bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of Genetic Alterations in the NLRP3 and CARD8 Genes in Health and Disease
Authors: Paramel G. V. , Sirsjö A. , Fransén K.
Published: February 2015

The complexity of a common inflammatory disease is influenced by multiple genetic and environmental factors contributing to the susceptibility of disease. Studies have reported that these exogenous and endogenous components may perturb the balance of innate immune response by activating the NLRP3 inflammasome. The multimeric NLRP3 complex results in the caspase‐1 activation and the release of potent inflammatory cytokines, like IL‐1β. Several studies have been performed on the association of the genetic alterations in genes encoding NLRP3 and CARD8 with the complex diseases with inflammatory background, like inflammatory bowel disease, cardiovascular diseases, rheumatoid arthritis, and type 1 diabetes. The aim of the present review is therefore to summarize the literature regarding genetic alterations in these genes and their association with health and disease.
Coenzyme Q10 Inhibits the Aging of Mesenchymal Stem Cells Induced by D-Galactose through Akt/mTOR Signaling
Authors: Zhang Dayong , Yan Bingxi , Yu Shanshan , Zhang Chong , Wang Baoming , Wang Yayan , Wang Junbo , Yuan Zhanggen , Zhang Lihuang , Pan Jianping
Published: February 2015

Increasing evidences indicate that reactive oxygen species are the main factor promoting stem cell aging. Recent studies have demonstrated that coenzyme Q10 (CoQ10) plays a positive role in organ and cellular aging. However, the potential for CoQ10 to protect stem cell aging has not been fully evaluated, and the mechanisms of cell senescence inhibited by CoQ10 are still poorly understood. Our previous study had indicated that D-galactose (D-gal) can remarkably induce mesenchymal stem cell (MSC) aging through promoting intracellular ROS generation. In this study, we showed that CoQ10 could significantly inhibit MSC aging induced by D-gal. Moreover, in the CoQ10 group, the expression of p-Akt and p-mTOR was clearly reduced compared with that in the D-gal group. However, after Akt activating by CA-Akt plasmid, the senescence-cell number in the CoQ10 group was significantly higher than that in the control group. These results indicated that CoQ10 could inhibit D-gal-induced MSC aging through the Akt/mTOR signaling.
How to Be 80 Year Old and Have a VO2maxof a 35 Year Old
Authors: Karlsen Trine , Leinan Ingeborg Megård , Bækkerud Fredrik Hjulstad , Lundgren Kari Margrethe , Tari Atefe , Steinshamn Sigurd Loe , Støylen Asbjørn , Rognmo Øivind
Published: February 2015

Background. To discuss the cardiovascular and pulmonary physiology and common risk factors of an 80-year-old man with a world record maximal oxygen uptake of 50 mL·kg−1·min−1.Methods. Case report.Results. His maximal oxygen uptake of 3.31 L·min−1, maximal heart rate of 175 beats·min−1, and maximal oxygen pulse of 19 mL·beats−1are high. He is lean (66.6 kg) and muscular (49% skeletal muscle mass). His echo parameters of mitral flow (left ventricular filling,E= 82 cm·s−1andE/A= 1.2) were normal for 40- to 60-year-old men. Systolic and diastolic function increased adequately during exercise, with no increase in left ventricular filling pressure. He has excellent pulmonary function (FVC = 4.31 L, FEV1 = 3.41, FEV1/FVC = 0.79, and DLCO = 12.0 Si1) and normal FMD and blood volumes (5.8 L). He has a high level of daily activity (10,900 steps·day−1and 2:51 hours·day−1of physical activity) and a lifelong history of physical activity.Conclusion. The man is in excellent cardiopulmonary fitness and is highly physically active. His cardiac and pulmonary functions are above expectations for his age, and his VO2maxis comparable to that of an inactive 25-year-old and of a normal, active 35-year-old Norwegian man.
Omega-3 Polyunsaturated Fatty Acids Upregulate 15-PGDH Expression in Cholangiocarcinoma Cells by Inhibiting miR-26a/b Expression
Authors: Yao Lu , Han Chang , Song Kyoungsub , Zhang Jinqiang , Lim Kyu , Wu Tong
Published: February 2015

Prostaglandin E2 (PGE2) is a proinflammatory lipid mediator that promotes cancer growth. The 15-hydroxyprostaglandin dehydrogenase (15-PGDH) catalyzes oxidation of the 15(S)-hydroxyl group of PGE2, leading to its inactivation. Therefore, 15-PGDH induction may offer a strategy to treat cancers that are driven by PGE2, such as human cholangiocarcinoma. Here, we report that omega-3 polyunsaturated fatty acids (ω-3 PUFA) upregulate 15-PGDH expression by inhibiting miR-26a and miR-26b, thereby contributing to ω-3 PUFA-induced inhibition of human cholangiocarcinoma cell growth. Treatment of human cholangiocarcinoma cells (CCLP1 and TFK-1) with ω-3 PUFA (DHA) or transfection of these cells with the Fat-1 gene (encoding Caenorhabditis elegans desaturase, which converts ω-6 PUFA to ω-3 PUFA) significantly increased 15-PGDH enzymes levels, but with little effect on the activity of the 15-PGDH gene promoter. Mechanistic investigations revealed that this increase in 15-PGDH levels in cells was mediated by a reduction in the expression of miR-26a and miR-26b, which target 15-PGDH mRNA and inhibit 15-PGDH translation. These findings were extended by the demonstration that overexpressing miR-26a or miR-26b decreased 15-PGDH protein levels, reversed ω-3 PUFA-induced accumulation of 15-PGDH protein, and prevented ω-3 PUFA-induced inhibition of cholangiocarcinoma cell growth. We further observed that ω-3 PUFA suppressed miR-26a and miR-26b by inhibiting c-myc, a transcription factor that regulates miR-26a/b. Accordingly, c-myc overexpression enhanced expression of miR-26a/b and ablated the ability of ω-3 PUFA to inhibit cell growth. Taken together, our results reveal a novel mechanism for ω-3 PUFA-induced expression of 15-PGDH in human cholangiocarcinoma and provide a preclinical rationale for the evaluation of ω-3 PUFA in treatment of this malignancy. Cancer Res; 75(7); 1388–98. ©2015 AACR.
Evolutionary Action Score of TP53 Coding Variants Is Predictive of Platinum Response in Head and Neck Cancer Patients
Authors: Osman Abdullah A. , Neskey David M. , Katsonis Panagiotis , Patel Ameeta A. , Ward Alexandra M. , Hsu Teng-Kuei , Hicks Stephanie C. , McDonald Thomas O. , Ow Thomas J. , Alves Marcus Ortega , Pickering Curtis R. , Skinner Heath D. , Zhao Mei , Sturgis Eric M. , Kies Merrill S. , El-Naggar Adel , Perrone Federica , Licitra Lisa , Bossi Paolo , Kimmel Marek , Frederick Mitchell J. , Lichtarge Olivier , Myers Jeffrey N.
Published: February 2015

