bluuebunny/crossref_metadata_2025 huggingface dataset:
Disruption of the sugar-sensing receptor T1R2 attenuates metabolic derangements associated with diet-induced obesity
Authors: Smith Kathleen R. , Hussain Tania , Karimian Azari Elnaz , Steiner Jennifer L. , Ayala Julio E. , Pratley Richard E. , Kyriazis George A.
Published: February 2016

Sweet taste receptors (STRs) on the tongue mediate gustatory sweet sensing, but their expression in the gut, pancreas, and adipose tissue suggests a physiological contribution to whole body nutrient sensing and metabolism. However, little is known about the function and contribution of these sugar sensors during metabolic stress induced by overnutrition and subsequent obesity. Here, we investigated the effects of high-fat/low-carbohydrate (HF/LC) diet on glucose homeostasis and energy balance in mice with global disruption of the sweet taste receptor protein T1R2. We assessed body composition, energy balance, glucose homeostasis, and tissue-specific nutrient metabolism in T1R2 knockout (T1R2-KO) mice fed a HF/LC diet for 12 wk. HF/LC diet-fed T1R2-KO mice gained a similar amount of body mass as did WT mice, but had reduced fat mass and increased lean mass relative to WT mice. T1R2-KO mice were also hyperphagic and hyperactive. Ablation of the T1R2 sugar sensor protected mice from HF/LC diet-induced hyperinsulinemia and altered substrate utilization, including increased rates of glucose oxidation and decreased liver triglyceride (TG) accumulation, despite normal intestinal fat absorption. Finally, STRs ( T1r2/T1r3) were upregulated in the adipose tissue of WT mice in response to HF/LC diet, and their expression positively correlated with fat mass and glucose intolerance. The chemosensory receptor T1R2, plays an important role in glucose homeostasis during diet-induced obesity through the regulation of yet to be identified molecular mechanisms that alter energy disposal and utilization in peripheral tissues.
Iliopsoas Abscess Possibly due toKlebsiella pneumoniaeInfection after Chemoradiotherapy for Hypopharyngeal Cancer
Authors: Hyo Yukiyoshi , Fujisaki Tomoya , Hyo Rui , Tanaka Hiroki , Harada Tamotsu
Published: February 2016

Iliopsoas abscess was once an uncommon condition but now occurs somewhat more frequently due to the increasing number of immunocompromised patients, such as those with diabetes. We encountered a case of iliopsoas abscess following chemoradiotherapy for hypopharyngeal cancer. A 60-year-old man was admitted for a sore throat and left neck swelling. Hypopharyngeal cancer was diagnosed, but the patient refused surgery. After two rounds of chemotherapy, febrile neutropenia developed and chest computed tomography (CT) revealed an iliopsoas abscess. The platelet count was low but recovered after administration of antibiotics and could not be explained by puncture of the abscess. CT-guided drainage eventually improved his symptoms. Even for disorders of the head and neck region, iliopsoas abscess should be suspected in immunocompromised patients who develop a fever. CT and magnetic resonance imaging should be performed at an early stage as it is important to determine whether surgical drainage is indicated.
A Comparative Study of New Aspergillus Strains for Proteolytic Enzymes Production by Solid State Fermentation
Authors: Ortiz Gastón Ezequiel , Noseda Diego Gabriel , Ponce Mora María Clara , Recupero Matías Nicolás , Blasco Martín , Albertó Edgardo
Published: February 2016

A comparative study of the proteolytic enzymes production using twelve Aspergillus strains previously unused for this purpose was performed by solid state fermentation. A semiquantitative and quantitative evaluation of proteolytic activity were carried out using crude enzymatic extracts obtained from the fermentation cultures, finding seven strains with high and intermediate level of protease activity. Biochemical, thermodynamics, and kinetics features such as optimum pH and temperature values, thermal stability, activation energy (Ea), quotient energy (Q10), Km, and Vmax were studied in four enzymatic extracts from the selected strains that showed the highest productivity. Additionally, these strains were evaluated by zymogram analysis obtaining protease profiles with a wide range of molecular weight for each sample. From these four strains with the highest productivity, the proteolytic extract of A. sojae ATCC 20235 was shown to be an appropriate biocatalyst for hydrolysis of casein and gelatin substrates, increasing its antioxidant activities in 35% and 125%, respectively.
Mother-to-Child Transmission of HIV Infection and Its Determinants among Exposed Infants on Care and Follow-Up in Dire Dawa City, Eastern Ethiopia
Authors: Wudineh Fisseha , Damtew Bereket
Published: February 2016

Since the scale-up for prevention of mother-to-child transmission (PMTCT) services, rates of HIV infection among exposed infants have significantly declined. However, current achievements fell short of achieving the target sets. We investigated mother-to-child transmission (MTCT) of HIV infection and its determinants among HIV-exposed infants on care at Dilchora Referral Hospital in Dire Dawa City Administration. A retrospective institutional cohort study was conducted by reviewing follow-up records of HIV-exposed infants who were enrolled into care. Infants’ HIV serostatus was the outcome measure of the study. Bivariate and multivariate logistic regressions were employed to identify significant determinants. Of the 382 HIV-exposed infants enrolled into care, 60 (15.7%) became HIV positive. Rural residence (AOR: 3.29; 95% CI: 1.40, 7.22), home delivery (AOR: 3.35; 95% CI: 1.58, 8.38), infant not receiving ARV prophylaxis at birth (AOR: 5.83; 95% CI: 2.84, 11.94), mixed feeding practices (AOR: 42.21; 95% CI: 8.31, 214.38), and mother-child pairs neither receiving ARV (AOR: 4.42; 95% CI: 2.01, 9.82) were significant independent determinants of MTCT of HIV infection. Our findings suggest additional efforts to intensify scale-up of PMTCT services in rural setting and improve institutional delivery and postnatal care for HIV positive mothers and proper follow-up for HIV-exposed infants.
Therapeutic and Safety Evaluation of Combined Aqueous Extracts ofAzadirachta indicaandKhaya senegalensisin Chickens Experimentally Infected withEimeriaOocysts
Authors: Gotep J. G. , Tanko J. T. , Forcados G. E. , Muraina I. A. , Ozele N. , Dogonyaro B. B. , Oladipo O. O. , Makoshi M. S. , Akanbi O. B. , Kinjir H. , Samuel A. L. , Onyiche T. E. , Ochigbo G. O. , Aladelokun O. B. , Ozoani H. A. , Viyoff V. Z. , Dapuliga C. C. , Atiku A. A. , Okewole P. A. , Shamaki D. , Ahmed M. S. , Nduaka C. I.
Published: February 2016

