bluuebunny/crossref_metadata_2025 huggingface dataset:
Five‐factor model personality domains in the prediction of Axis II personality disorders: An exploratory study in late adulthood women non‐clinical sample
Authors: Henriques‐Calado Joana , Duarte‐Silva Maria Eugénia , Junqueira Diana , Sacoto Carlota , Keong Ana Marta
Published: December 2013

Relationships between Axis II personality disorders (DSM‐IV) and the five‐factor model were explored in a non‐clinical sample of late adulthood women. The sample consists of 90 women (M = 72.29 years of age, standard deviation = 7.10), who were administered with two measures, the NEO‐FFI and the Personality Diagnostic Questionnaire‐4+. Some personality disorders scales such as paranoid, schizotypal, borderline and dependent demonstrate a differentiated pattern of five‐factor model domain predictors. Low agreeableness predicted schizoid, narcissistic and antisocial; histrionic, obsessive‐compulsive and negativistic were predicted by high neuroticism and low agreeableness; high neuroticism and low extraversion, in turn, predicted dependent and depressive scales. Also, two clusters of personality disorders are identified, one associated with low agreeableness and another with low agreeableness and high neuroticism. This study suggest that some traits become maladaptive personality traits, and correspond more closely to psychopathology, when they become opposite to what would be expected in line with studies in normal late adulthood development. Copyright © 2013 John Wiley & Sons, Ltd.
Sulphur dioxide insertion into tin―carbon bonds: solvent effects and the nature of the transition state
Authors: Fong Clifford W. , Kitching William
Published: December 2013

Data describing the insertion of sulphur dioxide into the carbon―tin bond of a range of substituted phenyltrimethyltin compounds in methanol and benzene solvents have been reconsidered. The reaction in methanol is cleanly second order, but the reaction in benzene has both a second‐order and third‐order component, the latter ascribable to an initial equilibrium formation of a SO2 complex with the phenyl ring followed by the insertion of a second SO2 molecule into the carbon–tin bond. Molecular orbital calculations have identified the transition states (TS) and the favoured reaction pathways for the second‐order and third‐order reaction pathways in benzene. The effects of solvents on TS and enthalpies of reaction have also been examined. New insights into the types of TS involved in electrophilic substitution reactions are revealed. Copyright © 2013 John Wiley & Sons, Ltd.
Three‐dimensional structure of a sugar N‐formyltransferase from Francisella tularensis
Authors: Zimmer Alex L. , Thoden James B. , Holden Hazel M.
Published: December 2013

N‐formylated sugars have been observed on the O‐antigens of such pathogenic Gram‐negative bacteria as Campylobacter jejuni and Francisella tularensis. Until recently, however, little was known regarding the overall molecular architectures of the N‐formyltransferases that are required for the biosynthesis of these unusual sugars. Here we demonstrate that the protein encoded by the wbtj gene from F. tularensis is an N‐formyltransferase that functions on dTDP‐4‐amino‐4,6‐dideoxy‐d‐glucose as its substrate. The enzyme, hereafter referred to as WbtJ, demonstrates a strict requirement for N10‐formyltetrahydrofolate as its carbon source. In addition to the kinetic analysis, the three‐dimensional structure of the enzyme was solved in the presence of dTDP‐sugar ligands to a nominal resolution of 2.1 Å. Each subunit of the dimeric enzyme is dominated by a “core” domain defined by Met 1 to Ser 185. This core motif harbors the active site residues. Following the core domain, the last 56 residues fold into two α‐helices and a β‐hairpin motif. The hairpin motif is responsible primarily for the subunit:subunit interface, which is characterized by a rather hydrophobic pocket. From the study presented here, it is now known that WbtJ functions on C‐4′ amino sugars. Another enzyme recently investigated in the laboratory, WlaRD, formylates only C‐3′ amino sugars. Strikingly, the quaternary structures of WbtJ and WlaRD are remarkably different. In addition, there are several significant variations in the side chains that line their active site pockets, which may be important for substrate specificity. Details concerning the kinetic and structural properties of WbtJ are presented.
Characterization of the divalent metal binding site of bacterial polysaccharide deacetylase using crystallography and quantum chemical calculations
Authors: Munan Shaik Md , Bhattacharjee Nicholus , Bhattacharjee Anirban , Field Martin J. , Zanotti Giuseppe
Published: December 2013

Peptidoglycan deacetlyase (HP0310, HpPgdA) from the gram‐negative pathogen Helicobacter pylori, is the enzyme responsible for a peptidoglycan modification that counteracts the host immune response. In a recent study, we determined the crystallographic structure of the enzyme, which is a homo‐tetramer (Shaik et al., PloS One 2011;6:e19207). The metal‐binding site, which is essential for the enzyme's catalytic activity, is visible within the structure, but we were unable to identify the nature of the metal itself. In this study, we have obtained a higher‐resolution crystal structure of the enzyme, which shows that the ion bound is, in fact, zinc. Analysis of the structure of the four sites, one per monomer, and quantum chemical calculations of models of the site in the presence of different divalent metal ions show an intrinsic preference for zinc, but also significant flexibility of the site so that binding of other ions can eventually occur. Proteins 2014; 82:1311–1318. © 2013 Wiley Periodicals, Inc.
FOLFOX 4 Combined with Herbal Medicine for Advanced Colorectal Cancer: A Systematic Review
Authors: Chen Menghua , May Brian H. , Zhou Iris W. , Xue Charlie C. L. , Zhang Anthony L.
Published: December 2013