TP53 is the most frequently altered gene in head and neck squamous cell carcinoma (HNSCC), with mutations occurring in over two thirds of cases; however, the predictive response of these mutations to cisplatin-based therapy remains elusive. In the current study, we evaluate the ability of the Evolutionary Action score of TP53-coding variants (EAp53) to predict the impact of TP53 mutations on response to chemotherapy. The EAp53 approach clearly identifies a subset of high-risk TP53 mutations associated with decreased sensitivity to cisplatin both in vitro and in vivo in preclinical models of HNSCC. Furthermore, EAp53 can predict response to treatment and, more importantly, a survival benefit for a subset of head and neck cancer patients treated with platinum-based therapy. Prospective evaluation of this novel scoring system should enable more precise treatment selection for patients with HNSCC. Cancer Res; 75(7); 1205–15. ©2015 AACR.
Galectin-3 Shapes Antitumor Immune Responses by Suppressing CD8+ T Cells via LAG-3 and Inhibiting Expansion of Plasmacytoid Dendritic Cells
Authors: Kouo Theodore , Huang Lanqing , Pucsek Alexandra B. , Cao Minwei , Solt Sara , Armstrong Todd , Jaffee Elizabeth
Published: February 2015

Galectin-3 is a 31-kDa lectin that modulates T-cell responses through several mechanisms, including apoptosis, T-cell receptor (TCR) cross-linking, and TCR downregulation. We found that patients with pancreatic ductal adenocarcinoma (PDA) who responded to a granulocyte-macrophage colony-stimulating factor–secreting allogeneic PDA vaccine developed neutralizing antibodies to galectin-3 after immunization. We show that galectin-3 binds activated antigen-committed CD8+ T cells only in the tumor microenvironment. Galectin-3–deficient mice exhibit improved CD8+ T-cell effector function and increased expression of several inflammatory genes. Galectin-3 binds to LAG-3, and LAG-3 expression is necessary for galectin-3–mediated suppression of CD8+ T cells in vitro. Lastly, galectin-3–deficient mice have elevated levels of circulating plasmacytoid dendritic cells, which are superior to conventional dendritic cells in activating CD8+ T cells. Thus, inhibiting galectin-3 in conjunction with CD8+ T-cell–directed immunotherapies should enhance the tumor-specific immune response. Cancer Immunol Res; 3(4); 412–23. ©2015 AACR.
Virotherapy with a Semliki Forest Virus–Based Vector Encoding IL12 Synergizes with PD-1/PD-L1 Blockade
Authors: Quetglas José I. , Labiano Sara , Aznar M. Ángela , Bolaños Elixabet , Azpilikueta Arantza , Rodriguez Inmaculada , Casales Erkuden , Sánchez-Paulete Alfonso R. , Segura Víctor , Smerdou Cristian , Melero Ignacio
Published: February 2015

Virotherapy and checkpoint inhibitors can be combined for the treatment of cancer with complementarity and potential for synergistic effects. We have developed a cytolytic but nonreplicative viral vector system based on Semliki Forest virus that encodes IL12 (SFV-IL12). Following direct intratumoral injection, infected cells release transgenic IL12, die, and elicit an inflammatory response triggered by both abundantly copied viral RNA and IL12. In difficult-to-treat mouse cancer models, such as those derived from MC38 and bilateral B16-OVA, SFV-IL12 synergized with an anti–PD-1 monoclonal antibody (mAb) to induce tumor regression and prolong survival. Similar synergistic effects were attained upon PD-L1 blockade. Combined SFV-IL12 + anti–PD-1 mAb treatment only marginally increased the elicited cytotoxic T-lymphocyte response over SFV-IL12 as a single agent, at least when measured by in vivo killing assays. In contrast, we observed that SFV-IL12 treatment induced expression of PD-L1 on tumor cells in an IFNγ-dependent fashion. PD-L1–mediated adaptive resistance thereby provides a mechanistic explanation of the observed synergistic effects achieved by the SFV-IL12 + anti–PD-1 mAb combination. Cancer Immunol Res; 3(5); 449–54. ©2015 AACR.
Committing Cytomegalovirus-Specific CD8 T Cells to Eliminate Tumor Cells by Bifunctional Major Histocompatibility Class I Antibody Fusion Molecules
Authors: Schmittnaegel Martina , Levitsky Victor , Hoffmann Eike , Georges Guy , Mundigl Olaf , Klein Christian , Knoetgen Hendrik
Published: February 2015

