bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparing a disease-specific and a generic health-related quality of life instrument in subjects with asthma from the general population
Authors: Puhan Milo A , Gaspoz Jean-Michel , Bridevaux Pierre-Olivier , Schindler Christian , Ackermann-Liebrich Ursula , Rochat Thierry , Gerbase Margaret W
Published: February 2008

Background

Few epidemiologic studies have assessed health-related quality of life (HRQL) of asthma patients from a general population and it is unclear which instrument is best suitable for this purpose. We investigated the validity of the Asthma Quality of Life Questionnaire (AQLQ) and the SF-36 completed by individuals with asthma from the population-based SAPALDIA (Swiss study on air pollution and lung diseases in adults) cohort.

Methods

The study included 258 participants with a physician-diagnosed asthma who had completed the AQLQ and SF-36. We assessed floor and ceiling effects, internal consistency reliability and cross-sectional validity witha priorihypotheses that correlations between the specific HRQL domains (e.g. "symptoms" or "physical functioning") and the corresponding external validation measures (respiratory symptoms, need for doctor visits, limitation in activities due to asthma and lung function) would capture similar aspects and be correlated moderately (≥ 0.3) to strongly (≥ 0.5), whereas non-corresponding domains be correlated weakly with each other (<0.3).

Results

The AQLQ showed pronounced ceiling effects with all median domain scores above 6 (scores varied from 1–7). For the SF-36, ceiling effects were present in 5 out of 8 domains. Cronbach's alpha was >0.7 for all AQLQ and SF-36 domains. Correlations between the AQLQ domains "respiratory symptoms", "activity limitation" and "environmental exposure", and the validation measures ranged from 0.29–0.57. Correlations between the "emotional function" domain and the validation measures were also in this range (0.31–0.55) and not as low as we hypothesized. For the SF-36, correlations between "physical functioning" and "role physical", and the validation measures ranged from 0.25–0.56, whereas "role emotional" and "mental health" correlated with these measures from 0.01–0.23.

Conclusion

The AQLQ and the SF-36 showed fairly good internal consistency. Both instruments are limited by ceiling effects, but they appear less pronounced in the SF-36, which also shows a better discrimination between different aspects of HRQL. The SF-36 may therefore be a more valid measure of HRQL than the AQLQ when applied to individuals with asthma from the general population.
Epstein-Barr virus latent membrane protein-1 (LMP-1) 30-bp deletion and Xho I-loss is associated with type III nasopharyngeal carcinoma in Malaysia
Authors: See Hui Shien , Yap Yoke Yeow , Yip Wai Kien , Seow Heng Fong
Published: February 2008

Background

Nasopharyngeal carcinoma (NPC) is a human epithelial tumour with high prevalence amongst Chinese in Southern China and South East Asia and is associated with the Epstein-Barr virus (EBV). The viral genome harbours an oncogene, namely, the latent membrane protein 1 (LMP1) gene and known variants such as the 30-bp deletion and loss of Xho I restriction site have been found. Less is known about the relationship between these variants and the population characteristics and histological type.

Methods

In this study, the EBV LMP1 gene variants from 42 NPC and 10 non-malignant archived formalin fixed, paraffin-embedded tissues, as well as plasma from another 35 patients with nasopharyngeal carcinoma were determined by using Polymerase Chain Reaction (PCR). Statistical analysis was performed by using SPSS programme.

Results

LMP1 30-bp deletion was detected in 19/34 (55.9%) of NPC tissues, 7/29 (24.1%) of plasma but absent in non-malignant tissues (8/8). Coexistence of variants with and without 30bp deletion was found only in 5/29 (17.2%) plasma samples but not in NPC tissues. The loss of Xho I restriction site in LMP1 gene was found in 34/39 (87.2%) of the NPC tissues and 11/30 (36.7%) of plasma samples. None of the non-malignant nasopharyngeal tissues (8/8) harbour Xho I-loss variants. LMP1 30-bp deletion was detected in 16/18 Chinese versus 3/15 Malays and 13/16 type III (undifferentiated carcinoma) versus 1/6 type I (keratinizing squamous cell carcinoma). Xho I-loss was found in 19/19 Chinese versus 14/19 Malays and 18/18 type III (undifferentiated) versus 2/5 type I (keratinizing squamous cell carcinoma). Statistical analysis showed that these variants were associated with ethnic race (30-bp deletion, p < 0.05; Xho I-loss, p = 0.046) and histological type of NPC (30-bp deletion, p = 0.011; Xho I-loss, p = 0.006). Nineteen out of 32 NPC tissues (19/32; 59.4%) and 6/24 (25%) of plasma samples showed the coexistence of both the 30-bp deletion and the loss of Xho I restriction site. A significant relationship was found with the Chinese race but not histological type.

Conclusion

The incidence rate of 56% for LMP1 30-bp deletion was lower compared to previously reported rates of 75–100% in NPC tissues. Coexistence of variants with and without 30-bp deletion was found only in 5/29 plasma samples. The incidence rate of Xho I restriction site loss in NPC was comparable to other studies from endemic regions such as Southern China. For the first time, the presence of LMP1 30-bp deletion or Xho I-loss was associated with the Chinese race and type III NPC. Both these variants were not found in non-malignant tissues. The influence of these variants on disease progression and outcome in Chinese and type III NPC requires further investigation.
A case of virilization induced by a Krukenberg tumor from gastric cancer
Authors: Hornung Matthias , Vogel Peter , Schubert Thomas , Schlitt Hans-Jürgen , Bolder Ulrich
Published: February 2008

Background

The Krukenberg tumor represents ovarian metastases associated with gastric cancer or other gastrointestinal malignancies. Histology shows typical mucus-production and numerous signet-ring cells. Occasionally Krukenberg tumors have endocrine function and, as a consequence, some patients demonstrate hirsutism and virilization.

