bluuebunny/crossref_metadata_2025 huggingface dataset:
Visual Field Defect after Cardiac Surgery: The Striking Role of Interdisciplinary Collaboration
Authors: Nuzzi Raffaele , Lavia Carlo
Published: December 2015

Perioperative visual loss (POVL) is a potentially devastating complication that can occur following ocular or nonocular surgery. The leading causes of this disease are retinal vascular occlusions, ischemic optic neuropathies, and cortical blindness. POVL pathogenesis is strictly influenced by surgery, anesthesia, and patients’ comorbidities. We report of a 55-year-old caucasian man who presented with complaints of sudden painless loss of vision and unilateral campimetric deficit. We recorded a preserved visual acuity but at fundus examination a bilateral ischemic optic neuropathy (ION) was suspected. Our hypothesis was supported by uncommon and peculiar visual field defects and a history of cardiovascular surgery shortly before was a striking data. When we examined his medical records we found strong accordance with what is reported in literature to be risk factors for postoperative ION development. He presented intraoperative hypotension, anemia, and hypothermia, he was older than 50 years, and surgery lasted for more than five hours. We are currently monitoring his visual acuity and visual fields which remain unchanged. As there is no proved therapy for such severe adverse events, we recommend intraoperative check of blood pressure, blood loss, and body temperature, associated with repeated eye checks and patients’ interview.
In Vivo Confocal Microscopy of the Human Cornea in the Assessment of Peripheral Neuropathy and Systemic Diseases
Authors: Wang Ellen F. , Misra Stuti L. , Patel Dipika V.
Published: December 2015

In vivo confocal microscopy (IVCM) of the living human cornea offers the ability to perform repeated imaging without tissue damage. Studies using corneal IVCM have led to significant contributions to scientific and clinical knowledge of the living cornea in health and pathological states. Recently the application of corneal IVCM beyond ophthalmology to wider clinical and research fields has been demonstrated. Abnormalities of the corneal subbasal nerve plexus have been associated with many forms of peripheral neuropathy and Langerhans cells correlate with systemic inflammatory states. There is a rapidly growing evidence base investigating the use of corneal IVCM in many systemic conditions and a well-established evidence base for IVCM imaging of the corneal subbasal plexus in diabetic peripheral neuropathy. This paper reviews the potential use of corneal IVCM in general clinical practice as a noninvasive method of assessing peripheral neuropathies, monitoring inflammatory states and clinical therapeutic response.
The Accuracy of Point-of-Care Creatinine Testing in the Emergency Department
Authors: Moreno Moises , Schwartz Adam , Dvorkin Ronald
Published: December 2015

Objective. To determine the accuracy of Point-Of-Care testing (PoCT) creatinine values when compared to standard central laboratory testing (IDMS) and to demonstrate if and how a discrepancy could lead to improper risk stratification for contrast induced nephropathy (CIN). Methods. We conducted a descriptive retrospective chart review of patients seen in the Emergency Department of a single suburban, community, and academic medical center. We included patients who presented to the department between March 2013 and September 2014 who had blood samples analyzed by both PoCT and IDMS. Results. Mean IDMS creatinine values were 0.23 mg/dL higher when compared with i-Stat values. 95% of the time, the IDMS creatinine value was variable and ranged from −0.45 mg/dL to +0.91 mg/dL when compared to the i-Stat creatinine. When using i-Stat creatinine values to calculate GFR, 47 out of 156 patients had risk category variations compared to using the IDMS value. This affected 30.1% of the total eligible sample population (22.9% to 37.3% with 95% CI). Conclusion. We found a significant discrepancy between PoCT and IDMS creatinine values and found that this discrepancy could lead to improper risk stratification for CIN.
Modeling Neurological Disease by Rapid Conversion of Human Urine Cells into Functional Neurons
Authors: Zhang Shu-Zhen , Ma Li-Xiang , Qian Wen-Jing , Li Hong-Fu , Wang Zhong-Feng , Wang Hong-Xia , Wu Zhi-Ying
Published: December 2015

Somatic cells can be directly converted into functional neurons by ectopic expression of defined factors and/or microRNAs. Since the first report of conversion mouse embryonic fibroblasts into functional neurons, the postnatal mouse, and human fibroblasts, astroglia, hepatocytes, and pericyte‐derived cells have been converted into functional dopaminergic and motor neurons both in vitro and in vivo. However, it is invasive to get all these materials. In the current study, we provide a noninvasive approach to obtain directly reprogrammed functional neurons by overexpression of the transcription factors Ascl1, Brn2, NeuroD, c‐Myc, and Myt1l in human urine cells. These induced neuronal (iN) cells could express multiple neuron‐specific proteins and generate action potentials. Moreover, urine cells from Wilson’s disease (WD) patient could also be directly converted into neurons. In conclusion, generation of iN cells from nonneural lineages is a feasible and befitting approach for neurological disease modeling.
Protective Effect of Peroxisome Proliferator‐Activated Receptor α Activation against Cardiac Ischemia‐Reperfusion Injury Is Related to Upregulation of Uncoupling Protein‐3
Authors: Song Jong Wook , Kim Hyo Jung , Lee Hyelin , Kim Jae-woo , Kwak Young-Lan
Published: December 2015

