bluuebunny/crossref_metadata_2025 huggingface dataset:
THE GEOMETRICAL EFFECTS ON ELECTRONIC SPECTRUM AND PERSISTENT CURRENTS IN MESOSCOPIC POLYGON
Authors: ZHANG SHENGLI , WANG QI , ZHANG ERHU
Published: February 2009

In this paper, a new mesoscopic polygon which possesses smooth transition at its corners is proposed. Because of the particularity of structure, this kind of mesoscopic polygon can also be a geometrical superlattice. The geometrical effects on the electron states and persistent current are investigated comprehensively in the presence of magnetic flux. We find that the particular geometric structure of the polygon induces an effective periodic potential which results in gaps in the energy spectrum. The changes of gaps show the consistency with the geometrical two-ness of this new polygon. This electronic structure and the corresponding physical properties are found to be periodic with period ϕ0 in the magnetic flux ϕ and can be controlled by the geometric method. We also consider the Rahsba spin-orbit interaction which double the energy levels splitting and leads to an additional small zigzag in one period of the persistent current. These new phenomena may be useful for the applications in quantum device design in the future.
Tissue-specific deiodinase regulation during food restriction and low replacement dose of leptin in rats
Authors: Araujo R. L. , Andrade B. M. , da Silva M. L. , Ferreira A. C. F. , Carvalho D. P.
Published: February 2009

The relationship between thyroid function and leptin has been extensively studied; however, the mechanisms underlying the changes in thyroid hormone economy that occur during caloric deprivation remain elusive. Our goal was to evaluate the thyroid function of rats submitted to 40% food restriction after chronic leptin replacement. Caloric restriction for 25 days led to significantly reduced serum leptin, thyroid-stimulating hormone (TSH), thyroxine (T4), and triiodothyronine (T3) and increased serum corticosterone, while liver, kidney, and thyroid type I deiodinase (D1) and brown adipose tissue (BAT) type II deiodinase (D2) activities were decreased and hypothalamic D2 was significantly increased. Interestingly, thyroid iodide uptake was unchanged by caloric restriction, but thyroperoxidase (TPO) activity was significantly reduced. Leptin replacement for the last 10 days of caloric restriction normalized serum leptin and TSH levels, but serum T4and T3levels and thyroid D1 and TPO activities were not reestablished. Also, a negative effect of leptin administration on Na+-I−symporter function was detected. Liver and kidney D1 and hypothalamic and BAT D2 were normalized by leptin, while pituitary D2 was significantly decreased. In conclusion, a tissue-specific modulation of deiodinases might be implicated in the normalization of thyroid function during leptin replacement in food-restricted rats. Although leptin restores the hypothalamus-pituitary axis during food restriction, it exerts a direct negative effect on the thyroid gland; thus normalization of serum thyroid hormones might depend on changes in deiodinase activities and the long-term thyroid stimulation by TSH to counterbalance the direct negative effects of leptin on the thyroid gland.
Asymmetrical dimethylarginine triggers lipolysis and inflammatory response via induction of endoplasmic reticulum stress in cultured adipocytes
Authors: Zhou Qiu Gen , Zhou Min , Hou Fan Fan , Peng Xin
Published: February 2009

Protein energy wasting, a state of decreased stores of body protein and fat, is a risk factor for mortality in advanced chronic kidney disease (CKD). Little is known about the mechanism underlying loss of fat in CKD. Accumulation of asymmetric dimethylarginine (ADMA) is prevalent in advanced CKD. Here we assessed the effect of ADMA on cellular perturbation in cultured 3T3-L1 adipocytes. Exposure of adipocytes to ADMA induced lipolysis and decreased perilipin A, with no alteration of lipases expression or activity. ADMA treatment also upregulated the expression of inflammatory adipocytokines via activation of nuclear factor-κB (NF-κB). Blocking the inflammatory responses with NF-κB inhibitor partly inhibited the ADMA-induced lipolysis. Furthermore, ADMA treatment triggered endoplasmic reticulum (ER) stress, revealed by phosphorylation of PKR-like eukaryotic initiation factor 2α kinase, eukaryotic translational initiation factor 2α, c-Jun NH2-terminal kinase, and overexpression of glucose-regulated protein 78. Treatment with ER stress inhibitor completely abolished the ADMA-induced lipolysis and inflammatory responses. Moreover, conditioned medium from the ADMA-treated adipocytes increased protein degradation in cultured C2C12myotubes, suggesting that the ADMA-induced adipocyte perturbation may promote skeletal muscle proteolysis. These data suggest that elevated ADMA promoted the adipocyte perturbation through induction of ER stress, which might have implication for protein energy wasting in CKD.
How form follows functional genomics: gene expression profiling gastric epithelial cells with a particular discourse on the parietal cell
Authors: Capoccia Benjamin J. , Huh Won Jae , Mills Jason C.
Published: February 2009

