bluuebunny/crossref_metadata_2025 huggingface dataset:
Photosystem I shows a higher tolerance to sorbitol‐induced osmotic stress than photosystem II in the intertidal macro‐algae Ulva prolifera (Chlorophyta)
Authors: Gao Shan , Zheng Zhenbing , Gu Wenhui , Xie Xiujun , Huan Li , Pan Guanghua , Wang Guangce
Published: March 2014

The photosynthetic performance of the desiccation‐tolerant, intertidal macro‐algae Ulva prolifera was significantly affected by sorbitol‐induced osmotic stress. Our results showed that photosynthetic activity decreased significantly with increases in sorbitol concentration. Although the partial activity of both photosystem I (PS I) and photosystem II (PS II) was able to recover after 30 min of rehydration, the activity of PS II decreased more rapidly than PS I. At 4 M sorbitol concentration, the activity of PS II was almost 0 while that of PS I was still at about one third of normal levels. Following prolonged treatment with 1 and 2 M sorbitol, the activity of PS I and PS II decreased slowly, suggesting that the effects of moderate concentrations of sorbitol on PS I and PS II were gradual. Interestingly, an increase in non‐photochemical quenching occurred under these conditions in response to moderate osmotic stress, whereas it declined significantly under severe osmotic stress. These results suggest that photoprotection in U. prolifera could also be induced by moderate osmotic stress. In addition, the oxidation of PS I was significantly affected by osmotic stress. P700+ in the thalli treated with high concentrations of sorbitol could still be reduced, as PS II was inhibited by 3‐(3,4‐dichlorophenyl)‐1,1‐dimethylurea (DCMU), but it could not be fully oxidized. This observation may be caused by the higher quantum yield of non‐photochemical energy dissipation in PS I due to acceptor‐side limitation (Y(NA)) during rehydration in seawater containing DCMU.
Characterization of OsLCT1, a cadmium transporter from indica rice (Oryza sativa)
Authors: Uraguchi Shimpei , Kamiya Takehiro , Clemens Stephan , Fujiwara Toru
Published: March 2014

Molecular understanding of cadmium (Cd) transport in indica rice (Oryza sativa) is still insufficient, although indica rice generally has a potential to accumulate higher Cd in shoots and grains than japonica rice. We have previously demonstrated that OsLCT1 is a Cd transporter gene responsible for grain Cd accumulation in the japonica model cultivar Nipponbare. In this study, we isolated OsLCT1 cDNA from Kasalath, a model indica (aus subgroup) cultivar and conducted cation transport activity assays in yeast and mRNA expression analysis in plants. The deduced amino acid sequence of Kasalath OsLCT1 is 91.2% identical and 93.8% similar to that of Nipponbare OsLCT1. We established the yeast heterologous system expressing the Kasalath allele of OsLCT1. Elemental profiling of the yeast cells suggested an efflux activity of Kasalath OsLCT1 for Cd, K, Mg, Ca and Mn, but not for Fe, Zn, Cu and Na. This substrate specificity was identical to that of the Nipponbare version. Quantitative real time‐polymerase chain reaction (RT‐PCR) showed that expression of OsLCT1 in Kasalath was higher in reproductive stage than in vegetative stage. The expression level of OsLCT1 was significantly higher in Kasalath than in Nipponbare. Phylogenetic analysis found several LCT1‐like genes only in grass plants. OsLCT1 is the sole copy in the rice genome and is conserved among each rice subgroup. These newly found low‐affinity cation transporter (LCT) homologs will provide a basis for further understanding of LCT‐mediated Cd transport.
Hanging Drop Monoculture for Selection of Optimal Antioxidants During In Vitro Maturation of Porcine Oocytes
Authors: Ishikawa S , Machida R , Hiraga K , Hiradate Y , Suda Y , Tanemura K
Published: March 2014

Contents

We analysed the effect of three antioxidants that have different functional mechanisms on the in vitro maturation (IVM) of porcine oocytes. Single oocyte monoculture using the hanging drop (HD) system has some advantages such as improving analysis efficiency brought by the smaller number of samples than the number of oocytes cultured in one drop. Direct effects of ligands on single oocytes could also be detected without considering the effects of paracrine factors from other oocytes. After 22 h of pre‐culture, denuded oocytes were cultured for 22 h with 0.01 and 0.1 μg/ml of L‐carnitine (LC), lactoferrin (LF) or sulforaphane (SF) in the presence/non‐presence of oxidant stress induced by H2O2 supplementation to evaluate the reducing effects against oxidative stress on nuclear maturation. As a result, compared with LC and SF, LF showed effective reduction in oxidative stress at a lower concentration (0.01 μg/ml), suggesting that LF is a more effective antioxidant in porcine oocyte IVM. Additionally, LF also increased maturation rate even in culture without H2O2. Our results clearly suggest that the HD monoculture system is useful for screening the substances that affect porcine oocyte culture.
How to Model a Child in School? A Dynamic Macrosimulation Study for Tanzania
Authors: Schuerenberg‐Frosch Hannah
Published: March 2014

Universal primary education is regarded as one of the key pillars of sustainable development. The positive influence of education on growth is supported by many empirical studies. However, the effects of education on labour supply, poverty reduction and welfare as well as subsistence agriculture are hardly traceable in an econometric set‐up, given the complex interactions and the long‐term nature of education. An economy‐wide dynamic simulation model provides a well‐suited toolkit to analyse the effects of increased school provision in these aspects and provides insights into the intertemporal aspects of the schooling decision of children.

