bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel role for the non‐catalytic intracellular domain of Neprilysins in muscle physiology
Authors: Panz Mareike , Vitos‐Faleato Jessica , Jendretzki Arne , Heinisch Jürgen J. , Paululat Achim , Meyer Heiko 
Published: May 2012

AbstractBackground informationNeprilysins (Neps) are membrane‐bound M13 endopeptidases responsible for the activation and/or inactivation of peptide signalling events on cell surfaces. By hydrolysing their respective substrates, mammalian Neps are crucial to the metabolism of numerous bioactive peptides, especially in the nervous, immune, cardiovascular and inflammatory systems. On the basis of their involvement in essential physiological processes, proteins of the Nep family constitute putative therapeutic agents as well as targets in different diseases, including Alzheimer's disease.ResultsWe here demonstrate that overexpression of Neprilysin 4 (Nep4) in Drosophila melanogaster leads to a severe muscle degeneration phenotype. This phenotype is observed for overexpression of full‐length Nep4 in somatic muscles and is accompanied by severely impaired movement of larvae and lethality in late larval development. On the contrary, down‐regulation of expression caused only the latter two effects. By expressing several mutated and truncated forms of Nep4 in transgenic animals, we show that the intracellular domain is responsible for the observed phenotypes while catalytic activity of the enzyme was apparently dispensable. A yeast two‐hybrid screen identified a yet uncharacterised carbohydrate kinase as a first interaction partner of the intracellular domain of Nep4.ConclusionsThese data demonstrate that the physiological significance of Nep4 is not limited to its function as an active peptidase but that the enzyme's intracellular N‐terminus is affecting muscle integrity, independent of the protein's enzymatic activity. To our knowledge, this is the first report of an intracellular Nep domain being involved in muscle integrity.
BClI polymorphism of the glucocorticoid receptor gene is associated with increased obesity, impaired glucose metabolism and dyslipidaemia in patients with Addison's disease
Authors: Giordano Roberta , Marzotti Stefania , Berardelli Rita , Karamouzis Ioannis , Brozzetti Annalisa , D'Angelo Valentina , Mengozzi Giulio , Mandrile Giorgia , Giachino Daniela , Migliaretti Giuseppe , Bini Vittorio , Falorni Alberto , Ghigo Ezio , Arvat Emanuela 
Published: May 2012

AbstractObjectAlthough glucocorticoids are essential for health, several studies have shown that glucocorticoids replacement in Addison's disease might be involved in anthropometric and metabolic impairment, with increased cardiovascular risk, namely if conventional doses are used. As the effects of glucocorticoids are mediated by the glucocorticoid receptor, encoded by NR3C1 gene, different polymorphisms in the NR3C1 gene have been linked to altered glucocorticoid sensitivity in general population as well as in patients with obesity or metabolic syndrome.DesignWe investigated the impact of glucocorticoid receptor gene polymorphisms, including the BclI, N363S and ER22/23EK variants, on anthropometric parameters (BMI and waist circumference), metabolic profile (HOMA, OGTT and serum lipids) and ACTH levels in 50 patients with Addison's disease (34 women and 16 men, age 20–82 year) under glucocorticoids replacement.ResultsNeither N363S nor ER22/23EK variants were significantly associated with anthropometric, metabolic or hormonal parameters, while patients carrying the homozygous BclI polymorphism GG (n = 4) showed higher (P < 0·05) BMI, waist circumference, HOMA and 2‐h glucose levels after OGTT, as well as total cholesterol and triglycerides than those with wild‐type genotype CC (n = 28) or heterozygous CG (n = 18). The totality of GG patients was connoted by abdominal adiposity, impaired glucose tolerance/diabetes mellitus or dyslipidaemia, while a lower percentage of CC or CG patients showed some anthropometric and metabolic alterations.ConclusionThese results suggest that BclI polymorphism may influence the sensitivity to glucocorticoids in patients with Addison's disease and may contribute, along with other factors, to the increase in central adiposity, impaired glucose metabolism and dyslipidaemia.
ACTH‐secreting pituitary microadenomas are associated with a higher prevalence of central hypothyroidism compared to other microadenoma types
Authors: Mathioudakis Nestoras , Thapa Sritika , Wand Gary S. , Salvatori Roberto 
Published: May 2012

