742 research outputs found

    The double point surfaces of immersions in complex projective spaces

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    See a full text for abstractEThOS - Electronic Theses Online ServiceKing faisal FundationCultural BureauGBUnited Kingdo

    Individual Variation in Dietary Wariness Is Predicted by Head Color in a Specialist Feeder, the Gouldian Finch

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    Shifts in resource availability due to environmental change are increasingly confronting animals with unfamiliar food types. Species that can rapidly accept new food types may be better adapted to ecological change. Intuitively, dietary generalists are expected to accept new food types when resources change, while dietary specialists would be more averse to adopting novel food. However, most studies investigating changes in dietary breadth focus on generalist species and do not delve into potential individual predictors of dietary wariness and the social factors modulating these responses. We investigated dietary wariness in the Gouldian finch, a dietary specialist, that is expected to avoid novel food. This species occurs in two main head colors (red, black), which signal personality in other contexts. We measured their initial neophobic responses (approach attempts before first feed and latency to first feed) and willingness to incorporate novel food into their diet (frequency of feeding on novel food after first feed). Birds were tested in same-sex pairs in same and different head color pairings balanced across experiments 1 and 2. Familiar and novel food (familiar food dyed) were presented simultaneously across 5 days for 3 h, each. Gouldian finches fed on the familiar food first demonstrating food neophobia, and these latencies were repeatable. Birds made more approach attempts before feeding on novel than familiar food, particularly red-headed birds in experiment 1 and when partnered with a black-headed bird. Individuals consistently differed in their rate of incorporation of novel food, with clear differences between head colors; red-headed birds increased their feeding visits to novel food across experimentation equaling their familiar food intake by day five, while black-headed birds continually favored familiar food. Results suggest consistent among individual differences in response to novel food with red-headed birds being adventurous consumers and black-headed birds dietary conservatives. The differences in food acceptance aligned with responses to novel environments on the individual level (found in an earlier study) providing individuals with an adaptive combination of novelty responses across contexts in line with potential differences in movement patterns. Taken together, these novelty responses could aid in population persistence when faced with environmental changes

    Neurovisceral phenotypes in the expression of psychiatric symptoms

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    This review explores the proposal that vulnerability to psychological symptoms, particularly anxiety, originates in constitutional differences in the control of bodily state, exemplified by a set of conditions that include Joint Hypermobility, Postural Tachycardia Syndrome and Vasovagal Syncope. Research is revealing how brainbody mechanisms underlie individual differences in psychophysiological reactivity that can be important for predicting, stratifying and treating individuals with anxiety disorders and related conditions. One common constitutional difference is Joint Hypermobility, in which there is an increased range of joint movement as a result of a variant of collagen. Joint hypermobility is over-represented in people with anxiety, mood and neurodevelopmental disorders. It is also linked to stress-sensitive medical conditions such as irritable bowel syndrome, chronic fatigue syndrome and fibromyalgia. Structural differences in 'emotional' brain regions are reported in hypermobile individuals, and many people with joint hypermobility manifest autonomic abnormalities, typically Postural Tachycardia Syndrome. Enhanced heart rate reactivity during postural change and as recently recognised factors causing vasodilatation (as noted post prandially, post exertion and with heat) is characteristic of Postural Tachycardia Syndrome, and there is a phenomenological overlap with anxiety disorders, which may be partially accounted for by exaggerated neural reactivity within ventromedial prefrontal cortex. People who experience Vasovagal Syncope, a heritable tendency to fainting induced by emotional challenges (and needle/blood phobia), are also more vulnerable to anxiety disorders. Neuroimaging implicates brainstem differences in vulnerability to faints, yet the structural integrity of the caudate nucleus appears important for the control of fainting frequency in relation to parasympathetic tone and anxiety. Together there is clinical and neuroanatomical evidence to show that common constitutional differences affecting autonomic responsivity are linked to psychiatric symptoms, notably anxiety

    Parenting gifted and talented children: What are the key child behaviour and parenting issues?