Case presentation

Here we report a case of virilization associated with an extensive gastric adenocarcinoma and Krukenberg tumor in a premenopausal woman. Virilization occurred three months after diagnosis of gastric cancer and the ovarian tumors. Palliative chemotherapy was initiated as primary therapy, but gastric outlet obstruction required a gastrojejunostomy. In addition, oopherectomy was performed to relieve abdominal tension and to abate hormonal effects. It is likely that virilization of the patient could have been prevented by earlier oopherectomy prior to development of hormone production.

Conclusion

Despite the limitation in survival time early oopherectomy should be considered to prevent the development of virilization even in palliative situations if a Krukenberg tumor is diagnosed with gastric cancer.
Prevention of airway inflammation with topical cream containing imiquimod and small interfering RNA for natriuretic peptide receptor
Authors: Wang Xiaoqin , Xu Weidong , Mohapatra Subhra , Kong Xiaoyuan , Li Xu , Lockey Richard F , Mohapatra Shyam S
Published: February 2008

Background

Asthma is a complex disease, characterized by reversible airway obstruction, hyperresponsiveness and chronic inflammation. Principle pharmacologic treatments for asthma include bronchodilating beta2-agonists and anti-inflammatory glucocorticosteroids; but these agents do not target the main cause of the disease, the generation of pathogenic Th2 cells. We previously reported reduction in allergic inflammation in mice deficient in the ANP receptor NPRA. Here we determined whether siRNA for natriuretic peptide receptor A (siNPRA) protected against asthma when administered transdermally.

Methods

Imiquimod cream mixed with chitosan nanoparticles containing either siRNA green indicator (siGLO) or siNPRA was applied to the skin of mice. Delivery of siGLO was confirmed by fluorescence microscopy. The anti-inflammatory activity of transdermal siNPRA was tested in OVA-sensitized mice by measuring airway hyperresponsiveness, eosinophilia, lung histopathology and pro-inflammatory cytokines.

Results

SiGLO appearing in the lung proved the feasibility of transdermal delivery. In a mouse asthma model, BALB/c mice treated with imiquimod cream containing siNPRA chitosan nanoparticles showed significantly reduced airway hyperresponsiveness, eosinophilia, lung histopathology and pro-inflammatory cytokines IL-4 and IL-5 in lung homogenates compared to controls.

Conclusion

These results demonstrate that topical cream containing imiquimod and siNPRA nanoparticles exerts an anti-inflammatory effect and may provide a new and simple therapy for asthma.
Prostate-specific antigen at or before age 50 as a predictor of advanced prostate cancer diagnosed up to 25 years later: A case-control study
Authors: Ulmert David , Cronin Angel M , Björk Thomas , O'Brien Matthew F , Scardino Peter T , Eastham James A , Becker Charlotte , Berglund Göran , Vickers Andrew J , Lilja Hans
Published: February 2008

Background

Based on a large, representative unscreened cohort from Malmö, Sweden, we have recently reported that a single prostate-specific antigen (PSA) measurement at or before age 50 is a strong predictor of prostate cancer occurring up to 25 years subsequently. We aimed to determine whether this association holds for advanced cancers, defined as clinical stage T3 or higher, or skeletal metastasis at the time of the cancer diagnosis.

Methods

In 1974–1986 blood samples were obtained from a cohort of 21,277 men aged up to 50. Through 1999, 498 men were diagnosed with prostate cancer, and of these 161 had locally advanced or metastatic prostate cancers. Three controls, matched for age and date of venipuncture, were selected for each case. Conditional logistic regression was used to test associations between molecular markers and advanced cancer.

Results

Median time from venipuncture to diagnosis was 17 years. Levels of all PSA forms and hK2 were associated with case status. Total PSA was a strong and statistically significant predictor of subsequent advanced cancer (area under the curve 0.791; p < 0.0005). Two-thirds of the advanced cancer cases occurred in men with the top 20% of PSA levels (0.9 ng/ml or higher).

Conclusion

A single PSA test taken at or before age 50 is a very strong predictor of advanced prostate cancer diagnosed up to 25 years later. This suggests the possibility of using an early PSA test to risk-stratify patients so that men at highest risk are the focus of the most intensive screening efforts.
Leiomyosarcoma of the skin with osteoclast-like giant cells: a case report
Authors: Sarma Deba P , Santos Eric E , Wang Bo
Published: February 2008

Introduction

Osteoclast-like giant cells have been noted in various malignant tumors, such as, carcinomas of pancreas and liver and leiomyosarcomas of non-cutaneous locations, such as, uterus and rectum. We were unable to find any reported case of a leiomyosarcoma of the skin where osteoclast-like giant cells were present in the tumor.

Case presentation

We report a case of a 59-year-old woman with a cutaneous leiomyosarcoma associated with osteoclast-like giant cells arising from the subcutaneous artery of the leg. The nature of the giant cells is discussed in light of the findings from the immunostaining as well as survey of the literature.

Conclusion

A rare case of cutaneous leiomyosarcoma with osteoclast-like giant cells is reported. The giant cells in the tumor appear to be reactive histiocytic cells.
Functional protein divergence in the evolution of Homo sapiens
Authors: Lopez-Bigas Nuria , De Subhajyoti , Teichmann Sarah A
Published: February 2008

Background

Protein-coding regions in a genome evolve by sequence divergence and gene gain and loss, altering the gene content of the organism. However, it is not well understood how this has given rise to the enormous diversity of metazoa present today.

