bluuebunny/crossref_metadata_2025 huggingface dataset:
Rumseyite, [Pb2OF]Cl, the first naturally occurring fluoroxychloride mineral with the parent crystal structure for layered lead oxychlorides
Authors: Turner R. W. , Siidra O. I. , Krivovichev S. V. , Stanley C. J. , Spratt J.
Published: November 2012

Rumseyite, ideally [Pb2OF]Cl, is a new mineral species which is associated with calcite, cerussite, diaboleite, hydrocerussite and undifferentiated Mn oxides in a small cavity in 'hydrocerussite' from a manganese pod at Merehead quarry, Somerset, England. Rumseyite is tetragonal, I4/mmm, a = 4.065(1), c = 12.631(7) Å, V = 208.7(1) Å3, Z = 2. The mineral is translucent pale orange-brown with a white streak and vitreous lustre. It is brittle with perfect {100} cleavage; Dcalc = 7.71 g cm–3 (for the ideal formula, [Pb2OF]Cl). The mean refractive index in air at 589 nm is 2.15. The six strongest reflections in the X-ray powder-diffraction pattern [dmeas in Å, (Irel), (hkl)] are as follows: 2.923(100)(013), 2.875(68)(110), 3.848(41)(011), 6.306(17)(002), 1.680(14)(123), 2.110(12)(006). The crystal structure of rumseyite is based on alternating [OFPb2] and Cl layers. Rumseyite is related to other layered Pb oxyhalides. Fluorine and oxygen are statistically disordered over one crystallographic site. Rumseyite is named in honour of Michael Scott (Mike) Rumsey (1980– ), Curator and Collections Manager at the NHM (London), who discovered the mineral. The mineral and name have been approved by the IMA Commission on New Mineral Names and Classification (IMA 2011-091). The holotype specimen is in the collections of the Natural History Museum, London (specimen number BM1970,110).
High-temperature synchrotron X-ray powder diffraction study of Cs2XSi5O12(X = Cd, Cu, Zn) leucites
Authors: Bell A. M. T. , Henderson C. M. B.
Published: November 2012

Synchrotron X-ray powder diffraction data have been collected on three synthetic leucite analogues with the general formula Cs2XSi5O12(X = Cd, Cu, Zn) between 295 and 1173 K. All three samples have the orthorhombic Pbca leucite structure at room temperature with ordered framework T-site cations. The sample with X = Cd retains the Pbca structure over the whole of the investigated temperature range. The sample with X = Cu also retains the Pbca structure, but there is a transition to a less distorted structure with a larger unit-cell volume at ∼333 K. The sample with X = Zn shows evidence for a transition to a previously unknown Pa cubic structure, with some T-site cation disorder, at 566 K, on heating. This transition is reversible on cooling to 633 K.
Searching for resistance genes to Bursaphelenchus xylophilus using high throughput screening
Authors: Santos Carla S , Pinheiro Miguel , Silva Ana I , Egas Conceição , Vasconcelos Marta W
Published: November 2012

Background

Pine wilt disease (PWD), caused by the pinewood nematode (PWN; Bursaphelenchus xylophilus), damages and kills pine trees and is causing serious economic damage worldwide. Although the ecological mechanism of infestation is well described, the plant’s molecular response to the pathogen is not well known. This is due mainly to the lack of genomic information and the complexity of the disease. High throughput sequencing is now an efficient approach for detecting the expression of genes in non-model organisms, thus providing valuable information in spite of the lack of the genome sequence. In an attempt to unravel genes potentially involved in the pine defense against the pathogen, we hereby report the high throughput comparative sequence analysis of infested and non-infested stems of Pinus pinaster (very susceptible to PWN) and Pinus pinea (less susceptible to PWN).

Results

Four cDNA libraries from infested and non-infested stems of P. pinaster and P. pinea were sequenced in a full 454 GS FLX run, producing a total of 2,083,698 reads. The putative amino acid sequences encoded by the assembled transcripts were annotated according to Gene Ontology, to assign Pinus contigs into Biological Processes, Cellular Components and Molecular Functions categories. Most of the annotated transcripts corresponded to Picea genes-25.4-39.7%, whereas a smaller percentage, matched Pinus genes, 1.8-12.8%, probably a consequence of more public genomic information available for Picea than for Pinus. The comparative transcriptome analysis showed that when P. pinaster was infested with PWN, the genes malate dehydrogenase, ABA, water deficit stress related genes and PAR1 were highly expressed, while in PWN-infested P. pinea, the highly expressed genes were ricin B-related lectin, and genes belonging to the SNARE and high mobility group families. Quantitative PCR experiments confirmed the differential gene expression between the two pine species.

Conclusions

Defense-related genes triggered by nematode infestation were detected in both P. pinaster and P. pinea transcriptomes utilizing 454 pyrosequencing technology. P. pinaster showed higher abundance of genes related to transcriptional regulation, terpenoid secondary metabolism (including some with nematicidal activity) and pathogen attack. P. pinea showed higher abundance of genes related to oxidative stress and higher levels of expression in general of stress responsive genes. This study provides essential information about the molecular defense mechanisms utilized by P. pinaster and P. pinea against PWN infestation and contributes to a better understanding of PWD.
ST proteins, a new family of plant tandem repeat proteins with a DUF2775 domain mainly found in Fabaceae and Asteraceae
Authors: Albornos Lucía , Martín Ignacio , Iglesias Rebeca , Jiménez Teresa , Labrador Emilia , Dopico Berta
Published: November 2012

Background

Many proteins with tandem repeats in their sequence have been described and classified according to the length of the repeats: I) Repeats of short oligopeptides (from 2 to 20 amino acids), including structural cell wall proteins and arabinogalactan proteins. II) Repeats that range in length from 20 to 40 residues, including proteins with a well-established three-dimensional structure often involved in mediating protein-protein interactions. (III) Longer repeats in the order of 100 amino acids that constitute structurally and functionally independent units. Here we analyse ShooT specific (ST) proteins, a family of proteins with tandem repeats of unknown function that were first found in Leguminosae, and their possible similarities to other proteins with tandem repeats.

