bluuebunny/crossref_metadata_2025 huggingface dataset:
DNA barcoding for identification of sand flies (Diptera: Psychodidae) in India
Authors: KUMAR N. PRADEEP , SRINIVASAN R. , JAMBULINGAM P.
Published: January 2012

About 50 species of sand flies have been reported to be prevalent in India. We explored the utility of the DNA barcode approach towards species identification of these medically important insects. A total of 62 specimens belonging to seven morphologically identified species of two genera,PhlebotomusandSergentomyia, collected from Puducherry Union Territory, Maharashtra and Rajasthan states of India were subjected to the analysis. Neighbor‐joining (NJ) analysis of DNA barcode sequences identified the individuals of seven morphological species into eight distinct species, as presented in the designed NJ tree. This methodology delineated morphologically identified species,S. bailyi,into two genetically isolated groups. Also, this study characterizes DNA barcodes ofP. argentipesandP. papatasi,the vector species of leishmaniasis in India, for the first time.
Is Major Depression a Risk for Bladder, Bowel, and Sexual Dysfunction?
Authors: ITO Takashi , SAKAKIBARA Ryuji , SHIMIZU Eiji , KISHI Masahiko , TSUYUZAKI Yohei , TATENO Fuyuki , UCHIYAMA Tomoyuki , YAMAMOTO Tatsuya
Published: January 2012

Objectives: Although major depression may accompany bladder, bowel and sexual (pelvic organs) dysfunction, no prospective, controlled surveys have been available. The aim of the present study was to study the risk of pelvic organ dysfunction in major depression.

Methods: Two hundred and twenty‐four depression patients in the psychiatry clinic (97 men, 127 women; average age 42 years; 128 drug‐naÏve, 96 medicated) and 391 age‐matched local individuals who were undergoing an annual health survey underwent a questionnaire devised for neurologic and psychiatric cohorts.

Results: Compared with control, in the drug‐naÏve group the frequency of dysfunction was significantly higher for urinary urgency (20.9% of the women, 25.9% of the men, P < 0.01), urinary incontinence (9.1%, women), retardation in initiating urination (13.1%, men); constipation (23.8%, 14.8%), diarrhea (20.3%, 21.8%); decrease in libido (42%, men), sexual intercourse (70.7%, 78.7%) orgasm (63.6%, 65.0%), erection (92.7% of the men); and quality of life indices. No difference was found in the frequency of all three items between the drug‐naÏve group and the medicated group.

Conclusion: The results of the present study suggest that major depression is a risk for all bladder, bowel and sexual dysfunction, and it significantly worsens quality of life in patients. This finding presumably reflects that pelvic organ function is under emotional control. Amelioration of bladder, bowel, and sexual dysfunction is therefore an important target to treat patients with major depression.
Antimicrobial Resistance in Campylobacter spp. Isolated from Ontario Sheep Flocks and Associations between Antimicrobial use and Antimicrobial Resistance
Authors: Scott L. , Menzies P. , Reid‐Smith R. J. , Avery B. P. , McEwen S. A. , Moon C. S. , Berke O.
Published: January 2012

The objectives of this study were to determine the prevalence of antimicrobial resistance (AMR) in faecal Campylobacter spp. from lambs and adult sheep and associations between antimicrobial use (AMU) and AMR. A total of 275 faecal samples collected during initial and final visits from 51 sheep flocks, including one feedlot, across southern Ontario were tested for the presence of Campylobacter spp. Campylobacter jejuni was detected in 52% (143/275) of the faecal samples, Campylobacter coli in 7% (19/275), Campylobacter lari in 1% (2/275) and 2% (4/275) were non‐speciated Campylobacter. Broth microdilution was used to test antimicrobial susceptibility of 162 isolates to nine antimicrobials. Campylobacter jejuni isolates (n = 142) were resistant to tetracycline (39%), ciprofloxacin (4%), nalidixic acid (4%) and telithromycin (1%). C. coli isolates (n = 19) were resistant to tetracycline (74%), and azithromycin, clindamycin, erythromycin, and telithromycin (5%). The C. lari isolate displayed resistance to nalidixic acid. No statistically significant associations were found between AMU and AMR during multivariate modelling in this study.
Service and Price Competition When Customers Are Naive
Authors: Li Li , Jiang Li , Liu Liming
Published: January 2012

We consider a system of two service providers each with a separate queue. Customers choose one queue to join upon arrival and can switch between queues in real time before entering service to maximize their spot utility, which is a function of price and queue length. We characterize the steady‐state distribution for queue lengths, and then investigate a two‐stage game in which the two service providers first simultaneously select service rates and then simultaneously charge prices. Our results indicate that neither service provider will have both a faster service and a lower price than its competitor. When price plays a less significant role in customers’ service selection relative to queue length or when the two service providers incur comparable costs for building capacities, they will not engage in price competition. When price plays a significant role and the capacity costs at the service providers sufficiently differ, they will adopt substitutable competition instruments: the lower cost service provider will build a faster service and the higher cost service provider will charge a lower price. Comparing our results to those in the existing literature, we find that the service providers invest in lower service rates, engage in less intense price competition, and earn higher profits, while customers wait in line longer when they are unable to infer service rates and are naive in service selection than when they can infer service rates to make sophisticated choices. The customers’ jockeying behavior further lowers the service providers’ capacity investment and lengthens the customers’ duration of stay.
Information‐Sensitive Replenishment when Inventory Records Are Inaccurate
Authors: Mersereau Adam J.
Published: January 2012

