bluuebunny/crossref_metadata_2025 huggingface dataset:
Facile synthesis of SrCO3 nanostructures in methanol/water solution without additives
Authors: Li Lishuo , Lin Rongyi , Tong Zhangfa , Feng Qingge
Published: June 2012

Highly dispersive strontium carbonate (SrCO3) nanostructures with uniform dumbbell, ellipsoid, and rod-like morphologies were synthesized in methanol solution without any additives. These SrCO3 were characterized by X-ray diffraction, field emission scanning electron microscopy, and N2 adsorption-desorption. The results showed that the reaction temperature and the methanol/water ratio had important effects on the morphologies of SrCO3 particles. The dumbbell-like SrCO3 exhibited a Broader-Emmett-Teller surface area of 14.9 m2 g−1 and an average pore size of about 32 nm with narrow pore size distribution. The formation mechanism of the SrCO3 crystal was preliminary presented.
Excellent resistive memory characteristics and switching mechanism using a Ti nanolayer at the Cu/TaOx interface
Authors: Rahaman Sheikh Ziaur , Maikap Siddheswar , Tien Ta-Chang , Lee Heng-Yuan , Chen Wei-Su , Chen Frederick T , Kao Ming-Jer , Tsai Ming-Jinn
Published: June 2012

Excellent resistive switching memory characteristics were demonstrated for an Al/Cu/Ti/TaOx/W structure with a Ti nanolayer at the Cu/TaOx interface under low voltage operation of ± 1.5 V and a range of current compliances (CCs) from 0.1 to 500 μA. Oxygen accumulation at the Ti nanolayer and formation of a defective high-κ TaOx film were confirmed by high-resolution transmission electron microscopy, energy dispersive X-ray spectroscopy, and X-ray photo-electron spectroscopy. The resistive switching memory characteristics of the Al/Cu/Ti/TaOx/W structure, such as HRS/LRS (approximately 104), stable switching cycle stability (>106) and multi-level operation, were improved compared with those of Al/Cu/TaOx/W devices. These results were attributed to the control of Cu migration/dissolution by the insertion of a Ti nanolayer at the Cu/TaOx interface. In contrast, CuOx formation at the Cu/TaOx interface was observed in an Al/Cu/TaOx/W structure, which hindered dissolution of the Cu filament and resulted in a small resistance ratio of approximately 10 at a CC of 500 μA. A high charge-trapping density of 6.9 × 1016 /cm2 was observed in the Al/Cu/Ti/TaOx/W structure from capacitance-voltage hysteresis characteristics, indicating the migration of Cu ions through defect sites. The switching mechanism was successfully explained for structures with and without the Ti nanolayer. By using a new approach, the nanoscale diameter of Cu filament decreased from 10.4 to 0.17 nm as the CC decreased from 500 to 0.1 μA, resulting in a large memory size of 7.6 T to 28 Pbit/sq in. Extrapolated 10-year data retention of the Ti nanolayer device was also obtained. The findings of this study will not only improve resistive switching memory performance but also aid future design of nanoscale nonvolatile memory.
Growth of GeSi nanoislands on nanotip-patterned Si (100) substrates with a stress-induced self-limiting interdiffusion
Authors: Tang Ruifan , Huang Kai , Lai Hongkai , Li Cheng , Wu Zhiming , Kang Junyong
Published: June 2012

GeSi nanoislands grown on nanotip pre-patterned Si substrates at various temperatures are investigated. Nanoislands with a high density and narrow size distribution can be obtained within an intermediate temperature range, and the Ge atom diffusion length is comparable to half of the average distance of the Si nanotips. The Ge concentration distributions at the center and edge of the GeSi nanoislands are measured by scanning transmission electron microscopy. The results reveal that there is a Si core at the center of the GeSi nanoisland, but the Ge concentration presents a layered distribution above the Si nanotips. The radial component of the stress field in Ge layer near the Ge/Si interface on the planar, and the nanotip regions is qualitatively discussed. The difference of the stress field reveals that the experimentally observed concentration profile can be ascribed to the stress-induced interdiffusion self-limiting effect of the Si nanotips.
Synthesis and characterization of maleimide-functionalized polystyrene-SiO2/TiO2 hybrid nanocomposites by sol–gel process
Authors: Ramesh Sivalingam , Sivasamy Arumugam , Kim Joo-Hyung
Published: June 2012

Maleimide-functionalized polystyrene (PSMA-SiO2/TiO2) hybrid nanocomposites were prepared by sol–gel reaction starting from tratraethoxysilane (TEOS) and titanium isopropoxide in the solution of polystyrene maleimide in 1,4-dioxane. The hybrid films were obtained by the hydrolysis and polycondensation of TEOS and titanium isopropoxide in maleimide-functionalized polystyrene solution followed by the Michael addition reaction. The transparency of polymer (PSMA-SiO2/TiO2) hybrid was prepared from polystyrene titanium isopropoxide using the γ-aminopropyltriethoxy silane as crosslinking agent by in situ sol–gel process via covalent bonding between the organic–inorganic hybrid nanocomposites. The maleimide-functionalized polystyrene was synthesized by Friedel-Crafts reaction from N-choloromethyl maleimide. The FTIR spectroscopy data conformed the occurrence of Michael addition reaction between the pendant maleimide moieties of the styrene and γ-aminopropyltriethoxysilane. The chemical structure and morphology of PSMA-SiO2/TiO2 hybrid nanocomposites were characterized by FTIR, nuclear magnetic resonance (NMR), 13 C NMR, SEM, XRD, and TEM analyses. The results also indicate that the inorganic particles are much smaller in the ternary systems than in the binary systems; the shape of the inorganic particles and compatibility for maleimide-functionalized polystrene and inorganic moieties are varied with the ratio of the inorganic moieties in the hybrids. Furthermore, TGA and DSC results indicate that the thermal stability of maleimide-functionalized polystyrene was enhanced through the incorporation of the inorganic moieties in the hybrid materials.
Nm23/nucleoside diphosphate kinase-A as a potent prognostic marker in invasive pancreatic ductal carcinoma identified by proteomic analysis of laser micro-dissected formalin-fixed paraffin-embedded tissue
Authors: Takadate Tatsuyuki , Onogawa Tohru , Fujii Kiyonaga , Motoi Fuyuhiko , Mikami Sayaka , Fukuda Tetsuya , Kihara Makoto , Suzuki Takashi , Takemura Taro , Minowa Takashi , Hanagata Nobutaka , Kinoshita Kengo , Morikawa Takanori , Shirasaki Keiichi , Rikiyama Toshiki , Katayose Yu , Egawa Shinichi , Nishimura Toshihide , Unno Michiaki
Published: June 2012