Results

To obtain a global view of human genomic evolution, we quantify the divergence of proteins by functional category at different evolutionary distances from human.

Conclusion

This analysis highlights some general systems-level characteristics of human evolution: regulatory processes, such as signal transducers, transcription factors and receptors, have a high degree of plasticity, while core processes, such as metabolism, transport and protein synthesis, are largely conserved. Additionally, this study reveals a dynamic picture of selective forces at short, medium and long evolutionary timescales. Certain functional categories, such as 'development' and 'organogenesis', exhibit temporal patterns of sequence divergence in eukaryotes relative to human. This framework for a grammar of human evolution supports previously postulated theories of robustness and evolvability.
Ancora: a web resource for exploring highly conserved noncoding elements and their association with developmental regulatory genes
Authors: Engström Pär G , Fredman David , Lenhard Boris
Published: February 2008

Metazoan genomes contain arrays of highly conserved noncoding elements (HCNEs) that span developmental regulatory genes and define regulatory domains. We describe Ancora http://ancora.genereg.net, a web resource that provides data and tools for exploring genomic organization of HCNEs for multiple genomes. Ancora includes a genome browser that shows HCNE locations and features novel HCNE density plots as a powerful tool to discover developmental regulatory genes and distinguish their regulatory elements and domains.
Multistep regulation of telomerase during differentiation of HL60 cells
Authors: Yamada Osamu , Ozaki Kohji , Nakatake Mayuka , Akiyama Masaharu , Kawauchi Kiyotaka , Matsuoka Rumiko
Published: February 2008

Using three different differentiation agents (1α, 25 dihydroxyvitamin D3, all-trans-retinoic acid, and Am80), down-regulation of telomerase activity was found to be a common response during the monocytic or granulocytic differentiation of human acute myeloblastic leukemia cell line 60 (HL60) cells. Rapid down-regulation of telomerase transcription occurred during early differentiation of HL60 cells prior to G1 arrest. Akt kinase activity was suppressed after 6 h of differentiation along with inhibition of telomerase activity, and the extent of the suppression that occurred while maintaining telomerase protein expression suggested the post-translational regulation of telomerase activity. Recombinant Akt dose-dependently increased telomerase activity, and telomerase was inhibited at the transcriptional and post-translational levels by LY294002, suggesting that PI-3K/Akt is one of the key signaling proteins involved in telomerase regulation. Each of the three differentiation agents caused a significant increase of signaling proteins (including Akt) at 3 days after the initiation of differentiation. Changes of acetyl-histone H4, which regulates transcription of the telomerase gene, were observed before the activation of Akt. This finding suggests that epigenetic control of telomerase transcription occurs before activation of Akt during the late stage of differentiation. These results indicate that telomerase activity is regulated by at least two mechanisms during granulocytic and monocytic differentiation, with one mechanism being transcriptional and the other being post-translational.
Gender-Specific Changes in Bone Turnover and Skeletal Architecture in Igfbp-2-Null Mice
Authors: DeMambro V. E. , Clemmons D. R. , Horton L. G. , Bouxsein M. L. , Wood T. L. , Beamer W. G. , Canalis E. , Rosen C. J.
Published: February 2008

IGF-binding protein-2 (IGFBP-2) is a 36-kDa protein that binds to the IGFs with high affinity. To determine its role in bone turnover, we compared Igfbp2−/− mice with Igfbp2+/+ colony controls. Igfbp2−/− males had shorter femurs and were heavier than controls but were not insulin resistant. Serum IGF-I levels in Igfbp2−/− mice were 10% higher than Igfbp2+/+ controls at 8 wk of age; in males, this was accompanied by a 3-fold increase in hepatic Igfbp3 and Igfbp5 mRNA transcripts compared with Igfbp2+/+ controls. The skeletal phenotype of the Igfbp2−/− mice was gender and compartment specific; Igfbp2−/− females had increased cortical thickness with a greater periosteal circumference compared with controls, whereas male Igfbp2−/− males had reduced cortical bone area and a 20% reduction in the trabecular bone volume fraction due to thinner trabeculae than Igfbp2+/+ controls. Serum osteocalcin levels were reduced by nearly 40% in Igfbp2−/− males, and in vitro, both CFU-ALP+ preosteoblasts, and tartrate-resistant acid phosphatase-positive osteoclasts were significantly less abundant than in Igfbp2+/+ male mice. Histomorphometry confirmed fewer osteoblasts and osteoclasts per bone perimeter and reduced bone formation in the Igfbp2−/− males. Lysates from both osteoblasts and osteoclasts in the Igfbp2−/− males had phosphatase and tensin homolog (PTEN) levels that were significantly higher than Igfbp2+/+ controls and were suppressed by addition of exogenous IGFBP-2. In summary, there are gender- and compartment-specific changes in Igfbp2−/− mice. IGFBP-2 may regulate bone turnover in both an IGF-I-dependent and -independent manner.
Positive Regulation of Steroidogenic Acute Regulatory Protein Gene Expression through the Interaction between Dlx and GATA-4 for Testicular Steroidogenesis
Authors: Nishida Hisayo , Miyagawa Shinichi , Vieux-Rochas Maxence , Morini Monica , Ogino Yukiko , Suzuki Kentaro , Nakagata Naomi , Choi Hueng-Sik , Levi Giovanni , Yamada Gen
Published: February 2008

