bluuebunny/crossref_metadata_2025_split huggingface dataset:
Engineered Zinc Finger Protein–Mediated VEGF-A Activation Restores Deficient VEGF-A in Sensory Neurons in Experimental Diabetes
Authors: Pawson Elizabeth J. , Duran-Jimenez Beatriz , Surosky Richard , Brooke Heather E. , Spratt S. Kaye , Tomlinson David R. , Gardiner Natalie J. 
Published: November 2009

OBJECTIVE
The objectives of the study were to evaluate retrograde axonal transport of vascular endothelial growth factor A (VEGF-A) protein to sensory neurons after intramuscular administration of an engineered zinc finger protein activator of endogenous VEGF-A (VZ+434) in an experimental model of diabetes, and to characterize the VEGF-A target neurons.

RESEARCH DESIGN AND METHODS
We compared the expression of VEGF-A in lumbar (L)4/5 dorsal root ganglia (DRG) of control rats and VZ+434-treated and untreated streptozotocin (STZ)-induced diabetic rats. In addition, axonal transport of VEGF-A, activation of signal transduction pathways in the DRG, and mechanical sensitivity were assessed.

RESULTS
VEGF-A immunoreactivity (IR) was detected in small- to medium-diameter neurons in DRG of control rats. Fewer VEGF-A-IR neurons were observed in DRG from STZ-induced diabetic rats; this decrease was confirmed and quantified by Western blotting. VZ+434 administration resulted in a significant increase in VEGF-A protein expression in ipsilateral DRG, 24 h after injection. VEGF-A was axonally transported to the DRG via the sciatic nerve. VZ+434 administration resulted in significant activation of AKT in the ipsilateral DRG by 48 h that was sustained for 1 week after injection. VZ+434 protected against mechanical allodynia 8 weeks after STZ injection.

CONCLUSIONS
Intramuscular administration of VZ+434 increases VEGF-A protein levels in L4/5 DRG, correcting the deficit observed after induction of diabetes, and protects against mechanical allodynia. Elevated VEGF-A levels result from retrograde axonal transport and are associated with altered signal transduction, via the phosphatidylinositol 3′-kinase pathway. These data support a neuroprotective role for VEGF-A in the therapeutic actions of VZ+434 and suggest a mechanism by which VEGF-A exerts this activity.
Depletion of Liver Kupffer Cells Prevents the Development of Diet-Induced Hepatic Steatosis and Insulin Resistance
Authors: Huang Wan , Metlakunta Anantha , Dedousis Nikolaos , Zhang Pili , Sipula Ian , Dube John J. , Scott Donald K. , O'Doherty Robert M. 
Published: November 2009

OBJECTIVE
Increased activity of the innate immune system has been implicated in the pathogenesis of the dyslipidemia and insulin resistance associated with obesity and type 2 diabetes. In this study, we addressed the potential role of Kupffer cells (liver-specific macrophages, KCs) in these metabolic abnormalities.

RESEARCH DESIGN AND METHODS
Rats were depleted of KCs by administration of gadolinium chloride, after which all animals were exposed to a 2-week high-fat or high-sucrose diet. Subsequently, the effects of these interventions on the development of hepatic insulin resistance and steatosis were assessed. In further studies, the effects of M1-polarized KCs on hepatocyte lipid metabolism and insulin sensitivity were addressed.

RESULTS
As expected, a high-fat or high-sucrose diet induced steatosis and hepatic insulin resistance. However, these metabolic abnormalities were prevented when liver was depleted of KCs. In vitro, KCs recapitulated the in vivo effects of diet by increasing hepatocyte triglyceride accumulation and fatty acid esterification, and decreasing fatty acid oxidation and insulin responsiveness. To address the mechanisms(s) of KC action, we inhibited a panel of cytokines using neutralizing antibodies. Only neutralizing antibodies against tumor necrosis factor-α (TNFα) attenuated KC-induced alterations in hepatocyte fatty acid oxidation, triglyceride accumulation, and insulin responsiveness. Importantly, KC TNFα levels were increased by diet in vivo and in isolated M1-polarized KCs in vitro.

