bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of a multidimensional infection control approach on central line-associated bloodstream infections rates in adult intensive care units of 8 cities of Turkey: findings of the International Nosocomial Infection Control Consortium (INICC)
Authors: Leblebicioglu Hakan , Öztürk Recep , Rosenthal Victor Daniel , Akan Özay Arıkan , Sirmatel Fatma , Ozdemir Davut , Uzun Cengiz , Turgut Huseyin , Ersoz Gulden , Koksal Iftíhar , Özgültekin Asu , Esen Saban , Ulger Fatma , Dilek Ahmet , Yilmaz Hava , Dikmen Yalim , Aygún Gökhan , Tulunay Melek , Oral Mehmet , Ünal Necmettin , Cengiz Mustafa , Yilmaz Leyla , Geyik Mehmet Faruk , Şahin Ahmet , Erdogan Selvi , Sacar Suzan , Sungurtekin Hülya , Uğurcan Doğaç , Kaya Ali , Kuyucu Necdet , Yýlmaz Gürdal , Kaya Selçuk , Ulusoy Hülya , İnan Asuman
Published: May 2013

Background

Central line-associated bloodstream infections (CLABs) have long been associated with excess lengths of stay, increased hospital costs and mortality attributable to them. Different studies from developed countries have shown that practice bundles reduce the incidence of CLAB in intensive care units. However, the impact of the bundle strategy has not been systematically analyzed in the adult intensive care unit (ICU) setting in developing countries, such as Turkey. The aim of this study is to analyze the impact of the International Nosocomial Infection Control Consortium (INICC) multidimensional infection control approach to reduce the rates of CLAB in 13 ICUs of 13 INICC member hospitals from 8 cities of Turkey.

Methods

We conducted active, prospective surveillance before-after study to determine CLAB rates in a cohort of 4,017 adults hospitalized in ICUs. We applied the definitions of the CDC/NHSN and INICC surveillance methods. The study was divided into baseline and intervention periods. During baseline, active outcome surveillance of CLAB rates was performed. During intervention, the INICC multidimensional approach for CLAB reduction was implemented and included the following measures: 1- bundle of infection control interventions, 2- education, 3- outcome surveillance, 4- process surveillance, 5- feedback of CLAB rates, and 6- performance feedback on infection control practices. CLAB rates obtained in baseline were compared with CLAB rates obtained during intervention.

Results

During baseline, 3,129 central line (CL) days were recorded, and during intervention, we recorded 23,463 CL-days. We used random effects Poisson regression to account for clustering of CLAB rates within hospital across time periods. The baseline CLAB rate was 22.7 per 1000 CL days, which was decreased during the intervention period to 12.0 CLABs per 1000 CL days (IRR 0.613; 95% CI 0.43 – 0.87; P 0.007). This amounted to a 39% reduction in the incidence rate of CLAB.

Conclusions

The implementation of multidimensional infection control approach was associated with a significant reduction in the CLAB rates in adult ICUs of Turkey, and thus should be widely implemented.
Upregulation of triglyceride synthesis in skeletal muscle overexpressing DGAT1
Authors: Yang Feifei , Wei Zhuying , Ding Xiangbin , Liu Xinfeng , Ge Xiuguo , Song Guimin , Li Guangpeng , Guo Hong
Published: May 2013

The gene encoding diacylglycerol acyltransferase (DGAT1) is a functional and positional candidate gene for milk and intramuscular fat content. A bovine DGAT1 overexpression vector was constructed containing mouse MCK promoter and bovine DGAT1 cDNA. MCK-DGAT1 transgene in FVB mice was researched in present study. The transgene DGAT1 had a high level of expression in contrast to the endogenous DGAT1 in posterior tibial muscle of the transgenic mice, but a low expression level in the cardiac muscle. Compared with wild-type mice, triglyceride and DGAT1 content were approximately fourfold and 50% increased in posterior tibial muscle of the transgenic mice, respectively, while a little increase in cardiac muscle.
Longitudinal study of rural health workforce in five counties in China: research design and baseline description
Authors: Xu Huiwen , Zhang Weijun , Zhang Xiulan , Qu Zhiyong , Wang Xiaohua , Sa Zhihong , Li Yafang , Zhao Shuliang , Qi Xuan , Tian Donghua
Published: May 2013

Background

The village doctors have served rural residents for many decades in China, and their role in rural health system has been highly praised in the world; unfortunately, less attention has been paid to the health workforce during the ambitious healthcare reform in recent years. Therefore, we conducted a longitudinal study to explore the current situation and track the future evolution of the rural healthcare workforce.

Methods

The self-administered structured Village Clinic Questionnaire and Village Doctor Questionnaire, which were modified from the official questionnaires of the Ministry of Health, were constructed after three focus groups, in-depth interviews in Hebei Province, and a pilot survey in Sichuan Province. Using a stratified multistage cluster sampling process, we gathered baseline data for a longitudinal survey of village doctors, village clinics from Changshu County, Liyang County, Yongchuan District, Mianzhu County, and Jingning County in China in 2011. Well-trained interviewers and strict procedures were employed to ensure the quality of this survey. Descriptive and correlation analyses were performed with Stata 12.0.