Background

Pancreatic cancer is among the most lethal malignancies worldwide. This study aimed to identify a novel prognostic biomarker, facilitating treatment selection, using mass spectrometry (MS)-based proteomic analysis with formalin-fixed paraffin-embedded (FFPE) tissue.

Results

The two groups with poor prognosis (n = 4) and with better prognosis (n = 4) had been carefully chosen among 96 resected cases of pancreatic cancer during 1998 to 2007 in Tohoku University Hospital. Although those 2 groups had adjusted background (UICC-Stage IIB, Grade2, R0, gemcitabine adjuvant), there was a significant difference in postoperative mean survival time (poor 21.0 months, better 58.1 months, P = 0.0067). Cancerous epithelial cells collected from FFPE tissue sections by laser micro-dissection (LMD) were processed for liquid chromatography-tandem mass spectrometry (LC-MS/MS). In total, 1099 unique proteins were identified and 6 proteins showed different expressions in the 2 groups by semi-quantitative comparison. Among these 6 proteins, we focused on Nm23/Nucleoside Diphosphate Kinase A (NDPK-A) and immunohistochemically confirmed its expression in the cohort of 96 cases. Kaplan-Meier analysis showed high Nm23/NDPK-A expression to correlate with significantly worse overall survival (P = 0.0103). Moreover, in the multivariate Cox regression model, Nm23/NDPK-A over-expression remained an independent predictor of poor survival with a hazard ratio of 1.97 (95% CI 1.16-3.56, P = 0.0110).

Conclusions

We identified 6 candidate prognostic markers for postoperative pancreatic cancer using FFPE tissues and immunohistochemically demonstrated high Nm23/NDPK-A expression to be a useful prognostic marker for pancreatic cancer.
Control of the olive fruit fly using genetics-enhanced sterile insect technique
Authors: Ant Thomas , Koukidou Martha , Rempoulakis Polychronis , Gong Hong-Fei , Economopoulos Aris , Vontas John , Alphey Luke
Published: June 2012

Background

The olive fruit fly, Bactrocera oleae, is the major arthropod pest of commercial olive production, causing extensive damage to olive crops worldwide. Current control techniques rely on spraying of chemical insecticides. The sterile insect technique (SIT) presents an alternative, environmentally friendly and species-specific method of population control. Although SIT has been very successful against other tephritid pests, previous SIT trials on olive fly have produced disappointing results. Key problems included altered diurnal mating rhythms of the laboratory-reared insects, resulting in asynchronous mating activity between the wild and released sterile populations, and low competitiveness of the radiation-sterilised mass-reared flies. Consequently, the production of competitive, male-only release cohorts is considered an essential prerequisite for successful olive fly SIT.

Results

We developed a set of conditional female-lethal strains of olive fly (named Release of Insects carrying a Dominant Lethal; RIDL®), providing highly penetrant female-specific lethality, dominant fluorescent marking, and genetic sterility. We found that males of the lead strain, OX3097D-Bol, 1) are strongly sexually competitive with wild olive flies, 2) display synchronous mating activity with wild females, and 3) induce appropriate refractoriness to wild female re-mating. Furthermore, we showed, through a large proof-of-principle experiment, that weekly releases of OX3097D-Bol males into stable populations of caged wild-type olive fly could cause rapid population collapse and eventual eradication.

Conclusions

The observed mating characteristics strongly suggest that an approach based on the release of OX3097D-Bol males will overcome the key difficulties encountered in previous olive fly SIT attempts. Although field confirmation is required, the proof-of-principle suppression and elimination of caged wild-type olive fly populations through OX3097D-Bol male releases provides evidence for the female-specific RIDL approach as a viable method of olive fly control. We conclude that the promising characteristics of OX3097D-Bol may finally enable effective SIT-based control of the olive fly.
Postembryonic neuronal addition in Zebrafish dorsal root ganglia is regulated by Notch signaling
Authors: McGraw Hillary Faye , Snelson Corey D , Prendergast Andrew , Suli Arminda , Raible David W
Published: June 2012

Background

The sensory neurons and glia of the dorsal root ganglia (DRG) arise from neural crest cells in the developing vertebrate embryo. In mouse and chick, DRG formation is completed during embryogenesis. In contrast, zebrafish continue to add neurons and glia to the DRG into adulthood, long after neural crest migration is complete. The molecular and cellular regulation of late DRG growth in the zebrafish remains to be characterized.

