bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exon‐disrupting deletions of NRXN1 in idiopathic generalized epilepsy
Authors: Møller Rikke S. , Weber Yvonne G. , Klitten Laura L. , Trucks Holger , Muhle Hiltrud , Kunz Wolfram S. , Mefford Heather C. , Franke Andre , Kautza Monika , Wolf Peter , Dennig Dieter , Schreiber Stefan , Rückert Ina‐Maria , Wichmann H.‐Erich , Ernst Jan P. , Schurmann Claudia , Grabe Hans J. , Tommerup Niels , Stephani Ulrich , Lerche Holger , Hjalgrim Helle , Helbig Ingo , Sander Thomas ,   EPICURE Consortium
Published: January 2013

SummaryPurposeNeurexins are neuronal adhesion molecules located in the presynaptic terminal, where they interact with postsynaptic neuroligins to form a transsynaptic complex required for efficient neurotransmission in the brain. Recently, deletions and point mutations of the neurexin 1 (NRXN1) gene have been associated with a broad spectrum of neuropsychiatric disorders. This study aimed to investigate if NRXN1 deletions also increase the risk of idiopathic generalized epilepsies (IGEs).MethodsWe screened for deletions involving the NRXN1 gene in 1,569 patients with IGE and 6,201 controls using high‐density oligonucleotide microarrays.Key FindingsWe identified exon‐disrupting deletions of NRXN1 in 5 of 1,569 patients with IGE and 2 of 6,201 control individuals (p = 0.0049; odds ratio (OR) 9.91, 95% confidence interval (CI) 1.92–51.12). A complex familial segregation pattern in the IGE families was observed, suggesting that heterozygous NRXN1 deletions are susceptibility variants. Intriguingly, we identified a second large copy number variant in three of five index patients, supporting an involvement of heterogeneous susceptibility alleles in the etiology of IGE.SignificanceWe conclude that exon‐disrupting deletions of NRXN1 represent a genetic risk factor in the genetically complex predisposition of common IGE syndromes.
Hyperinsulinaemia increases vascular resistance and endothelin‐1 expression in the equine digit
Authors: Gauff F. , Patan‐Zugaj B. , Licka T. F. 
Published: January 2013

SummaryReasons for performing studyInsulin leads to overexpression of endothelin‐1 (ET‐1) in the endothelium of insulin‐resistant rodents. If this is also the case in equine laminar tissue, this could explain the predisposition of insulin‐resistant horses to laminitis.ObjectivesTo investigate the effect of hyperinsulinaemia on metabolism and vascular resistance of the isolated equine digit in a model of extracorporeal perfusion.Study designRandomised, controlled study with interventional group, with blinded evaluation of histology results.MethodAfter exsanguination, equine digits (n = 11) and autologous blood were collected at an abattoir. One digit served as a hyperinsulinaemic pilot limb, 5 digits were assigned to the hyperinsulinaemic perfusion (IP) group and 5 to the control perfusion (CP) group. Digits were perfused for 10 h at a defined perfusion rate of 12 ml/min/kg. After the first hour of perfusion (equilibration period), insulin was added to the reservoir of theIPdigits. Perfusion pressure, glucose consumption, lactate and lactate dehydrogenase were monitored. Vascular resistance was calculated as perfusion pressure (in millimetres of mercury) in relation to the flow rate (in millilitres per minute). After perfusion, histology samples of the dorsal hoof wall (haematoxylin & eosin or periodic acid–Schiff) were evaluated. Immunohistology with a polyclonal rabbit‐derived anti‐endothelin antibody was used for detection ofET‐1.ResultsIn theIPgroup, the mean insulin concentration in the plasma of the perfusate was 142 ± 81 μiu/ml, while insulin concentration was <3 μiu/ml in theCPgroup. Mean vascular resistance was significantly higher (P<0.01) in theIPgroup (2.04 ± 1.13 mmHg/ml/min) than in theCPgroup (1.31 ± 0.55 mmHg/ml/min). Histology of theIPgroup samples showed significantly more vessels with an open lumen, increased width of the secondary epidermal lamellae and formation of oedema. In the lamellar vessels (veins and arteries) and nerve fibres,ET‐1 expression was much more prominent in theIPgroup than in theCPgroup samples.ConclusionsShort‐term hyperinsulinaemia leads to increased vascular resistance in the equine digit and increased expression ofET‐1 in the laminar tissue.
Staphylococcus aureus skin colonization is promoted by barrier disruption and leads to local inflammation
Authors: Wanke Ines , Skabytska Yuliya , Kraft Beatrice , Peschel Andreas , Biedermann Tilo , Schittek Birgit 
Published: January 2013