Coccidiosis is a disease of economic importance in poultry causing morbidity and mortality. Reports show thatAzadirachta indicaandKhaya senegalensishave been used individually in the treatment of avian coccidiosis. We thus investigated the efficacy and safety of the combined aqueous extracts of these plants for the treatment of experimentally induced coccidiosis in broiler chickens using oocyst count, oxidative stress biomarkers, serum biochemistry, histology, and haematological parameters. The phytochemical screening revealed the presence of tannins, saponins, cardiac glycosides, and steroids in both extracts. In addition, alkaloids and flavonoids were present inAzadirachta indica.There was significant (p<0.05) dose dependent decrease in oocyst count across the treatment groups with 400 mg/kg of the combined extract being the most efficacious dose. Immunomodulatory and erythropoietic activity was observed. There were decreased intestinal lesions and enhanced antioxidant activity across the treatment groups compared to the negative control. Administration of the combined extract did not cause damage to the liver as ALT, AST, and ALP levels were significantly reduced in the uninfected chickens treated with the extracts compared to control suggesting safety at the doses used. The combined aqueous extracts ofK. senegalensisstem bark andAzadirachta indicaleaves were ameliorative in chickens infected with coccidiosis.
Application of PK/PD Modeling in Veterinary Field: Dose Optimization and Drug Resistance Prediction
Authors: Ahmad Ijaz , Huang Lingli , Hao Haihong , Sanders Pascal , Yuan Zonghui
Published: February 2016

Among veterinary drugs, antibiotics are frequently used. The true mean of antibiotic treatment is to administer dose of drug that will have enough high possibility of attaining the preferred curative effect, with adequately low chance of concentration associated toxicity. Rising of antibacterial resistance and lack of novel antibiotic is a global crisis; therefore there is an urgent need to overcome this problem. Inappropriate antibiotic selection, group treatment, and suboptimal dosing are mostly responsible for the mentioned problem. One approach to minimizing the antibacterial resistance is to optimize the dosage regimen. PK/PD model is important realm to be used for that purpose from several years. PK/PD model describes the relationship between drug potency, microorganism exposed to drug, and the effect observed. Proper use of the most modern PK/PD modeling approaches in veterinary medicine can optimize the dosage for patient, which in turn reduce toxicity and reduce the emergence of resistance. The aim of this review is to look at the existing state and application of PK/PD in veterinary medicine based onin vitro,in vivo, healthy, and disease model.
Exercise Training Attenuates Upregulation of p47phox and p67phox in Hearts of Diabetic Rats
Authors: Sharma Neeru M. , Rabeler Brandon , Zheng Hong , Raichlin Eugenia , Patel Kaushik P.
Published: February 2016

Exercise training (ExT) is currently being used as a nonpharmacological strategy to improve cardiac function in diabetic patients. However, the molecular mechanism(s) underlying its beneficial effects remains poorly understood. Oxidative stress is known to play a key role in the pathogenesis of diabetic cardiomyopathy and one of the enzyme systems that produce reactive oxygen species is NADH/NADPH oxidase. The goal of this study was to investigate the effect of streptozotocin‐ (STZ‐) induced diabetes on expression of p47phox and p67phox, key regulatory subunits of NADPH oxidase, in cardiac tissues and determine whether ExT can attenuate these changes. Four weeks after STZ treatment, expression of p47phox and p67phox increased 2.3‐fold and 1.6‐fold, respectively, in left ventricles of diabetic rats and these increases were attenuated with three weeks of ExT, initiated 1 week after onset of diabetes. In atrial tissues, there was increased expression of p47phox (74%), which was decreased by ExT in diabetic rats. Furthermore, increased collagen III levels in diabetic hearts (52%) were significantly reduced by ExT. Taken together, ExT attenuates the increased expression of p47phox and p67phox in the hearts of diabetic rats which could be an underlying mechanism for improving intracardiac matrix and thus cardiac function and prevent cardiac remodeling in diabetic cardiomyopathy.
Protective Effect of Decursin Extracted from Angelica gigas in Male Infertility via Nrf2/HO‐1 Signaling Pathway
Authors: Bae Woong Jin , Ha U. Syn , Choi Jin Bong , Kim Kang Sup , Kim Su Jin , Cho Hyuk Jin , Hong Sung Hoo , Lee Ji Youl , Wang Zhiping , Hwang Sung Yeoun , Kim Sae Woong
Published: February 2016

