bluuebunny/crossref_metadata_2025 huggingface dataset:
Fast Universal Spectrophotopolarimeter for Robotic Telescopes
Authors: Plokhotnichenko Vladimir , Beskin Grigory , Karpov Sergey , Bondar Sergey , de-Boer Vjacheslav , Lioubetski Alexandre , Badjin Dmitry
Published: March 2010

FUSP is the automatic multimode spectrophotopolarimeter aimed to the study of fast optical transients in the photometric, photopolarimetric (instant measurement of linear polarization), and spectropolarimetric (with or without the slit) modes. The mode change is automatic depending on the transient brightness and the purposes of the observations and may be performed in half a second. The instrument may be equipped with either fast EM‐CCD or a position‐sensitive detector which may provide temporal resolution up to 1 microsecond. FUSP is the robotic instrument for the robotic telescopes.
Stability and Stabilization of Impulsive Stochastic Delay Difference Equations
Authors: Wu Kaining , Ding Xiaohua , Wang Liming
Published: March 2010

When an impulsive control is adopted for a stochastic delay difference
system (SDDS), there are at least two situations that should be contemplated. If the
SDDS is stable, then what kind of impulse can the original system tolerate to keep
stable? If the SDDS is unstable, then what kind of impulsive strategy should be taken
to make the system stable? Using the Lyapunov‐Razumikhin technique, we
establish criteria for the stability of impulsive stochastic delay difference equations
and these criteria answer those questions. As for applications, we consider a kind of
impulsive stochastic delay difference equation and present some corollaries to our
main results.
Comparison of the Pharmacological Effects of Paricalcitol and Doxercalciferol on the Factors Involved in Mineral Homeostasis
Authors: Wu-Wong J. Ruth , Nakane Masaki , Gagne Gerard D. , Brooks Kristin A. , Noonan William T.
Published: March 2010

Vitamin D receptor agonists (VDRAs) directly suppress parathyroid hormone (PTH) mRNA expression. Different VDRAs are known to have differential effects on serum calcium (Ca), which may also affect serum PTH levels since serum Ca regulates PTH secretion mediated by the Ca-sensing receptor (CaSR). In this study, we compared the effects of paricalcitol and doxercalciferol on regulating serum Ca and PTH, and also the expression of PTH, VDR, and CaSR mRNA. The 5/6 nephrectomized (NX) Sprague-Dawley rats on a normal or hyperphosphatemia-inducing diet were treated with vehicle, paricalcitol, or doxercalciferol for two weeks. Both drugs at the tested doses (0.042–0.33 g/kg) suppressed PTH mRNA expression and serum PTH effectively in the 5/6 NX rats, but paricalcitol was less potent in raising serum Ca than doxercalciferol. In pig parathyroid cells, paricalcitol and the active form of doxercalciferol induced VDR translocation from the cytoplasm into the nucleus, suppressed PTH mRNA expression and inhibited cell proliferation in a similar manner, although paricalcitol induced the expression of CaSR mRNA more effectively. The multiple effects of VDRAs on modulating serum Ca, parathyroid cell proliferation, and the expression of CaSR and PTH mRNA reflect the complex involvement of the vitamin D axis in regulating the mineral homeostasis system.
Wide and Fast: Monitoring the Sky in Subsecond Domain with the FAVOR and TORTORA Cameras
Authors: Karpov Sergey , Beskin Grigory , Bondar Sergey , Guarnieri Adriano , Bartolini Corrado , Greco Giuseppe , Piccioni Adalberto
Published: March 2010

In order to detect and investigate short stochastic optical flares from a number of variable astrophysical objects (GRBs, SNe, flare stars, CVs, X‐Ray binaries) of unknown localizations as well as near‐earth objects (NEOs), both
natural and artificial, it is necessary to perform the systematic monitoring of large regions of the sky with high temporal resolution. Here we discuss the criteria for a system that is able to perform such a task and describe two cameras we created for wide‐field monitoring with high temporal resolution—FAVOR and TORTORA. Also, we describe basic principles of real‐time data processing for the high frame rates needed to achieve subsecond temporal resolution on a typical hardware.
The Bumble Bees of Ukraine: Species Distribution and Floral Preferences
Authors: Konovalova Irene B.
Published: March 2010

The bumble bees were studied in Ukraine between 2002 and 2009 under field conditions, by examining historical and recent collections and by the literature data. Forty one species are reported from the whole territory, 32 of them being recorded from the forest-steppe zone. Ten species are rare in all their habitats:B. confusus,B. distinguendus,B. fragrans,B. gerstaeckeri,B. ruderatus,B. armeniacus,B. mesomelas,B. laesus,B. veteranus, andB. cullumanus. The present persistence of the steppe speciesB. armeniacus,B. laesus, andB. cullumanusis restricted to the eastern part of the country, andB. fragrans—to the Crimean Peninsula. The information on distribution, abundance, habitat, and floral preferences of bumble bees is also provided.
Floral Resources and Nesting Requirements of the Ground-Nesting Social Bee,Lasioglossum malachurum(Hymenoptera: Halictidae), in a Mediterranean Semiagricultural Landscape
Authors: Polidori Carlo , Rubichi Alice , Barbieri Valeria , Trombino Luca , Donegana Marta
Published: March 2010

