bluuebunny/crossref_metadata_2025 huggingface dataset:
A Fortunate Half-Century
Authors: Ostriker Jeremiah P.
Published: September 2016

The author has had the happy opportunity to work and study in the field of theoretical astrophysics during a half-century of unparalleled observational discovery. Quasars, pulsars, large-scale cosmic structure, galaxy evolution, and many other phenomena were discovered using revolutionary new observational techniques. In the same period of time, analytical tools ranging from new disciplines like plasma physics to enormously enhanced computational facilities became available, giving theoreticians the machinery to make some sense of this new world. At the start of the era the extragalactic world was largely framed as a quasi-homogeneous Universe of static galaxies formed by unknown and in fact unexamined processes. By the end of the period there was widespread acceptance of a self-consistent, evolving cosmological model amenable to calculation and comprehension. The author was fortunate indeed to have had the chance to collaborate with many wonderfully talented colleagues during this exciting time, attempting to unravel the multiple cosmic puzzles that nature delivered to us.
GLP-1 inhibits VEGFA-mediated signaling in isolated human endothelial cells and VEGFA-induced dilation of rat mesenteric arteries
Authors: Egholm Cecilie , Khammy Makhala Michell , Dalsgaard Thomas , Mazur Aleksandra , Tritsaris Katerina , Hansen Anker J. , Aalkjaer Christian , Dissing Steen
Published: September 2016

We investigated the acute effects of glucagon-like peptide-1 (GLP-1), GLP-1(1–36), and GLP-1(7–36) on vascular endothelial growth factor-A (VEGFA)-induced endothelium-dependent signaling and vasodilation. Our hypothesis was that GLP-1 released from intestinal l-cells modulates processes related to PLCγ activation, Src, and endothelial NOS (eNOS) signaling, thereby controlling endothelial vessel tone. By using RT-PCR analysis, we found mRNA for the GLP-1 receptor (GLP-1R) in human dermal microvascular endothelial cells (HDMEC), human retinal microvascular endothelial cells, and rat arteries. In isolated rat mesenteric resistance arteries precontracted with the thromboxane analog U46619 to 80–90% of maximum contraction, VEGFA (25 ng/ml) caused a small and gradual relaxation (28.9 ± 3.9%). Pretreatment of arteries with either GLP-1(1–36) (500 nM) or GLP-1(7–36) (1 nM) abolished the VEGFA-induced relaxation. VEGFA-induced relaxations were also inhibited in endothelial-denuded arteries and in arteries pretreated with the nitric oxide synthase (NOS) inhibitor, Nω-nitro-l-arginine methyl ester (100 μM). In vivo studies on male Wistar rats also revealed that GLP-1(7–36) inhibited VEGFA-induced vasodilation of the same arteries. In isolated endothelial cells, GLP-1(1–36) and GLP-1(7–36) caused a reduction in VEGFA-induced phosphorylation of PLCγ. Ca2+imaging of endothelial cells and rat mesenteric resistance arteries using fura-2, revealed that both GLP-1 analogs caused a reduction in VEGFA-induced Ca2+signaling. GLP-1(1–36) also reduced VEGFA-induced eNOS phosphorylation in HDMEC. In conclusion, GLP-1 reduced relaxation induced by VEGFA in resistance arteries by inhibiting VEGFR2-mediated Ca2+signaling and endothelial NO synthesis. GLP-1, on its own, also induced phosphorylation of Src and ERK1/2 that can lead to proliferation and is implicated in vessel permeability.
Resistance-based interval exercise acutely improves endothelial function in type 2 diabetes
Authors: Francois Monique E. , Durrer Cody , Pistawka Kevin J. , Halperin Frank A. , Little Jonathan P.
Published: September 2016

Different modes of exercise, disease, and training status can modify endothelial shear stress and result in distinct effects on endothelial function. To date, no study has examined the influence of type 2 diabetes (T2D) and training status on the acute endothelial response to different modes of interval exercise (INT). We examined the effect of a single session of resistance- and cardio-based INT compared with a time-matched control on endothelial function in 12 age-matched T2D participants, 12 untrained, and 11 trained adults (aged 56 ± 7 yr). Flow-mediated dilation (%FMD) of the brachial artery was assessed at baseline and immediately, 1, and 2 h after an acute bout of cardio interval (C-INT), resistance interval (R-INT), and seated control (CTL); these interventions were randomized and separated by >2 days. C-INT involved seven 1-min cycling intervals at 85% of peak power with 1-min recovery between. R-INT involved the same pattern of seven 1-min intervals using leg resistance exercises. Endothelial function (%FMD) was improved after R-INT in all groups (Condition × Time interaction, P < 0.01), an effect that was most robust in T2D where %FMD was higher immediately (+4.0 ± 2.8%), 1 h (+2.5 ± 2.5%), and 2 h (+1.9 ± 1.9%) after R-INT compared with CTL ( P < 0.01 for all). C-INT improved %FMD in T2D at 1-h postexercise (+1.6 ± 2.2%, P = 0.03) compared with CTL. In conclusion, R-INT acutely improves endothelial function throughout the 2-h postexercise period in T2D patients. The long-term impact of resistance exercise performed in an interval pattern is warranted.
H2S concentrations in the heart after acute H2S administration: methodological and physiological considerations
Authors: Sonobe Takashi , Haouzi Philippe
Published: September 2016