Inspired by recent empirical work on inventory record inaccuracy, we consider a periodic review inventory system with imperfect inventory records and unobserved lost sales. Record inaccuracies are assumed to arrive via an error process that perturbs physical inventory but is unobserved by the inventory manager. The inventory manager maintains a probability distribution around the physical inventory level that he updates based on sales observations using Bayes Theorem. The focus of this study is on understanding, approximating, and evaluating optimal forward‐looking replenishment in this environment. By analyzing one‐ and two‐period versions of the problem, we demonstrate several mechanisms by which the error process and associated record inaccuracy can impact optimal replenishment. Record inaccuracy generally brings an incentive for a myopic manager to increase stock to buffer the added uncertainty. On the other hand, a forward‐looking manager will stock less than a myopic manager, in part to improve information content for future decisions. Using an approximate partially observed dynamic programming policy and associated bound, we numerically corroborate our analytical findings and measure the effectiveness of an intelligent myopic heuristic. We find that the myopic heuristic is likely sufficiently good in practical settings targeting high service levels.
Emerging Market Penetration, Inventory Supply, and Financial Performance
Authors: Han Chaodong , Dong Yan , Dresner Martin
Published: January 2012

Realizing potential benefits from emerging market penetration requires firms to address inherent supply chain challenges. A major challenge is for firms to manage costly inventories to address demand and supply risks in emerging markets. However, emerging market penetration may offer opportunities for firms to lower inventory levels, reduce costs, and improve operating performance. Using data for 482 manufacturing firms over the 5‐year period, 2003–2007, obtained from the COMPUSTAT Industrial and Segment Databases, this article examines the relationships between emerging market penetration, inventory supply, and financial performance. Our results show that a multinational firm's sales penetration into emerging markets is associated with fewer days of inventory supply and improved financial performance. As emerging market penetration may allow firms to operate with lower inventory supply, the positive effect from emerging market penetration, such as labor cost reductions, may be enhanced due to inventory cost savings.
Genome Sequence of Pseudomonas stutzeri SDM-LAC, a Typical Strain for Studying the Molecular Mechanism of Lactate Utilization
Authors: Jiang Tianyi , Gao Chao , Su Fei , Zhang Wen , Hu Chunhui , Dou Peipei , Zheng Zhaojuan , Tao Fei , Ma Cuiqing , Xu Ping
Published: January 2012

Pseudomonas stutzeri
SDM-LAC is an efficient lactate utilizer with various applications in biocatalysis. Here we present a 4.2-Mb assembly of its genome. The annotated four adjacent genes form a lactate utilization operon, which could provide further insights into the molecular mechanism of lactate utilization.
Complete Genome Sequence of the Fenitrothion-Degrading Burkholderia sp. Strain YI23
Authors: Lim Jong Sung , Choi Beom Soon , Choi Ah Young , Kim Kyung Duk , Kim Dong In , Choi Ik Young , Ka Jong-Ok
Published: January 2012

Burkholderia
species are ubiquitous in soil environments. Many
Burkholderia
species isolated from various environments have the potential to biodegrade man-made chemicals.
Burkholderia
sp. strain YI23 was isolated from a golf course soil and identified as a fenitrothion-degrading bacterium. In this study, we report the complete genome sequence of
Burkholderia
sp. strain YI23.
Genome Sequence of Deep-Sea Manganese-Oxidizing Bacterium Marinobacter manganoxydans MnI7-9
Authors: Wang Haifang , Li Hang , Shao Zongze , Liao Shuijiao , Johnstone Laurel , Rensing Christopher , Wang Gejiao
Published: January 2012

Here we report the draft genome of
Marinobacter manganoxydans
MnI7-9, isolated from a deep-sea hydrothermal vent in the Indian Ocean and capable of oxidizing manganese even when there is a very high concentration of Mn
2+
. The strain also displayed high resistance and adsorption ability toward many metal(loid)s.
Complete Genome Sequence of Brucella suis VBI22, Isolated from Bovine Milk
Authors: Tae Hongseok , Shallom Shamira , Settlage Robert , Hawkins Gregory N. , Adams L. Garry , Garner Harold R.
Published: January 2012

Brucella suis
is the causative agent of swine brucellosis and is known to be able to infect several different hosts, including cattle, dogs, and horses, without causing disease symptoms. Here we report the complete genome sequence of
Brucella suis
VBI22, which was isolated from raw milk from an infected cow.
Genome Sequence for “Candidatus Mycoplasma haemominutum,” a Low-Pathogenicity Hemoplasma Species
Authors: Barker Emily N. , Darby Alistair C. , Helps Chris R. , Peters Iain R. , Hughes Margaret A. , Radford Alan D. , Novacco Marilisa , Boretti Felicitas S. , Hofmann-Lehmann Regina , Tasker Séverine
Published: January 2012

We present the genome sequence of “
Candidatus
Mycoplasma haemominutum” strain Birmingham 1, a low-pathogenicity feline hemoplasma strain.
Draft Genome Sequence of Probiotic Strain Lactobacillus rhamnosus R0011
Authors: Tompkins Thomas A. , Barreau Guillaume , de Carvalho Vanessa G.
Published: January 2012

Lactobacillus rhamnosus
R0011 is a commercially available probiotic that is widely used in human dietary supplements and pharmaceutical products. We prepared a draft genome sequence consisting of 10 contigs totaling 2,900,620 bases and a G+C content of 46.7% for this strain.
Amylin improves the effect of leptin on insulin sensitivity in leptin-resistant diet-induced obese mice
Authors: Kusakabe Toru , Ebihara Ken , Sakai Takeru , Miyamoto Licht , Aotani Daisuke , Yamamoto Yuji , Yamamoto-Kataoka Sachiko , Aizawa-Abe Megumi , Fujikura Junji , Hosoda Kiminori , Nakao Kazuwa
Published: January 2012