AbstractExperimental mouse models of bacterial skin infections that have been described show that pathogenic microorganisms can readily invade the epidermis and dermis to produce localized infections. We used an epicutaneous mouse skin infection model to determine how the level of barrier disruption by tape‐stripping correlates with persistence of Staphylococcus aureus skin colonization, concomitant induction of cutaneous inflammation and infection. Furthermore, we investigated how murine skin responds to S. aureus colonization in a physiologic setting by analysing proinflammatory cytokines and antimicrobial peptides in mouse skin. We show that previous cutaneous damage allows skin inflammation to develop and favours S. aureus persistence leading to cutaneous colonization, suggesting an interdependence of cutaneous bacteria and skin. Our study suggests that skin barrier defects favour S. aureus skin colonization, which is associated with profound cutaneous inflammation.
Photoprotective effect of libanoridin isolated from Corydalis heterocarpa on UVB stressed human keratinocyte cells
Authors: Ahn Byul‐Nim , Kim Jung‐Ae , Kong Chang‐Suk , Seo Youngwan , Kim Se‐Kwon 
Published: January 2013

AbstractUltraviolet‐B (UVB) irradiation acts primarily on the epidermal basal cell layer of the skin, inducing harmful biological effects. In this study, we have investigated the effect of libanoridin isolated from Corydalis heterocarpa against UVB‐induced damage in human keratinocyte (HaCaT) cells and the molecular mechanism underlying those effects. Treatment with libanoridin inhibited the cell cytotoxicity and LDH induced by UVB exposure at 40 mJ/cm2. Additionally, expression levels of type IV collagenases (MMP‐2, MMP‐9) were decreased by libanoridin. Furthermore, MMP tissue inhibitors were enhanced followed by treatment with libanoridin. Moreover, UVB‐induced activation of phosphorylation of three MAPKs such as JNK, ERK, p38 and AP‐1 transcription factor were decreased by treatment with libanoridin.Our present study demonstrates that libanoridin has the abilities to inhibit UVB‐induced cellular damage via ASK1‐MAPK and AP‐1 signalling pathways. Therefore, libanoridin may be used as an effective natural compound to prevent skin damage due to UVB exposure.
Anterior gradient 2 and 3 – two prototype androgen‐responsive genes transcriptionally upregulated by androgens and by oestrogens in prostate cancer cells
Authors: Bu Huajie , Schweiger Michal R. , Manke Thomas , Wunderlich Andrea , Timmermann Bernd , Kerick Martin , Pasqualini Lorenza , Shehu Erald , Fuchsberger Christian , Cato Andrew C. B. , Klocker Helmut 
Published: January 2013

Androgens and oestrogens have been implicated in prostatic carcinogenesis and tumour progression. Although the actions of androgens have been studied extensively, the mechanisms underlying oestrogen signalling in prostate cancer are not fully understood. In the present study, we analyzed the effect of androgens and oestrogens on the expression of anterior gradient 2 (AGR2) and anterior gradient 3 (AGR3), comprising two highly‐related genes encoding secretory proteins that are expressed in prostate cancer and one of which (AGR2) has been associated with tumour metastasis. Quantitative reverse‐transcriptase PCR and western blot analysis showed androgen induction of AGR2 and AGR3 in three androgen receptor positive cell lines, starting at concentrations of 0.1 nm. Both AGR genes were also transcriptionally activated by ≥ 5 nm oestradiol but not by isotype selective or nonselective oestrogen receptor agonists in DUCaP cells that harbour a high‐level of wild‐type androgen receptor. A functional androgen receptor but not oestrogen receptor turned out to be required for both androgen and oestrogen regulation. This pattern of androgen and oestrogen regulation was confirmed in VCaP cells and was also observed for FKBP5, a well‐characterized androgen‐regulated gene. Genome‐wide chromatin‐immunoprecipitation studies coupled with deep sequencing identified androgen receptor binding sites localized in the distal promoter and intron regions of the AGR2 and AGR3 genes, respectively. The androgen responsiveness of these enhancers was verified by luciferase reporter gene assays and site‐directed mutagenesis analysis. Androgen treatment also induced p300 and RNA Pol II recruitment to androgen receptor enhancers of AGR2 and initiated local chromatin remodelling and the formation of RNA Pol II‐containing androgen receptor transcription complexes.
Validity and reproducibility of the revised oral assessment guide applied by community health workers
Authors: Ribeiro Marco Tulio F. , Ferreira Raquel C. , Vargas Andrea M.D. , e Ferreira Efigênia Ferreira 
Published: January 2013