Results

ST protein sequences were only found in dicotyledonous plants, limited to several plant families, mainly the Fabaceae and the Asteraceae. ST mRNAs accumulate mainly in the roots and under biotic interactions. Most ST proteins have one or several Domain(s) of Unknown Function 2775 (DUF2775). All deduced ST proteins have a signal peptide, indicating that these proteins enter the secretory pathway, and the mature proteins have tandem repeat oligopeptides that share a hexapeptide (E/D)FEPRP followed by 4 partially conserved amino acids, which could determine a putative N-glycosylation signal, and a fully conserved tyrosine. In a phylogenetic tree, the sequences clade according to taxonomic group. A possible involvement in symbiosis and abiotic stress as well as in plant cell elongation is suggested, although different STs could play different roles in plant development.

Conclusions

We describe a new family of proteins called ST whose presence is limited to the plant kingdom, specifically to a few families of dicotyledonous plants. They present 20 to 40 amino acid tandem repeat sequences with different characteristics (signal peptide, DUF2775 domain, conservative repeat regions) from the described group of 20 to 40 amino acid tandem repeat proteins and also from known cell wall proteins with repeat sequences. Several putative roles in plant physiology can be inferred from the characteristics found.
The contribution of FTO and UCP-1SNPs to extreme obesity, diabetes and cardiovascular risk in Brazilian individuals
Authors: Ramos Adauto V , Bastos-Rodrigues Luciana , Resende Bruna A , Friedman Eitan , Campanha-Versiani Luciana , Miranda Debora M , Sarquis Marta , De Marco Luiz
Published: November 2012

Background

Obesity has become a common human disorder associated with significant morbidity and mortality and adverse effects on quality of life. Sequence variants in two candidate genes, FTO and UCP-1, have been reported to be overrepresented in obese Caucasian population. The association of these genes polymorphisms with the obesity phenotype in a multiethnic group such as the Brazilian population has not been previously reported.

Methods

To assess the putative contribution of both FTO and UCP-1 to body mass index (BMI) and cardiovascular risk we genotyped SNPs rs9939609 (FTO) and rs6536991, rs22705565 and rs12502572 (UCP-1) from 126 morbidly obese subjects (BMI 42.9 ± 5.6 kg/m2, mean ± SE) and 113 normal-weight ethnically matched controls (BMI 22.6 ± 3.5 kg/m2, mean ± SE). Waist circumference, blood pressure, glucose and serum lipids were also measured. Each sample was also genotyped for 40 biallelic short insertion/deletion polymorphism (indels) for ethnic assignment and to estimate the proportion of European, African and Amerindian biogeographical ancestry in the Brazilian population.

Results

Cases did not differ from controls in the proportions of genomic ancestry. The FTO SNP rs9939609 and UCP-1 SNP rs6536991 were significantly associated with BMI (p= 0.04 and p<0.0001 respectively). An allele dose dependent tendency was observed for BMI for rs6536991 sample of controls. No other significant associations between any SNP and hypertension, hyperlipidemia and diabetes were noted after correction for BMI and no significant synergistic effect between FTO and UCP-1 SNPs with obesity were noted. There was not an association between rs9939609 (FTO) and rs6536991 (UCP-1) in with maximum weight loss after 1 year in 94 obese patients who underwent bariatric surgery.

Conclusion

Our data are consistent with FTO rs9939609 and UCP-1 rs6536991 common variants as contributors to obesity in the Brazilian population.
The utility of the Hopkins Verbal Learning Test (Chinese version) for screening dementia and mild cognitive impairment in a Chinese population
Authors: Shi Jing , Tian Jinzhou , Wei Mingqing , Miao Yingchun , Wang Yongyan
Published: November 2012

Background

The Hopkins Verbal Learning Test (HVLT) has been validated for detecting dementia in English-speaking populations. However, no studies have examined the Chinese version of the HVLT scale, and appropriate cut-off scores for dementia in the Chinese population remain unclear.

Methods

631 subjects aged 60 and over were recruited at a memory clinic at Dongzhimen Hospital in Beijing. Of these, 249 were classified as exhibiting normal cognition (NC), 134 were diagnosed with mild cognitive impairment (MCI), 97 were diagnosed with Alzheimer’s disease (AD), 14 met the diagnosis for vascular dementia (VaD), and 50 were diagnosed with other types of dementia, including mixed dementia. The discriminative capacity of the HVLT total learning score, recognition score and total score were calculated to determine their sensitivity and specificity for detecting MCI, AD and other dementias, and various cut-off scores.

Results

HVLT scores were affected by age, education and sex. The HVLT total learning score exhibited an optimal balance between sensitivity and specificity using a cut-off score of 15.5 for distinguishing AD and other types of dementia from NC using the ROC curve, with sensitivity of 94.7% for distinguishing AD and all types of dementia, and specificity of 92.5% for detecting AD and 93.4% for detecting all types of dementias. We stratified the AD and MCI groups by age, and calculated the validity in each age group. In the 50–64 years age group, when the cutoff score was 18.5, the sensitivity of 0.955 and specificity of 0.921 were obtained for discriminating the NC and AD groups, and in the 65–80 years group, and optimal sensitivity and specificity values (0.948 and 0.925, respectively) were obtained with a cutoff score of 14.5.