Activation of peroxisome proliferator‐activated receptor α (PPARα) confers cardioprotection, while its mechanism remains elusive. We investigated the protective effect of PPARα activation against cardiac ischemia‐reperfusion injury in terms of the expression of uncoupling protein (UCP). Myocardial infarct size and UCP expression were measured in rats treated with WY‐14643 20 mg/kg, a PPARα ligand, or vehicle. WY‐14643 increased UCP3 expression in vivo. Myocardial infarct size was decreased in the WY‐14643 group (76 ± 8% versus 42 ± 12%, P<0.05). During reperfusion, the incidence of arrhythmia was higher in the control group compared with the WY‐14643 group (9/10 versus 3/10, P<0.05). H9c2 cells were incubated for 24 h with WY‐14643 or vehicle. WY‐14643 increased UCP3 expression in H9c2 cells. WY‐14643 decreased hypoxia‐stimulated ROS production. Cells treated with WY‐14643 were more resistant to hypoxia‐reoxygenation than the untreated cells. Knocking‐down UCP3 by siRNA prevented WY‐14643 from attenuating the production of ROS. UCP3 siRNA abolished the effect of WY‐14643 on cell viability against hypoxia‐reoxygenation. In summary, administration of PPARα agonist WY‐14643 mitigated the extent of myocardial infarction and incidence of reperfusion‐induced arrhythmia. PPARα activation conferred cytoprotective effect against hypoxia‐reoxygenation. Associated mechanisms involved increased UCP3 expression and resultant attenuation of ROS production.
NRF2 Regulates HER2 and HER3 Signaling Pathway to Modulate Sensitivity to Targeted Immunotherapies
Authors: Khalil Hilal S. , Langdon Simon P. , Kankia Ibrahim H. , Bown James , Deeni Yusuf Y.
Published: December 2015

NF‐E2 related factor‐2 (NRF2) is an essential transcription factor for multiple genes encoding antioxidants and detoxification enzymes. NRF2 is implicated in promoting cancer therapeutic resistance by its detoxification function and crosstalk with proproliferative pathways. However, the exact mechanism of this intricate connectivity between NRF2 and growth factor induced proliferative pathway remains elusive. Here, we have demonstrated that pharmacological activation of NRF2 by tert‐butylhydroquinone (tBHQ) upregulates the HER family receptors, HER2 and HER3 expression, elevates pAKT levels, and enhances the proliferation of ovarian cancer cells. Preactivation of NRF2 also attenuates the combined growth inhibitory effects of HER2 targeting monoclonal antibodies, Pertuzumab and Trastuzumab. Further, tBHQ caused transcriptional induction of HER2 and HER3, while SiRNA‐mediated knockdown of NRF2 prevented this and further caused transcriptional repression and enhanced cytotoxicity of the HER2 inhibitors. Hence, NRF2 regulates both HER2 and HER3 receptors to influence cellular responses to HER2 targeting monoclonal antibodies. This deciphered crosstalk mechanism reinforces the role of NRF2 in drug resistance and as a relevant anticancer target.
SOD2 Mediates Amifostine‐Induced Protection against Glutamate in PC12 Cells
Authors: Jia Ji , Zhang Lei , Shi Xiaolei , Wu Mingchun , Zhou Xiang , Liu Xiaonan , Huo Tingting
Published: December 2015

Background. Cytoprotectant amifostine attenuates radiation‐induced oxidative injury by increasing intracellular manganese superoxide dismutase (SOD2) in peripheral tissue. However, whether amifostine could protect neuronal cells against oxidative injury has not been reported. The purpose of this study is to explore the protection of amifostine in PC12 cells. Methods. PC12 cells exposed to glutamate were used to mimic neuronal oxidative injury. SOD assay kit was taken to evaluate intracellular Cu/Zn SOD (SOD1) and SOD2 activities; western blot analysis and immunofluorescence staining were performed to investigate SOD2 protein expression; MTT, lactate dehydrogenase (LDH), release and cell morphology were used to evaluate cell injury degree, and apoptotic rate and cleaved caspase‐3 expression were taken to assess apoptosis; mitochondrial superoxide production, intracellular reactive oxygen species (ROS), and glutathione (GSH) and catalase (CAT) levels were evaluated by reagent kits. Results. Amifostine increased SOD2 activity and expression, decreased cell injury and apoptosis, reduced mitochondrial superoxide production and intracellular ROS generation, and restored intracellular GSH and CAT levels in PC12 cells exposed to glutamate. SOD2‐siRNA, however, significantly reversed the amifostine‐induced cytoprotective and antioxidative actions. Conclusion. SOD2 mediates amifostine‐induced protection in PC12 cells exposed to glutamate.
Elevated Levels of Urinary Markers of Oxidative DNA and RNA Damage in Type 2 Diabetes with Complications
Authors: Liu Xinle , Gan Wei , Zou Yuangao , Yang Bin , Su Zhenzhen , Deng Jin , Wang Lanlan , Cai Jianping
Published: December 2015

The mechanisms underlying progression of type 2 diabetes are complex and varied. Recent studies indicated that oxidative stress provided a new sight. To further assess the relationship between nucleic acid oxidation and complications in patients with type 2 diabetes and explore its possible molecular mechanisms, we studied 1316 subjects, including 633 type 2 diabetes patients and 683 age‐ and sex‐matched healthy controls. Urinary levels of DNA oxidation marker 8‐oxo‐7,8‐dihydro‐2′‐deoxyguanosine (8‐oxodGuo) and RNA oxidation marker 8‐oxo‐7,8‐dihydroguanosine (8‐oxoGuo) were measured by ultraperformance liquid chromatography and mass spectrometry (UPLC‐MS/MS). Serum glucose, HbA1c, total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides (TG) were also determined. The results showed significantly elevated levels of both the urinary 8‐oxodGuo and 8‐oxoGuo in diabetes patients with/without complications compared with age‐matched healthy control subjects (p = 0.02 and p < 0.001, resp.). Patients with complications, especially macrovascular complications, exhibited higher levels of 8‐oxoGuo than those without complications, while there was no difference in the concentrations of serum glucose and lipids. The finding indicates the role for oxidative damage to DNA and RNA, as a molecular mechanism contributing to the progression of type 2 diabetes. Elevated levels of 8‐oxoGuo may be a risk factor for type 2 diabetes complications, especially in diabetic macrovascular complications.
[Retracted] Nitroxyl (HNO): A Reduced Form of Nitric Oxide with Distinct Chemical, Pharmacological, and Therapeutic Properties
Authors: Shoman Mai E. , Aly Omar M.
Published: December 2015