Leptin enhances insulin sensitivity in addition to reducing food intake and body weight. Recently, amylin, a pancreatic β-cell-derived hormone, was shown to restore a weight-reducing effect of leptin in leptin-resistant diet-induced obesity. However, whether amylin improves the effect of leptin on insulin sensitivity in diet-induced obesity is unclear. Diet-induced obese (DIO) mice were infused with either saline (S), leptin (L; 500 μg·kg−1·day−1), amylin (A; 100 μg·kg−1·day−1), or leptin plus amylin (L/A) for 14 days using osmotic minipumps. Food intake, body weight, metabolic parameters, tissue triglyceride content, and AMP-activated protein kinase (AMPK) activity were examined. Pair-feeding and weight-matched calorie restriction experiments were performed to assess the influence of food intake and body weight reduction. Continuous L/A coadministration significantly reduced food intake, increased energy expenditure, and reduced body weight, whereas administration of L or A alone had no effects. L/A coadministration did not affect blood glucose levels during ad libitum feeding but decreased plasma insulin levels significantly (by 48%), suggesting the enhancement of insulin sensitivity. Insulin tolerance test actually showed the increased effect of insulin in L/A-treated mice. In addition, L/A coadministration significantly decreased tissue triglyceride content and increased AMPKα2 activity in skeletal muscle (by 67%). L/A coadministration enhanced insulin sensitivity more than pair-feeding and weight-matched calorie restriction. In conclusion, this study demonstrates the beneficial effect of L/A coadministration on glucose and lipid metabolism in DIO mice, indicating the possible clinical usefulness of L/A coadministration as a new antidiabetic treatment in obesity-associated diabetes.
Muscle-derived expression of the chemokine CXCL1 attenuates diet-induced obesity and improves fatty acid oxidation in the muscle
Authors: Pedersen Line , Olsen Caroline Holkmann , Pedersen Bente Klarlund , Hojman Pernille
Published: January 2012

Serum levels and muscle expression of the chemokine CXCL1 increase markedly in response to exercise in mice. Because several studies have established muscle-derived factors as important contributors of metabolic effects of exercise, this study aimed at investigating the effect of increased expression of muscle-derived CXCL1 on systemic and intramuscular metabolic parameters, with focus on fatty acid oxidation and oxidative metabolism in skeletal muscle. By overexpression of CXCL1 in the tibialis cranialis muscle in mice, significant elevations in muscle and serum CXCL1 within a physiological range were obtained. At 3 mo of high-fat feeding, visceral and subcutaneous fat mass were 32.4 ( P < 0.01) and 22.4% ( P < 0.05) lower, respectively, in CXCL1-overexpressing mice compared with control mice. Also, chow-fed CXCL-transfected mice had 35.4% ( P < 0.05) lower visceral fat mass and 33.4% ( P < 0.05) lower subcutaneous fat mass compared with chow-fed control mice. These reductions in accumulation of adipose tissue were accompanied by improved glucose tolerance and insulin sensitivity. Furthermore, in CXCL1-transfected muscles, muscular ex vivo fatty acid oxidation was significantly enhanced compared with control muscles (chow fed: 2.2-fold, P < 0.05; high-fat fed: 2-fold, P < 0.05) and also showed increased expression levels of major fatty acid oxidation genes (CD36, CPT I, and HADH). Finally, CXCL1 expression was associated with increased muscle mRNA expression of VEGF and CD31, suggesting a role for CXCL1 in muscle angiogenesis. In conclusion, our data show that overexpression of CXCL1 within a physiological range attenuates diet-induced obesity, likely mediated through a CXCL1-induced improvement of fatty acid oxidation and oxidative capacity in skeletal muscle tissue.
Signal transduction pathways in FSH regulation of rat Sertoli cell proliferation
Authors: Riera María F. , Regueira Mariana , Galardo María N. , Pellizzari Eliana H. , Meroni Silvina B. , Cigorraga Selva B.
Published: January 2012

The final number of Sertoli cells reached during the proliferative periods determines sperm production capacity in adulthood. It is well known that FSH is the major Sertoli cell mitogen; however, little is known about the signal transduction pathways that regulate the proliferation of Sertoli cells. The hypothesis of this investigation was that FSH regulates proliferation through a PI3K/Akt/mTORC1 pathway, and additionally, AMPK-dependent mechanisms counteract FSH proliferative effects. The present study was performed in 8-day-old rat Sertoli cell cultures. The results presented herein show that FSH, in addition to increasing p-Akt, p-mTOR, and p-p70S6K levels, increases p-PRAS40 levels, probably contributing to improving mTORC1 signaling. Furthermore, the decrease in FSH-stimulated p-Akt, p-mTOR, p-p70S6K, and p-PRAS40 levels in the presence of wortmannin emphasizes the participation of PI3K in FSH signaling. Additionally, the inhibition of FSH-stimulated Sertoli cell proliferation by the effect of wortmannin and rapamycin point to the relevance of the PI3K/Akt/mTORC1 signaling pathway in the mitotic activity of FSH. On the other hand, by activating AMPK, several interesting observations were made. Activation of AMPK produced an increase in Raptor phosphorylation, a decrease in p70S6K phosphorylation, and a decrease in FSH-stimulated Sertoli cell proliferation. The decrease in FSH-stimulated cell proliferation was accompanied by an increased expression of the cyclin-dependent kinase inhibitors (CDKIs) p19INK4d, p21Cip1, and p27Kip1. In summary, it is concluded that FSH regulates Sertoli cell proliferation with the participation of a PI3K/Akt/mTORC1 pathway and that AMPK activation may be involved in the detention of proliferation by, at least in part, a decrease in mTORC1 signaling and an increase in CDKI expression.
Fibroblast growth factor-23 abolishes 1,25-dihydroxyvitamin D3-enhanced duodenal calcium transport in male mice
Authors: Khuituan Pissared , Teerapornpuntakit Jarinthorn , Wongdee Kannikar , Suntornsaratoon Panan , Konthapakdee Nipaporn , Sangsaksri Jintana , Sripong Chanakarn , Krishnamra Nateetip , Charoenphandhu Narattaphol
Published: January 2012