In this study, we have tried to characterize the limits of the approach typically used to determine H2S concentrations in the heart based on the amount of H2S evaporating from heart homogenates—spontaneously, after reaction with a strong reducing agent, or in a very acidic solution. Heart homogenates were prepared from male rats in control conditions or after H2S infusion induced a transient cardiogenic shock (CS) or cardiac asystole (CA). Using a method of determination of gaseous H2S with a detection limit of 0.2 nmol, we found that the process of homogenization could lead to a total disappearance of free H2S unless performed in alkaline conditions. Yet, after restoration of neutral pH, free H2S concentration from samples processed in alkaline and nonalkaline milieus were similar and averaged ∼0.2–0.4 nmol/g in both control and CS homogenate hearts and up to 100 nmol/g in the CA group. No additional H2S was released from control, CS, or CA hearts by using the reducing agent tris(2-carboxyethyl)phosphine or a strong acidic solution (pH < 2) to “free” H2S from combined pools. Of note, the reducing agent DTT produced a significant sulfide artifact and was not used. These data suggest that 1) free H2S found in heart homogenates is not a reflection of H2S present in a “living” heart and 2) the pool of combined sulfides, released in a strong reducing or acidic milieu, does not increase in the heart in a measurable manner even after toxic exposure to sulfide.
Selection-, age-, and exercise-dependence of skeletal muscle gene expression patterns in a rat model of metabolic fitness
Authors: Ren Yu-yu , Koch Lauren G. , Britton Steven L. , Qi Nathan R. , Treutelaar Mary K. , Burant Charles F. , Li Jun Z.
Published: September 2016

Intrinsic aerobic exercise capacity can influence many complex traits including obesity and aging. To study this connection we established two rat lines by divergent selection of untrained aerobic capacity. After 32 generations the high capacity runners (HCR) and low capacity runners (LCR) differed in endurance running distance and body fat, blood glucose, other health indicators, and natural life span. To understand the interplay among genetic differences, chronological age, and acute exercise we performed microarray-based gene expression analyses in skeletal muscle with a 2×2×2 design to simultaneously compare HCR and LCR, old and young animals, and rest and exhaustion. Transcripts for mitochondrial function are expressed higher in HCRs than LCRs at both rest and exhaustion and for both age groups. Expression of cell adhesion and extracellular matrix genes tend to decrease with age. This and other age effects are more prominent in LCRs than HCRs, suggesting that HCRs have a slower aging process and this may be partly due to their better metabolic health. Strenuous exercise mainly affects transcription regulation and cellular response. The effects of any one factor often depend on the other two. For example, there are ∼140 and ∼110 line-exercise “interacting” genes for old and young animals, respectively. Many genes highlighted in our study are consistent with prior reports, but many others are novel. The gene- and pathway-level statistics for the main effects, either overall or stratified, and for all possible interactions, represent a rich reference dataset for understanding the interdependence among lines, aging, and exercise.
An Improved Ant Colony Algorithm for Solving the Path Planning Problem of the Omnidirectional Mobile Vehicle
Authors: Zhao Jiang , Cheng Dingding , Hao Chongqing
Published: September 2016

This paper presents an improved ant colony algorithm for the path planning of the omnidirectional mobile vehicle. The purpose of the improved ant colony algorithm is to design an appropriate route to connect the starting point and ending point of the environment with obstacles. Ant colony algorithm, which is used to solve the path planning problem, is improved according to the characteristics of the omnidirectional mobile vehicle. And in the improved algorithm, the nonuniform distribution of the initial pheromone and the selection strategy with direction play a very positive role in the path search. The coverage and updating strategy of pheromone is introduced to avoid repeated search reducing the effect of the number of ants on the performance of the algorithm. In addition, the pheromone evaporation coefficient is segmented and adjusted, which can effectively balance the convergence speed and search ability. Finally, this paper provides a theoretical basis for the improved ant colony algorithm by strict mathematical derivation, and some numerical simulations are also given to illustrate the effectiveness of the theoretical results.
Th17 Cells Exhibit Antitumor Effects in MDS Possibly through Augmenting Functions of CD8+ T Cells
Authors: Li Jing , Yue Lanzhu , Wang Huaquan , Liu Chunyan , Liu Hui , Tao Jinglian , Qi Weiwei , Wang Yihao , Zhang Wei , Fu Rong , Shao Zonghong
Published: September 2016

Th17 cells are a newly found subset of distinct CD4+ Th effector cells’ family and are found to play an important role in cancers. Myelodysplastic syndromes (MDS) are a common malignant hematological disease. Here, we showed that both the percentage and the function of Th17 cells were elevated in low-risk MDS while being decreased in high-risk MDS. Levels of upstream molecules of Th17 cells, IL-6 and IL-23, were higher in low-risk MDS but lower in high-risk MDS patients. The abnormal percentage of Th17 cells was closely related to clinical parameters including karyotype, morphologic blast percentage of bone marrow, peripheral absolute neutrophil count, and hemoglobin concentration. Furthermore, expression rates of perforin and granzyme B in BM CD3+CD8+ cells (cytotoxic T lymphocyte, CTL) positively correlated with levels of IL-17 but negatively correlated with BM blast percentage and could be significantly increased after stimulation with human recombinant IL-17 (rhIL-17). Our results suggested that Th17 cells might play an antitumor effect in the pathogenesis of MDS through IL-17/CTL pathway.
ATM Expression Predicts Veliparib and Irinotecan Sensitivity in Gastric Cancer by Mediating P53-Independent Regulation of Cell Cycle and Apoptosis
Authors: Subhash Vinod Vijay , Tan Shi Hui , Yeo Mei Shi , Yan Fui Leng , Peethala Praveen C. , Liem Natalia , Krishnan Vaidehi , Yong Wei Peng
Published: September 2016