Tumor cells escape immune eradication through multiple mechanisms, including loss of antigenicity and local suppression of effector lymphocytes. To counteract these obstacles, we aimed to direct the unique cytomegalovirus (CMV)-specific immune surveillance against tumor cells. We developed a novel generation of fusion proteins composed of a tumor antigen–specific full immunoglobulin connected to a single major histocompatibility class I complex bearing a covalently linked virus-derived peptide (pMHCI–IgG). Here, we show that tumor antigen–expressing cancer cells, which are decorated with pMHCI–IgGs containing a HLA-A*0201 molecule associated with a CMV-derived peptide, are specifically eliminated through engagement of antigen-specific CD8+ T cells isolated from peripheral blood mononuclear cell preparations of CMV-infected humans. These CD8+ T cells act without additional expansion, preactivation, or provision of costimulatory signals. Elimination of tumor cells is induced at similar concentrations and with similar time kinetics as those seen with bispecific T-cell engagers (BiTE). However, while BiTE-like reagents indiscriminately activate T cells through binding to the T-cell receptor complex, pMHCI–IgGs selectively engage antigen-specific, constantly renewable, differentiated effector cytotoxic T lymphocytes to tumor cells, thereby representing a novel class of anticancer immunotherapeutics with potentially improved safety and efficacy profiles. Cancer Immunol Res; 3(7); 764–76. ©2015 AACR.
The Nucleus Accumbens: A Comprehensive Review
Authors: Salgado Sanjay , Kaplitt Michael G.
Published: February 2015

There is increasing interest among functional neurosurgeons in the potential for novel therapies to impact upon diseases beyond movement disorders and pain. A target of increasing interest is the nucleus accumbens (NAc), which has long been studied as a key brain region mediating a variety of behaviors, including reward and satisfaction. As such, focal modulation of the biology of the NAc with deep brain stimulation or novel biological therapies such as gene therapy or cell transplantation could have a major impact upon disorders such as depression and drug addiction. In order to both develop appropriate therapies and then deliver them in an effective fashion, a thorough understanding of the biology, physiology, and anatomy of the NAc is critical. Here, we review the existing literature regarding several areas critical to the development of new therapies, including the known pharmacology, physiology, and connectivity of the NAc, as well as evidence supporting the potential for various NAc surgical therapies in animal models. We then review the relevant anatomy of the NAc, with particular attention to the surgical anatomy, imaging, and targeting necessary to facilitate a proper localization and delivery of new agents to this region. The NAc is a fascinating and potentially rich target for stereotactic neurosurgical intervention, and analysis of existing information regarding all aspects of this structure should help potentiate therapeutic advances and reduce complications from future studies of neurosurgical intervention in this region for a variety of disorders.
Using the Accelerometers Integrated in Smartphones to Evaluate Essential Tremor
Authors: Senova Suhan , Querlioz Damien , Thiriez Claire , Jedynak Pierre , Jarraya Béchir , Palfi Stéphane
Published: February 2015

Background/Aims: Evaluation of tremor constitutes a crucial step from the diagnosis to the initial treatment and follow-up of patients with essential tremor. The severity of tremor can be evaluated using clinical rating scales, accelerometry, or electrophysiology. Clinical scores are subjectively given, may be affected by intra- and interevaluator variations due to different experience, delays between consultations, and subtle changes in tremor severity. Existing medical devices are not routinely used: they are expensive, time-consuming, not easily accessible. We aimed at showing that a smartphone application using the accelerometers embedded in smartphones is effective for quantifying the tremor of patients presenting with essential tremor. Methods: We developed a free iPhone/iPod application, Itremor, and evaluated different parameters on 8 patients receiving deep brain stimulation of the ventral intermediate nucleus of the thalamus: average and maximum accelerations, time above 1 g of acceleration, peak frequency, typical magnitude of tremor, for postural and action tremors, on and off stimulation. Results: We demonstrated good correlations between the parameters measured with Itremor and clinical score in all conditions. Itremor evaluation enabled higher discriminatory power and degree of reproducibility than clinical scores. Conclusion: Itremor can be used for routine objective evaluation of essential tremor, and may facilitate adjustment of the treatment.
Rhabdomyolysis in the Setting of Induced Hypothyroidism and Statin Therapy: A Case Report
Authors: Jbara Yaser , Bricker Dean
Published: February 2015

Mild elevation of creatine kinase (CK) is common in untreated hypothyroidism, but severe myositis and overt rhabdomyolysis are rare. Similarly, muscle pain and CK elevation are potential side effects of statin therapy, yet rhabdomyolysis is likewise rare in the absence of medication interactions adversely affecting statin metabolism. The coexistence of statin therapy and hypothyroid states may synergistically increase the risk of myopathy. We describe a case of rhabdomyolysis attributable to induced hypothyroidism in a patient on chronic statin medication who was anticipating adjuvant radioiodine (131I) therapy for a thyroid carcinoma
Eruptive Disseminated Pyogenic Granulomas following Lightning Injury
Authors: Netchiporouk Elena , Moreau Linda , Ramirez Lucie P. , Castillo Patricia A.C. , Bravo Francisco P. , Del Solar Manuel C. , Sasseville Denis , Ramos César
Published: February 2015