Split hand/foot malformation (SHFM) is syndromic ectrodactyly often associated with mental retardation and/or craniofacial defects. Several clinical reports previously described urogenital dysplasia such as micropenis, hypospadias, and small testis in SHFM patients. Genetic lesions in the Dlx5 and Dlx6 (Dlx5/6) locus are associated with the human genetic disorder SHFM type 1. Although Dlx5/6 are expressed in the testis, their possible function of Dlx5/6 during testis differentiation has not been described. In this study, we show that Dlx5/6 are expressed in the fetal Leydig cells during testis development. We examined the effect of Dlx5 expression on the promoter activation of the steroidogenic acute regulatory protein (StAR) gene, which is essential for gonadal and adrenal steroidogenesis, in a Leydig cell line. Dlx5 efficiently activates the StAR promoter when GATA-4, another transcription factor essential for testicular steroidogenesis, was coexpressed. The transcriptional activation required the GATA-4-recognition element in the StAR promoter region and Dlx5 can physically interact with GATA-4. Furthermore, we herein show that the double inactivation of Dlx5 and Dlx6 in the mouse leads to decreased testosterone level and abnormal masculinization phenotype. These results suggest that Dlx5 and Dlx6 participate in the control of steroidogenesis during testis development. The findings of this study may open the way to analyze human congenital birth defects.
Transcriptional Activation of Signal Transducer and Activator of Transcription (STAT) 3 and STAT5B Partially Mediate Homeobox A1-Stimulated Oncogenic Transformation of the Immortalized Human Mammary Epithelial Cell
Authors: Mohankumar Kumarasamypet M. , Perry Jo K. , Kannan Nagarajan , Kohno Kimitoshi , Gluckman Peter D. , Emerald B. Starling , Lobie Peter E.
Published: February 2008

We have previously demonstrated that the p44/42 MAPK pathway is one pathway involved in homeobox (HOX) A1-stimulated oncogenesis. However, inhibition of MAPK kinase 1 does not completely prevent HOXA1-stimulated oncogenic transformation, suggesting the involvement of additional signal transduction pathways. Here, we report that forced expression of HOXA1 in immortalized human mammary epithelial cells significantly increased levels of signal transducer and activator of transcription (STAT) 3, 5A, and 5B mRNA by transcriptional up-regulation. The protein levels of STAT3 and 5B, but not STAT5A, and protein phosphorylation levels of STAT3 and 5B were significantly increased by forced expression of HOXA1. Forced expression of STAT3 or STAT5B was sufficient to transform oncogenically an immortalized human mammary epithelial cell line. Accordingly, inhibition of STAT3 or STAT5B activity with dominant negative STAT3 or STAT5B abrogated the ability of HOXA1 to stimulate cell proliferation, survival, oncogenic transformation, and generation of large disorganized multiacinar structures in three-dimensional culture. These results suggest that HOXA1 partially mediates oncogenic transformation of the immortalized human mammary epithelial cell through modulation of the STAT3 and STAT5B pathways.
The Balance between Oligodendrocyte and Astrocyte Production in Major White Matter Tracts Is Linearly Related to Serum Total Thyroxine
Authors: Sharlin David S. , Tighe Daniel , Gilbert Mary E. , Zoeller R. Thomas
Published: February 2008

Thyroid hormone (TH) may control the ratio of oligodendrocytes to astrocytes in white matter by acting on a common precursor of these two cell types. If so, then TH should produce an equal but opposite effect on the density of these two cells types across all TH levels. To test this, we induced graded TH insufficiency by treating pregnant rats with increasing doses of propylthiouracil. Propylthiouracil induced a dose-dependent decrease in serum T4 in postnatal d 15 pups, a dose-dependent decrease in the density of MAG-positive oligodendrocytes, and an equal increase in the density of glial fibrillary acidic protein-positive astrocytes in both the corpus callosum and anterior commissure. Linear regression analyses demonstrated a strong correlation between glial densities and serum T4; this correlation was positive for astrocytes and negative for oligodendrocytes. Surprisingly, oligodendrocyte density in the corpus callosum was more sensitive to changes in TH than in the anterior commissure, as indicated by the slope of the regressions. Furthermore, we measured an overall reduction in the cellular density that was independent of changes in myelin-associated glycoprotein and glial fibrillary acidic protein-positive cells. These data strongly support the interpretation that TH controls the balance of production of oligodendrocytes and astrocytes in major white matter tracts of the developing brain by acting on a common precursor of these cell types. Moreover, these findings indicate that major white matter tracts may differ in their sensitivity to TH insufficiency.
Increased Energy Expenditure Contributes More to the Body Weight-Reducing Effect of Rimonabant than Reduced Food Intake in Candy-Fed Wistar Rats
Authors: Herling Andreas W. , Kilp Susanne , Elvert Ralf , Haschke Guido , Kramer Werner
Published: February 2008