When the cutoff score was 21.5 in HVLT total recall, an optimal balance was obtained between sensitivity and specificity (69.1% and 70.7%, respectively) in distinguishing MCI from NC.

Conclusion

A cut-off score of 15.5 in the HVLT total learning score led to high discriminative capacity between the dementia and NC groups. This suggests that the HVLT total learning score can provide a useful tool for discriminating dementia, but not MCI, from NC in clinical and epidemiological practice.
Lessons drawn from research utilization in the maternal iodine supplementation policy development in Thailand
Authors: Tonmukayakul Utsana , Velasco Román Pérez , Tantivess Sripen , Teerawattananon Yot
Published: November 2012

In this paper, the authors share their experience on evidence utilization in the development of Thailand’s maternal iodine supplementation policy in 2009–2010. Observations and reflections on their experience of engaging with research for policymaking are illustrated. The case study indicates that rapid approaches in conducting research, namely a targeted literature review and cross-sectional survey of professionals’ opinions and current practices were efficient in achieving the timeliness of evidence provision. In addition pro-activity, trust and interaction between researchers and policymakers enhanced the research–policy integration. The Thai experience may be useful for other developing countries which pursue evidence-informed policymaking, despite differences in the health system context.
Correction of vitamin D deficiency in critically ill patients - VITdAL@ICU study protocol of a double-blind, placebo-controlled randomized clinical trial
Authors: Amrein Karin , Schnedl Christian , Berghold Andrea , Pieber Thomas R , Dobnig Harald
Published: November 2012

Background

Vitamin D deficiency is associated with multiple adverse health outcomes including increased morbidity and mortality in the general population and in critically ill patients. However, no randomized controlled trial has evaluated so far whether treatment with sufficiently large doses of vitamin D can improve clinical outcome of patients in an intensive care setting.

Methods/design

The VITdAL@ICU trial is an investigator-initiated, non-commercial, double-blind, placebo-controlled randomized clinical trial. This study compares high-dose oral cholecalciferol (vitamin D3) versus placebo treatment in a mixed population of 480 critically ill patients with low 25-hydroxyvitamin-D levels at study enrollment (≤ 20ng/ml). Following an initial loading dose of 540,000 IU of vitamin D3, patients receive 90,000 IU of vitamin D3 on a monthly basis for 5 months. The study is designed to compare clinical outcome in the two study arms with the primary endpoint being length of hospital stay. Secondary endpoints include among others length of ICU stay, the percentage of patients with 25(OH)D levels > 30 ng/ml at day 7, ICU and hospital mortality and duration of mechanical ventilation. We describe here the VITdAL@ICU study protocol for the primary report.

Discussion

This trial is designed to evaluate whether high-dose vitamin D3 is able to improve morbidity and mortality in a mixed population of adult critically ill patients and correct vitamin D deficiency safely.

Trial registration

ClinicalTrials: NCT01130181
Associations of the FTO rs9939609 and the MC4R rs17782313 polymorphisms with type 2 diabetes are modulated by diet, being higher when adherence to the Mediterranean diet pattern is low
Authors: Ortega-Azorín Carolina , Sorlí Jose V , Asensio Eva M , Coltell Oscar , Martínez-González Miguel Ángel , Salas-Salvadó Jordi , Covas Maria-Isabel , Arós Fernando , Lapetra José , Serra-Majem Lluís , Gómez-Gracia Enrique , Fiol Miquel , Sáez-Tormo Guillermo , Pintó Xavier , Muñoz Miguel Angel , Ros Emilio , Ordovás Jose M , Estruch Ramon , Corella Dolores
Published: November 2012

Background

Although the Fat Mass and Obesity (FTO) and Melanocortin-4 Receptor (MC4R) genes have been consistently associated with obesity risk, the association between the obesity-risk alleles with type 2 diabetes is still controversial. In some recent meta-analyses in which significant results have been reported, the associations disappeared after adjustment for body mass index (BMI). However gene-diet interactions with dietary patterns have not been investigated. Our main aim was to analyze whether these associations are modulated by the level of adherence to the Mediterranean Diet (MedDiet).

Methods

Case-control study in 7,052 high cardiovascular risk subjects (3,430 type 2 diabetes cases and 3,622 non-diabetic subjects) with no differences in BMI. Diet was assessed by validated questionnaires. FTO-rs9939609 and MC4R-rs17782313 were determined. An aggregate genetic score was calculated to test additive effects. Gene-diet interactions were analyzed.

Results

Neither of the polymorphisms was associated with type 2 diabetes in the whole population. However, we found consistent gene-diet interactions with adherence to the MedDiet both for the FTO- rs9939609 (P-interaction=0.039), the MC4R-rs17782313 (P-interaction=0.009) and for their aggregate score (P-interaction=0.006). When adherence to the MedDiet was low, carriers of the variant alleles had higher type 2 diabetes risk (OR=1.21, 95%CI: 1.03-1.40; P=0.019 for FTO- rs9939609 and OR=1.17, 95%CI:1.01-1.36; P=0.035 for MC4R-rs17782313) than wild-type subjects. However, when adherence to the MedDiet was high, these associations disappeared (OR=0.97, 95%CI: 0.85-1.16; P=0.673 for FTO- rs9939609 and OR=0.89, 95%CI:0.78-1.02; P=0.097 for MC4R-rs17782313). These gene-diet interactions remained significant even after adjustment for BMI. As MedDiet is rich in folate, we also specifically examined folate intake and detected statistically significant interaction effects on fasting plasma glucose concentrations in non-diabetic subjects. However these findings should be interpreted with caution because folate intake may simply reflect a healthy dietary pattern.