Nitroxyl (HNO), the one‐electron reduced form of nitric oxide (NO), shows a distinct chemical and biological profile from that of NO. HNO is currently being viewed as a vasodilator and positive inotropic agent that can be used as a potential treatment for heart failure. The ability of HNO to react with thiols and thiol containing proteins is largely used to explain the possible biological actions of HNO. Herein, we summarize different aspects related to HNO including HNO donors, chemistry, biology, and methods used for its detection.
BMI1, ALDH1A1, and CD133 Transcripts Connect Epithelial‐Mesenchymal Transition to Cancer Stem Cells in Lung Carcinoma
Authors: Koren Ana , Rijavec Matija , Kern Izidor , Sodja Eva , Korosec Peter , Cufer Tanja
Published: December 2015

Epithelial‐mesenchymal transition (EMT) is the underlying mechanism of tumor invasion and metastasis. Evidences from lung cancer cellular models show EMT can trigger conversion to a cancer stem cell (CSC) phenotype. In this study, we assessed mRNA expression levels of EMT‐inducing transcription factors (BMI1, TWIST1), CSC (CD133, ALDH1A1), and epithelial (EpCAM) markers in primary tumor and whole blood samples obtained from 57 patients with operable non‐small‐cell lung cancer (NSCLC) as well as in circulating tumor cells (CTCs) of 13 patients with metastatic disease; then possible associations between marker expressions were evaluated. In primary tumors as well as in whole blood, correlations between BMI1 and ALDH1A1 and between BMI1 and CD133 mRNA expressions were identified. No correlations between TWIST1 and CSC markers were observed. BMI1 mRNA expression in tumors positively correlated with BMI1 mRNA expression in blood. The immunohistochemical analysis confirmed coexpression of BMI1 and CSC markers in tumors. Gene expression profiling in CTCs revealed upregulated expression of EMT/CSC markers in CTCs. Our results suggest CSCs are present in both, tumor tissue and blood of NSCLC patients, whereas Bmi1 may play an important role in initiation and maintenance of CSCs and might be involved in the blood‐borne dissemination of NSCLC.
Autoantibodies in Autoimmune Hepatitis
Authors: Muratori Luigi , Deleonardi Gaia , Lalanne Claudine , Barbato Erica , Tovoli Alessandra , Libra Alessia , Lenzi Marco , Cassani Fabio , Muratori Paolo
Published: December 2015

Background: The detection of diagnostic autoantibodies such as antinuclear antibodies (ANA), anti-smooth muscle antibodies (SMA), anti-liver/kidney microsomal type 1 (anti-LKM1), anti-liver cytosol type 1 (anti-LC1) and anti-soluble liver antigen (anti-SLA) is historically associated with the diagnosis of autoimmune hepatitis. Key Messages: When autoimmune hepatitis is suspected, the detection of one or any combination of diagnostic autoantibodies, by indirect immunofluorescence or immuno-enzymatic techniques with recombinant antigens, is a pivotal step to reach a diagnostic score of probable or definite autoimmune hepatitis. Conclusions: Diagnostic autoantibodies (ANA, SMA, anti-LKM1, anti-LC1, anti-SLA) are a cornerstone in the diagnosis of autoimmune hepatitis. Other ancillary autoantibodies, associated with peculiar clinical correlations, appear to be assay-dependent and institution-specific, and validation studies are needed.
Therapy of Primary Biliary Cirrhosis: Novel Approaches for Patients with Suboptimal Response to Ursodeoxycholic Acid
Authors: Parés Albert
Published: December 2015

Primary biliary cirrhosis (PBC) is a chronic cholestatic disease of presumed autoimmune pathogenesis, characterized by the inflammation and damage of the intrahepatic intermediate and small bile ducts, which eventually results in cirrhosis. A number of randomized and observational and pilot studies using several agents were carried out in the 80s, but no clear results or even harmful effects were reported. Over the past 2 decades, increasing evidence indicates that ursodeoxycholic acid (UDCA) - 13 to 16 mg/kg/day - is the treatment of choice for patients with PBC. Biochemical response to UDCA, assessed at 1 year, clearly predicts the long-term outcome, since in UDCA, responders survival is similar to that estimated for the matched control population. However, about 40% of patients have incomplete biochemical response and increased risk of progression and decreased survival free of transplantation. Patients with suboptimal biochemical response to UDCA outline the group in whom further single or combined treatments with UDCA are needed. Accordingly, data on the effect of fibrates alone or in combination with UDCA, and budesonide in combination with UDCA have been reported. The combined treatment of UDCA and fibrates in patients without optimal biochemical response to UDCA improves the degree of cholestasis and may minimize the long-term management of these patients. The results of the combined therapy of UDCA with budesonide are appealing but they should be established in large randomized trials. The effect of new agents such obeticholic acid are promising, since the addition of this farnesoide-X-receptor agonist bile acid in patients with stable UDCA dosage and increased alkaline phosphatase levels results in an improvement of cholestasis as compared to placebo, with a parallel decrease of aminotransferases and immunoglobulin M, as well as one surrogate marker of bile acid synthesis. New molecular therapies are currently being investigated.
Pathogenesis and Management of Pruritus in PBC and PSC
Authors: Kremer Andreas E. , Namer Barbara , Bolier Ruth , Fischer Michael J. , Oude Elferink Ronald P. , Beuers Ulrich
Published: December 2015