The CB1 receptor antagonist, rimonabant, affects the endocannabinoid system and causes a sustained reduction in body weight (BW) despite the transient nature of the reduction in food intake. Therefore, in a multiple-dose study, female candy-fed Wistar rats were treated with rimonabant (10 mg/kg) and matched with pair-fed rats to distinguish between hypophagic action and hypothesized effects on energy expenditure. Within the first week of treatment, rimonabant reduced BW nearly to levels of standard rat chow-fed rats. Evaluation of energy balance (energy expenditure measured by indirect calorimetry in relation to metabolizable energy intake calculated by bomb calorimetry) revealed that increased energy expenditure based on increased fat oxidation contributed more to sustained BW reduction than reduced food intake. A mere food reduction through pair feeding did not result in comparable effects because animals reduced their energy expenditure to save energy stores. Because fat oxidation measured by indirect calorimetry increased immediately after dosing in the postprandial state, the acute effect of rimonabant on lipolysis was investigated in postprandial male rats. Rimonabant elevated free fatty acids postprandially, demonstrating an inherent pharmacological activity of rimonabant to induce lipolysis and not secondarily postabsorptively due to reduced food intake. We conclude that the weight-reducing effect of rimonabant was due to continuously elevated energy expenditure based on increased fat oxidation driven by lipolysis from fat tissue as long as fat stores were elevated. When the amount of endogenous fat stores declined, rimonabant-induced increased energy expenditure was maintained by a re-increase in food intake.
Control of the Hypothalamo-Pituitary-Adrenal Axis in the Neonatal Period: Adrenocorticotropin and Corticosterone Stress Responses Dissociate in Vasopressin-Deficient Brattleboro Rats
Authors: Zelena Dóra , Domokos Ágnes , Barna István , Mergl Zsuzsa , Haller József , Makara Gábor B.
Published: February 2008

In adulthood the hypothalamo-pituitary-adrenal axis is controlled by both CRH and arginine vasopressin (AVP). However, in neonates CRH secretion is very low, whereas AVP secretion is fully functional. This suggests that the role of AVP is more pronounced in young than in adult rats. We investigated the role of AVP by studying stress responses in 5, 10, and 20-d-old AVP-deficient Brattleboro rats. Two different stressors were applied: 24-h maternal separation and Hypnorm Grove Oxford UK injections. In heterozygous controls (that do express AVP), both stressors increased plasma ACTH and corticosterone. The ACTH stress response disappeared in AVP-deficient rats, demonstrating that during the perinatal period, the secretion of this hormone is controlled by AVP. Surprisingly, corticosterone responses remained intact in AVP-deficient rats. Similar findings were obtained after 1-, 4-, 12-, and 24-h long maternal separations. Thus, preserved corticosterone stress responses were not explained by changes in the timing of ACTH secretion. In vitro experiments suggested that the dissociation of ACTH and corticosterone stress responses can only be partly explained by higher ACTH responsiveness of the adrenal cortex in AVP-deficient rats. Together, our results show that in neonatal periods, AVP is crucial for the expression of ACTH stress responses, but neither AVP nor ACTH is necessary for the induction of corticosterone stress responses. Discrepant ACTH and corticosterone stress responses may reflect compensatory mechanisms activated by AVP deficiency, but disparate findings suggest that they rather depict a neonate-specific mechanism of hypothalamo-pituitary-adrenal-axis control.
Peroxisome Proliferator-Activated Receptor-γ Agonist Rosiglitazone Reverses the Adverse Effects of Diet-Induced Obesity on Oocyte Quality
Authors: Minge Cadence E. , Bennett Brenton D. , Norman Robert J. , Robker Rebecca L.
Published: February 2008

Obesity and its physiological consequences are increasingly prevalent among women of reproductive age and are associated with infertility. To investigate, female mice were fed a high-fat diet until the onset of insulin resistance, followed by assessments of ovarian gene expression, ovulation, fertilization, and oocyte developmental competence. We report defects to ovarian function associated with diet-induced obesity (DIO) that result in poor oocyte quality, subsequently reduced blastocyst survival rates, and abnormal embryonic cellular differentiation. To identify critical cellular mediators of ovarian responses to obesity induced insulin resistance, DIO females were treated for 4 d before mating with an insulin-sensitizing pharmaceutical: glucose and lipid-lowering AMP kinase activator, 5-aminoimidazole 4-carboxamide-riboside, 30 mg/kg·d; sodium salicylate, IκK inhibitor that reverses insulin resistance, 50 mg/kg·d; or peroxisome proliferator activated receptor-γ agonist rosiglitazone, 10 mg/kg·d. 5-aminoimidazole 4-carboxamide-riboside or sodium salicylate treatment did not have significant effects on the reproductive parameters examined. However, embryonic development to the blastocyst stage was significantly improved when DIO mice were treated with rosiglitazone, effectively repairing development rates. Rosiglitazone also normalized DIO-associated abnormal blastomere allocation to the inner cell mass. Such improvements to oocyte quality were coupled with weight loss, improved glucose metabolism, and changes in ovarian mRNA expression of peroxisome proliferator activated receptor-regulated genes, Cd36, Scarb1, and Fabp4 cholesterol transporters. These studies demonstrate that peri-conception treatment with select insulin-sensitizing pharmaceuticals can directly influence ovarian functions and ultimately exert positive effects on oocyte developmental competence. Improved blastocyst quality in obese females treated with rosiglitazone before mating indicates that peroxisome proliferator activated receptor-γ is a key target for metabolic regulation of ovarian function and oocyte quality.
Endothelin-Converting Enzyme-1 Degrades Internalized Somatostatin-14
Authors: Roosterman Dirk , Kempkes Cordula , Cottrell Graeme S. , Padilla Benjamin E. , Bunnett Nigel W. , Turck Christoph W. , Steinhoff Martin
Published: February 2008