We develop a macroeconomic model that explicitly includes education and human capital allocation, and takes into account that the possibility of child labour increases the opportunity costs of human capital formation. In an application for Tanzania, we find that a large‐scale investment programme in education might have a negative effect on both gross domestic product (GDP) growth and high‐skilled labour supply in the short term but leads to higher GDP and welfare as well as significantly reduced child labour supply in the medium to long term.
“Taking Back Our Country”: Tea Party Membership and Support for Punitive Crime Control Policies
Authors: Pickett Justin T. , Tope Daniel , Bellandi Rose
Published: March 2014

The Tea Party Movement (TPM) emerged shortly after the 2008 election, with members rallying behind the call to “take back our country.” Many observers suggest that the movement represents, in part, a racialized backlash against the election of Barack Obama, the nation's first black president, motivated by perceived threats to the racial hierarchy. Racial threat theory predicts that if the TPM is motivated by and reinforces racial concerns, racialized support for punitive crime policies that disproportionately impact blacks should be higher among Tea Partiers. Drawing on recent national survey data, this study tests this prediction. The results show that TPM membership is positively associated with punitiveness and that this relationship is mediated, in part, by Tea Partiers’ animus toward blacks. We discuss the import of these findings for competing accounts of the TPM, racial threat theory, and the argument that the United States has become a “post‐racial society.”
Weed seedling herbivory by field cricket Teleogryllus emma (Orthoptera: Gryllidae) in relation to the depth of seedling emergence
Authors: Ichihara Minoru , Uchida Satoshi , Fujii Sei , Yamashita Masayuki , Sawada Hitoshi , Inagaki Hidehiro
Published: March 2014

This study aimed to determine whether seedling herbivory by the field cricket, Teleogryllus emma (Ohmachi et Matsuura), promoted the mortality of Italian ryegrass (Lolium multiflorum Lam.), a non‐native grass weed in Japan, whether the impact of seedling herbivory differed depending on the depth of seedling emergence and the influence of cricket density on seedling mortality. First, the seedlings at emergence depths of 0, 1 and 2 cm were exposed to the cricket for 2 days in plastic cups and the amount of seedling mortality by herbivory was calculated. The level of mortality of 60 seedlings that emerged from seeds on the soil surface was 92.4%, significantly higher than that of the seedlings that emerged from seeds at depths of 1 cm (10.8%) and 2 cm (9.6%). Second, the seedlings at the emergence depths of 0 and 1 cm were exposed to the crickets at four different densities (zero, one, two and three individuals per 5700 cm2) for 5 days in plastic containers and the amount of seedling mortality by herbivory was calculated. The level of mortality by herbivory of the seedlings that emerged from 100 seeds on the soil surface was higher (33.3–61.3%) than that of the seedlings that emerged from seeds at a depth of 1 cm (4.7–13.1%) in the containers with one‐to‐three crickets. The level of seedling mortality tended to increase with an increasing cricket density. These results suggest that seedling herbivory by crickets is an important factor in weed mortality, particularly in no‐till fields and in field margins, where the seeds are more prevalent near the soil surface.
A block matching‐based registration algorithm for localization of locally advanced lung tumors
Authors: Robertson Scott P. , Weiss Elisabeth , Hugo Geoffrey D.
Published: March 2014

Purpose:

To implement and evaluate a block matching‐based registration (BMR) algorithm for locally advanced lung tumor localization during image‐guided radiotherapy.

Methods:

Small (1 cm3), nonoverlapping image subvolumes (“blocks”) were automatically identified on the planning image to cover the tumor surface using a measure of the local intensity gradient. Blocks were independently and automatically registered to the on‐treatment image using a rigid transform. To improve speed and robustness, registrations were performed iteratively from coarse to fine image resolution. At each resolution, all block displacements having a near‐maximum similarity score were stored. From this list, a single displacement vector for each block was iteratively selected which maximized the consistency of displacement vectors across immediately neighboring blocks. These selected displacements were regularized using a median filter before proceeding to registrations at finer image resolutions. After evaluating all image resolutions, the global rigid transform of the on‐treatment image was computed using a Procrustes analysis, providing the couch shift for patient setup correction. This algorithm was evaluated for 18 locally advanced lung cancer patients, each with 4–7 weekly on‐treatment computed tomography scans having physician‐delineated gross tumor volumes. Volume overlap (VO) and border displacement errors (BDE) were calculated relative to the nominal physician‐identified targets to establish residual error after registration.

Results:

Implementation of multiresolution registration improved block matching accuracy by 39% compared to registration using only the full resolution images. By also considering multiple potential displacements per block, initial errors were reduced by 65%. Using the final implementation of the BMR algorithm, VO was significantly improved from 77% ± 21% (range: 0%–100%) in the initial bony alignment to 91% ± 8% (range: 56%–100%;p < 0.001). Left‐right, anterior‐posterior, and superior‐inferior systematic BDE were 3.2, 2.4, and 4.4 mm, respectively, with random BDE of 2.4, 2.1, and 2.7 mm. Margins required to include both localization and delineation uncertainties ranged from 5.0 to 11.7 mm, an average of 40% less than required for bony alignment.