The cellular composition and morphology of the stomach epithelium have been described in detail; however, the molecular mechanisms that regulate the differentiation of the various cell lineages as well as the function of mature gastric cells are far less clear. Recently, dissection of the molecular anatomy of the stomach has been boosted by the advent of functional genomics, which allows investigators to determine patterns of gene expression across virtually the entire cellular transcriptome. In this review, we discuss the impact of functional genomic studies on the understanding of gastric epithelial physiology. We show how functional genomic studies have uncovered genes that are useful as new cell lineage-specific markers of differentiation and provide new insights into cell physiology. For example, vascular endothelial growth factor B (Vegfb) has been identified as a parietal cell-specific marker that may allow parietal cells to regulate the mucosal vascular network. We also discuss how functional genomics has identified aberrantly expressed genes in disease states. Human epididymis 4 (HE4), for example, was recently identified as a metaplasia-induced gene product in mice based on microarray analysis. Finally, we will examine how analysis of higher-order patterns of gene expression can go beyond simply identifying individual genes to show how cells work as integrated systems. Specifically, we show how application of a Gene Ontology (GO) analysis of gene expression patterns from multiple tissues identifies the gastric parietal cell as an outlier, unlike other differentiated cell lineages in the stomach or elsewhere in the body.
Feasibility Study of Particle-Assisted Laser Ablation of Brain Tumors in Orthotopic Canine Model
Authors: Schwartz Jon A. , Shetty Anil M. , Price Roger E. , Stafford R. Jason , Wang James C. , Uthamanthil Rajesh K. , Pham Kevin , McNichols Roger J. , Coleman Chris L. , Payne J. Donald
Published: February 2009

We report on a pilot study showing a proof of concept for the passive delivery of nanoshells to an orthotopic tumor where they induce a local, confined therapeutic response distinct from that of normal brain resulting in the photothermal ablation of canine transmissible venereal tumor (cTVT) in a canine brain model. cTVT fragments grown in severe combined immunodeficient mice were successfully inoculated in the parietal lobe of immunosuppressed, mixed-breed hound dogs. A single dose of near-IR (NIR)–absorbing, 150-nm nanoshells was infused i.v. and allowed time to passively accumulate in the intracranial tumors, which served as a proxy for an orthotopic brain metastasis. The nanoshells accumulated within the intracranial cTVT, suggesting that its neovasculature represented an interruption of the normal blood-brain barrier. Tumors were thermally ablated by percutaneous, optical fiber–delivered, NIR radiation using a 3.5-W average, 3-minute laser dose at 808 nm that selectively elevated the temperature of tumor tissue to 65.8 ± 4.1°C. Identical laser doses applied to normal white and gray matter on the contralateral side of the brain yielded sublethal temperatures of 48.6 ± 1.1°C. The laser dose was designed to minimize thermal damage to normal brain tissue in the absence of nanoshells and compensate for variability in the accumulation of nanoshells in tumor. Postmortem histopathology of treated brain sections showed the effectiveness and selectivity of the nanoshell-assisted thermal ablation. [Cancer Res 2009;69(4):1659–67]
Cross-talk between Tumor and Endothelial Cells Involving the Notch3-Dll4 Interaction Marks Escape from Tumor Dormancy
Authors: Indraccolo Stefano , Minuzzo Sonia , Masiero Massimo , Pusceddu Irene , Persano Luca , Moserle Lidia , Reboldi Andrea , Favaro Elena , Mecarozzi Marco , Di Mario Giuseppina , Screpanti Isabella , Ponzoni Maurilio , Doglioni Claudio , Amadori Alberto
Published: February 2009

The Notch ligand Dll4 has a recognized role during both physiologic and tumor angiogenesis, as it contributes to regulate Notch activity in endothelial cells (EC). The effects of Dll4 on Notch signaling in tumor cells expressing Notch receptors remain, however, largely unknown. Here, we report that escape of human T-cell acute lymphoblastic leukemia (T-ALL) cells or colorectal cancer cells from dormancy is associated with Dll4 expression in the tumor microenvironment and increased Notch3 signaling in tumor cells. Dll4 was expressed at early time points during the angiogenic process, and its expression preceded perfusion of the newly established vessels. Treatment of EC with angiogenic factors induced Dll4 expression and increased Notch3 activation in cocultured T-ALL cells. Neutralization of Dll4 greatly reduced EC-mediated activation of Notch 3 signaling in T-ALL cells and blocked tumorigenesis. Moreover, silencing Notch3 by RNA interference had marked antiproliferative and proapoptotic effects on T-ALL cells in vitro and reduced tumorigenicity in vivo. Our results elucidate a novel mechanism by which a direct interplay between endothelial and tumor cells promotes survival and triggers tumor growth. [Cancer Res 2009;69(4):1314–23]
Recapitulation of Pancreatic Neuroendocrine Tumors in Human Multiple Endocrine Neoplasia Type I Syndrome via Pdx1-Directed Inactivation of Men1
Authors: Shen H.-C. Jennifer , He Mei , Powell Anathea , Adem Asha , Lorang Dominique , Heller Charles , Grover Amelia C. , Ylaya Kris , Hewitt Stephen M. , Marx Stephen J. , Spiegel Allen M. , Libutti Steven K.
Published: February 2009