Agonist-induced internalization of somatostatin receptors (ssts) determines subsequent cellular responsiveness to peptide agonists and influences sst receptor scintigraphy. To investigate sst2A trafficking, rat sst2A tagged with epitope was expressed in human embryonic kidney cells and tracked by antibody labeling. Confocal microscopical analysis revealed that stimulation with sst and octreotide induced internalization of sst2A. Internalized sst2A remained sequestrated within early endosomes, and 60 min after stimulation, internalized sst2A still colocalized with β-arrestin1-enhanced green fluorescence protein (EGFP), endothelin-converting enzyme-1 (ECE-1), and rab5a. Internalized 125I-Tyr11-SST-14 was rapidly hydrolyzed by endosomal endopeptidases, with radioactive metabolites being released from the cell. Internalized 125I-Tyr1-octreotide accumulated as an intact peptide and was released from the cell as an intact peptide ligand. We have identified ECE-1 as one of the endopeptidases responsible for inactivation of internalized SST-14. ECE-1-mediated cleavage of SST-14 was inhibited by the specific ECE-1 inhibitor, SM-19712, and by preventing acidification of endosomes using bafilomycin A1. ECE-1 cleaved SST-14 but not octreotide in an acidic environment. The metallopeptidases angiotensin-1 converting enzyme and ECE-2 did not hydrolyze SST-14 or octreotide. Our results show for the first time that stimulation with SST-14 and octreotide induced sequestration of sst2A into early endosomes and that endocytosed SST-14 is degraded by endopeptidases located in early endosomes. Furthermore, octreotide was not degraded by endosomal peptidases and was released as an intact peptide. This mechanism may explain functional differences between octreotide and SST-14 after sst2A stimulation. Moreover, further investigation of endopeptidase-regulated trafficking of neuropeptides may result in novel concepts of neuropeptide receptor inactivation in cancer diagnosis.
Obesity and Hypertriglyceridemia Produce Cognitive Impairment
Authors: Farr Susan A. , Yamada Kelvin A. , Butterfield D. Allan , Abdul H. Mohammad , Xu Lin , Miller Nicole E. , Banks William A. , Morley John E.
Published: February 2008

Obesity is associated with cognitive impairments. Long-term mechanisms for this association include consequences of hyperglycemia, dyslipidemia, or other factors comprising metabolic syndrome X. We found that hypertriglyceridemia, the main dyslipidemia of metabolic syndrome X, is in part responsible for the leptin resistance seen in obesity. Here we determined whether triglycerides have an immediate and direct effect on cognition. Obese mice showed impaired acquisition in three different cognitive paradigms: the active avoidance T-maze, the Morris water maze, and a food reward lever press. These impairments were not attributable to differences in foot shock sensitivity, swim speed, swimming distance, or voluntary milk consumption. Impaired cognition in obese mice was improved by selectively lowering triglycerides with gemfibrozil. Injection into the brain of the triglyceride triolein, but not of the free fatty acid palmitate, impaired acquisition in normal body weight mice. Triolein or milk (97% of fats are triglycerides), but not skim milk (no triglycerides), impaired maintenance of the N-methyl-d-aspartate component of the hippocampal long-term synaptic potential. Measures of oxidative stress in whole brain were reduced by gemfibrozil. We conclude that triglycerides mediate cognitive impairment as seen in obesity, possibly by impairing maintenance of the N-methyl-d-aspartate component of hippocampal long-term potentiation, and that lowering triglycerides can reverse the cognitive impairment and improve oxidative stress in the brain.
Elasticity, unexpected contractility and the identification of actin and myosin in lobster arteries
Authors: Wilkens J. L. , Cavey M. J. , Shovkivska I. , Zhang M. L. , Keurs H. E. D. J. ter
Published: February 2008

Lobster arteries, which exhibit non-uniform elasticity when stretched, have a trilaminar organization. The inner layer is an elastic connective tissue and the outer layer is a collagenous connective tissue; the middle layer of an artery is an aggregation of cells containing microfilaments. Arterial cells possess actin, myosin and tropomyosin. Except for the dorsal abdominal artery,striated muscle cells are not evident in the walls of any of the vessels. The neurotransmitter glutamic acid and the neurohormone proctolin elicit slow circumferential contractions in all of the arteries leaving the lobster heart. Only the dorsal abdominal artery contracts when stimulated electrically. Longitudinal strips of the arteries do not respond to either drugs or electrical stimulation. Arterial contraction will have profound effects on resistance to blood flow and may be an important component of the control mechanisms regulating blood distribution.
Response properties of electrosensory units in the midbrain tectum of the paddlefish (Polyodon spathula Walbaum)
Authors: Hofmann M. H. , Jung S. N. , Siebenaller U. , Preißner M. , Chagnaud B. P. , Wilkens L. A.
Published: February 2008

Paddlefish use their peculiar rostrum to detect minute electric fields from their main prey, small water fleas. Electroreceptors over the rostrum and head sense these fields and send the information into a single hindbrain area, the dorsal octavolateral nucleus (DON). From there, information is sent to various midbrain structures, including the tectum. The response properties of primary afferent fibers and DON units has been well investigated, but nothing is known about electrosensory units in the midbrain. Here we recorded the responses of single units in the midbrain tectum and DON to uniform electric fields. Tectal units exhibited little spontaneous activity and responded to sine waves with a few, well phase-locked spikes. Phase locking was still significant at amplitudes one order of magnitude lower than in the DON. If stimulated with sinusoidal electric fields of different frequencies, phase locking in DON units decreased proportionally with frequency whereas the response of tectal units depended little on frequency. This is in agreement with behavioral studies showing that relevant frequencies range from DC to ca 20 Hz.
Feeding kinematics, suction and hydraulic jetting capabilities in bearded seals (Erignathus barbatus)
Authors: Marshall Christopher D. , Kovacs Kit M. , Lydersen Christian
Published: February 2008