Background: Pyogenic granuloma (PG) is a common benign acquired vascular tumor. It classically presents as a solitary friable nodule on the face or distal extremities. Disseminated eruption is rare and can occur spontaneously or secondary to various triggers, including burn injury. To date, the literature reports only 13 cases of eruptive PGs following burn injury, most from exposure to boiling milk or water. We report the first case of disseminated eruptive PGs following a lightning injury. Case: A 17-year-old previously healthy boy developed second- and third-degree burns following lightning injury. Two weeks later, he developed widespread dark-purple polypoid exophytic tumors ranging from 1 to 10 cm in diameter extending beyond the limits of the initial burn injury. The lesions were friable and often formed erosions and crusts. The patient was otherwise well and laboratory and microbiological investigations were normal. Excisional biopsy of a lesion was diagnostic of PG and the patient was treated with surgical excision of the lesions, without recurrence. Conclusion: The exact pathogenesis of multiple PGs remains unknown. Several pathogenic mechanisms have been suggested, including production of angiogenic factors that stimulate endothelial proliferation and formation of minute arteriovenous fistulas by trauma.
Establishing a Supportive Care Register Improves End-of-Life Care for Patients with Advanced Chronic Kidney Disease
Authors: Harrison Jennifer K. , Clipsham Laura E. , Cooke Caroline M. , Warwick Graham , Burton James O.
Published: February 2015

Background: End-of-life care for patients with advanced chronic kidney disease (CKD) is recognised as an important area for improvement. These patients have a significant mortality and, although some is unpredictable, there is a role for the nephrology multi-disciplinary team (MDT) and palliative care physicians to engage in advance care planning and support patients to discuss their preferences. Methods: Retrospective and prospective data were obtained to conduct a comparison observational study to assess the impact of introducing a supportive care register on the end-of-life care for patients with advanced CKD. An electronic supportive care register was implemented. This required a programme of multi-disciplinary staff education, collaborative working with Palliative Care to establish renal-specific protocols and dissemination activities. The impact of the intervention was assessed by analysing all deaths in two six-month periods where all those with an eGFR <15 ml/min/1.73 m2 at the time of their death were included. Results: A total of 91 patients were included. Post-intervention, there was a 25.4% (95% CI: 6.5-44.3%, p = 0.008) improvement in patients having a documented discussion about end-of-life planning. There was also a 19.7% (95% CI: 4.0-35.5%, p = 0.01) improvement in establishing the place of death. All patients who expressed a preferred place of death died there. The intervention increased engagement with the wider MDT and led to significant improvements in access to specialist palliative care services. Conclusions: These results show that the interventions implemented to introduce a supportive care register resulted in meaningful improvements to the end-of-life care for patients in our region with advanced CKD.
Arterial Stiffness in Children: Pediatric Measurement and Considerations
Authors: Savant Jonathan D. , Furth Susan L. , Meyers Kevin E.C.
Published: February 2015

Background: Arterial stiffness is a natural consequence of aging, accelerated in certain chronic conditions, and predictive of cardiovascular events in adults. Emerging research suggests the importance of arterial stiffness in pediatric populations. Methods: There are different indices of arterial stiffness. The present manuscript focuses on carotid-femoral pulse wave velocity and pulse wave analysis, although other methodologies are discussed. Also reviewed are specific measurement considerations for pediatric populations and the literature describing arterial stiffness in children with certain chronic conditions (primary hypertension, obesity, diabetes, chronic kidney disease, hypercholesterolemia, genetic syndromes involving vasculopathy, and solid organ transplant recipients). Conclusions: The measurement of arterial stiffness in children is feasible and, under controlled conditions, can give accurate information about the underlying state of the arteries. This potentially adds valuable information about the functionality of the cardiovascular system in children with a variety of chronic diseases well beyond that of the brachial artery blood pressure.
Prácticas de crianza, temperamento y comportamiento prosocial de estudiantes de educación básica
Authors: Aguirre-Dávila Eduardo
Published: February 2015

En este artículo presento los resultados de la investigación en la que indago por la relación entre las prácticas de crianza, el temperamento de los niños y niñas, y su comportamiento prosocial. La muestra fue de 281 padres y madres (M = 40.1 años y DS = 7.0) de familia con hijos e hijas (M = 11.3 años y DS = 0.9) que cursaban quinto y sexto grado de la educación básica, pertenecientes a diferentes estratos socioeconómicos. Apliqué tres instrumentos: el Cuestionario de Prácticas de Crianza (CPC-P) versión padres, el Inventario de Temperamento y Carácter Juvenil (JTCI) versión padres, y la Escala de Comportamiento Prosocial para adolescentes. Para el análisis de los resultados utilicé la regresión logística. Los resultados muestran que la asociación entre las variables prácticas de crianza y temperamento de los niños y niñas predicen su comportamiento prosocial.
Bienestar Subjetivo y Calidad de Vida en la Infancia en Chile
Authors: Oyanedel Juan Carlos , Alfaro Jaime , Mella Camila
Published: February 2015

El artículo presenta los resultados de la Encuesta Internacional sobre Bienestar Subjetivo infantil (ISCWeB), aplicada en Chile en el año 2012. El cuestionario fue aplicado a una muestra de 2.734 niños y niñas, de 8, 10 y 12 años, residentes de las tres principales zonas urbanas del país. Los resultados dan cuenta de una alta satisfacción con la vida, existiendo diferencias al considerar las variables nivel socioeconómico y sexo, así como también distintos aspectos. Los ámbitos mejor evaluados corresponden a la familia, bienes materiales, y salud; en detrimento de aspectos como el barrio y el colegio. Asimismo, se observa que el conocimiento y percepción de que se respetan los derechos de los niños y niñas, disminuye con la edad. Las conclusiones enfatizan la necesidad de profundizar en el estudio de esta temática.
Temporal Trends in the Incidence and Prognosis of Aortic Stenosis
Authors: Martinsson Andreas , Li Xinjun , Andersson Charlotte , Nilsson Johan , Smith J. Gustav , Sundquist Kristina
Published: February 2015

Background—

The aging of Western populations is expected to result in increasing occurrence of aortic stenosis (AS), but data are limited. Recent studies have reported declining incidence and mortality for other major heart diseases. We aimed to study temporal trends in the incidence and prognosis for AS in Sweden.