Despite being widely recognized as the important bone-derived phosphaturic hormone, whether fibroblast growth factor (FGF)-23 modulated intestinal calcium absorption remained elusive. Since FGF-23 could reduce the circulating level of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], FGF-23 probably compromised the 1,25(OH)2D3-induced intestinal calcium absorption. FGF-23 may also exert an inhibitory action directly through FGF receptors (FGFR) in the intestinal cells. Herein, we demonstrated by Ussing chamber technique that male mice administered 1 μg/kg 1,25(OH)2D3 sc daily for 3 days exhibited increased duodenal calcium absorption, which was abolished by concurrent intravenous injection of recombinant mouse FGF-23. This FGF-23 administration had no effect on the background epithelial electrical properties, i.e., short-circuit current, transepithelial potential difference, and resistance. Immunohistochemical evidence of protein expressions of FGFR isoforms 1–4 in mouse duodenal epithelial cells suggested a possible direct effect of FGF-23 on the intestine. This was supported by the findings that FGF-23 directly added to the serosal compartment of the Ussing chamber and completely abolished the 1,25(OH)2D3-induced calcium absorption in the duodenal tissues taken from the 1,25(OH)2D3-treated mice. However, direct FGF-23 exposure did not decrease the duodenal calcium absorption without 1,25(OH)2D3 preinjection. The observed FGF-23 action was mediated by MAPK/ERK, p38 MAPK, and PKC. Quantitative real-time PCR further showed that FGF-23 diminished the 1,25(OH)2D3-induced upregulation of TRPV5, TRPV6, and calbindin-D9k, but not PMCA1b expression in the duodenal epithelial cells. In conclusion, besides being a phosphatonin, FGF-23 was shown to be a novel calcium-regulating hormone that acted directly on the mouse intestine, thereby compromising the 1,25(OH)2D3-induced calcium absorption.
Influence of chronic and acute spinal cord injury on skeletal muscle Na+-K+-ATPase and phospholemman expression in humans
Authors: Boon Hanneke , Kostovski Emil , Pirkmajer Sergej , Song Moshi , Lubarski Irina , Iversen Per O. , Hjeltnes Nils , Widegren Ulrika , Chibalin Alexander V.
Published: January 2012

Na+-K+-ATPase is an integral membrane protein crucial for the maintenance of ion homeostasis and skeletal muscle contractibility. Skeletal muscle Na+-K+-ATPase content displays remarkable plasticity in response to long-term increase in physiological demand, such as exercise training. However, the adaptations in Na+-K+-ATPase function in response to a suddenly decreased and/or habitually low level of physical activity, especially after a spinal cord injury (SCI), are incompletely known. We tested the hypothesis that skeletal muscle content of Na+-K+-ATPase and the associated regulatory proteins from the FXYD family is altered in SCI patients in a manner dependent on the severity of the spinal cord lesion and postinjury level of physical activity. Three different groups were studied: 1) six subjects with chronic complete cervical SCI, 2) seven subjects with acute, complete cervical SCI, and 3) six subjects with acute, incomplete cervical SCI. The individuals in groups 2 and 3 were studied at months 1, 3, and 12 postinjury, whereas individuals with chronic SCI were compared with an able-bodied control group. Chronic complete SCI was associated with a marked decrease in [3H]ouabain binding site concentration in skeletal muscle as well as reduced protein content of the α1-, α2-, and β1-subunit of the Na+-K+-ATPase. In line with this finding, expression of the Na+-K+-ATPase α1- and α2-subunits progressively decreased during the first year after complete but not after incomplete SCI. The expression of the regulatory protein phospholemman (PLM or FXYD1) was attenuated after complete, but not incomplete, cervical SCI. In contrast, FXYD5 was substantially upregulated in patients with complete SCI. In conclusion, the severity of the spinal cord lesion and the level of postinjury physical activity in patients with SCI are important factors controlling the expression of Na+-K+-ATPase and its regulatory proteins PLM and FXYD5.
Characterization of Bglu3, a mouse fasting glucose locus, and identification of Apcs as an underlying candidate gene
Authors: Li Jing , Lu Zongji , Wang Qian , Su Zhiguang , Bao Yongde , Shi Weibin
Published: January 2012

Bglu3 is a quantitative trait locus for fasting glucose on distal chromosome 1 identified in an intercross between C57BL/6 (B6) and C3H/HeJ (C3H) apolipoprotein E-deficient (apoE−/−) mice. This locus was subsequently replicated in two separate mouse intercrosses. The objective of this study was to characterize Bglu3 through construction and analysis of a congenic strain and identify underlying candidate genes. Congenic mice were constructed by introgressing a genomic region harboring Bglu3 from C3H.apoE−/− into B6.apoE−/− mice. Mice were started with a Western diet at 6 wk of age and maintained on the diet for 12 wk. Gene expression in the liver was analyzed by microarrays. Congenic mice had significantly higher fasting glucose levels and developed more significant glucose intolerance compared with B6.apoE−/− mice on the Western diet. Microarray analysis revealed 336 genes to be differentially expressed in the liver of congenic mice. Further pathway analysis suggested a role for acute phase response signaling in regulating glucose intolerance. Apcs, encoding an acute phase response protein serum amyloid P (SAP), is located underneath the linkage peak of Bglu3. Multiple single nucleotide polymorphisms between B6 and C3H mice were detected within and surrounding Apcs. Apcs expression in the liver was significantly higher in congenic and C3H mice compared with B6 mice. The Western diet consumption led to a gradual rise in plasma SAP levels, which was accompanied by rising fasting glucose in both B6 and C3H apoE−/− mice. Expression of C3H Apcs in B6.apoE−/− mice aggravated glucose intolerance. Bglu3 is confirmed to be a locus affecting diabetes susceptibility, and Apcs is a probable candidate gene.
New Strategies in Melanoma: Molecular Testing in Advanced Disease
Authors: Woodman Scott E. , Lazar Alexander J. , Aldape Kenneth D. , Davies Michael A.
Published: January 2012