Conclusions

These novel results suggest that the association of the FTO-rs9939609 and the MC4R-rs17782313 polymorphisms with type 2 diabetes depends on diet and that a high adherence to the MedDiet counteracts the genetic predisposition.
Design and testing of a synthetic biology framework for genetic engineering of Corynebacterium glutamicum
Authors: Ravasi Pablo , Peiru Salvador , Gramajo Hugo , Menzella Hugo G
Published: November 2012

Background

Synthetic biology approaches can make a significant contribution to the advance of metabolic engineering by reducing the development time of recombinant organisms. However, most of synthetic biology tools have been developed for Escherichia coli. Here we provide a platform for rapid engineering of C. glutamicum, a microorganism of great industrial interest. This bacteria, used for decades for the fermentative production of amino acids, has recently been developed as a host for the production of several economically important compounds including metabolites and recombinant proteins because of its higher capacity of secretion compared to traditional bacterial hosts like E. coli. Thus, the development of modern molecular platforms may significantly contribute to establish C. glutamicum as a robust and versatile microbial factory.

Results

A plasmid based platform named pTGR was created where all the genetic components are flanked by unique restriction sites to both facilitate the evaluation of regulatory sequences and the assembly of constructs for the expression of multiple genes. The approach was validated by using reporter genes to test promoters, ribosome binding sites, and for the assembly of dual gene operons and gene clusters containing two transcriptional units. Combinatorial assembly of promoter (tac, cspB and sod) and RBS (lacZ, cspB and sod) elements with different strengths conferred clear differential gene expression of two reporter genes, eGFP and mCherry, thus allowing transcriptional “fine-tuning”of multiple genes. In addition, the platform allowed the rapid assembly of operons and genes clusters for co-expression of heterologous genes, a feature that may assist metabolic pathway engineering.

Conclusions

We anticipate that the pTGR platform will contribute to explore the potential of novel parts to regulate gene expression, and to facilitate the assembly of genetic circuits for metabolic engineering of C. glutamicum. The standardization provided by this approach may provide a means to improve the productivity of biosynthetic pathways in microbial factories for the production of novel compounds.
ATP and luciferase assays to determine the rate of drug action in in vitro cultures of Plasmodium falciparum
Authors: Khan Tasmiyah , van Brummelen Anna C , Parkinson Christopher J , Hoppe Heinrich C
Published: November 2012

Background

Knowledge of the rate of action of compounds against cultured malaria parasites is required to determine the optimal time-points for drug mode of action studies, as well as to predict likely in vivo parasite clearance rates in order to select optimal hit compounds for further development. In this study, changes in parasite ATP levels and transgenic luciferase reporter activity were explored as means to detect drug-induced stress in cultured parasites.

Methods

In vitro cultures of Plasmodium falciparum 3D7 wild-type or firefly luciferase-expressing parasites were incubated with a panel of six anti-malarial compounds for 10 hours and parasite ATP levels or luciferase activity determined at two-hour intervals using luminescence-based reagents. For comparative purposes, parasite morphology changes were evaluated by light microscopy, as well as the extent to which parasites recover after 48 hours from a six-hour drug treatment using a parasite lactate dehydrogenase assay.

Results

Changes in parasite ATP levels displayed three phenotypes: mild or no change (chloroquine, DFMO); 2–4 fold increase (mefloquine, artemisinin); severe depletion (ritonavir, gramicidin). The respective phenotypes and the rate at which they manifested correlated closely with the extent to which parasites recovered from a six-hour drug treatment (with the exception of chloroquine) and the appearance and severity of morphological changes observed by light microscopy. Luciferase activity decreased profoundly in parasites treated with mefloquine, artemisinin and ritonavir (34-67% decrease in 2 hours), while chloroquine and DFMO produced only mild changes over 10 hours. Gramicidin yielded intermediate decreases in luciferase activity.

Conclusions

ATP levels and luciferase activity respond rapidly to incubation with anti-malarial drugs and provide quantitative read-outs to detect the appearance and magnitude of drug-induced stress in cultured parasites. The correlation between the observed changes and irreversible parasite toxicity is not yet sufficiently clear to predict clinical clearance rates, but may be useful for ranking compounds against each other and standard drugs vis-à-vis rate of action and for determining early time-points for drug mode of action studies.
Enhanced nanoscale resistive switching memory characteristics and switching mechanism using high-Ge-content Ge0.5Se0.5 solid electrolyte
Authors: Rahaman Sheikh Ziaur , Maikap Siddheswar , Das Atanu , Prakash Amit , Wu Ya Hsuan , Lai Chao-Sung , Tien Ta-Chang , Chen Wei-Su , Lee Heng-Yuan , Chen Frederick T , Tsai Ming-Jinn , Chang Liann-Be
Published: November 2012