In order to adopt correct conservation strike plans to maintain bee pollination activity it is necessary to know the species' resource utilisation and requirements. We investigated the floral resources and the nesting requirements of the eusocial beeLasioglossum malachurumKirby at various sites in a Mediterranean landscape. Analysis of bees' pollen loads showed that Compositae was the more exploited family, although interpopulations differences appeared in the pollen types used. From 5 to 7 pollen types were used by bees, but only as few as 1–1.9 per load. Variations of the pollen spectrum through the annual nesting cycle were conspicuous. At all sites, bees nested in horizontal ground areas with high soil hardness, low acidity, and rare superficial stones. On the other side, the exploited soil was variable in soil granulometry (although always high in % of silt or sand) and it was moderately variable in content of organic matter and highly variable in vegetation cover. Creation of ground patches with these characteristics in proximity of both cultivated and natural flowering fields may successfully promote colonization of new areas by this bee.
Hybrid Carbon Fibers/Carbon Nanotubes Structures for Next Generation Polymeric Composites
Authors: Al-Haik M. , Luhrs C. C. , Reda Taha M. M. , Roy A. K. , Dai L. , Phillips J. , Doorn S.
Published: March 2010

Pitch-based carbon fibers are commonly used to produce polymeric carbon fiber structural composites. Several investigations have reported different methods for dispersing and subsequently aligning carbon nanotubes (CNTs) as a filler to reinforce polymer matrix. The significant difficulty in dispersing CNTs suggested the controlled-growth of CNTs on surfaces where they are needed. Here we compare between two techniques for depositing the catalyst iron used toward growing CNTs on pitch-based carbon fiber surfaces. Electrochemical deposition of iron using pulse voltametry is compared to DC magnetron iron sputtering. Carbon nanostructures growth was performed using a thermal CVD system. Characterization for comparison between both techniques was compared via SEM, TEM, and Raman spectroscopy analysis. It is shown that while both techniques were successful to grow CNTs on the carbon fiber surfaces, iron sputtering technique was capable of producing more uniform distribution of iron catalyst and thus multiwall carbon nanotubes (MWCNTs) compared to MWCNTs grown using the electrochemical deposition of iron.
Where Artificial Intelligence and Neuroscience Meet: The Search for Grounded Architectures of Cognition
Authors: van der Velde Frank
Published: March 2010

The collaboration between artificial intelligence and neuroscience can produce an understanding of the mechanisms in the brain that generate human cognition. This article reviews multidisciplinary research lines that could achieve this understanding. Artificial intelligence has an important role to play in research, because artificial intelligence focuses on the mechanisms that generate intelligence and cognition. Artificial intelligence can also benefit from studying the neural mechanisms of cognition, because this research can reveal important information about the nature of intelligence and cognition itself. I will illustrate this aspect by discussing the grounded nature of human cognition. Human cognition is perhaps unique because it combines grounded representations with computational productivity. I will illustrate that this combination requires specific neural architectures. Investigating and simulating these architectures can reveal how they are instantiated in the brain. The way these architectures implement cognitive processes could also provide answers to fundamental problems facing the study of cognition.
The Aromatase Inhibitor Fadrozole and the 5-Reductase Inhibitor Finasteride Affect Gonadal Differentiation and Gene Expression in the Frog Silurana tropicalis
Authors: Duarte-Guterman P. , Langlois V.S. , Hodgkinson K. , Pauli B.D. , Cooke G.M. , Wade M.G. , Trudeau V.L.
Published: March 2010

Aromatase (cyp19) and the 5α- and 5β-reductases (srd5alpha and srd5beta) are important enzymes for vertebrate sexual development. We investigated the effects of inhibition of cyp19 by fadrozole (FAD), and srd5alpha and srd5beta by finasteride (FIN) during anuran larval development. Chronic exposures of Silurana (Xenopus) tropicalis from Nieuwkoop-Faber stage 12 until stage 60 were performed using either 2 µM FAD or 25 µM FIN. Histological analysis of exposed metamorphic frogs revealed that both treatments induced intersex individuals (presence of testicular oocytes). FAD treatment resulted in 55% male, 30% female and 15% intersex, while FIN treatment produced 27% male, 53% female and 20% intersex. Real-time RT-PCR analysis of hepatic sex steroid- and thyroid hormone-related gene expression demonstrated that FAD-induced intersex animals had higher srd5alpha1, srd5alpha2 and eralpha mRNA levels than control and FAD males. In contrast, FIN-induced intersex had low srd5alpha1, srd5alpha2, srd5beta and dio3 and high dio2 mRNA levels. FIN-treated males exhibited high trbeta, dio2 and a lower dio3 mRNA levels. We conclude that chemically induced intersex animals display different gene expression profiles than non-exposed animals and that, although morphologically similar, intersex animals produced by different chemicals have different endocrine pathophysiologies.
Protein Aggregates and Novel Presenilin Gene Variants in Idiopathic Dilated Cardiomyopathy
Authors: Gianni Davide , Li Airong , Tesco Giuseppina , McKay Kenneth M. , Moore John , Raygor Kunal , Rota Marcello , Gwathmey Judith K. , Dec G. William , Aretz Thomas , Leri Annarosa , Semigran Marc J. , Anversa Piero , Macgillivray Thomas E. , Tanzi Rudolph E. , del Monte Federica
Published: March 2010

Background—

Heart failure is a debilitating condition resulting in severe disability and death. In a subset of cases, clustered as idiopathic dilated cardiomyopathy (iDCM), the origin of heart failure is unknown. In the brain of patients with dementia, proteinaceous aggregates and abnormal oligomeric assemblies of β-amyloid impair cell function and lead to cell death.