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal syndrome caused by mutations in the MEN1 tumor suppressor gene. Whereas the protein product of MEN1, menin, is ubiquitously expressed, somatic loss of the remaining wild-type MEN1 allele results in tumors primarily in parathyroid, pituitary, and endocrine pancreas. To understand the endocrine specificity of the MEN1 syndrome, we evaluated biallelic loss of Men1 by inactivating Men1 in pancreatic progenitor cells using the Cre-lox system. Men1 deletion in progenitor cells that differentiate into exocrine and endocrine pancreas did not affect normal pancreas morphogenesis and development. However, mice having homozygous inactivation of the Men1 in pancreas developed endocrine tumors with no exocrine tumor manifestation, recapitulating phenotypes seen in the MEN1 patients. In the absence of menin, the endocrine pancreas showed increase in cell proliferation, vascularity, and abnormal vascular structures; such changes were lacking in exocrine pancreas. Further analysis revealed that these endocrine manifestations were associated with up-regulation in vascular endothelial growth factor expression in both human and mouse MEN1 pancreatic endocrine tumors. Together, these data suggest the presence of cell-specific factors for menin and a permissive endocrine environment for MEN1 tumorigenesis in endocrine pancreas. Based on our analysis, we propose that menin's ability to maintain cellular and microenvironment integrity might explain the endocrine- restrictive nature of the MEN1 syndrome. [Cancer Res 2009;69(5):1858–66]
Targeted Cancer Therapeutics
Authors: Hait William N.
Published: February 2009

Targeted therapies can be defined as drugs developed against a specific target based on its important biological function in cancer. In contrast, nontargeted therapies are drugs identified by phenotypic screening of natural products or chemical libraries against established cancer cell lines or preclinical animal models without a priori knowledge of the target. Targeted therapies are designed to selectively inhibit a target that is abnormal in malignant compared with normal tissues; these drugs often affect proximal events in signaling pathways that drive abnormal growth and have relatively low toxicity. In contrast, nontargeted therapies affect proteins or nucleic acids that may or may not be abnormal in malignant compared with normal tissues; these drugs often target the downstream consequences of activated signaling pathways, e.g., DNA synthesis and microtubule assembly, and are toxic. Whereas targeted therapies are highly effective in selected hematopoietic malignancies, most have shown limited efficacy against complex solid tumors. In contrast, nontargeted drugs include some of the most effective yet most toxic drugs in the oncology pharmacopoeia. In the future, advances in genomics, proteomics, biology, biomarkers, chemistry, and protein engineering will coalesce to accelerate the development of increasingly selective and effective targeted therapies. Understanding the target in context will help identify biomarkers predictive of response. Finally, a detailed understanding of the target's structure and function will help anticipate and identify mechanism of drug resistance and help design drugs and combinations of drugs that retain activity. [Cancer Res 2009;69(4):1263–7]
Anti–Programmed Death-1 Synergizes with Granulocyte Macrophage Colony-Stimulating Factor–Secreting Tumor Cell Immunotherapy Providing Therapeutic Benefit to Mice with Established Tumors
Authors: Li Betty , VanRoey Melinda , Wang Changyu , Chen Tseng-hui Timothy , Korman Alan , Jooss Karin
Published: February 2009

Purpose: The purpose of the present study was to evaluate granulocyte macrophage colony-stimulating factor (GM-CSF)–secreting tumor cell immunotherapy, which is known to stimulate potent and long-lasting antigen-specific immune responses, in combination with PD-1 blockade, which has been shown to augment cellular immune responses.

Experimental Design: Survival studies were done in the B16 melanoma and CT26 colon carcinoma tumor models. Immune monitoring studies were done in the B16 model. GM-CSF–secreting tumor cell immunotherapy was administered s.c. and the anti–PD-1 antibody was administered i.p.

Results: The studies reported here show that combining PD-1 blockade with GM-CSF–secreting tumor cell immunotherapy prolonged the survival of tumor-bearing animals compared with animals treated with either therapy alone. Prolonged survival correlated with strong antigen-specific T-cell responses detected by tetramer staining and an in vivo CTL assay, higher secretion levels of proinflammatory cytokines by splenocytes, and the persistence of functional CD8+ T cells in the tumor microenvironment. Furthermore, in the biweekly multiple treatment setting, repeated antigen-specific T-cell expansion was only observed following administration of the cellular immunotherapy with the PD-1 blockade and not when the cellular immunotherapy or PD-1 blockade was used as monotherapy.

Conclusion: The combination of PD-1 blockade with GM-CSF–secreting tumor cell immunotherapy leads to significantly improved antitumor responses by augmenting the tumor-reactive T-cell responses induced by the cellular immunotherapy. Readministration of the cellular immunotherapy with the anti–PD-1 antibody in subsequent immunotherapy cycles was required to reactivate these T-cell responses.
Inhibition of Akt inhibits growth of glioblastoma and glioblastoma stem-like cells
Authors: Gallia Gary L. , Tyler Betty M. , Hann Christine L. , Siu I-Mei , Giranda Vincent L. , Vescovi Angelo L. , Brem Henry , Riggins Gregory J.
Published: February 2009