ObjectiveTo determine the validity and reproducibility of the Revised Oral Assessment Guide (ROAG) as pre‐diagnostic tool used in elderly citizens by community health workers (CHWs) of the Family Health Strategy (FHS).Material and methodsInitially, we adjusted the English version to Portuguese and then developed a training program for use of ROAG, with the participation of CHWs, in selected districts that had the highest enrolled number of elderly people in the city. The elderly persons were distributed among 10 previously trained CHWs. To assess the validity of the ROAG, a CHW and a dentist (considered as the gold standard) independently evaluated the same individual. The reproducibility of the ROAG was evaluated by each of the CHWs examining 5–6 elderly individuals twice with a 7‐day interval.ResultsThe sensitivity ranged from 0.17 for evaluation of saliva to 0.80 for voice. The specific ranged from 0.69 for teeth/dentures to 0.98 for saliva using mirror and the accuracy ranged from 0.92 for swallow to 0.64 for mucosa. The intra‐rater reproducibility of the ROAG was perfect for evaluation of voice, lips and swallow (κ = 1.000).ConclusionWhen used by trained CHWs, the ROAG is a tool with high sensitivity and specificity to assess voice, swallowing, tongue and teeth/dentures. Moreover, it can efficiently detect patients showing no alteration in lips, saliva, mucosa and gums. High reproducibility was observed in almost all the categories. Trained CHWs can use this tool to improve the access of elderly patients to dental services.
Evaluation of the efficacy of a topical sialogogue spray containing malic acid 1% in elderly people with xerostomia: a double‐blind, randomized clinical trial
Authors: Gómez‐Moreno Gerardo , Cabrera‐Ayala Maribel , Aguilar‐Salvatierra Antonio , Guardia Javier , Ramírez‐Fernández María Piedad , González‐Jaranay Maximino , Calvo‐Guirado José Luis 
Published: January 2013

ObjectiveThe aim of this study was to evaluate the clinical efficacy of a topical sialogogue spray containing 1% malic acid for elderly people affected by xerostomia.Material and methodsThis research took the form of a double‐blind, randomized clinical trial. Forty‐one individuals (mean age: 78.7 years) with xerostomia were divided into two groups: for the first ‘intervention group’ (21 subjects) a topical sialogogue spray (1% malic acid) was applied, while for the second ‘control group’ (20 subjects), a placebo spray was applied; for both groups, the sprays were applied on demand during 2 weeks. The Xerostomia Inventory (XI) was used to evaluate xerostomia levels before and after product/placebo application. Unstimulated and stimulated salivary flows rates, before and after spray application, were measured.ResultsXI scores decreased significantly (clinically meaningful) from 36.4 ± 7.3 points to 29.1 ± 7.1 (p < 0.05) with an XI difference of 7.2 ± 6.1, after the combination among 1% malic acid with xylitol and fluoride application. After 2 weeks of 1% malic acid application, unstimulated and stimulated salivary flows rates increased significantly (p < 0.05).ConclusionA topical sialogogue spray containing 1% malic acid improved xerostomia in an elderly population and increased unstimulated and stimulated salivary flows rates.
Retrospective cohort study of the incidence and risk of fever in elderly people living at home: A pragmatic aspect of home medical management in Japan
Authors: Yokobayashi Kenichi , Matsushima Masato , Fujinuma Yasuki , Tazuma Susumu 
Published: January 2013

