bluuebunny/crossref_metadata_2025_split huggingface dataset:
Random aggregates in newly produced platelet units are associated with platelet activation and release of the immunomodulatory factors sCD40L and RANTES
Authors: Sandgren Per , Meinke Stephan , Eckert Elias , Douagi Iyadh , Wikman Agneta , Höglund Petter 
Published: July 2013

BackgroundIn connection with platelet (PLT) production, random but transient aggregates sometimes form in the newly produced units. The underlying mechanisms as well as the impact on cellular level of this phenomenon are unknown. Hypothetically, random occurrence of aggregates may induce biochemical changes leading to PLT activation and release of immunomodulatory factors from the PLTs.Study Design and MethodsPLTs were aliquoted and prepared with an automated system for PLT pooling (OrbiSac, Terumo BCT) for a three‐arm nonpaired study design (n = 8). Initially aggregated PLT units in SSP+ were selected by visual inspection and compared to unaffected PLT units stored in SSP+ or 100% plasma. Cellular, metabolic, and functional variables were analyzed, including the concentrations of RANTES, sCD40L, and sTWEAK in the bags during a 9‐day storage period.ResultsIsolated aggregated PLTs show signs of spontaneous activation and respond less efficiently to TRAP stimulation. RANTES, sCD40L, and sTWEAK accumulated in the various PLT units during storage but sCD40L and RANTES accumulated in the initially aggregated PLT units to higher concentrations than the reference units and PLTs stored in 100% plasma (p < 0.001). Over time, the levels of sTWEAK increased more in the plasma storage environment compared with PLT units stored in SSP+ (p < 0.001).ConclusionOur data indicate that random occurrence of aggregates may lead to higher activation level and increased release of immunomodulatory factors from the PLTs.
Plasma protein S residues 37–50 mediate its binding to factor Va and inhibition of blood coagulation
Authors: Mesters Rolf , Fernández José , Hackeng Tilman , Nakasone Ryon , Griffin John , Heeb Mary 
Published: July 2013

SummaryProtein S (PS) is an anticoagulant plasma protein whose deficiency is associated with increased risk of venous thrombosis. PS directly inhibits thrombin generation by the blood coagulation pathways by several mechanisms, including by binding coagulation factors (F) Va and Xa. To identify PS sequences that mediate inhibition of FVa activity, antibodies and synthetic peptides based on PS sequence were prepared and employed in plasma coagulation assays, purified component prothrombinase assays, binding assays, and immunoblots. In the absence of activated protein C, monoclonal antibody (Mab) S4 shortened FXa-induced clotting in normal plasma but not in PS-depleted plasma. Mab S4 also blocked PS inhibition of FVa-dependent prothrombinase activity in purified component assays in the absence or presence of phospholipids and inhibited binding of PS to immobilised FVa. Epitope mapping identified N-terminal region residues 37–67 of PS as this antibody’s epitope. A peptide representing PS residues 37–50 inhibited FVa-dependent prothrombinase activity in a noncompetitive manner, with 50% inhibition observed at 11 µM peptide, whereas a peptide with a D-amino acid sequence of 37–50 was ineffective. FVa, but not FXa, bound specifically to the immobilised peptide representing residues 37–50, and the peptide inhibited binding of FVa to immobilised PS. These data implicate PS residues 37–50 as a binding site for FVa that mediates, at least in part, the direct inhibition of FVa-dependent procoagulant activity by PS.
The Influence of Loop Current Position on Winter Sea Surface Temperatures in the Florida Straits
Authors: Rudzin Johna E. , Morey Steven L. , Bourassa Mark A. , Smith Shawn R. 
Published: July 2013

