bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early onset absence epilepsy: 1 in 10 cases is caused by GLUT1 deficiency
Authors: Arsov Todor , Mullen Saul A. , Damiano John A. , Lawrence Kate M. , Huh Linda L. , Nolan Melinda , Young Helen , Thouin Anaïs , Dahl Hans‐Henrik M. , Berkovic Samuel F. , Crompton Douglas E. , Sadleir Lynette G. , Scheffer Ingrid E. 
Published: October 2012

SummaryGlucose transporter 1 (GLUT1) deficiency caused by mutations of SLC2A1 is an increasingly recognized cause of genetic generalized epilepsy. We previously reported that >10% (4 of 34) of a cohort with early onset absence epilepsy (EOAE) had GLUT1 deficiency. This study uses a new cohort of 55 patients with EOAE to confirm that finding. Patients with typical absence seizures beginning before 4 years of age were screened for solute carrier family 2 (facilitated glucose transporter), member 1 (SLC2A1) mutations or deletions. All had generalized spike‐waves on electroencephalography (EEG). Those with tonic and/or atonic seizures were excluded. Mutations were found in 7 (13%) of 55 cases, including five missense mutations, an in‐frame deletion leading to loss of a single amino acid, and a deletion spanning two exons. Over both studies, 11 (12%) of 89 probands with EOAE have GLUT1 deficiency. Given the major treatment and genetic counseling implications, this study confirms that SLC2A1 mutational analysis should be strongly considered in EOAE.
Structural basis for dual inhibitory role of tamarind Kunitz inhibitor (TKI) against factor Xa and trypsin
Authors: Patil Dipak N. , Chaudhary Anshul , Sharma Ashwani K. , Tomar Shailly , Kumar Pravindra 
Published: October 2012

A Kunitz type dual inhibitor (TKI) of factor Xa (FXa) and trypsin was found in tamarind. It also shows prolongation of blood coagulation time. The deduced 185 amino acid sequence of TKI by cDNA cloning and sequence analysis revealed that it belongs to the Kunitz type soybean trypsin inhibitor (STI) family; however, it has a distorted Kunitz signature sequence due to insertion of Asn15 in the motif. TKI exhibited a competitive inhibitory activity against both FXa (Ki = 220 nm) and porcine pancreatic trypsin (Ki = 3.2 nm). The crystal structure of TKI shows a β‐trefoil fold similar to Kunitz STI inhibitors; however, a distinct mobile reactive site, an inserted residue and loop β7β8 make it distinct from classical Kunitz inhibitors. The crystal structure of TKI‐trypsin and a 3D model of TKI‐FXa complex revealed that the distinct reactive site loop probably plays a role in dual inhibition. The reactive site of TKI interacts with an active site and two exosites (36 loop and autolysis loop) of FXa. Apart from Arg66 (P1), Arg64 (P3) is one of the most important residues responsible for the specificity of TKI towards FXa. Along with the reactive site loop (β4β5), loops β1 and β7β8 also interact with FXa and could further confer selectivity for FXa. We also present the role of inserted Asn15 in the stabilization of complexes. To the best of our knowledge, this is the first structure of FXa inhibitor belonging to the Kunitz type inhibitor family and its unique structural and sequence features make TKI a novel potent inhibitor.DatabaseThe complete nucleotide of TKI was deposited in the NCBI gene databank with accession no. HQ385502. The atomic coordinates and structure factor files for the structure of TKI and TKI:PPT complex have been deposited in the Protein Data Bank with accession numbers 4AN6 and 4AN7, respectivelyStructured digital abstract

TKI and TKI bind by x-ray crystallography (View interaction)
TKI and PPT bind by x-ray crystallography (View interaction)
Active site analysis of yeast flavohemoglobin based on its structure with a small ligand or econazole
Authors: El Hammi Emna , Warkentin Eberhard , Demmer Ulrike , Marzouki Nejib M. , Ermler Ulrich , Baciou Laura 
Published: October 2012