Results

In the present study, we use transgenic zebrafish lines to examine neuronal addition during postembryonic DRG growth. Neuronal addition is continuous over the period of larval development. Fate-mapping experiments support the hypothesis that new neurons are added from a population of resident, neural crest-derived progenitor cells. Conditional inhibition of Notch signaling was used to assess the role of this signaling pathway in neuronal addition. An increase in the number of DRG neurons is seen when Notch signaling is inhibited during both early and late larval development.

Conclusions

Postembryonic growth of the zebrafish DRG comes about, in part, by addition of new neurons from a resident progenitor population, a process regulated by Notch signaling.
Molecular genetic studies and delineation of the oculocutaneous albinism phenotype in the Pakistani population
Authors: Jaworek Thomas J , Kausar Tasleem , Bell Shannon M , Tariq Nabeela , Maqsood Muhammad Imran , Sohail Asma , Ali Muhmmmad , Iqbal Furhan , Rasool Shafqat , Riazuddin Saima , Shaikh Rehan S , Ahmed Zubair M
Published: June 2012

Background

Oculocutaneous albinism (OCA) is caused by a group of genetically heterogeneous inherited defects that result in the loss of pigmentation in the eyes, skin and hair. Mutations in the TYR, OCA2, TYRP1 and SLC45A2 genes have been shown to cause isolated OCA. No comprehensive analysis has been conducted to study the spectrum of OCA alleles prevailing in Pakistani albino populations.

Methods

We enrolled 40 large Pakistani families and screened them for OCA genes and a candidate gene, SLC24A5. Protein function effects were evaluated using in silico prediction algorithms and ex vivo studies in human melanocytes. The effects of splice-site mutations were determined using an exon-trapping assay.

Results

Screening of the TYR gene revealed four known (p.Arg299His, p.Pro406Leu, p.Gly419Arg, p.Arg278*) and three novel mutations (p.Pro21Leu, p.Cys35Arg, p.Tyr411His) in ten families. Ex vivo studies revealed the retention of an EGFP-tagged mutant (p.Pro21Leu, p.Cys35Arg or p.Tyr411His) tyrosinase in the endoplasmic reticulum (ER) at 37°C, but a significant fraction of p.Cys35Arg and p.Tyr411His left the ER in cells grown at a permissive temperature (31°C). Three novel (p.Asp486Tyr, p.Leu527Arg, c.1045-15 T > G) and two known mutations (p.Pro743Leu, p.Ala787Thr) of OCA2 were found in fourteen families. Exon-trapping assays with a construct containing a novel c.1045-15 T > G mutation revealed an error in splicing. No mutation in TYRP1, SLC45A2, and SLC24A5 was found in the remaining 16 families. Clinical evaluation of the families segregating either TYR or OCA2 mutations showed nystagmus, photophobia, and loss of pigmentation in the skin or hair follicles. Most of the affected individuals had grayish-blue colored eyes.

Conclusions

Our results show that ten and fourteen families harbored mutations in the TYR and OCA2 genes, respectively. Our findings, along with the results of previous studies, indicate that the p.Cys35Arg, p.Arg278* and p.Gly419Arg alleles of TYR and the p.Asp486Tyr and c.1045-15 T > G alleles of OCA2 are the most common causes of OCA in Pakistani families. To the best of our knowledge, this study represents the first documentation of OCA2 alleles in the Pakistani population. A significant proportion of our cohort did not have mutations in known OCA genes. Overall, our study contributes to the development of genetic testing protocols and genetic counseling for OCA in Pakistani families.
Central syntropic effects elicited by trigeminal proprioceptive equilibrium in Alzheimer’s disease: a case report
Authors: De Cicco Vincenzo
Published: June 2012

Introduction

The presented patient, affected by Alzheimer’s disease, underwent neuropsychological evaluation and functional magnetic resonance imaging investigation under occlusal proprioceptive un-balance and re-balance conditions. Saccadic and pupillometric video-oculographic examinations were performed in order to detect connected trigeminal proprioceptive motor patterns able to interfere with reticular formation cerebellum functions linked to visual and procedural processes prematurely altered in Alzheimer’s disease.

Case presentation

A 66-year-old Caucasian man, affected by Alzheimer’s disease and with a neuropsychological evaluation issued by the Alzheimer’s Evaluation Unit, underwent an electromyographic investigation of the masseter muscles in order to assess their functional balance. The patient showed a bilateral lack of all inferior molars. The extreme myoelectric asymmetry in dental occlusion suggested the rebalancing of masseter muscular functions through concurrent transcutaneous stimulation of the trigeminal nerve supramandibular and submandibular motor branches. The above-mentioned method allows detection of symmetric craniomandibular muscular relation that can be kept constant through the use of a cusp bite modeled on the inferior dental arch, called orthotic-syntropic bite. A few days later, the patient underwent a new neuropsychological investigation, together with a functional magnetic resonance imaging study, and saccadic, pupillometric video-oculographic examinations in occlusal un-balance and re-balance conditions.

Conclusions

Comparative data analysis has shown that a re-balanced occlusal condition can improve a patient’s cognitive-attentive functions. Moreover, the saccadic and pupillometric video-oculographic investigations have proven useful both in analyzing reticulo-cerebellar subcortical systems, prematurely altered in Alzheimer’s disease, and in implementing neurological evaluations.
A user-friendly software to easily count Anopheles egg batches
Authors: Mollahosseini Ali , Rossignol Marie , Pennetier Cédric , Cohuet Anna , Anjos António dos , Chandre Fabrice , Shahbazkia Hamid Reza
Published: June 2012

Background

Studies on malaria vector ecology and development/evaluation of vector control strategies often require measures of mosquito life history traits. Assessing the fecundity of malaria vectors can be carried out by counting eggs laid by Anopheles females. However, manually counting the eggs is time consuming, tedious, and error prone.