CONCLUSIONS
These data demonstrate a role for liver macrophages in diet-induced alterations in hepatic lipid metabolism and insulin sensitivity, and suggest a role for these cells in the etiology of the metabolic abnormalities of obesity/type 2 diabetes.
Cellular Production of n-3 PUFAs and Reduction of n-6–to–n-3 Ratios in the Pancreatic β-Cells and Islets Enhance Insulin Secretion and Confer Protection Against Cytokine-Induced Cell Death
Authors: Wei Dong , Li Jie , Shen Miaoda , Jia Wei , Chen Nuoqi , Chen Tao , Su Dongming , Tian Haoming , Zheng Shusen , Dai Yifan , Zhao Allan 
Published: November 2009

OBJECTIVETo evaluate the direct impact of n-3 polyunsaturated fatty acids (n-3 PUFAs) on the functions and viability of pancreatic β-cells.RESEARCH DESIGN AND METHODSWe developed an mfat-1 transgenic mouse model in which endogenous production of n-3 PUFAs was achieved through overexpressing a C. elegans n-3 fatty acid desaturase gene, mfat-1. The islets and INS-1 cells expressing mfat-1 were analyzed for insulin secretion and viability in response to cytokine treatment.RESULTSThe transgenic islets contained much higher levels of n-3 PUFAs and lower levels of n-6 PUFAs than the wild type. Insulin secretion stimulated by glucose, amino acids, and glucagon-like peptide-1 (GLP-1) was significantly elevated in the transgenic islets. When challenged with tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and γ-interferon (IFN-γ), the transgenic islets completely resisted cytokine-induced cell death. Adenoviral transduction of mfat-1 gene in wild-type islets and in INS-1 cells led to acute changes in the cellular levels of n-3- and n-6 PUFAs and recapitulated the results in the transgenic islets. The expression of mfat-1 led to decreased production of prostaglandin E2 (PGE2), which in turn contributed to the elevation of insulin secretion. We further found that cytokine-induced activation of NF-κB and extracellular signal–related kinase 1/2 (ERK1/2) was significantly attenuated and that the expression of pancreatic duodenal hemeobox-1 (PDX-1), glucokinase, and insulin-1 was increased as a result of n-3 PUFA production.CONCLUSIONSStable cellular production of n-3 PUFAs via mfat-1 can enhance insulin secretion and confers strong resistance to cytokine-induced β-cell destruction. The utility of mfat-1 gene in deterring type 1 diabetes should be further explored in vivo.
Antigen-Specific Dependence of Tr1-Cell Therapy in Preclinical Models of Islet Transplant
Authors: Gagliani Nicola , Jofra Tatiana , Stabilini Angela , Valle Andrea , Atkinson Mark , Roncarolo Maria-Grazia , Battaglia Manuela 
Published: November 2009

OBJECTIVE
In type 1 diabetes, allogeneic pancreatic islet transplant restores insulin production, but life-threatening immunosuppression is required to avoid graft rejection. Induction of antigen (Ag)–specific tolerance by cell therapy with regulatory T-cells (Tregs) represents an attractive alternative approach but its therapeutic efficacy in islet transplant remains to be determined. Among the different subsets of CD4+ Tregs, the T inducible regulatory type 1 (Tr1) cells can be generated from naive T-cells in the presence of interleukin-10 (IL-10) and represent one promising therapeutic choice. This study was designed to define the efficacy of Tr1-cell therapy in preclinical models of islet transplant.

RESEARCH DESIGN AND METHODS
Non–Ag-specific polyclonal Tr1 cells and donor Ag-specific Tr1 cells were transferred, in the absence of any pharmacological treatment, in two distinct mouse models of islet transplant. The two models differed in their therapeutic stringency, based on the mean rejection time of untreated mice that underwent a transplant.

