bluuebunny/crossref_metadata_2025 huggingface dataset:
Seedling Performance Associated with Live or Herbicide Treated Tall Fescue
Authors: Halvorson Jonathan J. , Belesky David P. , Godwin Harry W.
Published: February 2015

Tall fescue is an important forage grass which can host systemic fungal endophytes. The association of host grass and endophyte is known to influence herbivore behavior and host plant competition for resources. Establishing legumes into existing tall fescue sods is a desirable means to acquire nitrogen and enhance the nutritive value of forage for livestock production. Competition from existing tall fescue typically must be controlled to ensure interseeding success. We used a soil-on-agar method to determine if soil from intact, living (L), or an herbicide killed (K) tall fescue sward influenced germination and seedling growth of three cultivars of tall fescue (E+, MaxQ, and E−) or legumes (alfalfa, red clover, and white clover). After 30 days, seedlings were larger and present in greater numbers when grown in L soil rather than K soil. Root growth of legumes (especially white clover) and tall fescue (especially MaxQ) were not as vigorous in K soil as L soil. While shoot biomass was similar for all cultivars of tall fescue in L soil, MaxQ produced less herbage when grown in K soil. Our data suggest establishing legumes or fescue cultivars may not be improved by first killing the existing fescue sod and seedling performance can exhibit significant interseasonal variation, related only to soil conditions.
Trajectory Tracking and Stabilization of a Quadrotor Using Model Predictive Control of Laguerre Functions
Authors: Chipofya Mapopa , Lee Deok Jin , Chong Kil To
Published: February 2015

This paper presents a solution to stability and trajectory tracking of a quadrotor system using a model predictive controller designed using a type of orthonormal functions called Laguerre functions. A linear model of the quadrotor is derived and used. To check the performance of the controller we compare it with a linear quadratic regulator and a more traditional linear state space MPC. Simulations for trajectory tracking and stability are performed in MATLAB and results provided in this paper.
The Inhibitory Effect of Kakkonto, Japanese Traditional (Kampo) Medicine, on Brain Penetration of Oseltamivir Carboxylate in Mice with Reduced Blood-Brain Barrier Function
Authors: Ohara Kousuke , Oshima Shinji , Fukuda Nanami , Ochiai Yumiko , Maruyama Ayumi , Kanamuro Aki , Negishi Akio , Honma Seiichi , Ohshima Shigeru , Akimoto Masayuki , Takenaka Shingo , Kobayashi Daisuke
Published: February 2015

Oseltamivir phosphate (OP) is used to treat influenza virus infections. However, its use may result in central nervous system (CNS) adverse effects. In Japan, OP is used with Kampo formulations to improve clinical effectiveness. We evaluated the potential for using Kampo formulations to reduce CNS adverse effects by quantifying the CNS distribution of oseltamivir and its active metabolite oseltamivir carboxylate (OC) when administered with maoto and kakkonto. We administered lipopolysaccharide (LPS) by intraperitoneal injection to C57BL/6 mice to reduce blood-brain barrier function. Saline, maoto, and kakkonto were administered orally at the same time as LPS. OP was orally administered 4 hours after the last LPS injection and the migration of oseltamivir and OC was examined. Additionally, we examined the brain distribution of OC following intravenous administration. Changes in OC concentrations in the brain suggest that, in comparison to LPS-treated control mice, both Kampo formulations increased plasma levels of OC, thereby enhancing its therapeutic effect. Additionally, our findings suggest kakkonto may not only improve the therapeutic effect of oseltamivir but also reduce the risk of CNS-based adverse effects. Considering these findings, it should be noted that administration of kakkonto during periods of inflammation has led to increased OAT3 expression.
Ascertainment and Verification of End-Stage Renal Disease and End-Stage Liver Disease in the North American AIDS Cohort Collaboration on Research and Design
Authors: Kitahata Mari M. , Drozd Daniel R. , Crane Heidi M. , Van Rompaey Stephen E. , Althoff Keri N. , Gange Stephen J. , Klein Marina B. , Lucas Gregory M. , Abraham Alison G. , Lo Re Vincent , McReynolds Justin , Lober William B. , Mendes Adell , Modur Sharada P. , Jing Yuezhou , Morton Elizabeth J. , Griffith Margaret A. , Freeman Aimee M. , Moore Richard D.
Published: February 2015

The burden of HIV disease has shifted from traditional AIDS-defining illnesses to serious non-AIDS-defining comorbid conditions. Research aimed at improving HIV-related comorbid disease outcomes requires well-defined, verified clinical endpoints. We developed methods to ascertain and verify end-stage renal disease (ESRD) and end-stage liver disease (ESLD) and validated screening algorithms within the largest HIV cohort collaboration in North America (NA-ACCORD). Individuals who screened positive among all participants in twelve cohorts enrolled between January 1996 and December 2009 underwent medical record review to verify incident ESRD or ESLD using standardized protocols. We randomly sampled 6% of contributing cohorts to determine the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ESLD and ESRD screening algorithms in a validation subcohort. Among 43,433 patients screened for ESRD, 822 screened positive of which 620 met clinical criteria for ESRD. The algorithm had 100% sensitivity, 99% specificity, 82% PPV, and 100% NPV for ESRD. Among 41,463 patients screened for ESLD, 2,024 screened positive of which 645 met diagnostic criteria for ESLD. The algorithm had 100% sensitivity, 95% specificity, 27% PPV, and 100% NPV for ESLD. Our methods proved robust for ascertainment of ESRD and ESLD in persons infected with HIV.
Changes of pH inβ-Lactoglobulin andβ-Casein Solutions during High Pressure Treatment
Authors: Olsen Karsten , Jespersen Bo B. , Orlien Vibeke
Published: February 2015