SummaryContextUnlike pituitary macroadenomas, microadenomas (micros) are not commonly associated with hypopituitarism. In clinical practice, we have observed that patients with ACTH‐secreting micros have a higher than expected prevalence of central hypothyroidism (HT), and we speculated that this effect might be because of glucocorticoid‐induced suppression of the hypothalamic–pituitary–thyroid axis.ObjectiveTo determine whether there is a difference in the prevalence of central HT among ACTH micros compared to other types of microadenoma, and if so, to investigate whether this is directly related to the degree of hypercortisolism.Design, setting and patientsRetrospective study of 149 newly diagnosed patients with pituitary micros: 34 ACTH‐secreting, 72 prolactin‐secreting (PRLomas) and 43 clinically nonfunctioning adenomas (NFAs).Main outcomes measuresPrevalence of central HT, correlation between normalized free T4 or TSH vs normalized urinary free cortisol (UFC) or salivary cortisol.ResultsThe prevalence of central HT was significantly higher in the ACTH compared to the non‐ACTH adenomas: 18% (ACTH), 1% (PRL) and 0% (NFAs). The mean normalized free T4 was lower in the ACTH micros compared to the non‐ACTH micros (1·29 ± 0·06 vs 1·50 ± 0·23, P = 0·0001). There was no correlation between the degree of hypercortisolism, as reflected by 24‐h urine free cortisol and salivary cortisol, and free T4 or TSH levels among the ACTH adenomas. Similarly, there were no differences in mean UFC or salivary cortisol between ACTH adenomas with and without central HT. Following transsphenoidal adenomectomy, central HT recovered in three of six patients with ACTH micros.ConclusionsThese findings suggest that patients with ACTH‐secreting microadenomas should always, at a minimum, undergo testing for central HT. However, given the potential for recovery of thyroid function following cure of Cushing disease, we recommend withholding thyroid hormone replacement until after pituitary surgery.
Expanded spatial extent of the Medieval Climate Anomaly revealed in lake‐sediment records across the boreal region in northwest Ontario
Authors: Laird Kathleen R. , Haig Heather A. , Ma Susan , Kingsbury Melanie V. , Brown Thomas A. , Lewis C. F. Michael , Oglesby Robert J. , Cumming Brian F. 
Published: May 2012

AbstractMulti‐decadal to centennial‐scale shifts in effective moisture over the past two millennia are inferred from sedimentary records from six lakes spanning a ~250 km region in northwest Ontario. This is the first regional application of a technique developed to reconstruct drought from drainage lakes (open lakes with surface outlets). This regional network of proxy drought records is based on individual within‐lake calibration models developed using diatom assemblages collected from surface sediments across a water‐depth gradient. Analysis of diatom assemblages from sediment cores collected close to the near‐shore ecological boundary between benthic and planktonic diatom taxa indicated this boundary shifted over time in all lakes. These shifts are largely dependent on climate‐driven influences, and can provide a sensitive record of past drought. Our lake‐sediment records indicate two periods of synchronous signals, suggesting a common large‐scale climate forcing. The first is a period of prolonged aridity during the Medieval Climate Anomaly (MCA, c. 900‐1400 CE). Documentation of aridity across this region expands the known spatial extent of the MCA megadrought into a region that historically has not experienced extreme droughts such as those in central and western north America. The second synchronous period is the recent signal of the past ~100 years, which indicates a change to higher effective moisture that may be related to anthropogenic forcing on climate. This approach has the potential to fill regional gaps, where many previous paleo‐lake depth methods (based on deeper centrally located cores) were relatively insensitive. By filling regional gaps, a better understanding of past spatial patterns in drought can be used to assess the sensitivity and realism of climate model projections of future climate change. This type of data is especially important for validating high spatial resolution, regional climate models.
The effectiveness of adhering to clinical‐practice guidelines for anxiety disorders in secondary mental health care: the results of a cohort study in the Netherlands
Authors: van Dijk Maarten K. , Oosterbaan Desiree B. , Verbraak Marc J. P. M. , van Balkom Anton J. L. M. 
Published: May 2012