RESULTS
Transfer of polyclonal Tr1 cells engendered graft tolerance only in the nonstringent mouse model. Conversely, cell therapy with Ag-specific Tr1 cells induced an IL-10–dependent tolerance in the stringent mouse model of islet transplant. The therapeutic advantage of Ag-specific Tr1 cells over polyclonal Tr1 cells was due to their donor Ag specificity.

CONCLUSIONS
These results demonstrate that Tr1-cell therapy leads to tolerance in settings of islet transplant and that its therapeutic efficacy is highly dependent on the antigen specificity of these cells.
Prokineticin 2 Is a Hypothalamic Neuropeptide That Potently Inhibits Food Intake
Authors: Gardiner James V. , Bataveljic Attia , Patel Neekhil A. , Bewick Gavin A. , Roy Debabrata , Campbell Daniel , Greenwood Hannah C. , Murphy Kevin G. , Hameed Saira , Jethwa Preeti H. , Ebling Francis J.P. , Vickers Steven P. , Cheetham Sharon , Ghatei Mohammad A. , Bloom Stephen R. , Dhillo Waljit S. 
Published: November 2009

OBJECTIVE
Prokineticin 2 (PK2) is a hypothalamic neuropeptide expressed in central nervous system areas known to be involved in food intake. We therefore hypothesized that PK2 plays a role in energy homeostasis.

RESEARCH DESIGN AND METHODS
We investigated the effect of nutritional status on hypothalamic PK2 expression and effects of PK2 on the regulation of food intake by intracerebroventricular (ICV) injection of PK2 and anti-PK2 antibody. Subsequently, we investigated the potential mechanism of action by determining sites of neuronal activation after ICV injection of PK2, the hypothalamic site of action of PK2, and interaction between PK2 and other hypothalamic neuropeptides regulating energy homeostasis. To investigate PK2's potential as a therapeutic target, we investigated the effect of chronic administration in lean and obese mice.

RESULTS
Hypothalamic PK2 expression was reduced by fasting. ICV administration of PK2 to rats potently inhibited food intake, whereas anti-PK2 antibody increased food intake, suggesting that PK2 is an anorectic neuropeptide. ICV administration of PK2 increased c-fos expression in proopiomelanocortin neurons of the arcuate nucleus (ARC) of the hypothalamus. In keeping with this, PK2 administration into the ARC reduced food intake and PK2 increased the release of α-melanocyte–stimulating hormone (α-MSH) from ex vivo hypothalamic explants. In addition, ICV coadministration of the α-MSH antagonist agouti-related peptide blocked the anorexigenic effects of PK2. Chronic peripheral administration of PK2 reduced food and body weight in lean and obese mice.

CONCLUSIONS
This is the first report showing that PK2 has a role in appetite regulation and its anorectic effect is mediated partly via the melanocortin system.
Cost-Effectiveness of the Diabetes Care Protocol, a Multifaceted Computerized Decision Support Diabetes Management Intervention That Reduces Cardiovascular Risk
Authors: Cleveringa Frits G.W. , Welsing Paco M.J. , van den Donk Maureen , Gorter Kees J. , Niessen Louis W. , Rutten Guy E.H.M. , Redekop William K. 
Published: November 2009

OBJECTIVE
The Diabetes Care Protocol (DCP), a multifaceted computerized decision support diabetes management intervention, reduces cardiovascular risk of type 2 diabetic patients. We performed a cost-effectiveness analysis of DCP from a Dutch health care perspective.

RESEARCH DESIGN AND METHODS
A cluster randomized trial provided data of DCP versus usual care. The 1-year follow-up patient data were extrapolated using a modified Dutch microsimulation diabetes model, computing individual lifetime health-related costs, and health effects. Incremental costs and effectiveness (quality-adjusted life-years [QALYs]) were estimated using multivariate generalized estimating equations to correct for practice-level clustering and confounding. Incremental cost-effectiveness ratios (ICERs) were calculated and cost-effectiveness acceptability curves were created. Stroke costs were calculated separately. Subgroup analyses examined patients with and without cardiovascular disease (CVD+ or CVD− patients, respectively).

