bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Understanding of Spasticity: Implications for Practice
Authors: Bhimani Rozina , Anderson Lisa
Published: September 2014

Spasticity is a poorly understood phenomenon. The aim of this paper is to understand the effect of spasticity on daily life and identify bedside strategies that enhance patient’s function and improve comfort. Spasticity and clonus result from an upper motor neuron lesion that disinhibits the tendon stretch reflex; however, they are differentiated in the fact that spasticity results in a velocity dependent tightness of muscle whereas clonus results in uncontrollable jerks of the muscle. Clinical strategies that address function and comfort are paramount. This is a secondary content analysis using a qualitative research design. Adults experiencing spasticity associated with neuromuscular disorder were asked to participate during inpatient acute rehabilitation. They were asked to complete a semistructured interview to explain and describe the nature of their experienced spasticity on daily basis. Spasticity affects activities of daily living, function, and mobility. Undertreated spasticity can lead to pain, immobility, and risk of falls. There were missed opportunities to adequately care for patients with spasticity. Bedside care strategies identified by patients with spasticity are outlined. Uses of alternative therapies in conjunction with medications are needed to better manage spasticity. Patient reports on spasticity are important and should be part of clinical evaluation and practice.
Characterization of Polysaccharide by HPLC: Extraction and Anticancer Effects
Authors: Gao Liming , Di Ya , Wu Jiandong , Shi Ming , Zheng Fulu
Published: September 2014

Cervical cancer is a serious health hazard for women’s reproductive system cancer; the method of treatment for cervical cancer is still in surgery, chemotherapy, and radiotherapy as the basic means, but with many complications. The effects of natural medicines for cervical cancer are increasingly becoming the focus of people’s attentions. By studying the polysaccharide of cervical cancer in mice, we found that shark cartilage polysaccharide can increase the serum levels of T-SOD and GSH and decrease MDA level significantly in the tumor mice. The distribution of the drug in the tissue was determined by HPLC method; the drug can be drawn in the liver and kidney the highest, followed by the spleen, lung, and brain levels being the lowest. Polysaccharide can inhibit tumor growth in the mice which may be connected with the enhanced immunity and the antioxidant capacity.
Myeloid Sarcoma Presenting with Leukemoid Reaction in a Child Treated for Acute Lymphoblastic Leukemia
Authors: Canbolat Ayhan Aylin , Timur Cetin , Sonmez Seyma , Zemheri Ebru , Yoruk Asım
Published: September 2014

Background.Myeloid sarcoma is an extramedullary neoplasm of immature myeloid cells. Our study reports a presentation of myeloid sarcoma which presented with severe leukemoid reaction as a secondary malignancy in a patient who was treated for acute lymphoblastic leukemia previously. The case emphasizes the difficulties in diagnosis of patients who do not have concomitant leukemia.Case Presentation.A 6-year-old girl who was treated for acute lymphoblastic leukemia previously presented with fatigue, paleness, and hepatosplenomegaly. Peripheral blood smear and bone marrow aspirate examination did not demonstrate any blasts in spite of severe leukemoid reaction with a white cell count 158000/mm3. FDG/PET CT revealed slight uptake in cervical and supraclavicular lymph nodes. Excisional lymph node biopsy was performed from these lymph nodes and it showed myeloid sarcoma.Conclusion.Myeloid sarcoma can develop as a secondary malignancy in children who are treated for acute lymphoblastic leukemia. It can be associated with severe leukemoid reaction and diagnosis may be difficult if there is not concomitant leukemia. PET/CT is helpful in such cases.
The Rhizome Mixture of Anemarrhena asphodeloides and Coptidis chinensis Ameliorates Acute and Chronic Colitis in Mice by Inhibiting the Binding of Lipopolysaccharide to TLR4 and IRAK1 Phosphorylation
Authors: Jeong Jin-Ju , Jang Se-Eun , Hyam Supriya R. , Han Myung Joo , Kim Dong-Hyun
Published: September 2014

In the previous study, the mixture of the rhizome of Anemarrhena asphodeloides (AA, family Liliaceae) and the rhizome of Coptidis chinensis (CC, family Ranunculaceae) (AC‐mix) improved TNBS‐ or oxazolone‐induced colitis in mice. Therefore, to investigate its anticolitic mechanism, we measured its effect in acute and chronic DSS‐induced colitic mice and investigated its anti‐inflammatory mechanism in peritoneal macrophages. AC‐mix potently suppressed DSS‐induced body weight loss, colon shortening, myeloperoxidase activity, and TNF‐α, IL‐1β, and IL‐6 expressions in acute or chronic DSS‐stimulated colitic mice. Among AC‐mix ingredients, AA, CC, and their main constituents mangiferin and berberine potently inhibited the expression of proinflammatory cytokines TNF‐α and IL‐1β, as well as the activation of NF‐κB in LPS‐stimulated peritoneal macrophages. AA and mangiferin potently inhibited IRAK phosphorylation, but CC and berberine potently inhibited the binding of LPS to TLR4 on macrophages, as well as the phosphorylation of IRAK1. AC‐mix potently inhibited IRAK phosphorylation and LPS binding to TLR4 on macrophages. Based on these findings, AC‐mix may ameliorate colitis by the synergistic inhibition of IRAK phosphorylation and LPS binding to TLR4 on macrophages.
Determine the Compressive Strength of Calcium Silicate Bricks by Combined Nondestructive Method
Authors: Brozovsky Jiri
Published: September 2014

