bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leptin into the ventrolateral medulla facilitates chemorespiratory response in leptin‐deficient (ob/ob) mice
Authors: Bassi M. , Furuya W. I. , Menani J. V. , Colombari D. S. A. , do Carmo J. M. , da Silva A. A. , Hall J. E. , Moreira T. S. , Wenker I. C. , Mulkey D. K. , Colombari E. 
Published: February 2014

AbstractAimLeptin, an adipocyte‐derived hormone, is suggested to participate in the central control of breathing. We hypothesized that leptin may facilitate ventilatory responses to chemoreflex activation by acting on respiratory nuclei of the ventrolateral medulla. The baseline ventilation and the ventilatory responses to CO2 were evaluated before and after daily injections of leptin into the retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG) for 3 days in obese leptin‐deficient (ob/ob) mice.MethodsMale ob/ob mice (40–45 g, n = 7 per group) received daily microinjections of vehicle or leptin (1 μg per 100 nL) for 3 days into the RTN/pFRG. Respiratory responses to CO2 were measured by whole‐body plethysmography.ResultsUnilateral microinjection of leptin into the RTN/pFRG in ob/ob mice increased baseline ventilation (VE) from 1447 ± 96 to 2405 ±174 mL min−1 kg−1 by increasing tidal volume (VT) from 6.4 ± 0.4 to 9.1 ± 0.8 mL kg−1 (P < 0.05). Leptin also enhanced ventilatory responses to 7% CO2 (Δ = 2172 ± 218 mL min−1 kg−1, vs. control: Δ = 1255 ± 105 mL min−1 kg−1), which was also due to increased VT (Δ = 4.71 ± 0.51 mL kg−1, vs. control: Δ = 2.27 ± 0.20 mL kg−1), without changes in respiratory frequency. Leptin treatment into the RTN/pFRG or into the surrounding areas decreased food intake (83 and 70%, respectively), without significantly changing body weight.ConclusionThe present results suggest that leptin acting in the respiratory nuclei of the ventrolateral medulla improves baseline VE and VT and facilitates respiratory responses to hypercapnia in ob/ob mice.
Ex Vivo production of platelets from stem cells
Authors: Avanzi Mauro P. , Mitchell William Beau 
Published: February 2014

SummaryStem cell technology holds great promise for transfusion medicine, and generation of platelets from stem cells would be transformative. Platelet transfusions are life saving for millions of people and the clinical demand for platelets continues to increase: there is a real need to increase the supply of platelets. Accordingly, there is great interest in the potential of producing platelets from stem cells for clinical use. There has been initial success in ex vivo generation of platelets from stem cells using cord blood stem cells, embryonic stem cells and induced pluripotent stem cells. However, the platelet yields achieved by these strategies have not been sufficient for clinical purposes. This review provides updated information about the current strategies of ex vivo generation of platelets. Megakaryocytopoiesis and platelet generation, along with the importance of genetic determinants of these processes, are reviewed in the context of efforts to generate these products from stem cells. Current challenges and rate‐limiting steps in ex vivo platelet generation are discussed, together with strategies to overcome them. While much work remains, great progress has been made, moving ex vivo generation of platelets ever closer to the clinic.
PARADIGM SHIFT: A MEAN FIELD GAME APPROACH
Authors: Besancenot Damien , Dogguy Habib 
Published: February 2014

ABSTRACTThis paper analyses the consequences of young researchers' scientific choice on the dynamics of sciences. We develop a simple two state mean field game model to analyse the competition between two paradigms based on Kuhn's theory of scientific revolution. The dynamics of the model are driven by the scientific choice of young researchers at the beginning of their career. Despite the possibility of multiple equilibria, the model exhibits at least one stable solution in which both para digms coexist. The occurrence of shocks on the parameters may induce the shift from one paradigm to the other. During this shift, researchers' choice is proved to be having a great impact on the evolution of sciences.
Reduced Vascular Endothelial Growth Factor and Capillary Density in the Occipital Cortex in Dementia with Lewy Bodies
Authors: Miners Scott , Moulding Hayley , de Silva Rohan , Love Seth 
Published: February 2014

