bluuebunny/crossref_metadata_2025 huggingface dataset:
MIR‐137 Suppresses Growth and Invasion, is Downregulated in Oligodendroglial Tumors and Targets CSE1L
Authors: Li Kay Ka‐Wai , Yang Ling , Pang Jesse Chung‐Sean , Chan Aden Ka‐Yin , Zhou Liangfu , Mao Ying , Wang Yin , Lau Kin‐Mang , Poon Wai Sang , Shi Zhifeng , Ng Ho‐Keung
Published: December 2012

MicroRNA‐137 (miR‐137) expression has been reported to be decreased in astrocytic tumors in two expression profiling studies but its role in the pathogenesis of oligodendroglial tumors is still limited. In this study, we demonstrate that miR‐137 expression is significantly downregulated in a cohort of 35 oligodendroglial tumors and nine glioma cell lines compared with normal brains. Lower miR‐137 expression is associated with shorter progressive‐free survival and overall survival. Restoration of miR‐137 expression in an oligodendroglial cells TC620, and also glioblastoma cells of U87 and U373 significantly suppressed cell growth, anchorage‐independent growth, as well as invasion. Demethylation and deacetylation treatments resulted in upregulation of miR‐137 expression in TC620 cells. In silico analysis showed that CSE1 chromosome segregation 1‐like (yeast) (CSE1L) is a potential target gene of miR‐137. Luciferase reporter assay demonstrated that miR‐137 negatively regulates CSE1L by interaction between miR‐137 and complementary sequences in the 3′ UTR of CSE1L. Immunohistochemistry revealed that CSE1L is upregulated in oligodendroglial tumors. Knockdown of CSE1L resulted in similar outcomes as overexpressing miR‐137 in oligodendroglioma cells and glioblastoma cells. Overall, our data suggest that miR‐137 regulates growth of glioma cells and targets CSE1L, providing further understanding in the tumorigenesis of gliomas.
Prospects in the Total Synthesis of Protein Therapeutics
Authors: Chalker Justin M.
Published: December 2012

Protein therapeutics are gaining headway in the treatment and prevention of a variety of maladies. Critical to the success and growing use of biologic‐level pharmaceuticals is the development of methods for their precise synthesis. This review highlights the emerging techniques for the total synthesis of proteins, with a special focus on the possibility of accessing therapeutic targets through chemoselective peptide ligations.
Peptide Scanning for Studying Structure‐Activity Relationships in Drug Discovery
Authors: Jamieson Andrew G. , Boutard Nicolas , Sabatino David , Lubell William D.
Published: December 2012

Peptide‐based therapeutics have grown in importance over the last few decades. Furthermore, peptides have been extensively used as lead compounds in the drug discovery process to investigate the nature of chemical space required for molecular recognition and activity at a variety of targets. This critical commentary reviews scanning techniques, which employ natural and non‐proteinogenic amino acids to facilitate understanding of structural requirements for peptide biological activity. The value of sequence analysis by such methods is highlighted by examples, in which the elements for peptide affinity and activity have been elucidated and employed to prepare peptidomimetic leads for drug development.
Accounting for Receptor Flexibility and Enhanced Sampling Methods in Computer‐Aided Drug Design
Authors: Sinko William , Lindert Steffen , McCammon J. Andrew
Published: December 2012

Protein flexibility plays a major role in biomolecular recognition. In many cases, it is not obvious how molecular structure will change upon association with other molecules. In proteins, these changes can be major, with large deviations in overall backbone structure, or they can be more subtle as in a side‐chain rotation. Either way the algorithms that predict the favorability of biomolecular association require relatively accurate predictions of the bound structure to give an accurate assessment of the energy involved in association. Here, we review a number of techniques that have been proposed to accommodate receptor flexibility in the simulation of small molecules binding to protein receptors. We investigate modifications to standard rigid receptor docking algorithms and also explore enhanced sampling techniques, and the combination of free energy calculations and enhanced sampling techniques. The understanding and allowance for receptor flexibility are helping to make computer simulations of ligand protein binding more accurate. These developments may help improve the efficiency of drug discovery and development. Efficiency will be essential as we begin to see personalized medicine tailored to individual patients, which means specific drugs are needed for each patient’s genetic makeup.
The Future of Peptide‐based Drugs
Authors: Craik David J. , Fairlie David P. , Liras Spiros , Price David
Published: December 2012

The suite of currently used drugs can be divided into two categories – traditional ‘small molecule’ drugs with typical molecular weights of <500 Da but with oral bioavailability, and much larger ‘biologics’ typically >5000 Da that are not orally bioavailable and need to be delivered via injection. Due to their small size, conventional small molecule drugs may suffer from reduced target selectivity that often ultimately manifests in human side‐effects, whereas protein therapeutics tend to be exquisitely specific for their targets due to many more interactions with them, but this comes at a cost of low bioavailability, poor membrane permeability, and metabolic instability. The time has now come to reinvestigate new drug leads that fit between these two molecular weight extremes, with the goal of combining advantages of small molecules (cost, conformational restriction, membrane permeability, metabolic stability, oral bioavailability) with those of proteins (natural components, target specificity, high potency). This article uses selected examples of peptides to highlight the importance of peptide drugs, some potential new opportunities for their exploitation, and some difficult challenges ahead in this field.
Expanding the Number of ‘Druggable’ Targets: Non‐Enzymes and Protein–Protein Interactions
Authors: Makley Leah N. , Gestwicki Jason E.
Published: December 2012