The paper deals with the application of combined nondestructive method for assessment of compressive strength of calcium silicate bricks. In this case, it is a combination of the rebound hammer method and ultrasonic pulse method. Calibration relationships for determining compressive strength of calcium silicate bricks obtained from nondestructive parameter testing for the combined method as well as for the L-type Schmidt rebound hammer and ultrasonic pulse method are quoted here. Calibration relationships are known for their close correlation and are applicable in practice. The highest correlation between parameters from nondestructive measurement and predicted compressive strength is obtained using the SonReb combined nondestructive method. Combined nondestructive SonReb method was proved applicable for determination of compressive strength of calcium silicate bricks at checking tests in a production plant and for evaluation of bricks built in existing masonry structures.
Energy-Efficient Policy Based on Cross-Layer Cooperation in Wireless Communication
Authors: Zhang Juan , Jiang Hong , Jiang Hesong , Chen Chunmei
Published: September 2014

Cooperative communication has emerged as a new wireless network communication concept, in which parameter optimization such as cross-layer cooperation plays an important role. Heuristic evaluation postdecision state learning algorithm (HE-PDS) is proposed in cross-layer cooperation. The proposed algorithm exploits the determinate state information and jointly considers the transmitting power and channel state condition at the physical layer and the buffer congestion control at the media access control layer. The experimental results show that the cumulative average total costs of HE-PDS algorithm decrease about ten times and 8% under the maximum delay and throughput constraints and the power costs decrease about 50% and 28% under various delay limits and about 100% and 56% under the different throughput constraints than the traditional Q algorithm and PDS algorithm, demonstrating that the proposed algorithm has much better energy-efficient performance and faster convergence speed and outperforms the traditional Q learning algorithm and PDS learning algorithm.
The Tissue Response and Degradation of Electrospun Poly(ε‐caprolactone)/Poly(trimethylene‐carbonate) Scaffold in Subcutaneous Space of Mice
Authors: Jiang Tao , Zhang Guoquan , He Wentong , Li Hui , Jin Xun
Published: September 2014

Due to the advantage of controllability on the mechanical property and the degradation rates, electrospun PCL/PTMC nanofibrous scaffold could be appropriate for vascular tissue engineering. However, the tissue response and degradation of electrospun PCL/PTMC scaffold in vivo have never been evaluated in detail. So, electrospun PCL/PTMC scaffolds with different blend ratios were prepared in this study. Mice subcutaneous implantation showed that the continuous degradation of PCL/PTMC scaffolds induced a lasted macrophage‐mediated foreign body reaction, which could be in favor of the tissue regeneration in graft.
Comparative Evaluation of Cytotoxic and Apoptogenic Effects of Several Coumarins on Human Cancer Cell Lines: Osthole Induces Apoptosis in p53-Deficient H1299 Cells
Authors: Shokoohinia Yalda , Hosseinzadeh Leila , Alipour Maryam , Mostafaie Ali , Mohammadi-Motlagh Hamid-Reza
Published: September 2014

Natural products are excellent resources for finding lead structures for the development of chemotherapeutic agents. Coumarins are a class of natural compounds found in a variety of plants. In this study, we evaluated the cytotoxic potential of coumarins isolated fromPrangos ferulacea(L.) Lindl. in PC3, SKNMC, and H1299 (p53 null) human carcinoma cell lines. Osthole proved to be an outstanding potent cytotoxic agent especially against PC3 cells. Isoimperatorin exhibited moderate inhibitory effect against SKNMC and PC3 cell lines. Oxypeucedanin and braylin did not display any cytotoxic activity. In the next set of experiments, the apoptotic potentials of osthole and isoimperatorin were investigated. Induction of apoptosis by isoimperatorin was accompanied by an increase in activation of caspase-3, -8, and -9 in SKNMC cells and caspase-3 and -9 in PC3 cells. Moreover, isoimperatorin induced apoptosis by upregulating Bax and Smac/DIABLO genes in PC3 and SKNMC cells. Osthole induced apoptosis by downregulating antiapoptotic Bcl-2 in only PC3 cells and upregulating the proapoptotic genes Bax and Smac/DIABLO in PC3, SKNMC, and H1299 cells. The effects of osthole on H1299 cells are important because the loss of p53 has been associated with poor clinical prognosis in cancer treatment.
Improving Vehicle Safety: A New Methodology for Vehicle Steering System Inspection by Means of Forces Measure
Authors: García-Pozuelo D. , Díaz V. , Boada M. J. L.
Published: September 2014

Some mechanical systems, such as steering, brakes, and suspension, critically affect the safety of the vehicle. These systems are subject to wear through use and time, changing their status throughout the lifetime of a vehicle. It is, therefore, essential to develop adequate components and procedures of inspection that ensure the correct operation of these systems. Moreover, the steering inspection must guarantee certain requirements, such as, being able to test any vehicle steering system and being low priced. In addition, one of the most important requirements for any inspection procedure is to provide the measurements in a short time. This fact conditions the measurement process and sensors to be employed. The current steering system that measures the steering angles is time consuming. The aim of this research is to introduce a steering system inspection based on forces measured by means of a dynamometer plate. The main features of the proposed system ensure minimum testing time, and simple operation and avoid manipulation of the vehicle. In addition, precise and objective limits for acceptance and rejection have been established. Therefore, the proposed procedure meets all the requirements for the periodic motor vehicle inspection (PMVI).
Systematic Expression Profiling Analysis Identifies Specific MicroRNA-Gene Interactions that May Differentiate between Active and Latent Tuberculosis Infection
Authors: Wu Lawrence Shih-Hsin , Lee Shih-Wei , Huang Kai-Yao , Lee Tzong-Yi , Hsu Paul Wei-Che , Weng Julia Tzu-Ya
Published: September 2014