Methods and Results—

We have similarly characterized fibrillar and oligomeric assemblies in the hearts of iDCM patients, pointing to abnormal protein aggregation as a determinant of iDCM. We also showed that oligomers alter myocyte Ca
2+
homeostasis. Additionally, we have identified 2 new sequence variants in the presenilin-1 (
PSEN1
) gene promoter leading to reduced gene and protein expression. We also show that presenilin-1 coimmunoprecipitates with SERCA2a.

Conclusions—

On the basis of these findings, we propose that 2 mechanisms may link protein aggregation and cardiac function: oligomer-induced changes on Ca
2+
handling and a direct effect of
PSEN1
sequence variants on excitation-contraction coupling protein function.
Effect of Rosiglitazone on Progression of Coronary Atherosclerosis in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease
Authors: Gerstein Hertzel C. , Ratner Robert E. , Cannon Christopher P. , Serruys Patrick W. , García-García Héctor M. , van Es Gerrit-Anne , Kolatkar Nikheel S. , Kravitz Barbara G. , Miller Diane M. , Huang Chun , Fitzgerald Peter J. , Nesto Richard W. ,   the APPROACH Study Group
Published: March 2010

Background—

Rosiglitazone has several properties that may affect progression of atherosclerosis. The Assessment on the Prevention of Progression by Rosiglitazone on Atherosclerosis in Diabetes Patients With Cardiovascular History (APPROACH) study was undertaken to determine the effect of the thiazolidinedione rosiglitazone on coronary atherosclerosis as assessed by intravascular ultrasound compared with the sulfonylurea glipizide.

Methods and Results—

This was a randomized, double-blind, controlled 18-month study in 672 patients aged 30 to 80 years with established type 2 diabetes mellitus treated by lifestyle, 1 oral agent, or submaximal doses of 2 oral agents who had at least 1 atherosclerotic plaque with 10% to 50% luminal narrowing in a coronary artery that had not undergone intervention during a clinically indicated coronary angiography or percutaneous coronary intervention. The primary outcome was change in percent atheroma volume in the longest and least angulated epicardial coronary artery that had not undergone intervention. Secondary outcomes included change in normalized total atheroma volume and change in total atheroma volume in the most diseased baseline 10-mm segment. Rosiglitazone did not significantly reduce the primary outcome of percent atheroma volume compared with glipizide (−0.64%; 95% confidence interval, −1.46 to 0.17;
P
=0.12). The secondary outcome of normalized total atheroma volume was significantly reduced by rosiglitazone compared with glipizide (−5.1 mm
3
; 95% confidence interval, −10.0 to −0.3;
P
=0.04); however, no significant difference between groups was observed for the change in total atheroma volume within the most diseased baseline 10-mm segment (−1.7 mm
3
; 95% confidence interval, −3.9 to 0.5;
P
=0.13).

Conclusions—

Rosiglitazone did not significantly decrease the primary end point of progression of coronary atherosclerosis more than glipizide in patients with type 2 diabetes mellitus and coronary atherosclerosis.

Clinical Trial Registration—

http://www.clinicaltrials.gov. Unique Identifier: NCT00116831.
Emergence of Ethnic Differences in Blood Pressure in Adolescence
Authors: Harding Seeromanie , Whitrow Melissa , Lenguerrand Erik , Maynard Maria , Teyhan Alison , Cruickshank J. Kennedy , Der Geoff
Published: March 2010

The cause of ethnic differences in cardiovascular disease remains a scientific challenge. Blood pressure tracks from late childhood to adulthood. We examined ethnic differences in changes in blood pressure between early and late adolescence in the United Kingdom. Longitudinal measures of blood pressure, height, weight, leg length, smoking, and socioeconomic circumstances were obtained from London, United Kingdom, schoolchildren of White British (n=692), Black Caribbean (n=670), Black African (n=772), Indian (n=384), and Pakistani and Bangladeshi (n=402) ethnicity at 11 to 13 years and 14 to 16 years. Predicted age- and ethnic-specific means of blood pressure, adjusted for anthropometry and social exposures, were derived using mixed models. Among boys, systolic blood pressure did not differ by ethnicity at 12 years, but the greater increase among Black Africans than Whites led to higher systolic blood pressure at 16 years (+2.9 mm Hg). Among girls, ethnic differences in mean systolic blood pressure were not significant at any age, but while systolic blood pressure hardly changed with age among White girls, it increased among Black Caribbeans and Black Africans. Ethnic differences in diastolic blood pressure were more marked than those for systolic blood pressure. Body mass index, height, and leg length were independent predictors of blood pressure, with few ethnic-specific effects. Socioeconomic disadvantage had a disproportionate effect on blood pressure for girls in minority groups. The findings suggest that ethnic divergences in blood pressure begin in adolescence and are particularly striking for boys. They signal the need for early prevention of adverse cardiovascular disease risks in later life.
Preserved Oxygenation Despite Reduced Blood Flow in Poststenotic Kidneys in Human Atherosclerotic Renal Artery Stenosis
Authors: Gloviczki Monika L. , Glockner James F. , Lerman Lilach O. , McKusick Michael A. , Misra Sanjay , Grande Joseph P. , Textor Stephen C.
Published: March 2010