Methods

In this paper we present a newly developed software for high precision automatic egg counting. The software written in the Java programming language proposes a user-friendly interface and a complete online manual. It allows the inspection of results by the operator and includes proper tools for manual corrections. The user can in fact correct any details on the acquired results by a mouse click. Time saving is significant and errors due to loss of concentration are avoided.

Results

The software was tested over 16 randomly chosen images from 2 different experiments. The results show that the proposed automatic method produces results that are close to the ground truth.

Conclusions

The proposed approaches demonstrated a very high level of robustness. The adoption of the proposed software package will save many hours of labor to the bench scientist. The software needs no particular configuration and is freely available for download on: http://w3.ualg.pt/∼hshah/eggcounter/.
RETRACTED ARTICLE: Hypermethylation of the 5′ CpG island of the p14ARF flanking exon 1β in human colorectal cancer displaying a restricted pattern of p53 overexpression concomitant with increased MDM2 expression
Authors: Nyiraneza Christine , Sempoux Christine , Detry Roger , Kartheuser Alex , Dahan Karin
Published: June 2012

Background

It has been suggested that inactivation of p14ARF, a tumor suppressor central to regulating p53 protein stability through interaction with the MDM2 oncoprotein, abrogates p53 activity in human tumors retaining the wild-type TP53 gene. Differences in expression of tumor suppressor genes are frequently associated with cancer. We previously reported on a pattern of restricted p53 immunohistochemical overexpression significantly associated with microsatellite instability (MSI), low TP53 mutation frequency, and MDM2 overexpression in colorectal cancers (CRCs). In this study, we investigated whether p14ARF alterations could be a mechanism for disabling the p53 pathway in this subgroup of CRCs.

Results

Detailed maps of the alterations in the p14ARF gene were determined in a cohort of 98 CRCs to detect both nucleotide and copy-number changes. Methylation-specific PCR combined with bisulfite sequencing was used to evaluate the prevalence and distribution of p14ARF methylation. p14ARF alterations were then correlated with MSI status, TP53 mutations, and immunohistochemical expression of p53 and MDM2. The frequency of p14ARF mutations was extremely low (1/98; 1%), whereas coexistence of methylated and unmethylated alleles in both tumors and normal colon mucosa was common (91/98; 93%). Only seven of ninety-eight tumors (7%) had a distinct pattern of methylation compared with normal colon mucosa. Evaluation of the prevalence and distribution of p14ARF promoter methylation in a region containing 27 CpG sites in 35 patients showed a range of methylated CpG sites in tumors (0 to 25 (95% CI 1 to 13) versus 0 to 17 (95% CI 0 to 2)) in adjacent colon mucosa (P = 0.004). Hypermethylation of the p14ARF promoter was significantly correlated with the restricted p53 overexpression pattern (P = 0.03), and MDM2 overexpression (P = 0.02), independently of MSI phenotype. Although no significant correlation between p14ARF methylation and TP53 mutational status was seen (P = 0.23), methylation involving the proximal CpG sites within the 5′ CpG flanking exon 1β was present more frequently in tumors with restricted p53 overexpression than in those with diffuse p53 overexpression (range of methylated clones 17 to 36% (95% CI 24 to 36%) versus range 0 to 3% (95% CI 0 to 3%), P = 0. 0003).

Conclusion

p14ARF epigenetic silencing may represent an important deregulating mechanism of the p53-MDM2-p14ARF pathway in CRCs exhibiting a restricted p53 overexpression pattern.
Long-Term Disease-Specific Functioning Among Prostate Cancer Survivors and Noncancer Controls in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial
Authors: Taylor Kathryn L. , Luta George , Miller Anthony B. , Church Timothy R. , Kelly Scott P. , Muenz Larry R. , Davis Kimberly M. , Dawson David L. , Edmond Sara , Reding Douglas , Mabie Jerome E. , Riley Thomas L.
Published: June 2012

Purpose

Within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO), we assessed the long-term disease-specific functioning among prostate cancer (PCa) survivors versus noncancer controls, the impact of trial arm (screening/usual care) on functioning, and the effect of treatment modality on functioning.

Patients and Methods

PCa survivors (n = 529), 5 to 10 years postdiagnosis, were frequency-matched to noncancer controls (n = 514) for race, screening center, year of enrollment, and trial arm. Participants completed a telephone interview regarding PCa-specific symptomatology. Weights accounted for patient selection from the five PLCO screening centers. Propensity-score methods were used to balance groups of interest with respect to demographic and medical characteristics.

Results

Weighted linear regression analyses revealed poorer sexual and urinary function among PCa survivors compared with noncancer controls (P < .001). Trial arm was not significantly related to any outcome (P > .31). Compared with radical prostatectomy patients (n = 201), radiation-therapy patients (n = 110) reported better sexual (P < .05) and urinary (P < .001) functioning but poorer bowel outcomes (P < .05). Survivors who received treatment combinations including androgen deprivation (n = 207) reported significantly poorer hormone-related symptoms compared with radical prostatectomy patients (P < .05).