Abstract
Influences of the Gulf of Mexico's Loop Current (LC) position on the sea surface temperature (SST) in the Florida Straits (FS) during the winter season are investigated. Satellite-derived SST data are analyzed on the basis of the LC configuration (mature or immature) as determined by satellite altimetry analyses. Cumulative distributions of FS SSTs for both LC phases during the months of January and February show greater likelihood of cooler SSTs in the FS during a mature LC than during an immature LC. This work suggests that differing transit times of LC water parcels during mature and immature phases result in differences in heat loss of the LC near-surface water. This may contribute to the observed SST differences in FS during mature and immature LC phases via temperature advection.
CCN and Vertical Velocity Influences on Droplet Concentrations and Supersaturations in Clean and Polluted Stratus Clouds
Authors: Hudson James G. , Noble Stephen 
Published: July 2013

Abstract
Cloud microphysics and cloud condensation nuclei (CCN) measurements from two marine stratus cloud projects are presented and analyzed. Results show that the increase of cloud droplet concentrations Nc with CCN concentrations NCCN rolls off for NCCN at 1% supersaturation (S)N1% above 400 cm−3. Moreover, at such high concentrations Nc was not so well correlated with NCCN but tended to be more closely related to vertical velocity W or variations of W (σw). This changeover from predominate Nc dependence on NCCN to Nc dependence on W or σw is due to the higher slope k of CCN spectra at lower S, which is made more relevant by the lower cloud S that is forced by higher NCCN. Higher k makes greater influence of W or σw variations than NCCN variations on Nc. This changeover at high NCCN thus seems to limit the indirect aerosol effect (IAE).
On the other hand, in clean-air stratus cloud S often exceeded 1% and decreased to slightly less than 0.1% in polluted conditions. This means that smaller CCN [those with higher critical S (Sc)], which are generally more numerous than larger CCN (lower Sc), are capable of producing stratus cloud droplets, especially when they are advected into clean marine air masses where they can induce IAE. Positive correlations between turbulence σw and NCCN are attributed to greater differential latent heat exchange of smaller more numerous cloud droplets that evaporate more readily. Such apparent CCN influences on cloud dynamics tend to support trends that oppose conventional IAE, that is, less rather than greater cloudiness in polluted environments.
The ENSO-Related West Pacific Sea Surface Temperature Gradient
Authors: Hoell Andrew , Funk Chris 
Published: July 2013

El Niño–Southern Oscillation (ENSO) events are accompanied by an anomalous zonal sea surface temperature (SST) gradient over the west Pacific Ocean, defined here as the west Pacific SST gradient (WPG). The WPG is defined as the standardized difference between area-averaged SST over the central Pacific Ocean (Niño-4 region) and west Pacific Ocean (0°–10°N, 130°–150°E). While the direction of the WPG follows ENSO cycles, the magnitude of the gradient varies considerably between individual El Niño and La Niña events. In this study, El Niño and La Niña events are grouped according to the magnitude of the WPG, and tropical SST, circulations, and precipitation are examined for the period 1948–2011. Until the 1980s the WPG showed little trend as the west and central Pacific warmed at similar rates; however, the west Pacific has recently warmed faster than the central Pacific, which has resulted in an increased WPG during La Niña events.The temporal evolution and distribution of tropical Pacific SST as well as the near-surface tropical Pacific zonal wind, divergence, and vertical velocity are considerably different during ENSO events partitioned according to the strength of the WPG. Modifications to the tropical circulation, resulting in changes to Indo– west Pacific precipitation, are linked to strong and consistent circulation and precipitation modifications throughout the Northern Hemisphere during winter.
Eddy-Induced Modulation of Turbulent Dissipation over Rough Topography in the Southern Ocean
Authors: Brearley J. Alexander , Sheen Katy L. , Naveira Garabato Alberto C. , Smeed David A. , Waterman Stephanie 
Published: July 2013