This systematic review evaluates the clinical evidence for the addition of herbal medicines (HMs) to FOLFOX 4 for advanced colorectal cancer (ACRC) in terms of tumor response rate (tRR), survival, quality of life and reduction in adverse events (AEs). Seven electronic databases were searched for randomized controlled trials (RCTs) of FOLFOX4 combined with HMs compared to FOLFOX4 alone. Outcome data for 13 randomized controlled trials were analysed using Review Manager 5.1. Risk of bias for objective outcomes including tumor response and survival was judged as low. Publication bias was not evident. Meta‐analyses found the addition of HMs improved tRR (RR 1.25, 95%CI 1.06–1.47, I2 = 0%), one year survival (RR 1.51, 95%CI 1.19–1.90, I2 = 0%) and quality of life in terms of Karnofsky Performance Status (KPS) gained (RR 1.84, 95%CI 1.54‐2.19, I2 = 0%); alleviated grade 3 and 4 chemotherapy‐related AEs for neutropenia (RR 0.33, 95%CI 0.18‐0.60, I2 = 0%), nausea and vomiting (RR 0.34, 95%CI 0.17‐0.67, I2 = 0%) and neurotoxicity (RR 0.39, 95%CI 0.15‐1.00, I2 = 0%), compared to FOLFOX4 alone. The most frequently used herbs were Astragalus membranaceus, Panax ginseng, Atractylodes macrocephala, Poria cocos, Coix lachryma‐jobi and Sophora flavescens. In experimental studies, each of these herbs has shown actions that could have contributed to improved tumor response. Copyright © 2013 John Wiley & Sons, Ltd.
Determination of low levels of 2H‐labeling using high‐resolution mass spectrometry: Application in studies of lipid flux and beyond
Authors: Herath Kithsiri B. , Zhong Wendy , Yang Jiong , Mahsut Ablatt , Rohm Rory J. , Shah Vinit , Castro‐Perez Jose , Zhou Haihong , Attygalle Athula B. , Kang Ling , Singh Sheo , Johns Douglas G. , Cleary Michele A. , Hubbard Brian K. , Previs Stephen F. , Roddy Thomas P.
Published: December 2013

RATIONALE

The ability to measure low levels of 2H‐labeling is important in studies of metabolic flux, e.g. one can estimate lipid synthesis by administering 2H2O and then measuring the incorporation of 2H into fatty acids. Unfortunately, the analyses are complicated by the presence of more abundant naturally occurring stable isotopes, e.g. 13C. Conventional approaches rely on coupling gas chromatographic separation of lipids with either quadrupole‐mass spectrometry (q‐MS) and/or pyrolysis‐isotope ratio mass spectrometry (IRMS). The former is limited by high background labeling (primarily from 13C) whereas the latter is not suitable for routine high‐throughput analyses.

METHODS

We have contrasted the use of continuous flow‐pyrolysis‐IRMS against high‐resolution mass spectrometry (i.e. Qq‐FT‐ICR MS) for measuring the 2H‐enrichment of fatty acids and peptides.

RESULTS

In contrast to IRMS, which requires ~30 min per analysis, it is possible to measure the 2H‐enrichment of palmitate via direct infusion high‐resolution mass spectrometry (HRMS) in ~3 min per sample. In addition, Qq‐FT‐ICR MS enabled measurements of the 2H‐enrichment of peptides (which is not possible using IRMS).

CONCLUSIONS

High‐resolution mass spectrometry can be used to measure low levels of 2H‐labeling so we expect that this approach will enhance studies of metabolic flux that rely on 2H‐labeled tracers, e.g. 2H2O. However, since the high‐resolution analyses require greater amounts of a given analyte one potential limitation centers on the overall sensitivity. Presumably, future advances can overcome this barrier. Copyright © 2013 John Wiley & Sons, Ltd.
Drying method has no substantial effect on δ15N or δ13C values of muscle tissue from teleost fishes
Authors: Bessey Cindy , Vanderklift Mathew A.
Published: December 2013

RATIONALE

Stable isotope analysis (SIA) is a powerful tool in many fields of research that enables quantitative comparisons among studies, if similar methods have been used. The goal of this study was to determine if three different drying methods commonly used to prepare samples for SIA yielded different δ15N and δ13C values.

METHODS

Muscle subsamples from 10 individuals each of three teleost species were dried using three methods: (i) oven, (ii) food dehydrator, and (iii) freeze‐dryer. All subsamples were analysed for δ15N and δ13C values, and nitrogen and carbon content, using a continuous flow system consisting of a Delta V Plus mass spectrometer and a Flush 1112 elemental analyser via a Conflo IV universal interface. The δ13C values were normalized to constant lipid content using the equations proposed by McConnaughey and McRoy.

RESULTS

Although statistically significant, the differences in δ15N values between the drying methods were small (mean differences ≤0.21‰). The differences in δ13C values between the drying methods were not statistically significant, and normalising the δ13C values to constant lipid content reduced the mean differences for all treatments to ≤0.65‰. A statistically significant difference of ~2% in C content existed between tissues dried in a food dehydrator and those dried in a freeze‐dryer for two fish species. There was no significant effect of fish size on the differences between methods.