Methods and Results—

With the use of nationwide registers, all adult patients in the Swedish population with a first diagnosis of AS, heart failure, acute myocardial infarction, and aortic valve replacement for AS between 1989 and 2009 were identified and followed up until the end of 2010 for all-cause and cardiovascular-related mortality. The age-adjusted incidence of AS in Sweden declined from 15.0 to 11.4 in men and 9.8 to 7.1 in women per 100 000 between 1989 to 1991 and 2007 to 2009, and the median age at diagnosis increased by 4 years for both men and women. The age- and sex-adjusted relative risk of 1- and 3-year mortality in 2007 to 2009 was 0.58 (95% confidence interval, 0.53–0.63) and 0.60 (95% confidence interval, 0.56–0.65), respectively, compared with 1989 to 1991. Similar improvements were observed for heart failure and acute myocardial infarction. Findings were broadly consistent across subgroups. Postoperative mortality at 30 days declined despite increased median age at diagnosis.

Conclusions—

Incidence and mortality rates in AS in Sweden declined between 1989 and 2009 to an extent similar to that observed for heart failure and acute myocardial infarction. These findings could suggest that improved risk factor control and cardiovascular therapy, combined with increased use of aortic valve replacement in the elderly and reduced perioperative mortality in aortic valve replacement, have translated into favorable effects for AS.
Nucleotide-Binding Oligomerization Domain 2 Receptor Is Expressed in Platelets and Enhances Platelet Activation and Thrombosis
Authors: Zhang Si , Zhang Shenghui , Hu Liang , Zhai Lili , Xue Ruyi , Ye Jianqin , Chen Leilei , Cheng Guanjun , Mruk Jozef , Kunapuli Satya P. , Ding Zhongren
Published: February 2015

Background—

Pattern recognition receptor nucleotide-binding oligomerization domain 2 (NOD2) is well investigated in immunity, but its expression and function in platelets has never been explored.

Method and Results—

Using reverse transcription polymerase chain reaction and Western blot, we show that both human and mouse platelets express NOD2, and its agonist muramyl dipeptide induced NOD2 activation as evidenced by receptor dimerization. NOD2 activation potentiates platelet aggregation and secretion induced by low concentrations of thrombin or collagen, and clot retraction, as well. These potentiating effects of muramyl dipeptide were not seen in platelets from NOD2-deficient mice. Plasma from septic patients also potentiates platelet aggregation induced by thrombin or collagen NOD2 dependently. Using intravital microscopy, we found that muramyl dipeptide administration accelerated in vivo thrombosis in a FeCl
3
-injured mesenteric arteriole thrombosis mouse model. Platelet depletion and transfusion experiments confirmed that NOD2 from platelets contributes to the in vivo thrombosis in mice. NOD2 activation also accelerates platelet-dependent hemostasis. We further found that platelets express receptor-interacting protein 2, and provided evidence suggesting that mitogen activated-protein kinase and nitric oxide/soluble guanylyl cyclase/cGMP/protein kinase G pathways downstream of receptor-interacting protein mediate the role of NOD2 in platelets. Finally, muramyl dipeptide stimulates proinflammatory cytokine interleukin-1β maturation and accumulation in human and mouse platelets NOD2 dependently.

Conclusions—

NOD2 is expressed in platelets and functions in platelet activation and arterial thrombosis, possibly during infection. To our knowledge, this is the first study on NOD-like receptors in platelets that link thrombotic events to inflammation.
Influence of Maternal Angiogenic Factors During Pregnancy on Microvascular Structure in School-Age Children
Authors: Gishti Olta , Jaddoe Vincent W.V. , Felix Janine F. , Reiss Irwin , Hofman Albert , Ikram Mohammad Kamran , Steegers Eric A.P. , Gaillard Romy
Published: February 2015

Reduced placental growth factor (PlGF) levels and higher soluble fms-like tyrosine kinase (sFlt-1) levels in mothers during pregnancy may have persistent effects on vascular structures in their offspring. We examined whether angiogenic factors during pregnancy also affect childhood retinal microvasculature in a population-based prospective cohort study among 3505 mothers and their children. We measured maternal PlGF and sFlt-1 in the first and second trimester of pregnancy. At the age of 6, we measured childhood retinal arteriolar and venular calibers from digitized retinal photographs. We performed multiple linear regression models, taking maternal and childhood sociodemographic and lifestyle-related characteristics, birth characteristics, and childhood current body mass index and blood pressure into account. We observed that first trimester maternal PlGF and sFlt-1 levels were not associated with childhood retinal arteriolar caliber. Lower second trimester maternal PlGF levels, but not sFlt-1 levels, were associated with narrower childhood retinal arteriolar caliber (difference: −0.09 SD score [95% confidence interval, −0.16 to 0.01], per SD score decrease in PlGF). This association was not explained by maternal and childhood sociodemographic and lifestyle-related characteristics, birth characteristics, or childhood current body mass index and blood pressure. Maternal PlGF and sFlt-1 levels in the first or second trimester were not associated with childhood retinal venular caliber. Our results suggest that lower maternal second trimester PlGF levels affect the microvascular development in the offspring, leading to narrower retinal arteriolar caliber in childhood. Further studies are needed to confirm these findings and to explore the underlying mechanisms and long-term cardiovascular consequences.
Novel Retro-Inverso Peptide Inhibitor Reverses Angiotensin Receptor Autoantibody–Induced Hypertension in the Rabbit
Authors: Li Hongliang , Kem David C. , Zhang Ling , Huang Bing , Liles Campbell , Benbrook Alexandria , Gali Hariprasad , Veitla Vineet , Scherlag Benjamin J. , Cunningham Madeleine W. , Yu Xichun
Published: February 2015