Flavohemoglobins (flavoHbs) serve various microorganisms as the major protective enzymes against NO˙‐mediated toxicity. FlavoHbs dominantly function as an NO˙ dioxygenase (), the required electron being shuttled from NAD(P)H via FAD to the heme iron. The X‐ray structures of the flavoHb from Saccharomyces cerevisae presented in complex with an unknown small ligand (Yhb) and with econazole (YhbE) at 2.1 and 3.0 Å resolutions, respectively, reveal a high architectural accordance between prokaryotic and eukaryotic family members. The active site is characterized by a proximal heme side with a strictly conserved histidine, glutamate and tyrosine triad and a highly variable distal heme side with helix shifts up to 10 Å mainly dependent on the presence/absence and size of the bound ligand. In yeast flavoHb, the small heme iron ligand adjusts a catalytically productive active site geometry that reliably suggests the NO and O2 binding site. O2 is activated by its ligation to an electron‐rich heme iron and a hydrogen bond to Tyr29 and Gln53. High active site similarities between eukaryotic Yhb and bacterial single‐domain globins argue for identical biochemical reactions. Binding of the bulky econazole implies a large‐scale induced‐fit process concerning, in particular, an outwards shift of helices B and E to increase the active site pocket. Yeast Yhb and Ralstonia eutropha flavoHb both structurally studied in complex with econazole indicate conformational differences between the inhibitors and the polypeptide primarily caused by stable binding of a phospholipid to the latter and by distinct loop D structures.DatabaseStructural data and final coordinates of Yhb and Yhb‐econazole are available in the Protein Data Bank under the accession numbers 4G1V and 4G1B
Vegetation–microclimate feedbacks in woodland–grassland ecotones
Authors: D'Odorico Paolo , He Yufei , Collins Scott , De Wekker Stephan F. J. , Engel Vic , Fuentes Jose D. 
Published: October 2012

AbstractAimClimatic conditions exert a strong control on the geographic distribution of many woodland‐to‐grassland transition zones (or ‘tree lines’). Because woody plants have, in general, a weaker cold tolerance than herbaceous vegetation, their altitudinal or latitudinal limits are strongly controlled by cold sensitivity. While temperature controls on the dynamics of woodland–grassland ecotones are relatively well established, the ability of woody plants to modify their microclimate and to create habitat for seedling establishment and growth may involve a variety of processes that are still not completely understood. Here we investigate feedbacks between vegetation and microclimatic conditions in the proximity to woodland–grassland ecotones.LocationWe concentrate on arctic and alpine tree lines, the transition between mangrove forests and salt marshes in coastal ecosystems, and the shift from shrubland to grassland along temperature gradients in arid landscapes.MethodsWe review the major abiotic and biotic mechanisms underlying the ability of woody plants to alter the nocturnal microclimate by increasing the temperatures they are exposed to.ResultsWe find that in many arctic, alpine, desert and coastal landscapes the presence of trees or shrubs causes nocturnal warming thereby favouring the establishment and survival of woody plants.Main conclusionBecause of this feedback, trees and shrubs may establish in areas that would be otherwise unsuitable for their survival. Thus, in grassland–woodland transition zones both vegetation covers may be (alternative) stable states of the landscape, thereby affecting the way tree lines may migrate in response to regional and global climate change.
Discrimination capacity in species distribution models depends on the representativeness of the environmental domain
Authors: Jiménez‐Valverde Alberto , Acevedo Pelayo , Barbosa A. Márcia , Lobo Jorge M. , Real Raimundo 
Published: October 2012

AbstractAimWhen faced with dichotomous events, such as the presence or absence of a species, discrimination capacity (the ability to separate the instances of presence from the instances of absence) is usually the only characteristic that is assessed in the evaluation of the performance of predictive models. Although neglected, calibration or reliability (how well the estimated probability of presence represents the observed proportion of presences) is another aspect of the performance of predictive models that provides important information. In this study, we explore how changes in the distribution of the probability of presence make discrimination capacity a context‐dependent characteristic of models. For the first time, we explain the implications that ignoring the context dependence of discrimination can have in the interpretation of species distribution models.InnovationIn this paper we corroborate that, under a uniform distribution of the estimated probability of presence, a well‐calibrated model will not attain high discrimination power and the value of the area under the curve will be 0.83. Under non‐uniform distributions of the probability of presence, simulations show that a well‐calibrated model can attain a broad range of discrimination values. These results illustrate that discrimination is a context‐dependent property, i.e. it gives information about the performance of a certain algorithm in a certain data population.Main conclusionsIn species distribution modelling, the discrimination capacity of a model is only meaningful for a certain species in a given geographic area and temporal snapshot. This is because the representativeness of the environmental domain changes with the geographical and temporal context, which unavoidably entails changes in the distribution of the probability of presence. Comparative studies that intend to generalize their results only based on the discrimination capacity of models may not be broadly extrapolated. Assessment of calibration is especially recommended when the models are intended to be transferred in time or space.
Infrared and Raman imaging spectroscopy of ex vivo skin
Authors: Flach Carol R. , Moore David J. 
Published: October 2012