Pruritus is a preeminent symptom in patients with chronic cholestatic liver disorders such as primary biliary cirrhosis and primary sclerosing cholangitis. More than two-thirds of these patients experience itching during the course of their disease. This symptom is also frequently observed in patients with other causes of cholestasis such as cholangiocarcinoma, inherited forms of cholestasis and intrahepatic cholestasis of pregnancy, but may accompany almost any other liver disease. The pathogenesis of pruritus of cholestasis remains largely elusive. Increased concentrations of bile salts, histamine, serotonin, progesterone metabolites and endogenous opioids have been controversially discussed as potential pruritogens. However, for these molecules, neither a correlation with itch intensity nor a causative link could be established. The G protein-coupled receptor for bile salts, TGR5, has been shown to be expressed in dorsal root ganglia and give rise to itch in rodents, albeit upon stimuli with suprapathological concentrations of bile salts. The potent neuronal activator lysophosphatidic acid (LPA) and its forming enzyme, autotaxin (ATX), could be identified in the serum of patients with cholestatic pruritus. ATX activity correlated with itch severity and effectiveness of several anti-pruritic therapeutic interventions in cholestatic patients. Thus, the ATX-LPA-axis may represent a key element in the pathogenesis of this agonizing symptom. Treatment options for pruritus of cholestasis remain limited to a few evidence-based and several experimental medical and interventional therapies. The current guideline-based recommendations include the anion exchange resins colestyramine, the pregnane X receptor-agonist and enzyme inducer rifampicin, the μ-opioid antagonist naltrexone, and the selective serotonin reuptake inhibitors sertraline. Still, a considerable part of patients is unresponsive to these drugs and requires experimental approaches including phototherapy, plasmapheresis, albumin dialysis or nasobiliary drainage. This review outlines the current knowledge on pathogenesis of cholestatic pruritus and summarizes evidence-based and experimental therapeutic interventions for cholestatic patients with itch.
Overlap Syndromes
Authors: Chazouillères Olivier
Published: December 2015

Background: Some patients present with features of both primary biliary cirrhosis (PBC) or primary sclerosing cholangitis (PSC) on the one hand and autoimmune hepatitis (AIH) on the other hand, either simultaneously or consecutively. The term ‘overlap syndrome (OS)' is used to describe these settings, but lack of universal agreement on what precisely constitutes an OS has generated considerable confusion. The low prevalence of OS (roughly 10% of PBC or PSC) has made it impracticable to perform randomized controlled trials. It remains unclear whether this syndrome forms a distinct entity or is a variant of PBC, PSC or AIH. Key Messages: Moderate to severe interface hepatitis is a fundamental component and histology is vital in evaluating patients with overlap presentation. Use of the International Autoimmune Hepatitis Group criteria for the diagnosis of OS is not recommended. For PBC-AIH OS, EASL has provided diagnostic criteria and, in most cases, it is possible to define one primary disorder (‘dominant' disease), usually PBC. Patients with OS seem to have a more severe disease compared to conventional PBC. PSC-AIH OS is assumed to exist in a considerable part of mainly young patients with autoimmune liver disease and long-term progression towards cirrhosis seems to occur in the majority of cases. In children, the hepatitic feature can be very dominant, and up to 50% of pediatric AIH have cholangiographic abnormalities suggestive of PSC (autoimmune sclerosing cholangitis). Treatment of OS is empiric and includes ursodeoxycholic acid for the cholestatic component (depending on local policy for PSC) and immunosuppressive agents for the hepatitic component, either simultaneously or sequentially. The dominant clinical feature should be treated first and therapy adjusted according to the response. Conclusions: OS is not uncommon but should not be over-diagnosed in order not to expose unnecessarily PBC or PSC patients to the risk of steroid side effects. Therapy has to be individualized and not be static.
Pain in the Early Phase of Pediatric Pancreatitis (PINEAPPLE Trial): Pre-Study Protocol of a Multinational Prospective Clinical Trial
Authors: Zsoldos Fanni , Párniczky Andrea , Mosztbacher Dóra , Tóth Anna , Lásztity Natália , Hegyi Peter ,   on behalf of the Hungarian Pancreatic Study Group and the International Association of Pancreatology
Published: December 2015

Background: There are unexpectedly large differences between the incidences of acute pancreatitis (AP) as indicated by different hospitals. Retrospective studies suggest that the reason behind this is the large differences that exist between the local managements of abdominal pain at emergency units. Unfortunately, no evidence-based medicine (EBM) guidelines are available to give proper instruction concerning the necessity of serum pancreatic enzyme measurement during abdominal pain. Summary: Pain in Early Phase of Pediatric Pancreatitis (PINEAPPLE) is an observational, multinational observational clinical trial to explore the route from the first sign of abdominal pain to the diagnosis of pancreatitis (PINEAPPLE trial). The PINEAPPLE-R subtrial is a retrospective review on the records of children (patients under 18) appearing at emergency units - a review of their clinical symptoms, results of imaging examinations and laboratory parameters. The PINEAPPLE-P subtrial is a prospective trial designed to develop a fast and simple EBM guideline that helps to evaluate (in a reliable and cost-efficient way) the necessity of pancreatic enzyme test and abdominal ultrasonography (or even computed tomography) when a child has abdominal pain. The trial has been registered at the ISRCTN registry and has received the relevant ethical approval. Key Message: The PINEAPPLE trial will help to recognize AP in children in a highly efficient manner.
Angiotensin-(1-7)/Mas Signaling Inhibits Lipopolysaccharide-Induced ADAM17 Shedding Activity and Apoptosis in Alveolar Epithelial Cells
Authors: Ma Xinhua , Xu Daomiao , Ai Yuhang , Zhao Shuangping , Zhang Lina , Ming Guangfeng , Liu Zhiyong
Published: December 2015