A commonly activated signaling cascade in many human malignancies, including glioblastoma multiforme, is the Akt pathway. This pathway can be activated via numerous upstream alterations including genomic amplification of epidermal growth factor receptor, PTEN deletion, or PIK3CA mutations. In this study, we screened phosphatidylinositol 3-kinase/Akt small-molecule inhibitors in an isogenic cell culture system with an activated Akt pathway secondary to a PIK3CA mutation. One small molecule, A-443654, showed the greatest selective inhibition of cells with the mutant phenotype. Based on these findings, this inhibitor was screened in vitro against a panel of glioblastoma multiforme cell lines. All cell lines tested were sensitive to A-443654 with a mean IC50 of ∼150 nmol/L. An analogue of A-443654, methylated at a region that blocks Akt binding, was on average 36-fold less active. Caspase assays and dual flow cytometric analysis showed an apoptotic mechanism of cell death. A-443654 was further tested in a rat intracranial model of glioblastoma multiforme. Animals treated intracranially with polymers containing A-443654 had significantly extended survival compared with control animals; animals survived 79% and 43% longer than controls when A-443654-containing polymers were implanted simultaneously or in a delayed fashion, respectively. This small molecule also inhibited glioblastoma multiforme stem-like cells with similar efficacy compared with traditionally cultured glioblastoma multiforme cell lines. These results suggest that local delivery of an Akt small-molecule inhibitor is effective against experimental intracranial glioma, with no observed resistance to glioblastoma multiforme cells grown in stem cell conditions. [Mol Cancer Ther 2009;8(2):386–93]
Blood flow and Vd (water): both biomarkers required for interpreting the effects of vascular targeting agents on tumor and normal tissue
Authors: Kötz Barbara , West Catharine , Saleem Azeem , Jones Terry , Price Patricia
Published: February 2009

Positron emission tomography studies with oxygen-15–labeled water provide in vivo quantitative tissue perfusion variables—blood flow and fractional volume of distribution of water [Vd (water)]. To investigate the relationship between perfusion variables and the effect of vascular-targeting agents on vasculature, we measured tissue perfusion in tumors, spleen, kidney, and liver before and after treatment with combretastatin-A4-phosphate, a combination of nicotinamide and carbogen (N/C), and interferon (IFN). We observed that mean tumor blood flow and Vd (water) was lower than in kidney, liver, and spleen at baseline. Blood flow and Vd (water) were related in tumor (r = 0.62; P = 0.004) at baseline, but not in other normal tissues evaluated, where minimal variations in Vd (water) were observed over a wide range of blood flow. Despite the relationship between blood flow and Vd (water) in tumors before intervention, vascular-targeting agent–induced changes in these perfusion variables were not correlated. In contrast, changes in blood flow and Vd (water) correlated in kidney and spleen after N/C and in kidney after combretastatin-A4-phosphate. The close relation between blood flow and Vd (water) in tumors but not normal tissue may reflect barriers to fluid exchange in tumors because of necrosis and/or increased interstitial fluid pressure and underlies the importance and interdependence of these positron emission tomography perfusion variables under these conditions. As blood flow and Vd (water) signify different aspects of tissue perfusion, the differential effects of interventions on both variables, flow and Vd (water), should therefore be reported in future studies. [Mol Cancer Ther 2009;8(2):303–9]
Up-Regulation of Connective Tissue Growth Factor in Endothelial Cells by the Microtubule-Destabilizing Agent Combretastatin A-4
Authors: Samarin Jana , Rehm Margot , Krueger Bettina , Waschke Jens , Goppelt-Struebe Margarete
Published: February 2009

Incubation of microvascular endothelial cells with combretastatin A-4 phosphate (CA-4P), a microtubule-destabilizing compound that preferentially targets tumor vessels, altered cell morphology and induced scattering of Golgi stacks. Concomitantly, CA-4P up-regulated connective tissue growth factor (CTGF/CCN2), a pleiotropic factor with antiangiogenic properties. In contrast to the effects of other microtubule-targeting agents such as colchicine or nocodazole, up-regulation of CTGF was only detectable in sparse cells, which were not embedded in a cell monolayer. Furthermore, CA-4P induced CTGF expression in endothelial cells, forming tube-like structures on basement membrane gels. Up-regulation of CTGF by CA-4P was dependent on Rho kinase signaling and was increased when p42/44 mitogen-activated protein kinase was inhibited. Additionally, FoxO transcription factors were identified as potent regulators of CTGF expression in endothelial cells. Activation of FoxO transcription factors by inhibition of phosphatidylinositol 3-kinase/AKT signaling resulted in a synergistic increase in CA-4P-mediated CTGF induction. CA-4P-mediated expression of CTGF was thus potentiated by the inhibition of kinase pathways, which are targets of novel antineoplastic drugs. Up-regulation of CTGF by low concentrations of CA-4P may thus occur in newly formed tumor vessels and contribute to the microvessel destabilization and antiangiogenic effects of CA-4P observed in vivo. (Mol Cancer Res 2009;7(2):180–8)
Digoxin Therapy Does Not Improve Outcomes in Patients With Advanced Heart Failure on Contemporary Medical Therapy
Authors: Georgiopoulou Vasiliki V. , Kalogeropoulos Andreas P. , Giamouzis Grigorios , Agha Syed A. , Rashad Mohammad A. , Waheed Sana , Laskar Sonjoy , Smith Andrew L. , Butler Javed
Published: February 2009

Background—

The impact of digoxin on outcomes of patients with advanced heart failure (HF) receiving optimal contemporary therapy is not known.