Tuberculosis (TB) is the second most common cause of death from infectious diseases. About 90% of those infected are asymptomatic—the so-called latent TB infections (LTBI), with a 10% lifetime chance of progressing to active TB. To further understand the molecular pathogenesis of TB, several molecular studies have attempted to compare the expression profiles between healthy controls and active TB or LTBI patients. However, the results vary due to diverse genetic backgrounds and study designs and the inherent complexity of the disease process. Thus, developing a sensitive and efficient method for the detection of LTBI is both crucial and challenging. For the present study, we performed a systematic analysis of the gene and microRNA profiles of healthy individuals versus those affected with TB or LTBI. Combined with a series of in silico analysis utilizing publicly available microRNA knowledge bases and published literature data, we have uncovered several microRNA-gene interactions that specifically target both the blood and lungs. Some of these molecular interactions are novel and may serve as potential biomarkers of TB and LTBI, facilitating the development for a more sensitive, efficient, and cost-effective diagnostic assay for TB and LTBI for the Taiwanese population.
Human Umbilical Cord Mesenchymal Stem Cells Infected with Adenovirus ExpressingHGFPromote Regeneration of Damaged Neuron Cells in a Parkinson’s Disease Model
Authors: Liu Xin-Shan , Li Jin-Feng , Wang Shan-Shan , Wang Yu-Tong , Zhang Yu-Zhen , Yin Hong-Lei , Geng Shuang , Gong Hui-Cui , Han Bing , Wang Yun-Liang
Published: September 2014

Parkinson’s disease (PD) is a neurodegenerative movement disorder that is characterized by the progressive degeneration of the dopaminergic (DA) pathway. Mesenchymal stem cells derived from human umbilical cord (hUC-MSCs) have great potential for developing a therapeutic agent as such. HGF is a multifunctional mediator originally identified in hepatocytes and has recently been reported to possess various neuroprotective properties. This study was designed to investigate the protective effect of hUC-MSCs infected by an adenovirus carrying theHGFgene on the PD cell model induced by MPP+ on human bone marrow neuroblastoma cells. Our results provide evidence that the cultural supernatant from hUC-MSCs expressing HGF could promote regeneration of damaged PD cells at higher efficacy than the supernatant from hUC-MSCs alone. And intracellular free Ca2+obviously decreased after treatment with cultural supernatant from hUC-MSCs expressing HGF, while the expression of CaBP-D28k, an intracellular calcium binding protein, increased. Therefore our study clearly demonstrated that cultural supernatant of MSC overexpressingHGFwas capable of eliciting regeneration of damaged PD model cells. This effect was probably achieved through the regulation of intracellular Ca2+levels by modulating of CaBP-D28k expression.
Crop Depredation by Birds in Deccan Plateau, India
Authors: Kale Manoj Ashokrao , Dudhe Nandkishor , Kasambe Raju , Bhattacharya Prosun
Published: September 2014

Extent of crop depredation in agricultural fields of groundnut, pearl millet, peas, sorghum and sunflower was assessed in Pune, Akola and Amravati, the three productive districts of Maharashtra, India. The study included interviews with the farmers, identification of the bird species responsible for the crop depredation and actual field assessment of damage. The problem of crop depredation is severe for the crops mostly during harvesting season. Most farmers were not satisfied with the conventional bird repelling techniques. A maximum depredation was observed bySorghumcrops by house sparrowsPasser domesticus, baya weaversPloceus philippinus,and rose-ringed parakeetsPsittacula krameri, accounting to 52% of the total damage. Blue rock pigeonsColumba liviadamaged 42% of the peas crop (chick peas and pigeon peas), while house sparrows and baya weaver damaged the groundnut crop by 26% in the sampling plots. House sparrowPasser domesticusand baya weaverPloceus philippinusdamaged the groundnut crop in the sampling plots just after the sowing period. The sustainable solution for reducing crop depredation is a need for the farmers and also such techniques will help avoid direct or indirect effects of use of lethal bird control techniques on bird species.
A Novel Broadband Printed Dipole Antenna and Its Application for TD-LTE Communications
Authors: Wang Can , Ge Yuehe
Published: September 2014

Novel double-sided printed dipole antennas are proposed and investigated in this paper. Two pairs of identical T-shape metallic loadings are connected to the traditional double-sided printed dipole, enhancing the operating bandwidth. Simulations show that the proposed printed dipole without the reflecting ground plane gives a bandwidth of up to 90.7% forS11<-10 dBor 84.9% forS11<-15 dB, which is significantly greater than those of the traditional printed dipole. The proposed dipole is then applied to design a dual-polarized printed dipole antenna, mounted on a ground plane. Measurements for the prototype show a bandwidth of 68.8% forS11<-10 dB, covering the entire TD-LTE band. The gain is about 6–8 dBi and the isolation is over 24 dB over the bandwidth.
Modified Fractional Variational Iteration Method for Solving the Generalized Time-Space Fractional Schrödinger Equation
Authors: Hong Baojian , Lu Dianchen
Published: September 2014