Results

After four months of surveying, 1,982 Village Doctor Questionnaires were collected, and the response rate was 88.1%. There were 1,507 (76.0%) male and 475 (24.0%) female doctors, with an average age of 51.3 years. The majority of village doctors (58.5%) practiced both western medicine and Traditional Chinese Medicine, and 91.2% of the doctors received their education below college level. Their practice methods were not correlated with education level (P = 0.43), but closely related to the way they obtained their highest degree (that is, prior to starting work or as on-the-job training) (P < 0.01). The mean income of the village doctors was 1,817 (95% CI 1,733 to 1,900) RMB per month in 2011; only 757 (41.3%) doctors had pensions, and the self-reported expected pension was 1,965 RMB per month.

Conclusions

Village doctors in rural China are facing critical challenges, including aging, gender imbalance, low education, and a lack of social protection. This study may be beneficial for making better policies for the development of the health workforce and China’s healthcare reform.
SATB1 is overexpressed in metastatic prostate cancer and promotes prostate cancer cell growth and invasion
Authors: Mao Lijun , Yang Chunhua , Wang Junqi , Li Wang , Wen Rumin , Chen Jiacun , Zheng Junnian
Published: May 2013

Background

Special AT-rich sequence binding protein 1 (SATB1) is a nuclear factor that functions as the global chromatin organizer to regulate chromatin structure and gene expression gene expression. SATB1 has been shown to be abnormally expressed in various types of cancer. However, the expression and role of SATB1 in prostate cancer remain unclear.

Methods

120 cases of prostatic carcinoma and 60 cases of benign prostate hyperplasia were analyzed for SATB1 expression by immunohistochemistry. LNCaP, DU-145, and PC3 prostate cancer cells were examined for SATB1 expression by Western blot analysis. Cell proliferation and invasion was evaluated by CCK8 and transwell invasion assay, respectively.

Results

SATB1 staining was stronger in prostatic carcinomas with metastasis than in those without metastasis, but was absent in benign prostate hyperplasia. Furthermore, SATB1 expression was positively correlated with bone metastasis and the Gleason score. SATB1 overexpression promoted the proliferation and invasion of LNCaP cells while SATB1 knockdown inhibited the proliferation and invasion of DU-145 cells.

Conclusions

These findings provide novel insight into oncogenic role of SATB1 in prostate cancer, suggesting that SATB1 is a promising biomarker and therapeutic target for prostate cancer.
The evolution of machining-induced surface of single-crystal FCC copper via nanoindentation
Authors: Zhang Lin , Huang Hu , Zhao Hongwei , Ma Zhichao , Yang Yihan , Hu Xiaoli
Published: May 2013

The physical properties of the machining-induced new surface depend on the performance of the initial defect surface and deformed layer in the subsurface of the bulk material. In this paper, three-dimensional molecular dynamics simulations of nanoindentation are preformed on the single-point diamond turning surface of single-crystal copper comparing with that of pristine single-crystal face-centered cubic copper. The simulation results indicate that the nucleation of dislocations in the nanoindentation test on the machining-induced surface and pristine single-crystal copper is different. The dislocation embryos are gradually developed from the sites of homogeneous random nucleation around the indenter in the pristine single-crystal specimen, while the dislocation embryos derived from the vacancy-related defects are distributed in the damage layer of the subsurface beneath the machining-induced surface. The results show that the hardness of the machining-induced surface is softer than that of pristine single-crystal copper. Then, the nanocutting simulations are performed along different crystal orientations on the same crystal surface. It is shown that the crystal orientation directly influences the dislocation formation and distribution of the machining-induced surface. The crystal orientation of nanocutting is further verified to affect both residual defect generations and their propagation directions which are important in assessing the change of mechanical properties, such as hardness and Young's modulus, after nanocutting process.
Cognitive and cerebrovascular improvements following kinin B1 receptor blockade in Alzheimer’s disease mice
Authors: Lacoste Baptiste , Tong Xin-Kang , Lahjouji Karim , Couture Réjean , Hamel Edith
Published: May 2013

Background

Recent evidence suggests that the inducible kinin B1 receptor (B1R) contributes to pathogenic neuroinflammation induced by amyloid-beta (Aβ) peptide. The present study aims at identifying the cellular distribution and potentially detrimental role of B1R on cognitive and cerebrovascular functions in a mouse model of Alzheimer’s disease (AD).

Methods

Transgenic mice overexpressing a mutated form of the human amyloid precursor protein (APPSwe,Ind, line J20) were treated with a selective and brain penetrant B1R antagonist (SSR240612, 10 mg/kg/day for 5 or 10 weeks) or vehicle. The impact of B1R blockade was measured on i) spatial learning and memory performance in the Morris water maze, ii) cerebral blood flow (CBF) responses to sensory stimulation using laser Doppler flowmetry, and iii) reactivity of isolated cerebral arteries using online videomicroscopy. Aβ burden was quantified by ELISA and immunostaining, while other AD landmarks were measured by western blot and immunohistochemistry.

Results

B1R protein levels were increased in APP mouse hippocampus and, prominently, in reactive astrocytes surrounding Aβ plaques. In APP mice, B1R antagonism with SSR240612 improved spatial learning, memory and normalized protein levels of the memory-related early gene Egr-1 in the dentate gyrus of the hippocampus. B1R antagonism restored sensory-evoked CBF responses, endothelium-dependent dilations, and normalized cerebrovascular protein levels of endothelial nitric oxide synthase and B2R. In addition, SSR240612 reduced (approximately 50%) microglial, but not astroglial, activation, brain levels of soluble Aβ1-42, diffuse and dense-core Aβ plaques, and it increased protein levels of the Aβ brain efflux transporter lipoprotein receptor-related protein-1 in cerebral microvessels.