The pH changes in the milk systems,β-lactoglobulin B,β-casein, and mixture ofβ-lactoglobulin andβ-casein (pH 7 and ionic strength 0.08 M) were measuredin situduring increasing pressure up to 500 MPa. An initial decrease to pH 6.7 was observed from 0.1 to 150 MPa forβ-lactoglobulin, followed by an increase to pH 7.3 at 500 MPa. The initial decrease is suggested to be caused by the deprotonation of histidine, while the increase is suggested to result from an increase of hydroxide ions due to the loss of tertiary structure. The change in pH of theβ-casein solution displayed an almost linear increasing pressure dependency up to a pH of 7.7 at 500 MPa. The limited tertiary structure ofβ-casein could allow exposure of all amino acids; thus the increase of pH can be caused by binding of water protons resulting in an increase of hydroxide ions. Addition ofβ-casein toβ-lactoglobulin (1:1) was found to suppress the initial pH decrease found for theβ-lactoglobulin solution. The pH change of the mixture did not suggest any intermolecular interaction, and a simple additive model is proposed to calculate the pH change of the mixture from the corresponding individual samples.
Antimycobacterial and Nitric Oxide Production Inhibitory Activities of Ocotea notata from Brazilian Restinga
Authors: Costa Isabela Francisca Borges , Calixto Sanderson Dias , Heggdorne de Araujo Marlon , Konno Tatiana Ungaretti Paleo , Tinoco Luzineide Wanderley , Guimarães Denise Oliveira , Lasunskaia Elena B. , Leal Ivana Ramos Correa , Muzitano Michelle Frazão
Published: February 2015

The genus Ocotea (Lauraceae) is distributed mainly in tropical and subtropical regions. Some species of this genus as O. puberula and O. quixos have been described in the literature, showing antibacterial activity. And Ocotea macrophylla showed anti‐inflammatory activity with inhibition of COX‐1, COX‐2, and LOX‐5. The purpose of this study was the phytochemical investigation of the plant species Ocotea notata from Restinga Jurubatiba National Park, Macaé, RJ, Brazil, and the search for antimycobacterial fractions and compounds. The crude extract was evaluated for antimycobacterial activity and presented 95.75 ± 2.53% of growth inhibition at 100 µg/mL. Then, it was subjected to a liquid‐liquid partition and subsequently was chemically investigated by HPLC, revealing the major presence of flavonoids. In this process the partition fractions hexane, ethyl acetate, and butanol are shown to be promising in the antimycobacterial assay. In addition, ethyl acetate fraction was chromatographed and afforded two flavonoids identified by MS and NMR as afzelin and isoquercitrin. The isolated flavonoids afzelin and isoquercitrin were evaluated for their antimycobacterial activity and for their ability to inhibit NO production by macrophages stimulated by LPS; both flavonoids isoquercitrin (Acet22) and afzelin (Acet32) were able to inhibit the production of NO by macrophages. The calculated IC50 of Acet22 and Acet32 was 1.03 and 0.85 µg/mL, respectively.
Altered Viral Replication and Cell Responses by Inserting MicroRNA Recognition Element into PB1 in Pandemic Influenza A Virus (H1N1) 2009
Authors: Shen Xiaoyue , Sun Wenkui , Shi Yi , Xing Zheng , Su Xin
Published: February 2015

Objective. MicroRNAs (miRNAs) are endogenous noncoding RNAs that spatiotemporally modulate mRNAs in a posttranscriptional manner. Engineering mutant viruses by inserting cell‐specific miRNA recognition element (MRE) into viral genome may alter viral infectivity and host responses in vital tissues and organs infected with pandemic influenza A virus (H1N1) 2009 (H1N1pdm). Methods. In this study, we employed reverse genetics approach to generate a recombinant H1N1pdm with a cell‐specific miRNA target sequence inserted into its PB1 genomic segment to investigate whether miRNAs are able to suppress H1N1pdm replication. We inserted an MRE of microRNA‐let‐7b (miR‐let‐7b) into the open reading frame of PB1 to test the feasibility of creating a cell‐restricted H1N1pdm virus since let‐7b is abundant in human bronchial epithelial cells. Results. miR‐let‐7b is rich in human bronchial epithelial cells (HBE). Incorporation of the miR‐let‐7b‐MRE confers upon the recombinant H1N1pdm virus susceptibility to miR‐let‐7b targeting, suggesting that the H1N1pdm and influenza A viruses can be engineered to exert the desired replication restrictive effect and decrease infectivity in vital tissues and organs. Conclusions. This approach provides an additional layer of biosafety and thus has great potential for the application in the rational development of safer and more effective influenza viral vaccines.
Desmoplasia in Primary Tumors and Metastatic Lesions of Pancreatic Cancer
Authors: Whatcott Clifford J. , Diep Caroline H. , Jiang Ping , Watanabe Aprill , LoBello Janine , Sima Chao , Hostetter Galen , Shepard H. Michael , Von Hoff Daniel D. , Han Haiyong
Published: February 2015

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is characterized by high levels of fibrosis, termed desmoplasia, which is thought to hamper the efficacy of therapeutics treating PDAC. Our primary focus was to evaluate differences in the extent of desmoplasia in primary tumors and metastatic lesions. As metastatic burden is a primary cause for mortality in PDAC, the extent of desmoplasia in metastases may help to determine whether desmoplasia targeting therapeutics will benefit patients with late-stage, metastatic disease.

Experimental Design: We sought to assess desmoplasia in metastatic lesions of PDAC and compare it with that of primary tumors. Fifty-three patients' primaries and 57 patients' metastases were stained using IHC staining techniques.