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    Objective: The literature on gifted and talented children is limited. Little is known about the types and nature of difficulties experienced by gifted and talented children, and even less known about parenting issues related to parenting a gifted and talented child. The aim of the present study was to describe children's behavioural and emotional adjustment, and the factors that contribute to children's difficulties, as well as to examine the styles of discipline used by parents of gifted and talented children and their level of confidence in managing specific parenting tasks

    A repurposing strategy for Hsp90 inhibitors demonstrates their potency against filarial nematodes

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    Novel drugs are required for the elimination of infections caused by filarial worms, as most commonly used drugs largely target the microfilariae or first stage larvae of these infections. Previous studies, conducted in vitro, have shown that inhibition of Hsp90 kills adult Brugia pahangi. As numerous small molecule inhibitors of Hsp90 have been developed for use in cancer chemotherapy, we tested the activity of several novel Hsp90 inhibitors in a fluorescence polarization assay and against microfilariae and adult worms of Brugia in vitro. The results from all three assays correlated reasonably well and one particular compound, NVP-AUY922, was shown to be particularly active, inhibiting Mf output from female worms at concentrations as low as 5.0 nanomolar after 6 days exposure to drug. NVP-AUY922 was also active on adult worms after a short 24 h exposure to drug. Based on these in vitro data, NVP-AUY922 was tested in vivo in a mouse model and was shown to significantly reduce the recovery of both adult worms and microfilariae. These studies provide proof of principle that the repurposing of currently available Hsp90 inhibitors may have potential for the development of novel agents with macrofilaricidal properties

    How valid are current diagnostic criteria for dental erosion?

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    In principle, there is agreement about the clinical diagnostic criteria for dental erosion, basically defined as cupping and grooving of the occlusal/incisal surfaces, shallow defects on smooth surfaces located coronal from the enamel–cementum junction with an intact cervical enamel rim and restorations rising above the adjacent tooth surface. This lesion characteristic was established from clinical experience and from observations in a small group of subjects with known exposure to acids rather than from systematic research. Their prevalence is higher in risk groups for dental erosion compared to subjects not particularly exposed to acids, but analytical epidemiological studies on random or cluster samples often fail to find a relation between occurrence or severity of lesions and any aetiological factor. Besides other aspects, this finding might be due to lack of validity with respect to diagnostic criteria. In particular, cupping and grooving might be an effect of abrasion as well as of erosion and their value for the specific diagnosis of erosion must be doubted. Knowledge about the validity of current diagnostic criteria of different forms of tooth wear is incomplete, therefore further research is needed

    The prevalence of dental erosion and associated risk factors in 12-13-year-old school children in Southern China

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    <p>Abstract</p> <p>Background</p> <p>Dental erosion has been investigated in developed and developing countries and the prevalence varies considerably in different countries, geographic locations, and age groups. With the lifestyle of the Chinese people changing significantly over the decades, dental erosion has begun to receive more attention. However, the information about dental erosion in China is scarce. The purpose of this study was to explore the prevalence of dental erosion and associated risk factors in 12-13-year-old school children in Guangzhou, Southern China.</p> <p>Methods</p> <p>This cross-sectional survey was performed by two trained, calibrated examiners. A stratified random sample of 12-13-year-old children (774 boys and 725 girls) from 10 schools was examined for dental erosion using the diagnostic criteria of Eccles and the index of O'Sullivan was applied to record the distribution, severity, and amount of the lesions. Data on the socio-economic status, health behaviours, and general health involved in the etiology of dental erosion were obtained from a self-completed questionnaire. The analyses were performed using SPSS software.</p> <p>Results</p> <p>At least one tooth surface with signs of erosion was found in 416 children (27.3%). The most frequently affected teeth were the central incisors (upper central incisors, 16.3% and 15.9%; lower central incisors, 17.4% and 14.8%). The most frequently affected surface was the incisal or occlusal edge (43.2%). The loss of enamel contour was present in 54.6% of the tooth surfaces with erosion. Of the affected tooth surfaces, 69.3% had greater than one-half of the tooth surface was affected. The results from logistic regression analysis demonstrated that the children who were female, consumed carbonated drinks once a week or more, and those whose mothers were educated to the primary level tended to have more dental erosion.</p> <p>Conclusions</p> <p>Dental erosion in 12-13-year-old Chinese school children is becoming a significant problem. A strategy of offering preventive care, including more campaigns promoting a healthier lifestyle for those at risk of dental erosion should be conducted in Chinese children and their parents.</p

    Quantifying prediction of pathogenicity for within-codon concordance (PM5) using 7541 functional classifications of BRCA1 and MSH2 missense variants.