Methods and Results—

We retrospectively reviewed data of 455 advanced HF patients referred for transplant evaluation (age, 52�12 years; ejection fraction, 18.3�8%); 227 (49.9%) were on digoxin at baseline. Primary outcome was death (n=101), urgent transplantation (n=14), or ventricular assist device implantation (n=4); secondary outcomes included HF and all-cause hospitalizations. Digoxin use was evaluated (1) in the original cohort; (2) in a propensity score–matched subset (n=322); (3) as a time-dependent covariate; and (4) after adjustment for Seattle Heart Failure Score. Patients were on optimal therapy: angiotensin-II modulation, 92.5%; β-blockers, 91.2%; aldosterone antagonists, 45.6%; and devices, 71.0%. After a median of 27 months, 83 of 277 (36.6%) patients treated with digoxin versus 36 of 228 (15.8%) patients without digoxin met primary outcome (hazard ratio [HR], 2.28; 95% CI, 1.51 to 3.43;
P
<0.001). This risk persisted in the matched subset (HR, 1.73; 95% CI, 1.09 to 2.75;
P
=0.021) and with time-varying digoxin use (HR, 2.05; 95% CI, 1.23 to 3.41;
P
=0.011). Digoxin was associated with higher risk among patients in sinus rhythm compared with atrial fibrillation. Digoxin was not associated with improvement in either all-cause or HF hospitalization rates. These results were similar across sex and race and when adjusted for Seattle Heart Failure Score and renal function.

Conclusion—

This study suggests that digoxin therapy may be of no benefit in patients with advanced HF referred for cardiac transplantation who received optimal medical therapy. Treatment with digoxin should be used cautiously in such patients because of risk for adverse outcomes.
Determining the Preferred Percent-Predicted Equation for Peak Oxygen Consumption in Patients With Heart Failure
Authors: Arena Ross , Myers Jonathan , Abella Joshua , Pinkstaff Sherry , Brubaker Peter , Moore Brian , Kitzman Dalane , Peberdy Mary Ann , Bensimhon Daniel , Chase Paul , Forman Daniel , West Erin , Guazzi Marco
Published: February 2009

Background—

Peak oxygen consumption (V
o
2
) is routinely assessed in patients with heart failure undergoing cardiopulmonary exercise testing. The purpose of the present investigation was to determine the prognostic ability of several established peak V
o
2
prediction equations in a large heart failure cohort.

Methods and Results—

One thousand one hundred sixty-five subjects (70% males; age, 57.0�13.8 years; ischemic etiology, 43%) diagnosed with heart failure underwent cardiopulmonary exercise testing. Percent-predicted peak V
o
2
was calculated according to normative values proposed by Wasserman and Hansen (equation), Jones et al (equation), the Cooper Clinic (below low fitness threshold), a Veteran’s Administration male referral data set (4 equations), and the St James Take Heart Project for women (equation). The prognostic significance of percent-predicted V
o
2
values derived from the 2 latter, sex-specific equations were assessed collectively. There were 179 major cardiac events (117 deaths, 44 heart transplantations, and 18 left ventricular assist device implantations) during the 2-year tracking period (annual event rate, 10%). Measured peak V
o
2
and all percent-predicted peak V
o
2
calculations were significant univariate predictors of adverse events (χ
2
≥31.9,
P
<0.001) and added prognostic value to ventilatory efficiency (VE/V
co
2
slope), the strongest cardiopulmonary exercise testing predictor of adverse events (χ
2
=150.7,
P
<0.001), in a multivariate regression. The Wasserman/Hansen prediction equation provided optimal prognostic information.

Conclusions—

Actual peak V
o
2
and the percent-predicted models included in this analysis all were significant predictors of adverse events. It seems that the percent-predicted peak V
o
2
value derived from the Wasserman/Hansen equations may outperform other expressions of this cardiopulmonary exercise testing variable.
Cardiovascular Risk Factors and Atherosclerosis in Young Women
Authors: Knoflach Michael , Kiechl Stefan , Penz Daniela , Zangerle Alexandra , Schmidauer Christoph , Rossmann Andrea , Shingh Mahavir , Spallek Ralf , Griesmacher Andrea , Bernhard David , Robatscher Peter , Buchberger Waltraud , Draxl Walter , Willeit Johann , Wick Georg
Published: February 2009

Background and Purpose—

Little research has been conducted into risk factors of atherosclerosis development in young women.

Methods—

This cross-sectional study enrolled 205 18- to 22-year-old female students from the Educational Centre for Allied Health Professions. A broad array of risk conditions and lifestyle behaviors was carefully assessed. Intima media thickness (IMT) was used as a well-established surrogate for atherosclerosis and a predictor of vascular risk. High IMT was defined as levels exceeding the 90th percentile in the common and/or internal carotid arteries.

Results—

In multivariable logistic regression analysis, systolic blood pressure, family history for hypertension, lipoprotein(a), homocysteine, T-cell immune reaction against human heat shock protein 60, and exposure to environmental tobacco smoke and exhaust gases emerged as independent predictors of high IMT. Obesity, metabolic syndrome, and classical risk factors other than high blood pressure were rare and unrelated to IMT. Findings were similar once focusing on IMT as a continuous variable.

Conclusion—

In female youngsters displaying initiating stages of vascular pathology, blood pressure level and numerous nontraditional risk conditions showed a significant relation to high IMT. Our study indicates that (auto)immune processes, high lipoprotein(a), and environmental exposure to tobacco smoke and traffic exhaust may play a role in early atherogenesis.
Sex Differences in Stroke Epidemiology
Authors: Appelros Peter , Stegmayr Birgitta , Terént Andreas
Published: February 2009

Background and Purpose—

Epidemiological studies, mainly based on Western European surveys, have shown that stroke is more common in men than in women. In recent years, sex-specific data on stroke incidence, prevalence, subtypes, severity and case-fatality have become available from other parts of the world. The purpose of this article is to give a worldwide review on sex differences in stroke epidemiology.