Conclusion

These findings show a selective upregulation of astroglial B1R in the APP mouse brain, and the capacity of the B1R antagonist to abrogate amyloidosis, cerebrovascular and memory deficits. Collectively, these findings provide convincing evidence for a role of B1R in AD pathogenesis.
Anatomy and development of the larval nervous system in Echinococcus multilocularis
Authors: Koziol Uriel , Krohne Georg , Brehm Klaus
Published: May 2013

Background

The metacestode larva of Echinococcus multilocularis (Cestoda: Taeniidae) develops in the liver of intermediate hosts (typically rodents, or accidentally in humans) as a labyrinth of interconnected cysts that infiltrate the host tissue, causing the disease alveolar echinococcosis. Within the cysts, protoscoleces (the infective stage for the definitive canid host) arise by asexual multiplication. These consist of a scolex similar to that of the adult, invaginated within a small posterior body. Despite the importance of alveolar echinococcosis for human health, relatively little is known about the basic biology, anatomy and development of E. multilocularis larvae, particularly with regard to their nervous system.

Results

We describe the existence of a subtegumental nerve net in the metacestode cysts, which is immunoreactive for acetylated tubulin-α and contains small populations of nerve cells that are labeled by antibodies raised against several invertebrate neuropeptides. However, no evidence was found for the existence of cholinergic or serotoninergic elements in the cyst wall. Muscle fibers occur without any specific arrangement in the subtegumental layer, and accumulate during the invaginations of the cyst wall that form brood capsules, where protoscoleces develop. The nervous system of the protoscolex develops independently of that of the metacestode cyst, with an antero-posterior developmental gradient. The combination of antibodies against several nervous system markers resulted in a detailed description of the protoscolex nervous system, which is remarkably complex and already similar to that of the adult worm.

Conclusions

We provide evidence for the first time of the existence of a nervous system in the metacestode cyst wall, which is remarkable given the lack of motility of this larval stage, and the lack of serotoninergic and cholinergic elements. We propose that it could function as a neuroendocrine system, derived from the nervous system present in the bladder tissue of other taeniids. The detailed description of the development and anatomy of the protoscolex neuromuscular system is a necessary first step toward the understanding of the developmental mechanisms operating in these peculiar larval stages.
Analytical technologies for influenza virus-like particle candidate vaccines: challenges and emerging approaches
Authors: Thompson Christine M , Petiot Emma , Lennaertz Alexandre , Henry Olivier , Kamen Amine A
Published: May 2013

Influenza virus-like particle vaccines are one of the most promising ways to respond to the threat of future influenza pandemics. VLPs are composed of viral antigens but lack nucleic acids making them non-infectious which limit the risk of recombination with wild-type strains. By taking advantage of the advancements in cell culture technologies, the process from strain identification to manufacturing has the potential to be completed rapidly and easily at large scales. After closely reviewing the current research done on influenza VLPs, it is evident that the development of quantification methods has been consistently overlooked. VLP quantification at all stages of the production process has been left to rely on current influenza quantification methods (i.e. Hemagglutination assay (HA), Single Radial Immunodiffusion assay (SRID), NA enzymatic activity assays, Western blot, Electron Microscopy). These are analytical methods developed decades ago for influenza virions and final bulk influenza vaccines. Although these methods are time-consuming and cumbersome they have been sufficient for the characterization of final purified material. Nevertheless, these analytical methods are impractical for in-line process monitoring because VLP concentration in crude samples generally falls out of the range of detection for these methods. This consequently impedes the development of robust influenza-VLP production and purification processes. Thus, development of functional process analytical techniques, applicable at every stage during production, that are compatible with different production platforms is in great need to assess, optimize and exploit the full potential of novel manufacturing platforms.
An efficient flat-surface collar-free grafting method for Arabidopsis thaliana seedlings
Authors: Marsch-Martínez Nayelli , Franken John , Gonzalez-Aguilera Karla L , de Folter Stefan , Angenent Gerco , Alvarez-Buylla Elena R
Published: May 2013

Background

Grafting procedures are an excellent tool to study long range signalling processes within a plant. In the last decade, suitable flat-surface grafting procedures for young Arabidopsis seedlings using a collar to support the graft have been developed, allowing the study of long-range signals from a molecular perspective.

Results

In the modification presented here, scion and stock are put together on the medium without supporting elements, while cotyledons are removed from the scion, resulting in increased grafting success that can reach up to 100%. At the same time, the protocol enables to process as many as 36 seedlings per hour, which combined with the high success percentage represents increased efficiency per time unit.

Conclusions

Growing cotyledons usually push the scion and the rootstock away in the absence of a supporting element. Removing them at the grafting step greatly improved success rate and reduced post-grafting manipulations.
Estimation of bovine leukemia virus (BLV) proviral load harbored by lymphocyte subpopulations in BLV-infected cattle at the subclinical stage of enzootic bovine leucosis using BLV-CoCoMo-qPCR
Authors: Panei Carlos Javier , Takeshima Shin-nosuke , Omori Takashi , Nunoya Tetsuo , Davis William C , Ishizaki Hiroshi , Matoba Kazuhiro , Aida Yoko
Published: May 2013

Background

Bovine leukemia virus (BLV) is associated with enzootic bovine leukosis (EBL), which is the most common neoplastic disease of cattle. BLV infection may remain clinically silent at the aleukemic (AL) stage, cause persistent lymphocytosis (PL), or, more rarely, B cell lymphoma. BLV has been identified in B cells, CD2+ T cells, CD3+ T cells, CD4+ T cells, CD8+ T cells, γ/δ T cells, monocytes, and granulocytes in infected cattle that do not have tumors, although the most consistently infected cell is the CD5+ B cell. The mechanism by which BLV causes uncontrolled CD5+ B cell proliferation is unknown. Recently, we developed a new quantitative real-time polymerase chain reaction (PCR) method, BLV-CoCoMo-qPCR, which enabled us to demonstrate that the proviral load correlates not only with BLV infection, as assessed by syncytium formation, but also with BLV disease progression. The present study reports the distribution of BLV provirus in peripheral blood mononuclear cell subpopulations isolated from BLV-infected cows at the subclinical stage of EBL as examined by cell sorting and BLV-CoCoMo-qPCR.