A disintegrin and metalloproteinase (ADAM) 17, constitutively expressed in alveolar epithelium, is the pivotal shedding enzyme mediating acute lung inflammation. On the other hand, angiotensin (Ang)-(1-7)/Mas signaling has been shown to improve acute respiratory distress syndrome and protect alveolar epithelial cells from apoptosis. In this study, we explored the effect of Ang-(1-7)/Mas signaling on the expression and activity of ADAM17 and assessed its impact on apoptosis in lipopolysaccharide (LPS)-treated human alveolar epithelial cells. LPS markedly induced the shedding activity of ADAM17 in alveolar epithelial cells, which was blocked by selective c-Jun N-terminal kinase (JNK) inhibitor SP600125. Ang-(1-7) concentration-dependently inhibited LPS-induced ADAM17 shedding activity, which was abolished by selective Mas blocker A779 and Mas shRNA. LPS and Ang-(1-7) showed no significant effect on the expression of ADAM17. Overexpression of ADAM17 synergized with LPS on increasing the shedding activity of ADAM17 and apoptosis in alveolar epithelial cells, counteracting the inhibitory effects of Ang-(1-7). In addition, LPS significantly increased the JNK activity in alveolar epithelial cells; Ang-(1-7) concentration-dependently inhibited LPS-induced JNK activity, which was abolished by A779 and Mas shRNA. In conclusion, this study suggests that Ang-(1-7)/Mas signaling inhibits LPS-induced alveolar epithelial cell apoptosis by inhibiting LPS-induced shedding activity of ADAM17, likely by a JNK-dependent mechanism.
The Role of Toll-Like Receptors and Myeloid Differentiation Factor 88 in Bjerkandera adusta-Induced Lung Inflammation
Authors: He Miao , Ichinose Takamichi , Song Yuan , Yoshida Yasuhiro , Kobayashi Fumihisa , Maki Teruya , Yoshida Seiichi , Takano Hirohisa , Shibamoto Takayuki , Sun Guifan
Published: December 2015

Background: Recently, a cluster of patients with an intractable allergic fungal cough who were characterized by sensitization to Bjerkandera adusta was reported. In the present study, the role of Toll-like receptors and myeloid differentiation factor 88 (MyD88) in B. adusta-induced lung inflammation was investigated. Methods: Wild-type (WT), TLR2-/-,TLR4-/-, and MyD88-/- BALB/c mice were intratracheally challenged with B. adusta 4 times at 2-week intervals. Lung pathology, bronchoalveolar lavage fluid (BALF) cytological profiles, and inflammatory mediators in BALF were investigated. Bone marrow-derived macrophages (BMDM) from TLR2-/-,TLR4-/-, TLR2/4-/-, TLR7/9-/-,MyD88-/-, and WT C57BL/6J mice were stimulated with B. adusta for 12 h, and inflammatory mediators in the culture medium were measured. Results:B. adusta caused lung inflammation along with Th2 cytokine [interleukin (IL)-5 and IL-13] and eosinophil-related chemokine [eotaxin and monocyte chemotactic protein (MCP-3)] production, an increase in eosinophils in BALF, and eosinophil infiltration in the airways in WT and TLR4-/- mice. However, Th2 and eosinophil-related responses in TLR2-/- and MyD88-/- mice were low or undetectable. The induction of neutrophils and IL-6, IL-12, IL-17A, and MCP-1 in the BALF of MyD88-/- mice was attenuated compared to that in WT mice. The induction of IL-6, TNF-α, MCP-1, and macrophage inflammatory protein-1α was reduced or undetectable in B. adusta-stimulated BMDM from TLR7/9-/- and MyD88-/- mice compared to WT mice. Conclusions: These results suggest that TLR2 and the adapter protein MyD88 may play an important role in the induction of eosinophils by B. adusta. However, TLR7/9-MyD88 might be important in the induction of neutrophils and the relevant inflammatory mediators, especially IL-17A.
Association between Sarcopenic Obesity and Bone Mineral Density in Middle-Aged and Elderly Korean
Authors: Chung Jae Ho , Hwang Hee Jin , Shin Hyun-Young , Han Chang Hoon
Published: December 2015

Objectives: To identify the prevalence of osteosarcopenic obesity and to evaluate the association between sarcopenic obesity and bone mineral density in middle-aged and elderly Korean. Methods: This study included 3,385 males and 4,064 females (age ≥50 years and in the stage of menopause) who participated in the Korean National Health and Nutrition Examination Survey (KNHANES) from 2008 to 2011. The cutoff value for sarcopenia was 7.26 kg/m2 for men and 5.45 kg/m2 for female. The fat mass was >30% for men and 40% for female; these values were used to define obesity. Based on the combination of sarcopenia and obesity status, all subjects were classified as sarcopenic obese (SO), sarcopenic nonobese (SNO), nonsarcopenic obese (NSO), or nonsarcopenic nonobese. Results: The incidence rates of sarcopenia, sarcopenic obesity, and osteosarcopenic obesity were 31.5, 5.1, and 4.1%, respectively. Following adjustment, the ORs for osteoporosis were 8.67 in the SO group (95% CI 4.19-17.94), 3.85 in the SNO group (95% CI 2.61-5.67), and 1.88 in the NSO group (95% CI 0.72-4.91) in men and 2.93 in the SO group (95% CI 1.99-4.32), 1.71 in the SNO group (95% CI 1.31-2.23), and 0.58 in the NSO group (95% CI 0.43-0.78) in women. Conclusions: Sarcopenic obesity is associated with the development of osteoporosis among the middle-aged and elderly Korean population.
The Effects of Potassium Channels in Human Internal Mammary Artery
Authors: Afsar Selim , Hemsinli Dogus , Ozyazgan Sibel , Akkan Ahmet Gökhan , Arslan Caner
Published: December 2015