Higher testicular temperature results in altered spermatogenesis due to heat‐related oxidative stress. We examined the effects of decursin extracted from Angelica gigas Nakai on antioxidant activity in vitro and in a cryptorchidism‐induced infertility rat model. TM3 Leydig cell viability was measured based on oxidative stress according to treatment. Either distilled water or AG 400 mg/kg of A. gigas extract was administered orally for 4 weeks after unilateral cryptorchidism was induced. After 1, 2, and 4 weeks, six rats from the control group and six rats from treatment group were sacrificed. Testicular weight, semen quality, antioxidant activities, nuclear factor erythroid 2‐related factor 2 (Nrf2) protein, and mRNA expression of Nrf2‐regulated genes were analyzed. Treatment with A. gigas extract (1) protected TM3 cells against oxidative stress in a dose‐dependent manner, (2) improved the mean weight of the cryptorchid testis, (3) maintained sperm counts, motility, and spermatogenic cell density, (4) decreased levels of 8‐hydroxy‐2‐deoxyguanosine (8‐OHdG) and increased levels of superoxide dismutase (SOD), (5) significantly increased Nrf2 and heme oxygenase‐1 (HO‐1), and (6) significantly decreased apoptosis. This study suggests that decursin extracted from A. gigas is a supplemental agent that can reduce oxidative stress by Nrf2‐mediated upregulation of HO‐1 in rat experimentally induced unilateral cryptorchidism and may improve cryptorchidism‐induced infertility.
A Precise-Mask-Based Method for Enhanced Image Inpainting
Authors: Zhang Wanxu , Ru Yi , Meng Hongqi , Liu Min , Ma Xiaolei , Wang Lin , Jiang Bo
Published: February 2016

Mask of damage region is the pretreatment step of the image inpainting, which plays a key role in the ultimate effect. However, state-of-the-art methods have attached significance to the inpainting model, and the mask of damage region is usually selected manually or by the conventional threshold-based method. Since manual method is time-consuming and the threshold-based method does not have the same precision for different images, we herein report a new method for automatically constructing the precise mask by the joint filtering of guided filtering andL0smoothing. It can accurately locate the boundary of damaged region in order to effectively segment the damage region and then greatly improves the ultimate effect of image inpainting. The experimental results show that the proposed method is superior to state-of-the-art methods in the step of constructing inpainting mask, especially for the damaged region with inconspicuous boundary.
Effectiveness and Optical Quality of Topical 3.0% Diquafosol versus 0.05% Cyclosporine A in Dry Eye Patients following Cataract Surgery
Authors: Lee Jang Hoon , Song In Seok , Kim Kyoung Lae , Yoon Sam Young
Published: February 2016

Purpose.To evaluate the effectiveness and optical quality of 3.0% topical diquafosol versus 0.05% cyclosporine A in dry eye patients following cataract surgery.Methods.In total, 40 eyes of 40 patients newly diagnosed with dry eye syndrome 1 week after cataract surgery were randomized to receive either 3.0% diquafosol ophthalmic solution six times daily or 0.05% cyclosporine A twice daily for 3 months. Outcome measures were tear film break-up time (TBUT), results on Schirmer 1 test, ocular surface staining score, the ocular surface disease index (OSDI) score, and higher-order aberrations (HOAs). Measurements were taken at baseline and at 1, 2, and 3 months.Results.In the diquafosol group, TBUT showed higher outcomes than the cyclosporine A group at 1 and 3 months. Both groups showed increased scores on Schirmer 1 test. The ocular surface staining score decreased in all periods in both groups. Vertical coma and total HOAs decreased more in the cyclosporine A group than in the diquafosol group at 3 months.Conclusion.Both 3.0% diquafosol and 0.05% cyclosporine A were effective in treating dry eye after cataract surgery. Diquafosol was more effective in increasing the tear secretion, but cyclosporine A was more effective in improving optical aberrations.
Therapeutic Effects of Chinese Medicine Herb Pair, Huzhang and Guizhi, on Monosodium Urate Crystal‐Induced Gouty Arthritis in Rats Revealed by Anti‐Inflammatory Assessments and NMR‐Based Metabonomics
Authors: Han Bin , Huang Huizhu , Li Zhong , Gong Mengjuan , Shi Wan , Zhu Chunxia , Gu Zulian , Zou Zhongjie
Published: February 2016

The present study was undertaken to evaluate the therapeutic effects of Huzhang‐Guizhi herb pair (HG), firstly included in Hu‐Zhang Power documented in Taiping Shenghui Fang, on monosodium urate (MSU) crystals‐induced gouty arthritis in rats. We found that pretreatment with HG in rats with gouty arthritis could significantly attenuate the ankle joint swelling, and this beneficial antigout effect might be mediated, at least in part, by inhibiting tumor necrosis factor‐alpha (TNF‐α) and interleukin‐1 beta (IL‐1β) production in synovial fluid as well as nuclear transcription factor‐κB p65 (NF‐κB p65) protein expression in synovial tissue. Moreover, metabonomic analysis demonstrated that 5 and 6 potential biomarkers associated with gouty arthritis in plasma and urine, respectively, which were mainly involved in energy metabolism, amino acid metabolism, and gut microbe metabolism, were identified. HG could reverse the pathological process of MSU‐induced gouty arthritis through regulating the disturbed metabolic pathways. These results provided important mechanistic insights into the protective effects of HG against MSU‐induced gouty arthritis in rats.
Proinflammatory and Anti-Inflammatory Cytokines Mediated by NF-κB Factor as Prognostic Markers in Mammary Tumors
Authors: Martins Gustavo Rodrigues , Gelaleti Gabriela Bottaro , Moschetta Marina Gobbe , Maschio-Signorini Larissa Bazela , Zuccari Debora Ap. Pires de Campos
Published: February 2016