Results

Phenotypic characterization of five BLV-infected but clinically normal cattle with a proviral load of > 100 copies per 1 × 105 cells identified a high percentage of CD5+ IgM+ cells (but not CD5- IgM+ B cells, CD4+ T cells, or CD8+T cells). These lymphocyte subpopulations were purified from three out of five cattle by cell sorting or using magnetic beads, and the BLV proviral load was estimated using BLV-CoCoMo-qPCR. The CD5+ IgM+ B cell population in all animals harbored a higher BLV proviral load than the other cell populations. The copy number of proviruses infecting CD5- IgM+ B cells, CD4+ cells, and CD8+ T cells (per 1 ml of blood) was 1/34 to 1/4, 1/22 to 1/3, and 1/31 to 1/3, respectively, compared with that in CD5+ IgM+ B cells. Moreover, the BLV provirus remained integrated into the genomic DNA of CD5+ IgM+ B cells, CD5- IgM+ B cells, CD4+ T cells, and CD8+ T cells, even in BLV-infected cattle with a proviral load of <100 copies per 105 cells.

Conclusions

The results of the recent study showed that, although CD5+ IgM+ B cells were the main cell type targeted in BLV-infected but clinically normal cattle, CD5- IgM+ B cells, CD4+ cells, and CD8+ T cells were infected to a greater extent than previously thought.
Multi-institutional comparison of treatment planning using stereotactic ablative body radiotherapy for hepatocellular carcinoma – benchmark for a prospective multi-institutional study
Authors: Eriguchi Takahisa , Takeda Atsuya , Oku Yohei , Ishikura Satoshi , Kimura Tomoki , Ozawa Shuichi , Nakashima Takeo , Matsuo Yukinori , Nakamura Mitsuhiro , Matsumoto Yasuo , Yamazaki Sadanori , Sanuki Naoko , Ito Yoshinori
Published: May 2013

Introduction

Several single institution phase I and phase II trials of stereotactic ablative body radiotherapy (SABR) for liver tumors have reported promising results and high local control rates of over 90%. However, there are wide variations in dose and fractionation due to different prescription policies and treatment methods across SABR series that have been published to date.

This study aims to assess and minimize inter-institutional variations in treatment planning using SABR for hepatocellular carcinoma (HCC) in preparation for a prospective multi-institutional study.

Methods

Four institutions (A-D) participated in this study. Each institution was provided with data from four cases, including planning and diagnostic CT images and clinical information, and asked to implement three plans (a practice plan and protocol plans 1 and 2). Practice plans were established based on the current treatment protocols at each institution. In protocol plan 1, each institution was instructed to prescribe 40 Gy in five fractions within 95% of the planning target volume (PTV). After protocol plan 1 was evaluated, we made protocol plan 2, The additional regulation to protocol plan 1 was that 40 Gy in five fractions was prescribed to a 70% isodose line of the global maximum dose within the PTV. Planning methods and dose volume histograms (DVHs) including the median PTV D50 (Dm50) and the median normal liver volume that received 20 Gy or higher (Vm20) were compared.

Results

In the practice plan, Dm50 was 48.4 Gy (range, 43.6-51.2 Gy). Vm20 was 15.9% (range, 12.2-18.9%). In protocol plan 1, the Dm50 at institution A was higher (51.2 Gy) than the other institutions (42.0-42.2 Gy) due to differences in dose specifications. In protocol plan 2, variations in DVHs were reduced. The Dm50 was 51.9 Gy (range, 51.0-53.1 Gy), and the Vm20 was 12.3% (range, 10.4-13.2%). The homogeneity index was nearly equivalent at all institutions.

Conclusions

There were notable inter-institutional differences in practice planning using SABR to treat HCC. The range of PTV and normal liver DVH values was reduced when the dose was prescribed to an isodose line within the PTV. In multi-institutional studies, detailed dose specifications based on collaboration are necessary.
Development and specification of cerebellar stem and progenitor cells in zebrafish: from embryo to adult
Authors: Kaslin Jan , Kroehne Volker , Benato Francesca , Argenton Francesco , Brand Michael
Published: May 2013

Background

Teleost fish display widespread post-embryonic neurogenesis originating from many different proliferative niches that are distributed along the brain axis. During the development of the central nervous system (CNS) different cell types are produced in a strict temporal order from increasingly committed progenitors. However, it is not known whether diverse neural stem and progenitor cell types with restricted potential or stem cells with broad potential are maintained in the teleost fish brain.