Conclusions:

BMR is a promising approach for automatic lung tumor localization. Further evaluation is warranted to assess the accuracy and robustness of BMR against other potential localization strategies.
Genome Sequences of Four Italian Streptococcus thermophilus Strains of Dairy Origin
Authors: Treu Laura , Vendramin Veronica , Bovo Barbara , Campanaro Stefano , Corich Viviana , Giacomini Alessio
Published: March 2014

This report describes the genome sequences of four
Streptococcus thermophilus
strains, namely, TH982, TH985, TH1477, and 1F8CT, isolated from different dairy environments from the Campania and the Veneto regions in Italy. These data are aimed at increasing the genomic information available on this species, which is of paramount importance for the dairy industry.
Genome Sequence of the Acute Urethral Catheter Isolate Pseudomonas aeruginosa MH38
Authors: Wibberg Daniel , Tielen Petra , Blom Jochen , Rosin Nathalie , Schobert Max , Tüpker Reinhilde , Schatschneider Sarah , Spilker Dominik , Albersmeier Andreas , Goesmann Alexander , Vorhölter Frank-Jörg , Pühler Alfred , Jahn Dieter
Published: March 2014

Pseudomonas aeruginosa
is a major nosocomial bacterial pathogen causing complicated catheter-associated urinary tract infections (CAUTIs). Here, we present the 6.9-Mb draft genome sequence of
P. aeruginosa
MH38 isolated from an acute nosocomial CAUTI. It exhibits resistance to several antibiotics but revealed low-level production of virulence factors.
Complete Genome Sequence of Magnetospirillum gryphiswaldense MSR-1
Authors: Wang Xu , Wang Qing , Zhang Weijia , Wang Yinjia , Li Li , Wen Tong , Zhang Tongwei , Zhang Yang , Xu Jun , Hu Junying , Li Shuqi , Liu Lingzi , Liu Jinxin , Jiang Wei , Tian Jiesheng , Li Ying , Schüler Dirk , Wang Lei , Li Jilun
Published: March 2014

We report the complete genomic sequence of
Magnetospirillum gryphiswaldense
MSR-1 (DSM 6361), a type strain of the genus
Magnetospirillum
belonging to the
Alphaproteobacteria
. Compared to the reported draft sequence, extensive rearrangements and differences were found, indicating high genomic flexibility and “domestication” by accelerated evolution of the strain upon repeated passaging.
Draft Genome Sequence and Annotation of the Entomopathogenic Bacterium Xenorhabdus szentirmaii Strain DSM16338
Authors: Gualtieri Maxime , Ogier Jean-Claude , Pagès Sylvie , Givaudan Alain , Gaudriault Sophie
Published: March 2014

We report the genome sequence of
Xenorhabdus szentirmaii
DSM16338 (4.84 Mb), a symbiont of the entomopathogenic nematode
Steinernema rarum
. This strain produces antimicrobial activity.
Lipodystrophy among patients with HIV infection on antiretroviral therapy: a systematic review protocol
Authors: Lana Lorena Gomes Cunha , Junqueira Daniela Rezende Garcia , Perini Edson , Menezes de Pádua Cristiane
Published: March 2014

Introduction

Lipodystrophy is a frequent and disfiguring adverse effect of antiretroviral therapy (ART) in patients with HIV. It affects the quality of life of the patient and adherence to treatment, and generates new needs for comprehensive healthcare services. The aim of this study will be to conduct a systematic review of the literature from observational studies and describe lipodystrophy among patients with HIV infection during current or previous use of ART.

Methods and analysis

A systematic review of observational studies published in MEDLINE, CINAHL, LILACS, EMBASE and International Pharmaceutical Abstracts will be carried out. Citations of included studies will be checked to identify additional studies not identified in the electronic searches. It will include any observational study that considered lipodystrophy as the primary or secondary outcome and that had enrolled adolescent and adult patients with HIV infection who were on current or previous ART for at least 6 months. Data extraction and analysis will be performed independently by two reviewers. The extracted data will be discussed, decisions documented and, where necessary, the authors of the studies will be contacted for clarification. Measures of frequency, prevalence and incidence of lipodystrophy will be stratified according to definition, method of diagnosis and risk factors of the outcome.

Ethics and dissemination

Ethics is not required given this is a protocol for a systematic review. The findings of this study will be widely disseminated through peer-reviewed publications and conference presentations. Updates of the review will be conducted to inform and guide healthcare practice.

Protocol registration

PROSPERO—42013005450.
Mapping patient safety: a large-scale literature review using bibliometric visualisation techniques
Authors: Rodrigues S P , van Eck N J , Waltman L , Jansen F W
Published: March 2014

Background

The amount of scientific literature available is often overwhelming, making it difficult for researchers to have a good overview of the literature and to see relations between different developments. Visualisation techniques based on bibliometric data are helpful in obtaining an overview of the literature on complex research topics, and have been applied here to the topic of patient safety (PS).

Methods

On the basis of title words and citation relations, publications in the period 2000–2010 related to PS were identified in the Scopus bibliographic database. A visualisation of the most frequently cited PS publications was produced based on direct and indirect citation relations between publications. Terms were extracted from titles and abstracts of the publications, and a visualisation of the most important terms was created. The main PS-related topics studied in the literature were identified using a technique for clustering publications and terms.

Results

A total of 8480 publications were identified, of which the 1462 most frequently cited ones were included in the visualisation. The publications were clustered into 19 clusters, which were grouped into three categories: (1) magnitude of PS problems (42% of all included publications); (2) PS risk factors (31%) and (3) implementation of solutions (19%). In the visualisation of PS-related terms, five clusters were identified: (1) medication; (2) measuring harm; (3) PS culture; (4) physician; (5) training, education and communication. Both analysis at publication and term level indicate an increasing focus on risk factors.