Identification of synthetically lethal cellular targets and synergistic drug combinations is important in cancer chemotherapy as they help to overcome treatment resistance and increase efficacy. The Ataxia Telangiectasia Mutated (ATM) kinase is a nuclear protein that plays a major role in the initiation of DNA repair signaling and cell-cycle check points during DNA damage. Although ATM was shown to be associated with poor prognosis in gastric cancer, its implications as a predictive biomarker for cancer chemotherapy remain unexplored. The present study evaluated ATM-induced synthetic lethality and its role in sensitization of gastric cancer cells to PARP and TOP1 inhibitors, veliparib (ABT-888) and irinotecan (CPT-11), respectively. ATM expression was detected in a panel of gastric cell lines, and the IC50 against each inhibitors was determined. The combinatorial effect of ABT-888 and CPT-11 in gastric cancer cells was also determined both in vitro and in vivo. ATM deficiency was found to be associated with enhanced sensitivity to ABT-888 and CPT-11 monotherapy, hence suggesting a mechanism of synthetic lethality. Cells with high ATM expression showed reduced sensitivity to monotherapy; however, they showed a higher therapeutic effect with ABT-888 and CPT-11 combinatorial therapy. Furthermore, ATM expression was shown to play a major role in cellular homeostasis by regulating cell-cycle progression and apoptosis in a P53-independent manner. The present study highlights the clinical utility of ATM expression as a predictive marker for sensitivity of gastric cancer cells to PARP and TOP1 inhibition and provides a deeper mechanistic insight into ATM-dependent regulation of cellular processes. Mol Cancer Ther; 15(12); 3087–96. ©2016 AACR.
Combining Nonclinical Experiments with Translational PKPD Modeling to Differentiate Erlotinib and Gefitinib
Authors: Eigenmann Miro J. , Frances Nicolas , Hoffmann Gerhard , Lavé Thierry , Walz Antje-Christine
Published: September 2016

We quantitatively compare the efficacy of two approved EGFR tyrosine kinase inhibitors, erlotinib and gefitinib, based on in vivo and in vitro data and show how a modeling approach can be used to scale from animal to humans. Gefitinib shows a higher tumor uptake in cancer patients, and we explored the potential impact on pharmacologic and antitumor activity in in vitro and in xenograft mice. Tumor growth inhibition was monitored, and the pharmacokinetics (PK) in plasma and tumor, as well as temporal changes of phospho-Erk (pErk) signals were examined in patient-derived tumor xenograft mice. These data were integrated in a translational PKPD model, allowing us to project an efficacious human dose, which we retrospectively compared with prescribed doses for cancer patients. In vitro experiments showed that cell-cycle arrest was similar for erlotinib and gefitinib. Similar pERK biomarker responses were obtained despite a 6.6-fold higher total tumor exposure for gefitinib. The PKPD model revealed a 3.7-fold higher in vivo potency for gefitinib, which did not translate into a lower anticipated efficacious dose in humans. The model-based dose prediction matched the recommended clinical doses well. These results suggest that despite having lower total tumor-to-plasma ratios, active drug exposure at target site is higher for erlotinib. Considering the PK properties, this translates in a 50% lower recommended daily dose of erlotinib in cancer patients. In summary, total exposure at target site is not suitable to rank compounds, and an integrated modeling and experimental approach can assess efficacy more accurately. Mol Cancer Ther; 15(12); 3110–9. ©2016 AACR.
CT-707, a Novel FAK Inhibitor, Synergizes with Cabozantinib to Suppress Hepatocellular Carcinoma by Blocking Cabozantinib-Induced FAK Activation
Authors: Wang Dan-Dan , Chen Ying , Chen Zi-Bo , Yan Fang-Jie , Dai Xiao-Yang , Ying Mei-Dan , Cao Ji , Ma Jian , Luo Pei-Hua , Han Yong-Xin , Peng Yong , Sun Ying-Hui , Zhang Hui , He Qiao-Jun , Yang Bo , Zhu Hong
Published: September 2016

Hepatocellular carcinoma is among the leading causes of cancer-related deaths worldwide, and the development of new treatment regimens is urgently needed to improve therapeutic approach. In our study, we found that the combination of a Met inhibitor, cabozantinib, and a novel FAK inhibitor, CT-707, exerted synergistic antitumor effects against hepatocellular carcinoma in vitro and in vivo. Interestingly, further studies showed that therapeutic concentrations of cabozantinib increased the phosphorylation of FAK, which might attenuate the antitumor activity of cabozantinib. The simultaneous exposure to CT-707 effectively inhibited the activation of FAK that was induced by cabozantinib, which contributes to the synergistic effect of the combination. Furthermore, cabozantinib increased the mRNA and protein levels of integrin α5, which is a canonical upstream of FAK, and the introduction of cilengitide to block integrin function could abrogate FAK activation by cabozantinib, indicating that cabozantinib upregulated the phosphorylation of FAK in an integrin-dependent manner. Similar synergy was also observed on PHA-665752, another selective MET inhibitor, indicating that this observation might be a common characteristic of MET-targeting strategies. Our findings not only favor the development of the novel FAK inhibitor CT-707 as a therapeutic agent against hepatocellular carcinoma but also provide a new strategy of combining MET and FAK inhibitors to potentiate the anticancer activities of these two types of agents for treating hepatocellular carcinoma patients. Mol Cancer Ther; 15(12); 2916–25. ©2016 AACR.
Oncogenic Receptor Tyrosine Kinases Directly Phosphorylate Focal Adhesion Kinase (FAK) as a Resistance Mechanism to FAK-Kinase Inhibitors
Authors: Marlowe Timothy A. , Lenzo Felicia L. , Figel Sheila A. , Grapes Abigail T. , Cance William G.
Published: September 2016

Focal adhesion kinase (FAK) is a major drug target in cancer and current inhibitors targeted to the ATP-binding pocket of the kinase domain have entered clinical trials. However, preliminary results have shown limited single-agent efficacy in patients. Despite these unfavorable data, the molecular mechanisms that drive intrinsic and acquired resistance to FAK-kinase inhibitors are largely unknown. We have demonstrated that receptor tyrosine kinases (RTK) can directly bypass FAK-kinase inhibition in cancer cells through phosphorylation of FAK's critical tyrosine 397 (Y397). We also showed that HER2 forms a direct protein–protein interaction with the FAK-FERM-F1 lobe, promoting direct phosphorylation of Y397. In addition, FAK-kinase inhibition induced two forms of compensatory RTK reprogramming: (i) the rapid phosphorylation and activation of RTK signaling pathways in RTKHigh cells and (ii) the long-term acquisition of RTKs novel to the parental cell line in RTKLow cells. Finally, HER2+ cancer cells displayed resistance to FAK-kinase inhibition in 3D growth assays using a HER2 isogenic system and HER2+ cancer cell lines. Our data indicate a novel drug resistance mechanism to FAK-kinase inhibitors whereby HER2 and other RTKs can rescue and maintain FAK activation (pY397) even in the presence of FAK-kinase inhibition. These data may have important ramifications for existing clinical trials of FAK inhibitors and suggest that individual tumor stratification by RTK expression would be important to predict patient response to FAK-kinase inhibitors. Mol Cancer Ther; 15(12); 3028–39. ©2016 AACR.
AMPKα2 Regulates Bladder Cancer Growth through SKP2-Mediated Degradation of p27
Authors: Kopsiaftis Stavros , Sullivan Katie L. , Garg Isha , Taylor John A. , Claffey Kevin P.
Published: September 2016