Following sequencing and assembly of the human genome, the preferred methods for identification of new drug targets have changed dramatically. Modern tactics such as genome‐wide association studies (GWAS) and deep sequencing are fundamentally different from the pharmacology‐guided approaches used previously, in which knowledge of small molecule ligands acting at their cellular targets was the primary discovery engine. A consequence of the ‘target‐first, pharmacology‐second’ strategy is that many predicted drug targets are non‐enzymes, such as scaffolding, regulatory or structural proteins, and their activities are often dependent on protein–protein interactions (PPIs). These types of targets create unique challenges to drug discovery efforts because enzymatic turnover cannot be used as a convenient surrogate for compound potency. Moreover, it is often challenging to predict how ligand binding to non‐enzymes might affect changes in protein function and/or pathobiology. Thus, in the postgenomic era, targets might be strongly implicated by molecular biology‐based methods, yet they often later earn the designation of ‘undruggable’. Can the scope of available targets be widened to include these promising, but challenging, non‐enzymes? In this review, we discuss advances in high‐throughput screening (HTS) technology and chemical library design that are emerging to deal with these challenges.
Adolescent Personality Development and Identity Formation
Authors: Klimstra Theo
Published: December 2012

Personality development is not only about changes in traits but also about changes in other layers of the self, such as the identity layer. Forming one's identity is thought to be the key developmental task of adolescence, but profound changes in personality traits also occur in this period. In this article, I summarize research on these processes, including research on adolescent personality trait development from a variable‐centered and a typological point of view. With regard to identity formation, I also describe contemporary models to measure identity formation and address the importance of examining identity formation on a day‐to‐day level. Despite obvious theoretical ties between personality traits and identity formation, few studies have examined how these processes affect one another across time.
Non‐surgical management methods of noncavitated carious lesions
Authors: Tellez Marisol , Gomez Juliana , Kaur Sundeep , Pretty Iain A. , Ellwood Roger , Ismail Amid I.
Published: December 2012

Objective

To critically appraise all evidence related to the efficacy of nonsurgical caries preventive methods to arrest or reverse the progression of noncavitated carious lesions (NCCls).

Methods

A detailed search of Medline (via OVID), Cochrane Collaboration, Scielo, and EMBASE identified 625 publications. After title and abstract review, 103 publications were selected for further review, and 29 were finally included. The final publications evaluated the following therapies: fluorides (F) in varying vehicles (toothpaste, gel, varnish, mouthrinse, and combination), chlorhexidine (CHX) alone or in combination with F, resin infiltration (I), sealants (S), xylitol (X) in varying vehicles (lozenges, gum, or in combination with F and/or xylitol), casein phosphopeptide amorphous calcium phosphate (CPP‐ACP) or in combination with calcium fluoride phosphate. All included studies were randomized clinical trials, were conducted with human subjects and natural NCCls, and reported findings that can yield outcomes measures such as caries incidence/increments, percentage of progression and/or arrest, odds ratio progression test to control, fluorescence loss/mean values, changes in lesion area/volume and lesion depth. Data were extracted from the selected studies and checked for errors. The quality of the studies was evaluated by three different methods (ADA, Cochrane, author's consensus).

Results

Sample size for these trials ranged between 15 and 3903 subjects, with a duration between 2 weeks and 4.02 years. More than half of the trials assessed had moderate to high risk of bias or may be categorized as ‘poor’. The great majority (65.5%) did not use intention to treat analysis, 21% did not use any blinding techniques, and 41% reported concealment allocation procedures. Slightly more than half of the trials (55%) factored in background exposure to other fluoride sources, and only 41% properly adjusted for potential confounders.

Conclusions

Fluoride interventions (varnishes, gels, and toothpaste) seem to have the most consistent benefit in decreasing the progression and incidence of NCCls. Studies using xylitol, CHX, and CPP‐ACP vehicles alone or in combination with fluoride therapy are very limited in number and in the majority of the cases did not show a statistically significant reduction. Sealants and resin infiltration studies point to a potential consistent benefit in slowing the progression or reversing NCCls.
A centralized approach to out‐of‐province genetic testing leads to cost savings: the Alberta experience
Authors: Lilley M , Christian S , Blumenschein P , Chan S , Somerville M
Published: December 2012

The Genetic Resource Center (GRC) is a centralized process for requesting genetic testing that is not available within the province (Alberta, Canada). In order to assess potential cost savings associated with this process, all applications received by the GRC in 2010 were reviewed, and cost savings were recorded for statistical analysis. Seven areas of cost savings were identified: (i) negotiated pricing, (ii) laboratory selection, (iii) testing setup in‐province, (iv) duplicate testing, (v) inappropriate testing, (vi) sequential testing and (vii) testing offered within the province.The total test cost of the 615 applications submitted in 2010 without the GRC process would have been $766,783 (Canadian dollars). A total cost savings of $112,201 was achieved through the GRC, which represents 15% of the total cost of requested testing ($112,201/$766,783). This is the first study to examine areas of cost savings for genetic testing sent out‐of‐province. The greatest cost savings resulted from the areas of laboratory selection and negotiated pricing. A centralized process to manage out‐of‐province genetic test requests results in consistency in testing and significant cost savings.
Edaravone Protects HT22 Neurons from H2O2‐induced Apoptosis by Inhibiting the MAPK Signaling Pathway
Authors: Zhao Zhong‐Yan , Luan Ping , Huang Shi‐Xiong , Xiao Song‐Hua , Zhao Jia , Zhang Bei , Gu Bei‐Bei , Pi Rong‐Biao , Liu Jun
Published: December 2012