Based on He’s variational iteration method idea, we modified the fractional variational iteration method and applied it to construct some approximate solutions of the generalized time-space fractional Schrödinger equation (GFNLS). The fractional derivatives are described in the sense of Caputo. With the help of symbolic computation, some approximate solutions and their iterative structure of the GFNLS are investigated. Furthermore, the approximate iterative series and numerical results show that the modified fractional variational iteration method is powerful, reliable, and effective when compared with some classic traditional methods such as homotopy analysis method, homotopy perturbation method, adomian decomposition method, and variational iteration method in searching for approximate solutions of the Schrödinger equations.
Efficient Estimators Using Auxiliary Variable under Second Order Approximation in Simple Random Sampling and Two-Phase Sampling
Authors: Singh Rajesh , Sharma Prayas
Published: September 2014

This paper suggests some estimators for population mean of the study variable in simple random sampling and two-phase sampling using information on an auxiliary variable under second order
approximation. Bahl and Tuteja (1991) and Singh et al. (2008) proposed some efficient estimators and studied the properties of the estimators to the first order of approximation. In this paper, we have tried to find out the second order biases and mean square errors of these estimators using information on auxiliary variable based on simple random sampling and two-phase sampling. Finally, an empirical study is carried out to judge the merits of the estimators over others under first and second order of approximation.
Upregulation of IGF1R by Mutant RAS in Leukemia and Potentiation of RAS Signaling Inhibitors by Small-Molecule Inhibition of IGF1R
Authors: Weisberg Ellen , Nonami Atsushi , Chen Zhao , Nelson Erik , Chen Yongfei , Liu Feiyang , Cho HaeYeon , Zhang Jianming , Sattler Martin , Mitsiades Constantine , Wong Kwok-Kin , Liu Qingsong , Gray Nathanael S. , Griffin James D.
Published: September 2014

Purpose: Activating mutations in the RAS oncogene occur frequently in human leukemias. Direct targeting of RAS has proven to be challenging, although targeting of downstream RAS mediators, such as MEK, is currently being tested clinically. Given the complexity of RAS signaling, it is likely that combinations of targeted agents will be more effective than single agents.

Experimental Design: A chemical screen using RAS-dependent leukemia cells was developed to identify compounds with unanticipated activity in the presence of an MEK inhibitor and led to identification of inhibitors of IGF1R. Results were validated using cell-based proliferation, apoptosis, cell-cycle, and gene knockdown assays; immunoprecipitation and immunoblotting; and a noninvasive in vivo bioluminescence model of acute myeloid leukemia (AML).

Results: Mechanistically, IGF1R protein expression/activity was substantially increased in mutant RAS-expressing cells, and suppression of RAS led to decreases in IGF1R. Synergy between MEK and IGF1R inhibitors correlated with induction of apoptosis, inhibition of cell-cycle progression, and decreased phospho-S6 and phospho-4E-BP1. In vivo, NSG mice tail veins injected with OCI-AML3-luc+ cells showed significantly lower tumor burden following 1 week of daily oral administration of 50 mg/kg NVP-AEW541 (IGF1R inhibitor) combined with 25 mg/kg AZD6244 (MEK inhibitor), as compared with mice treated with either agent alone. Drug combination effects observed in cell-based assays were generalized to additional mutant RAS-positive neoplasms.

Conclusions: The finding that downstream inhibitors of RAS signaling and IGF1R inhibitors have synergistic activity warrants further clinical investigation of IGF1R and RAS signaling inhibition as a potential treatment strategy for RAS-driven malignancies. Clin Cancer Res; 20(21); 5483–95. ©2014 AACR.
High-Throughput Drug Screen Identifies Chelerythrine as a Selective Inducer of Death in a TSC2-null Setting
Authors: Medvetz Doug , Sun Yang , Li Chenggang , Khabibullin Damir , Balan Murugabaskar , Parkhitko Andrey , Priolo Carmen , Asara John M. , Pal Soumitro , Yu Jane , Henske Elizabeth P.
Published: September 2014

Tuberous sclerosis complex (TSC) is an autosomal dominant syndrome associated with tumors of the brain, heart, kidney, and lung. The TSC protein complex inhibits the mammalian or mechanistic target of rapamycin complex 1 (mTORC1). Inhibitors of mTORC1, including rapamycin, induce a cytostatic response in TSC tumors, resulting in temporary disease stabilization and prompt regrowth when treatment is stopped. The lack of TSC-specific cytotoxic therapies represents an important unmet clinical need. Using a high-throughput chemical screen in TSC2-deficient, patient-derived cells, we identified a series of molecules antagonized by rapamycin and therefore selective for cells with mTORC1 hyperactivity. In particular, the cell-permeable alkaloid chelerythrine induced reactive oxygen species (ROS) and depleted glutathione (GSH) selectively in TSC2-null cells based on metabolic profiling. N-acetylcysteine or GSH cotreatment protected TSC2-null cells from chelerythrine's effects, indicating that chelerythrine-induced cell death is ROS dependent. Induction of heme-oxygenase-1 (HMOX1/HO-1) with hemin also blocked chelerythrine-induced cell death. In vivo, chelerythrine inhibited the growth of TSC2-null xenograft tumors with no evidence of systemic toxicity with daily treatment over an extended period of time. This study reports the results of a bioactive compound screen and the identification of a potential lead candidate that acts via a novel oxidative stress–dependent mechanism to selectively induce necroptosis in TSC2-deficient tumors.