AbstractBackground  While studies into the implementation of clinical practice guidelines for mental health care are scarce, studies on the effectiveness of implementing practice guidelines for anxiety disorders appear to be entirely non‐existent.Objective  To examine whether adherence to anxiety disorder clinical practice guidelines in secondary mental health care yields superior treatment results than non‐adherence.Method  A closed‐cohort study of 181 outpatients with an anxiety disorder or hypochondriasis who were treated in a routine mental health setting. Preceding the inclusion of these 181 patients, a start was made on the implementation of the Dutch national multidisciplinary practice guidelines for anxiety disorders. Patients were asked to complete several questionnaires before the start of treatment and again 1 year later. The medical records of these patients were reviewed to assess guideline adherence. Ultimately, adherence or non‐adherence to the different treatment algorithms described in the guidelines was related to changes in the severity of psychiatric symptomatology, psychiatric functioning, general well‐being and satisfaction with treatment.Results  Compared with patients whose treatment did not adhere to the guidelines, those whose treatment adhered to the guidelines were found to have greater symptom reduction after 1 year (P < 0.01). The latter group of patients also rated their satisfaction with their treatment significantly higher (P = 0.01). No significant differences were found after 1 year with respect to changes in impairment of functioning and quality of life in the two groups of patients.Conclusions  Adherence to anxiety disorder guidelines yields superior treatment results and increased patient satisfaction with treatment when compared with patients whose treatment did not adhere to the clinical guidelines. These results should encourage a more widespread implementation of such guidelines in mental health care facilities.
Evaluating weed diversity with indices of varying complexity in north‐eastern Italy
Authors: OTTO S , VASILEIADIS V P , MASIN R , ZANIN G 
Published: May 2012

Otto S, Vasileiadis VP, Masin R & Zanin G (2012). Evaluating weed diversity with indices of varying complexity in north‐eastern Italy. Weed Research52, 373–382.SummaryWeed diversity is one of the focuses of attention of researchers, and it can be evaluated with different indices, mainly based on species richness and community evenness. In intensive cropping systems, much of the diversity is concentrated in semi‐natural areas in the neighbouring habitats of arable fields. This study assessed weed diversity for seedbank and vegetation in an organically farmed valley in north‐eastern Italy. Assessment was carried out with indices based on species abundance, together with Rényi diversity that also considers abundance distribution and Rao’s quadratic entropy, which considers dissimilarity between species. A complete quadratic entropy approach for weeds is described. It is known that landscape context may affect community structure, and as an example of application of diversity indices in weed research, the correlation with the surrounding landscape complexity was evaluated. Results show that a community can be relatively balanced with even just a few species. With diversity indices based on species abundance only, it is therefore difficult to quantify balance. The Rényi diversity can overcome this limit, and the quadratic entropy can isolate extreme communities. In conclusion, the diversity of a weed community can be better evaluated using more diversity indexes, and the quadratic entropy can provide new criteria for ranking the diversity and combine a number of traits into a single numerical descriptor. The correlation between landscape complexity and weed diversity is low but confirms that agro‐environmental schemes should consider the management of fields and landscape together.
Debate: Idiopathic short stature should be treated with growth hormone
Authors: Ambler Geoffrey R , Fairchild Jan , Wilkinson Dominic JC 
Published: May 2012

AbstractIn this paper we outline the case for and against the treatment of idiopathic short stature with growth hormone. Drs Ambler and Fairchild argue that many of those with ‘idiopathic’ short stature are not ‘short, normal children’ and will ultimately receive molecular diagnoses. They also argue that there is a subset of children who suffer negative psychosocial consequences of their stature for whom growth hormone therapy is effective. Growth hormone has a very good safety record and is likely to be as cost‐effective in idiopathic short‐stature as in some other conditions that are currently funded. Dr Wilkinson counters that short stature is not associated with physical or psychological illness, and that there is no evidence that growth hormone improves psychological or physical wellbeing. Moreover, growth hormone for idiopathic short stature represents a form of enhancement rather than treatment, and is not a fair use of resources. Socially mediated disadvantage should be treated by attention to prejudice and not by hormone treatment.
A thermo‐damage strength model for ceramic material including an embedded crack with an arbitrarily shaped front
Authors: LI W. , WANG R. , LI D. , FANG D. 
Published: May 2012