Aims

Oxidative stress is frequently implicated in the pathology of neurodegenerative diseases. This study aimed to investigate the effects and their underlying mechanism(s) of edaravone upon hydrogen peroxide (H2O2)–induced oxidative stress and apoptosis in HT22 cells, a murine hippocampal neuronal model.

Methods

HT22 cells were treated with H2O2 in the presence of various concentrations of edaravone or in its absence. A CCK‐8 assay, Hoechst 33342 staining, and flow cytometry were used to detect cytotoxicity and apoptosis. In addition, the levels of reactive oxygen species (ROS) and the expression of Bcl‐2, Bax, p‐ERK 1/2, p‐JNK, and p‐P38 proteins in HT22 cells were examined.

Results

Exogenous H2O2 decreased cell viability in a concentration‐dependent manner and was associated with increased apoptosis and ROS production. Moreover, H2O2 significantly activated and upregulated the expression of p‐ERK 1/2, p‐JNK, and p‐P38, while edaravon protected HT22 cells against H2O2‐induced injury by inhibiting the production of ROS and activating the MAPK signaling pathway.

Conclusions

Our results provide the first evidence that edaravone can protect H2O2‐induced cell injury in HT22 neurons via its antioxidant action. These findings suggest that edaravone may be useful in the treatment of neurodegenerative disorders in which oxidative stress has been principally implicated.
How Do Children Restrict Their Linguistic Generalizations? An (Un‐)Grammaticality Judgment Study
Authors: Ambridge Ben
Published: December 2012

A paradox at the heart of language acquisition research is that, to achieve adult‐like competence, children must acquire the ability to generalize verbs into non‐attested structures, while avoiding utterances that are deemed ungrammatical by native speakers. For example, children must learn that, to denote the reversal of an action, un‐ can be added to many verbs, but not all (e.g., roll/unroll; close/*unclose). This study compared theoretical accounts of how this is done. Children aged 5–6 (N = 18), 9–10 (N = 18), and adults (N = 18) rated the acceptability of un‐ prefixed forms of 48 verbs (and, as a control, bare forms). Across verbs, a negative correlation was observed between the acceptability of ungrammatical un‐ prefixed forms (e.g., *unclose) and the frequency of (a) the bare form and (b) alternative forms (e.g., open), supporting the entrenchment and pre‐emption hypotheses, respectively. Independent ratings of the extent to which verbs instantiate the semantic properties characteristic of a hypothesized semantic cryptotype for un‐ prefixation were a significant positive predictor of acceptability, for all age groups. The relative importance of each factor differed for attested and unattested un‐ forms and also varied with age. The findings are interpreted in the context of a new hybrid account designed to incorporate the three factors of entrenchment, pre‐emption, and verb semantics.
From Genes to Community: Exploring Translational Science in Adolescent Health Research
Authors: Miller Elizabeth
Published: December 2012

Addressing complex adolescent health problems such as youth violence and teen pregnancy requires innovative strategies to promote protective social environments, increase healthier behaviors, and reduce the impact of health risk behaviors into adulthood. Multilevel, interdisciplinary, and translational approaches are needed to address these challenges in adolescent health. In May 2012, a group of adolescent health researchers participated in a 1‐day research symposium titled “From Genes to Community: Exploring Translational Science in Adolescent Health Research,” sponsored by the Clinical and Translational Science Institute (CTSI) of the University of Pittsburgh and the Division of Adolescent Medicine, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center. The research symposium offered opportunities for adolescent health researchers to share examples of translational research as well as to identify potential collaborations to promote translational research. This and subsequent issues of Clinical and Translational Science will include papers from this symposium. The studies and reviews presented range from how basic biobehavioral sciences such as functional neuroimaging and decision science can be made relevant for intervention development as well as improving strategies for community‐partnered knowledge transfer of cutting‐edge research findings to promote adolescent health and well‐being. Clin Trans Sci 2012; Volume 5: 480–481
How commonly do children with complex cerebral arteriopathy have renovascular disease?
Authors: Willsher Alex , Roebuck Derek J , Ng Joanne , Ganesan Vijeya
Published: December 2012

Aim

To describe the frequency of renovascular abnormalities and hypertension in an opportunistic cohort of children with complex cerebrovascular disease from a single tertiary/quaternary referral centre.

Method

This was a retrospective case note and imaging review of children who had had cerebral and renal angiography, with a diagnosis of moyamoya or other occlusive cerebrovascular disease (OCVD). Hypertension was defined as at least three systolic blood pressure readings of the 95th centile or above.