Methods—

We searched PubMed, tables-of-contents, review articles, and reference lists for community-based studies including information on sex differences. In some areas, such as secular trends, ischemic subtypes and stroke severity, noncommunity-based studies were also reviewed. Male/female ratios were calculated.

Results—

We found 98 articles that contained relevant sex-specific information, including 59 incidence studies from 19 countries and 5 continents. The mean age at first-ever stroke was 68.6 years among men, and 72.9 years among women. Male stroke incidence rate was 33% higher and stroke prevalence was 41% higher than the female, with large variations between age bands and between populations. The incidence rates of brain infarction and intracerebral hemorrhage were higher among men, whereas the rate of subarachnoidal hemorrhage was higher among women, although this difference was not statistically significant. Stroke tended to be more severe in women, with a 1-month case fatality of 24.7% compared with 19.7% for men.

Conclusions—

Worldwide, stroke is more common among men, but women are more severely ill. The mismatch between the sexes is larger than previously described.
Quality of Care in Women With Ischemic Stroke in the GWTG Program
Authors: Reeves Mathew J. , Fonarow Gregg C. , Zhao Xin , Smith Eric E. , Schwamm Lee H.
Published: February 2009

Background and Purpose—

Prior studies have suggested worse poststroke outcomes in women. We sought to examine sex differences in quality of care (QOC) in the Get With The Guidelines-Stroke (GWTG-Stroke) program.

Methods—

We analyzed the relationships between sex and QOC as well as outcomes (in-hospital mortality and discharge home) using multivariable logistic regression models in 383 318 acute ischemic stroke admissions from 1139 hospitals that participated in the GWTG-Stroke program between 2003 to 2008. QOC was measured using 7 predefined performance measures and a defect-free care summary measure (defined as the proportion of patients who received all eligible interventions).

Results—

Compared to men, women were older and more likely to present by ambulance. They were also more likely to have a past medical history of atrial fibrillation or hypertension, and less likely to have a history of heart disease, dyslipidemia, or smoking. Although sex differences in individual performance measures were relatively modest they consistently identified women as being less likely to receive care compared to men. Overall, women received less defect-free care than men (66.3% versus 71.1%, adjusted odds ratio [aOR]=0.86; 95% confidence interval [CI] 0.85 to 0.87) and were less likely to be discharged home (41.0% versus 49.5%, aOR=0.84, 95% CI 0.83 to 0.85). Although crude mortality was higher in women (6.0% versus 5.2%), this difference was eliminated after risk adjustment (aOR=1.03, 95% CI 0.99 to 1.06).

Conclusions—

Quality of care for women with ischemic stroke was lower than that for men, and women were less likely to be discharged home. Further study is warranted to identify the causes and consequences of these sex-based differences in care.
Annual dynamics of sperm production and storage in the Mediterranean Gecko, Hemidactylus turcicus, in the southeastern United States
Authors: Eckstut Mallory E. , Lemons Erica Rottmann , Sever David M.
Published: February 2009

The Mediterranean Gecko, Hemidactylus turcicus, is an invasive species found
in warmer regions throughout the world, including the southern United
States. In Louisiana, H. turcicus appears to be free of competition and has
been rapidly expanding its range in the past several decades. However, in
Florida and Texas, H. turcicus is heavily out-competed by closely related
competitors that do not occur in Louisiana, including H. frenatus, of which
a substantial amount of reproductive morphology and ecology is known.
Although the reproductive cycle of H. turcicus has been studied in Florida
and Louisiana, little is known about the seasonal variation of their oviduct
and if they are capable of storing sperm, which can have substantial
implications for reproductive competition. We analysed sperm production,
storage and seasonal variation in the testes and oviducts of H. turcicus
using light and electron microscopy. Previous studies found that female H.
frenatus store sperm in the uterine-infundibular region for up to 36 weeks,
and that their oviducts are active year-round. In H. turcicus, we found that
sperm are stored in the uterine-infundibular region of the oviduct, and
sperm are stored from May through August. Hemidactylus turcicus has one
breeding season per year, producing three to four clutches between May and
August, but between September and February minimal activity occurs in the
oviduct. Additionally, male H. turcicus are producing sperm throughout the
entire reproductive season, but whether females utilize stored sperm to
fertilize eggs or if they mate continually throughout the spring and summer
is unknown.
Variation of body size, age structure and growth of a temperate frog, Rana chensinensis, over an elevational gradient in Northern China
Authors: Ma Xiaoyan , Tong Lina , Lu Xin
Published: February 2009

Identifying the patterns of body size, age and growth in relation to
environments may help us to understand the evolution of life history of
organisms. This study compared the variability in these demographic traits
of a temperate frog, Rana chensinensis, among populations from Northern
China located at three elevations (567, 1470 and 1700 m) with distinct mean
annual temperature (12.1, 5.8 and 3.9°C). Overall, frogs from higher
elevations tended to be larger in body size, partially because despite
shorter growing seasons, they lived longer as a result of delayed maturity.
However, discordance with the expected cline was detected between
neighboring populations and the variation was sex specific. Adult females
became significantly older and larger as elevation varied from 567 m to 1470
m, but the two traits no longer increased with an elevational shift from
1470 m to 1700 m. Adult males at 1470 m were similar in age and size to
animals at 567 m but significantly younger and smaller than those at 1700 m.
This suggested that sexes could be exposed to different pressures along
elevation gradients with females being stronger than males in life history
responses to the elevation-induced environmental change. We also showed that
factors other than age also contributed to size differences both among
populations and between the sexes.
Mitochondrial phylogeography of Testudo graeca in the Western Mediterranean: Old complex divergence in North Africa and recent arrival in Europe
Authors: Fritz Uwe , Harris D. James , Fahd Soumia , Rouag Rachid , Graciá Martínez Eva , Giménez Casalduero Andrés , Široký Pavel , Kalboussi Mohsen , Jdeidi Tarek B. , Hundsdörfer Anna K.
Published: February 2009