Implications: This study demonstrates that TSC2-deficient tumor cells are hypersensitive to oxidative stress–dependent cell death, and provide critical proof of concept that TSC2-deficient cells can be therapeutically targeted without the use of a rapalog to induce a cell death response. Mol Cancer Res; 13(1); 50–62. ©2014 AACR.
Serine Catabolism Regulates Mitochondrial Redox Control during Hypoxia
Authors: Ye Jiangbin , Fan Jing , Venneti Sriram , Wan Ying-Wooi , Pawel Bruce R. , Zhang Ji , Finley Lydia W.S. , Lu Chao , Lindsten Tullia , Cross Justin R. , Qing Guoliang , Liu Zhandong , Simon M. Celeste , Rabinowitz Joshua D. , Thompson Craig B.
Published: September 2014

The de novo synthesis of the nonessential amino acid serine is often upregulated in cancer. In this study, we demonstrate that the serine catabolic enzyme, mitochondrial serine hydroxymethyltransferase (SHMT2), is induced when MYC-transformed cells are subjected to hypoxia. In mitochondria, SHMT2 can initiate the degradation of serine to CO2 and NH4+, resulting in net production of NADPH from NADP+. Knockdown of SHMT2 in MYC-dependent cells reduced cellular NADPH:NADP+ ratio, increased cellular reactive oxygen species, and triggered hypoxia-induced cell death. In vivo, SHMT2 suppression led to impaired tumor growth. In MYC-amplified neuroblastoma patient samples, there was a significant correlation between SHMT2 and hypoxia-inducible factor-1 α (HIF1α), and SHMT2 expression correlated with unfavorable patient prognosis. Together, these data demonstrate that mitochondrial serine catabolism supports tumor growth by maintaining mitochondrial redox balance and cell survival.

Significance: In this study, we demonstrate that the mitochondrial enzyme SHMT2 is induced upon hypoxic stress and is critical for maintaining NADPH production and redox balance to support tumor cell survival and growth. Cancer Discov; 4(12); 1406–17. ©2014 AACR.

See related commentary by Martínez-Reyes and Chandel, p. 1371

This article is highlighted in the In This Issue feature, p. 1355
In vivo activation and functions of the protease factor XII
Authors: Björkqvist Jenny , Nickel Katrin , Stavrou Evi , Renné Thomas
Published: September 2014

Combinations of proinflammatory and procoagulant reactions are the unifying principle for a variety of disorders affecting the cardiovascular system. Factor XII (FXII, Hageman factor) is a plasma protease that initiates the contact system. The biochemistry of the contact system in vitro is well understood; however, its in vivo functions are just beginning to emerge. The current review concentrates on activators and functions of the FXII-driven contact system in vivo. Elucidating its physiologic activities offers the exciting opportunity to develop strategies for the safe interference with both thrombotic and inflammatory diseases.
The influence of type 2 diabetes on fibrin clot properties in patients with coronary artery disease
Authors: Neergaard-Petersen Søs , Hvas Anne-Mette , Kristensen Steen , Grove Erik , Larsen Sanne , Phoenix Fladia , Kurdee Zeyad , Grant Peter , Ajjan Ramzi
Published: September 2014

Type 2 diabetes mellitus (T2DM) increases the risk of coronary thrombosis and both conditions are associated with altered fibrin clot properties. However, the influence of T2DM on fibrin clot properties in patients with coronary artery disease (CAD) remains unclear. We aimed to investigate the influence of T2DM on fibrin clot properties in patients with CAD. Fibrin clot structure and fibrinolysis were investigated in 581 CAD patients (148 with T2DM) using turbidimetric assays, confocal and scanning electron microscopy. Clots made from plasma and plasma-purified fibrinogen were studied, and plasma levels of inflammatory markers were analysed. T2DM patients had increased clot maximum absorbance compared with non-diabetic patients (0.36 ± 0.1 vs 0.33 ± 0.1 au; p=0.01), displayed longer lysis time (804 [618;1002] vs 750 [624;906] seconds; p=0.03) and showed more compact fibrin structure assessed by confocal and electron microscopy. Fibrinogen levels were elevated in T2DM (p< 0.001), but clots made from purified fibrinogen showed no differences in fibrin properties in the two populations. Adjusting for fibrinogen levels, T2DM was associated with C-reactive protein and complement C3 plasma levels, with the former correlating with clot maximum absorbance (r=0.24, p< 0.0001) and the latter with lysis time (r=0.30, p< 0.0001). Independent of fibrinogen levels, females had more compact clots with prolonged lysis time compared with males (all p-values< 0.001). In conclusion, T2DM is associated with prothrombotic changes in fibrin clot properties in patients with CAD. This is related to quantitative rather than qualitative changes in fibrinogen with a possible role for inflammatory proteins.
Platelets in neonates: Central mediators in haemostasis, antimicrobial defence and inflammation
Authors: Schulze Harald , Andres Oliver , Speer Christian P.
Published: September 2014

Platelets are not only centrally involved in haemostasis, but also in antimicrobial defence and inflammation. Since evaluation of platelet physiology in the particular patient group of preterm and term neonatal infants is highly restricted for ethical reasons, there are hardly any data available in healthy and much less in extremely immature or ill neonates. By summarising current knowledge and addressing both platelet researchers and neonatologists, we describe neonatal platelet count and morphology, report on previous analyses of neonatal platelet function in primary haemostasis and provide insights into recent advances in platelet immunology that considerably impacts our clinical view on the critically ill neonatal infant. We conclude that neonatal platelets, originating from liver megakaryocytes, substantially differ from adult platelets and may play a pivotal role in the pathophysiology of neonatal sepsis or intraventricular haemorrhage, both complications which seriously augment perinatal morbidity and mortality.
Factor Va alternative conformation reconstruction using atomic force microscopy
Authors: Chaves Rui , Dahmane Selma , Odorico Michael , Nicolaes Gerry , Pellequer Jean-Luc
Published: September 2014