Abstract
Mesoscale eddies are universal features of the ocean circulation, yet the processes by which their energy is dissipated remain poorly understood. One hypothesis argues that the interaction of strong geostrophic flows with rough bottom topography effects an energy transfer between eddies and internal waves, with the breaking of these waves causing locally elevated dissipation focused near the sea floor. This study uses hydrographic and velocity data from a 1-yr mooring cluster deployment in the Southern Ocean to test this hypothesis. The moorings were located over a small (~10 km) topographic obstacle to the east of Drake Passage in a region of high eddy kinetic energy, and one was equipped with an ADCP at 2800-m depth from which internal wave shear variance and dissipation rates were calculated. Examination of the ADCP time series revealed a predominance of upward-propagating internal wave energy and a significant correlation (r = 0.45) between shear variance levels and subinertial near-bottom current speeds. Periods of strong near-bottom flow coincided with increased convergence of eddy-induced interfacial form stress in the bottom 1500 m. Predictions of internal wave energy radiation were made from theory using measured near-bottom current speeds, and the mean value of wave radiation (5.3 mW m−2) was sufficient to support the dissipated power calculated from the ADCP. A significant temporal correlation was also observed between radiated and dissipated power. Given the ubiquity of strong eddy flows and rough topography in the Southern Ocean, the transfer from eddy to internal wave energy is likely to be an important term in closing the ocean energy budget.
Development of a self-replicating plasmid system for Mycoplasma hyopneumoniae
Authors: Maglennon Gareth A , Cook Beth S , Matthews Dominic , Deeney Alannah S , Bossé Janine T , Langford Paul R , Maskell Duncan J , Tucker Alexander W , Wren Brendan W , Rycroft Andrew N ,   BRaDP1T consortium
Published: July 2013

Abstract

Mycoplasma hyopneumoniae is a prevalent swine respiratory pathogen that is a major cause of economic loss to pig producers. Control is achieved by a combination of antimicrobials, vaccination and management practices, but current vaccines offer only partial control and there is a need for improved preventative strategies. A major barrier to advances in understanding the pathogenesis of M. hyopneumoniae and in developing new vaccines is the lack of tools to genetically manipulate the organism. We describe the development and optimisation of the first successful plasmid-based system for the genetic manipulation of M. hyopneumoniae. Our artificial plasmids contain the origin of replication (oriC) of M. hyopneumoniae along with tetM, conferring resistance to tetracycline. With these plasmids, we have successfully transformed M. hyopneumoniae strain 232 by electroporation, generating tetracycline resistant organisms. The persistence of extrachromosomal plasmid and maintenance of plasmid DNA over serial passages shows that these artificial plasmids are capable of self-replication in M. hyopneumoniae. In addition to demonstrating the amenability of M. hyopneumoniae to genetic manipulation and in optimising the conditions necessary for successful transformation, we have used this system to determine the minimum functional oriC of M. hyopneumoniae. In doing so, we have developed a plasmid with a small oriC that is stably maintained over multiple passages that may be useful in generating targeted gene disruptions. In conclusion, we have generated a set of plasmids that will be valuable in studies of M. hyopneumoniae pathogenesis and provide a major step forward in the study of this important swine pathogen.
Small ruminant lentivirus genetic subgroups associate with sheep TMEM154 genotypes
Authors: Sider Lucia H , Heaton Michael P , Chitko-McKown Carol G , Harhay Greg P , Smith Timothy PL , Leymaster Kreg A , Laegreid William W , Clawson Michael L 
Published: July 2013

Abstract
Small ruminant lentiviruses (SRLVs) are prevalent in North American sheep and a major cause of production losses for the U.S. sheep industry. Sheep susceptibility to SRLV infection is influenced by genetic variation within the ovine transmembrane 154 gene (TMEM154). Animals with either of two distinct TMEM154 haplotypes that both encode glutamate at position 35 of the protein (E35) are at greater risk of SRLV infection than those homozygous with a lysine (K35) haplotype. Prior to this study, it was unknown if TMEM154 associations with infection are influenced by SRLV genetic subgroups. Accordingly, our goals were to characterize SRLVs naturally infecting sheep from a diverse U.S. Midwestern flock and test them for associations with TMEM154 E35K genotypes. Two regions of the SRLV genome were targeted for proviral amplification, cloning, sequence analysis, and association testing with TMEM154 E35K genotypes: gag and the transmembrane region of env. Independent analyses of gag and env sequences showed that they clustered in two subgroups (1 and 2), they were distinct from SRLV subtypes originating from Europe, and that subgroup 1 associated with hemizygous and homozygous TMEM154 K35 genotypes and subgroup 2 with hemi- and homozygous E35 genotypes (gag p < 0.001, env p = 0.01). These results indicate that SRLVs in the U.S. have adapted to infect sheep with specific TMEM154 E35K genotypes. Consequently, both host and SRLV genotypes affect the relative risk of SRLV infection in sheep.
Incidence and outcome of newly-diagnosed tuberculosis in schizophrenics: a 12-year, nationwide, retrospective longitudinal study
Authors: Kuo Shu-Chen , Chen Yung-Tai , Li Szu-Yuan , Lee Yi-Tzu , Yang Albert C , Chen Te-Li , Liu Chia-Jen , Chen Tzeng-Ji , Su Ih-Jen , Fung Chang-Phone 
Published: July 2013