Results

Of 34 children (12 males, 22 females; median age 5y 11mo, range 2mo‐15y 3mo; 20 with moyamoya, 14 with OCVD), primary presentation was neurological in 29 (arterial ischaemic stroke, transient ischaemic attack, or headache) and with hypertension in five. Renovascular abnormalities were identified in 17, of whom 10 had main renal artery stenosis. Renovascular involvement was not predictable according to arteriopathy diagnosis. Blood pressure was rarely plotted on centile charts. Using the 50th height centile for blood pressure, and based on a median of five systolic blood pressure readings per patient, 20 out of 34 met the definition for hypertension (15/29 patients with primary neurological presentation).

Interpretation

Renovascular abnormalities were common in this group of children with complex cerebrovascular disease. Blood pressure was frequently abnormal but rarely measured and infrequently plotted on centile charts. Neurologists should be alert to potential systemic vascular involvement and its sequelae in children with complex cerebrovascular disease.
Reproducibility of two functional field exercise tests for children with cerebral palsy who self‐propel a manual wheelchair
Authors: Verschuren Olaf , Ketelaar Marjolijn , De Groot Janke , Vila Nova FÁbio , Takken Tim
Published: December 2012

Aim

The aim of this study was to examine the test–retest reproducibility (reliability and agreement) of the 6‐minute push test (6MPT) and the one‐stroke push test (1SPT), and construct validity of the 6MPT in children with cerebral palsy (CP) who self‐propel a manual wheelchair.

Method

Seventy‐three children and adolescents with spastic CP (51 males, 22 females; mean age 11y 9mo, SD 3y 7mo, range 4–18y; three unilateral, 70 bilateral) using a manual wheelchair for at least part of the day were recruited from and tested in different rehabilitation settings in the Netherlands and Brazil. Participants were classified as Gross Motor Function Classification System (GMFCS) level II (n=7), III (n=36), or IV (n=30).

Results

Intraclass correlation coefficients (ICCs) for distance covered on the 6MPT (mean distance 266.5m, SD 120.6m) and the 1SPT (mean distance 4.5m, SD 2.7m) showed excellent reliability (ICC=0.97) for both tests. There was a significant correlation between the 6MPT and the 1SPT (r=0.73; p<0.001), and between the 6MPT and heart rate during the 6MPT (r=0.29, p=0.014).

Interpretation

These results indicate that both the 6MPT and the 1SPT test are reproducible functional tests for young people with CP who self‐propel a wheelchair. Agreement for the 6MPT seems relatively large for children who perform short distances. Construct validity is supported for the 6MPT in children with CP.
Employment Protection, Flexibility and Firms' Strategic Location Decisions under Uncertainty
Authors: Dewit Gerda , Leahy Dermot , Montagna Catia
Published: December 2012

We construct a model in which oligopolistic firms decide between locating in a country where employment protection implies costly output adjustments and in one without employment protection. Using a two‐period three‐stage game with uncertainty, we demonstrate that location is influenced by both flexibility and strategic concerns. The strategic effects under Cournot work towards domestic anchorage in the country with employment protection, while those under Bertrand do not. Strategic agglomeration can occur in the inflexible country under Cournot and even under Bertrand, provided that uncertainty and foreign direct investment costs are low.
Appropriate Health R&D and Intellectual Property Rights Reform in Developing Countries
Authors: Aksan Anna‐Maria
Published: December 2012

Welfare implications of imposing intellectual property rights (IPR) protection on health goods in developing countries are analysed using a North–South model. Consumption of health goods counteracts adverse effects of region‐specific diseases on labour supply. Health needs differ between consumers in innovating and imitating countries, weakening the benefits of southern IPR enforcement for the North and strengthening the benefits for the South. Southern regions with unique health needs are more likely to benefit from IPR enforcement if healthcare infrastructure is adequate and the southern market is large enough to stimulate sufficient innovation. There is then also interregional income convergence.
Global Fixed Capital Investment by Multinational Firms
Authors: Belderbos René , Fukao Kyoji , Ito Keiko , Letterie Wilko
Published: December 2012

We develop and test a model of the simultaneous determination of global gross fixed capital investments by multinational firms. We integrate a model of multi‐product firms choosing optimal manufacturing locations with a model of dynamic investment optimization. Firms adjust capital stocks in each location in accordance with the expected marginal profitability of capital. Analysis of 1504 fixed capital investment decisions by Japanese multinational firms confirms the prediction that investment is determined not only by total factor productivity, effective demand, and wage levels in the host country, but also by wage levels in other countries in which the firm operates.
Quantitative Myocardial Contrast Supine Bicycle Stress Echocardiography for Detection of Coronary Artery Disease
Authors: Miszalski‐Jamka Tomasz , Kuntz‐Hehner Stefanie , Tiemann Klaus , Karwat Krzysztof , Kostkiewicz Magdalena
Published: December 2012