Conclusion

This study demonstrated the persistence of clinically significant, long-term PCa treatment-related sexual and urinary adverse effects up to 10 years postdiagnosis. To our knowledge, this was the first comparison of prostate-related dysfunction among screened survivors versus screened noncancer controls and indicated that these long-term problems were attributable to PCa treatment and not to aging or comorbidities. Finally, differences in long-term adverse effects between treatment modalities are particularly relevant for patients and clinicians when making treatment decisions.
Which Hospice Patients With Cancer Are Able to Die in the Setting of Their Choice? Results of a Retrospective Cohort Study
Authors: Jeurkar Neha , Farrington Sue , Craig Teresa R. , Slattery Julie , Harrold Joan K. , Oldanie Betty , Teno Joan M. , Casarett David J.
Published: June 2012

Purpose

To determine which hospice patients with cancer prefer to die at home and to define factors associated with an increased likelihood of dying at home.

Methods

An electronic health record–based retrospective cohort study was conducted in three hospice programs in Florida, Pennsylvania, and Wisconsin. Main measures included preferred versus actual site of death.

Results

Of 7,391 patients, preferences regarding place of death were determined at admission for 5,837 (79%). After adjusting for other characteristics, patients who preferred to die at home were more likely to die at home (adjusted proportions, 56.5% v 37.0%; odds ratio [OR], 2.21; 95% CI, 1.77 to 2.76). Among those patients (n = 3,152) who preferred to die at home, in a multivariable logistic regression model, patients were more likely to die at home if they had at least one visit per day in the first 4 days of hospice care (adjusted proportions, 61% v 54%; OR, 1.23; 95% CI, 1.07 to 1.41), if they were married (63% v 54%; OR, 1.35; 95% CI, 1.10 to 1.44), and if they had an advance directive (65% v 50%; OR, 2.11; 95% CI, 1.54 to 2.65). Patients with moderate or severe pain were less likely to die at home (OR, 0.56; 95% CI, 0.45 to 0.64), as were patients with better functional status (higher Palliative Performance Scale score: < 40, 64.8%; 40 to 70, 50.2%; OR, 0.79; 95% CI, 0.67 to 0.93; > 70, 40.5%; OR, 0.53; 95% CI, 0.35 to 0.82).

Conclusion

Increased hospice visit frequency may increase the likelihood of patients being able to die in the setting of their choice.
Deficiency of Proton-Sensing Ovarian Cancer G Protein-Coupled Receptor 1 Attenuates Glucose-Stimulated Insulin Secretion
Authors: Nakakura Takashi , Mogi Chihiro , Tobo Masayuki , Tomura Hideaki , Sato Koichi , Kobayashi Masaki , Ohnishi Hiroshi , Tanaka Shigeyasu , Wayama Mitsutoshi , Sugiyama Tetsuya , Kitamura Tadahiro , Harada Akihiro , Okajima Fumikazu
Published: June 2012

Ovarian cancer G protein-coupled receptor 1 (OGR1) has been shown as a receptor for protons. In the present study, we aimed to know whether OGR1 plays a role in insulin secretion and, if so, the manner in which it does. To this end, we created OGR1-deficient mice and examined insulin secretion activity in vivo and in vitro. OGR1 deficiency reduced insulin secretion induced by glucose administered ip, although it was not associated with glucose intolerance in vivo. Increased insulin sensitivity and reduced plasma glucagon level may explain, in part, the unusual normal glucose tolerance. In vitro islet experiments revealed that glucose-stimulated insulin secretion was dependent on extracellular pH and sensitive to OGR1; insulin secretion at pH 7.4 to 7.0, but not 8.0, was significantly suppressed by OGR1 deficiency and inhibition of Gq/11 proteins. Insulin secretion induced by KCl and tolbutamide was also significantly inhibited, whereas that induced by several insulin secretagogues, including vasopressin, a glucagon-like peptide 1 receptor agonist, and forskolin, was not suppressed by OGR1 deficiency. The inhibition of insulin secretion was associated with the reduction of glucose-induced increase in intracellular Ca2+ concentration. In conclusion, the OGR1/Gq/11 protein pathway is activated by extracellular protons existing under the physiological extracellular pH of 7.4 and further stimulated by acidification, resulting in the enhancement of insulin secretion in response to high glucose concentrations and KCl.
Somitogenesis
Authors: Maroto Miguel , Bone Robert A. , Dale J. Kim
Published: June 2012

A segmented body plan is fundamental to all vertebrate species and this bestows both rigidity and flexibility on the body. Segmentation is initiated through the process of somitogenesis. This article aims to provide a broad and balanced cross-species overview of somitogenesis and to highlight the key molecular and cellular events involved in each stage of segmentation. We highlight where our understanding of this multifaceted process relies on strong experimental evidence as well as those aspects where our understanding still relies largely on models.
Planar cell polarity controls directional Notch signaling in theDrosophilaleg
Authors: Capilla Amalia , Johnson Ruth , Daniels Maki , Benavente María , Bray Sarah J. , Galindo Máximo Ibo
Published: June 2012

The generation of functional structures during development requires tight spatial regulation of signaling pathways. Thus, in Drosophila legs, in which Notch pathway activity is required to specify joints, only cells distal to ligand-producing cells are capable of responding. Here, we show that the asymmetric distribution of planar cell polarity (PCP) proteins correlates with this spatial restriction of Notch activation. Frizzled and Dishevelled are enriched at distal sides of each cell and hence localize at the interface with ligand-expressing cells in the non-responding cells. Elimination of PCP gene function in cells proximal to ligand-expressing cells is sufficient to alleviate the repression, resulting in ectopic Notch activity and ectopic joint formation. Mutations that compromise a direct interaction between Dishevelled and Notch reduce the efficacy of repression. Likewise, increased Rab5 levels or dominant-negative Deltex can suppress the ectopic joints. Together, these results suggest that PCP coordinates the spatial activity of the Notch pathway by regulating endocytic trafficking of the receptor.
Characterization of a canine model of glycogen storage disease type IIIa
Authors: Yi Haiqing , Thurberg Beth L. , Curtis Sarah , Austin Stephanie , Fyfe John , Koeberl Dwight D. , Kishnani Priya S. , Sun Baodong
Published: June 2012