AimIn Japan, many elderly patients are managed at home, and fever is a common problem. This study examined the incidence of fever events in elderly patients on home medical management, and underlying disorders from the pragmatic standpoint. This study also investigated whether the care‐need level determined at the start of home care predicts fever onset.MethodsThe participants were patients aged ≥65 years who received home medical management from one clinic from 1 July 2008 to 30 June 2009. End‐points were onset of fever, diagnosis at time of fever onset and outcome. The incidence of fever was determined using the Kaplan–Meier method and compared using the log–rank test. To evaluate the effect of care‐need level on fever, Cox's proportional hazards model was used to adjust for confounding variables.ResultsA total 105 patients were included, with 100% follow up. The median observation period was 364 days. There were 64 fever events, for a fever incidence of 2.3/1000 patient‐days (95% CI 1.8–2.9); fever occurred at least once in 42.6% of participants. Fever was significantly more likely to occur in care‐need level 5 than in ≤4, with a risk ratio of 2.4. The most common diagnosis for all fever events was pneumonia/bronchitis, followed by urinary tract infection, and skin and soft tissue infection. Nearly 80% of cases were cured at home.ConclusionsFever occurred in approximately half of the participants over 1 year, and was more likely in patients requiring the highest care level; nearly 80% of cases were cured at home. Geriatr Gerontol Int 2013; 13: 887–893.
Late immune tolerance induction in haemophilia A patients
Authors: Meeks S. L. , Chapman R. L. , Kempton C. , Dunn A. L. 
Published: January 2013

SummaryThe incidence of inhibitor development in patients with severe haemophilia A is approximately 30%. Immune tolerance induction (ITI) is commonly utilized to eradicate these antibodies and is successful in 63–100% of cases. Potential predictors of a poor outcome in ITI include a high preinduction titre, high historical peak titre, older age at start of ITI and prolonged interval from diagnosis to start of ITI. The goal of this study was to characterize the outcomes of patients from our centre who have undergone late ITI, many of whom had poor prognostic features. Medical records of patients in our centre with severe/moderately severe haemophilia A (<2% FVIII activity) and history of inhibitor were reviewed. Data were abstracted from all patients who attempted late ITI. Nine patients underwent late ITI between January 1999 and December 2011. Within this cohort, 7 (78%) patients were black, 6 (67%) were <21 years old and 4 (44%) had a family history of inhibitor. Three patients had previously received ITI unsuccessfully. To date, 4 (44%) patients are tolerized (persistently negative inhibitor titre, FVIII recovery >66% and successfully treated with FVIII products ±FVIII t½ of >6 h). Three patients are partially tolerized (have low responding inhibitor, variable FVIII recovery and successfully treated with FVIII products). Two patients are not tolerized. Some patients with haemophilia A and long‐standing inhibitors may benefit from ITI.
Stilling the tremors: Resurrecting HIV services in Haiti's post‐earthquake tent cities
Authors: Ghose Toorjo , Boucicaut Edner , King Charles , Shubert Virginia , Doyle Andrea 
Published: January 2013

The January 12, 2010 earthquake in Haiti severely undermined HIV service provision in the country. Almost 10 percent of Haitians were displaced and now live in temporary tent communities. Little is known about how HIV services are being provided to Haitians with HIV in these encampments. This study addresses this lacuna by conducting a process evaluation of the manner in which a collaboration among Haitian community‐based HIV service providers, a US‐based HIV service provider, and a US‐based academic research team resurrected HIV services in the encampments. Efforts to set up HIV services in the encampments proceeded through three stages: (i) an initial crisis response that activated established networks and identified feasible goals; (ii) the development of services by building research capacity, conducting needs assessments, addressing logistical challenges, and establishing community‐based services; and (iii) the sustaining of the initiative by targeting resources and negotiating in the political arena. Implications of the protocol for future efforts are discussed.Key Practitioner Message: ● Resurrecting HIV services in post‐disaster zones; ● Utilizing cross‐country, provider–academic partnerships to develop service capacity; ● Targeting structural barriers to establish HIV services in resource‐poor settings.
Comparative metatranscriptomic signatures of wood and paper feeding in the gut of the termite Reticulitermes flavipes (Isoptera: Rhinotermitidae)
Authors: Raychoudhury R. , Sen R. , Cai Y. , Sun Y. , Lietze V.‐U. , Boucias D. G. , Scharf M. E. 
Published: January 2013