Atherosclerotic renal artery stenosis reduces blood flow and perfusion pressures to the poststenotic kidney producing renovascular hypertension and threatening glomerular filtration rate. Little is known regarding regional tissue oxygenation in human renovascular disease that develops slowly. We compared stenotic and contralateral kidneys regarding volume, tissue perfusion, blood flow measured by multidetector computed tomography, and blood oxygen level–dependent magnetic resonance values in the cortex and medulla in 14 patients with unilateral stenosis (mean: 71% by quantitative computed tomography) and in 14 essential hypertensive patients during 150 mEq/d of sodium intake and renin-angiotensin blockade. Stenotic kidney volume was reduced compared with the contralateral kidney (118.6±9.9 versus 155.4±13.7 mL;
P
<0.01), as was total blood flow (269.7±42.2 versus 383.7±49;
P
=0.02), mainly because of reduced cortical volume. Tissue perfusion was similar but lower than essential hypertension (1.5 versus 1.2 mL/min per milliliter;
P
<0.05). Blood oxygen level–dependent MR at 3 T confirmed elevated R2* values (a measure of deoxyhemoglobin) in deep medullary regions in all 3 sets of kidneys (38.9±0.7 versus cortex 17.8±0.36 s
−1
;
P
<0.0001). Despite reduced blood flow, R2* values did not differ between atherosclerotic and essential hypertensive kidneys, although furosemide-suppressible fall in medullary R2* was reduced in stenotic kidneys (5.7±1.8 versus 9.4±1.9 s
−1
;
P
<0.05). Renal venous oxygen levels from the stenotic kidney were higher than those from essential hypertensives (65.1±2.2 versus 58.1±1.2;
P
=0.006). These data indicate that, although stenosis reduced blood flow and volume, cortical and medullary oxygenation was preserved under these conditions.
Impairment in Function and Expression of Transient Receptor Potential Vanilloid Type 4 in Dahl Salt-Sensitive Rats
Authors: Gao Feng , Wang Donna H.
Published: March 2010

To examine the role of transient receptor potential vanilloid type 4 (TRPV4) channels in the development of salt-sensitive hypertension, male Dahl salt-sensitive (DS) and -resistant (DR) rats were fed a low-salt (LS) or high-salt (HS) diet for 3 weeks. DS-HS but not DR-HS rats developed hypertension. 4α-Phorbol-12,13-didecanoate (a selective TRPV4 activator; 2.5 mg/kg IV) decreased mean arterial pressure in all of the groups with the greatest effects in DR-HS and the least in DS-HS rats (
P
<0.05). Depressor effects of 4α-phorbol-12,13-didecanoate but not dihydrocapsaicin (a selective TRPV1 agonist; 30 μg/kg IV) were abolished by ruthenium red (a TRPV4 antagonist; 3 mg/kg IV) in all of the groups. Blockade of TRPV4 with ruthenium red increased mean arterial pressure in DR-HS rats only (
P
<0.05). TRPV4 protein contents were decreased in the renal cortex, medulla, and dorsal root ganglia in DS-HS compared with DS-LS rats but increased in dorsal root ganglia and mesenteric arteries in DR-HS compared with DR-LS rats (
P
<0.05). Mean arterial pressure responses to blockade of small- and large-/intermediate-conductance Ca
2+
-activated K
+
channels (Maxiκ channels) with apamin and charybdotoxin, respectively, were examined. Apamin (100 μg/kg) plus charybdotoxin (100 μg/kg) abolished 4α-phorbol-12,13-didecanoate–induced hypotension in DR-LS, DR-HS, and DS-LS rats only. Thus, HS-induced enhancement of TRPV4 function and expression in sensory neurons and resistant vessels in DR rats may prevent salt-induced hypertension possibly via activation of Maxiκ channels given that blockade of TRPV4 elevates mean arterial pressure. In contrast, HS-induced suppression of TRPV4 function and expression in sensory neurons and kidneys in DS rats may contribute to increased salt sensitivity.
Intracerebral Hemorrhage in Cocaine Users
Authors: Martin-Schild Sheryl , Albright Karen C. , Hallevi Hen , Barreto Andrew D. , Philip Maria , Misra Vivek , Grotta James C. , Savitz Sean I.
Published: February 2010

Background and Purpose—

Cocaine is a cause of intracerebral hemorrhage (ICH), but there are no large studies that have characterized the location, pathology, and outcome of patients with cocaine-associated ICH.

Methods—

We performed a retrospective analysis of all patients admitted to our stroke service from 2004 to 2007 who had nontraumatic ICH and urine drug screens positive for cocaine and compared them with similar patients who had negative drug screens for cocaine.

Results—

We identified 45 patients with cocaine-associated ICH and 105 patients with cocaine-negative ICH. There were no significant differences in age or gender, but there was a significantly higher incidence of black patients in the cocaine-positive group. Cocaine-associated ICH patients had higher admission blood pressures, significantly more subcortical hemorrhages, and higher rates of intraventricular hemorrhage compared to patients with cocaine-negative ICH. Cocaine-positive patients had worse functional outcome, defined as modified Rankin Scale score >3 at the time of discharge (OR, 4.90; 95% CI, 2.19–10.97), and were less likely to be discharged home or to inpatient rehabilitation. Patients with cocaine-associated ICH were nearly 3-times more likely to die during their acute hospitalization when compared to cocaine-negative patients.