Conclusions

A bibliometric visualisation approach makes it possible to analyse large amounts of literature. This approach is very useful for improving one's understanding of a complex research topic such as PS and for suggesting new research directions or alternative research priorities. For PS research, the approach suggests that more research on implementing PS improvement initiatives might be needed.
Freeman Dyson: Some early recollections
Authors: Longuet-Higgins Michael
Published: March 2014

The author has known Freeman Dyson since they were both at school in Winchester, England. The friendship has continued ever since.
Free Vibration of Castellated Beams with Web Shear and Rotary Inertia Effects
Authors: Gu Jian-Zu
Published: March 2014

This paper presents analytically obtained free vibration frequencies of castellated beams, that take into account the effects of both web shear and rotary inertia. The results show that the rotary inertia effect on the free vibration frequencies is very important for beams with no or weak effect from web shear. However, for beams where the web shear effect is dominant the rotary inertia effect can be almost ignored.
Gastric and lower esophageal sphincter pressures during nausea: a study using visual motion-induced nausea and high-resolution manometry
Authors: Schaub Nora , Ng Kee , Kuo Paul , Aziz Qasim , Sifrim Daniel
Published: March 2014

Nausea is the subjective unpleasant sensation that immediately precedes vomiting. Studies using barostats suggest that gastric fundus and lower esophageal sphincter (LES) relaxation precede vomiting. Unlike barostat, high-resolution manometry allows less invasive, detailed measurements of fundus pressure (FP) and axial movement of the gastroesophageal junction (GEJ). Nausea was induced in 12 healthy volunteers by a motion video and rated on a visual analog scale. FP was measured as the mean value of the five pressure channels that were clearly positioned below the LES. After intubation, a baseline (BL) recording of 15 min was obtained. This was followed by presentation of the motion video (at least 10 min, maximum 20 min) followed by 30 min recovery recording. Throughout the experiment we recorded autonomic nervous system (ANS) parameters [blood pressure, heart rate (HR), and cardiac vagal tone (CVT), which reflects efferent vagal activity]. Ten out of 12 subjects showed a drop in FP during peak nausea compared with BL (−4.0 ± 0.8 mmHg; P = 0.005), and 8/10 subjects showed a drop in LES pressure (−8.8 ± 2.5 mmHg; P = 0.04). Peak nausea preceded peak fundus and LES pressure drop. Nausea was associated with configuration changes at the GEJ such as LES shortening and esophageal lengthening. During nausea we observed a significantly increased HR and decreased CVT. In conclusion, nausea is associated with a drop in fundus and LES pressure, configuration changes at the GEJ as well as changes in the ANS activity such as an increased sympathetic tone (increased HR) and decreased parasympathetic tone (decreased CVT).
Acid-base balance in the developing marsupial: from ectotherm to endotherm
Authors: Andrewartha Sarah J. , Cummings Kevin J. , Frappell Peter B.
Published: March 2014

Marsupial joeys are born ectothermic and develop endothermy within their mother's thermally stable pouch. We hypothesized that Tammar wallaby joeys would switch from α-stat to pH-stat regulation during the transition from ectothermy to endothermy. To address this, we compared ventilation (V̇e), metabolic rate (V̇o2), and variables relevant to blood gas and acid-base regulation and oxygen transport including the ventilatory requirements (V̇e/V̇o2and V̇e/V̇co2), partial pressures of oxygen (PaO2), carbon dioxide (PaCO2), pHa, and oxygen content (CaO2) during progressive hypothermia in ecto- and endothermic Tammar wallabies. We also measured the same variables in the well-studied endotherm, the Sprague-Dawley rat. Hypothermia was induced in unrestrained, unanesthetized joeys and rats by progressively dropping the ambient temperature (Ta). Rats were additionally exposed to helox (80% helium, 20% oxygen) to facilitate heat loss. Respiratory, metabolic, and blood-gas variables were measured over a large body temperature (Tb) range (∼15–16°C in both species). Ectothermic joeys displayed limited thermogenic ability during cooling: after an initial plateau, V̇o2decreased with the progressive drop in Tb. The Tb of endothermic joeys and rats fell despite V̇o2nearly doubling with the initiation of cold stress. In all three groups the changes in V̇o2were met by changes in V̇e, resulting in constant V̇e/V̇o2and V̇e/V̇co2, blood gases, and pHa. Thus, although thermogenic capability was nearly absent in ectothermic joeys, blood acid-base regulation was similar to endothermic joeys and rats. This suggests that unlike some reptiles, unanesthetized mammals protect arterial blood pH with changing Tb, irrespective of their thermogenic ability and/or stage of development.
Maintaining Glycogen Synthase Kinase-3 Activity Is Critical for mTOR Kinase Inhibitors to Inhibit Cancer Cell Growth
Authors: Koo Junghui , Yue Ping , Gal Anthony A. , Khuri Fadlo R. , Sun Shi-Yong
Published: March 2014

mTOR kinase inhibitors that target both mTORC1 and mTORC2 are being evaluated in cancer clinical trials. Here, we report that glycogen synthase kinase-3 (GSK3) is a critical determinant for the therapeutic response to this class of experimental drugs. Pharmacologic inhibition of GSK3 antagonized their suppressive effects on the growth of cancer cells similarly to genetic attenuation of GSK3. Conversely, expression of a constitutively activated form of GSK3β sensitized cancer cells to mTOR inhibition. Consistent with these findings, higher basal levels of GSK3 activity in a panel of human lung cancer cell lines correlated with more efficacious responses. Mechanistic investigations showed that mTOR kinase inhibitors reduced cyclin D1 levels in a GSK3β-dependent manner, independent of their effects on suppressing mTORC1 signaling and cap binding. Notably, selective inhibition of mTORC2 triggered proteasome-mediated cyclin D1 degradation, suggesting that mTORC2 blockade is responsible for GSK3-dependent reduction of cyclin D1. Silencing expression of the ubiquitin E3 ligase FBX4 rescued this reduction, implicating FBX4 in mediating this effect of mTOR inhibition. Together, our findings define a novel mechanism by which mTORC2 promotes cell growth, with potential implications for understanding the clinical action of mTOR kinase inhibitors. Cancer Res; 74(9); 2555–68. ©2014 AACR.
Curcumin Promotes Autophagic Survival of a Subset of Colon Cancer Stem Cells, Which Are Ablated by DCLK1-siRNA
Authors: Kantara Carla , O'Connell Malaney , Sarkar Shubhashish , Moya Stephanie , Ullrich Robert , Singh Pomila
Published: March 2014