AbstractIn dementia with Lewy bodies (DLB), blood flow tends to be reduced in the occipital cortex. We previously showed elevated activity of the endothelin and angiotensin pathways in Alzheimer's disease (AD). We have measured endothelin‐1 (ET‐1) level and angiotensin‐converting enzyme (ACE) activity in the occipital cortex in DLB and control brains. We also measured vascular endothelial growth factor (VEGF); factor VIII‐related antigen (FVIIIRA) to indicate microvessel density; myelin‐associated glycoprotein (MAG), a marker of ante‐mortem hypoperfusion; total α‐synuclein (α‐syn) and α‐synuclein phosphorylated at Ser129 (α‐syn‐p129). In contrast to findings in AD, ACE activity and ET‐1 level were unchanged in DLB compared with controls. VEGF and FVIIIRA levels were, however, significantly lower in DLB. VEGF correlated positively with MAG concentration (in keeping with a relationship between reduction in VEGF and hypoperfusion), and negatively with α‐syn and α‐syn‐p129 levels. Both α‐syn and α‐syn‐p129 levels increased in human SH‐SY5Y neuroblastoma cells after oxygen‐glucose deprivation (OGD), and VEGF level was reduced in SH‐SY5Y cells overexpressing α‐syn. Taken together, our findings suggest that reduced microvessel density rather than vasoconstriction is responsible for lower occipital blood flow in DLB, and that the loss of microvessels may result from VEGF deficiency, possible secondary to the accumulation of α‐syn.
Human papillomavirus and p53 mutations in head and neck squamous cell carcinoma among Japanese population
Authors: Maruyama Hiromi , Yasui Toshimichi , Ishikawa‐Fujiwara Tomoko , Morii Eiichi , Yamamoto Yoshifumi , Yoshii Tadashi , Takenaka Yukinori , Nakahara Susumu , Todo Takeshi , Hongyo Tadashi , Inohara Hidenori 
Published: February 2014

We aimed to reveal the prevalence and pattern of human papillomavirus (HPV) infection and p53 mutations among Japanese head and neck squamous cell carcinoma (HNSCC) patients in relation to clinicopathological parameters. Human papillomavirus DNA and p53 mutations were examined in 493 HNSCCs and its subset of 283 HNSCCs. Oropharyngeal carcinoma was more frequently HPV‐positive than non‐oropharyngeal carcinoma (34.4% vs 3.6%, P < 0.001), and HPV16 accounted for 91.1% of HPV‐positive tumors. In oropharyngeal carcinoma, which showed an increasing trend of HPV prevalence over time (P < 0.001), HPV infection was inversely correlated with tobacco smoking, alcohol drinking, p53 mutations, and a disruptive mutation (P = 0.003, <0.001, <0.001, and <0.001, respectively). The prevalence of p53 mutations differed significantly between virus‐unrelated HNSCC and virus‐related HNSCC consisting of nasopharyngeal and HPV‐positive oropharyngeal carcinomas (48.3% vs 7.1%, P < 0.001). Although p53 mutations were associated with tobacco smoking and alcohol drinking, this association disappeared in virus‐unrelated HNSCC. A disruptive mutation was never found in virus‐related HNSCC, whereas it was independently associated with primary site, such as the oropharynx and hypopharynx (P = 0.01 and 0.03, respectively), in virus‐unrelated HNSCC. Moreover, in virus‐unrelated HNSCC, G:C to T:A transversions were more frequent in ever‐smokers than in never‐smokers (P = 0.04), whereas G:C to A:T transitions at CpG sites were less frequent in ever‐smokers than in never‐smokers (P = 0.04). In conclusion, HNSCC is etiologically classified into virus‐related and virus‐unrelated subgroups. In virus‐related HNSCC, p53 mutations are uncommon with the absence of a disruptive mutation, whereas in virus‐unrelated HNSCC, p53 mutations are common, and disruptive mutagenesis of p53 is related with oropharyngeal and hypopharyngeal carcinoma.
Retrieval of various aspirated foreign bodies by flexible cryoprobe: in vitro feasibility study
Authors: Fruchter Oren , Kramer Mordechai R. 
Published: February 2014

AbstractIntroductionRetrieval of aspirated foreign bodies (FB) by flexible bronchoscopy is challenging. Many types of ancillary equipment, including forceps, grasping claws, snares, balloon‐tipped catheters and magnets, have been developed to allow FB extraction using flexible bronchoscopes. The ability to remove a FB by flexible cryoprobe (cryoextraction) depends on the cryoadhesive properties of the retrieved object, which in turn depends on its physical properties.ObjectivesOur aim was to explore ex vivo on a lung model the cryoadhesive properties of various commonly aspirated objects.MethodsThe tested FB compromised of nine organic and nine inorganic commonly aspirated objects. An attempt was made to retrieve each object from a lung model by flexible cryoprobe at 5 and 10 s application time and following rinsing by normal saline.ResultsWhereas most organic objects (for example chicken and fish bones) were retrievable by cryoprobe, most inorganic objects (for example safety pin and paper clip) are not retrievable by cryoadhesion. On the other hand, several inorganic objects (for example dental cup) despite their low water content were cryoadhesive.ConclusionFB retrieval by cryoprobe is feasible for many organic and inorganic aspirated objects. However, the cryoadhesive properties of most inorganic FB and several organic objects is unpredictable, hence, if the nature of the FB is known, an identical object should be used to practice the technique of retrieval in vitro, prior to attempting to perform the procedure in the patient.
The role ofTc‐99mDTPAaerosol scintigraphy in the differential diagnosis ofCOPDand asthma
Authors: Karacavus Seyhan , Intepe Yavuz S. 
Published: February 2014