RESULTS
Excluding stroke, DCP patients lived longer (0.14 life-years, P = NS), experienced more QALYs (0.037, P = NS), and incurred higher total costs (€1,415, P = NS), resulting in an ICER of €38,243 per QALY gained. The likelihood of cost-effectiveness given a willingness-to-pay threshold of €20,000 per QALY gained is 30%. DCP had a more favorable effect on CVD+ patients (ICER = €14,814) than for CVD− patients (ICER = €121,285). Coronary heart disease costs were reduced (€−587, P &lt; 0.05).

CONCLUSIONS
DCP reduces cardiovascular risk, resulting in only a slight improvement in QALYs, lower CVD costs, but higher total costs, with a high cost-effectiveness ratio. Cost-effective care can be achieved by focusing on cardiovascular risk factors in type 2 diabetic patients with a history of CVD.
Evaluation of Serum 1,5 Anhydroglucitol Levels as a Clinical Test to Differentiate Subtypes of Diabetes
Authors: Pal Aparna , Farmer Andrew J. , Dudley Christina , Selwood Mary P. , Barrow Beryl A. , Klyne Rhiannon , Grew Jilly P. , McCarthy Mark I. , Gloyn Anna L. , Owen Katharine R. 
Published: November 2009

OBJECTIVE
Assignment of the correct molecular diagnosis in diabetes is necessary for informed decisions regarding treatment and prognosis. Better clinical markers would facilitate discrimination and prioritization for genetic testing between diabetes subtypes. Serum 1,5 anhydroglucitol (1,5AG) levels were reported to differentiate maturity-onset diabetes of the young due to HNF1A mutations (HNF1A-MODY) from type 2 diabetes, but this requires further validation. We evaluated serum 1,5AG in a range of diabetes subtypes as an adjunct for defining diabetes etiology.

RESEARCH DESIGN AND METHODS
1,5AG was measured in U.K. subjects with: HNF1A-MODY (n = 23), MODY due to glucokinase mutations (GCK-MODY, n = 23), type 1 diabetes (n = 29), latent autoimmune diabetes in adults (LADA, n = 42), and type 2 diabetes (n = 206). Receiver operating characteristic curve analysis was performed to assess discriminative accuracy of 1,5AG for diabetes etiology.

RESULTS
Mean (SD range) 1,5AG levels were: GCK-MODY 13.06 μg/ml (5.74–29.74), HNF1A-MODY 4.23 μg/ml (2.12–8.44), type 1 diabetes 3.09 μg/ml (1.45–6.57), LADA 3.46 μg/ml (1.42–8.45), and type 2 diabetes 5.43 (2.12–13.23). Levels in GCK-MODY were higher than in other groups (P &lt; 10−4 vs. each group). HNF1A-MODY subjects showed no difference in unadjusted 1,5AG levels from type 2 diabetes, type 1 diabetes, and LADA. Adjusting for A1C revealed a difference between HNF1A-MODY and type 2 diabetes (P = 0.001). The discriminative accuracy of unadjusted 1,5AG levels was 0.79 for GCK-MODY versus type 2 diabetes and 0.86 for GCK-MODY versus HNF1A-MODY but was only 0.60 for HNF1A-MODY versus type 2 diabetes.

CONCLUSIONS
In our dataset, serum 1,5AG performed well in discriminating GCK-MODY from other diabetes subtypes, particularly HNF1A-MODY. Measurement of 1,5AG levels could inform decisions regarding MODY diagnostic testing.
Accumulation of Gene Polymorphisms Related to Plaque Disruption and Thrombosis Is Associated With Cerebral Infarction in Subjects With Type 2 Diabetes
Authors: Katakami Naoto , Takahara Mitsuyoshi , Kaneto Hideaki , Shimizu Ikki , Ohno Keizo , Ishibashi Fukashi , Osonoi Takeshi , Kashiwagi Atsunori , Kawamori Ryuzo , Shimomura Iichiro , Matsuhisa Munehide , Yamasaki Yoshimitsu 
Published: November 2009