Conclusion—

Recent cocaine ingestion is associated with hemorrhages that occur more frequently in subcortical locations, have a higher risk of intraventricular hemorrhage, and have a poor prognosis compared to patients with cocaine-negative, spontaneous ICH.
Putative GTPase GIMAP1 is critical for the development of mature B and T lymphocytes
Authors: Saunders Amy , Webb Louise M. C. , Janas Michelle L. , Hutchings Amanda , Pascall John , Carter Christine , Pugh Nicholas , Morgan Geoff , Turner Martin , Butcher Geoffrey W.
Published: March 2010

The guanosine triphosphatases (GTPases) of the immunity-associated protein (GIMAP) family of putative GTPases has been implicated in the regulation of T-lymphocyte development and survival. A mouse conditional knockout allele was generated for the immune GTPase gene GIMAP1. Homozygous loss of this allele under the influence of the lymphoid-expressed hCD2-iCre recombinase transgene led to severe (> 85%) deficiency of mature T lymphocytes and, unexpectedly, of mature B lymphocytes. By contrast there was little effect of GIMAP1 deletion on immature lymphocytes in either B or T lineages, although in vitro studies showed a shortening of the survival time of both immature and mature CD4+ single-positive thymocytes. These findings show a vital requirement for GIMAP1 in mature lymphocyte development/survival and draw attention to the nonredundant roles of members of the GIMAP GTPase family in these processes.
Ribosomopathies: human disorders of ribosome dysfunction
Authors: Narla Anupama , Ebert Benjamin L.
Published: March 2010

Ribosomopathies compose a collection of disorders in which genetic abnormalities cause impaired ribosome biogenesis and function, resulting in specific clinical phenotypes. Congenital mutations in RPS19 and other genes encoding ribosomal proteins cause Diamond-Blackfan anemia, a disorder characterized by hypoplastic, macrocytic anemia. Mutations in other genes required for normal ribosome biogenesis have been implicated in other rare congenital syndromes, Schwachman-Diamond syndrome, dyskeratosis congenita, cartilage hair hypoplasia, and Treacher Collins syndrome. In addition, the 5q− syndrome, a subtype of myelodysplastic syndrome, is caused by a somatically acquired deletion of chromosome 5q, which leads to haploinsufficiency of the ribosomal protein RPS14 and an erythroid phenotype highly similar to Diamond-Blackfan anemia. Acquired abnormalities in ribosome function have been implicated more broadly in human malignancies. The p53 pathway provides a surveillance mechanism for protein translation as well as genome integrity and is activated by defects in ribosome biogenesis; this pathway appears to be a critical mediator of many of the clinical features of ribosomopathies. Elucidation of the mechanisms whereby selective abnormalities in ribosome biogenesis cause specific clinical syndromes will hopefully lead to novel therapeutic strategies for these diseases.
Deadly allies: the fatal interplay between platelets and metastasizing cancer cells
Authors: Erpenbeck Luise , Schön Michael P.
Published: March 2010

The general notion that functional platelets are important for successful hematogenous tumor metastasis has been inaugurated more than 4 decades ago and has since been corroborated in numerous experimental settings. Thorough preclinical investigations have, at least in part, clarified some specifics regarding the involvement of platelet adhesion receptors, such as thrombin receptors or integrins, in the metastasis cascade. Pivotal preclinical experiments have demonstrated that hematogenous tumor spread was dramatically diminished when platelets were depleted from the circulation or when functions of platelet surface receptors were inhibited pharmacologically or genetically. Such insight has inspired researchers to devise novel antitumoral therapies based on targeting platelet receptors. However, several mechanistic aspects underlying the impact of platelet receptors on tumor metastasis are not fully understood, and agents directed against platelet receptors have not yet found their way into the clinic. In addition, recent results suggesting that targeted inhibition of certain platelet surface receptors may even result in enhanced experimental tumor metastasis have demonstrated vividly that the role of platelets in tumor metastasis is more complex than has been anticipated previously. This review gives a comprehensive overview on the most important platelet receptors and their putative involvement in hematogenous metastasis of malignant tumors.
CYLD regulates angiogenesis by mediating vascular endothelial cell migration
Authors: Gao Jinmin , Sun Lei , Huo Lihong , Liu Min , Li Dengwen , Zhou Jun
Published: March 2010

Cylindromatosis (CYLD) is a deubiquitinase that was initially identified as a tumor suppressor and has recently been implicated in diverse normal physiologic processes. In this study, we have investigated the involvement of CYLD in angiogenesis, the formation of new blood vessels from preexisting ones. We find that knockdown of CYLD expression significantly impairs angiogenesis in vitro in both matrigel-based tube formation assay and collagen-based 3-dimensional capillary sprouting assay. Disruption of CYLD also remarkably inhibits angiogenic response in vivo, as evidenced by diminished blood vessel growth into the angioreactors implanted in mice. Mechanistic studies show that CYLD regulates angiogenesis by mediating the spreading and migration of vascular endothelial cells. Silencing of CYLD dramatically decreases microtubule dynamics in endothelial cells and inhibits endothelial cell migration by blocking the polarization process. Furthermore, we identify Rac1 activation as an important factor contributing to the action of CYLD in regulating endothelial cell migration and angiogenesis. Our findings thus uncover a previously unrecognized role for CYLD in the angiogenic process and provide a novel mechanism for Rac1 activation during endothelial cell migration and angiogenesis.
R-Ras regulates β1-integrin trafficking via effects on membrane ruffling and endocytosis
Authors: Conklin Matthew W , Ada-Nguema Aude , Parsons Maddy , Riching Kristin M , Keely Patricia J
Published: March 2010

Background

Integrin-mediated cell adhesion and spreading is dramatically enhanced by activation of the small GTPase, R-Ras. Moreover, R-Ras localizes to the leading edge of migrating cells, and regulates membrane protrusion. The exact mechanisms by which R-Ras regulates integrin function are not fully known. Nor is much known about the spatiotemporal relationship between these two molecules, an understanding of which may provide insight into R-Ras regulation of integrins.