ABSTRACTA fracture strength model applied at room temperature for the embedded crack was obtained based on the stress intensity factor model for embedded crack with an arbitrarily shaped front and Griffith fracture criterion. With further research on temperature effect on strength of ultra high temperature ceramics (UHTCs), a thermo‐damage strength model including the effects of temperature and crack shape was applied to each temperature phase. The fracture strengths were studied and analyzed. The conclusions were compared with the results obtained using the finite element software ABAQUS. This study will provide a theoretical basis and guidance on the design and preparation of the UHTCs.
Nematomorph parasites indirectly alter the food web and ecosystem function of streams through behavioural manipulation of their cricket hosts
Authors: Sato Takuya , Egusa Tomohiro , Fukushima Keitaro , Oda Tomoki , Ohte Nobuhito , Tokuchi Naoko , Watanabe Katsutoshi , Kanaiwa Minoru , Murakami Isaya , Lafferty Kevin D. 
Published: May 2012

AbstractNematomorph parasites manipulate crickets to enter streams where the parasites reproduce. These manipulated crickets become a substantial food subsidy for stream fishes. We used a field experiment to investigate how this subsidy affects the stream community and ecosystem function. When crickets were available, predatory fish ate fewer benthic invertebrates. The resulting release of the benthic invertebrate community from fish predation indirectly decreased the biomass of benthic algae and slightly increased leaf break‐down rate. This is the first experimental demonstration that host manipulation by a parasite can reorganise a community and alter ecosystem function. Nematomorphs are common, and many other parasites have dramatic effects on host phenotypes, suggesting that similar effects of parasites on ecosystems might be widespread.
The evolution of salinity tolerance in Daphnia: a functional genomics approach
Authors: Latta Leigh C. , Weider Lawrence J. , Colbourne John K. , Pfrender Michael E. 
Published: May 2012

AbstractOne route to genetic adaptation in a novel environment is the evolution of ecological generalisation. Yet, identifying the cost that a generalist pays for the increased breadth of tolerance has proven elusive. We integrate phenotypic assays with functional genomics to understand how tolerance to a salinity gradient evolves, and we test the relationship between the fitness cost of this generalisation and the cost of transcription that arises from evolved differences in patterns of gene expression. Our results suggest that a salt‐tolerant genotype of Daphnia is characterised by constitutively expressed genes, which does not incur a loss of fitness or a cost of transcription relative to a salt‐intolerant genotype in low saline environments. We find that many genes whose expression pattern evolved in response to salinity are also involved in the response to predators, suggesting that the cost of generalisation may be due to trade‐offs along other environmental axes.
Preterm infants who are prone to distress: differential effects of parenting on 36‐month behavioral and cognitive outcomes
Authors: Poehlmann Julie , Hane Amanda , Burnson Cynthia , Maleck Sarah , Hamburger Elizabeth , Shah Prachi E. 
Published: May 2012

Background:  The differential susceptibility (DS) model suggests that temperamentally prone‐to‐distress infants may exhibit adverse outcomes in negative environments but optimal outcomes in positive environments. This study explored temperament, parenting, and 36‐month cognition and behavior in preterm infants using the DS model. We hypothesized that temperamentally prone to distress preterm infants would exhibit more optimal cognition and fewer behavior problems when early parenting was positive; and less optimal cognition and more behavior problems when early parenting was less positive.Methods:  Participants included 109 preterm infants (gestation <37 weeks) and their mothers. We assessed neonatal risk and basal vagal tone in the neonatal intensive care unit; infant temperament and parenting interactions at 9 months post‐term; and child behavior and cognitive skills at 36 months post‐term. Hierarchical regression analyses tested study hypotheses.Results:  Temperamentally prone‐to‐distress infants exhibited more externalizing problems if they experienced more critical parenting at 9 months (β = −.20, p < 0.05) but fewer externalizing problems with more positive parenting. Similarly, variations in maternal positive affect (β = .25, p < .01) and intrusive behaviors (β = .23, p < .05) at 9 months predicted 36‐month cognition at high but not at low levels of infant temperamental distress. Higher basal vagal tone predicted fewer externalizing problems (β = −.19, p < .05).Conclusions:  Early parenting behaviors relate to later behavior and development in preterm infants who are temperamentally prone to distress, and neonatal basal vagal tone predicts subsequent externalizing behaviors. These findings suggest that both biological reactivity and quality of caregiving are important predictors for later outcomes in preterm infants and may be considered as foci for developmental surveillance and interventions.
Hand posture in the grey mouse lemur during arboreal locomotion on narrow branches
Authors: Reghem E. , Byron C. , Bels V. , Pouydebat E. 
Published: May 2012