OBJECTIVEIt is believed that disruption of vulnerable atherosclerotic plaque and subsequent thrombus formation play critical roles in the pathogenesis of cerebral infarction. We simultaneously determined four relatively common genetic variants related to plaque rupture or subsequent local thrombus formation and evaluated the combined effect on cerebral infarction.RESEARCH DESIGN AND METHODSWe enrolled 3,094 Japanese type 2 diabetic subjects (62.7% male; aged 61.5 ± 8.4 years) and determined their genotypes regarding matrix metalloproteinase 9 C-1562T, coagulation factor XII (F12) C46T, von Willebrand factor (VWF) G-1051A, and plasminogen activator inhibitor (PAI-1) 675 4G/5G polymorphisms. The diagnosis of cerebral infarction was performed based on history, physical examination, and neuroimaging.RESULTSThe single association analysis revealed that there were no statistically significant associations between each polymorphism and the prevalence of cerebral infarction. Interestingly, the prevalence of cerebral infarction was higher with the increase of the total number of four concomitant unfavorable proatherothrombotic alleles in each subject (P value for linear trend = 0.004). Furthermore, a multiple logistic regression analysis showed that the number of proatherothrombotic alleles was a risk factor for cerebral infarction independently of conventional risk factors (odds ratio for one-point increase in the number of proatherothrombotic allele 1.15 [95% CI 1.05–1.26], P = 0.004).CONCLUSIONSAccumulation of gene polymorphisms related to plaque rupture and thrombus formation is likely associated with the prevalence of cerebral infarction in type 2 diabetic patients, suggesting that the combined information about these variants is useful to assess the risk of cerebral infarction.
Anti-DR5 mAb Ameliorate Adjuvant Arthritis Rats Through Inducing Synovial Cells Apoptosis
Authors: Li Wenzhu , Liu Zhongchen , Zhuang Guohong , Yin Ping , Tao Huiran , Qiu Jinghua , Hu Qingzhong , Zhang Jiakai 
Published: November 2009

Objective: Study the therapeutic effects and immunoregulatory mechanisms of anti-DR5 mAb on adjuvant arthritis (AA) rats. Methods: AA rats induced by CFA, were treated with anti-DR5 mAb through mainline administration. Effect on the synovial membranes of the tissues was detected by H&E staining. Flow cytometry and MTT assay were used for detecting the induced apoptosis in an in vitro system and TUNEL assay was used for analysis in an in vivo system. The involvement of the apoptotic pathway was further proved by a caspase inhibition assay. Results: Anti-DR5 mAb could induce synovial cell apoptosis in an in vitro system, which was related with the mRNA expression of DR5 on the cell surface. The mRNA expressions of c-myc and bcl-2 were decreased in synovial cells and those of p21, p53, and bax were increased. The protein expressions of caspase-8/3/9, RANKL, JNK2, and c-Jun were raised and that of bcl-2 was decreased. When the caspase inhibitor was added to the synovial cells treated with anti-DR5 mAb, it showed a dose-dependence inhibition effect, indicating that anti-DR5 mAb inducing apoptosis might be through the caspase pathway. Conclusion: This study shows that anti-DR5 mAb can ameliorate arthritic symptoms. The mechanisms of the treatment are related to the increase in synovial cell apoptosis by regulating the mRNA expression of DR5 and apoptosis-related genes, prolonging the duration of the cell cycle by modulation of the mRNA expression of cell cycle-related genes, and the protein expression of the molecules in the caspase pathway and RANKL, JNK2, and c-Jun.
Cak numerals
Authors: Keisuke Huziwara 
Published: November 2009