Melanoma is one of the most aggressive forms of skin cancer. The management of melanoma is evolving rapidly due to an improved understanding of the molecular heterogeneity of this disease and the development of effective, personalized, targeted therapy strategies. Although previous classification systems were based predominantly on clinical and histologic criteria, there is now a strong rationale for adding molecular markers to the diagnostic evaluation of these tumors. Research has shown that the types and prevalence of genetic alterations vary among melanoma subtypes. Thus, rational molecular testing should be based on an understanding of the events that are likely to occur in a given tumor and the clinical implications of test results. This review summarizes the existing data that support the rationale for molecular testing in clinically defined melanoma subtypes. Emerging challenges and controversies regarding the use of various molecular testing platforms, and their implications for clinical testing, are also discussed. Clin Cancer Res; 18(5); 1195–200. ©2012 AACR.
Randomized Study of Autologous Cytokine-Induced Killer Cell Immunotherapy in Metastatic Renal Carcinoma
Authors: Liu Liang , Zhang Weihong , Qi Xiuying , Li Hui , Yu Jinpu , Wei Sheng , Hao Xishan , Ren Xiubao
Published: January 2012

Purpose: The therapeutic benefit of the cytokine-induced killer (CIK) cells was unknown in the renal cell carcinoma (RCC). This prospectively randomized study was conducted to evaluate the effects of autologous CIK cell immunotherapy in patients with metastatic clear cell RCCs.

Experimental Design: From June 2005 to June 2008, 148 patients with metastatic clear cell RCC were randomized to autologous CIK cell immunotherapy (arm 1, n = 74), or interleukin-2 treatment combination with IFN-α-2a (arm 2, n = 74). The primary endpoint was overall survival (OS) and secondary endpoint was progression-free survival (PFS) evaluated by Kaplan–Meier analyses and treatment HRs with the Cox proportional hazards model.

Results: The 3-year PFS and OS in arm 1 were 18% and 61%, as compared with 12% and 23% in arm 2 (P = 0.031 and <0.001, respectively). The median PFS and OS in arm 1 were significantly longer than those in arm 2 (PFS, 12 vs. 8 months, P = 0.024; OS, 46 vs. 19 months, P < 0.001). Multivariate analyses indicated that the cycle count of CIK cell immunotherapy as a continuous variable was significantly associated with prolonged PFS [HR = 0.88; 95% confidence interval (CI), 0.84-0.93; P < 0.001] and OS (HR = 0.58; 95% CI, 0.48–0.69; P < 0.001) in arm 1.

Conclusion: The data suggested that CIK cell immunotherapy could improve the prognosis of metastatic clear cell RCC, and increased cycle count of CIK cell treatment could further enhance the beneficial effects. Clin Cancer Res; 18(6); 1751–9. ©2012 AACR.
PET Imaging of Tumor Growth: Not as Easy as It Looks
Authors: Shields Anthony F.
Published: January 2012

Positron emission tomography can be used to image tumor proliferation when combined with appropriate labeled tracers, such as the thymidine analog [18F]-3′-deoxy-3′-fluorothymidine. Although thymidine kinase 1 is the principal mechanism of cell trapping, other variables, such as the cellular level of native thymidine, may need to be considered. Clin Cancer Res; 18(5); 1189–91. ©2012 AACR.
Imexon Induces an Oxidative Endoplasmic Reticulum Stress Response in Pancreatic Cancer Cells
Authors: Sheveleva Elena V. , Landowski Terry H. , Samulitis Betty K. , Bartholomeusz Geoffrey , Powis Garth , Dorr Robert T.
Published: January 2012

Oxidative protein folding in the endoplasmic reticulum (ER) requires strict regulation of redox homeostasis. Disruption of the lumenal redox balance induces an integrated ER stress response that is associated with reduced protein translation, increased chaperone activity, and ultimately cell death. Imexon is a small-molecule chemotherapeutic agent that has been shown to bind glutathione (GSH) and induce oxidative stress in tumor cells; however, the mechanism of cytotoxicity is not well understood. In this report, we investigate the effects of imexon on the integrated ER stress response in pancreatic carcinoma cells. Acute exposure to imexon induces an ER stress response characterized by accumulation of the oxidized form of the oxidoreductase Ero1α, phosphorylation of eIF2α, and inhibition of protein synthesis. An RNA interference chemosensitization screen identified the eukaryotic translation initiation factor eIF2B5 as a target that enhanced imexon-induced growth inhibition of MiaPaCa-2 pancreatic cancer cells, but did not significantly augment the effects of imexon on protein synthesis. Concurrent reduction of intracellular thiols with N-acetyl cysteine reversed imexon activity, however cotreatment with superoxide scavengers had no effect, suggesting thiol binding may be a primary component of the oxidative effects of imexon. Moreover, the data suggest that disruption of the redox balance in the ER is a potential therapeutic target. Mol Cancer Res; 10(3); 392–400. ©2012 AACR.
The FUS3/KSS1-Type MAP KinaseGene FPK1 Is Involved in Hyphal Growth, Conidiation and Plant Infection of Fusarium proliferatum
Authors: Zhao Pei-Bao , Ren Ai-Zhi , Li Duo-Chuan
Published: January 2012