We demonstrate enhanced repeatable nanoscale bipolar resistive switching memory characteristics in Al/Cu/Ge0.5Se0.5/W, as compared with Al/Cu/Ge0.2Se0.8/W structures, including stable AC endurance (>105 cycles), larger average SET voltage (approximately 0.6 V), excellent data retention (>105 s) at 85°C, and a high resistance ratio (>104) with a current compliance of 8 μA and a small operation voltage of ±1.5 V. A small device size of 150 × 150 nm2 and a Cu nanofilament with a small diameter of 30 nm are both observed by high-resolution transmission electron microscope in the SET state. The Ge
x
Se1 − x
solid electrolyte compositions are confirmed by both energy-dispersive X-ray spectroscopy and X-ray photoelectron spectroscopy. The switching mechanism relies on the smaller barrier heights for holes rather than for electrons; the positively charged Cu
z+ ions (i.e., holes) migrate through the defects in the Ge
x
Se1 − x
solid electrolytes during SET/RESET operations. Hence, the Cu nanofilament starts to grow at the Ge0.5Se0.5/W interface, and starts to dissolve at the Cu/Ge0.5Se0.5 interface, as illustrated in the energy band diagrams. Owing to both the higher barrier for hole injection at the Cu/Ge0.5Se0.5 interface than at the Cu/Ge0.2Se0.8 interface and greater thermal stability, the resistive switching memory characteristics of the Al/Cu/Ge0.5Se0.5/W are improved relative to the Al/Cu/Ge0.2Se0.8/W devices. The Al/Cu/Ge0.5Se0.5/W memory device can also be operated with a low current compliance of 1 nA, and hence, a low SET/RESET power of 0.61 nW/6.4 pW is achieved. In addition, a large memory size of 1,300 Pbit/in2 is achieved with a small nanofilament diameter of 0.25 Å for a small current compliance of 1 nA.
A review of methods for detect human Papillomavirusinfection
Authors: Abreu André L P , Souza Raquel P , Gimenes Fabrícia , Consolaro Marcia E L
Published: November 2012

Human Papillomavirus (HPV) is the most common sexually transmitted virus. Worldwide, the most common high-risk (HR)-HPV are -16/18, and approximately 70% of cervical cancers (CC) are due to infection by these genotypes. Persistent infection by HR-HPV is a necessary but not sufficient cause of this cancer, which develops over a long period through precursor lesions, which can be detected by cytological screening. Although this screening has decreased the incidence of CC, HPV-related cervical disease, including premalignant and malignant lesions, continues to be a major burden on health-care systems. Although not completely elucidated, the HPV-driven molecular mechanisms underlying the development of cervical lesions have provided a number of potential biomarkers for both diagnostic and prognostic use in the clinical management of women with HPV-related cervical disease, and these biomarkers can also be used to increase the positive predictive value of current screening methods. In addition, they can provide insights into the biology of HPV-induced cancer and thus lead to the development of nonsurgical therapies. Considering the importance of detecting HPV and related biomarkers, a variety of methods are being developed for these purposes. This review summarizes current knowledge of detection methods for HPV, and related biomarkers that can be used to discriminate lesions with a high risk of progression to CC.
Expression of Nav1.7 in DRG Neurons Extends from Peripheral Terminals in the Skin to Central Preterminal Branches and Terminals in the Dorsal Horn
Authors: Black Joel A , Frézel Noémie , Dib-Hajj Sulayman D , Waxman Stephen G
Published: November 2012

Background:

Sodium channel Nav1.7 has emerged as a target of considerable interest in pain research, since loss-of-function mutations in SCN9A, the gene that encodes Nav1.7, are associated with a syndrome of congenital insensitivity to pain, gain-of-function mutations are linked to the debiliting chronic pain conditions erythromelalgia and paroxysmal extreme pain disorder, and upregulated expression of Nav1.7 accompanies pain in diabetes and inflammation. Since Nav1.7 has been implicated as playing a critical role in pain pathways, we examined by immunocytochemical methods the expression and distribution of Nav1.7 in rat dorsal root ganglia neurons, from peripheral terminals in the skin to central terminals in the spinal cord dorsal horn.

Results:

Nav1.7 is robustly expressed within the somata of peptidergic and non-peptidergic DRG neurons, and along the peripherally- and centrally-directed C-fibers of these cells. Nav1.7 is also expressed at nodes of Ranvier in a subpopulation of Aδ-fibers within sciatic nerve and dorsal root. The peripheral terminals of DRG neurons within skin, intraepidermal nerve fibers (IENF), exhibit robust Nav1.7 immunolabeling. The central projections of DRG neurons in the superficial lamina of spinal cord dorsal horn also display Nav1.7 immunoreactivity which extends to presynaptic terminals.

Conclusions:

The expression of Nav1.7 in DRG neurons extends from peripheral terminals in the skin to preterminal central branches and terminals in the dorsal horn. These data support a major contribution for Nav1.7 in pain pathways, including action potential electrogenesis, conduction along axonal trunks and depolarization/invasion of presynaptic axons. The findings presented here may be important for pharmaceutical development, where target engagement in the right compartment is essential.
Room-temperature super-extraction system (RTSES) optimizes the anxiolytic- and antidepressant-like behavioural effects of traditional Xiao-Yao-San in mice
Authors: Yin Shih-Hsi , Wang Ching-Cheng , Cheng Tain-Junn , Chang Chia-Yu , Lin Kao-Chang , Kan Wei-Chih , Wang Hsien-Yi , Kao Wenny Mei-Wen , Kuo Yen-Liang , Chen Jian-Chyi , Li Shun-Lai , Cheng Chia-Hui , Chuu Jiunn-Jye
Published: November 2012

Background

Xiao-Yao-San (XYS) is a Chinese medicinal formula for treating anxiety and depression. This study aims to evaluate the use of a room-temperature super-extraction system (RTSES) to extract the major active components of XYS and enhance their psycho-pharmacological effects.

Methods

The neuroprotective roles of XYS/RTSES against reserpine-derived neurotoxicity were evaluated using a glial cell injury system (in vitro) and a depression-like C57BL/6 J mouse model (in vivo). The anxiolytic-behavioural effects were measured by the elevated plus-maze (EPM) test and the antidepressant effects were evaluated by the forced swimming test (FST) and tail suspension test (TST). Glucose tolerance and insulin resistance were assayed by ELISA. The expression of 5-HT1A receptors in the prefrontal cortex was examined by western blotting.