Results: We observed a significant negative correlation between patient survival and extracellular matrix deposition in primary tumors. Kaplan–Meier curves for collagen I showed median survival of 14.6 months in low collagen patients, and 6.4 months in high-level patients (log rank, P < 0.05). Low-level hyaluronan patients displayed median survival times of 24.3 months as compared with 9.3 months in high-level patients (log rank, P < 0.05). Our analysis also indicated that extracellular matrix components, such as collagen and hyaluronan, are found in high levels in both primary tumors and metastatic lesions. The difference in the level of desmoplasia between primary tumors and metastatic lesions was not statistically significant.

Conclusions: Our results suggest that both primary tumors and metastases of PDAC have highly fibrotic stroma. Thus, stromal targeting agents have the potential to benefit PDAC patients, even those with metastatic disease. Clin Cancer Res; 21(15); 3561–8. ©2015 AACR.

See related commentary by Olive, p. 3366
Hotspot Mutation Panel Testing Reveals Clonal Evolution in a Study of 265 Paired Primary and Metastatic Tumors
Authors: Goswami Rashmi S. , Patel Keyur P. , Singh Rajesh R. , Meric-Bernstam Funda , Kopetz E. Scott , Subbiah Vivek , Alvarez Ricardo H. , Davies Michael A. , Jabbar Kausar J. , Roy-Chowdhuri Sinchita , Lazar Alexander J. , Medeiros L. Jeffrey , Broaddus Russell R. , Luthra Rajyalakshmi , Routbort Mark J.
Published: February 2015

Purpose: We used a clinical next-generation sequencing (NGS) hotspot mutation panel to investigate clonal evolution in paired primary and metastatic tumors.

Experimental Design: A total of 265 primary and metastatic tumor pairs were sequenced using a 46-gene cancer mutation panel capable of detecting one or more single-nucleotide variants as well as small insertions/deletions. Mutations were tabulated together with tumor type and percentage, mutational variant frequency, time interval between onset of primary tumor and metastasis, and neoadjuvant therapy status.

Results: Of note, 227 of 265 (85.7%) tumor metastasis pairs showed identical mutation calls. Of the tumor pairs with identical mutation calls, 160 (60.4%) possessed defining somatic mutation signatures and 67 (25.3%) did not exhibit any somatic mutations. There were 38 (14.3%) cases that showed at least one novel mutation call between the primary and metastasis. Metastases were almost two times more likely to show novel mutations (n = 20, 7.5%) than primary tumors (n = 12, 4.5%). TP53 was the most common additionally mutated gene in metastatic lesions, followed by PIK3CA and SMAD4. PIK3CA mutations were more often associated with metastasis in colon carcinoma samples.

Conclusions: Clinical NGS hotspot panels can be useful in analyzing clonal evolution within tumors as well as in determining subclonal mutations that can expand in future metastases. PIK3CA, SMAD4, and TP53 are most often involved in clonal divergence, providing potential targets that may help guide the clinical management of tumor progression or metastases. Clin Cancer Res; 21(11); 2644–51. ©2015 AACR.
Preclinical Pharmacological Evaluation of Letrozole as a Novel Treatment for Gliomas
Authors: Dave Nimita , Chow Lionel M.L. , Gudelsky Gary A. , LaSance Kathleen , Qi Xiaoyang , Desai Pankaj B.
Published: February 2015

We present data that letrozole, an extensively used aromatase inhibitor in the treatment of estrogen receptor–positive breast tumors in postmenopausal women, may be potentially used in the treatment of glioblastomas. First, we measured the in vitro cytotoxicity of letrozole and aromatase (CYP19A1) expression and activity in human LN229, T98G, U373MG, U251MG, and U87MG, and rat C6 glioma cell lines. Estrogen receptor (ER)-positive MCF-7 and ER-negative MDA-MB-231 cells served as controls. Cytotoxicity was determined employing the MTT assay, and aromatase activity using an immunoassay that measures the conversion of testosterone to estrogen. Second, in vivo activity of letrozole was assessed in Sprague–Dawley rats orthotopically implanted with C6 gliomas. The changes in tumor volume with letrozole treatment (4 mg/kg/day) were assessed employing μPET/CT imaging, employing [18F]-fluorodeoxyglucose (F18-FDG) as the radiotracer. Brain tissues were collected for histologic evaluations. All glioma cell lines included here expressed CYP19A1 and letrozole exerted considerable cytotoxicity and decrease in aromatase activity against these cells (IC50, 0.1–3.5 μmol/L). Imaging analysis employing F18-FDG μPET/CT demonstrated a marked reduction of active tumor volume (>75%) after 8 days of letrozole treatment. Immunohistochemical analysis revealed marked reduction in aromatase expression in tumoral regions of the brain after letrozole treatment. Thus, employing multifaceted tools, we demonstrate that aromatase may be a novel target for the treatment of gliomas and that letrozole, an FDA-approved drug with an outstanding record of safety may be repurposed for the treatment of such primary brain tumors, which currently have few therapeutic options. Mol Cancer Ther; 14(4); 857–64. ©2015 AACR.
PD-L1 Expression as a Predictive Biomarker in Cancer Immunotherapy
Authors: Patel Sandip Pravin , Kurzrock Razelle
Published: February 2015