CONCLUSIONS

No substantial effect of drying method was found on the δ15N or δ13C values of teleost muscle tissue. Copyright © 2013 John Wiley & Sons, Ltd.
Desorption/ionization induced by neutral cluster impact as a soft and efficient ionization source for ion trap mass spectrometry of biomolecules
Authors: Baur Markus , Gebhardt Christoph R. , Dürr Michael
Published: December 2013

RATIONALE

Desorption and ionization induced by neutral clusters (DINeC) using SO2 as cluster constituents was previously shown to produce clear and fragmentation‐free spectra with low background from samples prepared with standard oligopeptides. Here we demonstrate a more general applicability of this method based on examples from different classes of (bio‐)molecules. In order to make better use of the ions generated during the millisecond cluster‐pulse, the DINeC source was combined with an ion trap mass spectrometer.

METHODS

Desorption and ionization was induced by neutral SO2 clusters with a mean size of 103 to 104 molecules seeded in a pulsed He beam. The desorbed ions were accumulated in an ion trap over the whole pulse duration prior to mass spectrometric analysis. Samples were prepared by simply drop casting the respective aqueous solution of biomolecules on Si/SiO2 substrates.

RESULTS

Clear and fragmentation‐free spectra of oligopeptides were detected in single pulse operation mode. The very soft nature of the desorption process was demonstrated for phosphopeptides. DINeC spectra from bovine serum albumin samples after tryptic digest led to a clear identification of the original sequence using mass fingerprinting analysis. MSn capability was illustrated with two types of rhodamine dyes.

CONCLUSIONS

Desorption and ionization induced by neutral clusters can efficiently be combined with ion trap mass spectrometry since the pulse width and repetition rate of a typical pulsed cluster beam correspond well to the discontinuous accumulation time as well as the spectral rate of the ion trap. Clear mass spectra were obtained with such a setup for a variety of biosamples demonstrating the wider applicability of the DINeC process. Copyright © 2013 John Wiley & Sons, Ltd.
Structural elucidation of co‐eluted triglycerides in the marine diatom model organism Thalassiosira pseudonana by ultra‐performance liquid chromatography/quadrupole time‐of‐flight mass spectrometry
Authors: Li Shuang , Xu Jilin , Chen Jiao , Chen Juanjuan , Zhou Chengxu , Yan Xiaojun
Published: December 2013

RATIONALE

The precise identification of fatty acids at the sn‐2 position of triacylglycerols (TAGs), especially for positional regioisomers (AAB/ABA), needs to be established during mass spectrometry analysis. The detailed structural information about TAGs is significant not only for the assessment of biofuel quality, but also for the tracing of biosynthetic precursors.

METHODS

Total lipid was extracted from T. pseudonana by a modified Bligh and Dyer method. The qualitative analysis of TAGs in T. pseudonana was carried out using ultra‐performance liquid chromatography/electrospray ionization‐quadrupole time‐of‐flight mass spectrometry (UPLC/ESI‐Q‐TOF‐MS). The raw LC/MS data were analyzed using MassLynx software (version 4.1, Waters).

RESULTS

The acyl group at the sn‐2 position of the TAGs has been identified unequivocally by [M + Li‐R1/3COOH‐R2CH = CHCOOH]+ and the abundance of [M + Li‐R1/3COOH‐R2CH = CHCOOH]+ can be used to confirm whether the TAG isomers are co‐eluted. In total, twelve TAGs were identified in T. pseudonana based on the fragmentation patterns discussed above. The data indicated that only C16 fatty acids were located at the sn‐2 position, which was important to trace the biosynthetic precursors of TAGs.

CONCLUSIONS

We put forward a hypothesis that TAGs in T. pseudonana are only derived from lipids in chloroplasts through prokaryotic biosynthesis pathway based on the precise information of sn‐2 fatty acids, which is significant not only for the assessment of biofuel quality, but also for the tracing of biosynthetic precursors. Copyright © 2013 John Wiley & Sons, Ltd.
Development of a novel imidazolium‐based aromatic quaternary ammonium tag: Synthesis and application to the efficient analysis of cysteinyl‐peptides by mass spectrometry
Authors: Qiao Xiaoqiang , Wang Rui , Yan Hongyuan , Wang Tao , Zhao Qun , Zhang Lihua , Zhang Yukui
Published: December 2013

RATIONALE

Chemical derivatization is a very promising technique for improving analysis of peptides by mass spectrometry (MS). In this study, a novel kind of imidazolium‐based aromatic quaternary ammonium tag, 1‐[3‐[(2‐iodo‐1‐oxoethyl)amino]propyl]‐3‐butylimidazolium bromide (IPBI), designed with strong gas‐phase basicity and a permanent positive charge, was firstly synthesized and further used for derivatization of cysteinyl‐peptides with improved ionization efficiency and higher charge states.

METHODS

Both the model peptides and tryptic digests of proteins were used to evaluate the effect of IPBI derivatization on the MS performance of the derivatized peptides, and the results were further compared with the commonly used iodoacetamide (IAA) tag. Matrix‐assisted laser desorption/ionization time‐of‐flight (MALDI‐TOF)‐MS and electrospray ionization (ESI)‐MS were used to evaluate the ionization efficiency and charge states of the derivatized peptides.

RESULTS

With model peptides as samples, a nearly 100% derivatization efficiency and superior stability were achieved via IPBI derivatization. By further analysis of both standard peptides and tryptic protein digests, the ionization efficiency and charge states of IPBI‐derivatized peptides could be remarkably improved. For example, for protein bovine serum albumin, compared with the commercial available IAA tag, the identification efficiency of cysteinyl‐peptides was increased about 67% by combining with IPBI derivatization.