AbstractObjectiveChronic obstructive lung disease (COPD) and asthma are characterized as similar to each other in causing airway obstruction and being an inflammatory process. The purpose of this study was to investigate whether technetium‐99m diethylenetriaminepentaacetic acid (99mTc‐DTPA) aerosol scintigraphy could be used in the differential diagnosis of asthma andCOPD.MethodsEighty‐four patients (male/female: 32/52; mean age 50.2 ± 12.7 years) with obstructive lung disease and 30 healthy volunteers as the control group were enrolled in the study. The patients were divided into two groups asCOPDand asthma and also smoking subgroups. Alveolar clearance study was performed using a radiolabeled aerosol of99mTc‐DTPA. Mucociliary clearance was evaluated withT½, cap value and penetration index parameters. All patient underwent pulmonary function tests and Forced expiratory volume (FEV1), forced vital capacity (FVC) andFEV1/FVCparameters were obtained.ResultsThe mean ofT½values of99mTc‐DTPAaerosol andFEV1/FVCvalue among spirometric tests of the nonsmokingCOPDpatients were significantly lower than nonsmoking asthma patients (46.1 ± 14.3, 62.3 ± 18.7,P = 0.02; 65.2 ± 10.8, 81.4 ± 16.5,P = 0.04, respectively). The cap value was significantly higher in nonsmokingCOPDpatients (1.21 ± 0.49, 0.76 ± 0.22,P = 0.03). While there were no statistically and significantly different between control and asthmatic groups at the scintigraphic parameters and spirometric parameters, the mean ofT½values, cap value and spirometric parameters were statistically different between control andCOPDgroups (P < 0.05).ConclusionWe showed that assessment of mucociliary permeability with99mTc‐DTPAaerosol scintigraphy was a useful, easy to apply and a noninvasive technique to use in the differential diagnosis of nonsmokerCOPDand asthma.
Artemisia dracunculus L. extract ameliorates insulin sensitivity by attenuating inflammatory signalling in human skeletal muscle culture
Authors: Vandanmagsar B. , Haynie K. R. , Wicks S. E. , Bermudez E. M. , Mendoza T. M. , Ribnicky D. , Cefalu W. T. , Mynatt R. L. 
Published: February 2014

AimsBioactives of Artemisia dracunculus L. (termed PMI 5011) have been shown to improve insulin action by increasing insulin signalling in skeletal muscle. However, it was not known if PMI 5011's effects are retained during an inflammatory condition. We examined the attenuation of insulin action and whether PMI 5011 enhances insulin signalling in the inflammatory environment with elevated cytokines.MethodsMuscle cell cultures derived from lean, overweight and diabetic‐obese subjects were used. Expression of pro‐inflammatory genes and inflammatory response of human myotubes were evaluated by real‐time polymerase chain reaction (RT‐PCR). Insulin signalling and activation of inflammatory pathways in human myotubes were evaluated by multiplex protein assays.ResultsWe found increased gene expression of monocyte chemoattractant protein 1 (MCP1) and TNFα (tumour necrosis factor alpha), and basal activity of the NFkB (nuclear factor kappa‐light‐chain‐enhancer of activated B cells) pathway in myotubes derived from diabetic‐obese subjects as compared with myotubes derived from normal‐lean subjects. In line with this, basal Akt phosphorylation (Ser473) was significantly higher, while insulin‐stimulated phosphorylation of Akt (Ser473) was lower in myotubes from normal‐overweight and diabetic‐obese subjects compared with normal‐lean subjects. PMI 5011 treatment reduced basal phosphorylation of Akt and enhanced insulin‐stimulated phosphorylation of Akt in the presence of cytokines in human myotubes. PMI 5011 treatment led to an inhibition of cytokine‐induced activation of inflammatory signalling pathways such as Erk1/2 and IkBα (nuclear factor of kappa light polypeptide gene enhancer in B‐cells inhibitor, alpha)‐NFkB and moreover, NFkB target gene expression, possibly by preventing further propagation of the inflammatory response within muscle tissue.ConclusionsPMI 5011 improved insulin sensitivity in diabetic‐obese myotubes to the level of normal‐lean myotubes despite the presence of pro‐inflammatory cytokines.
Lixisenatide resensitizes the insulin‐secretory response to intravenous glucose challenge in people with type 2 diabetes – a study in both people with type 2 diabetes and healthy subjects
Authors: Becker R. H. A. , Stechl J. , Msihid J. , Kapitza C. 
Published: February 2014