The resurgence of cancer immunotherapy stems from an improved understanding of the tumor microenvironment. The PD-1/PD-L1 axis is of particular interest, in light of promising data demonstrating a restoration of host immunity against tumors, with the prospect of durable remissions. Indeed, remarkable clinical responses have been seen in several different malignancies including, but not limited to, melanoma, lung, kidney, and bladder cancers. Even so, determining which patients derive benefit from PD-1/PD-L1–directed immunotherapy remains an important clinical question, particularly in light of the autoimmune toxicity of these agents. The use of PD-L1 (B7-H1) immunohistochemistry (IHC) as a predictive biomarker is confounded by multiple unresolved issues: variable detection antibodies, differing IHC cutoffs, tissue preparation, processing variability, primary versus metastatic biopsies, oncogenic versus induced PD-L1 expression, and staining of tumor versus immune cells. Emerging data suggest that patients whose tumors overexpress PD-L1 by IHC have improved clinical outcomes with anti-PD-1–directed therapy, but the presence of robust responses in some patients with low levels of expression of these markers complicates the issue of PD-L1 as an exclusionary predictive biomarker. An improved understanding of the host immune system and tumor microenvironment will better elucidate which patients derive benefit from these promising agents. Mol Cancer Ther; 14(4); 847–56. ©2015 AACR.
SIRT1 Suppresses Doxorubicin-Induced Cardiotoxicity by Regulating the Oxidative Stress and p38MAPK Pathways
Authors: Ruan Yang , Dong Chunlin , Patel Jigar , Duan Chao , Wang Xinyue , Wu Xi , Cao Yuan , Pu Lianmei , Lu Dan , Shen Tao , Li Jian
Published: February 2015

Background: SIRT1, which belongs to the Sirtuin family of NAD-dependent enzymes, plays diverse roles in aging, metabolism, and disease biology. It could regulate cell survival and has been shown to be a protective factor in heart function. Hence, we verified the mechanism by which SIRT1 regulates doxorubicin induced cardiomyocyte injury in vivo and in vitro. Methods: We analyzed SIRT1 expression in doxorubicin-induced neonatal rat cardiomyocyte injury model and adult mouse heart failure model. SIRT1 was over-expressed in cultured neonatal rat cardiomyocyte by adenovirus mediated gene transfer. SIRT1 agonist resveratrol was used to treat the doxorubicin-induced heart failure mouse model. Echocardiography, reactive oxygen species (ROS) production, TUNEL, qRT-PCR, and Western blotting were performed to analyze cell survival, oxidative stress, and inflammatory signal pathways in cardiomyocytes. Results: SIRT1 expression was down-regulated in doxorubicin induced cardiomocyte injury, accompanied by elevated oxidative stress and cell apoptosis. SIRT1 over-expression reduced doxorubicin induced cardiomyocyte apoptosis with the attenuated ROS production. SIRT1 also reduced cell apoptosis by inhibition of p38MAPK phosphorylation and caspase-3 activation. The SIRT1 agonist resveratrol was able to prevent doxorubicin-induced heart function loss. Moreover, the SIRT1 inhibitor niacinamide could reverse SIRT1's protective effect in cultured neonatal rat cardiomyocytes. Conclusions: These results support the role of SIRT1 as an important regulator of cardiomyocyte apoptosis during doxorubicin-induced heart injury, which may represent a potential therapeutic target for doxorubicin-induced cardiomyopathy.
Characterization and Functions of Vascular Adventitial Fibroblast Subpopulations
Authors: An Sheng Jun , Liu Pei , Shao Tie Mei , Wang Zhi Jun , Lu Hai Gang , Jiao Zhan , Li Xue , Fu Jun Qiu
Published: February 2015

Background: Adventitial fibroblasts have been shown to play an important role in vascular remodeling and contribute to neointimal formation in vascular diseases. However, little is known about adventitial fibroblast subpopulations. This study explored the process of isolating rat thoracic aorta adventitial fibroblast subpopulations and characterized their properties following stimulation with angiotensin II (ANG II), a critical factor involved in cardiovascular diseases such as hypertension. Methods: Adventitial fibroblasts were isolated and cultured from rat aorta. Fibroblast subpopulations were individually expanded using cloning ring techniques. Cells were treated with ANG II (10 nM, 100 nM and 1 μM) for 0.5, 1, 1.5, 3, 6, 12, or 24 h, and ANG II-induced proliferation and migration were measured by MTT assay and Transwell. Cells were treated with ANG II (100 nM) in the presence or absence of ANG II receptor antagonists (100 μM), losartan (for AT1) and PD-123319 (for AT2). PreproET-1 mRNA and ET-1 were determined by RT-PCR and ELISA, respectively. Collagen type I was detected by western blotting. Results: Two major fibroblast subpopulations were found in the adventitia, epithelioid-like cells and spindle-like cells; Although ANG II promotes the growth of both subpopulations, epithelioid-like cell proliferation shows dose-dependency on ANG II from 10 nM to 1 μM, while proliferation of spindle-like cells reaches a peak value following 100 nM ANG II stimulation; ANG II stimulation enhanced epithelioid-like but not spindle-like cell migration; ANG II dose-dependently increased the expression of preproET-1 and collagen type I, and enhanced ET-1 secretion in epithelioid-like but not spindle-like cells, effects abolished by the AT1 receptor antagonist, but not with AT2 receptor antagonist. Conclusion: Adventitial fibroblasts are heterogeneous and epithelioid-like subpopulations with high sensitivity to ANG II stimulation may be implicated in the pathophysiological mechanisms of vascular remodeling, reparative processes and cardiovascular diseases.
MiR-940 Inhibited Pancreatic Ductal Adenocarcinoma Growth by Targeting MyD88
Authors: Song Bin , Zhang Chaoxiong , Li Gang , Jin Gang , Liu Cong
Published: February 2015