SynopsisThis primer describes and illustrates experimental protocols for both Fourier transform infrared (FTIR) spectroscopic imaging and confocal Raman mapping of ex vivo skin and thereby acquaints the reader with these measurement techniques, including the temporal and spatial limitations associated with each technique. The experimental conditions by which the unique ‘molecular histology’ information obtained from confocal Raman mapping and infrared spectroscopic mapping of ex vivo skin is generated will be described. Raman and FTIR spectra of tissue, when collected in spatially resolved arrays, permit the generation of ‘molecular images’ of tissue components and tissue organization without the use of fluorescent labels or chemical stains. To illustrate the molecular information from ex vivo skin that can be spectroscopically imaged with confocal Raman and infrared microspectroscopy, we have collected new data using both techniques and generated spectral images which illustrate the capacity of each technique to provide unique insights into skin histology, biochemistry and biophysics. Understanding the measurement possibilities and specific constraints of both approaches is a prerequisite to their meaningful use as powerful research tools in skin research.
Ageing with telecare: care or coercion in austerity?
Authors: Mort Maggie , Roberts Celia , Callén Blanca 
Published: October 2012

AbstractIn recent years images of independence, active ageing and staying at home have come to characterise a successful old age in western societies. ‘Telecare’ technologies are heavily promoted to assist ageing‐in‐place and a nexus of demographic ageing, shrinking healthcare and social care budgets and technological ambition has come to promote the ‘telehome’ as the solution to the problem of the ‘age dependency ratio’. Through the adoption of a range of monitoring and telecare devices, it seems that the normative vision of independence will also be achieved. But with falling incomes and pressure for economies of scale, what kind of independence is experienced in the telehome? In this article we engage with the concepts of ‘technogenarians’ and ‘shared work’ to illuminate our analysis of telecare in use. Drawing on European‐funded research we argue that home‐monitoring based telecare has the potential to coerce older people unless we are able to recognise and respect a range of responses including non‐use and ‘misuse’ in daily practice. We propose that re‐imagining the aims of telecare and redesigning systems to allow for creative engagement with technologies and the co‐production of care relations would help to avoid the application of coercive forms of care technology in times of austerity.
Brain talk: power and negotiation in children’s discourse about self, brain and behaviour
Authors: Singh Ilina 
Published: October 2012

AbstractThis article examines children’s discourse about self, brain and behaviour, focusing on the dynamics of power, knowledge and responsibility articulated by children. The empirical data discussed in this article are drawn from the study of Voices on Identity, Childhood, Ethics and Stimulants, which included interviews with 151 US and UK children, a subset of whom had a diagnosis of attention deficit/hyperactivity disorder. Despite their contact with psychiatric explanations and psychotropic drugs for their behaviour, children’s discursive engagements with the brain show significant evidence of agency and negotiated responsibility. These engagements suggest the limitations of current concepts that describe a collapse of the self into the brain in an age of neurocentrism. Empirical investigation is needed in order to develop agent‐centred conceptual and theoretical frameworks that describe and evaluate the harms and benefits of treating children with psychotropic drugs and other brain‐based technologies.
Effectiveness and safety of protease inhibitor‐based regimens in HIV‐infected Thai children failing first‐line treatment
Authors: Wattanutchariya N , Sirisanthana V , Oberdorfer P 
Published: October 2012