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    PURPOSE: Conditions and thresholds applied for evidence weighting of within-codon concordance (PM5) for pathogenicity vary widely between laboratories and expert groups. Because of the sparseness of available clinical classifications, there is little evidence for variation in practice. METHODS: We used as a truthset 7541 dichotomous functional classifications of BRCA1 and MSH2, spanning 311 codons of BRCA1 and 918 codons of MSH2, generated from large-scale functional assays that have been shown to correlate excellently with clinical classifications. We assessed PM5 at 5 stringencies with incorporation of 8 in silico tools. For each analysis, we quantified a positive likelihood ratio (pLR, true positive rate/false positive rate), the predictive value of PM5-lookup in ClinVar compared with the functional truthset. RESULTS: pLR was 16.3 (10.6-24.9) for variants for which there was exactly 1 additional colocated deleterious variant on ClinVar, and the variant under examination was equally or more damaging when analyzed using BLOSUM62. pLR was 71.5 (37.8-135.3) for variants for which there were 2 or more colocated deleterious ClinVar variants, and the variant under examination was equally or more damaging than at least 1 colocated variant when analyzed using BLOSUM62. CONCLUSION: These analyses support the graded use of PM5, with potential to use it at higher evidence weighting where more stringent criteria are met

    Is diagnosing exposed dentine a suitable tool for grading erosive loss?

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    Quantifying tooth wear in general and erosion in particular mostly is made by distinguishing between lesions restricted to enamel and lesions reaching the underlying dentine. Various scores for grading have been used, but in all systems, higher scores are given in cases of exposed dentine, thus, indicating a more severe stage of the condition. Clinical diagnosis of exposed dentine is made by assessing changes in colour or optical properties of the hard tissues. This paper aims to review the literature and discuss critically problems arising form this approach. It appears that classifying the severity of erosion by the area or depth of exposed dentine is difficult and poorly reproducible, and taking into account the variation of enamel thickness, the amount of tissue lost often is not related simply to the area of exposed dentine. There has still been very little longitudinal investigation of the significance of exposed dentine as a prognostic indicator. Further work and discussion is needed to reevaluate the explanative power of current grading procedures

    Effects of Antiepileptic Drugs on GABA Responses and on Reduction of GABA Responses by PTZ and DMCM on Mouse Neurons in Cell Culture