Protein conformational variability (or dynamics) for large macromolecules and its implication for their biological function attracts more and more attention. Collective motions of domains increase the ability of a protein to bind to partner molecules. Using atomic force microscopy (AFM) topographic images, it is possible to take snapshots of large multi-component macromolecules at the single molecule level and to reconstruct complete molecular conformations. Here, we report the application of a reconstruction protocol, named AFM-assembly, to characterise the conformational variability of the two C domains of human coagulation factor Va (FVa). Using AFM topographic surfaces obtained in liquid environment, it is shown that the angle between C1 and C2 domains of FVa can vary between 40° and 166°. Such dynamical variation in C1 and C2 domain arrangement may have important implications regarding the binding of FVa to phospholipid membranes.
CD36-Dependent 7-Ketocholesterol Accumulation in Macrophages Mediates Progression of Atherosclerosis in Response to Chronic Air Pollution Exposure
Authors: Rao Xiaoquan , Zhong Jixin , Maiseyeu Andrei , Gopalakrishnan Bhavani , Villamena Frederick A. , Chen Lung-Chi , Harkema Jack R. , Sun Qinghua , Rajagopalan Sanjay
Published: September 2014

Rationale:

Air pollution exposure has been shown to potentiate plaque progression in humans and animals. Our previous studies have suggested a role for oxidized lipids in mediating adverse vascular effect of air pollution. However, the types of oxidized lipids formed in response to air pollutants and how this occurs and their relevance to atherosclerosis are not fully understood.

Objective:

To investigate the mechanisms by which particulate matter <2.5 μm (PM
2.5
) induces progression of atherosclerosis.

Methods and Results:

Atherosclerosis-prone
ApoE
−/−
or
LDLR
−/−
mice were exposed to filtered air or concentrated ambient PM
2.5
using a versatile aerosol concentrator enrichment system for 6 months. PM
2.5
increased 7-ketocholesterol (7-KCh), an oxidatively modified form of cholesterol, in plasma intermediate density lipoprotein/low-density lipoprotein fraction and in aortic plaque concomitant with progression of atherosclerosis and increased CD36 expression in plaque macrophages from PM
2.5
-exposed mice. Macrophages isolated from PM
2.5
-exposed mice displayed increased uptake of oxidized lipids without alterations in their efflux capacity. Consistent with these finding, CD36-positive macrophages displayed a heightened capacity for oxidized lipid uptake. Deficiency of CD36 on hematopoietic cells diminished the effect of air pollution on 7-KCh accumulation, foam cell formation, and atherosclerosis.

Conclusions:

Our results suggest a potential role for CD36-mediated abnormal accumulations of oxidized lipids, such as 7-KCh, in air pollution–induced atherosclerosis progression.
Similar Effect of Autologous and Allogeneic Cell Therapy for Ischemic Heart Disease
Authors: Jansen of Lorkeers Sanne Johanna , Eding Joep Egbert Coenraad , Vesterinen Hanna Mikaela , van der Spoel Tycho Ids Gijsbert , Sena Emily Shamiso , Duckers Henricus Johannes , Doevendans Pieter Adrianus , Macleod Malcolm Robert , Chamuleau Steven Anton Jozef
Published: September 2014

Rationale:

In regenerative therapy for ischemic heart disease, use of both autologous and allogeneic stem cells has been investigated. Autologous cell can be applied without immunosuppression, but availability is restricted, and cells have been exposed to risk factors and aging. Allogeneic cell therapy enables preoperative production of potent cell lines and immediate availability of cell products, allowing off-the-shelf therapy. It is unknown which cell source is preferred with regard to improving cardiac function.

Objective:

We performed a meta-analysis of preclinical data of cell therapy for ischemic heart disease.

Methods and Results:

We conducted a systematic literature search to identify publications describing controlled preclinical trials of unmodified stem cell therapy in large animal models of myocardial ischemia. Data from 82 studies involving 1415 animals showed a significant improvement in mean left ventricular ejection fraction in treated compared with control animals (8.3%, 95% confidence interval, 7.1–9.5;
P
<0.001). Meta-regression revealed a similar difference in left ventricular ejection fraction in autologous (8.8%, 95% confidence interval, 7.3–10.3; n=981) and allogeneic (7.3%, 95% confidence interval, 4.4–10.2, n=331;
P
=0.3) cell therapies.

Conclusions:

Autologous and allogeneic cell therapy for ischemic heart disease show a similar improvement in left ventricular ejection fraction in large animal models of myocardial ischemia, compared with placebo. These results are important for the design of future clinical trials.
Direct Conversion of Adult Skin Fibroblasts to Endothelial Cells by Defined Factors
Authors: Han Jung-Kyu , Chang Sung-Hwan , Cho Hyun-Ju , Choi Saet-Byeol , Ahn Hyo-Suk , Lee Jaewon , Jeong Heewon , Youn Seock-Won , Lee Ho-Jae , Kwon Yoo-Wook , Cho Hyun-Jai , Oh Byung-Hee , Oettgen Peter , Park Young-Bae , Kim Hyo-Soo
Published: September 2014

Background—

Cell-based therapies to augment endothelial cells (ECs) hold great therapeutic promise. Here, we report a novel approach to generate functional ECs directly from adult fibroblasts.