CONCLUSIONS

The results indicated that the novel tag is an effective derivatization reagent for cysteinyl‐peptide identification. We hope it could be further used for high‐efficiency cysteinyl‐peptide identification in proteome research, especially those with low abundance and poor ionization efficiency. Copyright © 2013 John Wiley & Sons, Ltd.
Combining Multicriteria Decision‐Making Tools to Identify Critical Success Factors that Affect the Performance of Training Course Projects
Authors: Fu Hsin‐Pin , Chang Tien‐Hsiang , Kao Ling‐Jing , Chiu Chih‐Chou , Lu Cheng‐Chin
Published: December 2013

This paper combines two multicriteria decision‐making (MCDM) tools to identify the critical success factors (CSFs) that impact the performance of personnel training course projects in the semiconductor industry in Taiwan. The study collected the factors that influence performance by interviewing experts and constructed a hierarchical factor table. The fuzzy analytic hierarchy process was used to determine the weight of each factor, and the acceptance advantage concept of VlseKriterijumska Optimizacija I Kompromisno Resenje was used to objectively identify the CSFs. The study found four CSFs that affect project performance and proposed five practical implications. This paper verified that combining two MCDM tools can help training institutions to allocate their resources appropriately by focusing on the CSFs, identified by their weights, and thus, promote their training courses at lower cost and with greater efficiency. Copyright © 2013 John Wiley & Sons, Ltd.
Experimental and Numerical Investigations of the TRIP Effect in 1.4301 Austenitic Stainless Steel Under Static Loading
Authors: Gupta Satyapriya , Twardowski Raphael , Kucharczyk Pawel , Münstermann Sebastian
Published: December 2013

The TRIP effect enhances the work hardening behavior of steel and provides high strength and high ductility. In the design of TRIP‐assisted steel components based on numerical simulation, the TRIP effect must be considered to ensure a reliable stress analysis. The influence of the TRIP effect on the properties of the 1.4301 austenitic stainless steel was studied experimentally and numerically in order to evaluate the ability of a phase transformation model to quantitatively describe the TRIP effect for various loading conditions. Uniaxial tensile tests were carried out at different strain rates. During plastic deformation stress increased significantly indicating phase transformation. The martensite volume fraction was determined “in situ” using a ferritescope. The influence of temperature on the martensite formation was analyzed at different strain rates using a thermo camera. The experimentally characterized deformation behavior of the tested steel was simulated using a model based on Olson and Cohen approach, which was implemented as UHARD subroutine in the ABAQUS software. The phase transformation was simulated for two different specimen geometries under quasi‐static conditions.
Validation of post‐tensioning anchorage zones by laboratory testing and numerical simulation
Authors: Cervenka Vladimir , Ganz Hans Rudolf
Published: December 2013

Anchorage zones in post‐tensioned concrete structures offered by the construction industry are subject to a certification process, which checks compliance with codes of practice and safety requirements. This certification is based on load transfer tests on specimens, which represent the real structural solutions. Such tests can be supplemented by numerical simulations based on computational mechanics. Those simulations represent a powerful tool for interpreting test results and contribute to a better understanding of the structural behaviour of anchorage zones.
Review of possible mineral materials and production techniques for a building material on the moon
Authors: Wilhelm Sebastian , Curbach Manfred
Published: December 2013

This article provides an overview of the findings and production processes for the mineral materials that have been developed and tested worldwide in the past with regard to the establishment of a lunar base. Firstly, the aim of and procedure for constructing a lunar base are briefly outlined. Following that, the lunar environment factors and their influence on a possible structure are described. The paper then presents the advantages and disadvantages of the materials examined, such as sulphur concrete, cast basalt, lunar concrete or polymer concrete, on the one hand, as well as production processes investigated previously, such as sintering, geothermite reaction and 3D printing, on the other. One promising method is the dry‐mix/steam‐injection (DMSI) method for producing a lunar concrete as a possible material which was developed by T. D. Lin and is based on cement made from lunar resources.
Results of Intraoperative Neuromonitoring in Thyroid Surgery and Preoperative Vocal Cord Paralysis
Authors: Lorenz Kerstin , Abuazab Mohammed , Sekulla Carsten , Schneider Rick , Nguyen Thanh Phuong , Dralle Henning
Published: December 2013

Background

Systematic studies of intermittent intraoperative neuromonitoring (IONM) have shown that IONM enhances recurrent laryngeal nerve (RLN) identification via functional assessment, but does not significantly reduce rates of vocal cord (VC) paralysis (VCP). The reliability of functional nerve assessment depends on the preoperative integrity of VC mobility. The present study was therefore performed to analyze the validity of IONM in patients with pre‐existing VC paralysis.

Methods

Of 8,128 patients, 285 (3.5 %) with preoperative VCP underwent thyroid surgery using standardized IONM of the RLN and vagus nerves (VNs). VC function was assessed by pre‐ and postoperative direct videolaryngoscopy. Quantitative parameters of IONM in patients with VCP were compared with IONM in patients with intact VC function. Clinical symptoms and surgical outcomes of patients with pre‐existing VCP were analyzed.