Inflammation results in the production of cytokines, such as interleukin- (IL-) 4 and IL-10 with immunosuppressive properties or IL-6 and TNF-αwith procarcinogenic activity. Furthermore, NF-κB is the major link between inflammation and tumorigenesis. This study verified the interaction between active inflammatory cytokines in the tumor microenvironment and serum of female dogs with mammary tumors and their correlation with the clinicopathological characteristics and overall survival. Measurement of gene expression was performed by qPCR and protein levels by ELISA/Luminex. High gene and protein expression levels of NF-κB, IL-6, and TNF-αwere found in association with characteristics that reflect worse prognosis and a negative correlation between TNF-αprotein expression and survival time was observed (p<0.05). In contrast, high gene and protein expression levels of IL-4 and IL-10 were associated with characteristics of better prognosis and an increased level of IL-4 and a longer survival time of animals were obtained (p<0.05). In addition, there was a positive correlation between TNF-αand IL-6 expression in association with NF-κB. The results show a significant correlation of these cytokines with tumor development, associated with NF-κB expression and cytokines promodulation, showing that these biological factors could be used as predictive and prognostic markers in breast cancer.
A Potent HER3 Monoclonal Antibody That Blocks Both Ligand-Dependent and -Independent Activities: Differential Impacts ofPTENStatus on Tumor Response
Authors: Xiao Zhan , Carrasco Rosa A. , Schifferli Kevin , Kinneer Krista , Tammali Ravinder , Chen Hong , Rothstein Ray , Wetzel Leslie , Yang Chunning , Chowdhury Partha , Tsui Ping , Steiner Philipp , Jallal Bahija , Herbst Ronald , Hollingsworth Robert E. , Tice David A.
Published: February 2016

HER3/ERBB3 is a kinase-deficient member of the EGFR family receptor tyrosine kinases (RTK) that is broadly expressed and activated in human cancers. HER3 is a compelling cancer target due to its important role in activation of the oncogenic PI3K/AKT pathway. It has also been demonstrated to confer tumor resistance to a variety of cancer therapies, especially targeted drugs against EGFR and HER2. HER3 can be activated by its ligand (heregulin/HRG), which induces HER3 heterodimerization with EGFR, HER2, or other RTKs. Alternatively, HER3 can be activated in a ligand-independent manner through heterodimerization with HER2 in HER2-amplified cells. We developed a fully human mAb against HER3 (KTN3379) that efficiently suppressed HER3 activity in both ligand-dependent and independent settings. Correspondingly, KTN3379 inhibited tumor growth in divergent tumor models driven by either ligand-dependent or independent mechanisms in vitro and in vivo. Most intriguingly, while investigating the mechanistic underpinnings of tumor response to KTN3379, we discovered an interesting dichotomy in that PTEN loss, a frequently occurring oncogenic lesion in a broad range of cancer types, substantially blunted the tumor response in HER2-amplified cancer, but not in the ligand-driven cancer. To our knowledge, this represents the first study ascertaining the impact of PTEN loss on the antitumor efficacy of a HER3 mAb. KTN3379 is currently undergoing a phase Ib clinical trial in patients with advanced solid tumors. Our current study may help us optimize patient selection schemes for KTN3379 to maximize its clinical benefits. Mol Cancer Ther; 15(4); 689–701. ©2016 AACR.
Mathematical Method for Analysis of the Refractive Outcome after Toric Intraocular Lens Implantation
Authors: Jin Haiying , Ou Zhongmin , Guo Haike , Auffarth Gerd U. , Zhao Peiquan
Published: February 2016

Purpose: We aimed to develop a self-designed software programmed with a mathematical method that analyzes the refractive outcome after toric intraocular lens (IOL) implantation, taking the axis misalignment of the toric IOL into consideration. Methods: A mathematical method that can analyze the refractive outcome after toric IOL implantation was devised. Compared with the conventional method, which performs the analysis based on precise alignment of the IOL, optional meridian orientations of the toric IOL were taken into account in this method. Self-designed computer software was developed using the mathematical method. Results: Relatively high accordance was achieved between the mathematical analysis and the actual postoperative outcome. The mean predicted spherical power was 0.37 ± 0.74 dpt, and the mean measured spherical power was 0.37 ± 0.71 dpt (paired t test, p = 0.98). The mean predicted cylindrical power was -1.35 ± 0.86 dpt, and the mean measured cylindrical power was -1.42 ± 0.85 dpt (p = 0.27). The mean predicted change in the astigmatic axis was 33.7 ± 11.8°, and the mean measured parameter was 32.5 ± 15.4° (p = 0.49). Conclusions: The advantage of the present mathematical method is that the postoperative refractive outcome can be analyzed under IOL misalignment.
The Very Long-Term Outcome of Radiosurgery for Classical Trigeminal Neuralgia
Authors: Régis Jean , Tuleasca Constantin , Resseguier Noémie , Carron Romain , Donnet Anne , Yomo Shoji , Gaudart Jean , Levivier Marc
Published: February 2016

Background: Radiosurgery is one of the neurosurgical alternatives for intractable trigeminal neuralgia (TN). Objective: Although acceptable short-/mid-term outcomes have been reported, long-term results have not been well documented. Methods: We report the long-term results in 130 patients who underwent radiosurgery for classical TN and were subsequently monitored through at least 7 years (median = 9.9, range = 7-14.5) of follow-up. Results: The median age was 66.5 years. A total of 122 patients (93.8%) became pain free (median delay = 15 days) after the radiosurgery procedure (Barrow Neurological Institute, BNI class I-IIIa). The probability of remaining pain free without medication at 3, 5, 7 and 10 years was 77.9, 73.8, 68 and 51.5%, respectively. Fifty-six patients (45.9%) who were initially pain free experienced recurrent pain (median delay = 73.1 months). However, at 10 years, of the initial 130 patients, 67.7% were free of any recurrence requiring new surgery (BNI class I-IIIa). The new hypesthesia rate was 20.8% (median delay of onset = 12 months), and only 1 patient (0.8%) reported very bothersome hypesthesia. Conclusions: The long-term results were comparable to those from our general series (recently published), and the high probability of long-lasting pain relief and rarity of consequential complications of radiosurgery may suggest it as a first- and/or second-line treatment for classical, drug-resistant TN.
Association between Tumor Necrosis Factor-α (-238G/A and -308G/A) Gene Polymorphisms and Risk of Ischemic Stroke: A Meta-Analysis
Authors: Kumar Pradeep , Misra Shubham , Kumar Amit , Pandit Awadh Kishor , Chakravarty Kamalesh , Prasad Kameshwar
Published: February 2016