AbstractTermites are highly eusocial insects that thrive on recalcitrant materials like wood and soil and thus play important roles in global carbon recycling and also in damaging wooden structures. Termites, such as Reticulitermes flavipes (Rhinotermitidae), owe their success to their ability to extract nutrients from lignocellulose (a major component of wood) with the help of gut‐dwelling symbionts. With the aim to gain new insights into this enzymatic process we provided R. flavipes with a complex lignocellulose (wood) or pure cellulose (paper) diet and followed the resulting differential gene expression on a custom oligonucleotide‐microarray platform. We identified a set of expressed sequence tags (ESTs) with differential abundance between the two diet treatments and demonstrated the source (host/symbiont) of these genes, providing novel information on termite nutritional symbiosis. Our results reveal: (1) the majority of responsive wood‐ and paper‐abundant ESTs are from host and symbionts, respectively; (2) distinct pathways are associated with lignocellulose and cellulose feeding in both host and symbionts; and (3) sets of diet‐responsive ESTs encode putative digestive and wood‐related detoxification enzymes. Thus, this study illuminates the dynamics of termite nutritional symbiosis and reveals a pool of genes as potential targets for termite control and functional studies of termite‐symbiont interactions.
Robust error on magnetotelluric impedance estimates
Authors: Wawrzyniak Pierre , Sailhac Pascal , Marquis Guy 
Published: January 2013

ABSTRACTWe propose here a new, robust, methodology to estimate the errors on a magnetotelluric (MT) impedance tensor. This method is developed with the bounded influence remote‐reference processing (BIRRP) code in a single site configuration. The error is estimated by reinjecting an electric field residual obtained after the calculation of an impedance tensor into a tensor function calculation procedure. We show using synthetic examples that the error tensor calculated with our method yields a more reliable error estimate than the one calculated from Jackknife statistics. The modulus of realistic error estimates can be used as a quality control and an accurate inversion constraint of MT surveys. Moreover, reliable error estimates are necessary for new applications of MT to dynamic subsurface processes such as reservoir monitoring.
Laboratory determination of the full electrical resistivity tensor of heterogeneous carbonate rocks at elevated pressures
Authors: North Laurence , Best Angus I. , Sothcott Jeremy , MacGregor Lucy 
Published: January 2013

ABSTRACTWe describe a measurement system capable of determining the full resistivity tensor of core samples at elevated, geologically representative, pressures using a galvanic method. It is suitable for heterogeneous rocks where it is difficult to measure tensorial resistivity without bias from sample selection and heterogeneity. We demonstrate the efficacy of the system using both synthetic data and measurements on carbonate rock core samples. The apparatus employs a computer controlled array of 16 electrodes to inject current into, and measure boundary voltages on, a 5 cm diameter cylindrical sample. A computationally efficient FE algorithm is used to retrieve the full resistivity tensor from the measured voltages. The algorithm uses isotropic Finite Element code to calculate anisotropic solutions for samples of arbitrary geometry. Initial results from Jurassic limestone and Triassic dolomite samples, reveal cm‐scale heterogeneity and significant bulk anisotropy consistent with rock fabric observed in X‐ray Computed Tomography scan images.
Mating system in Mexican populations of the annual herb Solanum rostratum Dunal (Solanaceae)
Authors: Vallejo‐Marín M. , Solís‐Montero L. , Souto Vilaros D. , Lee M. Y. Q. 
Published: January 2013

AbstractTraditionally, annual colonising species are expected to have high rates of self‐fertilisation, although recent theoretical and empirical studies have shown that cross‐fertilisation can be selected for under heterogeneous pollination environments. Solanum rostratum is a self‐compatible annual herb that colonises disturbed habitats. Despite the lack of physiological mechanisms to prevent self‐fertilisation, pollen transfer between individuals is expected to be favoured because of its complex floral morphology. In previous studies of S. rostratum it has been shown that anther dimorphism within flowers results in precise pollen placement on the pollinator's body, and the presence of mirror‐image floral morphs within plants promotes outcrossing in experimental arrays. However, the mating system of natural populations of S. rostratum has never been assessed, and thus whether it is predominantly selfing or outcrossing remains unknown. We hypothesise that floral and inflorescence morphology of S. rostratum should facilitate cross‐fertilisation, making it a predominantly outcrossing despite its lack of a self‐incompatibility system. To test this hypothesis, we estimated outcrossing rates by genotyping 700 individuals at 13 microsatellite loci, sampled from four populations across a 690‐km transect in the species' native range. We found that populations had mean outcrossing rates of 0.70 ± 0.03, with multiple sires contributing to paternity of each progeny array (average effective number of sires = 8.97 ± 0.57). This indicates that natural populations S. rostratum have relatively high levels of outcrossing, probably facilitated by its floral and inflorescence morphology. We speculate that partial selfing in this species may be an unavoidable consequence of displaying multiple flowers at the same time (geitonogamy), as well as the result of self‐pollen transfer by illegitimate visitors.