We investigated the mitochondrial phylogeography of spur-thighed tortoises
(Testudo graeca) in the Western Mediterranean. In North Africa, four major
lineages (A-D) occur that together constitute a well-supported clade
corresponding to one of the six major clades within T. graeca; the North
African clade is sister to a Caucasian clade representing the subspecies T.
g. armeniaca. Phylogenetic relationships between the North African lineages
are badly resolved. Lineage A is distributed in Tunisia and adjacent
Algeria, lineage B in Algeria and northern Morocco, lineage C in the Libyan
Cyrenaica Peninsula, and lineage D north of the High Atlas Mts. and in the
Souss Valley (southern Morocco). Lineage B is subdivided into two subgroups,
B1 (eastern Morocco and Algeria) and B2 (north-western Morocco). Italian
tortoises harbour haplotypes of lineage A, Spanish tortoises of subgroup B1.
Based on a relaxed molecular clock calibrated with fossil evidence, the six
major mtDNA clades of T. graeca are estimated to have diverged approximately
4.2-1.8 Ma ago; the split between the clades representing the eastern
subspecies T. g. ibera and T. g. terrestris is younger than the split
between Western Mediterranean tortoises and T. g. armeniaca. The Western
Mediterranean lineages A-D were dated to have diverged at least 1.4-1.1 Ma
ago; B1 and B2 split approximately 0.7 Ma ago. Our results suggest that
Italian and Spanish tortoises were either introduced or originated from
trans-oceanic dispersal in historic or prehistoric times. Spur-thighed
tortoises invaded North Africa probably across Near Eastern landbridges that
emerged in the Late Tertiary. Their diversification in North Africa seems to
be correlated with habitat aridization cycles during the Pleistocene. The
ranges of the Western Mediterranean lineages largely correspond to the
distribution of morphologically defined subspecies in North Africa, with
exception of T. g. graeca and T. g. whitei, and of T. g. lamberti and T. g.
marokkensis, which are not differentiated. We propose to lump the first two
subspecies under the name of T. g. graeca and the latter under the name of
T. g. marokkensis. The complex differentiation of spur-thighed tortoises in
North Africa implies that the model of a bipartite east-west
differentiation, as proposed for other Maghrebian amphibians and reptiles,
may be too simplistic, reflecting incomplete locality sampling rather than
actual phylogeographic differentiation.
Measuring species diversity to determine land-use effects on reptile and amphibian assemblages
Authors: Hutchens Stan , DePerno Christopher
Published: February 2009

Populations of herpetofauna are declining globally primarily due to land-use practices (e.g., silviculture or conversion to agriculture) and declines require monitoring of all herpetofauna communities. Therefore, forest management plans for Bull Neck Swamp, a pocosin wetland in North Carolina, USA, initiated an inventory of the herpetofauna community. Our objectives were to: (1) derive diversity measures for four designated habitat preserves (i.e., Atlantic whitecedar [Chamaecyparis thyoides], Pond pine [Pinus serotina], Non-riverine Swamp, and Shoreline/Islands) and a Forest manageable area, (2) determine if there were benefits to habitat preserves for the herpetofauna community, and (3) provide recommendations for future monitoring. We employed 11 different sampling techniques across the four habitat preserves and Forest manageable area. Species richness estimates and similarity indices were derived using EstimateS 8.0. For post hoc comparisons, we derived species distributions with the Nestedness Temperature Calculator Program. Observed species richness ranged from 7 to 32 species (S = 13 to 44) and abundances ranged from 99 to 873 individuals. Similarity indices suggested species compositions were similar among habitats. Further, nestedness temperature (T = 12.6°C) indicated an even species distribution among assemblages. Comparable similarity indices among habitats, an even species distribution, and habitat continuity suggested management practices would have little impact on the herpetofauna community. Nevertheless, future management practices should be carefully considered and planned to mitigate effects to individual species. We recommend studies employ species richness, relative abundance, species composition, and distribution as conservation tools when inventorying or monitoring herpetofauna communities.
Genetic differentiation in two European tree frog (Hyla arborea) metapopulations in contrasted landscapes of western Switzerland
Authors: Dubey Sylvain , Ursenbacher Sylvain , Pellet Jérôme , Fumagalli Luca
Published: February 2009