Background: Structural and functional changes in potassium channels of vascular smooth muscle cells may contribute to the development of diseases such as hypertension. We aim to investigate the vascular effects of potassium channel openers and blockers in human internal mammary artery (HIMA). Methods: Remaining segments of HIMA from 18 consecutive patients undergoing coronary artery bypass surgery were obtained to examine the vascular effects of various potassium channel openers (staurosporine, hydrochlorothiazide and cromakalim) and potassium channel blockers (4-aminopyridin [4-AP], charybdotoxin [CTX] and glibenclamide [GLBC]). Results: Noradrenaline (NA)-induced maximal contractions were inhibited by all 3 K+-channel blockers but only fully inhibited by 4-AP (95.6%). Only NA-induced contractions were reversed by CTX. Only K+-induced maximal contractions were significantly inhibited by 4-AP (95.6%, p < 0.05). Only acetylcholine-induced relaxation was fully inhibited by CTX. Only sodium nitroprusside-induced relaxations in potassium chloride-precontracted strips could be reversed by GLBC. Conclusions: Drugs affecting potassium channels may be useful in the treatment of hypertension and management of perioperative vasospasm during the coronary artery bypass surgery.
The Isoquinolone Derived Prolyl Hydroxylase Inhibitor ICA Is a Potent Substrate of the Organic Anion Transporters 1 and 3
Authors: Schulz Kei , Hagos Yohannes , Burckhardt Gerhard , Schley Gunnar , Burzlaff Nikolai , Willam Carsten , Burckhardt Birgitta C.
Published: December 2015

Objective: Many cellular responses to hypoxia are mediated by the transcription factor complex hypoxia-inducible factor (HIF). HIF stability is governed by a family of dioxygenases called HIF prolyl hydroxylases (PHDs). Isoquinolone-derived PHD inhibitors, like 2-(1-chloro-4-hydroxyisoquinoline-3-carboxamido) acetate (ICA), which stabilize the intracellular HIF-α have been suggested as a potentially beneficial therapeutic strategy for the treatment of disorders associated with ischemia. To stabilize HIF-α, ICA has to be taken up into proximal tubule cells (PCTs) across the basolateral membrane by one of the organic anion transporters 1, 2 or 3 (OAT1, OAT2 or OAT3). The release into the urine across the luminal membrane may be mediated by OAT4. Method: To demonstrate interaction of ICA with human OAT1, OAT2, OAT3 and OAT4, ICA was tested on these transporters stably transfected in HEK293 cells by using p-aminohippurate (PAH), cGMP and estrone-3-sulfate (ES) as reference substrates, respectively. Results: Uptakes of PAH and ES in OAT1- and OAT3-transfected HEK293 cells were inhibited by ICA with half-maximal inhibition values of 0.29 ± 0.05 and 2.58 ± 0.16 µM, respectively. OAT2 was less sensitive to ICA. Efflux experiments identified ICA as an OAT1 and OAT3 substrate. Preloading OAT4-transfected HEK293 cells with ICA stimulated ES uptake by 18.3 ± 3.8%. Conclusion: The uptake of ICA across the basolateral membrane of PCTs occurs mainly by OAT1 and the efflux into the tubular lumen by OAT4.
Children of Rus’: From the Little Russian Idea to the Russian World
Authors: Bilenky Serhiy
Published: December 2015

This is a review of a book that traces the rise of Russian nationalism in Russia’s “southwestern borderlands” during the long 19th century. What gave rise to it was the so-called “Little Russian idea” that emphasized the existence of the Russian Orthodox organic nation that had originated in the right bank of the Dnieper. The elements of that idea survived well into the 20th century.
The Effect of Downwelling Longwave and Shortwave Radiation on Arctic Summer Sea Ice
Authors: Kapsch Marie-Luise , Graversen Rune Grand , Tjernström Michael , Bintanja Richard
Published: December 2015

The Arctic summer sea ice has diminished fast in recent decades. A strong year-to-year variability on top of this trend indicates that sea ice is sensitive to short-term climate fluctuations. Previous studies show that anomalous atmospheric conditions over the Arctic during spring and summer affect ice melt and the September sea ice extent (SIE). These conditions are characterized by clouds, humidity, and heat anomalies that all affect downwelling shortwave (SWD) and longwave (LWD) radiation to the surface. In general, positive LWD anomalies are associated with cloudy and humid conditions, whereas positive anomalies of SWD appear under clear-sky conditions. Here the effect of realistic anomalies of LWD and SWD on summer sea ice is investigated by performing experiments with the Community Earth System Model. The SWD and LWD anomalies are studied separately and in combination for different seasons. It is found that positive LWD anomalies in spring and early summer have significant impact on the September SIE, whereas winter anomalies show only little effect. Positive anomalies in spring and early summer initiate an earlier melt onset, hereby triggering several feedback mechanisms that amplify melt during the succeeding months. Realistic positive SWD anomalies appear only important if they occur after the melt has started and the albedo is significantly reduced relative to winter conditions. Simulations where both positive LWD and negative SWD anomalies are implemented simultaneously, mimicking cloudy conditions, reveal that clouds during spring have a significant impact on summer sea ice while summer clouds have almost no effect.
Different Responses of Sea Surface Temperature in the South China Sea to Various El Niño Events during Boreal Autumn
Authors: Tan Wei , Wang Xin , Wang Weiqiang , Wang Chunzai , Zuo Juncheng
Published: December 2015