Glycogen storage disease type IIIa (GSD IIIa) is an autosomal recessive disease caused by deficiency of glycogen debranching enzyme (GDE) in liver and muscle. The disorder is clinically heterogeneous and progressive, and there is no effective treatment. Previously a naturally occurring dog model for this condition was identified in curly-coated retrievers (CCR). The affected dogs carry a frame-shift mutation in the GDE gene and have no detectable GDE activity in liver and muscle. We characterized in detail the disease expression and progression in eight dogs from age 2 to 16 months. Monthly blood biochemistry revealed elevated and gradually increasing serum alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) activities; serum creatine phosphokinase (CPK) activity exceeded normal range after 12 months. Analysis of tissue biopsy specimens at 4, 12, and 16 months revealed abnormally high glycogen contents in liver and muscle of all dogs. Fasting liver glycogen content increased from 4 months to 12 months, but dropped at 16 months possibly caused by extended fibrosis; muscle glycogen content continually increased with age. Light microscopy revealed significant glycogen accumulation in hepatocytes at all ages. Liver histology showed progressive, age-related fibrosis. In muscle, scattered cytoplasmic glycogen deposits were present in most cells at 4 months, but large, lake-like accumulation developed by 12 and 16 months. Disruption of the contractile apparatus and fraying of myofibrils was observed in muscle at 12 and 16 months by electron microscopy. In conclusion, the CCR dogs are an accurate model of GSD IIIa that will improve our understanding of the disease progression and allow opportunities to investigate treatment interventions.
Deletion of a conserved regulatory element required for Hmx1 expression in craniofacial mesenchyme in the dumbo rat: a novel cause of congenital ear malformation
Authors: Quina Lely , Kuramoto Takashi , Luquetti Daniela V. , Cox Timothy C. , Serikawa Tadao , Turner Eric E.
Published: June 2012

Hmx1 is a homeodomain transcription factor expressed in the developing eye, peripheral ganglia, and branchial arches of avian and mammalian embryos. Recent studies have identified a loss-of-function allele at the HMX1 locus as the causative mutation in the oculo-auricular syndrome (OAS) in humans, characterized by ear and eye malformations. The mouse dumbo (dmbo) mutation, with similar effects on ear and eye development, also results from a loss-of-function mutation in the Hmx1 gene. A recessive dmbo mutation causing ear malformation in rats has been mapped to the chromosomal region containing the Hmx1 gene, but the nature of the causative allele is unknown. Here we show that dumbo rats and mice exhibit similar neonatal ear and eye phenotypes. In midgestation embryos, dumbo rats show a specific loss of Hmx1 expression in neural crest-derived craniofacial mesenchyme (CM), while Hmx1 is expressed normally in retinal progenitors, sensory ganglia, and in CM which is derived from mesoderm. High throughput resequencing of 1Mb of rat chromosome 14 from dmbo/dmbo rats, encompassing the Hmx1 locus, reveals numerous divergences from the rat genomic reference sequence, but no coding changes in Hmx1. Fine genetic mapping narrows the dmbo critical region to an interval of ~410Kb immediately downstream of the Hmx1 transcription unit, and further sequence analysis of this region reveals a 5,777bp deletion located ~80Kb downstream in dmbo/dmbo rats which is not apparent in 137 other rat strains. The dmbo deletion region contains a highly conserved domain of ~500bp which is a candidate distal enhancer, and which exhibits a similar relationship to Hmx genes in all vertebrate species for which data are available. We conclude that the rat dumbo phenotype is likely to result from loss of function of an ultraconserved enhancer specifically regulating Hmx1 expression in neural crest-derived CM. Dysregulation of Hmx1 expression is thus a candidate mechanism for congenital ear malformation, most cases of which remain unexplained.
Open transversus abdominis plane block and analgesic requirements in patients following right hemicolectomy
Authors: Brady RR , Ventham NT , Roberts DM , Graham C , Daniel T
Published: June 2012

INTRODUCTION

Reducing exogenously administered opioids in the post-operative period is associated with early return of bowel function and decreased post-operative complication rates. We evaluated the effectiveness of a surgeon-delivered open transversus abdominis plane (TAP) block as a method to reduce post-operative opioid requirements, sedation and inpatient stay.

METHODS

The patient cohort was identified from those who had undergone a right hemicolectomy for colonic cancer. Patients received either an open TAP block and post-operative patient controlled anaesthesia (PCA) (n=20) or were part of a control group who received subcutaneous local anaesthetic infiltration and PCA (n=16).

RESULTS

PCA morphine use was reduced within the first 24 hours post-operatively in the TAP block group compared with controls (42.1mg vs 72.3mg, p=0.002). Sedation was also reduced significantly in the early post-operative period (p<0.04). There was a non-significant trend towards reduced length of stay in the intervention group (8.2 vs 8.73 days). There were no recorded complications attributable to the open TAP block.