Results

To study the diversity and output of neural stem and progenitor cell populations in the zebrafish brain the cerebellum was used as a model brain region, because of its well-known architecture and development. Transgenic zebrafish lines, in vivo imaging and molecular markers were used to follow and quantify how the proliferative activity and output of cerebellar progenitor populations progress. This analysis revealed that the proliferative activity and progenitor marker expression declines in juvenile zebrafish before they reach sexual maturity. Furthermore, this correlated with the diminished repertoire of cell types produced in the adult. The stem and progenitor cells derived from the upper rhombic lip were maintained into adulthood and they actively produced granule cells. Ventricular zone derived progenitor cells were largely quiescent in the adult cerebellum and produced a very limited number of glia and inhibitory inter-neurons. No Purkinje or Eurydendroid cells were produced in fish older than 3 months. This suggests that cerebellar cell types are produced in a strict temporal order from distinct pools of increasingly committed stem and progenitor cells.

Conclusions

Our results in the zebrafish cerebellum show that neural stem and progenitor cell types are specified and they produce distinct cell lineages and sub-types of brain cells. We propose that only specific subtypes of brain cells are continuously produced throughout life in the teleost fish brain. This implies that the post-embryonic neurogenesis in fish is linked to the production of particular neurons involved in specific brain functions, rather than to general, indeterminate growth of the CNS and all of its cell types.
Time course changes of anti- and pro-apoptotic proteins in apigenin-induced genotoxicity
Authors: Papachristou Fotini , Chatzaki Ekaterini , Petrou Athanasios , Kougioumtzi Ioanna , Katsikogiannis Nikolaos , Papalambros Alexandros , Tripsianis Grigorios , Simopoulos Constantinos , Tsaroucha Alexandra K
Published: May 2013

Background

Apigenin (4′,5,7-trihydroxyflavone, AP), an active component of many medicinal Chinese herbs, exhibits anticancer propertiesin vitroandin vivo. This study aims to investigate the genotoxic, cytostatic, and cytotoxic effects of AP and time course changes in the levels of anti- and pro-apoptotic proteins involved in the DNA damage response in HepG2 cells.

Methods

The genotoxic potential of AP was determined by sister chromatid exchanges (SCEs) and chromosomal aberrations (CAs) analysis. The levels of cytostaticity and cytotoxicity were evaluated by the proliferation rate and mitotic indices, respectively. MTT was used to study cytotoxicity, while the induction of apoptosis and the expression of apoptosis-related proteins were determined by ELISA.

Results

At concentrations greater than 10 μM, AP decreased cell survival in a dose- (48 h: 10vs.20 μΜ,P < 0.001 and 20vs.50 μΜ,P = 0.005; 72 h: 10vs.20 μΜ,P < 0.001 and 20vs.50 μΜ,P = 0.001) and time-dependent manner (20 μΜ: 24vs.48 h,P < 0.001 and 48vs.72 h,P = 0.003; 50 μΜ: 24vs.48 h,P < 0.001 and 48vs.72 h,P < 0.001; 100 μΜ: 24vs.48 h,P < 0.001 and 48vs.72 h,P < 0.001). SCEs rates, cell proliferation, and mitotic divisions were also affected in a dose-dependent manner (P < 0.001). There was no change in the frequency of aberrant cells (1 μΜ ΑP:P = 0.554; 10 μM AP:P = 0.337; 20 μΜ AP:P = 0.239). Bcl-2 levels were reduced 3 h after AP administration (P = 0.003) and remained reduced throughout the 48 h observation period (6 h,P = 0.044; 12 h,P = 0.001; 24 h,P = 0.042; 48 h,P = 0.012). Bax and soluble Fas exhibited a transient upregulation 24 h after AP treatment. The Bax/Bcl-2 ratio was also increased at 12 h and remained increased throughout the 48 h observation period.

Conclusion

AP exhibited dose-dependent genotoxic potential in HepG2 cells. The protein levels of sFas, Bcl-2, and Bax were affected by AP to promote cell survival and cell death, respectively.
Brittle cornea syndrome: recognition, molecular diagnosis and management
Authors: Burkitt Wright Emma MM , Porter Louise F , Spencer Helen L , Clayton-Smith Jill , Au Leon , Munier Francis L , Smithson Sarah , Suri Mohnish , Rohrbach Marianne , Manson Forbes DC , Black Graeme CM
Published: May 2013

Brittle cornea syndrome (BCS) is an autosomal recessive disorder characterised by extreme corneal thinning and fragility. Corneal rupture can therefore occur either spontaneously or following minimal trauma in affected patients. Two genes, ZNF469 and PRDM5, have now been identified, in which causative pathogenic mutations collectively account for the condition in nearly all patients with BCS ascertained to date. Therefore, effective molecular diagnosis is now available for affected patients, and those at risk of being heterozygous carriers for BCS. We have previously identified mutations in ZNF469 in 14 families (in addition to 6 reported by others in the literature), and in PRDM5 in 8 families (with 1 further family now published by others). Clinical features include extreme corneal thinning with rupture, high myopia, blue sclerae, deafness of mixed aetiology with hypercompliant tympanic membranes, and variable skeletal manifestations. Corneal rupture may be the presenting feature of BCS, and it is possible that this may be incorrectly attributed to non-accidental injury. Mainstays of management include the prevention of ocular rupture by provision of protective polycarbonate spectacles, careful monitoring of visual and auditory function, and assessment for skeletal complications such as developmental dysplasia of the hip. Effective management depends upon appropriate identification of affected individuals, which may be challenging given the phenotypic overlap of BCS with other connective tissue disorders.
Molecular and cellular mechanisms of neutral lipid accumulation in diatom following nitrogen deprivation
Authors: Yang Zhi-Kai , Niu Ying-Fang , Ma Yu-Han , Xue Jiao , Zhang Meng-Han , Yang Wei-Dong , Liu Jie-Sheng , Lu Song-Hui , Guan Yuanfang , Li Hong-Ye
Published: May 2013

Background

Nitrogen limitation can induce neutral lipid accumulation in microalgae, as well as inhibiting their growth. Therefore, to obtain cultures with both high biomass and high lipid contents, and explore the lipid accumulation mechanisms, we implemented nitrogen deprivation in a model diatom Phaeodactylum tricornutum at late exponential phase.