AMP-activated protein kinase (AMPK) is the central metabolic regulator of the cell and controls energy consumption based upon nutrient availability. Due to its role in energy regulation, AMPK has been implicated as a barrier for cancer progression and is suppressed in multiple cancers. To examine whether AMPK regulates bladder cancer cell growth, HTB2 and HT1376 bladder cells were treated with an AMPK activator, 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR). AICAR treatment reduced proliferation and induced the expression of p27Kip1 (CDKN1B), which was mediated through an mTOR-dependent mechanism. Interestingly, AMPKα2 knockdown resulted in reduced p27 levels, whereas AMPKα1 suppression did not. To further determine the exact mechanism by which AMPKa2 regulates p27, HTB2 and HT1376 cells were transduced with an shRNA targeting AMPKα2. Stable knockdown of AMPKα2 resulted in increased proliferation and decreased p27 protein. The reduced p27 protein was determined to be dependent upon SKP2. Additionally, loss of AMPKα2 in a xenograft and a chemical carcinogen model of bladder cancer resulted in larger tumors with less p27 protein and high SKP2 levels. Consistent with the regulation observed in the bladder cancer model systems, a comprehensive survey of human primary bladder cancer clinical specimens revealed low levels of AMPKα2 and p27 and high levels of SKP2.

Implications: These results highlight the contribution of AMPKα2 as a mechanism for controlling bladder cancer growth by regulating proliferation through mTOR suppression and induction of p27 protein levels, thus indicating how AMPKα2 loss may contribute to tumorigenesis. Mol Cancer Res; 14(12); 1182–94. ©2016 AACR.
Clinical Response of a Patient to Anti–PD-1 Immunotherapy and the Immune Landscape of Testicular Germ Cell Tumors
Authors: Shah Shalin , Ward James E. , Bao Riyue , Hall Curtis R. , Brockstein Bruce E. , Luke Jason J.
Published: September 2016

Anti–Programed Death 1 (PD-1) is standard immunotherapy for multiple cancers, and the expression of one of its ligands, PD-L1, has been described in germ cell tumors (GCT). Neither the clinical activity of anti–PD-1 nor the incidence of an immunoresponsive tumor microenvironment has been described for GCTs. A patient initially diagnosed with melanoma via fine needle aspiration was treated with one dose of antibody to PD-1. A core needle biopsy was subsequently performed to acquire sufficient tissue for molecular analysis, which led to a change in diagnosis to metastatic embryonal carcinoma. The testicular GCT cohort of The Cancer Genome Atlas was analyzed using a T-cell gene signature associated with benefit from immunotherapy. Primary tumors (N = 134) were categorized as high (T-cell–inflamed), medium, or low (non–T-cell-inflamed) by their T-cell signature derived from RNAseq data. Anti–PD-1 induced decreases in serum markers and a 33% reduction in tumor volume. Gene expression revealed a T-cell–inflamed tumor microenvironment in 47% of testicular GCTs, including seminoma (83%) and nonseminoma (17%) tumor subtypes. Expression of alpha-fetoprotein (AFP) RNA correlated with lack of the T-cell signature, with increasing AFP RNA inversely correlating with the inflamed signature and expression of IFNγ-associated genes. These data suggest that GCTs can respond to anti–PD-1 and that gene expression profiling supports investigation of immunotherapy for treatment of GCTs. Cancer Immunol Res; 4(11); 903–9. ©2016 AACR.
Frequency of Depressive Syndromes in Elderly Individuals with No Cognitive Impairment, Mild Cognitive Impairment, and Alzheimer's Disease Dementia in a Memory Clinic Setting
Authors: Lee Jun Ho , Byun Min Soo , Yi Dahyun , Choe Young Min , Choi Hyo Jung , Baek Hyewon , Sohn Bo Kyung , Kim Hyun Jung , Lee Younghwa , Woo Jong Inn , Lee Dong Young
Published: September 2016

Aims: The aims of this study were to investigate the frequency of various depressive syndromes in elderly individuals with no cognitive impairment (NC), mild cognitive impairment (MCI), and Alzheimer's disease dementia (AD) in a memory clinic setting, and then to test whether severe and milder forms of depressive syndromes are differentially associated with the cognitive groups. Methods: For 216 NC, 478 MCI, and 316 AD subjects, we investigated the frequency of depressive syndromes, defined by three different categories: major and minor depressive disorder (MaDD and MiDD) according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, as well as depression according to the National Institute of Mental Health provisional diagnostic criteria for depression in Alzheimer's disease (NIMH-dAD). Results: The frequency of MaDD did not show any significant difference among NC, MCI, and AD. In contrast, the frequencies of MiDD and NIMH-dAD were higher than those of MaDD and showed significant group differences with a gradual increase from NC to AD. Conclusion: The findings suggest that the degenerative process of Alzheimer's disease contributes to the occurrence of mild depressive conditions, but not to severe depression.
Cerebrospinal Fluid Amyloid Beta and Tau Concentrations Are Not Modulated by 16 Weeks of Moderate- to High-Intensity Physical Exercise in Patients with Alzheimer Disease
Authors: Steen Jensen Camilla , Portelius Erik , Siersma Volkert , Høgh Peter , Wermuth Lene , Blennow Kaj , Zetterberg Henrik , Waldemar Gunhild , Gregers Hasselbalch Steen , Hviid Simonsen Anja
Published: September 2016