Tumor necrosis factor-α (TNF-α) is a proinflammatory pleiotropic cytokine which may contribute to the initiation and progression of ischemic stroke (IS). Thus far, numerous studies have been performed to examine the association between -238G/A (rs361525) and -308G/A (rs1800629) polymorphisms in the promoter regions of the TNF-α gene and susceptibility to IS, but results are still conflicting. The aim of this meta-analysis is to provide a relatively comprehensive account of the association between TNF-α -238G/A and -308G/A gene polymorphisms and susceptibility to IS. A literature search for eligible candidate gene studies published before April 20, 2015, was conducted in the PubMed, Medline, EMBASE and Google Scholar databases. The following combinations of main keywords were used: (‘Tumor Necrosis Factor-Alpha' or ‘TNF-α') and (‘ischemic stroke' or ‘cerebral infarction' or ‘IS') and (‘genetic polymorphism' or ‘single nucleotide polymorphisms' or ‘SNP'). Fixed- or random-effect models were used to estimate the pooled odds ratio (OR) and 95% confidence interval (CI). Meta-analysis was carried out by using RevMan 5.3 software. For TNF-α -238G/A gene polymorphism, 7 case-control studies with a total of 1,846 IS patients and 1,905 controls showed a significant association with susceptibility to IS under a dominant model (AA + GA vs. GG; OR, 1.40; 95% CI, 1.11-1.76; p value 0.004). For TNF-α -308G/A gene polymorphism, 16 case-control studies with a total of 5,651 IS patients and 5,792 controls showed a significant protective association with susceptibility to IS under a dominant model (AA + GA vs. GG; OR, 0.78, 95% CI, 0.63-0.97; p value 0.03). Our meta-analysis shows that TNF-α -238G/A gene polymorphism is more likely to be associated with the risk of IS in Caucasian populations as compared to Asian populations. However, TNF-α -308G/A gene polymorphism is more likely to be protective against IS in Asian populations as compared to Caucasian populations. Further large, well-designed prospective epidemiological studies are needed to confirm these findings.
The Frequency of Huntington Disease and Huntington Disease-Like 2 in the South African Population
Authors: Baine Fiona K. , Krause Amanda , Greenberg L. Jacquie
Published: February 2016

Background: Huntington disease (HD) has most recently been estimated to affect between 10.6 and 13.7 per 100,000 individuals in European populations. However, prevalence is known to differ geographically. In South Africa, the only published estimates are from a survey performed in the 1970s, an era when the disease was believed to be rare or absent in black individuals and molecular confirmation was absent. The disease phenotype in South Africa is currently attributable to mutations in both the huntington and junctophilin-3 genes, which underlie the well-known HD and the rarer HD-like 2 (HDL2) respectively. This study aimed at providing improved minimum estimates of disease frequency in South Africa, based on molecular genetic testing data. Methods: A review of all testing records for HD and HDL2 over a 20-year period was undertaken. HDL2 is virtually indistinguishable on clinical features, thus necessitating its inclusion. Results: Based on molecular diagnostic records, minimum estimates of disease frequency are: 5.1, 2.1 and 0.25 (per 100,000 individuals) for the white, mixed ancestry and black population groups respectively. Conclusion: Although ascertainment remains incomplete, these minimum estimates suggest that disease frequencies are significantly higher than those previously reported in South Africa.
Calcitriol Suppression of Parathyroid Hormone Fails to Improve Skeletal Properties in an Animal Model of Chronic Kidney Disease
Authors: Newman Christopher L. , Tian Nannan , Hammond Max A. , Wallace Joseph M. , Brown Drew M. , Chen Neal X. , Moe Sharon M. , Allen Matthew R.
Published: February 2016

Background: Chronic kidney disease (CKD) leads to complex metabolic changes and an increased risk of fracture. Currently, calcitriol is the standard of care as it effectively suppresses parathyroid hormone (PTH) levels in CKD patients. While calcitriol and its analogs improve BMD and reduce fractures in the general population, the extension of these benefits to patients with advanced kidney disease is unclear. Here, the impact of calcitriol on the skeleton was examined in the setting of reduction in PTH. Methods: Male Cy/+ rats, a PKD-like CKD model, were treated with either vehicle or calcitriol for 5 weeks. Their normal littermates served as controls. Animals were assessed for changes in mineral metabolism and skeletal parameters (microCT, histology, whole bone mechanics and bone quality). Results: PTH levels were significantly higher (12-fold) in animals with CKD compared to normal controls. CKD animals also exhibited negative changes in bone structural and mechanical properties. Calcitriol treatment resulted in a 60% suppression of PTH levels in animals with CKD. Despite these changes, it had no impact on bone volume (cortical or cancellous), bone turnover, osteoclast number or whole bone mechanical properties. Conclusions: These data indicate that while calcitriol effectively lowered PTH in rats with CKD, it did little to prevent the negative effects of secondary hyperparathyroidism on the skeleton.
Novel 6p21.3 Risk Haplotype Predisposes to Acute Coronary Syndrome
Authors: Sinisalo Juha , Vlachopoulou Efthymia , Marchesani Marja , Nokelainen Johanna , Mäyränpää Mikko I. , Lappalainen Jani , Paakkanen Riitta , Wennerström Annika , Salli Krista , Niemi Heikki J. , Männistö Satu , Salo Perttu , Junttila Juhani , Eskola Markku , Nikus Kjell , Arstila T. Petteri , Perola Markus , Huikuri Heikki , Karhunen Pekka J. , Kovanen Petri T. , Palotie Aarno , Havulinna Aki S. , Lluis-Ganella Carla , Marrugat Jaume , Elosua Roberto , Salomaa Veikko , Nieminen Markku S. , Lokki Marja-Liisa
Published: February 2016