Results

Neutral lipid contents per cell subsequently increased 2.4-fold, both the number and total volume of oil bodies increased markedly, and cell density rose slightly. Transcriptional profile analyzed by RNA-Seq showed that expression levels of 1213 genes (including key carbon fixation, TCA cycle, glycerolipid metabolism and nitrogen assimilation genes) increased, with a false discovery rate cut-off of 0.001, under N deprivation. However, most light harvesting complex genes were down-regulated, extensive degradation of chloroplast membranes was observed under an electron microscope, and photosynthetic efficiency declined. Further identification of lipid classes showed that levels of MGDG and DGDG, the main lipid components of chloroplast membranes, dramatically decreased and triacylglycerol (TAG) levels significantly rose, indicating that intracellular membrane remodeling substantially contributed to the neutral lipid accumulation.

Conclusions

Our findings shed light on the molecular mechanisms of neutral lipid accumulation and the key genes involved in lipid metabolism in diatoms. They also provide indications of possible strategies for improving microalgal biodiesel production.
Dock3 interaction with a glutamate-receptor NR2D subunit protects neurons from excitotoxicity
Authors: Bai Ning , Hayashi Hideki , Aida Tomomi , Namekata Kazuhiko , Harada Takayuki , Mishina Masayoshi , Tanaka Kohichi
Published: May 2013

Background

N-methyl-D-aspartate receptors (NMDARs) are critical for neuronal development and synaptic plasticity. Dysregulation of NMDARs is implicated in neuropsychiatric disorders. Native NMDARs are heteromultimeric protein complexes consisting of NR1 and NR2 subunits. NR2 subunits (NR2A–D) are the major determinants of the functional properties of NMDARs. Most research has focused on NR2A- and/or NR2B-containing receptors. A recent study demonstrated that NR2C- and/or NR2D-containing NMDARs are the primary targets of memantine, a drug that is widely prescribed to treat Alzheimer’s disease. Our laboratory demonstrated that memantine prevents the loss of retinal ganglion cells (RGCs) in GLAST glutamate transporter knockout mice, a model of normal tension glaucoma (NTG), suggesting that NR2D-containing receptors may be involved in RGC loss in NTG.

Results

Here we demonstrate that NR2D deficiency attenuates RGC loss in GLAST-deficient mice. Furthermore, Dock3, a guanine nucleotide exchange factor, binds to the NR2D C-terminal domain and reduces the surface expression of NR2D, thereby protecting RGCs from excitotoxicity.

Conclusions

These results suggest that NR2D is involved in the degeneration of RGCs induced by excitotoxicity, and that the interaction between NR2D and Dock3 may have a neuroprotective effect. These findings raise the possibility that NR2D and Dock3 might be potential therapeutic targets for treating neurodegenerative diseases such as Alzheimer’s disease and NTG.
Modified Brillouin function to explain the ferromagnetic behavior of surfactant-aided synthesized α-Fe2O3 nanostructures
Authors: Alborzi Avanaki Zahra , Hassanzadeh Ali
Published: May 2013

The α-Fe2O3nanoparticles have been synthesized using some surfactants in micro-emulsion method. Magnetization,M(H), of samples was measured at room temperature. Magnetic hysteresis loops were observed in all samples. A new magnetization function (H - Amodel) was offered to explain the field dependence of the magnetization behavior of α-Fe2O3. In this work, the magnetization curve of all samples was analyzed based onMBrillouin,MBrillouin-Akulov, andMBrillouin-(H-A) model. The experimental data have fitted with theMBrillouin-(H-A) model, and the best fitting parameters were analyzed.
The Politics of HPV Vaccination Policy Formation in the United States
Authors: Abiola Sara E. , Colgrove James , Mello Michelle M.
Published: May 2013

This article explores the political dimensions of policy formation for the human papillomavirus (HPV) vaccine through case studies of six states: California, Indiana, New Hampshire, New York, Texas, and Virginia. Using thematic content analysis of semistructured key informant interviews with policy stakeholders, newspaper articles, and archival materials, we describe the trajectory of public health policy developments for HPV immunization and analyze key influences on policy outcomes through the theoretical lens of the Multiple Streams framework. Specifically, we examine factors influencing the extent to which HPV was perceived as a problem meriting policy action; political forces that facilitated and impeded policy adoption, including interest-group opposition and structural and ideological features of the states' political environments; and factors affecting which policy alternatives received consideration. We find that effective policy entrepreneurship played a critical role in determining policy outcomes. We conclude by discussing lessons from the case of HPV vaccination for future efforts to craft vaccination policies.
How Do Public Health Safeguards in Indian Patent Law Affect Pharmaceutical Patenting in Practice?
Authors: Sampat Bhaven N. , Amin Tahir
Published: May 2013