Fusarium proliferatum is an important pathogen of maize that is responsible for ear rots, stalk rots and seeding blight worldwide. During the past decade, F. proliferatum has caused several severe epidemics of maize seedling blight in many areas of China, which led to significant losses in maize. To understand the molecular mechanisms in the fungal developmental regulation and pathogenicity, we isolated and characterized the FPK1 gene (GenBank accession No. HQ844224) encoding a MAP kinase homolog of FUS3/KSS1 in yeast. The gene includes a 1,242-bp DNA sequence from ATG to TAA, with a coding region of 1,068 bp, 3 introns (58 bp, 56 bp and 60 bp) and a predicted protein of 355 aa.The mutant ΔFPK1, which has a disruption of the FPK1 gene, showed reduced vegetative growth, fewer and shorter aerial mycelia, strongly impaired conidiation and spore germination, as well as deviant germ tube outgrowth. When the strain was inoculated in susceptible maize varieties, the infection of the mutant ΔFPK1 was delayed, and the infection efficiency was reduced compared to the wild-type strain. Complementation of the disruptions within the FPK1 open reading frame restored wild-type levels of conidiation, growth rate and virulence to maize seedlings. Our results indicated that the FPK1 gene functioned in hyphal growth, conidiation, spore germination and virulence in F. proliferatum.
Galleria mellonella as aModel for Studying Enterococcus faecium Host Persistence
Authors: Lebreton François , Le Bras Florian , Reffuveille Fany , Ladjouzi Rabia , Giard Jean-Christophe , Leclercq Roland , Cattoir Vincent
Published: January 2012

Enterococcus faecium is an opportunistic pathogen responsible for numerous outbreaks worldwide. The basis for the colonization capacities, host persistence and environmental stress response of the hospital-adapted clones emerging from E. faecium are poorly understood. In this study, we propose the use of Galleriamellonella as a simple nonmammalian model to assess E. faecium host persistence. Various strains (n = 10), including hospital-adapted, commensal or animal isolates and a SodA-deficient strain were used to assess the relevance of this model. Compared to Enterococcus faecalis, E. faecium strains do not appear very lethal in a Galleria killing assay. The ability of E. faecium strains to overcome host-immune responses and multiply within the host system was evaluated by monitoring bacterial loads following Galleria infection. Among the E. faecium strains, two hospital-adapted isolates displayed increased colonization ability. In contrast, inactivation of sodA, encoding a putative manganese-dependent superoxide dismutase, significantly reduced survival of E. faecium to Galleria defenses. Galleria appears to be a suitable and convenient surrogate model to study E. faecium survival to host defenses and the role of suspected virulence factors in the colonization process.
Gonadotropin-Inhibitory Hormone Is a Hypothalamic Peptide That Provides a Molecular Switch between Reproduction and Feeding
Authors: Clarke Iain J. , Smith Jeremy T. , Henry Belinda A. , Oldfield Brian J. , Stefanidis Aneta , Millar Robert P. , Sari Ika Puspita , Chng Keefe , Fabre-Nys Claude , Caraty Alain , Ang Beng Ti , Chan Louiza , Fraley Gregory S.
Published: January 2012

Objective: Gonadotropin-inhibitory hormone (GnIH)-3 is a neuropeptide that plays a major role in the regulation of reproduction and feeding in mammals. Materials and Methods: We measured endocrine and behavioural parameters of reproduction in sheep, and sexual behaviour in sheep, mice and cynomolgus monkeys. In addition, GnIH gene expression (in situ hybridization) was examined in ewes, and effects of GnIH-3 on food intake and energy expenditure were measured in various species. GnIH-3 was infused (i.v.) into ewes after an i.m. injection of estradiol benzoate to determine whether the peptide blocks the surge in luteinizing hormone (LH) secretion. Results: GnIH gene expression was reduced in the preovulatory period in ewes. Infusion (i.v.) of GnIH-3 blocked the estrogen-induced LH surge (in ewes). Intracerebroventricular infusion had no effect on female or male sexual behaviour in each of the three species, but increased food intake. There were no effects on energy expenditure in sheep or rats. GnIH increased fos protein (immunohistochemistry) was seen in orexigenic neurons (in sheep and rats), but also in anorexigenic neurons (in sheep). Conclusions: GnIH-3 reduces reproductive hormone levels and increases food intake in mammals without reducing energy expenditure. There is minimal effect on reproductive behaviour. The dual effect on reproduction and feeding suggests that GnIH-3 provides a molecular switch between these two functions. Blockade of the positive feedback effect of estrogen with parenteral infusion indicates that this peptide may have utility as a blocker of reproductive function in mammals.
Post-Transcriptional Regulation of the Alginate Biosynthetic Gene algD by the Gac/Rsm System in Azotobacter vinelandii
Authors: Manzo Joaquín , Cocotl-Yañez Miguel , Tzontecomani Tomás , Martínez Verónica M. , Bustillos Rocío , Velásquez Claudia , Goiz Yolanda , Solís Yuri , López Liliana , Fuentes Luis E. , Nuñez Cinthia , Segura Daniel , Espín Guadalupe , Castañeda Miguel
Published: January 2012