Activating autoantibodies to the angiotensin II type 1 receptor (AT1R) have been implicated in hypertensive disorders. We investigated whether AT1R antibodies produced in immunized rabbits will activate AT1R and contribute to hypertension by a direct contractile effect on the vasculature and whether they can be blocked by a novel decoy peptide. A multiple antigenic peptide containing the AT1R epitope AFHYESQ, which is the receptor-binding epitope of AT1R-activating autoantibodies, was used to immunize 6 rabbits. AT1R antibody activity was analyzed in AT1R-transfected cells, and their contractile effects were assayed using isolated perfused rat cremaster resistance arterioles. A retro-inverso
d
-amino acid epitope-mimetic peptide was tested for AT1R antibody inhibition in vitro and in vivo. All immunized animals produced high AT1R antibody titers and developed elevated blood pressure. No changes in measured blood chemistry values were observed after immunization. Rabbit anti-AT1R sera induced significant AT1R activation in transfected cells and vasoconstriction in the arteriole assay, both of which were blocked by losartan and the retro-inverso
d
-amino acid peptide. A single intravenous bolus injection of the retro-inverso
d
-amino acid peptide (1 mg/kg) into immunized rabbits dropped the mean arterial pressure from 122±11 to 82±6 mm Hg. Rabbit anti-AT1R sera partially suppressed angiotensin II–induced contraction of isolated rat cremaster arterioles, and the pressor response to angiotensin II infusion was attenuated in immunized animals. In conclusion, AT1R-activating autoantibodies and the retro-inverso
d
-amino acid peptide, respectively, have important etiologic and therapeutic implications in hypertensive subjects who harbor these autoantibodies.
Sex-Related Clustering of Intracranial Aneurysms Within Families
Authors: Sijtsma Laura C. , Rinkel Gabriel J.E. , Ruigrok Ynte M.
Published: February 2015

Background and Purpose—

Family history is important risk factor for intracranial aneurysms (ICA), but the pattern of inheritance is unsettled. If ICA within families would cluster according to sex, this may have implications for risk prediction and screening advice within families. We assessed the relationship between the sex of probands and their affected first-degree relatives (FDRs) within families with ICA.

Methods—

We used data from our prospectively collected database of families with known familial ICA. We calculated relative risks for a female affected proband having a female affected FDR as compared with a male affected proband having female affected FDR with corresponding 95% confidence intervals.

Results—

We included 148 families with 376 affected FDR. For a female proband the relative risk for having a female affected FDR compared with a male proband having an affected female FDR was 1.2 (95% confidence interval, 1.0–1.6).

Conclusions—

The clustering of ICA within families is greater in women than in men, with an excess of affected female FDR in female probands. However, because this excess is modest, our findings indicate that sex is not a relevant factor in risk prediction or screening advice in families with ICA.
The Security Bazaar: Business Interests and Islamist Power in Civil War Somalia
Authors: Ahmad Aisha
Published: February 2015

In civil wars across the world, certain Islamist groups have competed exceptionally well against their rivals. The conventional wisdom points to either religion or ethnic politics to explain Islamist success. These ideological and identity-based explanations, however, tend to overlook the powerful economic influence that the local business class has over civil war outcomes. Civil war can be modeled as a market for security, wherein protection must be purchased from multiple substate rackets. Using this market model, a close investigation of the Somali case reveals why and under what conditions the interests of the profit-driven business class align with those of ideologically motivated Islamist groups. Security costs are of critical importance to businesses in a civil war, and Islamists are uniquely competitive in lowering these costs. The business-Islamist alliance is therefore driven by rational, economic considerations, which can contribute to the rise of Islamist power.
The Impact of China on Cybersecurity: Fiction and Friction
Authors: Lindsay Jon R.
Published: February 2015

Exaggerated fears about the paralysis of digital infrastructure and the loss of competitive advantage contribute to a spiral of mistrust in U.S.-China relations. In every category of putative Chinese cyber threat, there are also considerable Chinese vulnerabilities and Western advantages. China has inadvertently degraded the economic efficiency of its networks and exposed them to foreign infiltration by prioritizing political information control over technical cyber defense. Although China also actively infiltrates foreign targets, its ability to absorb stolen data is questionable, especially at the most competitive end of the value chain, where the United States dominates. Similarly, China's military cyber capacity cannot live up to its aggressive doctrinal aspirations, even as its efforts to guide national information technology development create vulnerabilities that more experienced U.S. cyber operators can attack. Outmatched by the West, China is resorting to a strategy of international institutional reform, but it benefits too much from multistakeholder governance to pose a credible alternative. A cyber version of the stability-instability paradox constrains the intensity of cyber interaction in the U.S.-China relationship—and in international relations more broadly—even as lesser irritants continue to proliferate.
Unstable Icons, Contested Histories
Authors: Ryzova Lucie
Published: February 2015