Background: Physical exercise may have some effect on cognition in patients with Alzheimer disease (AD). However, the underlying biochemical effects are unclear. Animal studies have shown that amyloid beta (Aβ), one of the pathological hallmarks of AD, can be altered with high levels of physical activity. Aim: The objective of this study was to elucidate the effect of 16 weeks of moderate- to high-intensity physical exercise on the biomarkers of AD, with special emphasis on the amyloidogenic pathway. Methods: From a total of 53 patients with AD participating in the Preserving Cognition, Quality of Life, Physical Health and Functional Ability in Alzheimer's Disease: The Effect of Physical Exercise (ADEX) study we analyzed cerebrospinal fluid samples for Aβ species, total tau (t-tau), phosphorylated tau (p-tau) and soluble amyloid precursor protein (sAPP) species. We also assessed the patients for apolipoprotein E ε4 (ApoE ε4) genotype. Results: We found no effect of 16 weeks of physical exercise on the selected biomarkers, and no effect of ApoE ε4 genotype. Conclusion: Our findings suggest that the possible effect of physical exercise on cognition in patients with AD is not due to modulation of Aβ, t-tau, p-tau and sAPP species.
Desempenho e parâmetros séricos de ratos alimentados com dietas contendo soja integral crua
Authors: Campello Cláudio Cabral , Carvalho Vitor Luz , Vieira Karla Maia , Farias Davi Felipe , Brasil Isabel Cristiane Façanha , Maia Andréa Agaciana Bessa , Morais Janne Keila Sousa , Carvalho Ana Fontenele Urano , Vasconcelos Ilka Maria
Published: September 2016

O trabalho objetivou avaliar o efeito da substituição da proteína da clara de ovo por proteína de soja crua na dieta de ratos em crescimento sobre o ganho de peso, consumo de ração, eficiência alimentar e parâmetros séricos (proteínas totais, albumina, aminotransferases, uréia, creatinina e amilase pancreática), visando estabelecer limites biologicamente seguros para inclusão de soja crua na dieta dos animais por períodos de curta duração. Foram utilizados 24 ratos divididos aleatoriamente em seis grupos de quatro animais e alimentados com dietas contendo cinco percentuais de substituição de proteína da clara de ovo por proteína de soja (0, 25, 50, 75 e 100%) e um grupo com dieta aprotéica. Os animais foram mantidos por 10 dias com fornecimento de água e alimento ad libitum. Os resultados obtidos revelaram que não houve diferença significativa no consumo entre os tratamentos testados. O ganho de peso e a eficiência alimentar observados no tratamento com 25% de substituição foram equivalentes aos obtidos com clara do ovo como única fonte de proteína. Albumina sérica, aminotransferases e creatinina não foram afetadas pelo aumento do percentual de soja crua, mas houve aumento da concentração de uréia no soro a partir de 50% de substituição. Proteínas totais e amilase pancreática sérica foram afetadas pela proteína da soja crua somente acima de 75% de substituição. Análises de regressão demonstraram que a substituição da proteína da clara de ovo por proteína de soja crua em até 30% foi inócua para o desempenho e parâmetros séricos de ratos em crescimento.
Efeitos do estresse de trabalho sobre parâmetros seminais de cães da raça Rottweiler
Authors: Sobrinho Carlos De Almeida Baptista , Hatamoto-Zervoudakis Luciana Keiko , Barnabe Valquíria Hyppolito , Nichi Marcílio , Oliveira Claudio Alvarenga de
Published: September 2016

O presente trabalho teve como objetivo avaliar os efeitos do estresse de trabalho sobre a fertilidade de cães machos. Foram utilizados 18 cães da raça rottweiler, férteis, com idade média de 4 anos, distribuídos aleatoriamente em dois grupos: repouso (controle) e trabalho (tratamento). O tratamento era composto por 5 fases: 1-adaptação, 2- adestramento básico, 3-adestramento militar e condicionamento, 4- acampamento, 5-repouso. Durante todo o período experimental, foram feitas duas coletas de sêmen semanais, para avaliação do ejaculado. No final de cada fase foi realizada coleta de sangue para dosagem dos níveis plasmáticos de cortisol. Os dados foram analisados pelo SAS, á=5%. Observou-se efeito negativo do estresse sobre os parâmetros motilidade (72,63 vs. 57,62, p<0,0001) e vigor espermático (3,06 vs. 2,52, p<0,0001), porcentagem de defeitos maiores (16,01 vs. 26,80, p< 0,0001) e totais (29,61 vs. 40,34, p<0,0001). Observou-se interação (p<0,0001) entre tempo e tratamento sobre a variável cortisol, indicando que o tipo de agente estressante (fase) interfere no nível plasmático de cortisol. Com base nesses resultados, é possível concluir que o estresse de trabalho interferiu de maneira negativa na fertilidade dos cães.
Estudo retrospectivo das intussuscepções em cães
Authors: Oliveira-Barros Leda Marques , Matera Júlia Maria
Published: September 2016

Intussuscepção é uma causa comum de obstruções intestinais em pequenos animais. No presente estudo foram analisados, retrospectivamente, prontuários de 97 cães com diagnóstico de intussuscepção intestinal no período de Janeiro de 2000 a Julho de 2007. Foram avaliados dados referentes a raça, idade e sexo do animal, sintomas clínicos, meios de diagnóstico, tratamento e evolução do quadro. Animais com idade inferior a um ano apresentaram maior ocorrência. Diversos fatores foram relacionados como predisponentes, sendo a intoxicação prévia por carbamatos presente em 13 cães. A porção mais acometida foi a junção ileo-cólica e a enterectomia e enteroanastomose foram realizadas em 71% dos animais. Apenas três animais, não submetidos a enterectomia no primeiro procedimento, apresentaram recidiva do quadro. Três animais foram a óbito após a intervenção cirúrgica. O número expressivo de casos analisados associado à ausência de dados regionais até então existentes contribuiu para o conhecimento da afecção e de seu tratamento.
Avaliação do tratamento da hérnia perineal bilateral no cão por acesso dorsal ao ânus
Authors: Acaui Andrea , Stopiglia Angelo João , Matera Julia Maria , Cortopassi Silvia Renata Gaido , Lacerda Procássia Maria de Oliveira
Published: September 2016