Results

A total of 244 patients revealed negative, and 41 revealed positive IONM on the side of the VCP. VCP with positive IONM revealed significantly lower amplitudes of VN and RLN than intact VN (p = 0.010) and RLN (p = 0.011). Symptoms of patients with VCP included hoarseness (25 %), dyspnea (29 %), stridor (13 %), and dysphagia (13 %); 13 % were asymptomatic. New VCP occurred in five patients, ten needed tracheostomy for various reasons, and one patient died.

Conclusions

Patients with pre‐existing VCP revealed significantly reduced amplitude of ipsilateral VN and RLN, indicating retained nerve conductivity despite VC immobility. Preoperative laryngoscopy is therefore indispensable for reliable IONM and risk assessment, even in patients without voice abnormalities.
Treatment effect of coenzyme Q10 and an antioxidant cocktail in fibroblasts of patients with Sanfilippo disease
Authors: Matalonga Leslie , Arias Angela , Coll María Josep , Garcia‐Villoria Judit , Gort Laura , Ribes Antonia
Published: December 2013

Coenzyme Q10 (CoQ10) plays a key role in the exchange of electrons in lysosomal membrane, which contributes to protons’ translocation into the lumen and to the acidification of intra‐lysosomal medium, which is essential for the proteolytic function of hydrolases responsible ‐when deficient‐ of a wide range of inherited lysosomal diseases such as Sanfilippo syndromes. Our aim was to evaluate whether treatment with CoQ10 or with an antioxidant cocktail (α‐tocopherol, N‐acetylcysteine and α‐lipoic acid) were able to ameliorate the biochemical phenotype in cultured fibroblasts of Sanfilippo patients. Basal CoQ10 was analyzed in fibroblasts and Sanfilippo A patients showed decreased basal levels. However, no dysfunction in the CoQ10 biosynthesis pathways was found, revealing for the first time a secondary CoQ10 deficiency in Sanfilippo A fibroblasts. Cultured fibroblasts from five patients affected by Sanfilippo A and B diseases were treated with CoQ10 and an antioxidant cocktail. Upon CoQ10 treatment, none of the Sanfilippo A fibroblasts increased their residual enzymatic activity, but the two Sanfilippo B cell lines showed a statistically significant increase of their residual activity. The antioxidant treatment had no effect on the residual activity in all tested cell lines. Moreover, one Sanfilippo A and two Sanfilippo B fibroblasts showed a statistically significant reduction of glycosaminoglycans accumulation both, after 50 μmol/L CoQ10 and antioxidant treatment. Fibroblasts responsive to treatment enhanced their exocytosis levels. Our results are encouraging as some cellular alterations observed in Sanfilippo syndrome can be partially restored by CoQ10 or other antioxidant treatment in some patients.
Monogene Ionenkanalerkrankungen des Knochens
Authors: Stauber T. , Horn D. , Kornak U.
Published: December 2013

Obwohl Ionenkanäle eher mit der Generierung von Aktionspotenzialen in Verbindung gebracht werden, können sie auch in unterschiedlichster Weise die Entwicklung und Funktion von Knochenzellen und -gewebe beeinflussen, was durch die hier vorgestellten Skeletterkrankungen verdeutlicht werden soll. Jeder der grundlegenden Zelltypen, Chondrozyten, Osteoblasten, Osteozyten, Osteoklasten, kann in die Pathogenese involviert sein und in vielen Fällen ist das Zusammenspiel der verschiedenen zellulären Defekte nicht verstanden. Connexin 43 und TRPV4, 2 der genannten Membranproteine, transportieren v. a. Kalzium und stehen jeweils mit einem Spektrum an Skelettphänotypen in Verbindung. Hierbei scheint Connexin 43 v. a. als Regulator in Osteoblasten und Osteozyten zu fungieren, während TRPV4 eine wichtige Rolle in Chondrozyten spielt. Die anderen beiden Beispiele sind die chloridtransportierenden Proteine ANO5 und ClC-7, deren Defekt die gnathodiaphysäre Dysplasie bzw. die Osteopetrose nach sich zieht. Während die Funktion von ANO5 noch unklar ist, konnte die Funktion von ClC-7 in Osteoklasten detailliert beschrieben werden.
Erbliche Ionenkanalerkrankungen der Netzhaut
Authors: Reuter P. , Kohl S. , Bernd A. , Wissinger B.
Published: December 2013

Retinale Ionenkanalerkrankungen sind klinisch und genetisch sehr heterogen. Die bisher identifizierten krankheitsassoziierten Ionenkanäle umfassen zyklisch nukleotidgesteuerte (CNG-)Kanäle, spannungsgesteuerte Kalium- und Kalziumkanäle, einen einwärtsrektifizierenden Kaliumkanal, einen kalziumaktivierten Chloridkanal und den transienten Rezeptorpotenzialionenkanal TRPM1. Dieses breite Spektrum spiegelt sich auch in der resultierenden Pathophysiologie wieder. Mutationen in retinalen Ionenkanälen können die Detektion von Lichtreizen bzw. deren Umwandlung in ein elektrisches Signal oder die Weiterleitung des Signals von den Fotorezeptoren zu nachgeschalteten Neuronen beeinträchtigen. Einige Erkrankungen werden auch durch Mutationen in Ionenkanälen, die im retinalen Pigmentepithel lokalisiert sind, hervorgerufen. Dieses ist mit seinen unterstützenden Aufgaben für eine normale Netzhautfunktion essenziell.
The SSQ model of schizophrenic prodromal unfolding revised: An analysis of its causal chains based on the language of directed graphs
Authors: van Kampen D.
Published: December 2013

Objective

Except in broad outline, little is known about the most likely symptomatic trajectories in prodromal schizophrenia. The aim of this study is to delineate these pathways.