Feeding kinematics, suction and hydraulic jetting capabilities of bearded seals (Erignathus barbatus) were characterized during controlled feeding trials. Feeding trials were conducted both on land and in water, and allowed a choice between suction and biting, but food was also presented that could be ingested by suction alone. Four feeding phases, preparatory, jaw opening, hyoid depression and jaw closing were observed; the mean feeding cycle duration was 0.54±0.22 s, regardless of feeding mode(P>0.05). Subjects feeding on land used biting and suction 89.3%and 10.7% of the time, respectively. Subjects feeding in water used suction and hydraulic jetting 96.3% and 3.7% of the time, respectively. No biting behavior was observed underwater. Suction feeding was characterized by a small gape (2.7±0.85 cm), small gape angle (24.4±8.13°), pursing of the rostral lips to form a circular aperture, and pursing of the lateral lips to occlude lateral gape. Biting was characterized by large gape(7.3±2.2 cm), large gape angle (41.7±15.2°), and lip curling to expose the teeth. An excavation behavior in which suction and hydraulic jetting were alternated was used to extract food from recessed wells. The maximum subambient and suprambient pressures recorded were 91.2 and 53.4 kPa,respectively. The inclusion of suction data for phocids broadens the principle that suction feeding kinematics is conserved among aquatic vertebrates. Furthermore, bearded seals support predictions that mouth size, fluid flow speed, and elusiveness of prey consumed are among a suite of traits that determine the specific nature of suction feeding among species.
Vision in the nocturnal wandering spider Leucorchestris arenicola (Araneae: Sparassidae)
Authors: Nørgaard Thomas , Nilsson Dan-Eric , Henschel Joh R. , Garm Anders , Wehner Rüdiger
Published: February 2008

At night the Namib Desert spider Leucorchestris arenicola performs long-distance homing across its sand dune habitat. By disabling all or pairs of the spiders' eight eyes we found that homing ability was severely reduced when vision was fully abolished. Vision, therefore, seems to play a key role in the nocturnal navigational performances of L. arenicola. After excluding two or three pairs of eyes, the spiders were found to be able to navigate successfully using only their lateral eyes or only their anterior median eyes. Measurement of the eyes' visual fields showed that the secondary eyes combined have a near full (panoramic) view of the surroundings. The visual fields of the principal eyes overlap almost completely with those of the anterior lateral eyes. Electroretinogram recordings indicate that each eye type contains a single photopigment with sensitivity peaking at ∼525 nm in the posterior and anteriomedian eyes, and at ∼540 nm in the anteriolateral eyes. Theoretical calculations of photon catches showed that the eyes are likely to employ a combination of spatial and temporal pooling in order to function at night. Under starlit conditions, the raw spatial and temporal resolution of the eyes is insufficient for detecting any visual information on structures in the landscape, and bright stars would be the only objects visible to the spiders. However, by summation in space and time, the spiders can rescue enough vision to detect coarse landscape structures. We show that L. arenicola spiders are likely to be using temporal summation to navigate at night.
Physiological characterization of stolon regression in a colonial hydroid
Authors: Vogt Kimberly S. Cherry , Geddes Gabrielle C. , Bross Lori S. , Blackstone Neil W.
Published: February 2008

As with many colonial animals, hydractiniid hydroids display a range of morphological variation. Sheet-like forms exhibit feeding polyps close together with short connecting stolons, whereas runner-like forms have more distant polyps and longer connecting stolons. These morphological patterns are thought to derive from rates of stolon growth and polyp formation. Here,stolon regression is identified and characterized as a potential process underlying this variation. Typically, regression can be observed in a few stolons of a normally growing colony. For detailed studies, many stolons of a colony can be induced to regress by pharmacological manipulations of reactive oxygen species (e.g. hydrogen peroxide) or reactive nitrogen species (e.g. nitric oxide). The regression process begins with a cessation of gastrovascular flow to the distal part of the stolon. High levels of endogenous H2O2 and NO then accumulate in the regressing stolon. Remarkably, exogenous treatments with either H2O2 or an NO donor equivalently trigger endogenous formation of both H2O2 and NO. Cell death during regression is suggested by both morphological features, detected by transmission electron microscopy, and DNA fragmentation, detected by TUNEL. Stolon regression may occur when colonies detect environmental signals that favor continued growth in the same location rather than outward growth.
Modulatory effects of adenosine and adenine nucleotides on different heart preparations of the American lobster,Homarus americanus
Authors: Maurer Gereon , Wilkens Jerrel L. , Grieshaber Manfred K.
Published: February 2008

As shown previously, adenosine and the adenine nucleotides cause a rapid increase in heart rate (fH) and haemolymph velocity(vHL) when infused into intact American lobster(Homarus americanus). Here we compare the effects of adenosine and adenine nucleotides on different heart preparations in order to gain insight into their sites of action. In the semi-isolated (in situ) heart preparation where the heart is uncoupled from neural and hormonal influence AMP, ADP and ATP, but not adenosine increased contractile force. None of the purines altered fH. Thus, the adenine nucleotides directly affect the myocardium and not the fH-setting cardiac ganglion.

In cardioregulatory-denervated animals in which the cardiac ganglion only was severed from the central nervous system (CNS), purines caused a small and gradual increase in fH, indicating that in vivoan alteration of fH arises indirectly through the central nervous system which in turn sends the information to the heart viathe dorsal nerves. The gradual increase in fH of cardioregulatory-denervated animals may also result from neurohormones released into the circulatory system, although no significant changes in haemolymph concentration of dopamine, serotonin and octopamine were found during adenosine infusion.