Background—

The
HLA-DRB1*01
allele of the human leukocyte antigen has been associated with acute coronary syndrome. Genome-wide association studies have revealed associations with human leukocyte antigen and non–human leukocyte antigen genes of 3 major histocompatibility complex gene classes but not at allelic level.

Methods and Results—

We conducted a large-scale genetic analysis on a case–control cohort comprising 5376 acute coronary syndrome cases and 4852 unrelated controls from 4 populations of 2 European countries. We analyzed the risk candidate allele of
HLA-DRB1*01
by genomic real-time polymerase chain reaction together with high-density single nucleotide polymorphisms of the major histocompatibility complex to precisely identify risk loci for acute coronary syndrome with effective clinical implications. We found a risk haplotype for the disease containing single nucleotide polymorphisms from
BTNL2
and
HLA-DRA
genes and the
HLA-DRB1*01
allele. The association of the haplotype appeared in 3 of the 4 populations, and the direction of the effect was consistent in the fourth. Coronary samples from subjects homozygous for the disease-associated haplotype showed higher
BTNL2
mRNA levels (
r
=0.760;
P
<0.00001).We localized, with immunofluorescence staining, BTNL2 in CD68-positive macrophages of the coronary artery plaques. In homozygous cases, BTNL2 blocking, in T-cell stimulation assays, enhanced CD4
+
FOXP3
+
regulatory T cell proliferation significantly (blocking versus nonblocking;
P
<0.05).

Conclusions—

In cases with the risk haplotype for acute coronary syndrome, these results suggest involvement of enhanced immune reactions. BTNL2 may have an inhibitory effect on FOXP3
+
T cell proliferation, especially in patients homozygous for the risk alleles.

Clinical Trial Registration—

https://www.clinicaltrials.gov
; Unique Identifier: NCT00417534.
Elevated Plasma Cardiac Troponin T Levels Caused by Skeletal Muscle Damage in Pompe Disease
Authors: Wens Stephan C.A. , Schaaf Gerben J. , Michels Michelle , Kruijshaar Michelle E. , van Gestel Tom J.M. , in ‘t Groen Stijn , Pijnenburg Joon , Dekkers Dick H.W. , Demmers Jeroen A.A. , Verdijk Lex B. , Brusse Esther , van Schaik Ron H.N. , van der Ploeg Ans T. , van Doorn Pieter A. , Pijnappel W.W.M. Pim
Published: February 2016

Background—

Elevated plasma cardiac troponin T (cTnT) levels in patients with neuromuscular disorders may erroneously lead to the diagnosis of acute myocardial infarction or myocardial injury.

Methods and Results—

In 122 patients with Pompe disease, the relationship between cTnT, cardiac troponin I, creatine kinase (CK), CK-myocardial band levels, and skeletal muscle damage was assessed. ECG and echocardiography were used to evaluate possible cardiac disease. Patients were divided into classic infantile, childhood-onset, and adult-onset patients. cTnT levels were elevated in 82% of patients (median 27 ng/L, normal values <14 ng/L). Cardiac troponin I levels were normal in all patients, whereas CK-myocardial band levels were increased in 59% of patients. cTnT levels correlated with CK levels in all 3 subgroups (
P
<0.001). None of the abnormal ECGs recorded in 21 patients were indicative of acute myocardial infarction, and there were no differences in cTnT levels between patients with and without (n=90) abnormalities on ECG (median 28 ng/L in both groups). The median left ventricular mass index measured with echocardiography was normal in all the 3 subgroups. cTnT mRNA expression in skeletal muscle was not detectable in controls but was strongly induced in patients with Pompe disease. cTnT protein was identified by mass spectrometry in patient-derived skeletal muscle tissue.

Conclusions—

Elevated plasma cTnT levels in patients with Pompe disease are associated with skeletal muscle damage, rather than acute myocardial injury. Increased cTnT levels in Pompe disease and likely other neuromuscular disorders should be interpreted with caution to avoid unnecessary cardiac interventions.
Selective Targeting of a Novel Epsin–VEGFR2 Interaction Promotes VEGF-Mediated Angiogenesis
Authors: Rahman H.N. Ashiqur , Wu Hao , Dong Yunzhou , Pasula Satish , Wen Aiyun , Sun Ye , Brophy Megan L. , Tessneer Kandice L. , Cai Xiaofeng , McManus John , Chang Baojun , Kwak Sukyoung , Rahman Negar S. , Xu Wenjia , Fernandes Conrad , Mcdaniel John Michael , Xia Lijun , Smith Lois , Srinivasan R. Sathish , Chen Hong
Published: February 2016

Rationale
:

We previously reported that vascular endothelial growth factor (VEGF)-induced binding of VEGF receptor 2 (VEGFR2) to epsins 1 and 2 triggers VEGFR2 degradation and attenuates VEGF signaling. The epsin ubiquitin interacting motif (UIM) was shown to be required for the interaction with VEGFR2. However, the molecular determinants that govern how epsin specifically interacts with and regulates VEGFR2 were unknown.