O objetivo do presente estudo foi avaliar a evolução e as complicações pós-operatórias do tratamento de hérnias perineais bilaterais, por acesso dorsal ao ânus, em 14 cães com idade entre seis e 12 anos. Realizou-se incisão em forma de 'U' invertido, a qual se estendeu desde a porção lateral da tuberosidade isquiática do lado esquerdo, curvando-se em direção à linha mediana, dois centímetros dorsalmente ao ânus e dirigindo-se simetricamente para a extremidade da tuberosidade isquiática contralateral. Após redução da hérnia, os músculos do diafragma pélvico direito e esquerdo foram suturados pela técnica de elevação do músculo obturador interno. As complicações observadas no período pós-operatório foram incontinência fecal, contaminação da ferida, deiscência de pontos da sutura cutânea, incontinência urinária e recidiva em um cão 19 dias após procedimento cirúrgico. O acesso utilizado foi exequível e todos os cães submetidos à técnica operatória proposta não apresentaram recidivas em um período entre cinco e dez meses de avaliação pós-operatório.
Detecção do virus da anemia das galinhas em coinfecção com o vírus doença infecciosa bursal em frangos
Authors: Chacón Jorge Luiz , Nogueira Eliana Ottati , Bretano Liana , Gomes Cleide R. , Astolfi-Ferreira Claudete Serrano , Villarreal Laura , Ferreira Antonio José Piantino
Published: September 2016

Este estudo investigou a manifestação do vírus da Anemia Infecciosa das Aves (VAIA) em lotes de frangos que apresentavam retardo no crescimento e aumento da mortalidade observado a partir do quarto dia de idade. Clinicamente, as aves apresentavam depresão, palidez, despigmentação e retardo de crescimento. À necropsia, as aves apresentavam lesões compatíveis com a infecção pelo vírus da Anemia infecciosa das aves (VAIA). Amostras de fígado, baço e timo foram examinadas por PCR que amplifica um frangmento de 675 pb do gene VP-1 do VAIA. Todos os órgãos examinados foram positivos para o vírus da Anemia Infecciosa das Aves. Os demais patógenos, como adenovírus, reovírus, astrovírus, vírus da doença infecciosa bursal e coronavírus aviário não foram detectados pelas diferentes técnicas laboratoriais, como sorologia, PCR ou PAGE. Os resultados mostraram que o vírus da Anemia Infecciosa das Aves (VAIA) pode manifestar-se clinicamente nos primeiros dias de vida dos frangos - um fato ainda não reportado - associado ao vírus vacinal da doença infecciosa bursal (DIB) cepa forte pode induzir um persistente retardo de crescimento, por várias semanas, em frangos.
Reação de hemi-nested RT-PCR dirigida ao gene da hemaglutinina-esterase do Coronavírus Bovino
Authors: Souza Sibele Pinheiro de , Asano Karen Miyuki , Buitrago Laura Yaneth Villarreal , Silva Sheila De Oliveira Souza , Richtzenhain Leonardo José , Brandão Paulo Eduardo
Published: September 2016

O coronavírus bovino (BCoV) é um vírus RNA simples fita, de sentido positivo, não segmentado com envelope constituído de uma camada dupla de lipídios com quatro proteínas (HE, S, E e M) que resultam no aspecto de coroa dos vírions. Como a HE (hemaglutinina-esterase) é uma proteína polimórfica com uma função de receptor aglutinante secundária, estudos sobre a diversidade do gene HE podem possibilitar maiores informações sobre a evolução e interação hospedeiro-parasita do BCoV. Uma reação de hemi-nested RT-PCR foi desenvolvida para a amplificação de um produto de 441pb do gene HE do BCoV (nt 543 ao 562). Temperaturas ótimas de hibridização foram testadas em um termociclador com gradiente para a reação de hemi-nested e utilizada no protocolo final. A sensibilidade analítica foi determinada por meio da diluição serial na base 10 do BCoV amostra Kakegawa (título HA: 256) em uma suspensão fecal negativa para BCoV, resultando positiva até a diluição de 10-6, mostrando uma alta sensibilidade analítica sem inibição na PCR. O protocolo final da hemi-nested RT-PCR foi aplicado a 21 amostras fecais de vacas previamente positivas para BCoV e o sequenciamento de DNA do produto de 441pb de 14 amostras resultaram em sequências com elevado escore do gene HE do BCoV após a análise no BLAST/n. Essa hemi-nested RT-PCR é uma ferramenta poderosa para estudos de diversidade filogenética de linhagens de campo de BCoV e para estudos comparativos entre os diferentes genes dos Coronavírus.
Estudo do tempo de excreção renal pela cintilografia em felinos domésticos
Authors: Jarretta Georgea Bignardi , Bombonato Pedro Primo , De Martin Benedicto Wlademir
Published: September 2016

Na rotina clínica de felinos domésticos, algumas modalidades de diagnóstico por imagem, como a ultrassonografia, radiografia simples e urografia excretora, já são amplamente utilizadas. A cintilografia é uma técnica não invasiva, capaz de oferecer informações funcionais de rins individualmente, porém é considerada uma modalidade menos usual. O objetivo deste estudo foi verificar o tempo de excreção renal de felinos domésticos por meio da cintilografia, em animais com parâmetros ultrassonográficos e radiográficos dentro dos limites da normalidade. Foram utilizados 15 animais, nove machos e seis fêmeas, e estes foram divididos em grupos de animais não submetidos à anestesia e anestesiados. Foi estabelecido o tempo para o radiofármaco obter acúmulo máximo em cada um dos rins e o tempo para este acúmulo máximo ser reduzido à metade. Não houve diferença estatística entre os valores dos animais não-anestesiados e anestesiados, nem entre os rins esquerdo e direito, tampouco entre machos e fêmeas.
Utilização de eletroquimioterapia em neoplasias de origem epitelial ou mesenquimal localizadas em pele ou mucosas de cães
Authors: Silveira Lucia Maria Guedes , Brunner Carlos Henrique Maciel , Cunha Fernando Malagutti , Futema Fabio , Calderaro Franco Ferraro , Kozlowski Didio
Published: September 2016