Background: Pancreatic ductal adenocarcinoma (PDAC) is an almost universally lethal disease. Deregulation or dysfunction of miRNAs contribute to cancer development. The role of miR-940 in PDAC remains unclear. Methods: The level of miR-940 in PDAC tissues and cell lines was measured by qRT-PCR. MiR-940 was over-expressed by miRNAs mimics transfection and reduced by miRNAs antisense oligonucleotides (ASO) transfection. Cell proliferation was analyzed by MTT assay and cell apoptosis was evaluated by FACS analysis. Targeted genes were predicted by a bioinformatics algorithm and confirmed by a dual luciferase reporter assay. Myeloid differentiation primary response gene (88) (MyD88) protein level was assayed by immunohistochemistry and Western blot analysis. Results: Low miR-940 level and high MyD88 protein level in PDAC tissues were both correlated with low survival rate. Up-regulation of miR-940 inhibited PDAC cell lines growth while down-regulation induced cell growth. The 3' UTR of MyD88 was targeted by miR-940. Conclusions: Low level of miR-940 and high level of MyD88 in PDAC promoted PDAC cells growth which might be related to the low survival rate of PDAC patients. MiR-940 exerted its effect by targeting MyD88.
Nitro-Oleic Acid Attenuates OGD/R-Triggered Apoptosis in Renal Tubular Cells via Inhibition of Bax Mitochondrial Translocation in a PPAR-γ-Dependent Manner
Authors: Nie Huibin , Xue Xia , Li Jie , Liu Xiangchun , Lv Shasha , Guan Guangju , Liu Haiying , Liu Gang , Liu Shanshan , Chen Zhixin
Published: February 2015

Background: Nitroalkene derivatives of oleic acid (OA-NO2) serve as high-affinity ligand for PPAR-γ, which regulates apoptosis, oxidation and inflammation and plays a central role in ischemia-reperfusion injury. In the present study, we elucidated the protective mechanisms of OA-NO2 against renal ischemia-reperfusion injury. Methods: HK-2 cells were subjected to oxygen and glucose deprivation followed by re-oxygenation (OGD/R) to mimic renal ischemia-reperfusion injury. Cell apoptosis was analyzed by flow cytometry. Bax mitochondrial translocation, cytochrome c and apoptosis-inducing factor (AIF) cytosolic leakage and Akt/Gsk 3β phosphorylation were evaluated by Western blotting. Bax activation was visualized by immunocytochemistry. GW9662 and siRNA transfection were employed to examine the involvement of PPAR-γ. Results: OGD/R injury promoted mitochondrial translocation and activation of Bax, leakage of cytochrome c and AIF, subsequent caspase-3 activation, and eventually cell apoptosis. Pre-incubation with OA-NO2 (1.25 µM, 45min) inhibited Bax activation and blocked apoptotic cascade, while the protective effects were negated by GW9662 or PPAR-γ siRNA. Moreover, OA-NO2 restored Akt and Gsk 3β phosphorylation in a PPAR-γ-dependent way. Conclusion: These findings suggest that OA-NO2 attenuates OGD/R-induced apoptosis by inhibiting Bax translocation and activation and the subsequent mitochondria-dependent apoptotic cascade in a PPAR-γ dependent manner.
Increased Oxidative Stress and Mitochondrial Dysfunction in Zucker Diabetic Rat Liver and Brain
Authors: Raza Haider , John Annie , Howarth Frank Christopher
Published: February 2015

Background/Aims: The Zucker diabetic fatty (ZDF, FA/FA) rat is a genetic model of type 2 diabetes, characterized by insulin resistance with progressive metabolic syndrome. We have previously demonstrated mitochondrial dysfunction and oxidative stress in the heart, kidneys and pancreas of ZDF rats. However, the precise molecular mechanism of disease progression is not clear. Our aim in the present study was to investigate oxidative stress and mitochondrial dysfunction in the liver and brain of ZDF rats. Methods: In this study, we have measured mitochondrial oxidative stress, bioenergetics and redox homeostasis in the liver and brain of ZDF rats. Results: Our results showed increased reactive oxygen species (ROS) production in the ZDF rat brain compared to the liver, while nitric oxide (NO) production was markedly increased both in the brain and liver. High levels of lipid and protein peroxidation were also observed in these tissues. Glutathione metabolism and mitochondrial respiratory functions were adversely affected in ZDF rats when compared to Zucker lean (ZL, +/FA) control rats. Reduced ATP synthesis was also observed in the liver and brain of ZDF rats. Western blot analysis confirmed altered expression of cytochrome P450 2E1, iNOS, p-JNK, and IκB-a confirming an increase in oxidative and metabolic stress in ZDF rat tissues. Conclusions: Our data shows that, like other tissues, ZDF rat liver and brain develop complications associated with redox homeostasis and mitochondrial dysfunction. These results, thus, might have implications in understanding the etiology and pathophysiology of diabesity which in turn, would help in managing the disease associated complications.
Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women
Authors: Knapen Marjo H. J. , Braam Lavienja A. J. L. M. , Drummen Nadja E. , Bekers Otto , Hoeks Arnold P. G. , Vermeer Cees
Published: February 2015