Results

XYS/RTSES (300 μg/mL) diminished reserpine-induced glial cell death more effectively than either XYS (300 μg/mL) or fluoxetine (30 μM) at 24 h (P = 0.0481 and P = 0.054, respectively). Oral administration of XYS/RTSES (500 mg/kg/day) for 4 consecutive weeks significantly elevated the ratios of entries (open arms/closed arms; P = 0.0177) and shuttle activity (P = 0.00149) on the EPM test, and reduced the immobility time by 90% on the TST (P = 0.00000538) and FST (P = 0.0000053839). XYS/RTSES also improved the regulation of blood glucose (P = 0.0305) and increased the insulin sensitivity (P = 0.0093). The Western blot results indicated that the activation of cerebral 5-HT1A receptors may be involved in the mechanisms of XYS/RTSES actions.

Conclusion

The RTSES could provide a novel method for extracting effective anxiolytic- and antidepressant-like substances. XYS/RTSES improved the regulation of blood glucose and increased the insulin sensitivity in reserpine-induced anxiety and depression. Neuroprotection of glial cells and activation of cerebral 5-HT1A receptors were also involved.
Lessons learned obtaining informed consent in research with vulnerable populations in community health center settings
Authors: Riden Heather E , Grooms Kya N , Clark Cheryl R , Cohen Laura R , Gagne Josh , Tovar Dora A , Ommerborn Mark J , Orton Piper S , Johnson Paula A
Published: November 2012

Background

To improve equity in access to medical research, successful strategies are needed to recruit diverse populations. Here, we examine experiences of community health center (CHC) staff who guided an informed consent process to overcome recruitment barriers in a medical record review study.

Methods

We conducted ten semi-structured interviews with CHC staff members. Interviews were audiotaped, transcribed, and structurally and thematically coded. We used NVivo, an ethnographic data management software program, to analyze themes related to recruitment challenges.

Results

CHC interviewees reported that a key challenge to recruitment included the difficult balance between institutional review board (IRB) requirements for informed consent, and conveying an appropriate level of risk to patients. CHC staff perceived that the requirements of IRB certification itself posed a barrier to allowing diverse staff to participate in recruitment efforts. A key barrier to recruitment also included the lack of updated contact information on CHC patients. CHC interviewees reported that the successes they experienced reflected an alignment between study aims and CHC goals, and trusted relationships between CHCs and staff and the patients they recruited.

Conclusions

Making IRB training more accessible to CHC-based staff, improving consent form clarity for participants, and developing processes for routinely updating patient information would greatly lower recruitment barriers for diverse populations in health services research.
Phylogenetic relationship of the Brazilian isolates of the rat lungworm Angiostrongylus cantonensis (Nematoda: Metastrongylidae) employing mitochondrial COI gene sequence data
Authors: Monte Tainá C C , Simões Raquel O , Oliveira Ana Paula M , Novaes Clodoaldo F , Thiengo Silvana C , Silva Alexandre J , Estrela Pedro C , Júnior Arnaldo Maldonado
Published: November 2012

Background

The rat lungworm Angiostrongylus cantonensis can cause eosinophilic meningoencephalitis in humans. This nematode’s main definitive hosts are rodents and its intermediate hosts are snails. This parasite was first described in China and currently is dispersed across several Pacific islands, Asia, Australia, Africa, some Caribbean islands and most recently in the Americas. Here, we report the genetic variability among A. cantonensis isolates from different geographical locations in Brazil using mitochondrial cytochrome c oxidase subunit I (COI) gene sequences.

Methods

The isolates of A. cantonensis were obtained from distinct geographical locations of Brazil. Genomic DNAs were extracted, amplified by polymerase reaction, purified and sequenced. A partial sequence of COI gene was determined to assess their phylogenetic relationship.

Results

The sequences of A. cantonensis were monophyletic. We identified a distinct clade that included all isolates of A. cantonensis from Brazil and Asia based on eight distinct haplotypes (ac1, ac2, ac3, ac4, ac5, ac6, ac7 and ac8) from a previous study. Interestingly, the Brazilian haplotype ac5 is clustered with isolates from Japan, and the Brazilian haplotype ac8 from Rio de Janeiro, São Paulo, Pará and Pernambuco states formed a distinct clade. There is a divergent Brazilian haplotype, which we named ac9, closely related to Chinese haplotype ac6 and Japanese haplotype ac7.

Conclusion

The genetic variation observed among Brazilian isolates supports the hypothesis that the appearance of A. cantonensis in Brazil is likely a result of multiple introductions of parasite-carrying rats, transported on ships due to active commerce with Africa and Asia during the European colonization period. The rapid spread of the intermediate host, Achatina fulica, also seems to have contributed to the dispersion of this parasite and the infection of the definitive host in different Brazilian regions.
The influence of electromyographic biofeedback therapy on knee extension following anterior cruciate ligament reconstruction: a randomized controlled trial
Authors: Christanell Franz , Hoser Christian , Huber Reinhard , Fink Christian , Luomajoki Hannu
Published: November 2012

Background

Loss of knee extension and a deficit in quadriceps strength are frequently found following anterior cruciate ligament (ACL) reconstruction. The aim of this study was to investigate whether the addition of Eletromyographic Biofeedback (EMG BFB) therapy for the vastus medialis muscle to the in the early phase of the standard rehabilitation programme could improve the range of knee extension and strength after ACL reconstruction more than a standard rehabilitation programme. The correlation between EMG measurement and passive knee extension was also investigated.

Method

Sixteen patients, all of whom underwent endoscopic ACL reconstruction using patellar tendon autograft, were randomly assigned to two groups:

• Control group (8 patients): standard rehabilitation protocol; with full weight-bearing postoperative, knee brace (0° extension, 90° flexion), electrical stimulation, aquatics and proprioceptive training.

• The EMG BFB group (8 patients): EMG BFB was added to the standard rehabilitation protocol within the first postoperative week and during each session for the next 6 weeks.