In semi-isolated (in situ) hearts adenine nucleotides also increased haemolymph flow, as a consequence of increased heart contractile force, but again adenosine had no effect. These data show that in vivo adenosine does not influence the myocardium, only the adenine nucleotides affect the myocardium directly. Obviously adenosine possesses an indirect effect, perhaps on cardio-arterial valves and arterial resistance,but other, as yet unidentified, modifying factors are also possible.
Pharmacology of ionotropic and metabotropic glutamate receptors on neurons involved in feeding behavior in the pond snail, Helisoma trivolvis
Authors: Scannell Elizabeth , Dell'Ova Carly A. , Quinlan Elizabeth M. , Murphy A. Don , Kleckner Nancy W.
Published: February 2008

Glutamate is a key regulatory neurotransmitter in the triphasic central pattern generator controlling feeding behavior in the pond snail, Helisoma trivolvis. It excites phase two motor neurons while inhibiting those in phases one and three. However, the receptors that mediate this regulation are only partially characterized. The purpose of these experiments was to further characterize the glutamate receptors on three buccal neurons modulated by glutamate. Intracellular recordings from B5, B19 and B27 neurons were taken during the perfusion of isolated buccal ganglia with agonists that are selective for different vertebrate glutamate receptors. The firing rate of all three neurons was inhibited in a dose-dependent manner by glutamate, including that of B27, a phase 2 motor neuron known to be excited by glutamate in vivo. Quisqualate also reduced the firing rate in all three neurons, and(1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD), a relatively non-selective metabotropic glutamate receptor (mGluR) agonist,reduced the firing rate in B5 neurons, but not in B19 or B27 neurons. Agonists selective for vertebrate group I, II and III mGluRs did not affect the firing rate in any of the Helisoma buccal neurons tested, suggesting that mGluR agonist binding sites on these neurons do not closely resemble those on any vertebrate mGluR subtypes. An increase in frequency of action potentials was observed in all three cell types in the presence of 100 μmol l–1 kainate (KA), suggesting the presence of excitatory(S)-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/KA-like receptors. However, electrotonic coupling between B19 and B27 neurons, and a lack of effect of KA on isolated B19 neurons suggest the excitatory effects of KA on this neuron are indirect. These findings suggest the presence of multiple glutamate receptor subtypes in molluscan neurons that do not always resemble vertebrate receptors pharmacologically.
The functional morphology of color changing in a spider: development of ommochrome pigment granules
Authors: Insausti Teresita C. , Casas Jérôme
Published: February 2008

Studies on the formation of ommochrome pigment granules are very few,despite their generalized occurrence as screening pigments in insect eyes. This is particularly true for ommochrome granules responsible for epidermal coloration. The aims of this study were to characterize the localization of major body pigments in a color changing mimetic spider, Misumena vatia (Thomisidae), and to describe the formation and location of ommochrome pigment granules responsible for the spider's color change from white to yellow. The unpigmented cuticula of this spider is transparent. Both the guanine localized in guanine cells in the opisthosoma and the uric acid localized in epidermis cells in the prosoma are responsible for the white coloration. The bright yellow color is due to the combination of ommochrome pigment granules and the white reflectance from coincident guanine and/or uric acid. The formation of ommochrome pigment granules in epidermis cells proceeds via three distinctive steps. Translucent, UV fluorescent, progranules(type I) are produced by a dense network of endoplasmic reticulum associated with numerous mitochondria and glycogen rosettes. These progranules are present in white spiders only, and regularly distributed in the cytoplasm. The merging of several progranules of type I into a transient state(progranule type II) leads to the formation of granules (type III) characterized by their lack of fluorescence, their spherical sections and their osmophilic-electron-dense contents. They are found in yellow spiders and in the red stripes on the body sides. Their color varies from yellow to red. Thus, white spiders contain only type I granules,yellow tinted spiders contain type II and III granules and bright yellow spiders contain only type III granules. We present a synthetic view of the ontogeny of ommochrome granules. We discuss the physiology of color changing and the nature of the chemical compounds in the different types of granules. Extended studies on the ultrastructural modification and physiological processes associated with color change are required before any statement about the adaptiveness of the color change can be made.
Malvolio is a copper transporter inDrosophila melanogaster
Authors: Southon Adam , Farlow Ashley , Norgate Melanie , Burke Richard , Camakaris James
Published: February 2008

Divalent metal ion transporter 1 (DMT1; also known as SLC11A2) can transport several metals including Fe and Cu in mammalian systems. We set out to determine whether Malvolio (Mvl), the Drosophila melanogasterorthologue of DMT1, can also transport Cu. Overexpression of Mvlcaused Cu accumulation in Drosophila S2 cultured cells and conversely dsRNAi knockdown of endogenous Mvl reduced cellular Cu levels. Cell viability under Cu limiting conditions was reduced following dsRNAi knockdown. A homozygous viable Mvl loss-of-function mutant(Mvl97f) was sensitive to excess Cu and female Mvl97f flies were also sensitive to Cu limitation. An MtnA-EYFP reporter was used as a proxy measure of Cu distribution within Mvl97f/+ larvae. Under basal conditions Cu levels were reduced in the anterior midgut and proventriculus relative to control larvae. These results demonstrate Mvl is a functional Cu transporter and that despite partial functional redundancy with the Ctr1 proteins, Cu uptake through this pathway is necessary for optimal viability at the cellular and organismal levels.