Objective
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The goals for the present study were as follows: (1) to identify critical molecular determinants that drive the specificity of the epsin and VEGFR2 interaction and (2) to ascertain whether such determinants were critical for physiological angiogenesis in vivo.

Methods and Results
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Structural modeling uncovered 2 novel binding surfaces within VEGFR2 that mediate specific interactions with epsin UIM. Three glutamic acid residues in epsin UIM were found to interact with residues in VEGFR2. Furthermore, we found that the VEGF-induced VEGFR2–epsin interaction promoted casitas B-lineage lymphoma–mediated ubiquitination of epsin, and uncovered a previously unappreciated ubiquitin-binding surface within VEGFR2. Mutational analysis revealed that the VEGFR2–epsin interaction is supported by VEGFR2 interacting specifically with the UIM and with ubiquitinated epsin. An epsin UIM peptide, but not a mutant UIM peptide, potentiated endothelial cell proliferation, migration and angiogenic properties in vitro, increased postnatal retinal angiogenesis, and enhanced VEGF-induced physiological angiogenesis and wound healing.

Conclusions
:

Distinct residues in the epsin UIM and VEGFR2 mediate specific interactions between epsin and VEGFR2, in addition to UIM recognition of ubiquitin moieties on VEGFR2. These novel interactions are critical for pathophysiological angiogenesis, suggesting that these sites could be selectively targeted by therapeutics to modulate angiogenesis.
Nankani Women’s Spirituality and Ecology
Authors: Amenga-Etego Rose Mary
Published: February 2016

Nankani women are not only thought to believe they are spiritual beings; they are also made to understand that they are structurally interwoven with their ecosystem. From the mythical and proverbial saying, ‘he who wilfully kills a woman has invoked upon himself a curse that he can never fully rectify,’ to the religio-cultural symbolic representations of the woman as a calabash (vegetation) and/or and earthen pot (sand/clay), Nankani women are socialized to accept and recognise their integral place and role in their society’s life and wellbeing. Thus strategically entangled with the family, clan and the community’s beliefs and practices; the women believe they are purposefully situated to play their multi-tasking roles just as a pregnant woman nurtures and sustains the life within her. This paper provides some insights into Nankani women’s spirituality and ecology.
Turning Weapons into Flowers
Authors: Pu Xiumei
Published: February 2016

This essay explores the synergies between ecowomanism and Bön, a spiritual tradition that is indigenous to Tibet. It develops the concept of “ecospirituality,” a nature-inspired spiritual way of knowing and living, arguing that ecowomanism and Bön gravitate toward each other for their shared ecospiritual sensibility. This sensibility has the potential to generate and sustain possibilities for social and environment wellbeing. An examination of the ecospiritual synergies between ecowomanism and Bön can inspire new ways of knowing and help create constructive methods of making positive changes at individual, social, and environmental levels.
Seeds of Light, Flowers of Power, Fruits of Change
Authors: Maparyan Layli
Published: February 2016

Ecowomanism focuses on the relationships between humans and nature through a spiritualized lens. Three core principles of ecowomanism are Livingkind (all living things are of a type), Aliveness (life pervades all creation, visible and invisible), and Luminosity (all living things are filled with light and spirit). Ecowomanism makes a unique, spiritually infused, ecological activist praxis possible. Three notable exemplars of this praxis are Sister Chan Khong (who established Sweet Potato Farm in France as part of her mindfulness-based peace activism), Kiran Bedi (who elevated the dignity of prisoners through her beautification of Tihar Jail/Ashram in India), and Wangari Maathai (who conscientized members of the Kenyan military by helping them to see the value of protecting the natural environment and planting trees as part of the Green Belt Movement).
International Law and International Institutions: Implications for a Rising China
Authors: Kong Qingjiang , Ping Xiaojuan
Published: February 2016

There is a growing concern that China has become more assertive in its foreign policies. The fear is whether China’s economic growth may translate into modern and effective military advancement. This engenders the critical question of whether China feels comfortable in the current international order, which is defiPed by international law and institutions. This article argues that the Chinese approach to international law and institutions is tightly associated with its evolving attitudes towards them. With its opening-up, China now views multilateralism as a way for the international community to constrain the capriciousness of a superpower, and regards the international institutions simply as power sharing development. However, China’s integration in international institutions represents its attempt to work within international norms to pursue its interests. It also shows China’s effort to hedge against American influence, and signals China’s emergence as an active player in the international arena.
The Statutory Reform of Chinese Private International Law in Property Rights: A Silent Revolution
Authors: Huo Zhengxin
Published: February 2016

This article reviews the statutory reform of Chinese private international law from the perspective of property rights which concludes that notwithstanding the significant improvement, the new Private International Law Act of China are fraught with various defects. In the field of property, Article 37 and Article 38 are particularly problematic as the introduction of unlimited party autonomy into the choice-of-law rules for movables and res in transitu is theoretically indefensible and practically troublesome. Moreover, there are a number of defects or problems with Article 39 and Article 40 of the Act respectively. What’s more, the Act neglects some other important types of property that call for special treatment, such as cultural property, and assignment of debt. In the end, the article puts forward the corresponding suggestions for improvement.
Non-Covalent Fluorescent Labeling of Hairpin DNA Probe Coupled with Hybridization Chain Reaction for Sensitive DNA Detection
Authors: Song Luna , Zhang Yonghua , Li Junling , Gao Qiang , Qi Honglan , Zhang Chengxiao
Published: February 2016