Azotobacter vinelandii is a soil bacterium that produces the polysaccharide alginate. The two-component system GacS/GacA is required for alginate synthesis since a mutation in gacS or gacA significantly reduced the level of transcripts of algD, the gene encoding GDP-mannose dehydrogenase, a key enzyme of the alginate biosynthetic pathway. In many γ-proteobacteria, GacA homologs control the expression of small regulatory RNAs of the RsmZ/Y/X (CsrB/CsrC) family that interact with RsmA (CsrA) proteins. These proteins bind to their target mRNAs acting as translational repressors. The interaction of Rsm/Csr small RNAs with RsmA/CsrA counteract its repressor activity. In this study, one rsmA gene, seven rsmZ and two rsmY homologs were identified in the A. vinelandii genome. Two of the rsmZ homologs, named rsmZ1 and rsmZ2, together with rsmA, were characterized. Northern blot analysis was carried out to show that in A. vinelandii, GacA activates rsmZ1 and rsmZ2 transcription. We also showed that either overexpression of rsmA or inactivation of rsmZ1 or rsmZ2 diminished the production of alginate. In addition, interaction of RsmA with RsmZ1, RsmZ2 and the algD mRNA was demonstrated in vitro. These results show that GacS/A regulates alginate biosynthesis by post-transcriptional control of algD expression through the Rsm system.
The Expression of Preaxial Polydactyly Is Influenced by Modifying Genetic Elements and Is Not Maintained by Chromosomal Inversion in an Avian Biomedical Model
Authors: Robb E.A. , Delany M.E.
Published: January 2012

Polydactyly (Po) is a common mutation found in many vertebrates. The UCD-Po.003 congenic chicken line was previously characterized for Po inheritance (autosomal dominant) and the mutation was mapped to chromosome 2p. Here, we describe for the first time the range and variability of the phenotype in this congenic line. Further, we studied the hypothesis that a chromosomal inversion was responsible for the maintenance of a large (6.3 Mb) candidate gene region. Fluorescence in situ hybridization employing BACs encompassing a 10.7-Mb region of GGA2p showed that the Po chromosome was normal, i.e. exhibits the wild-type BAC order. Continued fine-mapping along with a change in breeding strategy reduced the size of the causative region to 1.43 Mb. Recent research indicates that the cause of preaxial Po resides within a 794-bp highly conserved zone of polarizing activity regulatory sequence (ZRS) element located in intron 5 of the LMBR1 gene; however, the ZRS polymorphism of interest is found in some but not all breeds of polydactylous chicken. Therefore, we sequenced the ZRS in 101 heterozygous and 30 unaffected (wild-type) individuals to establish the relevance of this region to the Po condition in the UCD-Po.003 congenic line. A single point mutation (C/A at coordinate GGA2p: 8,414,121) within the ZRS segregated with carrier status. The polydactylous UCD-Silkie line also maintains this SNP in addition to a single base deletion. An inheritance analysis of the phenotypic variation in UCD-Po.003 suggests recessive epistasis as the mode of inheritance for the additional modifying genetic elements, residing outside the ZRS, to impact the preaxial polydactyl phenotype. These results contribute to our understanding of the cause of Po in an important vertebrate model.
Despite Some Comprehension Problems the International Index of Erectile Function Is a Reliable Questionnaire in Erectile Dysfunction
Authors: Bayraktar Zeki , Atun Ali Ihsan
Published: January 2012

Objective: To investigate the reliability of the physician-assisted International Index of Erectile Function (IIEF). Patients and Methods: 374 patients who applied to our clinic with erectile dysfunction problems were asked to complete the IIEF questionnaire; 225 patients who visited the clinic again within 1–3 days completed the IIEF questionnaire again. All questions were answered by the patients themselves. At both visits, necessary explanations were provided by the physician to patients who requested assistance. Data obtained from the first and second questionnaires were compared. Results: There was a significant difference between the first and second questionnaires with respect to certain questions. Nevertheless, no significant difference was found between the IIEF.1 and IIEF.2 scores (p > 0.20) for the group overall or for any subgroups. The test-retest correlation coefficients for all patients were highly significant (r = 0.909, p < 0.01). A high degree of internal consistency was observed for each of the first and second physician-assisted IIEF questionnaires (Cronbach’s α 0.926 and 0.908, respectively, p < 0.001). Conclusions: Physician assistance increased the comprehensibility of the IIEF in elderly patients and in patients with low education levels. Despite some comprehension problems in these patient groups the physician-assisted IIEF questionnaire was found to be consistent and reliable in all patient groups.
Is Conventional Hemodialysis Enough to Manage Carbamazepine Intoxication?
Authors: Azak Alper , Koçak Gülay , Huddam Bülent , Duranay Murat
Published: January 2012

Hemodialysis (HD) is a technique that helps in the management of drug intoxications/overdoses – the most important point being the protein-binding rate of the molecules which have to be cleared. In cases where the drug is not bound to the proteins, conventional HD may be effective enough, but if the drug is highly bound to proteins then HD may be insufficient to be effective. Hemoperfusion and albumin dialysis are therefore appropriate alternatives. Herein we report a case of carbamazepine intoxication where conventional HD treatment was performed.
Thrombin Stimulates Synthesis of Macrophage Colony-Stimulating Factor, Granulocyte-Macrophage Colony-Stimulating Factor and Granulocyte Colony-Stimulating Factor by Human Proximal Tubular Epithelial Cells in Culture
Authors: Shimaya Yuko , Shimada Michiko , Shutto Yoshiko , Fujita Takeshi , Murakami Reiichi , Nakamura Norio , Yamabe Hideaki , Okumura Ken
Published: January 2012