Each patent attended a total of 16 outpatient physiotherapy sessions following surgery. High-Heel-Distance (HHD) Test, range of motion (ROM) and integrated EMG (iEMG) for vastus medialis were measured preoperatively, and at the 1, 2, 4 and 6-week follow ups. Additionally, knee function, swelling and pain were evaluated using standardized scoring scales.

Results

At 6 weeks, passive knee extension (p < 0.002) and the HHD Test were significantly (p < 0.01) better in the EMG BFB group compared to controls. Integrated EMG (vastus medialis) of the EMG BFB group also showed a significant increase after 2 (p < 0.01) and 6 (p < 0.01) weeks. At the 6-week follow up, no significant (p > 0.01) differences were found between the two groups for the assessment of knee function, swelling and pain.

Conclusion

The results indicate that EMG BFB therapy, in the early phase of rehabilitation after ACL reconstruction, is useful in enhancing knee extension. Improved innervation of the vastus medialis can play a key role in the development of postoperative knee extension. EMG BFB therapy is a simple, inexpensive and valuable adjunct to conventional therapeutic modalities.
Randomized Phase III Trial of Induction Chemotherapy With Docetaxel, Cisplatin, and Fluorouracil Followed by Surgery Versus Up-Front Surgery in Locally Advanced Resectable Oral Squamous Cell Carcinoma
Authors: Zhong Lai-ping , Zhang Chen-ping , Ren Guo-xin , Guo Wei , William William N. , Sun Jian , Zhu Han-guang , Tu Wen-yong , Li Jiang , Cai Yi-li , Wang Li-zhen , Fan Xin-dong , Wang Zhong-he , Hu Yong-jie , Ji Tong , Yang Wen-jun , Ye Wei-min , Li Jun , He Yue , Wang Yan-an , Xu Li-qun , Wang Bo-song , Kies Merrill S. , Lee J. Jack , Myers Jeffrey N. , Zhang Zhi-yuan
Published: November 2012

Purpose

To evaluate induction chemotherapy with docetaxel, cisplatin, and fluorouracil (TPF) followed by surgery and postoperative radiotherapy versus up-front surgery and postoperative radiotherapy in patients with locally advanced resectable oral squamous cell carcinoma (OSCC).

Patients and Methods

A prospective open-label phase III trial was conducted. Eligibility criteria included untreated stage III or IVA locally advanced resectable OSCC. Patients received two cycles of TPF induction chemotherapy (docetaxel 75 mg/m2 on day 1, cisplatin 75 mg/m2 on day 1, and fluorouracil 750 mg/m2 on days 1 to 5) followed by radical surgery and postoperative radiotherapy (54 to 66 Gy) versus up-front radical surgery and postoperative radiotherapy. The primary end point was overall survival (OS). Secondary end points included local control and safety.

Results

Of the 256 patients enrolled onto this trial, 222 completed the full treatment protocol. There were no unexpected toxicities, and induction chemotherapy did not increase perioperative morbidity. The clinical response rate to induction chemotherapy was 80.6%. After a median follow-up of 30 months, there was no significant difference in OS (hazard ratio [HR], 0.977; 95% CI, 0.634 to 1.507; P = .918) or disease-free survival (HR, 0.974; 95% CI, 0.654 to 1.45; P = .897) between patients treated with and without TPF induction. Patients in the induction chemotherapy arm with a clinical response or favorable pathologic response (≤ 10% viable tumor cells) had superior OS and locoregional and distant control.

Conclusion

Our study failed to demonstrate that TPF induction chemotherapy improves survival compared with up-front surgery in patients with resectable stage III or IVA OSCC.
Breast Cancer Follow-Up and Management After Primary Treatment: American Society of Clinical Oncology Clinical Practice Guideline Update
Authors: Khatcheressian James L. , Hurley Patricia , Bantug Elissa , Esserman Laura J. , Grunfeld Eva , Halberg Francine , Hantel Alexander , Henry N. Lynn , Muss Hyman B. , Smith Thomas J. , Vogel Victor G. , Wolff Antonio C. , Somerfield Mark R. , Davidson Nancy E.
Published: November 2012

Purpose

To provide recommendations on the follow-up and management of patients with breast cancer who have completed primary therapy with curative intent.

Methods

To update the 2006 guideline of the American Society of Clinical Oncology (ASCO), a systematic review of the literature published from March 2006 through March 2012 was completed using MEDLINE and the Cochrane Collaboration Library. An Update Committee reviewed the evidence to determine whether the recommendations were in need of updating.

Results

There were 14 new publications that met inclusion criteria: nine systematic reviews (three included meta-analyses) and five randomized controlled trials. After its review and analysis of the evidence, the Update Committee concluded that no revisions to the existing ASCO recommendations were warranted.

Recommendations

Regular history, physical examination, and mammography are recommended for breast cancer follow-up. Physical examinations should be performed every 3 to 6 months for the first 3 years, every 6 to 12 months for years 4 and 5, and annually thereafter. For women who have undergone breast-conserving surgery, a post-treatment mammogram should be obtained 1 year after the initial mammogram and at least 6 months after completion of radiation therapy. Thereafter, unless otherwise indicated, a yearly mammographic evaluation should be performed. The use of complete blood counts, chemistry panels, bone scans, chest radiographs, liver ultrasounds, pelvic ultrasounds, computed tomography scans, [18F]fluorodeoxyglucose–positron emission tomography scans, magnetic resonance imaging, and/or tumor markers (carcinoembryonic antigen, CA 15-3, and CA 27.29) is not recommended for routine follow-up in an otherwise asymptomatic patient with no specific findings on clinical examination.
Dishevelled limits Notch signalling through inhibition of CSL
Authors: Collu Giovanna M. , Hidalgo-Sastre Ana , Acar Ahmet , Bayston Laura , Gildea Clara , Leverentz Michael K. , Mills Christopher G. , Owens Thomas W. , Meurette Olivier , Dorey Karel , Brennan Keith
Published: November 2012