Methods

Taking into account existing clinical knowledge, the causal relationships between the 12 prodrome scales of the Schizotypic Syndrome Questionnaire (SSQ) were examined in a general-population sample by applying the mathematical theory of directed graphs. Use was made of two discovery algorithms implemented in the Tetrad-4 program, as well as of the graphical DAGitty program to test whether a particular model holds.

Results

A promising model was selected that may describe the causal pathways in schizophrenic prodromal unfolding. Testing this model by means of DAGitty, it was shown that the minimal testable implications, listed as conditional independences, and the direct and total effects in the model, identified after correction for bias, were as hypothesized. For practical reasons, a simpler version of the resulting SSQ model, containing only its principal pathways, was provided.

Conclusions

Although resembling an earlier model that was based on a series of LISREL analyses, the present model was believed to provide a more dependable description of schizophrenic prodromal unfolding, as it relies on methods that are less subject to the limitations involved in SEM.
Oral lichen planus: Malignant potential and diagnosis
Authors: Shirasuna Kanemitsu
Published: December 2013

Oral lichen planus (OLP) is one of the most common diseases of the oral mucosa. Clinically, it has specific and clearly identifiable features; bilateral symmetric presentation showing a lace‐like network of fine white lines (known as Wickham’s striae) is an essential element of OLP even if the lesion exhibits a mainly atrophic and erosive pattern. There are various lesions that resemble OLP clinically and histologically. These lesions are widely referred to as lichenoid reactions or lichenoid lesions (OLLs). OLLs include contact hypersensitivity to dental materials, drug‐induced lichenoid lesions, lichenoid reactions in chronic graft‐versus‐host disease, and other lesions that resemble OLP. The risk of malignant transformation of OLP is the subject of ongoing debate in the literature. Some authors have suggested that only OLLs, but not OLP, are of a premalignant nature and thus, should be categorized as “other dysplastic conditions.” Contrary to this suggestion, many cases of oral squamous cell carcinoma (OSCC) developing in patients with OLP presenting with no epithelial dysplasia have been reported. In addition, it has been reported that multiple events including multifocal dysplasia and/or OSCC subsequently occurred in some patients with OLP, suggesting possible field cancerization in OLP. In this paper, differential diagnosis between OLP and OLLs and their malignant potential are reviewed.
3-Fold Extremal Contractions of Types (IC) and (IIB)
Authors: Mori Shigefumi , Prokhorov Yuri
Published: December 2013

Let (X, C) be a germ of a 3-foldXwith terminal singularities along an irreducible reduced complete curveCwith a contractionf:(X, C) → (Z, o) such thatC=f−1(o)redand −KXis ample. Assume that (X, C) contains a point of type (IC) or (IIB). We complete the classification of such germs in terms of a general membercontainingC.
Prey switching by killer whales in the north-east Atlantic: observational evidence and experimental insights
Authors: Vongraven Dag , Bisther Anna
Published: December 2013

Studies in the Pacific have identified distinct killer whale ecotypes that are either specialized mammal- or fish-eaters. The different types have developed hunting strategies that would suggest specialization could be more advantageous than generalism. However, it has been suggested, based on long-term dietary markers of tooth wear and stable isotope values, that lineages in the North Atlantic are generalist, but with individual variation in the proportion of prey types consumed. Here, we present the results of ten years of observational and photo-identification data of a population of killer whales that follows the Norwegian spring-spawning stock of Atlantic herring. Although the whales were predominantly observed while feeding upon herring, one pod of herring-eating whales was also observed interacting with seals. This supports the hypothesis based on the long-term markers, of a degree of specialization, with a small number of groups persistently feeding upon mammals, but switching between herring and seals. We further investigated this prey switching by conducting playbacks of herring-eating killer whale sounds to harbour seals at haul-out sites on the herring spawning grounds. We recorded changes in behaviour consistent with an anti-predator response, suggesting the seals perceived the herring-eating killer whales as a potential predatory threat and had not habituated to their calls. This could be due to the risk of herring-eating killer whales switching to mammalian prey, or the difficulty of discriminating between killer whale pods due to the large population size and number of killer whale call dialects in this population, or a combination of both.
S-opsin knockout mice with the endogenous M-opsin gene replaced by an L-opsin variant
Authors: GREENWALD SCOTT H. , KUCHENBECKER JAMES A. , ROBERSON DANIEL K. , NEITZ MAUREEN , NEITZ JAY
Published: December 2013

Specific variants of human long-wavelength (L) and middle-wavelength (M) cone opsin genes have recently been associated with a variety of vision disorders caused by cone malfunction, including red-green color vision deficiency, blue cone monochromacy, myopia, and cone dystrophy. Strikingly, unlike disease-causing mutations in rhodopsin, most of the cone opsin alleles that are associated with vision disorders do not have deleterious point mutations. Instead, specific combinations of normal polymorphisms that arose by genetic recombination between the genes encoding L and M opsins appear to cause disease. Knockout/knock-in mice promise to make it possible to study how these deleterious cone opsin variants affect the structure, function, and viability of the cone photoreceptors. Ideally, we would like to evaluate different variants that cause vision disorders in humans against a control pigment that is not associated with vision disorders, and each variant should be expressed as the sole photopigment in each mouse cone, as is the case in humans. To evaluate the feasibility of this approach, we created a line of mice to serve as the control in the analysis of disease-causing mutations by replacing exon 2 through 6 of the mouse M-opsin gene with the corresponding cDNA for a human L-opsin variant that is associated with normal vision. Experiments reported here establish that the resulting pigment, which differs from the endogenous mouse M opsin at 35 amino acid positions, functions normally in mouse cones. This pigment was evaluated in mice with and without coexpression of the mouse short wavelength (S) opsin. Here, the creation and validation of two lines of genetically engineered mice that can be used to study disease-causing variants of human L/M-opsins, in vivo, are described.
The future of genomics for developmentalists
Authors: Plomin Robert , Simpson Michael A.
Published: December 2013