A eletroquimioterapia é caracterizada como um protocolo que agrega o uso de fármacos antineoplásicos à aplicação regional de pulsos elétricos, maximizando a concentração intracelular destes agentes, assim propiciando maior ação citotóxica dos mesmos. A bleomicina, um antimicrobiano dotado de propriedade antineoplásica, demonstra restrição no transporte através da membrana celular, dada sua composição molecular hidrofílica. Todavia, uma vez administrada via intralesional ou endovenosa associada à eletroporação, exibe citotoxicidade potencializada. Foram utilizados neste estudo 34 cães acometidos por neoformações solitárias de origem epitelial ou mesenquimal, situadas em pele ou membranas mucosas. Padronizou-se o protocolo eletroquimioterápico empregando-se sulfato de bleomicina, pela via intralesional, na dose de 1 U/cm³ de tumor. A eletroporação foi perfilada com eletrodo composto por agulhas, pulsos elétricos com tensão de 1000 V, em onda quadrada unipolar, com duração de 100 microsegundos, totalizando-se oito ciclos. Constatou-se remissão neoplásica integral em 30 cães (88,3%) e refratariedade ao protocolo em apenas quatro animais (11,7%). Inexistiram complicações e/ou efeitos adversos decorrentes do procedimento. O protocolo neste trabalho estudado revelou-se aplicável, eficaz e seguro na terapêutica antineoplásica em cães.
Estudo imunológico e genético de 10 isolados do vírus da raiva de morcegos do Rio de Janeiro, Sudeste do Brasil
Authors: Mota Carla Da Silva , Ito Fumio Honma , Silva Marlon Vicente , Sato Go , Kobayashi Yuki , Itou Takuya , Sakai Takeo
Published: September 2016

O presente trabalho visou estudar dez isolados de vírus da raiva de morcegos hematófagos e não-hematófagos do Estado do Rio de Janeiro em suas características genéticas quanto aos genes N e G. Além disso, estudou-se a resposta de camundongos vacinados com a vacina antirrábica produzida pela replicação da amostra Pitman-Moore em cultivo celular, frente ao desafio com estes isolados virais, utilizando-se um ensaio imunológico baseado no teste de potência NIH. A vacina antirrábica utilizada na imunização dos camundongos ofereceu proteção em mais de 80% dos camundongos vacinados com a diluição 1:5 da vacina, frente à maioria dos isolados. A análise filogenética do gene da proteína N apresentou um padrão de agregação dividido em variante de morcego hematófago e variante de morcego insetívoro, com todos os isolados de morcegos frugívoros Artibeus sp. tendo sido segregados com a variante característica de morcegos Desmodus rotundus. Foram observadas diferenças filogenéticas entre as variantes do vírus da raiva de morcego hematófago isoladas na Região Noroeste do Estado do Rio de Janeiro e aquelas isoladas nas Regiões Metropolitana e Sul do Estado. A substituição do resíduo ácido aspártico por ácido glutâmico na posição 118, encontradas na caracterização genética da proteína G dos isolados 704/97BR-DR e 151/98BR-DR, permite inferir que esta posição esteja relacionada à antigenicidade viral. Não foram observadas diferenças genéticas temporais entre os isolados estudados. A vacina antirrábica utilizada ofereceu proteção satisfatória contra a maioria dos isolados estudados.
Aspectos morfológicos, morfométricos e topográficos do aparelho digestório de Chinchilla lanigera
Authors: Castro Tiane Ferreira de , Dummer Rodrigo Jeske , Rickes Eduardo Madruga , Pereira Malcon Andrei Martinez
Published: September 2016

O objetivo deste estudo foi o de descrever os aspectos morfológicos e topográficos do Aparelho Digestório (AD) de chinchilas, mediante a dissecação de dez animais. Os segmentos do AD foram coletados e demarcados, seguido de análise volumétrica dos órgãos cavitários, por meio de injeção de solução salina a 60 °C, além da mensuração dos comprimentos dos órgãos tubulares. Nos órgãos parenquimatosos realizou-se a sua pesagem. Durante a análise da disposição dos órgãos, evisceração e medição, observou-se que a cavidade oral é característica de roedores, as glândulas salivares são semelhantes às de lagomorfos e órgãos como esôfago, estômago, duodeno, cólon transverso, fígado, pâncreas e baço apresentam-se dispostos de forma semelhante ao descrito nas outras espécies. Já o jejuno e o cólon descendente foram evidenciados muito extensos e dispostos de forma ondulatória, suspensos no teto da cavidade abdominal. O íleo assemelhou-se ao descrito para as outras espécies, porém sua disposição topográfica é da direita para esquerda, direcionando-se ao ceco, o qual se constitui de duas porções distintas e bem desenvolvidas. Ambas as partes encontram-se localizadas à esquerda do plano mediano. O cólon ascendente dispõe-se de forma bastante particular, ocorrendo a presença de uma alça dupla que realiza um looping junto ao fígado. Uma característica relevante foi evidenciada ao comparar-se o reto de machos e fêmeas, o qual apresenta maior comprimento nos machos. De posse dos resultados concluímos que, apesar da chinchila ser um roedor, há características próprias da espécie e também outras que se assemelham aos lagomorfos, constituindo uma relação entre essas ordens.
Hydrogen Sulfide Regulates Krüppel‐Like Factor 5 Transcription Activity via Specificity Protein 1 S‐Sulfhydration at Cys664 to Prevent Myocardial Hypertrophy
Authors: Meng Guoliang , Xiao Yujiao , Ma Yan , Tang Xin , Xie Liping , Liu Jieqiong , Gu Yue , Yu Ying , Park Chung‐Min , Xian Ming , Wang Xin , Ferro Albert , Wang Rui , Moore Philip K. , Zhang Zhiren , Wang Hong , Han Yi , Ji Yong
Published: September 2016

Background

Hydrogen sulfide (H
2
S) is a gasotransmitter that regulates multiple cardiovascular functions. Krüppel‐like factor 5 (KLF5) exerts diverse functions in the cardiovascular system. Whether and how H
2
S regulates KLF5 in myocardial hypertrophy is unknown.