AimsGlucagon‐like peptide‐1 (GLP‐1) receptor agonists improve blood glucose control by enhancing glucose‐sensitive insulin release, delaying gastric emptying and reducing postprandial glucagon secretion. The studies reported here investigated the insulin response to an intravenous (iv) glucose challenge after injection of lixisenatide (LIXI) 20 µg or placebo.MethodsTwo single‐centre, double‐blind, randomized, placebo‐controlled, single‐dose, crossover studies were performed in healthy subjects (HS) and people with type 2 diabetes mellitus (T2DM). Participants received subcutaneous LIXI or placebo 2 h before an iv glucose challenge. Study endpoints included first‐ and second‐phase insulin response, insulin concentration (INS), glucagon response and glucose disposal rate (Kglucose). LIXI exposure was measured over 12 h.ResultsLIXI 20 µg reached maximum concentration after 2 h and resensitized first‐phase insulin secretion by 2.8‐fold in T2DM to rates comparable with those in HS on placebo, and raised second‐phase insulin secretion by 1.6‐fold in T2DM. INS rose correspondingly and glucose disposal was accelerated by 1.8‐fold in T2DM. First‐phase insulin secretion and glucose disposal were also augmented by LIXI in HS, whereas second‐phase insulin secretion reduced blood glucose concentrations to below fasting levels and then ceased, accompanied by a rapid, short‐lasting rise in glucagon. Otherwise, suppression of glucagon release subsequent to augmentation of insulin release was unaffected in T2DM and in HS.ConclusionsLIXI resensitized the insulin response to an iv glucose challenge in people with T2DM, thereby accelerating glucose disposal to nearly physiological intensity, and did not impair counter‐regulation to low glucose levels by glucagon.
Headache‐attributed burden and its impact on productivity and quality of life in Russia: structured healthcare for headache is urgently needed
Authors: Ayzenberg I. , Katsarava Z. , Sborowski A. , Chernysh M. , Osipova V. , Tabeeva G. , Steiner T. J. 
Published: February 2014

Background and purposeThe study evaluated headache‐attributed burden and its impact on productivity and quality of life (QoL) in Russia. Its purpose was to support recommendations for change.MethodsA countrywide population‐based random sample of 2725 biologically unrelated adults (aged 18–65 years) in 35 cities and nine rural areas of Russia were interviewed in a door‐to‐door survey. The structured questionnaire enquired into symptom burden, functional disability, lost productive time and QoL (applying the WHOQoL‐8 question set), as well as willingness to pay (WTP) for adequate headache treatment, if it were available.ResultsMean lost paid‐work days due to headache in the previous 3 months were 1.9 ± 4.2, and mean lost household work days were 3.4 ± 5.7. The estimated annual indirect cost of primary headache disorders was USD 22.8 billion, accounting for 1.75% of gross domestic product. QoL was reduced by all types of primary headaches. According to WHOQoL‐8, it was significantly lower in those with headache on ≥15 days/month than in those with episodic headache (24.7 ± 4.6 vs. 28.1 ± 5.0; P < 0.05) and lower in those with migraine than in those with tension‐type headache (TTH) (27.1 ± 4.9 vs. 28.8 ± 5.0; P < 0.05). Average WTP for adequate headache treatment was RUB 455 ± 494 per month (median RUB 300), a sum sufficient in most cases, and correlated with illness severity (higher for headache on ≥15 days/month than for migraine, and for migraine than for TTH).ConclusionsHeadache is common, burdensome and costly in Russia and, manifestly, poorly mitigated by existing healthcare. Structured healthcare services for headache need to be urgently put in place.
Congenital hypothyroidism and dysmaturity syndrome in foals: First reported cases inEurope
Authors: Koikkalainen K. , Knuuttila A. , Karikoski N. , Syrjä P. , Hewetson M. 
Published: February 2014