The momentum of genomic science will carry it far into the future and into the heart of research on typical and atypical behavioral development. The purpose of this paper is to focus on a few implications and applications of these advances for understanding behavioral development. Quantitative genetics is genomic and will chart the course for molecular genomic research now that these two worlds of genetics are merging in the search for many genes of small effect. Although current attempts to identify specific genes have had limited success, known as the missing heritability problem, whole-genome sequencing will improve this situation by identifying all DNA sequence variations, including rare variants. Because the heritability of complex traits is caused by many DNA variants of small effect in the population, polygenic scores that are composites of hundreds or thousands of DNA variants will be used by developmentalists to predict children's genetic risk and resilience. The most far-reaching advance will be the widespread availability of whole-genome sequence for children, which means that developmentalists would no longer need to obtain DNA or to genotype children in order to use genomic information in research or in the clinic.
A translational neuroscience framework for the development of socioemotional functioning in health and psychopathology
Authors: Wiggins Jillian Lee , Monk Christopher S.
Published: December 2013

The development of socioemotional functioning is a complex process that occurs over a protracted time period and requires coordinating affective, cognitive, and social faculties. At many points in development, the trajectory of socioemotional development can be deleteriously altered due to a combination of environmental insults and individual vulnerabilities. The result can be psychopathology. However, researchers are just beginning to understand the neural and genetic mechanisms involved in the development of healthy and disordered socioemotional functioning. We propose a translational developmental neuroscience framework to understand the transactional process that results in socioemotional functioning in both healthy and disordered populations. We then apply this framework to healthy socioemotional development, pediatric anxiety, pediatric depression, and autism spectrum disorder, selectively reviewing current literature in light of the framework. Finally, we examine ways that the framework can help to frame future directions of research on socioemotional development and translational implications for intervention.
Adolescent brain development in normality and psychopathology
Authors: Luciana Monica
Published: December 2013

Since this journal's inception, the field of adolescent brain development has flourished, as researchers have investigated the underpinnings of adolescent risk-taking behaviors. Explanations based on translational models initially attributed such behaviors to executive control deficiencies and poor frontal lobe function. This conclusion was bolstered by evidence that the prefrontal cortex and its interconnections are among the last brain regions to structurally and functionally mature. As substantial heterogeneity of prefrontal function was revealed, applications of neuroeconomic theory to adolescent development led to dual systems models of behavior. Current epidemiological trends, behavioral observations, and functional magnetic resonance imaging based brain activity patterns suggest a quadratic increase in limbically mediated incentive motivation from childhood to adolescence and a decline thereafter. This elevation occurs in the context of immature prefrontal function, so motivational strivings may be difficult to regulate. Theoretical models explain this patterning through brain-based accounts of subcortical–cortical integration, puberty-based models of adolescent sensation seeking, and neurochemical dynamics. Empirically sound tests of these mechanisms, as well as investigations of biology–context interactions, represent the field's most challenging future goals, so that applications to psychopathology can be refined and so that developmental cascades that incorporate neurobiological variables can be modeled.
A quarter century of progress on the early detection and treatment of autism spectrum disorder
Authors: Dawson Geraldine , Bernier Raphael
Published: December 2013

The last 25 years have witnessed tremendous changes in our ability to detect autism very early in life and provide interventions that can significantly influence children's outcomes. It was once questioned whether autism could be recognized before children had developed language and symbolic play skills; now changes in early behaviors, as well as structural brain changes, have been documented in infants 6–12 months of age who later develop autism. Advances in brain imaging and genetics offer the possibility of detecting autism before the syndrome is fully manifest, thereby reducing or preventing symptoms from developing. Whereas the primary mode of behavioral intervention a few decades ago relied on operant conditioning, recent approaches integrate the methods of applied behavioral analysis within a developmental, relationship-focused intervention model that are implemented by both parents and clinicians. These interventions have been found to have positive effects on children's developmental trajectory, as measured by both behavioral and neurophysiological assessments. Future approaches will likely combine both behavioral and pharmacological treatments for children who have less robust responses to behavioral interventions. There has been a paradigm shift in the way that autism is viewed, evolving from a lifelong condition with a very poor prognosis to one in which significant gains and neuroplasticity is expected, especially when the condition is detected early and appropriate interventions are provided. The grand challenge for the future is to bridge the tremendous gap between research and the implementation of evidence-based practices in the broader community, both in the United States and worldwide. Significant disparities in access to appropriate health care for children with autism exist that urgently require advocacy and more resources.
Attention deficits and hyperactivity–impulsivity: What have we learned, what next?
Authors: Nigg Joel T.
Published: December 2013