The 1995 Trade Related Intellectual Property Rights (TRIPS) agreement required developing countries to grant product patents in pharmaceuticals. Developing countries have since explored various measures to ameliorate potential negative effects of the new laws on public health. A prominent example is India, whose post-TRIPS patent laws include a provision, section 3(d), that restricts patents on incremental pharmaceutical innovations. Its critics and supporters alike suggest that this provision makes Indian patent law very different from that in other jurisdictions. Yet there are concerns that given resource constraints facing the Indian patent office, this novel feature of Indian patent laws on the books may not have an effect on Indian patent prosecution in practice. We test this by examining the prosecution outcomes of 2,803 applications filed in both India and Europe, coded by whether they include claims that trigger 3(d) considerations. We find that having the 3(d) provision on the books does not translate into very different patent outcomes in practice in India, relative to Europe, a jurisdiction without this provision.
Are Local Laws the Key to Ending Childhood Lead Poisoning?
Authors: Korfmacher Katrina S. , Hanley Michael L.
Published: May 2013

Although lead paint was banned by federal law in 1978, it continues to poison children living in homes built before that time. The lifelong effects of childhood exposure to even small amounts of lead are well established by medical research. Federal and state laws have reduced rates of lead poisoning significantly in the past three decades. However, pockets of high rates of lead poisoning remain, primarily in low-income urban neighborhoods with older housing stock. Recently, several municipalities have passed local lead laws to reduce lead hazards in high-risk areas. There has been no systematic attempt to compare the design and effectiveness of these local policies. To address this gap, we conducted comparative case studies of eight innovative lead laws promulgated since 2000. The laws used a wide variety of legal structures and tools, although certain elements were common. The impact of the policies was intertwined with local housing, economic, and legal environments. While data do not yet exist to systematically evaluate the impact of these laws on lead poisoning rates, our analysis suggests that local laws hold great promise for reducing lead hazards in children's homes.
The Twenty-Year War Over England's National Health Service: A Report from the Battlefield
Authors: Klein Rudolf
Published: May 2013

This article analyzes the latest battle in the twenty-year war to change England's National Health Service (NHS), starting with the internal market reforms introduced by the Thatcher government and now carried one step farther by David Cameron's coalition government. The government's program of change is characterized by (1) its wide scope and the organizational upheavals involved and (2) the fact that it is being introduced at a time when the NHS faces unprecedented fiscal pressures. The legislation faced strong political, public, and professional hostility both from those who saw it as a crime against the founding principles of the NHS and from those who saw it as a disruptive blunder that created more problems than it solved. This article asks three questions. Why did the coalition government embark on a policy course guaranteed to lose it votes? How will the much-amended legislation work out in practice: what are the risks and uncertainties? What will be the program's impact: will it, like previous waves of change, disappoint both the prophets of doom and the visionaries of transformation? The conclusion drawn is that the essential, defining characteristics of the NHS are not under threat. It continues to be a publicly funded service, freely available to all. It is not being privatized. But it is moving toward the kind of pluralistic system that would have been established by Britain's last, wartime coalition government, had not Aneurin Bevan nationalized the hospital service in 1948.
A Response to Rudolf Klein: A Battle May Have Been Won but Perhaps Not the War
Authors: Hunter David J.
Published: May 2013

The British National Health Service (NHS) is undergoing possibly the most far-reaching set of changes in its sixty-five-year history. While some commentators (like Rudolf Klein) insist that little of substance is likely to change, others consider that the politics of reform may prove quite different on this occasion. The coalition government is committed to restructuring the welfare state and public services and to rolling back the state. The NHS as a popular monopoly public service runs counter to its neoliberal ideology. While (for now) remaining committed to a publicly funded system of health care that is largely free at point of use, the government wishes to encourage much greater diversity in the provision of care, including a much larger role for the for-profit private sector. Despite significant opposition to its proposals, few concessions have been forthcoming, and the legislation that passed onto the statute book in March 2012 remained essentially unchanged. Notwithstanding the lack of convincing evidence, the government is wedded to encouraging greater competition and choice. Thosewho believe the changes will amount to far less than its architects hope for are being too complacent and overlooking the strength of the government's ideological convictions. These threaten to dismantle the NHS and replace it with a more costly, fragmented, and less effective system of care that is driven by profit in place of the public interest.
Thyroid hormones correlate with resting metabolic rate, not daily energy expenditure, in two charadriiform seabirds
Authors: Elliott Kyle H. , Welcker Jorg , Gaston Anthony J. , Hatch Scott A. , Palace Vince , Hare James F. , Speakman John R. , Anderson W. Gary
Published: May 2013

Thyroid hormones affect in vitro metabolic intensity, increase basal metabolic rate (BMR) in the lab, and are sometimes correlated with basal and/or resting metabolic rate (RMR) in a field environment. Given the difficulty of measuring metabolic rate in the field—and the likelihood that capture and long-term restraint necessary to measure metabolic rate in the field jeopardizes other measurements—we examined the possibility that circulating thyroid hormone levels were correlated with RMR in two free-ranging bird species with high levels of energy expenditure (the black-legged kittiwake, Rissa tridactyla, and thick-billed murre, Uria lomvia). Because BMR and daily energy expenditure (DEE) are purported to be linked, we also tested for a correlation between thyroid hormones and DEE. We examined the relationships between free and bound levels of the thyroid hormones thyroxine (T4) and triiodothyronine (T3) with DEE and with 4-hour long measurements of post-absorptive and thermoneutral resting metabolism (resting metabolic rate; RMR). RMR but not DEE increased with T3 in both species; both metabolic rates were independent of T4. T3 and T4 were not correlated with one another. DEE correlated with body mass in kittiwakes but not in murres, presumably owing to the larger coefficient of variation in body mass during chick rearing for the more sexually dimorphic kittiwakes. We suggest T3 provides a good proxy for resting metabolism but not DEE in these seabird species.
Controlling DNA replication origins in response to DNA damage – inhibit globally, activate locally
Authors: Yekezare Mona , Gómez-González Belén , Diffley John F. X.
Published: May 2013

