareness in Visual Perception of Objects?MIND & LANGUAGE, Issue 5 2007JOHN CAMPBELL The first is Lynn Robertson's: (a) spatial awareness is a cause of object perception. A natural counterpoint is: (b) spatial awareness is a cause of your ability to make accurate verbal reports about a perceived object. Zenon Pylyshyn has criticized both. I argue that nonetheless, the burden of the evidence supports both (a) and (b). Finally, I argue conscious visual perception of an object has a different causal role to both: (i) non-conscious perception of the object, and (ii) experience, e.g. hallucination, that may be subjectively indiscriminable from, but is not, perception of the object. [source] Patterns of recurrent evolution and geographic parthenogenesis within apomictic polyploid Easter daises (Townsendia hookeri)MOLECULAR ECOLOGY, Issue 11 2006STACEY LEE THOMPSON Abstract Geographic patterns of parthenogenesis and the number of transitions from sexual diploidy to asexual (apomictic) autopolyploidy were examined for 40 populations of the Easter daisy, Townsendia hookeri. Analyses of pollen diameter and stainability characterized 15 sexual diploid and 25 apomictic polyploid populations from throughout the plant's western North American range. Sexual diploids were restricted to two Wisconsin refugia: Colorado/Wyoming, south of the ice sheets, and northern Yukon/Beringia. Chloroplast DNA sequencing uncovered 17 polymorphisms within the ndhF gene and trnK intron, yielding 10 haplotypes. Phylogenetic analyses indicated that five exclusively polyploid haplotypes were derived from four haplotypes that are shared among ploidies, conservatively inferring a minimum of four origins of apomictic polyploidy. Three of these apomictic polyploid origins were derived from southern sexual diploids, while the fourth origin was derived from northern sexual diploids. Analyses of regional diversity were suggestive of a formerly broad distribution for sexual diploids that has become subsequently fragmented, possibly due to the last round of glaciation. As sexual diploids were exclusively found north and south of the glacial maximum, while formerly glaciated areas were exclusively inhabited by asexual polyploids derived from both northern and southern sexual lineages, it is more likely that patterns of glaciation, as opposed to a particular latitudinal trend, played a causal role in the establishment of the observed pattern of geographic parthenogenesis in Easter daisies. [source] | ||||||||||||||||||||||||||||||||||||||||