Background: If compared with two‐dimensional echocardiography (2DE), quantitative myocardial contrast echocardiography (MCE) improves detection of coronary artery disease (CAD) during pharmacological stress, but there is paucity of data regarding quantitative MCE performed during supine bicycle stress. Objectives: To determine the feasibility and accuracy of quantitative MCE and assess its incremental benefit over 2DE for detection of CAD during supine bicycle stress. Methods: Sixty‐one consecutive patients (47 males, 14 females, mean age 57 ± 12 years) with suspected CAD, who were scheduled for coronary angiography, underwent 2DE and MCE supine bicycle stress. The diagnosis of obstructive CAD (≥50% stenosis) was based on inducible wall‐motion and myocardial perfusion abnormalities. For quantitative myocardial perfusion analysis, A, β, and Aβ reserve were derived from myocardial contrast replenishment curves. Results: Quantitative coronary angiography revealed ≥50% stenosis in 41, ≥70% stenosis in 18, single vessel disease in 24, and multivessel disease in 17 patients. If compared with 2DE, quantitative MCE was more sensitive (71% vs. 93%; P < 0.05) and more accurate (74% vs. 89%; P < 0.05) to detect obstructive CAD. The sensitivity of 2DE and quantitative MCE was 61% and 91% (P < 0.05) in 50–69% stenosis, and 63% and 92% (P < 0.05) in single vessel disease. No difference in sensitivity between 2DE and quantitative MCE was found in subjects with ≥70% stenosis (83% vs. 94%, P = NS) and multivessel disease (82% vs. 94%, P = NS). Conclusions: Quantitative MCE enhances sensitivity and accuracy of supine bicycle stress 2DE for detection of obstructive CAD, and this incremental benefit is especially present in less severe disease.
Frontal lobe connectivity and cognitive impairment in pediatric frontal lobe epilepsy
Authors: Braakman Hilde M. H. , Vaessen Maarten J. , Jansen Jacobus F. A. , Debeij‐van Hall Mariette H. J. A. , de Louw Anton , Hofman Paul A. M. , Vles Johan S. H. , Aldenkamp Albert P. , Backes Walter H.
Published: December 2012

Purpose:  Cognitive impairment is frequent in children with frontal lobe epilepsy (FLE), but its etiology is unknown. With functional magnetic resonance imaging (fMRI), we have explored the relationship between brain activation, functional connectivity, and cognitive functioning in a cohort of pediatric patients with FLE and healthy controls.

Methods:  Thirty‐two children aged 8–13 years with FLE of unknown cause and 41 healthy age‐matched controls underwent neuropsychological assessment and structural and functional brain MRI. We investigated to which extent brain regions activated in response to a working memory task and assessed functional connectivity between distant brain regions. Data of patients were compared to controls, and patients were grouped as cognitively impaired or unimpaired.

Key Findings:  Children with FLE showed a global decrease in functional brain connectivity compared to healthy controls, whereas brain activation patterns in children with FLE remained relatively intact. Children with FLE complicated by cognitive impairment typically showed a decrease in frontal lobe connectivity. This decreased frontal lobe connectivity comprised both connections within the frontal lobe as well as connections from the frontal lobe to the parietal lobe, temporal lobe, cerebellum, and basal ganglia.

Significance:  Decreased functional frontal lobe connectivity is associated with cognitive impairment in pediatric FLE. The importance of impairment of functional integrity within the frontal lobe network, as well as its connections to distant areas, provides new insights in the etiology of the broad‐range cognitive impairments in children with FLE.
A population‐based study of newly diagnosed epilepsy in infants
Authors: Eltze Christin M. , Chong Wui K. , Cox Tim , Whitney Andrea , Cortina‐Borja Mario , Chin Richard F. M. , Scott Rod C. , Cross J. Helen
Published: December 2012

Purpose:  Most published data on infants presenting with epilepsy originate from hospital/specialist clinic settings and may therefore not be representative of the general population. We carried out a population‐based study to estimate the incidence of epilepsy onset in infants, to characterize the range of phenotypes and associated structural brain abnormalities, and to determine whether specific epilepsy diagnoses could be established at onset.

Methods:  Children between 1 and 24 months of age with new‐onset epilepsy were ascertained over 13 months from the residents in 15 boroughs of North London. Classification based on clinical information, electroencephalography (EEG), and neuroimaging data was undertaken independently by two pediatric neurologists. Neuroimages were reviewed by two neuroradiologists blinded to clinical details.

Key Findings:  A total of 57 children were enrolled giving an ascertainment‐adjusted incidence of 70.1 (95% CI [56.3, 88.5])/100,000 children ≤2 years of age/year (ascertainment 76%). The incidence was highest among Asian children. An electroclinical syndrome was identified in 24 (42%) cases of which 21 were epileptic encephalopathies. Magnetic resonance (MR) images of 51 cases (89% of the total cohort) were reviewed. These demonstrated positive findings in 37 (72%) of 51 cases, of which 26 (51%) of 51 were etiologically relevant, and included developmental malformations in 11 (21%) of 51.

Significance:  In a population setting infantile onset epilepsy presents mostly with complex phenotypes commonly associated with structural brain abnormalities. Routine MR imaging at presentation is therefore justified. However, identification of specific electroclinical syndromes remains difficult at onset.
Chinese Immigrant Families and Christian Faith Community: A Qualitative Study
Authors: Lu Yaxin , Marks Loren , Apavaloiae Loredana
Published: December 2012