This study investigates variations of sea surface temperature (SST) anomalies in the South China Sea (SCS) during developing autumn of various El Niño events. The warm SST anomalies are observed in the SCS for canonical El Niño and El Niño Modoki I, whereas the cold SST anomalies are found for El Niño Modoki II. The ocean heat budget analyses show that the latent heat flux change induced by various types of El Niño events is a major contributor to the SCS SST variations. An anomalous anticyclone resides near the Philippine Sea for canonical El Niño and El Niño Modoki I, which induces the southerly wind anomalies over the SCS and thus weakens the climatological northeasterly in boreal autumn. The weakened surface wind speed reduces heat loss from the ocean, leading to a warmer state in the SCS. However, for El Niño Modoki II, the anomalous anticyclone shifts westward to the west of the SCS, and thus the northeasterly wind anomalies appear in the SCS. The northeasterly anomalies enhance the climatological northeasterly monsoon, increase the wind speed, and increase heat loss from the ocean, thus resulting in a cooling in the SCS. The anomalous anticyclone associated with El Niño events also increases shortwave radiation. The increases of the shortwave radiation can also contribute to the SCS warming for canonical El Niño and El Niño Modoki I in addition to the warm effect from the latent heat flux. Because the cooling effect from the latent heat flux is larger than that of the shortwave radiation for El Niño Modoki II, the SCS for El Niño Modoki II tends to be cool.
Internal Waves and Mixing near the Kerguelen Plateau
Authors: Meyer Amelie , Polzin Kurt L. , Sloyan Bernadette M. , Phillips Helen E.
Published: December 2015

In the stratified ocean, turbulent mixing is primarily attributed to the breaking of internal waves. As such, internal waves provide a link between large-scale forcing and small-scale mixing. The internal wave field north of the Kerguelen Plateau is characterized using 914 high-resolution hydrographic profiles from novel Electromagnetic Autonomous Profiling Explorer (EM-APEX) floats. Altogether, 46 coherent features are identified in the EM-APEX velocity profiles and interpreted in terms of internal wave kinematics. The large number of internal waves analyzed provides a quantitative framework for characterizing spatial variations in the internal wave field and for resolving generation versus propagation dynamics. Internal waves observed near the Kerguelen Plateau have a mean vertical wavelength of 200 m, a mean horizontal wavelength of 15 km, a mean period of 16 h, and a mean horizontal group velocity of 3 cm s−1. The internal wave characteristics are dependent on regional dynamics, suggesting that different generation mechanisms of internal waves dominate in different dynamical zones. The wave fields in the Subantarctic/Subtropical Front and the Polar Front Zone are influenced by the local small-scale topography and flow strength. The eddy-wave field is influenced by the large-scale flow structure, while the internal wave field in the Subantarctic Zone is controlled by atmospheric forcing. More importantly, the local generation of internal waves not only drives large-scale dissipation in the frontal region but also downstream from the plateau. Some internal waves in the frontal region are advected away from the plateau, contributing to mixing and stratification budgets elsewhere.
Rossby Waves and Eddies Observed at a Temperature Mooring in Northern South China Sea
Authors: Lin Y.-C. , Oey L.-Y. , Wang J. , Liu K.-K.
Published: December 2015

Annual Rossby waves in northern South China Sea had previously been studied using altimetry and model data; however, how they connect to subsurface temperature fluctuations has not been examined. This study analyzed a 22-month, surface to −500-m temperature time series at 18.3°N, 115.5°E, together with satellite and other data, to show the arrivals near z ≈ −300 m and deeper cool (warm) Rossby waves after their generation near the Luzon Strait in winter (summer). Temperature fluctuations with time scales of a few weeks, and with maximum anomalies near z ≈ −100 m, were also found embedded in the smooth Rossby waves and caused by propagating eddies. Eddy fluctuations and propagation past the mooring were of two types: southwestward from southwestern Taiwan, triggered by Kuroshio intrusion that produced anticyclone–cyclone pairs in late fall and winter, and eddies propagating westward from Luzon forced by annual anomalies of wind stress curl and Kuroshio path in the Luzon Strait
Tropical Transition of an Unnamed, High-Latitude, Tropical Cyclone over the Eastern North Pacific
Authors: Bentley Alicia M. , Metz Nicholas D.
Published: December 2015

In early November 2006, an unnamed tropical cyclone (TC) formed via the tropical transition (TT) process at 42°N over the eastern North Pacific. An extratropical cyclone (EC), developing downstream of a thinning upper-tropospheric trough over the eastern North Pacific, served as the precursor disturbance that would ultimately undergo TT. The TT of the unnamed TC was extremely unusual—occurring over ~16°C sea surface temperatures in a portion of the eastern North Pacific basin historically devoid of TC activity.

This paper 1) identifies the upper- and lower-tropospheric features linked to the formation of the EC that transitions into the unnamed TC, 2) provides a synoptic overview of the features and processes associated with the unnamed TC’s TT, and 3) discusses the landfall of the weakening cyclone along the west coast of North America. As observed in previous studies of TT, the precursor EC progresses through the life cycle of a marine extratropical frontal cyclone, developing a bent-back warm front on its northern and western sides and undergoing a warm seclusion process. Backward air parcel trajectories suggest that air parcels isolated in the center of the transitioning cyclone were warmed in the lower troposphere via sensible heating from the underlying sea surface. Vertical cross sections taken through the center of the cyclone during its life cycle reveal its transformation from an asymmetric, cold-core, EC into an axisymmetric, warm-core, TC during TT. Ensemble reforecasts initialized after TT highlight the relatively low forecast skill associated with the landfall of the weakening cyclone.
Precipitation Nowcasting with Three-Dimensional Space–Time Extrapolation of Dense and Frequent Phased-Array Weather Radar Observations
Authors: Otsuka Shigenori , Tuerhong Gulanbaier , Kikuchi Ryota , Kitano Yoshikazu , Taniguchi Yusuke , Ruiz Juan Jose , Satoh Shinsuke , Ushio Tomoo , Miyoshi Takemasa
Published: December 2015