Background/Aims: Colony-stimulating factors (CSFs) are well-known hematopoietic growth factors. Although recent studies revealed that CSFs are involved in many inflammatory conditions, the local production of CSFs and its regulation in the kidney is not well elucidated. Therefore, using cultured human proximal tubular epithelial cells (PTEC), we examined the effect of thrombin on CSFs production, since thrombin has been suggested to play an important role in tubulointerstitial injury. Methods: PTEC were incubated with thrombin (0.5–5.0 U/ml) and the effects on the production of macrophage CSF (M-CSF), granulocyte-macrophage CSF (GM-CSF) and granulocyte CSF (G-CSF) were measured in the cell supernatant by enzyme-linked immunosorbent assay, and the expressions of mRNA were analyzed by quantitative real-time reverse transcription polymerase chain reaction. Using argatroban, a direct thrombin inhibitor, we also examined the specific effect of thrombin. Results: Thrombin 5.0 U/ml significantly stimulated the production of M-CSF (p < 0.01) and G-CSF (p < 0.01), and 1.0 and 5.0 U/ml thrombin significantly stimulated GM-CSF (p < 0.02 and p < 0.01) in a dose-dependent manner. Thrombin 5.0 U/ml increased CSFs (M-CSF, p < 0.005; GM-CSF, p < 0.0005; G-CSF, p < 0.005) in a time-dependent manner. Thrombin also significantly enhanced the mRNA expressions of M-CSF (p < 0.01), GM-CSF (p < 0.05) and G-CSF (p < 0.01). These effects of thrombin were significantly reduced by the addition of argatroban (M-CSF, p < 0.01; GM-CSF, p < 0.01; G-CSF, p < 0.05). Conclusion: We demonstrated that thrombin significantly increased the production of CSFs by PTEC. These data suggest that the local production of CSFs in the tubulointerstitium may affect tubulointerstitial lesions in kidney injury.
Obstetric complications and pregnancy-related venous thromboembolism: The effect of low-molecular-weight heparin on their prevention in carriers of factor V Leiden or prothrombin G20210A mutation
Authors: Grandone Elvira , De Stefano Valerio , Tosetto Alberto , Palareti Gualtiero , Margaglione Maurizio , Castaman Giancarlo , Rossi Elena , Ciminello Angela , Valdrè Leila , Legnani Cristina , Luca Tiscia Giovanni , Bafunno Valeria , Carraro Sara , Rodeghiero Francesco , Simioni Paolo , Tormene Daniela
Published: January 2012

Whether the administration of low-molecular-weight heparin (LMWH) during pregnancy is effective in preventing obstetric complications and pregnancy-related venous thromboembolism (VTE) in women who are carriers of factor V Leiden (FVL) and/or prothrombin variant G20210A (PTm) is controversial. This observational study investigated the possible efficacy of pharmacological treatment with LMWH ± aspirin (ASA) in pregnancy outcomes in 1,011 pregnancies of 416 women with thrombophilia (FVL and/or PTm). Most patients were chosen on the basis of previous obstetrical complications (36%), or because of familial or personal history of venous/arterial thromboembolism (28% and 18%, respectively); 74 patients (18%) were incidentally identified. The outcome was evaluated according to the type of treatment and of the period of pregnancy when the treatment was started. After adjustment for observation before and after diagnosis of thrombophilia, previous miscarriages and VTE, parity, age and centre, we observed that LMWH had a protective effect on miscarriages (odds ratio [OR] 0.52, 95% confidence interval [CI] 0.29–0.94) and VTE (OR 0.05, 95% CI 0.01–0.21). ASA appeared to have no effect on the prevention of obstetric complications and VTE. A nested analysis performed in 116 women with two or more obstetric complications confirmed that the highest number of live births was recorded in the group under LMWH prophylaxis (OR 0.19, 95% CI 0.05–0.75). These results suggest that LMWH prophylaxis reduces the risk of obstetric complications in carriers of FVL and/or PTm, particularly in those with previous obstetric events. Furthermore, LMWH prophylaxis reduces the risk of pregnancy-related VTE.
Effects of oral anticoagulant therapy and haplotype 1 of the endothelial protein C receptor gene on activated protein C levels
Authors: Medina Pilar , Bonet Elena , Navarro Silvia , Martos Laura , Estellés Amparo , Ferrando Fernando , Vicente Vicente , Bertina Rogier M. , España Francisco
Published: January 2012

Oral anticoagulants (OACs) reduce activated protein C (APC) plasma levels less than those of protein C (PC) in lupus erythematosus and cardiac patients. Carriers of the H1 haplotype of the endothelial PC receptor gene (PROCR) have higher APC levels than non-carriers. We aimed to confirm these results in a large group of patients treated with OACs because of venous thromboembolism (VTE) and to assess whether the effect is influenced by the PROCR H1 haplotype. We evaluated APC, PC, and factor (F)II levels in 502 VTE patients (158 with and 344 without OACs) and in 322 healthy individuals. Mean APC, PC and FII levels were significantly lower in OAC patients than in patients not taking OACs. During anticoagulant therapy, the FII/PC ratios were independent of the PC values, whereas APC/FII and APC/PC ratios significantly increased when FII and PC levels decreased. Of the 22 OAC patients carrying the H1H1genotype, 11 (50%) showed APC/PCag ≥2.0 and 10 (45%) APC/ FIIag ratios ≥2.0, whereas for the 49 OAC patients non-carrying the H1 haplotype these figures were 6 (12%) and 4 (8%), respectively (p<0.001). Barium citrate adsorption of plasma from OAC patients showed that most of the circulating free and complexed APC, but only part of PCag, is fully carboxylated. In conclusion, during anticoagulant therapy VT patients have APC levels disproportionately higher than the corresponding PC levels, mainly due to the presence of the PROCR H1 haplotype. Furthermore, a sufficiently carboxylated PC Gla-domain seems to be essential for PC activation in vivo.