Curcumin is known to induce apoptosis of cancer cells by different mechanisms, but its effects on cancer stem cells (CSC) have been less investigated. Here, we report that curcumin promotes the survival of DCLK1-positive colon CSCs, potentially confounding application of its anticancer properties. At optimal concentrations, curcumin greatly reduced expression levels of stem cell markers (DCLK1/CD44/ALDHA1/Lgr5/Nanog) in three-dimensional spheroid cultures and tumor xenografts derived from colon cancer cells. However, curcumin unexpectedly induced proliferation and autophagic survival of a subset of DCLK1-positive CSCs. Spheroid cultures were disintegrated by curcumin in vitro but regrew within 30 to 40 days of treatment, suggesting a survival benefit from autophagy, permitting long-term persistence of colorectal cancer. Notably, RNA interference–mediated silencing of DCLK1 triggered apoptotic cell death of colon cancer cells in vitro and in vivo, and abolished colorectal cancer survival in response to curcumin; combination of DCLK1-siRNA and curcumin dramatically reversed CSC phenotype, contributing to attenuation of the growth of spheroid cultures and tumor xenografts. Taken together, our findings confirm a role of DCLK1 in colon CSCs and highlight DCLK1 as a target to enhance antitumor properties of curcumin. Cancer Res; 74(9); 2487–98. ©2014 AACR.
Thyroid Dyshormonogenesis and Associated Non-Thyroidal Anomalies in a Tertiary Care Hospital in India
Authors: Rather Tanveer A. , Khan Shoukat H. , Masoodi Shariq , Alai Mohd Sultan
Published: March 2014

Background: Dyshormonogenetic goiter refers to familial goiters owing to an inherited defect in the metabolism of thyroid hormones. Methods: 19 patients with clinical and biochemically proven hypothyroidism (low T3, FT4 and high TSH) were recruited for the study. All patients were subjected to (i) ultrasound of the neck to rule out thyroid dysgenesis and (ii) technetium-99m radionuclide thyroid scintigraphy and a perchlorate discharge test (PDT). Extrathyroidal malformations were identified by clinical ultrasound (USG) examination of the abdomen and pelvis and by echocardiography. Results: Out of 19 patients with elevated thyroid uptakes on technetium-99m thyroid scintigraphy, 12 (63%) had a positive PDT and 7 patients (37%) had a negative PDT. All patients were subjected to abdominopelvic USG and echocardiography. Out of 12 patients with a positive PDT, 5 (42%) had associated extrathyroid malformations, 2 had urogenital malformations, and cardiac abnormalities on echocardiography were present in 2 patients (17%). One patient (8%) had features of dysmorphism in the form of a high-arched palate, low-set ears and microcephaly. Conclusion: Congenital hypothyroidism due to dyshormogenesis is associated with a high prevalence of extrathyroidal malformations and needs to be managed as early as possible to ensure normal neurocognitive development of the children affected.
Intracranial Metastasis in a Patient with Hepatocellular Carcinoma and Gastric Cancer
Authors: Tawada Akinobu , Chiba Tetsuhiro , Ooka Yoshihiko , Yokota Hajime , Kanogawa Naoya , Motoyama Tenyu , Saito Tomoko , Ogasawara Sadahisa , Suzuki Eiichiro , Hanari Naoyuki , Matsubara Hisahiro , Saeki Naokatsu , Kambe Michiyo , Kishimoto Takashi , Nakatani Yukio , Yokosuka Osamu
Published: March 2014

A 76-year-old man was referred to our hospital with visual disturbance, weakness of the left upper and lower limbs, and gait disturbance. He had previously received transarterial chemoembolization for hepatocellular carcinoma (HCC) 3 and 10 years ago. When he had received radiofrequency ablation for HCC recurrence 2 years ago, total gastrectomy was also performed for his gastric cancer. Subsequently, sorafenib had been administrated for concomitant lung metastatic tumors. On admission, MRI revealed an intra-axial tumor with perifocal edema. The level of carcinoembryonic antigen, but not alpha-fetoprotein, markedly increased. The tumor was successfully removed by craniotomy and pathological examination revealed that it was composed of adenocarcinoma, which was consistent with the primary gastric cancer. After surgery, his neurological disturbances rapidly resolved. Additional gamma-knife treatment was also performed for another small brain metastasis detected after craniotomy. Subsequently, sorafenib administration was discontinued and S-1 was administered postoperatively. Successful treatment of intracranial metastasis of gastric cancer is important and meaningful, even in patients with multiple primary malignancies.
Differential Association of Plasma Angiopoietin-Like Proteins 3 and 4 With Lipid and Metabolic Traits
Authors: Mehta Nidhi , Qamar Arman , Qu Liming , Qasim Atif N. , Mehta Nehal N. , Reilly Muredach P. , Rader Daniel J.
Published: March 2014

Objective—

Angiopoietin-like protein 3 (ANGPTL3) and 4 (ANGPTL4) are secreted proteins that inhibit lipoprotein lipase in vitro. Genetic variants at the
ANGPTL3
and
ANGPTL4
gene loci are significantly associated with plasma lipid traits. The aim of this study was to evaluate the association of plasma ANGPTL3 and ANGPTL4 concentrations with lipid and metabolic traits in a large community-based sample.