The phased-array weather radar (PAWR) is a new-generation weather radar that can make a 100-m-resolution three-dimensional (3D) volume scan every 30 s for 100 vertical levels, producing ~100 times more data than the conventional parabolic-antenna radar with a volume scan typically made every 5 min for 15 scan levels. This study takes advantage of orders of magnitude more rapid and dense observations by PAWR and explores high-precision nowcasting of 3D evolution at 1–10-km scales up to several minutes, which are compared with conventional horizontal two-dimensional (2D) nowcasting typically at O(100) km scales up to 1–6 h. A new 3D precipitation extrapolation system was designed to enhance a conventional algorithm for dense and rapid PAWR volume scans. Experiments show that the 3D extrapolation successfully captured vertical motions of convective precipitation cores and outperformed 2D nowcasting with both simulated and real PAWR data.
Zamindars, inheritance law and the spread of the waqf in the United Provinces at the turn of the twentieth century
Authors: Singh Anantdeep
Published: December 2015

The second half of the nineteenth century witnessed the fragmentation and transfer of Muslim-owned estates in the United Provinces to Hindus of non-agrarian castes. This was followed by increasing usage of the waqf by Muslim landowners. This study looks at land-holding patterns in the United Provinces and use a comparative analysis of Hindu and Islamic inheritance laws to explain why land was transferred during the second half of the nineteenth century from Muslims to Hindus. It posits that the implementation of Islamic inheritance laws in the mid-nineteenth century led to increased fragmentation of Muslim-owned estates. The study also suggests that waqf became popular among Muslim landowners because it fulfilled two crucial functions that the Hindu joint family had fulfilled for Hindu landowners: First, it prevented estate fragmentation by circumventing the implementation of Islamic inheritance laws. Second, the waqf shielded assets of landowners by increasing costs of creditors seeking to recover their loans.
Towards financial inclusion: The post office of India as a financial institution, 1880–2010
Authors: Tumbe Chinmay
Published: December 2015

The Post Office of India has evolved tremendously from an institution of ‘communication’ to an important ‘financial’ institution of the early twenty-first century. This article traces the evolution of two key mass financial services offered by the Post Office over the past 130 years—money orders that have primarily served as a mechanism for internal and international migrants’ remittances and the small savings system that has mobilised deposits from millions of rural and urban citizens. It assesses the contribution of the Post Office in enhancing ‘financial inclusion’ in the twentieth century and argues that the financial history of modern India remains incomplete without integrating the Post Office—currently the largest bank in India in terms of network, accounts and personal deposits—as a key institutional actor in the narrative.
Transnational Histories and Subcontinental Pasts: A Review Essay
Authors: Balachandran G.
Published: December 2015

Nico Slate, Coloured Cosmopolitanism: The Shared Struggle for Freedom in the United States and India, Ranikhet: Permanent Black, 2012, pp. 321.

Vivek Bald, Bengali Harlem and the Lost Histories of South Asian America, Cambridge, MA: Harvard University Press, 2013, pp. 294.

Seema Sohi, Echoes of Mutiny: Race, Surveillance and Anticolonialism in North America, New York: Oxford University Press, 2014, pp. 271.
Book Review: Bhairabi Prasad Sahu, The Changing Gaze: Regions and the Constructions of Early India
Authors: Furui Ryosuke
Published: December 2015

Bhairabi Prasad Sahu, The Changing Gaze: Regions and the Constructions of Early India, New Delhi: Oxford University Press, 2013, pp. 341.
Book Review: Clive Dewey, Steamboats on the Indus
Authors: Gordon Stewart
Published: December 2015

Clive Dewey, Steamboats on the Indus, New Delhi: Oxford University Press, 2014, pp. 296.
Book Review: Francesca Orsini and Samira Sheikh, eds, After Timur Left: Culture and Circulation in Fifteenth Century North India
Authors: Flatt Emma J.
Published: December 2015

Francesca Orsini and Samira Sheikh, eds, After Timur Left: Culture and Circulation in Fifteenth Century North India, Delhi: Oxford University Press, 2014, pp. 500.
Book Review: Indrani Chatterjee, Forgotten Friends, Monks, Marriages and Memories of Northeast India
Authors: Kasturi Malavika
Published: December 2015

Indrani Chatterjee, Forgotten Friends, Monks, Marriages and Memories of Northeast India, Delhi: Oxford University Press, 2013, pp. 415.
Book Review: Philip Oldenburg, India, Pakistan, and Democracy: Solving the Puzzle of Divergent Paths and William Gould, Taylor C. Sherman and Sarah Ansari, eds, From Subjects to Citizens: Society and Everyday State in India and Pakistan
Authors: Malik Anushay
Published: December 2015

Philip Oldenburg, India, Pakistan, and Democracy: Solving the Puzzle of Divergent Paths, Delhi: Manohar, 2010, pp. 288.

William Gould, Taylor C. Sherman and Sarah Ansari, eds, From Subjects to Citizens: Society and Everyday State in India and Pakistan, 1947–1970, Delhi: Cambridge University Press, 2014, pp. 258.
Psychological Functions of Subjective Norms
Authors: Morris Michael W. , Liu Zhi
Published: December 2015

This article considers the social and psychological functions that norm-based thinking and behavior provide for the individual and the collectivity. We differentiate between two types of reference groups that provide norms: peer groups versus aspirational groups. We integrate functionalist accounts by distinguishing the functions served by the norms of different reference groups, different degrees of norm moralization, and different directions of responses to norm activation.
A Conclusion, Yet an Opening to Enriching the Normative Approach of Culture
Authors: Chiu Chi-yue , Gelfand Michele J. , Harrington Jesse R. , Leung Angela K.-y. , Liu Zhi , Morris Michael W. , Mu Yan , Shteynberg Garriy , Tam Kim-Pong , Wan Ching , Zou Xi
Published: December 2015

We compile in this article the target article authors’ thoughtful responses to the commentaries. Their responses identify some common threads across the rich contents of the commentary pieces, interlink the observation and theoretical propositions in the commentaries with broader streams of research, present new perspectives inspired by the commentary contributors, and pose provocative questions to further ignite research efforts on the normative analysis of culture.