AbstractPrimates are typically subdivided into two fundamentally different groups: Strepsirrhini and Haplorrhini. These two suborders are differentiated by several anatomical characteristics, among which are features of the wrist and hand. Whereas strepsirrhines are characterized by an ectaxonic hand with a longer fourth digit, haplorhines display a mesaxonic hand with a longer third digit. Two complementary studies suggest that (1) an ulnarly deviated hand with respect to the forearm during locomotion is typical for ectaxonic hands and thin branches whereas mesaxonic hands display a less‐deviated posture in relation to a more terrestrial type of locomotion; (2) ulnar deviations are not always produced by ectaxonic hands and may rather be associated with locomotion in an arboreal environment. The aim of this study was to explore how arboreal substrates influence the posture of the hand and the wrist in contact with the substrate. In this context, we assessed the grasping ability of the strepsirrhine Microcebus murinus, a highly arboreal species. Here we tested the effect of branch diameter (1 and 3 cm) and orientation (horizontal and vertical) on grasp choice during arboreal locomotion. Our results show that two hand postures were observed on horizontal substrates versus three‐hand postures on vertical substrates. When ulnar deviation was observed, it was typically observed on vertical substrates, particularly on thick ones. In conclusion, our data show that vertical substrates increase the variability in grasping hand postures for M. murinus and include the use of uncommon grasps compared with horizontal substrates. We suggest that more than the arboreal substrate, the frequent use of vertical supports may influence the hand biomechanics towards ulnar deviation as observed for lorisids and indriids.
Resiliency in Adolescents at High Risk for Substance Abuse: Flexible Adaptation via Subthalamic Nucleus and Linkage to Drinking and Drug Use in Early Adulthood
Authors: Weiland Barbara J. , Nigg Joel T. , Welsh Robert C. , Yau Wai‐Ying W. , Zubieta Jon‐Kar , Zucker Robert A. , Heitzeg Mary M. 
Published: May 2012

IntroductionThe personality trait resiliency is the ability to flexibly adapt impulse control relative to contextual demand. Low resiliency has been linked to later alcohol/drug problems. The underlying psychological and neural mechanisms are unknown, but neurocomputational models suggested relations between resiliency and working memory. Cortical–striatal connectivity has been proposed to underlie adaptive switches between cautious and risky behaviors.MethodsWorking memory was probed in sixty‐seven 18‐ to 22‐year‐olds from a larger community study of alcoholism, using the n‐back task during functional magnetic resonance imaging. Functional connectivity between task‐related regions was investigated with psychophysiological interaction analysis. Resiliency was measured in early teen years and related to early adulthood measures of drinking/drug use, task activation, and connectivity. Relationships with risk factors, including family history, age of drinking onset, and number of alcohol problems, were also investigated.ResultsHigher resiliency was related to lower levels of substance use, fewer alcohol problems, and better working memory performance. Whole‐brain regression revealed resiliency negatively correlated with activation of subthalamic nucleus (STN) and pallidum during the n‐back. High and Low resiliency quartile groups (n = 17 each) differed in coupling strength between STN and median cingulate cortex, a region of reduced activation during working memory. The high resiliency group had later onset of drinking, fewer alcohol problems, had used fewer illicit drugs, and were less likely to smoke cigarettes than their low resiliency counterparts.ConclusionsThese findings suggest that resiliency in early adolescence may protect against alcohol problems and drug use, although the direction of this effect is currently unknown. This protective factor may relate to executive functioning as supported by the finding of a neural link shared between resiliency and working memory in basal ganglia structures. The STN, a key basal ganglia structure, may adaptively link flexible impulse control with cognitive processing, potentially modulating substance use outcomes.