Like most other immigrants, Chinese immigrants in the U.S. have experienced challenges in acculturation to the American mainstream culture. Major challenges for Chinese immigrants include identity problems, language barriers, relationships problems, and lack of economic and social resources (Families and change: Coping with stressful events and transitions (pp. 307–332). New York: Sage). With respect to social resources, the Chinese Christian Church plays an important role in coping, acculturation, and assimilation processes for many Chinese immigrant families (Sociology of Religion, 67, 149–159). However, for some, conversion to the Chinese Christian Church becomes an existential as well as a social force—a source of meaning in their new life, and a source of transformation of their marriage and family life. This qualitative study examines the social, cultural, and spiritual roles of faith community in Chinese immigrants' marriages and family lives. Also, the research‐based connections between: (i) families and religion, and more specifically, (ii) Chinese Christian families and religion are examined.
Latina Immigrant Mothers: Negotiating New Food Environments to Preserve Cultural Food Practices and Healthy Child Eating
Authors: Greder Kimberly , de Slowing Flor Romero , Doudna Kimberly
Published: December 2012

Latina immigrant mothers face complex challenges as they try to ensure their children get adequate nourishment to grow up healthy in their new U.S. communities. Eighty‐three Latina immigrant mothers living in a rural area of a Midwestern state who had young children and low household incomes were interviewed to explore their satisfaction with the food their children were eating, as well as ecological factors that affected children's eating patterns. Three overarching themes emerged from the data: (i) Mothers as gatekeepers of healthy child eating; (ii) Barriers to healthy child eating; and (iii) Changing child eating patterns. Mothers retained their cultural identity as primary caregivers and wanted their children to consume nourishing food. Mothers varied in their ability to negotiate their new food environments to maintain cultural food practices and promote healthy child eating patterns. Family and consumer science professionals could facilitate opportunities to (i) link immigrant families to Extension Master Gardeners to learn techniques to successfully grow food in a new climate; (ii) bring immigrant families, school food service staff, growers and grocers together to strategize how to increase children's access to locally grown food at school; (iii) assist immigrant families in identifying strategies to maintain healthy cultural food traditions while consuming less fat, salt, and sugar; and (iv) increase representation of immigrant families on school and community program advisory committees to ensure policies and programs are informed by families. Such opportunities can strengthen social capital among immigrant families and their community and support healthy child eating patterns.
Mitochondrial dysfunction leads to impairment of insulin sensitivity and adiponectin secretion in adipocytes
Authors: Wang Chih‐Hao , Wang Ching‐Chu , Huang Hsin‐Chang , Wei Yau‐Huei
Published: December 2012

Adipocytes play an integrative role in the regulation of energy metabolism and glucose homeostasis in the human body. Functional defects in adipocytes may cause systemic disturbance of glucose homeostasis. Recent studies revealed mitochondrial abnormalities in the adipose tissue of patients with type 2 diabetes. In addition, patients with mitochondrial diseases usually manifest systemic metabolic disorder. However, it is unclear how mitochondrial dysfunction in adipocytes affects the regulation of glucose homeostasis. In this study, we induced mitochondrial dysfunction and overproduction of reactive oxygen species (ROS) by addition of respiratory inhibitors oligomycin A and antimycin A and by knockdown of mitochondrial transcription factor A (mtTFA), respectively. We found an attenuation of the insulin response as indicated by lower glucose uptake and decreased phosphorylation of Akt upon insulin stimulation of adipocytes with mitochondrial dysfunction. Furthermore, the expression of glucose transporter 4 (Glut4) and secretion of adiponectin were decreased in adipocytes with increased ROS generated by defective mitochondria. Moreover, the severity of insulin insensitivity was correlated with the extent of mitochondrial dysfunction. These results suggest that higher intracellular ROS levels elicited by mitochondrial dysfunction resulted in impairment of the function of adipocytes in the maintenance of glucose homeostasis through attenuation of insulin signaling, downregulation of Glut4 expression, and decrease in adiponectin secretion. Our findings substantiate the important role of mitochondria in the regulation of glucose homeostasis in adipocytes and also provide a molecular basis for the explanation of the manifestation of diabetes mellitus or insulin insensitivity in a portion of patients with mitochondrial diseases such as MELAS or MERRF syndrome.
Tetrameric structure of SUR2B revealed by electron microscopy of oriented single particles
Authors: Fotinou Constantina , Aittoniemi Jussi , de Wet Heidi , Polidori Ange , Pucci Bernard , Sansom Mark S. P. , Vénien‐Bryan Catherine , Ashcroft Frances M.
Published: December 2012

The ATP‐sensitive potassium (KATP) channel is a hetero‐octameric complex that links cell metabolism to membrane electrical activity in many cells, thereby controlling physiological functions such as insulin release, muscle contraction and neuronal activity. It consists of four pore‐forming Kir6.2 and four regulatory sulfonylurea receptor (SUR) subunits. SUR2B serves as the regulatory subunit in smooth muscle and some neurones. An integrative approach, combining electron microscopy and homology modelling, has been used to obtain information on the structure of this large (megadalton) membrane protein complex. Single‐particle electron microscopy of purified SUR2B tethered to a lipid monolayer revealed that it assembles as a tetramer of four SUR2B subunits surrounding a central hole. In the absence of an X‐ray structure, a homology model for SUR2B based on the X‐ray structure of the related ABC transporter Sav1866 was used to fit the experimental images. The model indicates that the central hole can readily accommodate the transmembrane domains of the Kir tetramer, suggests a location for the first transmembrane domains of SUR2B (which are absent in Sav1866) and suggests the relative orientation of the SUR and Kir6.2 subunits.