CONCLUSIONS

Open TAP blocks are safe and reduce post-operative opioid requirements and sedation after right hemicolectomies. They should be considered as part of a multimodal enhanced recovery approach to patients undergoing abdominal surgery via a transverse incision.
Human body projectiles implantation in victims of suicide bombings and implications for health and emergency care providers: the 7/7 experience
Authors: Patel HDL , Dryden S , Gupta A , Stewart N
Published: June 2012

INTRODUCTION

On 7 July 2005 four suicide bombings occurred on the London transport systems. In some of the injured survivors, bone fragments were embedded as biological foreign bodies. The aim of this study was to revisit those individuals who had sustained human projectile implantation injuries as a result of the bomb blasts at all scenes, review the process of body parts mapping and DNA identification at the scene, detail the management of such injuries and highlight the protocols that have been put in place for protection against blood borne pathogens.

METHODS

We retrospectively reviewed 12 instances of victims who sustained human body projectile implantation injuries. The Metropolitan Police and forensic scientists identified the human projectiles using DNA profiling and mapped these on the involved carriages and those found outside. All human projectiles included were greater than 3cm2.

RESULTS

Twelve cases had human projectile implantation injuries. Of these, two died at the scene and ten were treated in hospital. Projectiles were mapped at three of the four bomb blast sites. Our findings show that victims within a 2m radius of the blast had human projectile injuries. Eight of the allogenic bony fragments that were identified in the survivors originated from the suicide bomber. All the victims with an open wound should have prophylaxis against hepatitis B and serum stored for appropriate action against HIV and hepatitis C infection.

CONCLUSIONS

All victims following a suicide bombing should be assumed to have human body projectile implantation injuries with blood products or bony fragments. All immediate care providers should receive prophylaxis against hepatitis B virus and appropriate action should be taken against HIV and hepatitis C infection.
Analogue-based drug discovery: Contributions to medicinal chemistry principles and drug design strategies. Microtubule stabilizers as a case in point (Special Topic Article)
Authors: El-Dakdouki Mohammad H. , Erhardt Paul W.
Published: June 2012

The benefits of utilizing marketed drugs as starting points to discover new therapeutic agents have been well documented within the IUPAC series of books that bear the title Analogue-based Drug Discovery (ABDD). Not as clearly demonstrated, however, is that ABDD also contributes to the elaboration of new basic principles and alternative drug design strategies that are useful to the field of medicinal chemistry in general. After reviewing the ABDD programs that have evolved around the area of microtubule-stabilizing chemo-therapeutic agents, the present article delineates the associated research activities that additionally contributed to general strategies that can be useful for prodrug design, identifying pharmacophores, circumventing multidrug resistance (MDR), and achieving targeted drug distribution.
Association of PBEF gene polymorphisms with acute lung injury, sepsis, and pneumonia in a northeastern Chinese population
Authors: Liu Yaxin , Shao Yuxia , Yu Baiquan , Sun Liyan , Lv Fuzhen
Published: June 2012

Background: Several studies have suggested that pre-B-cell colony-enhancing factor (PBEF) gene polymorphisms are associated with susceptibility to and prognosis of acute lung injury (ALI) in several populations of Caucasians. The aim of this study was to detect the distribution of PBEF alleles and to evaluate any potential relationship between PBEF polymorphisms and ALI, sepsis, and pneumonia in the Han population of Northeast China.

Methods: Genotyping of two PBEF promoter single-nucleotide polymorphisms (SNPs), rs61330082 (C–1535T) and rs9770242 (T–1001G), were performed in patients with ALI (n=130), sepsis alone (n=107), bacterial pneumonia (n=195) and 150 healthy volunteers using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.

Results: We found no variation in the T-1001G allele of PBEF. The homozygous TT genotype was the only genotype. This result is different from that observed in Caucasians. The frequency of the -1543T allele was lower in patients with ALI and sepsis than that in healthy subjects ALI vs. healthy controls: OR=0.60, 95% CI 0.43–0.84, p=0.003; and sepsis vs. healthy controls: OR=0.69, 95% CI 0.49–0.99, p=0.04, respectively). The frequency of TT genotype of -1543T was significantly lower in patients with ALI and sepsis than in healthy subjects (ALI vs. healthy controls: OR=0.23, 95% CI 0.10–0.54, p=0.001; and sepsis vs. healthy controls: OR=0.36, 95% CI 0.15–0.83, p=0.02, respectively).

Conclusions: This study suggested that -1543T allele might be a protective factor for ALI and sepsis, but it apparently had no connection with pneumonia in northeastern Chinese Han patients.
A Comparison Study of Friction Measurements for Chip Seal
Authors: Lee Jusang , Lee Jaejun , Kim Y. Richard , Mun Sungho
Published: June 2012

This paper presents a development in measuring skid resistance in a laboratory performance test for chip seal. It is important to develop a relationship between the British pendulum test (BPT) and the locked-wheel skid test (LWST), or grip tester (GT). The chip seal is a typical pavement preservation treatment used by the North Carolina Dept. of Transportation (NCDOT). In North America, loss of skid resistance is a common road condition that indicates the need for a chip seal, as one of the major advantages of chip seal is an increase in skid resistance. Most agencies have a specified cycle in which skid resistance is measured as a part of their pavement-management system. These skid resistance measurements are invaluable when deciding which roads require chip seal [Gransberg, D. D. and James, D. M. B., “Chip Seal Best Practices,” NCHRP Synthesis of Highway Practice 342, Transportation Research Board of the National Academies, Washington, D.C., 2005]. In this study, skid resistance was evaluated on 14 selected chip seals using three different tests: the BPT, LWST, and GT. The correlation between British pendulum number (BPN) and skid number (SN) was relatively strong with an R2 value of 0.74. This finding indicated that the BPN measured in the laboratory could be utilized for predicting the SN, which cannot be measured in the laboratory.
Normal muscle glucose uptake in mice deficient in muscle GLUT4
Authors: Fam Barbara C , Rose Laura J , Sgambellone Rebecca , Ruan Zheng , Proietto Joseph , Andrikopoulos Sofianos
Published: June 2012