Cak is a Luish language of the Tibeto-Burman language family and it is spoken mainly in the Naikhyongchari subdistrict of Bandarban district, Chittagong Hill Tracts (henceforth, CHT),Bangladesh. In this paper, I briefly describe the Cak numeral system. Numerals in Cak are basically nouns. Cak has two series of cardinal numerals: one is the native Cak numerals and the other is borrowed from Marma. The difference between these two types of numerals is reflected in the classifiers that they take: Cak numerals take native Cak classifiers whereas the numerals borrowed from Marma take classifiers of Marma origin. The native Cak numeral for ‘one' is unique in two respects. First, it changes form according to its phonological environment. Second, it appears after classifiers, while the other numerals precede classifiers. Finally, I show that all the ordinal numerals are borrowed from Pali through Marma. Key words: Cak, Marma, numerals, numeral classifiers, Tibeto-Burman languagesDOI:	10.3329/dujl.v1i2.3714 The Dhaka University Journal of Linguistics: Vol. 1 No.2 August, 2008 Page: 1-10
Colour terms in Bengali: A linguistic analisis
Authors: Ansary Shakhawat , Baktiyara Farida 
Published: November 2009

A large number of colour terms is used both in oral and written form of all the languages of the present world. It is equally applicable for the Bangla language also. Since colour terms occupy an excessive place and play an important role in every language, innumerable researches have been conducted focusing their various aspects. It is doubtlessly sorrowful that research of this kind is void in Bangla. This paper is an attempt to make a list of colour terms used in Bangla, to point out their etymology, to analyze their structures and meanings and to find out their nature of social reflection and semiotic aspects.DOI:	10.3329/dujl.v1i2.3715 The Dhaka University Journal of Linguistics: Vol. 1 No.2 August, 2008 Page: 11-44
Gemination in Bangla: An optimality Theoretic Analysis
Authors: Kar Somdev 
Published: November 2009

This paper attempts to identify and analyze different types of gemination processes in Bangla. The focus is mainly on the phonological representation of sound combinations which forms a set of valid geminates in this language. I argue for three major types of gemination processes present in modern Bangla and a stratification strategy for the relavant lexical items based on their origin (SB, NB and OB, depending on the native vs. two type of borrowings). An analysis of these gemination processes are given in the framework of optimality theory (OT). Therefore, the constraint-based analysis of OT is organized in a threefold argument structure for each stratum. The conclusion is drawn towards an understanding of gemination processes of Bangla for different categories of lexical items and their phonological formuations.DOI:	10.3329/dujl.v1i2.3718 The Dhaka University Journal of Linguistics: Vol. 1 No.2 August, 2008 Page: 87-114
A socio-linguistics view of the resent mixed form used in Bengali
Authors: Nasrin Salma 
Published: November 2009

As a social phenomenon, language is frequently influenced by different social codes, orders, and customs of society. Apart from the structural variety of language, many social dimensions of languages, develop over the time, occur. Nowadays Bengali- a rich language of south Asia- is encountering such social dimensional changes, as it interacts with its complex socio-cultural components. More elaborately, Bengali exhibits frequently different sociolinguistic characteristics such as code switching and code mixing, bilingualism and multilingualism, social dialect and dialectal free variation, language maintenance and language shift. This paper provides a brief description of sociolinguistic terms mentioned above from the point of view of the recent changes in Bengali. Key words: speech community, sociolect, code switching code mixing, code shifting, language shiftDOI:	10.3329/dujl.v1i2.3719 The Dhaka University Jaurnal of Linguistics: Vol. 1 No.2 Augus, 2008 Page: 115-124
A Cognitive Psychological Explanation of Difficulties in Learning Katakana
Authors: Hossain Muhammad Salim , Uddin Muhammad Kamal 
Published: November 2009

Japanese is one of the difficult languages for the non-natives. Every year many Bangladeshi students enrolled in language schools to learn Japanese. However, many of them eventually fail to continue the course owing to the difficulties in learning Japanese. The present paper investigated which script of Japanese seems difficult for the learners. The findings indicated that Katakana seems to be difficult for the learners than the Hiragana. Two cognitive psychological explanations of the difficulties associated with in learning Japanese specially Katakana is offered and concludes by suggesting ways to reduce drops-out. Key words: Distinctive features, Hiragana, Katakana, Serial position effectDOI:	10.3329/dujl.v1i2.3721 The Dhaka University Journal of Linguistics: Vol. 1 No. 2 August, 2008 Page: 147-156