Observational data suggest a link between menaquinone (MK, vitamin K2) intake and cardiovascular (CV) health. However, MK intervention trials with vascular endpoints are lacking. We investigated long-term effects of MK-7 (180 μg MenaQ7/day) supplementation on arterial stiffness in a double-blind, placebo-controlled trial. Healthy postmenopausal women (n=244) received either placebo (n=124) or MK-7 (n=120) for three years. Indices of local carotid stiffness (intimamedia thickness IMT, Diameter end-diastole and Distension) were measured by echotracking. Regional aortic stiffness (carotid-femoral and carotid-radial Pulse Wave Velocity, cfPWV and crPWV, respectively) was measured using mechanotransducers. Circulating desphospho-uncarboxylated matrix Gla-protein (dp-ucMGP) as well as acute phase markers Interleukin-6 (IL-6), high-sensitive C-reactive protein (hsCRP), tumour necrosis factor-α (TNF-α) and markers for endothelial dysfunction Vascular Cell Adhesion Molecule (VCAM), E-selectin, and Advanced Glycation Endproducts (AGEs) were measured. At baseline dp-ucMGP was associated with IMT, Diameter, cfPWV and with the mean z-scores of acute phase markers (APMscore) and of markers for endothelial dysfunction (EDFscore). After three year MK-7 supplementation cfPWV and the Stiffness Index β significantly decreased in the total group, whereas distension, compliance, distensibility, Young’s Modulus, and the local carotid PWV (cPWV) improved in women having a baseline Stiffness Index β above the median of 10.8. MK-7 decreased dp-ucMGP by 50 % compared to placebo, but did not influence the markers for acute phase and endothelial dysfunction. In conclusion, long-term use of MK-7 supplements improves arterial stiffness in healthy postmenopausal women, especially in women having a high arterial stiffness.
Association of Objectively Measured Physical Activity With Cardiovascular Risk in Mobility‐limited Older Adults
Authors: Fitzgerald Jodi D. , Johnson Lindsey , Hire Don G. , Ambrosius Walter T. , Anton Stephen D. , Dodson John A. , Marsh Anthony P. , McDermott Mary M. , Nocera Joe R. , Tudor‐Locke Catrine , White Daniel K. , Yank Veronica , Pahor Marco , Manini Todd M. , Buford Thomas W. ,   the LIFE Study Research Group
Published: February 2015

Background

Data are sparse regarding the impacts of habitual physical activity (PA) and sedentary behavior on cardiovascular (CV) risk in older adults with mobility limitations.

Methods and Results

This study examined the baseline, cross‐sectional association between CV risk and objectively measured PA among participants in the Lifestyle Interventions and Independence for Elders (LIFE) study. The relationship between accelerometry measures and predicted 10‐year Hard Coronary Heart Disease (HCHD) risk was modeled by using linear regression, stratified according to CVD history. Participants (n=1170, 79±5 years) spent 642±111 min/day in sedentary behavior (ie, <100 accelerometry counts/min). They also spent 138±43 min/day engaging in PA registering 100 to 499 accelerometry counts/min and 54±37 min/day engaging in PA ≥500 counts/min. Each minute per day spent being sedentary was associated with increased HCHD risk among both those with (0.04%, 95% CI 0.02% to 0.05%) and those without (0.03%, 95% CI 0.02% to 0.03%) CVD. The time spent engaging in activities 100 to 499 as well as ≥500 counts/min was associated with decreased risk among both those with and without CVD (
P
<0.05). The mean number of counts per minute of daily PA was not significantly associated with HCHD risk in any model (
P
>0.05). However, a significant interaction was observed between sex and count frequency (
P
=0.036) for those without CVD, as counts per minute was related to HCHD risk in women (β=−0.94, −1.48 to −0.41;
P
<0.001) but not in men (β=−0.14, −0.59 to 0.88;
P
=0.704).

Conclusions

Daily time spent being sedentary is positively associated with predicted 10‐year HCHD risk among mobility‐limited older adults. Duration, but not intensity (ie, mean counts/min), of daily PA is inversely associated with HCHD risk score in this population—although the association for intensity may be sex specific among persons without CVD.

Clinical Trial Registration

URL:
www.clinicaltrials.gov
Unique identifier: NCT01072500
The Political Landscape Surrounding Anti-Cruelty Legislation in Canada
Authors: Verbora Antonio Robert
Published: February 2015

In 1998, the federal government launched a consultation process, which pointed out that nothing significant had been done to change federal anti-cruelty laws in Canada since 1892. The consultation process concluded that among other concerns, outdated wording of the law has prevented the prosecution of many serious nonhuman animal abusers. Since 1999, there have been a number of failed amendments to the Criminal Code anti-cruelty provisions. The study examines the trajectory of the proposed changes since 1999 to the present, using official transcripts of Canadian parliamentary debates, and seeks to understand the politics of animal cruelty legislation in Canada. Using thematic analysis, this paper explores how resistance to the amendments is articulated and rationalized, as well as the grounds upon which proponents argue in favor of amending the anti-cruelty provisions. The study ultimately sheds light on the failure to bring 19th century Canadian criminal laws into the 21st century.
Nonhuman Animal Cruelty, Bullying, and Behavioral Difficulties among Women
Authors: Sanders Cheryl E. , Henry Bill C.
Published: February 2015

The current study sought to examine the relationship between behavioral difficulties, animal abuse, and bullying among women. Five hundred female undergraduate students enrolled in Introductory Psychology completed surveys assessing animal abuse experiences, bullying behaviors, and victimization of bullying during their K-12 school years. Participants also completed the Strengths and Difficulties Questionnaire which evaluated their behavioral difficulties. Results revealed a significant relationship between animal abuse, bullying, and victimization experiences. Moreover, animal abusers displayed significantly more behavioral problems when compared to non-abusers. Results from regression analyses indicated that animal abuse, bullying and victimization were significant predictors of various behavioral issues. These results suggest that behavioral difficulties associated with female animal abusers are similar to those related to male perpetrators.
Soil nematode assemblages in an acid soil as affected by lime application
Authors: Zhao Jie , Zhao Cancan , Wan Songze , Wang Xiaoli , Zhou Lixia , Fu Shenglei
Published: February 2015