Structured digital abstract

SUR2B and SUR2B bind by electron microscopy (View interaction)

SUR2B and SUR2B bind by molecular sieving (View interaction)
Global climate change in large European rivers: long‐term effects on macroinvertebrate communities and potential local confounding factors
Authors: Floury Mathieu , Usseglio‐Polatera Philippe , Ferreol Martial , Delattre Cecile , Souchon Yves
Published: December 2012

Aquatic species living in running waters are widely acknowledged to be vulnerable to climate‐induced, thermal and hydrological fluctuations. Climate changes can interact with other environmental changes to determine structural and functional attributes of communities. Although such complex interactions are most likely to occur in a multiple‐stressor context as frequently encountered in large rivers, they have received little attention in such ecosystems. In this study, we aimed at specifically addressing the issue of relative long‐term effects of global and local changes on benthic macroinvertebrate communities in multistressed large rivers. We assessed effects of hydroclimatic vs. water quality factors on invertebrate community structure and composition over 30 years (1979–2008) in the Middle Loire River, France. As observed in other large European rivers, water warming over the three decades (+0.9 °C between 1979–1988 and 1999–2008) and to a lesser extent discharge reduction (−80 m3 s−1) were significantly involved in the disappearance or decrease in taxa typical from fast running, cold waters (e.g. Chloroperlidae and Potamanthidae). They explained also a major part of the appearance and increase of taxa typical from slow flowing or standing waters and warmer temperatures, including invasive species (e.g. Corbicula sp. and Atyaephyra desmarestii). However, this shift towards a generalist and pollution tolerant assemblage was partially confounded by local improvement in water quality (i.e. phosphate input reduction by about two thirds and eutrophication limitation by almost one half), explaining a significant part of the settlement of new pollution‐sensitive taxa (e.g. the caddisfly Brachycentridae and Philopotamidae families) during the last years of the study period. The regain in such taxa allowed maintaining a certain level of specialization in the invertebrate community despite climate change effects.
Latitudinal phytoplankton distribution and the neutral theory of biodiversity
Authors: Chust Guillem , Irigoien Xabier , Chave Jerome , Harris Roger P.
Published: December 2012

Aim

Recent studies have suggested that global diatom distributions are not limited by dispersal, in the case of both extant species and fossil species, but rather that environmental filtering explains their spatial patterns. Hubbell's neutral theory of biodiversity provides a framework in which to test these alternatives. Our aim is to test whether the structure of marine phytoplankton (diatoms, dinoflagellates and coccolithophores) assemblages across the Atlantic agrees with neutral theory predictions. We asked: (1) whether intersite variance in phytoplankton diversity is explained predominantly by dispersal limitation or by environmental conditions; and (2) whether species abundance distributions are consistent with those expected by the neutral model.

Location

Meridional transect of the Atlantic (50° N–50° S).

Methods

We estimated the relative contributions of environmental factors and geographic distance to phytoplankton composition using similarity matrices, Mantel tests and variation partitioning of the species composition based upon canonical ordination methods. We compared the species abundance distribution of phytoplankton with the neutral model using Etienne's maximum‐likelihood inference method.

Results

Phytoplankton communities are slightly more determined by niche segregation (24%), than by dispersal limitation and ecological drift (17%). In 60% of communities, the assumption of neutrality in species’ abundance distributions could not be rejected. In tropical zones, where oceanic gyres enclose large stable water masses, most communities showed low species immigration rates; in contrast, we infer that communities in temperate areas, out of oligotrophic gyres, have higher rates of species immigration.

Conclusions

Phytoplankton community structure is consistent with partial niche assembly and partial dispersal and drift assembly (neutral processes). The role of dispersal limitation is almost as important as habitat filtering, a fact that has been largely overlooked in previous studies. Furthermore, the polewards increase in immigration rates of species that we have discovered is probably caused by water mixing conditions and productivity.
Home ownership and fall‐related outcomes among older adults in South Korea
Authors: Do Young Kyung , Kim Cheong‐Seok
Published: December 2012

Aim

Many of the previously identified environmental risk factors for fall‐related outcomes (e.g. flooring, stairs and steps, kitchen, and bathrooms) are amenable to change, but the extent of the changes on these home‐related risk factors are conditional on home ownership of the elderly. This study aims to test whether lack of home ownership is associated with a higher risk of falls, and a higher likelihood of reporting fear of falling and activity limitations due to fear of falling among older adults in South Korea.

Methods

Using data from the first two waves (2006 and 2008) of the Korean Longitudinal Study of Aging, the associations between home ownership variables and three fall‐related outcomes were examined in two regression models. A logistic regression model of any falls in the past 2 years was estimated to examine whether older adults living in short‐term rental homes based on monthly rent have an increased risk of falls. A probit model accounting for sample selection was estimated to examine whether the two related outcomes, fear of falling and limiting activities due to fear of falling, are associated with home ownership status.

Results

Compared with owned home, short‐term rental home predicted a higher likelihood of incident of falls and activity limitation due to fear of falling.