The survival of threatened species as the European tree frog (Hyla arborea)
is strongly dependent on the genetic variability within populations, as well
as gene flow between them. In Switzerland, only two sectors in its western
part still harbour metapopulations. The first is characterised by a very
heterogeneous and urbanized landscape, while the second is characterised by
a uninterrupted array of suitable habitats. In this study, six
microsatellite loci were used to establish levels of genetic differentiation
among the populations from the two different locations. The results show
that the metapopulations have: (i) weak levels of genetic differentiation
(FST within metapopulation ≈ 0.04), (ii) no difference in levels of genetic
structuring between them, (iii) significant (p = 0.019) differences in terms
of genetic diversity (Hs) and observed heterozygozity (Ho), the
metapopulation located in a disturbed landscape showing lower values. Our
results suggest that even if the dispersal of H. arborea among contiguous
ponds seems to be efficient in areas of heterogeneous landscape, a loss of
genetic diversity can occur.
Body temperature, size, nuptial colouration and mating success in male Moor Frogs (Rana arvalis)
Authors: Hettyey Attila , Herczeg Gábor , Laurila Anssi , Crochet Pierre-André , Merilä Juha
Published: February 2009

Variation in colouration has rarely been related to sexual selection in
anuran amphibians, even though such a relationship has been proven for many
other vertebrate taxa. Male and female Moor Frogs (Rana arvalis) have a
cryptic brown colour pattern, but males develop a conspicuous blue nuptial
colouration during the reproductive season. To investigate the possibility
that colouration plays a role in sexual selection in this species, we
studied the temporal variation in blue colouration, determined if body size
or body temperature affected blueness and investigated if blueness of males
could be related to their mating success. Results confirmed previous
observations that males develop and maintain blue colouration for only a
very few nights during peak reproductive activity. Colouration of males was
unrelated to body size, but males exhibiting higher body temperatures were
somewhat bluer than males with lower body temperatures. Further, males in
amplexus had higher body temperatures than non-mated males. Finally, mating
success was positively related to blueness in small males, whereas in large
males no such relationship was detected. While our results align with the
hypothesis that the bright blue colouration of males may be a target of
sexual selection, alternative explanations are also discussed.
The complete mitochondrial DNA genome of Eremias brenchleyi (Reptilia: Lacertidae) and its phylogeny position within squamata reptiles
Authors: Rui Jinlong , Wang Yuting , Nie Liuwang
Published: February 2009

Squamata is the most diversified reptilian order that has been traditionally
classified into three suborders – Lacertilia, Serpentes and Amphisbaenia in
which Lacertilia have about 16-19 families. But the phylogenetic
relationships among major groups of Lacertilia remain controversial. In this
paper, the complete mitochondrial DNA sequence of Eremias brenchleyi was
determined by using long-and-accurate PCR (LA-PCR). The mtDNA sequence is 19
542 bp, making it the longest mitochondrial genome in squamates species
reported so far. It shows the typical vertebrate arrangement of genes. The
control region of E. brenchleyi was characterized by two conspicuous 65 bp
and 56 bp tandem repeats at its 5′ and 3′ terminus respectively. In order to
study the higher level relationships of squamates, the phylogenetic study
including all currently available squamates mitochondrial sequences was
carried out. We obtained a relationship of 16 families of lizards
(Lacertidae, Scincidae, Iguanidae, Chameleonidae, Agamidae, Trogonophidae,
Bipedidae, Shinisauridae, Helodermatidae, Amphisbaenidae, Gekkonidae,
Varanidae, Anguidae, Xantusiidae, Rhineuridae, Cordylidae) and 8 families of
Serpentes. The internal relationships within this group yielded high
bootstrap support and were more congruent with morphological analyses.
The relationship between immunocompetence during winter and subsequent reproductive decisions and survival in the Great Tit
Authors: Snoeijs Tinne , Adriaensen Frank , Pinxten Rianne , Matthysen Erik , Eens Marcel
Published: February 2009

The typical costs associated with parasitism have led to the suggestion that immunosuppression in the host may be an important mechanism mediating the life history cost of reproduction, defined as a decrease in residual reproductive value as a consequence of parental effort. More immunocompetent individuals have therefore been predicted to reveal higher fitness through more optimal reproductive decisions and increased survival. In this study, we simulated a challenge to the immune system of male and female great tits (Parus major) by injecting a novel but harmless antigen, sheep red blood cells (SRBC), and related the elicited immune response to (long-term) survival and reproductive traits, relevant to the determination of lifetime reproductive success in this species. In females, we could not detect any relationships between humoral immunocompetence and laying date, clutch size, or mean fledging mass during the breeding season following the winter period during which we assessed the immune response. Furthermore, immune response to SRBC did not predict survival of male and female great tits until the following breeding season as well as until the breeding season the year after. Overall, humoral immunological quality measured during winter did not predict important fitness components in great tits.
A phylogenetic perspective on absence and presence of a sex-limited polymorphism
Authors: Van Gossum Hans , Mattern Michelle.
Published: February 2009

Sex-limited polymorphism is widely distributed among animal taxa, but has only rarely been studied from a macro-evolutionary perspective. We investigate the evolution of female-limited polymorphism by mapping presence or absence of multiple discrete morphs on published phylogenetic trees for North American representatives of two damselfly genera. The results indicate that female polymorphy represents the ancestral condition based on the species included with subsequent loss and monomorphy representing the evolutionary end-point in most cases. According to one phylogeny, character optimization suggests that expression of the polymorphism may be lost (to a state of monomorphy) and gained again (back to polymorphy). Earlier work indicated that changes from polymorphy to monomorphy might be coupled with evolution of the mating system from polyandry to monandry. The results presented here, however, do not convincingly support such view.