Liming can affect soil biota through alterations in soil pH and soil structure. Many earlier studies monitored the responses of soil nematode communities to lime application but they did not come to a consensus and did not use indices of soil nematode community and multivariate statistical approaches developed over the past two decades. The present research explored the short-term effects of lime application on soil nematode communities in an acrisol in threeEucalyptusplantations in southern China. Nematodes were sampled from control and lime-treated plots at three periods from October 2011 to February 2012 at 0-10 cm and 10-20 cm soil depths. Repeated measures ANOVA showed that lime application significantly reduced the abundance of herbivores at 10-20 cm depth during the study. Lime application tended to increase the bacterivore index at 0-10 cm depth over time. Principal response curves of soil nematode community structure, in terms of nematode trophic group composition, revealed that the differences between control and lime application treatments increased over time, primarily because of the decline of fungivores in plots treated with lime. The decline in fungivores resulted mainly from declines ofFilenchusandDitylenchus. The results suggest that the fungal-mediated decomposition channel in the soil food web was suppressed by lime application. Our study also demonstrated that the sensitivity of different nematode genera to lime application varied widely, even for genera within the same trophic group. In particular, the abundance of several bacterivorous genera (Prismatolaimus,Plectus,Wilsonema,Protorhabditis,DiploscapterandHeterocephalobus) gradually declined and that ofRhabditonemaat 0-10 cm depth gradually increased following lime application during the study; two herbivorous genera,TrophotylenchulusandHelicotylenchus, had opposite responses to lime application at 0-10 cm depth. Integrating univariate statistical approaches with multivariate approaches facilitated the analysis of soil nematode responses to lime application.
Maritime Delimitation in the Arctic: Implications for Fisheries Jurisdiction and Cooperation in the Barents Sea
Authors: Dahl Irene
Published: February 2015

After 40 years of negotiations, Norway and Russia entered into the Barents Sea Treaty in 2010. The treaty fixes the delimitation line in the Barents Sea. During this period the parties succeeded in developing a body for cooperation on conservation and management of the shared/straddling fish stocks: the joint Norwegian-Russian Fisheries Commission. This article examines the effect of the treaty on fisheries jurisdiction and future fisheries cooperation between Norway and Russia.
An Environmental Management Strategy for the International Seabed Authority? The Legal Basis
Authors: Jaeckel Aline
Published: February 2015

The number of contracts granted by the International Seabed Authority (isa) to explore minerals on the seabed beyond national jurisdiction has increased greatly in recent years and commercial exploitation is scheduled to start in the near future. A core challenge is to establish adequate environmental protection measures, procedural safeguards, and institutional arrangements to balance commercial mining with environmental protection. This is especially important given the urgent need to utilize existing legal and institutional frameworks, such as the isa, to protect marine biodiversity in areas beyond national jurisdiction. This article analyses the isa’s mandate to adopt a comprehensive environmental management strategy. It outlines the legal basis of eight potential components of such a strategy. Although several of these have been endorsed by the isa on a temporary or ad hoc basis, substantial gaps remain. An environmental management strategy could provide for systematic environmental safeguards during both exploration and exploitation for minerals.
Criminal Justice beyond National Sovereignty. An Alternative Perspective on the Europeanisation of Criminal Law
Authors: Ouwerkerk Jannemieke
Published: February 2015

Over the past few decades the competences of the eu to enact legislation in criminal matters have significantly increased. Member States and criminal law experts have raised concerns: to what extent can national sovereignty and domestic interests regarding criminal justice be preserved? This paper argues that the perspective of national sovereignty should not be the primary concern in criminal justice affairs in the eu. It is proposed that eu legal measures in this area are primarily judged on whether they in their entirety contribute to a reasonable balance between effective law enforcement and adequate judicial protection of individuals. From this perspective, recent developments potentially contribute to redressing the balance in eu criminal law.
A new nomenclatural change in Polycarpon (Caryophyllaceae): P. tetraphyllum subsp. sauvagei comb. & stat. nov., an endemic taxon from Morocco
Authors: Iamonico Duilio
Published: February 2015

The recent molecular investigations by Kool et al. (2007) clearly showed the polyphyly of the genus Polycarpon Linnaeus (1759: 859, 881) which includes, in the new restricted sense, only the taxa belonging to the Polycarpon tetraphyllum clade, while the South American P. suffruticosum Grisebach (1874: 77−78), and P. coquimbense Gereau & Marticonema (1995: 154), and the widespread tropical P. prostratum (Forsskål 1775: 207) Ascherson & Schweinfurth (1889: 128) are to be excluded. Kool et al. (2007) also suggested treating all the members of the P. tetraphyllum group as a single species with the recognition of several subspecies. Accordingly, Iamonico (2013), and Iamonico & Domina (2015) proposed four new nomenclatural combinations [a further proposal about the northwestern American P. depressum Nuttal ex Torrey & Gray (1838: 174) is in preparation].
Cytospora species associated with canker disease of three anti-desertification plants in northwestern China

Authors: Fan Xinlei , Hyde Kevin D. , Yang Qin , Liang Yingmei , Ma Rong , Tian Chengming
Published: February 2015

Cytospora species are important phytopathogens causing severe canker disease with a worldwide distribution and broad host range. However, identification of taxa to species level is difficult due to poor phylogenetic understanding and lack of sequenced type species. Morphological and phylogenetic studies have been carried out on several important hosts such as Eucalyptus and Malus in China, Iran, and South Africa. In this study destructive canker diseases of the anti-desertification plants, Elaeagnus angustifolia, Hippophae rhamnoides, and Salix psammophila, were investigated in northwest China. Multilocus phylogenetic analyses of ITS, nrLSU, RPB2, and ACT gene regions, combined with detailed morphological analyses and comparison with ex-type strains revealed six Cytospora species, C. chrysosperma, C. elaeagni, C. hippophaes, C. nivea, C. populina comb. nov. and C. gigaspora sp. nov. causing cankers on these hosts. The novel species C. gigaspora has flat multiple locules with a conceptacle and unusually long 12 µm conidia. Detailed descriptions and molecular data for the Cytospora species causing cankers on the three psammophilic host plants are provided. Cytospora elaeagni and C. hippophaes have previously been recorded from Elaeagnus angustifolia and Hippophae rhamnoides, whereas the other species causing Cytospora canker of Elaeagnus angustifolia and Salix psammophila are new records.
First mature fruit description of Pietrosia laevitomentosa (Asteraceae) and its implications to the taxonomic position of the genus Pietrosia