Approach and Results—

Plasma ANGPTL3 and ANGPTL4 levels were measured in 1770 subjects using a validated ELISA assay. A Pearson unadjusted correlation analysis and a linear regression analysis adjusting for age, sex, and race were performed. ANGPTL3 levels were significantly positively associated with low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels (both
P
<2×10
−5
) but not triglycerides. In contrast, ANGPTL4 levels were significantly negatively associated with low-density lipoprotein cholesterol and high-density lipoprotein cholesterol (both
P
<2×10
−5
) and positively associated with triglycerides (
P
=0.003). In addition, ANGPTL4, but not ANGPTL3, levels were significantly positively associated with fasting blood glucose and metabolic syndrome.

Conclusions—

Despite having similar biochemical effects in vitro, plasma ANGPTL3 and ANGPTL4 concentrations have nearly opposite relationships with plasma lipids. ANGPTL4 is strongly negatively associated with low-density lipoprotein cholesterol and high-density lipoprotein cholesterol and positively with multiple features of the metabolic syndrome including triglycerides, whereas ANGPTL3 is positively associated with low-density lipoprotein cholesterol and high-density lipoprotein cholesterol and not with metabolic syndrome traits including triglycerides. Although ANGPTL3 and ANGPTL4 both inhibit lipoprotein lipase in vitro and influence lipoprotein metabolism in vivo, the physiology of these related proteins and their effects on lipoproteins is clearly divergent and complex.
Is a Diabetes Mellitus–Linked Amino Acid Signature Associated With β-Blocker–Induced Impaired Fasting Glucose?
Authors: Cooper-DeHoff Rhonda M. , Hou Wei , Weng Liming , Baillie Rebecca A. , Beitelshees Amber L. , Gong Yan , Shahin Mohamed H.A. , Turner Stephen T. , Chapman Arlene , Gums John G. , Boyle Stephen H. , Zhu Hongjie , Wikoff William R. , Boerwinkle Eric , Fiehn Oliver , Frye Reginald F. , Kaddurah-Daouk Rima , Johnson Julie A.
Published: March 2014

Background—

The 5-amino acid (AA) signature, including isoleucine, leucine, valine, tyrosine, and phenylalanine, has been associated with incident diabetes mellitus and insulin resistance. We investigated whether this same AA signature, single-nucleotide polymorphisms in genes in their catabolic pathway, was associated with development of impaired fasting glucose (IFG) after atenolol treatment.

Methods and Results—

Among 234 European American participants enrolled in the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) study and treated with atenolol for 9 weeks, we prospectively followed a nested cohort that had both metabolomics profiling and genotype data available for the development of IFG. We assessed the association between baseline circulating levels of isoleucine, leucine, valine, tyrosine, and phenylalanine, as well as single-nucleotide polymorphisms in
branched-chain amino-acid transaminase 1 (BCAT1) and phenylalanine hydroxylase (PAH
) with development of IFG. All baseline AA levels were strongly associated with IFG development. Each increment in standard deviation of the 5 AAs was associated with the following odds ratio and 95% confidence interval for IFG based on a fully adjusted model: isoleucine 2.29 (1.31–4.01), leucine 1.80 (1.10–2.96), valine 1.77 (1.07–2.92), tyrosine 2.13 (1.20–3.78), and phenylalanine 2.04 (1.16–3.59). The composite
P
value was 2×10
−5
. Those with
PAH
(rs2245360) AA genotype had the highest incidence of IFG (
P
for trend=0.0003).

Conclusions—

Our data provide important insight into the metabolic and genetic mechanisms underlying atenolol-associated adverse metabolic effects.

Clinical Trial Registration—

http://www.clinicaltrials.gov
; Unique Identifier: NCT00246519
Changes in Mipomersen Dosing Regimen Provide Similar Exposure With Improved Tolerability in Randomized Placebo‐Controlled Study of Healthy Volunteers
Authors: Flaim JoAnn D. , Grundy John S. , Baker Brenda F. , McGowan Mary P. , Kastelein John J. P.
Published: March 2014

Background

Mipomersen, an apolipoprotein B synthesis inhibitor, demonstrated significant reductions in low‐density lipoprotein (LDL) cholesterol, non‐high density lipoprotein cholesterol, and apolipoprotein B in 4 phase 3 studies at the
FDA
‐approved subcutaneous dose of 200 mg once weekly.

Methods and Results

A short‐term phase 1 study in healthy volunteers was conducted to evaluate the relative bioavailability, safety, and tolerability of mipomersen in 2 test dose regimens in reference to the 200 mg weekly dose regimen. Eighty‐four adults were randomized to 1 of 3 cohorts (30 mg once daily, 70 mg 3 times weekly, or 200 mg once weekly) and then mipomersen or placebo (3:1 ratio) for 3 weeks of treatment. Comparable mipomersen post‐distribution phase plasma concentrations were observed across the 3 dose regimens suggesting similar tissue exposure. Injection site reactions were reported, but did not lead to treatment discontinuation. The median incidence of these responses per injection was decreased by lowering the dose. Signals from a diverse panel of systemic inflammation markers were essentially indistinguishable between dose regimens and placebo treatment. The one exception was a modest transient post‐dose elevation of C‐reactive protein (
CRP
) in the mipomersen 200 mg weekly group. This elevation was not associated with an increase in other proinflammatory markers.