Notch and Wnt are highly conserved signalling pathways that are used repeatedly throughout animal development to generate a diverse array of cell types. However, they often have opposing effects on cell-fate decisions with each pathway promoting an alternate outcome. Commonly, a cell receiving both signals exhibits only Wnt pathway activity. This suggests that Wnt inhibits Notch activity to promote a Wnt-ON/Notch-OFF output; but what might underpin this Notch regulation is not understood. Here, we show that Wnt acts via Dishevelled to inhibit Notch signalling, and that this crosstalk regulates cell-fate specification in vivo during Xenopus development. Mechanistically, Dishevelled binds and directly inhibits CSL transcription factors downstream of Notch receptors, reducing their activity. Furthermore, our data suggest that this crosstalk mechanism is conserved between vertebrate and invertebrate homologues. Thus, we identify a dual function for Dishevelled as an inhibitor of Notch signalling and an activator of the Wnt pathway that sharpens the distinction between opposing Wnt and Notch responses, allowing for robust cell-fate decisions.
Different assemblies of Notch receptors coordinate the distribution of the major bronchial Clara, ciliated and neuroendocrine cells
Authors: Morimoto Mitsuru , Nishinakamura Ryuichi , Saga Yumiko , Kopan Raphael
Published: November 2012

In the developing lung, it is thought that the terminal buds of elongating airways contain a population of multipotent epithelial progenitors. As the bronchial tree extends, descendants of these cells give rise to lineage-restricted progenitors in the conducting airways via Notch signaling, which is involved in the establishment of epithelial Clara, ciliated and pulmonary neuroendocrine (NE) cell populations. However, the precise molecular details of this selection process are still emerging. Our stepwise removal of the three Notch receptors from the developing lung epithelium reveals that, whereas Notch2 mediates the Clara/ciliated cell fate decision with negligible contributions from Notch1 and Notch3, all three Notch receptors contribute in an additive manner to regulate the abundance of NE cells and the size of the presumptive pulmonary neuroepithelial body (pNEB) as a result of mutual interactions between NE cells and the Notch-dependent, SSEA-1+, CC10− cell population surrounding the pNEB (SPNC cells). Ectopic expression of the Notch1 or Notch2 intracellular domain was sufficient to induce SSEA-1+ cells and to suppress pNEB formation without expending Clara cells. We provide evidence that the additive functions of Notch receptors, together with other signaling pathways, maintains the expression of Hes1, a key regulator of NE cell fate, and that maintenance of Hes1 expression in epithelial cells is key to the regulation of pNEB size. These results suggest that two different assemblies of Notch receptors coordinate the numbers and distribution of the major epithelial cell types in the conducting airway during lung organogenesis.
Endocytic receptor-mediated control of morphogen signaling
Authors: Willnow Thomas E. , Christ Annabel , Hammes Annette
Published: November 2012

Receptor-mediated endocytosis provides a mechanism by which cells take up signaling molecules from the extracellular space. Recent studies have shown that one class of endocytic receptors, the low-density lipoprotein receptor-related proteins (LRPs), is of particular relevance for embryonic development. In this Primer, we describe how LRPs constitute central pathways that modulate morphogen presentation to target tissues and cellular signal reception, and how LRP dysfunction leads to developmental disturbances in many species.
LDL receptor-related protein-1 is a sialic-acid-independent receptor for myelin-associated glycoprotein that functions in neurite outgrowth inhibition by MAG and CNS myelin
Authors: Stiles Travis L. , Dickendesher Travis L. , Gaultier Alban , Fernandez-Castaneda Anthony , Mantuano Elisabetta , Giger Roman J. , Gonias Steven L.
Published: November 2012

In the injured adult mammalian central nervous system (CNS), products are generated that inhibit neuronal sprouting and regeneration. In recent years, most attention has focused on the myelin-associated inhibitory proteins (MAIs) Nogo-A, OMgp, and myelin-associated glycoprotein (MAG). Binding of MAIs to neuronal cell-surface receptors leads to activation of RhoA, growth cone collapse, and neurite outgrowth inhibition. In the present study, we identify low-density lipoprotein (LDL) receptor-related protein-1 (LRP1) as a high-affinity, endocytic receptor for MAG. In contrast with previously identified MAG receptors, binding of MAG to LRP1 occurs independently of terminal sialic acids. In primary neurons, functional inactivation of LRP1 with receptor-associated protein, depletion by RNA interference (RNAi) knock-down, or LRP1 gene deletion is sufficient to significantly reverse MAG and myelin-mediated inhibition of neurite outgrowth. Similar results are observed when LRP1 is antagonized in PC12 and N2a cells. By contrast, inhibiting LRP1 does not attenuate inhibition of neurite outgrowth caused by chondroitin sulfate proteoglycans. Mechanistic studies in N2a cells showed that LRP1 and p75NTR associate in a MAG-dependent manner and that MAG-mediated activation of RhoA may involve both LRP1 and p75NTR. LRP1 derivatives that include the complement-like repeat clusters CII and CIV bind MAG and other MAIs. When CII and CIV were expressed as Fc-fusion proteins, these proteins, purified full-length LRP1 and shed LRP1 all attenuated the inhibition of neurite outgrowth caused by MAG and CNS myelin in primary neurons. Collectively, our studies identify LRP1 as a novel MAG receptor that functions in neurite outgrowth inhibition.