Abstract

Background
To control tuberculosis (TB), it is critical to identify at risk populations. Schizophrenia is recognized as an important risk factor for TB. However, previous studies have been confounded by comorbidities, and reports of TB infection outcomes are rare. Therefore, the current nation-wide study aimed to compare the adjusted incidence and outcome of TB diseases in schizophrenics and the general population.

Method
Using the National Health Insurance Research Database from 1998 to 2009, this retrospective longitudinal study included 60,409 schizophrenics and general population matched for age, Charlson’s score, and comorbidities. Diagnosis of TB was based on the international classification of disease, ninth revision and use of anti-TB drugs. Unfavorable outcome for TB was defined as death, loss to follow-up, or use of anti-TB treatment for more than 9 months.

Results
The adjusted incidence of TB in schizophrenics was significantly higher than in the general population [hazard ratio, 1.52; 95% confidence interval (CI), 1.29-1.79; p < 0.001; Kaplan-Meier log-rank test, p < 0.001]. Cox regression revealed age and male gender as risk factors for newly-diagnosed TB. The outcome of TB was comparable in schizophrenics and the general population [odds ratio (OR), 0.78; 95% CI, 0.55-1.09; p =0.144]. Logistic regression revealed a statistical trend for diabetes mellitus to predict poor outcome in schizophrenics with TB (OR, 2.30; 95% CI, 0.96-5.74; p = 0.062).

Conclusions
Schizophrenics are at increased risk for TB, and screening may be warranted for those living in areas with high prevalence of TB.
Schedule-dependent antitumor effects of 5-fluorouracil combined with sorafenib in hepatocellular carcinoma
Authors: Deng Lifen , Ren Zhenggang , Jia Qingan , Wu Weizhong , Shen Hujia , Wang Yanhong 
Published: July 2013

Abstract

Background
Recently, a phase II clinical trial in hepatocellular carcinoma (HCC) has suggested that the combination of sorafenib and 5-fluorouracil (5-FU) is feasible and side effects are manageable. However, preclinical experimental data explaining the interaction mechanism(s) are lacking. Our objective is to investigate the anticancer efficacy and mechanism of combined sorafenib and 5-FU therapy in vitro in HCC cell lines MHCC97H and SMMC-7721.

Methods
Drug effects on cell proliferation were evaluated by cell viability assays. Combined-effects analyses were conducted according to the median-effect principle. Cell cycle distribution was measured by flow cytometry. Expression levels of proteins related to the RAF/MEK/ERK and STAT3 pathways and to cell cycle progression (cyclin D1) were determined by western blot analysis.

Results
Sorafenib and 5-FU alone or in combination showed significant efficacy in inhibiting cell proliferation in both cell lines tested. However, a schedule-dependent combined effect, associated with the order of compound treatments, was observed. Efficacy was synergistic with 5-FU pretreatment followed by sorafenib, but it was antagonistic with the reverse treatment order. Sorafenib pretreatment resulted in a significant increase in the half inhibitory concentration (IC50) of 5-FU in both cell lines. Sorafenib induced G1-phase arrest and significantly decreased the proportion of cells in S phase when administrated alone or followed by 5-FU. The RAF/MEK/ERK and STAT3 pathways were blocked and cyclin D1 expression was down regulated significantly in both cell lines by sorafenib; whereas, the kinase pathways were hardly affected by 5-FU, and cyclin D1 expression was up regulated.