Conclusions

This study demonstrated a similar drug exposure and overall safety profile between the 3 dosing regimens. Exploratory assessment of a diverse panel of biomarkers found no indication of a systemic inflammatory response to mipomersen treatment. These results support assessment of alternative dose regimens in longer‐term studies.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
01061814.
Extravascular Optical Coherence Tomography
Authors: Wicks Robert T. , Huang Yong , Zhang Kang , Zhao Mingtao , Tyler Betty M. , Suk Ian , Hwang Lee , Ruzevick Jacob , Jallo George , Brem Henry , Pradilla Gustavo , Kang Jin U.
Published: March 2014

Background and Purpose—

Extravascular optical coherence tomography (OCT), as a noninvasive imaging methodology with micrometer resolution, was evaluated in a murine model of carotid atherosclerosis by way of assessing the efficacy of pravastatin therapy.

Methods—

An OCT device was engineered for extravascular plaque imaging. Wild-type mice and apolipoprotein E–deficient (ApoE
−/−
) mice were randomized to 3 treatment groups: (1) wild-type on a diet of standard rodent chow (n=13); (2) ApoE
−/−
on a high-fat, atherosclerotic diet (HFD; n=13); and (3) ApoE
−/−
on a HFD given daily pravastatin (n=13). Mice were anesthetized and the left common carotid was surgically exposed. Three-dimensional (3D; 2 spatial dimensions+time) and 4D (3 spatial dimensions+time) OCT images of the vessel lumen patency were evaluated. After perfusion, in situ OCT imaging was performed for statistical comparison with the in vivo results and final histology.

Results—

Intraoperative OCT imaging positively identified carotid plaque in 100% of ApoE
−/−
mice on HFD. ApoE
−/−
mice on HFD had a significantly decreased lumen patency when compared with that in wild-type mice (
P
<0.001). Pravastatin therapy was found to increase lumen patency significantly in ApoE
−/−
mice on HFD (
P
<0.01; compared with ApoE
−/−
on HFD). The findings were confirmed with OCT imaging after perfusion and histology.

Conclusions—

OCT imaging offers the potential for real-time, detailed vessel lumen evaluation, potentially improving surgical accuracy and outcomes during cerebrovascular neurosurgical procedures. Pravastatin significantly increases vessel lumen patency in the ApoE
−/−
mouse on HFD.
Complementary redescription of Anacanthobatis ori (Wallace, 1967) and its assignment to Indobatis n. g. (Elasmobranchii, Anacanthobatidae), with comments on other legskates
Authors: WEIGMANN SIMON , STEHMANN MATTHIAS F.W. , THIEL RALF
Published: March 2014

Anacanthobatis ori is one of the least known species of the family Anacanthobatidae with only four juvenile specimens reported. The species remained assigned to the genus Anacanthobatis sensu lato due to the lack of an adult male as external and skeletal clasper characters are the essential diagnostic features for the differentiation of genera and subgenera within the family Anacanthobatidae. Since an adult male of A. ori became available, along with an adult female and six further juveniles, the authors reinvestigated the species and present its so far unknown diagnostic characters of clasper morphology and skeleton and scapulocoracoid. The clasper turned out to be the most complex one of all known anacanthobatids as the external components flag, slit, pseudosiphon-like cavity, pecten, and two sentinas are not known from any other anacanthobatid species. Furthermore, a dorsal terminal 1 cartilage is present but displaced proximally of the terminal clasper skeleton, the outer edge of dorsal terminal 2 is deeply serrated, the ventral terminal has a very long, curved, strap-like process, and the proximal part of accessory terminal 1 is embedded in the cavity of the baseball-glove-like head of accessory terminal 2. Due to the strong differences in external and internal clasper characters to all other known anacanthobatid species, A. ori is placed in its own, newly erected genus, Indobatis.
The Red Sea species of Cymo de Haan, 1833 (Decapoda, Brachyura, Xanthidae), associates of scleractinian corals
Authors: BRÖSING ANDREAS , AL-AIDAROOS ALI M. , TÜRKAY MICHAEL
Published: March 2014

Four species of Cymo, associates of scleractinian corals, from the Red Sea were studied using scanning electron and light microscopy. Characters based on the morphologies of the carapace, gonopods and digestive tract (gastric teeth) were investigated and described in detail. All Red Sea species are redescribed, distinguishing characters are identified and an identification key is provided. Cymo quadrilobatus is the most distinctive species, with prominent granules on the carapace and most of the surfaces of the chelipeds and walking legs, and four red spots on the dorsal surface of the carapace in contrast to the smooth or finely granular surfaces in the other three species. Cymo deplanatus is listed as new record for the Red Sea.
Climate Change Impacts on the Water Balance of the Colorado Headwaters: High-Resolution Regional Climate Model Simulations
Authors: Rasmussen Roy , Ikeda Kyoko , Liu Changhai , Gochis David , Clark Martyn , Dai Aiguo , Gutmann Ethan , Dudhia Jimy , Chen Fei , Barlage Mike , Yates David , Zhang Guo
Published: March 2014

A high-resolution climate model (4-km horizontal grid spacing) is used to examine the following question: How will long-term changes in climate impact the partitioning of annual precipitation between evapotranspiration and runoff in the Colorado Headwaters?