This essay discusses the contemporary circulation of digitized historical photographs in the Egyptian online world. On countless Facebook pages and blogs, vintage photographs of multiple genres—including “orientalist” photographs sold in late 19th century to western tourists, early 20th century postcards of the colonial metropolis, advertising shots published in mid-20th century Egyptian magazines, and private family photographs—are being unearthed, reactivated, and assigned with new meanings that are acutely contemporary. “Freed” from the confines of old dusty archives that once constrained their circulation, such “old” (or “vintage”) photographs become iconic en masse: they no longer stand simply for the thing, person or event depicted, but instead signify larger social values and relationships to the past. Their indexicality and iconicity goes hand in hand: it is precisely because they are photographs—images widely believed to have been created as mechanical, and thus objective, imprints of things that once undoubtedly “were there”—that they can perform the cultural work currently demanded of them as proofs of past truths. This ongoing re-deployment and re-signification of digitized old photographs (facilitated by digital technologies and social media) has two recent genealogies. First is the neoliberal rereading of modern Egyptian history in which colonialism becomes recast as a period of once-had-and-then-lost modernity; second is the difficult and confusing post-revolutionary present in which such “liberated,” but also inherently unstable icons serve to prove at once the necessity of a revolution as well as the reason why it has apparently failed.
From Icons to Emblematic Cases
Authors: Eldén Åsa , Ekal Berna
Published: February 2015

Over the last few years Turkey has seen a changed media visibility of gendered violence, mainly reflected in news and discussions about femicides (murders of women). Once treated as fait-divers, such news now appears on the first pages, or is given the status of ‘special news’. In this process, some cases have become what we call emblematic: stories given an importance reaching far beyond the individual case and thus important in the production of politics on violence against women. Analyzing the dynamics that create emblematic cases by way of the story of Ayşe Paşalı, we argue that not only important public figures, but also ‘ordinary’ people can gain iconic status in the media; this in turn enables the media to demand, on behalf of the women’s movement, that the state take action. Here the strategy of linking ‘ordinary’ cases was picked up by the media and contributed to push the state to show engagement.
Correction of the typification of Corydalis solida var. bracteosa and lectotypification of C. densiflora (Papaveraceae)
Authors: Conti Fabio , Uzunov Dimitar , Bartolucci Fabrizio
Published: February 2015

The genus Corydalis DC. in Lamarck & Candolle (1805: 637) (Papaveraceae) consists of about 440 species distributed in Eurasia, North America and Africa (Lidén & Zetterlund 1997). Corydalis densiflora C.Presl in Presl & Presl (1822: 10) was first described from Sicily based on material collected by C.B. Presl “in nemorosis Nebrodum” during a trip in Sicily in 1817 (Sutorý 2006). According to Lidén & Zetterlund (1997), C. densiflora occurs in peninsular Italy, Sicily and Algeria. The plants coming from Algeria have also been described as C. solida (Linnaeus 1753: 699) Clairville (1811: 371) var. bracteosa Battandier & Trabut (1905: 498), a taxon regarded by Lidén & Zetterlund (1997) as a synonym of C. densiflora. The aim of this paper is to identify and study the type material of both names and to clarify their distribution. This study was carried out within the initiative “Italian Loci Classici Census” (Domina et al. 2012, Peruzzi et al. 2015), aimed at providing data on the original material of the plants described from Italy (e.g. Di Pietro et al. 2012, Gallo et al. 2012, Peruzzi et al. 2012, 2013a, 2013b, Bartolucci & Conti 2013, Bartolucci et al. 2013, Bartolucci & Peruzzi 2014, Bartolucci & Domina 2014, Conti et al. 2014).
Water mites of the genus Unionicola Haldeman, 1842 (Acari, Hydrachnidia, Unionicolidae) in Russia
Authors: TUZOVSKIJ PETR V. , SEMENCHENKO KSENIA A.
Published: February 2015

This study presents a detailed taxonomic review of water mites of the genus Unionicola Haldeman, 1842 (Hygrobatoidea: Unionicolidae) found in the fauna of Russia during the long-term survey period of 1969–2013. The review includes (re)descriptions and illustrations of 21 Unionicola species found in this country: Unionicola intermedia (Koenike, 1882), U. crassipes (O.F. Müller, 1776), U. rossica sp.n., U. figuralis (Koch, 1836), U. gracilipalpis (Viets, 1908), U. markovensis Tuzovskij, 1990, U. minor (Soar, 1900), U. hankoi Szalay, 1927, U. aculeata (Koenike, 1890), U. aculeatella sp.n., U. bonzi (Claparède, 1869), U. inusitata Koenike, 1914, U. rezvoi Sokolow, 1931, U. samaraensis sp.n., U. setipella sp.n., U. setipes Sokolow, 1931, U. tricuspis (Koenike, 1895), U. japonensis Viets, 1933, U. primoryensis sp.n., U. ypsilophora (Bonz, 1783), U. arcuata (Wolcott, 1898). A key is presented for the Unionicola species of Russia based on males and females.
DNA barcoding and regional diversity of understudied Micropeplinae (Coleoptera: Staphylinidae) in Southwest China: phylogenetic implications
and a new Micropeplus from Mount Emei
Authors: GREBENNIKOV VASILY V. , SMETANA ALEŠ
Published: February 2015