Skeletal muscle insulin resistance is a major characteristic underpinning type 2 diabetes. Impairments in the insulin responsiveness of the glucose transporter,Glut4 (Slc2a4), have been suggested to be a contributing factor to this disturbance. We have produced muscle-specificGlut4knockout (KO) mice using Cre/LoxP technology on a C57BL6/J background and shown undetectable levels of GLUT4 in both skeletal muscle and heart. Our aim was to determine whether complete deletion of muscle GLUT4 does in fact lead to perturbations in glucose homoeostasis. Glucose tolerance, glucose turnover and 2-deoxyglucose uptake into muscle and fat under basal and insulin-stimulated conditions were assessed in 12-week-old KO and control mice using the oral glucose tolerance test (OGTT) and hyperinsulinaemic/euglycaemic clamp respectively. KO mice weighed ∼17% less and had significantly heavier hearts compared with control mice. Basally, plasma glucose and plasma insulin were significantly lower in the KO compared with control mice, which conferred normal glucose tolerance. Despite the lack of GLUT4 in the KO mouse muscle, glucose uptake was not impaired in skeletal muscle but was reduced in heart under insulin-stimulated conditions. Neither GLUT1 nor GLUT12 protein levels were altered in the skeletal muscle or heart tissue of our KO mice. High-fat feeding did not alter glucose tolerance in the KO mice but led to elevated plasma insulin levels during the glucose tolerance test. Our study demonstrates that deletion of muscle GLUT4 does not adversely affect glucose disposal and glucose tolerance and that compensation from other transporters may contribute to this unaltered homoeostasis of glucose.
The role of hereditary and environmental factors in autoimmune thyroid diseases
Authors: Balázs Csaba
Published: June 2012

Autoimmune thyroid diseases are the most common organ-specific autoimmune disorders affecting 5% to 10% of the population in Western countries. The clinical presentation varies from hyperthyroidism in Graves’ disease to hypothyroidism in Hashimoto’s thyroiditis. While the exact etiology of thyroid autoimmunity is not known, the interaction between genetic susceptibility and environmental factors appears to be of fundamental importance to initiate the process of thyroid autoimmunity. The identified autoimmune thyroid disease susceptibility genes include immune-modulating genes, such as the major histocompatibility complex, and thyroid-specific genes, including TSH receptor, thyroglobulin and thyroid peroxidase. The majority of the anti-TSH-receptor antibodies have a stimulating capacity and are responsible for hyperthyroidism. The anti-thyroglobulin- and anti-thyroid peroxidase antibodies belonging to the catalytic type of antibodies destroy the thyrocytes resulting in hypothyroidism. The appearance of anti-thyroid peroxidase antibodies precedes the induction of thyroiditis and the manifestation of hypothyroidism. The molecular analysis of thyroglobulin gene polymorphism is important in the mechanism of autoimmune thyroiditis. The autoantigen presentation by major histocompatibility complex molecules is a key point of the autoimmune mechanism. It has been shown that a HLA-DR variant containing arginine at position 74 of the DRβ1 chain confers a strong genetic susceptibility to autoimmune thyroid diseases, Graves’ disease and Hashimoto’s thyroiditis, while glutamine at position DRβ1-74 is protective. Human thyroglobulin 2098 peptide represents a strong and specific DRβ1-Arg74 binder, while a non-binding control peptide, thyroglobulin 2766 fails to induce this response. Moreover, thyroglobulin 2098 stimulated T-cells from individuals who were positive for thyroglobulin antibodies, demonstrating that thyroglobulin 2098 is an immunogenic peptide capable of being presented in vivo and activating T-cells in autoimmune thyroid diseases. Taken together these findings suggest that thyroglobulin 2098, a strong and specific binder to the disease-associated HLA-DRβ1-Arg74, is a major human T-cell epitope and it participates in the pathomechanism of the autoimmune thyroid disease. The exact nature of the role of environmental factors in the autoimmune thyroid disease is still not well known, but the importance of several factors such as iodine, drugs and infections has been reported. Further knowledge of the precise mechanisms of interaction between environmental factors and genes in inducing thyroid autoimmunity could result in the development of new strategies for diagnosis, prevention and treatment. Orv. Hetil., 2012, 153, 1013–1022.
Conhecimento, atitude e prática sobre fototerapia entre profissionais de enfermagem de hospitais de ensino
Authors: Machado Simone Pires Cavalcanti , Samico Isabella Chagas , Braga Taciana Duque de Almeida
Published: June 2012

Este artigo consiste em um estudo tipo inquérito CAP (Conhecimento, Atitude e Prática) com objetivo de avaliar o conhecimento, atitude e prática sobre fototerapia entre profissionais de Enfermagem de dois hospitais de ensino da cidade de Recife-PE, por meio de questionário semiestruturado aplicado a 111 profissionais. Para comparação das médias de acertos, foi utilizado o teste t de Student. Assim, verificaram-se maiores médias para a prática, seguidas das relacionadas à atitude e menores percentuais de acertos para o conhecimento. Na comparação das médias entre conhecimento e prática, as diferenças se mostraram estatisticamente significantes para todas as variáveis (p<0,05). Os resultados do estudo aqui apresentado apontam para a necessidade de implementação de atividades capazes de permitir um equilíbrio entre conhecimento, atitude e prática dos profissionais de Enfermagem sobre fototerapia.