Conclusions

The study findings suggest that the lack of home ownership with unstable housing tenure is an important risk factor for fall‐related outcomes among older adults in South Korea. Geriatr Gerontol Int 2013; 13: 867–873
Anemia in elderly patients: New insight into an old disorder
Authors: Andrès Emmanuel , Serraj Khalid , Federici Laure , Vogel Thomas , Kaltenbach Georges
Published: December 2012

Anemia is an important healthcare concern among the elderly. In these patients, the anemia is often mild, with a hemoglobin level >10 g/dL. It is usually well tolerated, but might be responsible for several proteiform and/or atypical presenting complaints. In the elderly, anemia is usually of multifactorial origin, including chronic inflammation, chronic kidney disease, nutrient deficiencies and iron deficiency (approximately two‐thirds of all cases). The remaining cases are unexplained (unknown etiology). In the elderly, the classic diagnosis of anemia, which is based on the mean corpuscular volume associated with a low hemoglobin level, might not be accurate. A predefined standardized diagnostic procedure should be followed. In the common case of frail elderly patients, all investigations should be carefully considered and invasive examinations undertaken where justified (risk–benefit balance). Nevertheless, most cases of anemia require further investigation and the underlying cause should be identified and treated whenever possible. Geriatr Gerontol Int 2013; 13: 519–527.
Therapeutic factor VIII does not trigger TLR1.2 and TLR2.6 signalling in vitro
Authors: Teyssandier M. , André S. , Gupta N. , Dasgupta S. , Bayry J. , Kaveri S. V. , Lacroix‐Desmazes S. ,   The ABIRISK consortium
Published: December 2012

The administration of therapeutic factor VIII (FVIII) to patients with haemophilia A induces the development of inhibitory anti‐FVIII IgG in a substantial number of patients. For an antigen‐specific immune response to develop, antigen‐presenting cells (APCs) need to mature and procure appropriate co‐stimulatory signals to T cells at the time of presentation of the endocytosed antigen. The nature of the danger signals that induce APC maturation, thus initiating the anti‐FVIII immune response, are yet ill‐characterized. Contradictory reports on a direct effect of therapeutic FVIII on APC maturation have been released. Here, we investigated whether FVIII directly triggers Toll‐like receptor 2 (TLR2) signalling. The capacity of human recombinant FVIII to promote the maturation of a mouse bone marrow macrophage cell line (BMA) was investigated by flow cytometry. In parallel, the triggering of TLR1.2 or TLR2.6‐expressing HEK293 cells by FVIII was analysed following transfection of the cells with a reporter construct for NFκB activity. In contrast, to zymosan, a known TLR2 agonist, human recombinant FVIII did not induce the maturation of mouse BMA macrophages, as analysed by the levels of expression of CD80, CD86, CD40 and I‐Ab at the cell surface. Furthermore, incubation of FVIII with cells expressing TLR2 paired with TLR1 or TLR6, failed to activate NFκB, whereas NKκB activity was triggered in the presence of zymosan. Our results confirm that FVIII alone is insufficient to trigger the maturation of APCs that is required to initiate an immune response.
Coma After Greater Occipital Nerve Blockade in a Patient With Previous Posterior Fossa Surgery
Authors: Sprenger Till , Seifert Christian L.
Published: December 2012

We here report the case of a patient who previously underwent posterior fossa surgery and was later treated with greater occipital nerve blockade for unilateral facial pain. The patient went into coma immediately post‐injection but made a full recovery without sequelae after intensive care treatment. Physicians should be aware of the risks of greater occipital nerve blockade after previous posterior fossa craniotomy.
The prognostic impact of human leukocyte antigen (HLA) class I antigen abnormalities in salivary gland cancer. A clinicopathological study of 288 cases
Authors: Müller Maximilian , Agaimy Abbas , Zenk Johannes , Ettl Tobias , Iro Heinrich , Hartmann Arndt , Seliger Barbara , Schwarz Stephan
Published: December 2012

Aims

To study abnormalities of proteins of the major histocompatibility complex class I in a series of 288 salivary gland carcinomas, and to correlate findings with patients’ overall survival (OS).

Methods and results

Protein expression of human leukocyte antigen (HLA)‐A, heavy chain (HC)‐10, β2‐microglobulin, low molecular weight polypeptides (LMP) 2 and 7, transporters associated with antigen processing (TAP) 1 and 2, calnexin, calreticulin, endoplasmic reticulum (ER) p57 and tapasin was evaluated by immunohistochemistry and semiquantitatively analyzed. As compared with normal salivary gland tissue, HLA‐A, LMP7, TAP2 and HLA class I were significantly down‐regulated in salivary gland carcinomas, whereas β2‐microglobulin, calnexin, LMP2, and TAP1 were upregulated. Expression of calreticulin, ERp57 and tapasin was unaltered. In univariate Kaplan–Meier analyses, low expression of LMP7 (P = 0.005) and high expression of β2‐microglobulin (P = 0.028), HLA‐A (P < 0.001), TAP1 (P = 0.01), and tapasin (P < 0.001) were significantly associated with shorter OS. In multivariate analysis incorporating tumour stage, nodal/distant metastasis, and grade, HLA‐A (P = 0.014), LMP7 (P = 0.033), and tapasin (P = 0.024), as well as distant metastasis (P = 0.012) and high tumour grade (P < 0.001), remained statistically significant.

Conclusion

The prognostic influence of up‐regulated HLA‐A and tapasin and down‐regulated LMP7 may provide a rationale for targeting these specific components of the antigen processing and presentation pathway in salivary gland carcinomas.