DNA replication in eukaryotic cells initiates from multiple replication origins that are distributed throughout the genome. Coordinating the usage of these origins is crucial to ensure complete and timely replication of the entire genome precisely once in each cell cycle. Replication origins fire according to a cell-type-specific temporal programme, which is established in the G1 phase of each cell cycle. In response to conditions causing the slowing or stalling of DNA replication forks, the programme of origin firing is altered in two contrasting ways, depending on chromosomal context. First, inactive or ‘dormant’ replication origins in the vicinity of the stalled replication fork become activated and, second, the S phase checkpoint induces a global shutdown of further origin firing throughout the genome. Here, we review our current understanding on the role of dormant origins and the S phase checkpoint in the rescue of stalled forks and the completion of DNA replication in the presence of replicative stress.
CORVET and HOPS tethering complexes–coordinators of endosome and lysosome fusion
Authors: Balderhaar Henning J. kleine , Ungermann Christian
Published: May 2013

Protein and lipid transport along the endolysosomal system of eukaryotic cells depends on multiple fusion and fission events. Over the past few years, the molecular constituents of both fission and fusion machineries have been identified. Here, we focus on the mechanism of membrane fusion at endosomes, vacuoles and lysosomes, and in particular on the role of the two homologous tethering complexes called CORVET and HOPS. Both complexes are heterohexamers; they share four subunits, interact with Rab GTPases and soluble NSF attachment protein receptors (SNAREs) and can tether membranes. Owing to the presence of specific subunits, CORVET is a Rab5 effector complex, whereas HOPS can bind efficiently to late endosomes and lysosomes through Rab7. Based on the recently described overall structure of the HOPS complex and a number of in vivo and in vitro analyses, important insights into their function have been obtained. Here, we discuss the general function of both complexes in yeast and in metazoan cells in the context of endosomal biogenesis and maturation.
Surface Modification of Hydroxy Carbonate Apatite Nanoparticles with PDMAEMA via Surface-initiated ATRP
Authors: Yu Faqi , Tang Xinde , Pei Meishan
Published: May 2013

A facile strategy for grafting poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA) on the surface of hydroxy carbonate apatite (HCA) nanoparticles via surface-initiated ATRP has been presented. SEM, FT-IR, TGA, N2 adsorption–desorption analysis, and DLS were employed for their characterization. The results demonstrated that the stimuli-responsive polymer had been successfully grafted onto the surface of HCA. The stimuli-responsive brushes attached to HCA could act as a switch to control the opening and closing of the pore on the surface of HCA. In this paper, the pH-responsive property was mainly focused on.
Photocatalytic Decomposition of Ethyl S-Diisopropylaminoethyl Methylphosphonothioate (VX) by Ag and Au Metal Deposited on TiO2 in Aqueous Phase
Authors: Kishi Shintarou , Hirakawa Tsutomu , Sato Keita , Komano Asuka , Nishimoto Chifumi K , Mera Nobuaki , Kugishima Masahiro , Sano Taizo , Negishi Nobuaki , Ichinose Hiromichi , Seto Yasuo , Takeuchi Koji
Published: May 2013

Ethyl S-diisopropylaminoethyl methylphosphonothioate (VX) in aqueous phase was decomposed by Ag– and Au–TiO2 photocatalyst. Photocatalytic decomposition rate, rVX, was accelerated in the order of Ag–TiO2 > Au–TiO2 > bare TiO2 as a consequence of improving charge separation and increasing partial decomposition of VX molecular structure. It was suggested that the photocatalytic decomposition of VX molecule at the Au– and Ag–TiO2 was carried out by C–N, P–S cleavage and oxygenation.
Behavior Characterization of Heat-stable Salt in Amine-based Solvent for CO2 Capture from Blast-furnace Gas
Authors: Yamamoto Shin , Higashii Takayuki
Published: May 2013

The generation behavior and the molecular structure of a heat-stable salt arising from coexistence between formic acid and an amine component contained in a CO2 solvent have been studied. The heat-stable salt is thought to be generated in a reversible endothermic reaction and reach reaction equilibrium in the amine solution. The heat-stable salt has been proven to be formamide of the amine that is believed to be generated in a dehydration reaction of ammonium formate.
Complex Formation in 8-Hydroxyquinoline-containing Titania Gel Films
Authors: Nishikiori Hiromasa , Todoroki Kenta , Natori Daichi , Setiawan Rudi Agus , Miyashita Kyohei , Fujii Tsuneo
Published: May 2013

8-Hydroxyquinoline (8-HQ)-dispersing titania gel films were prepared through a nitric acid-catalyzed sol–gel process and steam treatment. The complex was formed between the 8-HQ and the titania nanoparticle surface. A photocurrent was observed in electrodes containing the complex due to electron injection from the excited state of the complex into the titania conduction band. A larger amount of the complex was formed in titania electrodes containing zinc ions owing to its high electron affinity.
Palladium-catalyzed Carboboration: Borylative Coupling of Alkynes with Alkenes through Activation of Boron–Chlorine Bonds
Authors: Nakada Kanayo , Daini Masaki , Suginome Michinori
Published: May 2013

Alkynes tethered to a chloro(diisopropylamino)boryl group undergo palladium-catalyzed borylative coupling with styrenes and acrylates, giving substituted cyclic 1,3-dienylboronic acid derivatives in a stereoselective fashion.