This question is examined using a climate sensitivity approach in which eight years of current climate is compared to a future climate created by modifying the current climate signal with perturbation from the NCAR Community Climate System Model, version 3 (CCSM3), model forced by the A1B scenario for greenhouse gases out to 2050. The current climate period is shown to agree well with Snowpack Telemetry (SNOTEL) surface observations of precipitation (P) and snowpack, as well as streamflow and AmeriFlux evapotranspiration (ET) observations. The results show that the annual evaporative fraction (ET/P) for the Colorado Headwaters is 0.81 for the current climate and 0.83 for the future climate, indicating increasing aridity in the future despite a positive increase of precipitation. Runoff decreased by an average of 6%, reflecting the increased aridity.

Precipitation increased in the future winter by 12%, but decreased in the summer as a result of increased low-level inhibition to convection. The fraction of precipitation that fell as snow decreased from 0.83 in the current climate to 0.74 in the future. Future snowpack did not change significantly until January. From January to March the snowpack increased above ~3000 m MSL and decreased below that level. Snowpack decreased at all elevations in the future from April to July. The peak snowpack and runoff over the headwaters occurred 2–3 weeks earlier in the future simulation, in agreement with previous studies.
Vessel wall BAMBI contributes to hemostasis and thrombus stability
Authors: Salles-Crawley Isabelle I. , Monkman James H. , Ahnström Josefin , Lane David A. , Crawley James T. B.
Published: March 2014

Key Points

This is the first report to describe the influence of BAMBI on both hemostasis and thrombus stability. BAMBI present in the blood vessel wall (most likely the endothelium) rather than platelet BAMBI is required for thrombus stability.
Reconstruction of large-size abdominal wall defect using biodegradable poly-p-dioxanone mesh: an experimental canine study
Authors: Huang Kenan , Ding Xinyu , Lv Benbo , Wei Linyun , Sun Juxian , Xu Zhifei , Qin Xiong , Tang Hua
Published: March 2014

Background

Reconstruction of large-size abdominal wall defect (AWDs) is a huge challenge faced in current surgical practice. In this study, we aimed to evaluate the effectiveness and safety of biodegradable poly-p-dioxanone (PDO) mesh for reconstructing large-size AWDs in an experimental canine model.

Methods

Eighteen experimental canines were randomly and equally divided into three groups, namely, a PDO group, a Marlex group and a control group (n= 6 each). Following the creation of a 6 cm × 5.5 cm AWD, PDO mesh and Marlex mesh were used to reconstruct the defect in the PDO and Marlex groups, respectively. The defect was closed using relaxation sutures alone in the control group. Animals were killed 24 weeks after surgery, and reconstruction outcomes were evaluated using radiography, histology and biomechanical testing.

Results

All animals except those in the control group survived the experiment. The PDO group showed no wound dehiscence, herniation or infection, whereas the animals in the Marlex group exhibited marked foreign body reactions. The PDO group had less intraabdominal adhesion than the Marlex group. As shown by radiography, histology and biomechanical testing, PDO mesh exhibited complete degradation and favorable biochemical strength at 24 weeks postsurgery.

Conclusions

PDO mesh implantation is an effective, safe treatment modality for reconstructing large-size AWDs.
The thrombospondin-1 receptor CD36 is an important mediator of ovarian angiogenesis and folliculogenesis
Authors: Osz Kata , Ross Michelle , Petrik Jim
Published: March 2014

Background

Ovarian angiogenesis is a complex process that is regulated by a balance between pro- and anti-angiogenic factors. Physiological processes within the ovary, such as folliculogenesis, ovulation, and luteal formation are dependent upon adequate vascularization and anything that disrupts normal angiogenic processes may result in ovarian dysfunction, and possibly infertility. The objective of this study was to evaluate the role of the thrombospondin-1 (TSP-1) receptor CD36 in mediating ovarian angiogenesis and regulating ovarian function.

Methods

The role of CD36 was evaluated in granulosa cells in vitro and ovarian morphology and protein expression were determined in wild type and CD36 null mice.

Results

In vitro, CD36 inhibition increased granulosa cell proliferation and decreased apoptosis. Granulosa cells in which CD36 was knocked down also exhibited an increase in expression of survival and angiogenic proteins. Ovaries from CD36 null mice were hypervascularized, with increased expression of pro-angiogenic vascular endothelial growth factor (VEGF) and its receptor VEGFR-2. Ovaries from CD36 null mice contained an increase in the numbers of pre-ovulatory follicles and decreased numbers of corpora lutea. CD36 null mice also had fewer number of offspring compared to wild type controls.

Conclusions

The results from this study demonstrate that CD36 is integral to the regulation of ovarian angiogenesis by TSP-1 and the expression of these family members may be useful in the control of ovarian vascular disorders.
Generalized Thompson sampling for sequential decision-making and causal inference
Authors: Ortega Pedro A , Braun Daniel A
Published: March 2014

Purpose

Sampling an action according to the probability that the action is believed to be the optimal one is sometimes called Thompson sampling.

Methods

Although mostly applied to bandit problems, Thompson sampling can also be used to solve sequential adaptive control problems, when the optimal policy is known for each possible environment. The predictive distribution over actions can then be constructed by a Bayesian superposition of the policies weighted by their posterior probability of being optimal.

Results

Here we discuss two important features of this approach. First, we show in how far such generalized Thompson sampling can be regarded as an optimal strategy under limited information processing capabilities that constrain the sampling complexity of the decision-making process. Second, we show how such Thompson sampling can be extended to solve causal inference problems when interacting with an environment in a sequential fashion.

Conclusion

In summary, our results suggest that Thompson sampling might not merely be a useful heuristic, but a principled method to address problems of adaptive sequential decision-making and causal inference.