Results

GFP-R-Ras localized to the plasma membrane, most specifically in membrane ruffles, in Cos-7 cells. GFP-R-Ras was endocytosed from these ruffles, and trafficked via multiple pathways, one of which involved large, acidic vesicles that were positive for Rab11. Cells transfected with a dominant negative form of GFP-R-Ras did not form ruffles, had decreased cell spreading, and contained numerous, non-trafficking small vesicles. Conversely, cells transfected with the constitutively active form of GFP-R-Ras contained a greater number of ruffles and large vesicles compared to wild-type transfected cells. Ruffle formation was inhibited by knock-down of endogenous R-Ras with siRNA, suggesting that activated R-Ras is not just a component of, but also an architect of ruffle formation. Importantly, β1-integrin co-localized with endogenous R-Ras in ruffles and endocytosed vesicles. Expression of dominant negative R-Ras or knock down of R-Ras by siRNA prevented integrin accumulation into ruffles, impaired endocytosis of β1-integrin, and decreased β1-integrin-mediated adhesion. Knock-down of R-Ras also perturbed the dynamics of another membrane-localized protein, GFP-VSVG, suggesting a more global role for R-Ras on membrane dynamics. However, while R-Ras co-internalized with integrins, it did not traffic with VSVG, which instead moved laterally out of ruffles within the plane of the membrane, suggesting multiple levels of regulation of and by R-Ras.

Conclusions

Our results suggest that integrin function involves integrin trafficking via a cycle of membrane protrusion, ruffling, and endocytosis regulated by R-Ras, providing a novel mechanism by which integrins are linked to R-Ras through control of membrane dynamics.
An unedited 1.1 kb mitochondrial orfB gene transcript in the Wild Abortive Cytoplasmic Male Sterility (WA-CMS) system of Oryza sativa L. subsp. indica
Authors: Das Srirupa , Sen Supriya , Chakraborty Anirban , Chakraborti Papia , Maiti Mrinal K , Basu Asitava , Basu Debabrata , Sen Soumitra K
Published: March 2010

Background

The application of hybrid rice technology has significantly increased global rice production during the last three decades. Approximately 90% of the commercially cultivated rice hybrids have been derived through three-line breeding involving the use of WA-CMS lines. It is believed that during the 21st century, hybrid rice technology will make significant contributions to ensure global food security. This study examined the poorly understood molecular basis of the WA-CMS system in rice.

Results

RFLPs were detected for atp6 and orfB genes in sterile and fertile rice lines, with one copy of each in the mt-genome. The RNA profile was identical in both lines for atp6, but an additional longer orfB transcript was identified in sterile lines. 5' RACE analysis of the long orfB transcript revealed it was 370 bp longer than the normal transcript, with no indication it was chimeric when compared to the genomic DNA sequence. cDNA clones of the longer orfB transcript in sterile lines were sequenced and the transcript was determined unedited. Sterile lines were crossed with the restorer and maintainer lines, and fertile and sterile F1 hybrids were respectively generated. Both hybrids contained two types of orfB transcripts. However, the long transcript underwent editing in the fertile F1 hybrids and remained unedited in the sterile lines. Additionally, the editing of the 1.1 kb orfB transcript co-segregated with fertility restoring alleles in a segregating population of F2 progeny; and the presence of unedited long orfB transcripts was detected in the sterile plants from the F2 segregating population.

Conclusion

This study helped to assign plausible operative factors responsible for male-sterility in the WA cytoplasm of rice. A new point of departure to dissect the mechanisms governing the CMS-WA system in rice has been identified, which can be applied to further harness the opportunities afforded by hybrid vigor in rice.
Dual effect of Plasmodium-infected erythrocytes on dendritic cell maturation
Authors: Bettiol Esther , Carapau Daniel , Galan-Rodriguez Cristina , Ocaña-Morgner Carlos , Rodriguez Ana
Published: March 2010

Background

Infection with Plasmodium is the cause of malaria, a disease characterized by a high inflammatory response in the blood. Dendritic cells (DC) participate in both adaptive and innate immune responses, influencing the generation of inflammatory responses. DC can be activated through different receptors, which recognize specific molecules in microbes and induce the maturation of DC.

Methods

Using Plasmodium yoelii, a rodent malaria model, the effect of Plasmodium-infected erythrocytes on DC maturation and TLR responses have been analysed.

Results

It was found that intact erythrocytes infected with P. yoelii do not induce maturation of DC unless they are lysed, suggesting that accessibility of parasite inflammatory molecules to their receptors is a key issue in the activation of DC by P. yoelii. This activation is independent of MyD88. It was also observed that pre-incubation of DC with intact P. yoelii-infected erythrocytes inhibits the maturation response of DC to other TLR stimuli. The inhibition of maturation of DC is reversible, parasite-specific and increases with the stage of parasite development, with complete inhibition induced by schizonts (mature infected erythrocytes). Plasmodium yoelii-infected erythrocytes induce a broad inhibitory effect rendering DC non-responsive to ligands for TLR2, TLR3, TLR4, TLR5, TLR7 and TLR9.