ObjectivesVirological failure on first‐line nonnucleoside reverse transcriptase inhibitor (NNRTI)‐based treatment regimens has become a problem in HIV‐infected children on long‐term antiretroviral therapy (ART). Protease inhibitor (PI)‐based regimens are therefore often given to children failing NNRTI‐based regimens. The aim of the study was to assess the 48‐week effectiveness, safety and predictive factors for viral suppression of PI‐based regimens in HIV‐infected Thai children who had failed NNRTI‐based regimens.MethodsThis study assessed 41 HIV‐infected children who had failed first‐line NNRTI‐based regimens and were switched to PI‐based regimens for at least 48 weeks. We assessed their CD4 cell counts, plasma HIV RNA levels, weight‐for‐age and height‐for‐age z‐scores, and adverse events.ResultsThe children's median age was 9.5 years (range 1.5–15.8 years). At baseline, their median CD4 cell count was 276 cells/μL [interquartile range (IQR) 160–749 cells/μL], and their median plasma HIV RNA level was 4.5 log10 HIV‐1 RNA copies/mL (IQR 3.9–4.8 log10 copies/mL). After 48 weeks of PI‐based therapy, their CD4 cell counts increased to a median of 572 cells/μL (IQR 343–845 cells/μL) and in 73.2% plasma HIV RNA levels decreased to < 50 copies/mL. Their median weight‐for‐age and height‐for‐age z‐scores were stable over the period of the study. Diarrhoea occurred in 29.3% of patients. Triglyceride levels were significantly higher at weeks 24 and 48 in comparison to baseline measurements.ConclusionsPI‐based regimens are safe and effective for HIV‐infected Thai children who have failed first‐line NNRTI‐based regimens. However, long‐term follow‐up is warranted in order to ascertain the feasibility and sustainability of these new regimens.
Effect of dosage failed of first antiepileptic drug on subsequent outcome
Authors: Brodie Martin J. , Barry Sarah J. E. , Bamagous Ghazi A. , Kwan Patrick 
Published: October 2012

SummaryPurpose:  The recent definition of drug‐resistant epilepsy proposed by the International League Against Epilepsy (ILAE) stipulated failure of an adequate trial of two tolerated, appropriately chosen and used antiepileptic drug (AED) schedules to achieve seizure freedom. Doses failed were not specifically discussed. We explored the effect of the doses at which the first and second AED regimens failed on subsequent outcomes in a population of adults with newly diagnosed epilepsy followed for up to 20 years.Methods:  Patients in whom epilepsy was diagnosed and the first AED prescribed between July 1, 1982 and April 1, 2006, were followed until March 31, 2008. Dosage at which an AED failed was categorized according to the World Health Organization’s defined daily dose (DDD) for each drug. Cumulative incidence curves for time to final seizure freedom (no seizure for at least 1 year on unchanged dosage at last follow up) were stratified by whether the first regimen was failed at doses above or below the 25%, 50%, or 75% cutoffs for the DDD of each AED.Key Findings:  Among patients who had taken a second regimen (n = 327), those in whom the first AED failed at doses above the various cutoffs (particularly 50% and 75% DDD) had lower probability of becoming seizure‐free at last follow‐up (p = 0.06 for 25% DDD, p < 0.001 for both 50% and 75% DDD). The same difference was observed for patients who had taken a third regimen (n = 141; p = 0.23 for 25% DDD, p < 0.01 for 50% DDD; and p = 0.002 for 75% DDD). A trend to higher seizure‐free rate was observed in patients who had taken the third regimen when both the first and second regimens failed at <75% DDD. The difference remained significant after adjusting for covariates when using 50% DDD as the cutoff for patients who took a second regimen (hazard ratio 1.60, 95% confidence interval 1.08–2.37).Significance:  Higher failure dosage of the first AED predicts poorer subsequent outcome. This methodology could be used to refine further the ILAE definition of drug‐resistant epilepsy by exploring the doses need to fail to provide an adequate AED trial.
Clinical and Histological Findings of Denture Stomatitis as Related to Intraoral Colonization Patterns of Candida albicans, Salivary Flow, and Dry Mouth
Authors: Altarawneh Sandra , Bencharit Sompop , Mendoza Luisito , Curran Alice , Barrow David , Barros Silvana , Preisser John , Loewy Zvi G. , Gendreau Linda , Offenbacher Steven 
Published: October 2012