Methods and Results

In our study, hypertrophic myocardial samples in the clinic were collected and underwent histological and molecular biological analysis. Spontaneously hypertensive rats and neonatal rat cardiomyocytes were studied for functional and signaling responses to GYY4137, an H
2
S‐releasing compound. Expression of cystathionine γ‐lyase, a principal enzyme for H
2
S generation in heart, decreased in human hypertrophic myocardium, whereas KLF5 expression increased. After GYY4137 administration for 4 weeks, myocardial hypertrophy was inhibited in spontaneously hypertensive rats, as demonstrated by improvement in cardiac structural parameters, heart mass, size of cardiac myocytes, and expression of atrial natriuretic peptide. H
2
S diminished expression of KLF5 in myocardium of spontaneously hypertensive rats and in hypertrophic cardiomyocytes. H
2
S also inhibits platelet‐derived growth factor A promoter activity, decreased recruitment of KLF5 to the platelet‐derived growth factor A promoter, and reduced atrial natriuretic peptide expression in angiotensin II–stimulated cardiomyocytes, and these effects are suppressed by KLF5 knockdown. KLF5 promoter activity and KLF5 expression was also reversed by H
2
S. H
2
S increased the S‐sulfhydration on specificity protein 1 in cardiomyocytes. Moreover, H
2
S decreased KLF5 promoter activity; reduced KLF5 mRNA expression; attenuated specificity protein 1 binding activity with KLF5 promoter; and inhibited hypertrophy after specificity protein 1 mutated at Cys659, Cys689, and Cys692 but not Cys664 overexpression.

Conclusions

These findings suggest that H
2
S regulates KLF5 transcription activity via specificity protein 1 S‐sulfhydration at Cys664 to prevent myocardial hypertrophy.
Should Non-Jews be Regarded as Equal?
Authors: Zohar Zvi
Published: September 2016

This article provides a window into a variety of views and teachings about the equality of Jews and non-Jews that are found in the writings of Sephardic rabbis in modern times. Unlike almost all writing on Judaism in modern times, which has focused on religious thinkers living in Europe or in North America, my examples are drawn from the writings of rabbis living in Muslim-majority lands, i.e., in the Middle East and North Africa, where Judaism originated and where Jewish communities have existed continuously for millennia. These attitudes range from negative and antagonistic essentialist perspectives to ideals of mutual cultural enrichment and joint co-operation in the realization of righteousness and justice in the life of all peoples. The rich variety of attitudes and values exemplified in these texts is typical of the Jewish rabbinic tradition, in which a plurality of views exists on almost any topic.
Phoradendron longicaule (Viscaceae): a new species from Michoacán, Mexico
Authors: KUIJT JOB , STEINMANN VICTOR W.
Published: September 2016

Phoradendron longicaule (Viscaceae), a new, nearly leafless species of mistletoe from the Infiernillo-Zicuirán Biosphere Reserve of southern Michoacán, Mexico, is described and illustrated.  It occurs in a tropical deciduous forest at elevations of 400 to 500 m, and all known hosts belong to Fabaceae. The long, straight, pendulous stems and elongated vegetative internodes are distinctive features. It is most similar to P. nudum but differs by having 3 or 4 pistillate flowers per fertile bract, expanded albeit highly reduced leaves, and longer vegetative internodes. It is also similar to P. teretifolium from which it differs by having a pendulous habit, longer vegetative internodes, 3 or 4 pistillate flowers per fertile bract, and fruits on short internodes.
Saharan Dust and the Nonlinear Evolution of the African Easterly Jet–African Easterly Wave System
Authors: Grogan Dustin F. P. , Nathan Terrence R. , Chen Shu-Hua
Published: September 2016

The direct radiative effects of Saharan mineral dust (SMD) aerosols on the nonlinear evolution of the African easterly jet–African easterly wave (AEJ–AEW) system is examined using the Weather Research and Forecasting Model coupled to an online dust model. The SMD-modified AEW life cycles are characterized by four stages: enhanced linear growth, weakened nonlinear stabilization, larger peak amplitude, and smaller long-time amplitude. During the linear growth and nonlinear stabilization stages, the SMD increases the generation of eddy available potential energy (APE); this occurs where the maximum in the mean meridional SMD gradient is coincident with the critical surface. As the AEWs evolve beyond the nonlinear stabilization stage, the discrimination between SMD particle sizes due to sedimentation becomes more pronounced; the finer particles meridionally expand, while the coarser particles settle to the surface. The result is a reduction in the eddy APE at the base and the top of the plume.

The SMD enhances the Eliassen–Palm (EP) flux divergence and residual-mean meridional circulation, which generally oppose each other throughout the AEW life cycle. The SMD-modified residual-mean meridional circulation initially dominates to accelerate the flow but quickly surrenders to the EP flux divergence, which causes an SMD-enhanced deceleration of the AEJ during the linear growth and nonlinear stabilization stages. Throughout the AEW life cycle, the SMD-modified AEJ is elevated and the peak winds are larger than without SMD. During the first (second) half of the AEW life cycle, the SMD-modified wave fluxes shift the AEJ axis farther equatorward (poleward) of its original SMD-free position.