Conclusions

Despite the presence of inflammatory molecules within Plasmodium-infected erythrocytes, which are probably responsible for DC maturation induced by lysates, intact Plasmodium-infected erythrocytes induce a general inhibition of TLR responsiveness in DC. The observed effect on DC could play an important role in the pathology and suboptimal immune response observed during the disease. These results help to explain why immune functions are altered during malaria, and provide a system for the identification of a parasite-derived broad inhibitor of TLR-mediated signaling pathways.
Computational analysis of binding between malarial dihydrofolate reductases and anti-folates
Authors: Choowongkomon Kiattawee , Theppabutr Sasikrit , Songtawee Napat , Day Nicholas PJ , White Nicholas J , Woodrow Charles J , Imwong Mallika
Published: March 2010

Background

Plasmodium falciparum readily develops resistance to the anti-folates pyrimethamine and proguanil via a characteristic set of mutations in the dihydrofolate reductase (PfDHFR) gene that leads to reduced competitive drug binding at the enzyme's active site. Analogous mutations can be found in the DHFR gene in isolates of Plasmodium vivax (PvDHFR) although anti-folates have not been widely used for the treatment of this infection. Here the interactions between DHFR inhibitors and modelled structures of the DHFR enzymes of Plasmodium malariae (PmDHFR) and Plasmodium ovale (PoDHFR) are described, along with an investigation of the effect of recently reported mutations within PmDHFR.

Methods

DHFR models for PmDHFR and PoDHFR were constructed using the solved PfDHFR-TS and PvDHFR structures respectively as templates. The modelled structures were docked with three DHFR inhibitors as ligands and more detailed interactions were explored via simulation of molecular dynamics.

Results

Highly accurate models were obtained containing sets of residues that mediate ligand binding which are highly comparable to those mediating binding in known crystal structures. Within this set, there were differences in the relative contribution of individual residues to inhibitor binding. Modelling of PmDHFR mutant sequences revealed that PmDHFR I170M was associated with a significant reduction in binding energy to all DHFR inhibitors studied, while the other predicted resistance mutations had lesser or no effects on ligand binding.

Conclusions

Binding of DHFR inhibitors to the active sites of all four Plasmodium enzymes is broadly similar, being determined by an analogous set of seven residues. PmDHFR mutations found in field isolates influenced inhibitor interactions to a varying extent. In the case of the isolated I170M mutation, the loss of interaction with pyrimethamine suggests that DHFR-inhibitor interactions in P. malariae are different to those seen for DHFRs from P. falciparum and P. vivax.
PEEP titration guided by ventilation homogeneity: a feasibility study using electrical impedance tomography
Authors: Zhao Zhanqi , Steinmann Daniel , Frerichs Inéz , Guttmann Josef , Möller Knut
Published: March 2010

Introduction

Lung protective ventilation requires low tidal volume and suitable positive end-expiratory pressure (PEEP). To date, few methods have been accepted for clinical use to set the appropriate PEEP. The aim of this study was to test the feasibility of PEEP titration guided by ventilation homogeneity using the global inhomogeneity (GI) index based on electrical impedance tomography (EIT) images.

Methods

In a retrospective study, 10 anesthetized patients with healthy lungs mechanically ventilated under volume-controlled mode were investigated. Ventilation distribution was monitored by EIT. A standardized incremental PEEP trial (PEEP from 0 to 28 mbar, 2 mbar per step) was conducted. During the PEEP trial, "optimal" PEEP level for each patient was determined when the air was most homogeneously distributed in the lung, indicated by the lowest GI index value. Two published methods for setting PEEP were included for comparison based on the maximum global dynamic compliance and the intra-tidal compliance-volume curve.

Results

No significant differences in the results were observed between the GI index method (12.2 ± 4.6 mbar) and the dynamic compliance method (11.4 ± 2.3 mbar, P > 0.6), or between the GI index and the compliance-volume curve method (12.2 ± 4.9 mbar, P > 0.6).

Conclusions

According to the results, it is feasible and reasonable to use the GI index to select the PEEP level with respect to ventilation homogeneity. The GI index may provide new insights into the relationship between lung mechanics and tidal volume distribution and may be used to guide ventilator settings.
High-resolution transcription atlas of the mitotic cell cycle in budding yeast
Authors: Granovskaia Marina V , Jensen Lars J , Ritchie Matthew E , Toedling Joern , Ning Ye , Bork Peer , Huber Wolfgang , Steinmetz Lars M
Published: March 2010

Background

Extensive transcription of non-coding RNAs has been detected in eukaryotic genomes and is thought to constitute an additional layer in the regulation of gene expression. Despite this role, their transcription through the cell cycle has not been studied; genome-wide approaches have only focused on protein-coding genes. To explore the complex transcriptome architecture underlying the budding yeast cell cycle, we used 8 bp tiling arrays to generate a 5 minute-resolution, strand-specific expression atlas of the whole genome.

Results

We discovered 523 antisense transcripts, of which 80 cycle or are located opposite periodically expressed mRNAs, 135 unannotated intergenic non-coding RNAs, of which 11 cycle, and 109 cell-cycle-regulated protein-coding genes that had not previously been shown to cycle. We detected periodic expression coupling of sense and antisense transcript pairs, including antisense transcripts opposite of key cell-cycle regulators, like FAR1 and TAF2.