Methods and Results—

Eleven candidate genes that are key regulators of endothelial development were selected. Green fluorescent protein (GFP)–negative skin fibroblasts were prepared from Tie2-GFP mice and infected with lentiviruses allowing simultaneous overexpression of all 11 factors. Tie2-GFP
+
cells (0.9%), representing Tie2 gene activation, were detected by flow cytometry. Serial stepwise screening revealed 5 key factors (Foxo1, Er71, Klf2, Tal1, and Lmo2) that were required for efficient reprogramming of skin fibroblasts into Tie2-GFP
+
cells (4%). This reprogramming strategy did not involve pluripotency induction because neither Oct4 nor Nanog was expressed after 5 key factor transduction. Tie2-GFP
+
cells were isolated using fluorescence-activated cell sorting and designated as induced ECs (iECs). iECs exhibited endothelium-like cobblestone morphology and expressed EC molecular markers. iECs possessed endothelial functions such as
Bandeiraea simplicifolia
-1 lectin binding, acetylated low-density lipoprotein uptake, capillary formation on Matrigel, and nitric oxide production. The epigenetic profile of iECs was similar to that of authentic ECs because the promoters of VE-cadherin and Tie2 genes were demethylated. mRNA profiling showed clustering of iECs with authentic ECs and highly enriched endothelial genes in iECs. In a murine model of hind-limb ischemia, iEC implantation increased capillary density and enhanced limb perfusion, demonstrating the in vivo viability and functionality of iECs.

Conclusions—

We demonstrated the first direct conversion of adult fibroblasts to functional ECs. These results suggest a novel therapeutic modality for cell therapy in ischemic vascular disease.
Female, but not male, agonistic behaviour is associated with male reproductive success in stable bluebanded goby (Lythrypnus dalli) hierarchies
Authors: Solomon-Lane Tessa K. , Willis Madelyne C. , Pradhan Devaleena S. , Grober Matthew S.
Published: September 2014

In many social species, there are important connections between social behaviour and reproduction that provide critical insights into the evolution of sociality. In this study, we describe associations between agonistic behaviour and male reproductive success in stable social groups of bluebanded gobies (Lythrypnus dalli). This highly social, sex-changing species forms linear hierarchies of a dominant male and multiple subordinate females. Males reproduce with each female in the harem and care for the eggs. Since aggression tends to be associated with reduced reproduction in social hierarchies, we hypothesized that males in groups with high rates of aggression would fertilise fewer eggs. We also hypothesized that a male’s agonistic behaviour would be associated with his reproductive success. Dominants often exert substantial control over their harem, including control over subordinate reproduction. To address these hypotheses, we quantified egg laying/fertilisation over 13 days and observed agonistic behaviour. We show that there was a significant, negative association between male reproductive success and the total rate agonistic interactions by a group. While no male behaviours were associated with the quantity of eggs fertilised, female agonistic behaviour may be central to male reproductive success. We identified a set of models approximating male reproductive success that included three female behaviours: aggression by the highest-ranking female and approaches by the lowest-ranking female were negatively associated with the quantity of eggs fertilised by males in their groups, but the efficiency with which the middle-ranking female displaced others was positively associated with this measure. These data provide a first step in elucidating the behavioural mechanisms that are associated with L. dalli reproductive success.
Isotocin and sociality in the cooperatively breeding cichlid fish, Neolamprologus pulcher
Authors: Reddon Adam R. , Voisin Mathew R. , O’Connor Constance M. , Balshine Sigal
Published: September 2014

The ultimate functions of sociality, or the tendency to associate with conspecifics and to live within a social group, are increasingly well understood. However, the proximate mechanisms that mediate this behaviour have received less attention. The oxytocin family of nonapeptide hormones (including isotocin in teleost fish) is thought to play an important role in regulating social behaviour across a wide range of taxa and social contexts. In the current study, we investigated the influence of exogenous administration of isotocin and an oxytocin receptor antagonist on sociality in a cooperatively breeding fish, Neolamprologus pulcher. In our first experiment, we found that a high (and a low) dose of peripherally administered exogenous isotocin decreased the time spent associating with conspecifics in N. pulcher, while an intermediate dose had no effect relative to control. In our second experiment, we found that a peripheral administration of an oxytocin receptor antagonist increased grouping preference in male N. pulcher. The results of both experiments suggest that IT may inhibit grouping behaviour in this species. These results contribute to a growing body of literature suggesting that the broad generalization that the oxytocin family of nonapeptides facilitate grouping behaviour is overly simplistic, and that specific behavioural effects depend the study species and testing conditions.
Ephemeral work group formation of Jenu Kuruba honey collectors and late 19th Century Colorado silver prospectors
Authors: Demps Kathryn , Glover Klemetti Susan M.
Published: September 2014

Humans frequently form short-lived cooperative groups to accomplish subsistence and economic tasks. We explore the ecological and cultural factors behind ephemeral work-group formation in two disparate cultural contexts: groups foraging for wild honey in present day South India and groups prospecting for silver ore in the Elk Mountain Mining District of Colorado in the late 19th century. Contrary to traditional economic foraging predictions, we find little evidence that per capita yields are the most important factor in determining size and composition of ephemeral work groups. We explore factors in each of these cultures that may be of importance for group formation such as kinship, reputation, and pleasure. Models that only incorporate economic parameters will make poor predictions of how humans interact with their environments.
The social context of individual foraging behaviour in long-finned pilot whales (Globicephala melas)
Authors: Visser Fleur , Miller Patrick J.O. , Antunes Ricardo N. , Oudejans Machiel G. , Mackenzie Monique L. , Aoki Kagari , Lam Frans-Peter A. , Kvadsheim Petter H. , Huisman Jef , Tyack Peter L.
Published: September 2014