An enzyme-free signal amplification-based assay for DNA detection was developed using fluorescent hairpin DNA probes coupled with hybridization chain reaction (HCR). The hairpin DNAs were designed to contain abasic sites in the stem moiety. Non-covalent labeling of the hairpin DNAs was achieved when a fluorescent ligand was bound to the abasic sites through hydrogen bonding with the orphan cytosine present on the complementary strand, accompanied by quench of ligand fluorescence. As a result, the resultant probes, the complex formed between the hairpin DNA and ligand, showed almost no fluorescence. Upon hybridization with target DNA, the probe underwent a dehybridization of the stem moiety containing an abasic site. The release of ligand from the abasic site to the solution resulted in an effective fluorescent enhancement, which can be used as a signal. Compared with a sensing system without HCR, a 20-fold increase in the sensitivity was achieved using the sensing system with HCR. The fluorescent intensity of the sensing system increased with the increase in target DNA concentration from 0.5 nM to 100 nM. A single mismatched target ss-DNA could be effectively discriminated from complementary target DNA. Genotyping of a G/C single-nucleotide polymorphism of polymerase chain reaction (PCR) products was successfully demonstrated with the sensing system. Therefore, integrating HCR strategy with non-covalent labeling of fluorescent hairpin DNA probes provides a sensitive and cost-effective DNA assay.
What Can US Single-Payer Supporters Learn From the Swiss Rejection of Single Payer?
Authors: Chaufan Claudia
Published: February 2016

On September 27, 2014, Swiss voters rejected a proposal to replace their system of about 60 health insurance companies offering mandatory basic health coverage with a single public insurer, the state, which would offer taxpayer-funded coverage of all medically necessary care. The Swiss and the U.S. media, academia, and business sectors, from conservative and liberal camps, interpreted the results to mean a rejection of single payer and a preference for a privately run system, with important implications for health reform in the United States. While on the surface mainstream interpretations appear reasonable, I argue that they have little basis on fact because they rely on assumptions that, while untrue, are repeated as mantras that conveniently justify the continuation of a model of health insurance that is unraveling, less conspicuously in Switzerland, dramatically in the United States. To make my case, I describe the dominant narrative about Swiss health care and mainstream interpretations of the latest referendum on health reform, unpack the problem within these interpretations, and conclude by identifying what lessons the Swiss referendum contains for single payer advocates in the United States in particular and for those who struggle for social and economic rights more generally.
The Surprising Robustness of Surprising Events
Authors: Gelpi Christopher
Published: February 2016

Paolino presents two core critiques of “Performing on Cue.” First, he suggests that my dichotomous measures of support for the Iraq War bias against finding evidence of reinforcing cues. Second, he suggests that using party identification (ID) as a moderator for the treatment effects biases against finding an impact for elite cues. Unfortunately, Paolino’s statistical modeling choices do not reflect these theoretical concerns. His arguments about attitude strength and source credibility imply that the experimental treatments should have nonlinear effects. Yet Paolino relies on an ordinal logit model with a linear interaction of the treatments with a six-point index of party ID and Bush approval. A more appropriate approach for capturing Paolino’s critiques would estimate a multinomial logit model with categorical interaction effects between the treatments and the source credibility. These more appropriate statistical modeling choices reveal that the findings of “Performing on Cue” are very robust to the concerns raised by Paolino.
Reputation of Terror Groups Dataset
Authors: Tokdemir Efe , Akcinaroglu Seden
Published: February 2016

Violence against civilians is not the only tool among the arsenal of terrorists; it is only one of many. Up until now, there did not exist any quantitative data on the different strategies adopted by terror groups that measured the group’s popularity or its public support. The Reputation of Terror Groups dataset (RTG) addresses this void. To understand which terror groups build different types of reputation, to analyze the consequences of reputation building and how reputation changes with and influences conflict dynamics, we need to be able to measure the loaded concept of reputation. RTG is the first systematic measure for the reputation of terror groups across countries or time. The dataset includes 443 terror groups operating across 31 years, which makes a total of 2,641 observations. The large sample size of the RTG dataset allows comparisons of popularity among groups. Additionally, the dataset adopts a multivariable approach by examining multiple aspects of both positive and negative reputation building. Another novelty of the dataset is its measure of reputation with regard to each target, mainly its constituency and target audience. The RTG data can help us come up with new and novel ways of understanding terror groups, and contribute to bridging the gap between micro- and mezzo-level studies in the literature by showing how terror groups adopt different strategies in their constituency and target audience to pursue their goals. In this article, we give an overview assessment of the RTG dataset, display some interesting trends in the data, and explain the data collection procedure, its challenges, and its limitations.
A novel sensor fault diagnosis approach for time-varying delay systems with non-linear uncertainty
Authors: You Fuqiang , Li Hui , Zhang Yingwei , Guan Shouping
Published: February 2016

In this paper, a sensor fault diagnosis approach is presented for a class of time delay non-linear systems via the use of adaptive updating rules. The considered system is represented by a time-varying delay dynamical state space model, and is subjected to a non-linear vector, which represents the modelling uncertainty in the state equation. Firstly, a fault detector observer is constructed to detect the fault. Then, the method for choosing the threshold value is given. Furthermore, a fault diagnosis device is constructed to diagnose the fault. The Lyapunov stability theory is used to obtain the required adaptive tuning rules for the estimation of the sensor fault. An adaptive diagnosis algorithm is developed to obtain information on the sensor fault. Finally, a simulated numerical example and a robotic example are included to demonstrate the use of the proposed approach, and experimental results show that the proposed adaptive diagnosis algorithm can track the fault signal and that the proposed method is valid.