SummaryCongenital hypothyroidism and dysmaturity syndrome (CHD) in neonatal foals was first described in westernCanada in 1981 and remains an important problem for the westernCanadian horse industry. This syndrome is characterised by hyperplasia of the thyroid gland, increased gestational length and multiple congenital musculoskeletal abnormalities. This case series describes the first confirmed cases ofCHDinEurope and challenges contemporary opinion which suggests that this syndrome is distinct from congenital hypothyroidism associated with visible goitre.
Structure, diversity and evolution of myriapod hemocyanins
Authors: Pick Christian , Scherbaum Samantha , Hegedüs Elöd , Meyer Andreas , Saur Michael , Neumann Ruben , Markl Jürgen , Burmester Thorsten 
Published: February 2014

Oxygen transport in the hemolymph of many arthropods is mediated by hemocyanins, large copper‐containing proteins that are well‐studied in Chelicerata and Crustacea, but had long been considered unnecessary in the subphylum of Myriapoda. Only recently has it become evident that hemocyanins are present in Scutigeromorpha (Chilopoda) and Spirostreptida (Diplopoda). Here we present evidence for a more widespread occurrence of hemocyanin in the myriapods. By means of RT‐PCR, western blotting and database searches, hemocyanins were identified in the symphylansHanseniella audaxandSymphylella vulgaris, the chilopodScolopendra subspinipes dehaaniand the diplopodPolydesmus angustus. No hemocyanins were found in the diplopodsPolyxenus lagurus,Cylindroiulus punctatus,Glomeris marginata,Glomeris pustulataandArthrosphaera brandtii, or the chilopodsLithobius forficatus,Geophilus flavusandStrigamia maritima. This suggests multiple independent losses in myriapod taxa. Two independent hemocyanin subunits were found that were already present in the myriapod stem line. We specifically investigated the structure of the hemocyanin ofP. angustus, which consists of three distinct subunits that occur in an approximately equimolar ratio. As deduced by 3D electron microscopy, the quaternary structure is a 3 × 6‐mer that resembles the half structure of the 6 × 6‐mer hemocyanin fromScutigera coleoptrata. It was analyzed more closely by homology modeling of 1 × 6‐mers and their rigid‐body fitting to the electron density map of the 3 × 6‐mer. In addition, we obtained thecDNAsequence of a putative myriapod phenoloxidase. Phenoloxidases are related to the arthropod hemocyanins, but diverged before radiation of the arthropod subphyla.
Balance between climate change mitigation benefits and land use impacts of bioenergy: conservation implications for European birds
Authors: Meller Laura , Thuiller Wilfried , Pironon Samuel , Barbet‐Massin Morgane , Hof Andries , Cabeza Mar 
Published: February 2014

AbstractBoth climate change and habitat modification exert serious pressure on biodiversity. Although climate change mitigation has been identified as an important strategy for biodiversity conservation, bioenergy remains a controversial mitigation action due to its potential negative ecological and socio‐economic impacts which arise through habitat modification by land use change. While the debate continues, the separate or simultaneous impacts of both climate change and bioenergy on biodiversity have not yet been compared. We assess projected range shifts of 156 European bird species by 2050 under two alternative climate change trajectories: a baseline scenario, where the global mean temperature increases by 4 °C by the end of the century, and a 2 degrees scenario, where global concerted effort limits the temperature increase to below 2 °C. For the latter scenario, we also quantify the pressure exerted by increased cultivation of energy biomass as modelled byIMAGE2.4, an integrated land use model. The global bioenergy use in this scenario is in the lower end of the range of previously estimated sustainable potential. Under the assumptions of these scenarios, we find that the magnitude of range shifts due to climate change is far greater than the impact of land conversion to woody bioenergy plantations within the European Union, and that mitigation of climate change reduces the exposure experienced by species. However, we identified potential for local conservation conflict between priority areas for conservation and bioenergy production. These conflicts must be addressed by strict bioenergy sustainability criteria that acknowledge biodiversity conservation needs beyond existing protected areas and apply also to biomass imported from outside the European Union.
Poverty in Canada: Does Manufacturing Matter?
Authors: Deaton B. James , Hailu Getu , Zhou Xiaoye 
Published: February 2014

AbstractWe focus our research on this question: Does an expansion in the percentage of labour employed in the manufacturing sector lead to reductions in the poverty rate? While some research suggests that regional differences in the employment share of the manufacturing sector explain variation in poverty rates, we do not find empirical evidence of this poverty‐ameliorating effect in our regression analysis of Canadian Census Districts between the years 2001 and 2006.