Extensive litter sampling at eight forested localities in Yunnan and Sichuan detected 381 specimens of Micropeplinae rove beetles. DNA barcoding data from 85 representative specimens were analysed to delimit species and infer their relationships. Statistical methods were implemented to assess regional species diversity of understudied Micropeplinae. The total number of sampled Micropeplinae species varied between 14 and 17, depending on a splitting versus lumping approach for allopatric populations. A single Micropeplinae species was sampled in six of eight studied localities, three species were found on Mount Gongga, while ten species were discovered on hyperdiverse Mount Emei in Sichuan. All Micropeplinae specimens from our samples belong either to the genus Cerapeplus, or to three other inclusive groups temporarily retained inside Micropeplus sensu lato. Each of the three groups potentially represents a separate genus: tesserula group, sculptus group and Micropeplus sensu stricto. A new species Micropeplus jason sp. n. from Mount Emei in Sichuan is described. Numerous illustrations introduce regional fauna and clarify the discussed morphological characters.
Taxonomic review of Chinese species of ground beetles of the subgenus Pseudoophonus (genus Harpalus) (Coleoptera: Carabidae)
Authors: KATAEV BORIS M. , LIANG HONGBIN
Published: February 2015

A taxonomic review of 23 species of the subgenus Pseudoophonus Motschulsky, 1844, the genus Harpalus Latreille, 1802, occurring in China is given, and a key to these species is provided. The species are divided in three species groups and five subgroups, the distinctive characters of which are listed. The following new synonyms are established: Harpalus calceatus Duftschmid, 1812 = Anisodactylus propinquus Ballion, 1870, syn. n.; H. davidi (Tschitschérine, 1897) = H. kailiensis Huang, 1992, syn. n.; = H. adenticulatus Huang, 1992, syn. n.; = H. cilihumerus Huang, Hu & Sun, 1994, syn. n.; H. fokienensis Schauberger, 1930 = H. muciulus Huang, 1992, syn. n.; H. griseus (Panzer, 1796) = H. xinjiangensis Huang, Hu & Sun, 1994, syn. n.; H. hauserianus Schauberger, 1929 = H. disaogashimensis Huang, 1995, syn. n.; H. pastor pastor Motschulsky, 1844 = H. penglainus Huang, Hu & Sun, 1994, syn. n.; = H. chiloschizontus Huang, 1995, syn. n.; H. rufipes (DeGeer, 1774) = H. scabripectus Huang, Hu & Sun, 1994, syn. n.; H. singularis Tschitschérine, 1906 = H. chengjiangensis Huang, 1993, syn. n.; H. sinicus Hope, 1845 = H. periglabellus Huang, 1992, syn. n.; = H. longihornus Lei & Huang, 1997, syn. n.; and H. tridens Morawitz, 1862 = H. hypogeomysis Huang, 1993, syn. n.; = H. pilosus Huang, 1995, syn. n. Statuses of H. yinchuanensis Huang, 1993 and H. disimuciulus Huang, Lei, Yan & Hu, 1996 are discussed. Lectotypes are designated for H. capito Morawitz, 1862, H. japonicus Morawitz, 1862 and H. eous Tschitschérine, 1901. New data on distribution of Pseudoophonus species in China are provided. Harpalus babai Habu, 1973 is reported from China (Jiangxi) for the first time. The following taxa are recorded from the following Chinese provinces for the first time: H. ussuriensis Chaudoir, 1863 from Hunan; H. aenigma (Tschitschérine, 1897) from Hubei, Jiangxi, and Guangxi; H. pastor Motschulsky, 1844 from Beijing and Xizang; H. fokienensis Schauberger, 1930 from Anhui and Jiangxi; H. simplicidens Schauberger, 1929 from Beijing, Shanghai, and Fujian; H. coreanus (Tschitschérine, 1895) from Anhui, Henan, Zhejiang, Shanghai, Hubei, and Guangdong; H. suensoni Kataev, 1997 from Yunnan; H. sinicus Hope, 1845 from Hainan; H. davidi (Tschitschérine, 1897) from Zhejiang, Hunan, and Guizhou; H. pseudohauserianus Kataev, 2001 from Sichuan; H. indicus orientalis Kataev, 2014 from Xizang, Guangxi, and Guangdong; H. hauserianus Schauberger, 1929 from Xizang and Guizhou; H. singularis Tschitschérine, 1906 from Taiwan; and H. calceatus Duftschmid, 1812 from Guangxi. In addition, H. sinicus and H. singularis are reported from Laos for the first time.
Discovery of a second species of Aesalini from Taiwan, with description of the new species of the genus Echinoaesalus Zelenka, 1993 (Coleoptera: Lucanidae)
Authors: HUANG HAO , CHEN CHANG-CHIN
Published: February 2015

Echinoaesalus chungi Huang & Chen, new species is described from Pingtung, Taiwan. It is the second species of the tribe Aesalini known from Taiwan. This new species is similar to the Bornean species Echinoaesalus arayai Huang & Imura, 2011, but can be distinguished mainly by the smaller size of the entire body, the laterally hooked sulcus on mentum of male, the separated sulci on mentum of female, the bristles inserted anteriorly in the wall of the punctures on dorsal surface of the body, the 9th abdominal segment of male with relatively larger paired pleurites, the medial lobe of parameres with weakly pigmented dorsal surface on distal half and with the pigmented distal sclerite interrupted on dorsal surface, and female genitalia with longer styli, thinner hemisternites and shorter bursa copulatrix. A key to the males of Echinoaesalus species is given. Female genitalia are described in detail for the new species and Echinoaesalus arayai.
Pedunculate Molgula species (Ascidiidae, Molgulidae) from the French Antarctic sector. Redescription and taxonomic revision
Authors: MONNIOT FRANÇOISE , DETTAI AGNÈS
Published: February 2015

Following the Challenger Expedition in the southern Hemisphere, several international surveys have studied Antarctic ascidians. Several pedunculate Molgula were successively described under various names. From the French part of the Antarctic continent and the Kerguelen area, numerous Molgula were recently collected. They are described here in different species, but closely allied. Their taxonomy is revised with an historical review of the most detailed publications and a link to the ancient names.