Long-finned pilot whales (Globicephala melas) are highly social cetaceans that live in matrilineal groups and acquire their prey during deep foraging dives. We tagged individual pilot whales to record their diving behaviour. To describe the social context of this individual behaviour, the tag data were matched with surface observations at the group level using a novel protocol. The protocol comprised two key components: a dynamic definition of the group centred around the tagged individual, and a set of behavioural parameters quantifying visually observable characteristics of the group. Our results revealed that the diving behaviour of tagged individuals was associated with distinct group-level behaviour at the water’s surface. During foraging, groups broke up into smaller and more widely spaced units with a higher degree of milling behaviour. These data formed the basis for a classification model, using random forest decision trees, which accurately distinguished between bouts of shallow diving and bouts of deep foraging dives based on group behaviour observed at the surface. The results also indicated that members of a group to a large degree synchronised the timing of their foraging periods. This was confirmed by pairs of tagged individuals that nearly always synchronized their diving bouts. Hence, our study illustrates that integration of individual-level and group-level observations can shed new light on the social context of the individual foraging behaviour of animals living in groups.
Generic Terms for Domestic Animals in East Caucasian
Authors: Schulze Wolfgang
Published: September 2014

The present paper aims at a closer inspection of historical layers of the lexicon of East Caucasian by looking at a small set of lexical forms that are related to the world of concepts for domestic animals. The paper concentrates on these terms also in order to discuss the question to which extent the reconstructability of corresponding forms for Proto-East Caucasian may shed light on some of the economical patterns of the speakers of this language. It will be shown that much of the terminology for domestic animals has to be related to earlier or later loan layers or to innovative processes within the subgroups. The fact that very few of the terms occurring in one of the domains at issue (‘cow’, ‘horse’, ‘donkey’, ‘pig’, ‘sheep’, ‘goat’) can be reconstructed for Proto-East Caucasian is related to the assumption that lexical terms that are strongly related to the praxeological dimension of socioeconomic concepts tend to be rather instable and adaptable over times to changes with respect to these praxeological patterns. The paper also strongly advocates for a closer consideration and isolation of loan layers present in the individual East Caucasian languages prior to any enterprise aiming at the reconstruction of Proto-East Caucasian lexical units.
On Çerkezī’s Translation of Tha‘labī’s Qiṣaṣ al-Anbiyā’
Authors: Bayraktar Nesrin
Published: September 2014

This article focuses on Çerkezī’s translation of Tha‘labī’s Qiṣaṣ al-Anbiyā as a prominent source for the history of Old Anatolian Turkish. There are two extant copies of this translation in the libraries of Turkey. The first is a manuscript in two volumes, the second is a print copy. Çerkezī’s language shows lexical, morphological and phonetical features of Old Anatolian Turkish, as well as some caracteristics of Old Azerbaijani.
Review Article: The Yezidi Religion
Authors: Nicolaus Peter
Published: September 2014

The article presents a detailed discussion of several key issues concerning the essentials of the Yezidi identity―the Yezidi religion, particularly the folk pantheon and the conceptions of divinity, based upon the analysts of the recent monograph by Garnik S. Asatrian and Victoria Arakelova.
A revised generic arrangement for the eagle ray family Myliobatidae, with definitions for the valid genera
Authors: WHITE WILLIAM T.
Published: September 2014

The generic arrangement of the eagle rays (Family Myliobatidae) is revised and the genus Pteromylaeus Garman, 1913 is placed into the synonymy of Aetomylaeus Garman, 1908. Definitions are provided for the three valid genera, Aetobatus, Aetomylaeus and Myliobatis, and nomenclatural issues are discussed. Aetobatus differs from the latter two genera in having: a deeply notched nasal curtain, both jaws with a single row of chevron-shaped teeth, broadly rounded pectoral-fin free rear tips, pectoral fins separate from rostral lobe and joining head at level of eye. Aetomylaeus differs from the other two genera in having: pectoral fins separate from rostral lobe and joining head below level of eye, and stinging spine absent or present (usually not well developed when present). Myliobatis differs from the other two genera in having the pectoral fins joined to the rostral lobe by a subocular ridge. A list of valid species is provided, including a list of junior synonyms. Myliobatis australis Macleay, 1881 from southern Australia is placed into the synonymy of the previously considered endemic New Zealand species, M. tenuicaudatus Hector, 1877.
Riegeriana, a new genus for Physopelta apicalis, and checklist of the genus Iphita (Hemiptera: Heteroptera: Largidae) with description of one new species
Authors: STEHLÍK JAROSLAV L. , KMENT PETR
Published: September 2014

Riegeriana gen. nov. is described to accommodate Physopelta apicalis Walker, 1873. A lectotype of Ph. apicalis is de-signated. Iphita fasciata Stehlík & Jindra, 2008, syn. nov., is recognized as a new junior subjective synonym of Riegeriana apicalis. In addition, Iphita lata sp. nov. is described from southern India and a check-list of the species of the genus Iphita Stål, 1873 is provided. The etymology of Iphita nigris Ahmad & Abbas, 1992 and the lectotype designation of Dindymellus coimbatorensis Distant, 1919 are discussed. The following new or confirmed country records are provided: Iphita coimbatorensis (Distant, 1919) from India (Karnataka, Orissa); I. dubia (Breddin, 1901) from Indonesia (Papua); I. limbata Stål, 1870 from Cambodia, China (Hainan), India (Arunachal Pradesh), Indonesia (Sumatra, Kalimantan), Malaysia (Pahang: Tioman Island), and Vietnam; I. lycoides (Walker, 1873) from the Philippines (Panay Island).