The domains of self-regulation, self-control, executive function, inattention, and impulsivity cut across broad swathes of normal and abnormal development. Attention-deficit/hyperactivity disorder is a common syndrome that encompasses a portion of these domains. In the past 25 years research on attention-deficit/hyperactivity disorder has been characterized by dramatic advances in genetic, neural, and neuropsychological description of the syndrome as well as clarification of its multidimensional phenotypic structure. The limited clinical applicability of these research findings poses the primary challenge for the next generation. It is likely that clinical breakthroughs will require further refinement in describing heterogeneity or clinical/biological subgroups, renewed focus on the environment in the form of etiological events as well as psychosocial contexts of development, and integration of both with biological understanding.
“I can, therefore I must”: Fragility in the upper-middle classes
Authors: Luthar Suniya S. , Barkin Samuel H. , Crossman Elizabeth J.
Published: December 2013

We review evidence on a group recently identified as “at risk,” that is, youth in upwardly mobile, upper-middle class community contexts. These youngsters are statistically more likely than normative samples to show serious disturbance across several domains including drug and alcohol use, as well as internalizing and externalizing problems. Extant data on these problems are reviewed with attention to gender-specific patterns, presenting quantitative developmental research findings along with relevant evidence across other disciplines. In considering possible reasons for elevated maladjustment, we appraise multiple pathways, including aspects of family dynamics, peer norms, pressures at schools, and policies in higher education. All of these pathways are considered within the context of broad, exosystemic mores: the pervasive emphasis, in contemporary American culture, on maximizing personal status, and how this can threaten the well-being of individuals and of communities. We then discuss issues that warrant attention in future research. The paper concludes with suggestions for interventions at multiple levels, targeting youth, parents, educators, as well as policymakers, toward reducing pressures and maximizing positive adaptation among “privileged but pressured” youth and their families.
The developmental psychopathology of alcohol use and alcohol disorders: Research achievements and future directions
Authors: Chassin Laurie , Sher Kenneth J. , Hussong Andrea , Curran Patrick
Published: December 2013

The last 25 years have seen significant advances in our conceptualization of alcohol use and alcohol use disorders within a developmental framework, along with advances in our empirical understanding that have been potentiated by advances in quantitative methods. These include advances in understanding the heterogeneity of trajectories of alcohol outcomes; new insights about early childhood antecedents, and adolescence and emerging adulthood as important developmental periods for alcohol outcomes; a more nuanced understanding of the influences of developmental transitions, and their timing and contexts; a greater appreciation for the importance of considering multiple levels of analysis (including an increasing number of genetically informative studies); a continuing focus on studying multiple pathways underlying alcohol outcomes; and an increasing focus on studying the effects of alcohol exposure on future development. The current paper reviews these advances and suggests directions for future study.
Prefixal agreement and impersonal ‘il’ in Spoken French: Experimental evidence
Authors: CULBERTSON JENNIFER , LEGENDRE GÉRALDINE
Published: December 2013

In Spoken Continental French, the subject cliticilcan in some cases be dropped – for example in certain impersonal construction (e.g.faut que‘is necessary that’). This phenomenon is of particular interest in the context of claims that this variety of French is in fact a null subject language, with subject clitics acting as agreement affixes rather than true arguments (e.g. Roberge, 1990; Auger, 1994; Culbertson, 2010, among others). Under this view, theilin impersonals (and other constructions with less than fully referential subjects) is likewise an agreement marker, which can be dropped under some circumstances. Here we report the results of a controlled acceptability judgement task designed to probe features which affect the availability ofil-drop. Our findings suggest that verb frequency, subcategorisation by the verb for a quasi-argument vs. true expletive, and modal vs. non-modal status influenceil-drop. We discuss implications of this variation for an analysis of subject clitics as agreement affixes in Spoken French.
Leaving antegrade pulmonary blood flow results in reversal of flow in the azygous vein and decompression of the cavopulmonary circulation: mechanism of cyanosis defined with cardiac magnetic resonance imaging
Authors: Anwar Shafkat , Whitehead Kevin K. , Harris Matthew A.
Published: December 2013

We report the case of a 2.5-year-old patient with single-ventricle physiology who underwent cardiac magnetic resonance study for cyanosis after Kawashima operation. Magnetic resonance imaging study showed a veno-venous collateral redirecting systemic venous flow, responsible for cyanosis.
Pulmonary atresia and intact ventricular septum with transposed arterial trunks
Authors: Gupta Saurabh Kumar , Anderson Robert H. , Kothari Shyam S.
Published: December 2013

We report a case of pulmonary atresia with intact ventricular septum, but in the setting of transposed great arteries, and thus the left rather than the right ventricle was hypoplastic.
Cor triatriatum dexter and coarctation of the aorta – a rare association in a 7-year-old child with type 1 neurofibromatosis
Authors: Omeje Ikenna , Christov Georgi , Khambadkone Sachin , Hsia Tain-Yen
Published: December 2013

Cor triatriatum dexter is an extremely rare congenital anomaly of the right atrium. It occurs because of the persistence of the right sinus venosus valve, resulting in partitioning of the right atrium. Most of the described cases of cor triatriatum dexter in the literature were incidental findings on echocardiogram or at necropsy.

We present a case report of a 7-year-old girl who was referred to us for further assessment, with a possible diagnosis of coarctation of the aorta. Initial investigations confirmed not only the presence of a long segment coarctation of the aorta, but also a large obstructive membrane in the right atrium.

A catheter intervention was performed to stent the coarctation segment, and the fibro-muscular shelf in the right atrium was surgically resected.