AbstractPurpose: Multifactorial etiological factors contribute to denture stomatitis (DS), a type of oral candidiasis; however, unlike other oral candidiasis, DS can occur in a healthy person wearing a denture. In this study, we therefore attempt to explore the association between candida, denture, and mucosal tissue using (1) exfoliative cytology, (2) the candidal levels present in saliva, on mucosal tissues and on denture surfaces, and (3) the salivary flow rate and xerostomic symptoms.Materials and Methods: A cross‐sectional study enrolled 32 edentulous participants, 17 without DS as controls and 15 with DS (Newton's classification type II and III). Participants with systemic or other known oral conditions were excluded. Participants completed a xerostomia questionnaire, and salivary flow rates were measured. Samples of unstimulated whole saliva (UWS) and stimulated whole saliva (SWS) were collected. UWS was used for fungal culturing. Periodic acid‐Schiff (PAS) stain and quantitative exfoliative cytology were performed on samples from affected and unaffected mucosa from each participant. Levels of Candida species (albicans and non‐albicans) were determined in salivary samples (expressed as colony‐forming units, CFU), as well as from swab samples obtained from denture fitting surfaces, in addition to affected and unaffected mucosa.Results: There were no significant differences in salivary flow rates, mucosal wetness, or frequency of reported dry mouth comparing participants with and without DS. Exfoliative cytology of mucosal smears demonstrated significantly higher (p= 0.02) inflammatory cell counts in DS patients, as compared with smears of healthy denture‐wearers. Candida albicans was significantly more prevalent in saliva (p= 0.03) and on denture surfaces (p= 0.002) of DS participants, whereas mucosal candidal counts and the presence of cytological hyphae did not show significant difference comparing DS to healthy participants.Conclusions: In this investigation, we presented a unique group of healthy edentulous patients. This population may reflect the general DS population without systemic or other oral diseases. The prominent etiological factor for DS in this population is the presence of candida in denture and saliva. We found that other factors such as saliva flow/xerostomia, fitting of the denture, and the presence of candida in the mucosa, are less important in this population. Therefore, DS treatments in healthy patients should first focus on sanitization of an existing denture and/or fabrication of a new denture.
Diffusion of HEMA through Human Carious and Non‐Carious Dentin In Vitro
Authors: Tak Onjen , Usumez Aslihan 
Published: October 2012

AbstractPurpose: The aim of this study was to evaluate the diffusion of 2‐Hydroxyethyl methacrylate (HEMA) from resin cement through dentin both affected and unaffected by caries through high‐performance liquid chromatography (HPLC) at two time intervals.Materials and Methods: Ten freshly extracted restoration‐free, caries‐free and ten extracted carious human third molar teeth were used in this study. Standardized box‐shaped Class I inlay cavities (6 mm long, 3 mm wide, 2 mm deep) were prepared in all teeth with a high‐speed handpiece mounted on a standard cavity machine. In teeth affected by caries, after preparation, the remaining carious lesions were removed, with their removal guided by a proprietary caries detector dye. The remaining dentin thickness (RDT) between the pulpal wall of the cavity and the roof of the pulp chamber was measured at multiple points for each tooth so that groups of 10 teeth each were prepared with RDT 1.2 ± 0.5 mm. Lithium disilicate‐based ceramic inlays were manufactured to restore the prepared cavities. A polypropylene chamber was attached to the cementoenamel junction of each tooth to contain 1 ml distilled water. Then, ceramic inlays were cemented with chemically polymerized resin cement (Multilink Automix) according to the manufacturer's instructions. Water elutes were analyzed by HPLC at 4.32 minutes and 24 hours. HEMA diffusion amounts were analyzed using two‐way ANOVA and Tukey HSD tests (p < 0.05).Results: HEMA was detected in the pulp chamber elutes of all the teeth. The diffused HEMA amounts were not significantly different between the affected caries and the unaffected groups (p= 0.80) or between time periods (p= 0.44). The carious dentin did not influence the amount of HEMA diffused through the dentin to the pulp space.Conclusions: The highest amount of eluted HEMA concentration detected was not viewed as critical for pulp tissue since the diffused HEMA amounts were below the level of cytotoxicity, according to the literature.