Authors: Manole Anca
Published: February 2015

For the first time we describe the morphology and anatomy of mature achenes bearing fertile seeds of Pietrosia laevitomentosa, an endemic plant species in the Eastern Carpathians. The new diagnostic features of the genus Pietrosia justify its taxonomic recognition as separate from Andryala; those are the achene size (between 2.5 and 4.3 mm long), the deciduous pappus, the single-rimmed achene apex, the elongate exocarpic cells, the complete ring of mesocarpic sclerenchyma (up to 11-layered), and the number and localization of the vascular bundles (5 bundles, in the small ribs). Furthermore, our data may also serve to reconsider the species ecology and conservation strategies.
Primulina fengkaiensis (Gesneriaceae), a new species from limestone areas in Western Guangdong, China

Authors: Lin Ning Zu , BO PAN , MING KANG
Published: February 2015

Primulina fengkaiensis from western Guangdong, China, is described and illustrated. It is similar to the phylogenetically related P. baishouensis and P. gueilinensis in the shape and size of corolla, but differs by leaf blades being elliptic to elliptic–lanceolate, 10–21 × 4–8 cm, margin with serrate, leaf blade adaxially sparsely pubescent, petiole 0.6–1.5 cm wide, pedicel 2.2–4 (–7.5) cm long, cymes 3–9–flowered, stigma 4–5 mm long, lobes ovate.
A new cecidogenous species of Eugnosta Hübner (Lepidoptera: Tortricidae) associated with Baccharis salicifolia (Asteraceae) in the northern Chilean Atacama Desert: Life-history description and phylogenetic inferences
Authors: VARGAS HÉCTOR A. , POLLO PIETRO , BASILIO DANIEL S. , GONÇALVES GISLENE L. , MOREIRA GILSON R. P.
Published: February 2015

Eugnosta Hübner, 1825 (Lepidoptera, Tortricidae, Tortricinae, Cochylini, Cochylina) is reported for the first time in Chile. Male and female adults, the pupa, the last-instar larva, and galls of Eugnosta azapaensis Vargas & Moreira, sp. n., are described and illustrated from the Azapa Valley in the northern Atacama Desert. The larvae induce fusiform galls on shoots of the shrub Baccharis salicifolia (Ruiz & Pav.) Pers. (Asteraceae). An assessment of phylogenetic relationships of E. azapaensis with two congeneric species based on mitochondrial DNA is provided.
A new species of Deutonura (Collembola: Neanuridae: Neanurinae) from north-eastern Algeria, and characterisation of two intraspecific lineages by their barcodes
Authors: DEHARVENG LOUIS , ZOUGHAILECH ABDELMALEK , HAMRA-KROUA SALAH , PORCO DAVID
Published: February 2015

A new species of Deutonura, D. zana sp. nov., is described from north-eastern Algeria. It is morphologically similar in most characters to D. deficiens meridionalis and to D. luberonensis, both members of the D. phlegraea group, differing from the former by the absence of chaeta O on head, and from the later by the separation of tubercles Di and De on Th. I. The muscular insertion pattern of the new species is figured, and suggested as a potential new character for the taxonomy of Neanurinae. Deutonura zana sp. nov. is well characterised by its barcode sequence. Within the new species as morphologically defined, two groups of COI haplotypes, in individuals indistinguishable morphologically, are reported from two distinct mountain ranges. The need of a morphological assessment of demes diverging at significant infra-specific level in their barcodes is stressed.
Exploiting Existing Ground-Based Remote Sensing Networks to Improve High-Resolution Weather Forecasts
Authors: Illingworth A. J. , Cimini D. , Gaffard C. , Haeffelin M. , Lehmann V. , Löhnert U. , O’Connor E. J. , Ruffieux D.
Published: February 2015

A new generation of high-resolution (1 km) forecast models promises to revolutionize the prediction of hazardous weather such as windstorms, flash floods, and poor air quality. To realize this promise, a dense observing network, focusing on the lower few kilometers of the atmosphere, is required to verify these new forecast models with the ultimate goal of assimilating the data. At present there are insufficient systematic observations of the vertical profiles of water vapor, temperature, wind, and aerosols; a major constraint is the absence of funding to install new networks. A recent research program financed by the European Union, tasked with addressing this lack of observations, demonstrated that the assimilation of observations from an existing wind profiler network reduces forecast errors, provided that the individual instruments are strategically located and properly maintained. Additionally, it identified three further existing European networks of instruments that are currently underexploited, but with minimal expense they could deliver quality-controlled data to national weather services in near–real time, so the data could be assimilated into forecast models. Specifically, 1) several hundred automatic lidars and ceilometers can provide backscatter profiles associated with aerosol and cloud properties and structures with 30-m vertical resolution every minute; 2) more than 20 Doppler lidars, a fairly new technology, can measure vertical and horizontal winds in the lower atmosphere with a vertical resolution of 30 m every 5 min; and 3) about 30 microwave profilers can estimate profiles of temperature and humidity in the lower few kilometers every 10 min. Examples of potential benefits from these instruments are presented.