Conclusions

Our dataset presents the most comprehensive resource to date on gene expression during the budding yeast cell cycle. It reveals periodic expression of both protein-coding and non-coding RNA and profiles the expression of non-annotated RNAs throughout the cell cycle for the first time. This data enables hypothesis-driven mechanistic studies concerning the functions of non-coding RNAs.
Prognostic Value of Changes in Health-Related Quality of Life Scores During Curative Treatment for Esophagogastric Cancer
Authors: Djärv Therese , Metcalfe Chris , Avery Kerry N.L. , Lagergren Pernilla , Blazeby Jane M.
Published: March 2010

Purpose

Accumulating evidence suggests that health-related quality of life (HRQL) data before treatment predict survival, but the prognostic value of changes in HRQL scores after treatment is unknown. The aim of this study was to explore whether changes in HRQL scores in esophagogastric cancer predict survival.

Patients and Methods

Consecutive patients undergoing curative treatment completed HRQL questionnaires (EORTC QLQ-C30) at baseline and after six months and were followed up for at least five years. Cox proportional hazard models with adjustments assessed associations between baseline HRQL and survival and between changes in HRQL before and after treatment and survival.

Results

Overall, 216 patients initiated curative therapy, of whom169 completed treatment and survived 6 months. Of these, 132 (7%) had two complete HRQL assessments. Analyses adjusted for age, sex, performance status, tumor stage, and disease site revealed that a 10-point poorer dyspnea score at baseline was significantly associated with an 18% higher risk of death. Additional analyses to adjust for baseline HRQL and treatment showed that a 10-point change in physical function (hazard ratio [HR], 0.85; 95% CI, 0.76 to 0.96; P = .007), pain (HR, 1.20; 95% CI, 1.09 to 1.33; P < .001), and fatigue (HR, 1.16; 95% CI, 1.04 to 1.30; P = .009) scores was associated with better survival.

Conclusion

This exploratory study found longer survival beyond the 6 months after starting treatment to be associated with fewer problems with dyspnea before treatment and better recovery of physical function, pain, and fatigue after treatment. More research to confirm these findings and understand the results is needed.
Serum MicroRNA Signatures Identified in a Genome-Wide Serum MicroRNA Expression Profiling Predict Survival of Non–Small-Cell Lung Cancer
Authors: Hu Zhibin , Chen Xi , Zhao Yang , Tian Tian , Jin Guangfu , Shu Yongqian , Chen Yijiang , Xu Lin , Zen Ke , Zhang Chenyu , Shen Hongbing
Published: March 2010

Purpose

Recent findings that human serum contains stably expressed microRNA (miRNA) have revealed a great potential of serum miRNA signature as disease fingerprints to predict survival. We used genome-wide serum miRNA expression analysis to investigate the role of serum miRNA in predicting prognosis of non–small-cell lung cancer (NSCLC).

Patients and Methods

To control disease heterogeneity, we used patients with stages I to IIIa lung adenocarcinoma and squamous cell carcinoma, who were treated with both operation and adjuvant chemotherapies. In the discovery stage, Solexa sequencing followed by individual quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assays was used to test the difference in levels of serum miRNAs between 30 patients with longer survival (alive and mean survival time, 49.54 months) and 30 patients with shorter survival matched by age, sex, and stage (dead and mean survival time, 9.54 months). The detected serum miRNAs then were validated in 243 patients (randomly classified into two subgroups: n = 120 for the training set, and n = 123 for the testing set).

Results

Eleven serum miRNAs were found to be altered more than five-fold by Solexa sequencing between longer-survival and shorter-survival groups, and levels of four miRNAs (ie, miR-486, miR-30d, miR-1 and miR-499) were significantly associated with overall survival. The four-miRNA signature also was consistently an independent predictor of overall survival for both training and testing samples.

Conclusion

The four-miRNA signature from the serum may serve as a noninvasive predictor for the overall survival of NSCLC.
Translating Gene Expression Into Clinical Care: Sarcomas As a Paradigm
Authors: Nielsen Torsten O. , West Robert B.
Published: March 2010

Whereas most solid tumors are characterized by considerable genetic instability and molecular heterogeneity, sarcomas include many subtypes with very specific underlying molecular events driving oncogenesis. Gene expression profiling and other modern techniques have consequently had particular success in identifying the critical biologic pathways active in specific sarcomas, yielding insights which can be translated into useful diagnostic biomarkers. Public availability of data sets and new sequencing-based technologies will accelerate this process. Molecular studies have also identified oncogenic pathways of particular importance in sarcomas which can be targeted by investigational drugs. Examples include histone deacetylases in translocation-associated sarcomas of young adults, Akt/mammalian target of rapamycin in pleomorphic sarcomas, and macrophage colony-stimulating factor in tenosynovial giant cell tumor. Despite challenges in organization and accrual, future clinical trials of sarcomas need to be designed that take into account specific molecular subtypes as distinct diseases.
Theorizing in Motion
Authors: Coates Emily
Published: March 2010

In this article, Emily Coates discusses the work of three choreographers—Opiyo Okach, Yasmeen Godder, and Yvonne Rainer—whose work was shown at Yale University's Festival of International Dance in 2008. She examines their work from both global and local perspectives, suggesting various ways in which gesture, choreography, and dance knowledge circulates by physical exchange among dancers performing internationally. She describes these choreographers' work as joining tradition with innovation toward an integrated, globalized world.