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    The mechanisms of action of antiepileptic drugs effective against generalized absence seizures (antiabsence AEDs) remain uncertain. Antiabsence AEDs are generally effective against seizures induced in experimental animals by pentylenÉtÉtrazol (PTZ) and methyl-6,7-dimethoxy-4-ethyl-Β-carboline-3-carboxylate (DMCM), drugs which reduce GABAergic inhibition. Thus, antiabsence AEDs have been suggested to enhance GABAergic inhibition. We studied the effects of several AEDs on GABA responses recorded from mouse spinal cord neurons grown in primary dissociated cell culture. Four antiabsence AEDs were included: ethosuximide (ESM), dimethadione (DMO), sodium valproate (VPA), and diazepam (DZP). Two experimental AEDs, CGS 9896 and ZK 91296, with anticonvulsant action against PTZ- or DMCM-induced seizures were also included. Possible effects of the antiabsence and experimental AEDS on PTZ- and DMCM-induced inhibition of GABA responses were also evaluated. PTZ and DMCM revers-ibly reduced GABA responses in a concentration-dependent manner. PTZ complÉtÉly inhibited GABA responses at 10 mM (IC 50 of 1.1 mM), whereas DMCM-induced inhibition of GABA responses reached a plateau level of 39% of control values at 1 p.M (IC 50 of 33 nM). ESM (1,200 ΜM), DMO (6 mM), VPA (200 u.M), CGS 9896 (2 ΜM), and ZK 98% (2 Μ M ) did not alter GABA responses. DZP enhanced GABA responses in a concentration-dependent manner. The inhibition of GABA responses produced by PTZ 1 mM was unaltered by ESM (600 Μ M ), DMO (6 mM), CGS 9896 (1 Μ M), or ZK 9896 (1 ΜM)- Coapplication of VPA (200 ΜM) and PTZ (1 mM) slightly enhanced the PTZ effect. DZP (> 10 nM), however, reversed the PTZ-induced reduction of GABA responses. The DMCM (250 nM) inhibition of GABA-responses was unaltered by ESM (600 Μ.M), DMO (2 mM), or VPA (200 ΜM). CGS 9896 (2 Μ M ) and ZK 91296 (2 ΜM), however, antagonized the DMCM effect. DZP (> 10 nM) significantly reversed the DMCM-induced inhibition of GABA responses. The lack of effect of VPA, ESM, and DMO on postsynaptic GABA responses suggests that direct enhancement of postsynaptic GABA action is not a common mechanism of action of antiabsence AEDs. The AEDs DZP, CGS 98%, and ZK 912% all reversed DMCM, but not PTZ, reduction of GABA responses, suggesting that these AEDs blocked DMCM seizures by acting at benzodiazepine receptors. However, since only DZP enhanced GABA responses, it is unclear how CGS 98% and ZK 912% blocked PTZ seizures. Key Words: Anticonvulsants–GABA–Neuron culture–Cell culture–Spinal cord neurons–Convulsants. RESUMEN Los mecanismos de accidn de las medicaciones antiepilÉpticas eficaces contra los ataques generalizados de ausencia (AEDs antiausencia) permanecen inciertos. Los AEDs antiausencia son, generalmente, eficaces contra ataques experimentales inducidos por el pentilentetrazol (PTZ) y el metil-6,7-dimetoxy-4-etil-Pcarbolina-3-carboxilato (DMCM) en animates, medicaciones que reducen la inhibiciÓn GABAÉrgica. Hemos estudiado los efectos de varios AEDs sobre respuestas-GABA registradas en las neuronas de la mÉdula espinal de ratones que habian crecido en cultivos de cÉlulas primarieas disociadas. Cuatro AEDs antiausencia fueron incluidos: etoxusimida (ESM), dimetadiona (DMO), valproato sÓdico (VPA) y diazepan (DZP). TambtÉn se incluyeron dos AEDs experimentales, CGS 9896 y ZK 912%, con acciÓn anticonvulsiva contra los ataques inducidos por PTZ o DMCM. TambiÓn se valoraron los posibles efectos de los AEDs antiausencia y experimentales sobre el PTZ y la inhibiciÓn de las respuestas-GABA inducidas por el DMCM. El PTZ y el DMCM redujeron las respuestas-GABA de modo reversible y dependiendo de sus concentraciones. El PTZ inhibiÓ cmpleta-mente las respuestas-GABA a 10 mM (IC 50 de 1.1 mM) mientras que la inhibitiÓn de las respuestas GABA inducida por el DMCM alcanzÓ un nivel estable del 39% de los valores control con 1 Μ. M (IC 50 de 33 mM). La ESM (1200 Μ.M), la DMO (6 mM), el VPA (200 Μ M ), el CGS 98% (2 Μ M) y el ZK 98% (2 Μ M) no alteraron las respuestas-GABA. El DZP aumentÓ las respuestas GABA de una manera concentraciÓn-dependiente. La inhibition de las respuestas-GABA producidas por el PTZ (1 mM), no se altero con las ESM (600 Μ M), la DMO (6 mM), el CGS 98% (1 Μ M) o el ZK 98% (1 Μ .M). La co-aplicacion de VPA (200 Μ M) y el PTZ (1 mM) aument6 ligeramente los efectos del PTZ. Sin embargo el DZP (10 nM) revirtiÓ significativamente la inhibition de las respuestas GABA inducidas por el DMCM. La falta de efectos de CPA, ESM y DMO sobre las respuestas GABA post-sinÁpticas sugiere que el incremento de la acciÓn GABA post-sinÁptica no es un mecanismo comÚn de actuatiÓn de las AEDs antiausencia. Todas las AEDs DZP, CGS 98% y ZK 912% revirtieron la reduction de las respuestas GABA producidas por el DMCM pero no las inducidas por el PTZ lo que sugiere que estos AEDs bloquean los ataques DMCM actuando sobre los receptores de la benzodiazepina. Sin embargo, puesto que el incremento de las respuestas GABA sÓlÓ se produce por el DZP, permanece todavia sin aclarar el por quÉ el CGS 98% y el ZK 912% bloquean los ataques producidos por el PTZ. ZUSAMMENFASSUNG Der Wirkmechansimus von Antiepileptika gegen generalisierte Absencen ist unklar. Antiabsencemittel sind generell wirkungs-voll gegen PTZ- und Methyl-6,7-Dimethoxy-4-Äthyl-P-Carbolin-Β-Carboxylat (DMCM) induzierte tierexperimentelle AnfÄlle, also von Medikamenten, die die GABA-erge Inhibition reduzieren. Es wurde vermutet, daß Antiabsencemittel die GABA-erge Inhibition verstÄrken. Wir untersuchten die Wirkung von verschiedenen Antiepileptika auf GABA-Antworten in spinalen MÄuseneuronen, die in Zellkulturen gew-achsen waren. Es wurden 4 Absencemittel untersucht: Ethosux-imid (ESM), Dimethadion (DMD), Sodium Valproat (VPA) und Diazepam (DZP). ZusÄtzlich wurden 2 experimentelle Antiepileptika, CGS 98% und ZK 912%, die gegen PTZ0 oder DMCM-induzierte AnfÄlle wirkungsvoll sind, eingeschlossen. Mogliche Wirkungen der Antiabsence- und experimentellen Antiepileptika auf PTZ- und DMCM-induzierte Hemmung der GABA-Antworten wurden ebenfalls ausgewertet. PTZ und DMCM zeigten eine konzentrationsabhÄngige reversible Reduktion der GABA-Antworten. PTZ zeigte eine komplette Hemmung der GABA-Antworten bei 10 mM (IC 50 1,1 mM), DMCM-Hemmung der GABA-Antworten zeigte ein Plateau von 39% der Kontroll-werte bei 1 uJtf (ICJO von 33 mAfl. ESM (1200 uJtf), DMD (6 mM), VPA (200 Μ M), CGS 98% (2 Μ M) und ZK 98% (2 Μ M) anderten nicht die GABA-Antworten. DZP verstarkte die GABA-Antworten konzentrationsabhangig. Die durch PTZ (1 mM) hervorgerufene Hemmung der GABA-Antworten war bei ESM (600 Μ M), DMD (6 mM), CGS 98% (1 mAO und ZK 3836 (1 mM) unverÄndert. ZusÄtliche Anwendung von VPA (200 mM) und PTZ (1 mM) verstÄrkten geringfÜgig den PTZ-Effekt. DZP (10 nM) kehrte die durch PTZ hervorgerufene Reduktion der GABA-Antworten um. Die durch DMCM (250 nM) hervorgerufene Hemmung der GABA-Antworten war durch ESM (600 Μ .M), DMD (2 mM) und VPA (200 Μ M ) unbeeinflusst. CGS 98% (2 Μ M) und ZK 912% (2 Μ M ) antagonisierten die DMCM-Wirkung. DZP (>10 nM) kehrte die durch DMCM-induzierte Hemmung der GABA-Antworten um. Das Fehlen einer Wirkung von VPA. ESM und DMD auf die postsynaptischen GABA-Antworten legen nahe, daß eine direkte VerstÄrkung der postsynaptischen GABA-Aktion kein gemeinsamer Mechanis-mus der Antiabsencemittel darstellt. Die Antiepileptika DZP, CGS 98% und ZK 912% kehrten die DMCM-Wirkung auf die GABA-Antworten um, jedoch nicht die von PTZ, was vermuten lapt, daß diese Antiepileptika die DMCM-AnfÄlle Über die Wirkung an den Benzodiazipin-Rezeptoren verhinderte. Da jedoch nur DZP GABA-Antworten verstarkte, ist unklar, in welcher Weise CGS 98% und ZK 912% die PTZ-AnfaUe ver-hinderten.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65188/1/j.1528-1157.1989.tb05275.x.pd
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