Conclusions
Antitumor activity of sorafenib and 5-FU, alone or in combination, is seen in HCC cell lines. The nature of the combined effects, however, depends on the particular cell line and treatment order of the two compounds. Sorafenib appears to reduce sensitivity to 5-FU through down regulation of cyclin D1 expression by inhibiting RAF/MEK/ERK and STAT3 signaling, resulting in G1-phase arrest and reduction of the S-phase cell subpopulation when 5-FU is administrated after sorafenib, in which situation, combination treatment of the two agents results in antagonism; on the other hand, when sorafenib is administrated afterward, it can continue to work since it is not cell cycle specific, as a result, combination treatment of the two agents shows an additive-to-synergistic effect.
The association between self-reported lack of sleep, low vitality and impaired glucose tolerance: a Swedish cross-sectional study
Authors: Andersson Susanne , Ekman Inger , Friberg Febe , Bøg-Hansen Erik , Lindblad Ulf 
Published: July 2013

Abstract

Background
The increased incidence of impaired glucose tolerance (IGT), are serious public health issues, and several studies link sleeping disorders with increased risk of developing type 2 diabetes, impaired glucose tolerance and insulin resistance (IR). This study explore how self-reported lack of sleep and low vitality, are associated with IGT in a representative Swedish population.

Methods
A cross-sectional survey conducted in two municipalities in South-western Sweden. Participants aged 30–75 were randomly selected from the population in strata by sex and age. Altogether, 2,816 participants were surveyed with a participation rates at 76%. Participants with normal glucose tolerance (n=2,314), and those with IGT (n=213) were retained for analyses. The participants answered a questionnaire before the oral glucose tolerance test (OGTT). Associations for questions concerning sleeping disorders, vitality and IGT were analysed using logistic regression and were expressed as odds ratios (OR) with 95% CI.

Results
In men a statistically significant age-adjusted association was found between self-reported lack of sleep and IGT: OR 2.4 (95% CI: 1.1-5.4). It did not weaken after further adjustment for body mass index (BMI), smoking, education, and leisure time physical activity 2.3 (1.0-5.5, p=0.044). No such associations were found in females. Corresponding age-adjusted associations between low vitality and IGT in both men 2.8 (1.3-5.8), and women 2.0 (1.2-3.4) were successively lost with increasing adjustment.

Conclusions
Insufficient sleep seems independently associated with IGT in men, while low vitality was not independently associated with IGT neither in men nor women, when multiple confounders are considered. IGT should be considered in patients presenting these symptoms, and underlying mechanisms further explored.
Childhood infections, but not early life growth, influence hearing in the Newcastle thousand families birth cohort at age 14 years
Authors: Pearson Fiona , Mann Kay D , Nedellec Raphael , Rees Adrian , Pearce Mark S 
Published: July 2013

AbstractBackgroundWhile current research priorities include investigations of age-related hearing loss, there are concerns regarding effects on childhood hearing, for example through increased personal headphone use. By utilising historical data, it is possible to assess what factors may have increased hearing problems in children in the past, and this may be used to inform current public health policies to protect children against hearing loss and in turn reduce the long-term burden on individuals and services that may possible evolve. The aim of this study was to investigate which factors in early life significantly impacted on hearing level in childhood using existing data from the Newcastle Thousand Families Study, a 1947 birth cohort.MethodsData on early life factors, including growth, socio-economic status and illness, and hearing at age 14 years were collated for a representative subset of individuals from the cohort (n = 147). Factors were assessed using linear regression analysis to identify associations with hearing thresholds.ResultsMales were found to have lower hearing thresholds at 250 Hz, 500 Hz and 1 kHz. Main analyses showed no associations between hearing thresholds and early life growth or socio-economic indicators. An increasing number of ear infections from birth to age 13 years was associated with hearing thresholds at 250Hz (p = 0.04) and 500Hz (p = 0.03), which remained true for females (p = 0.050), but not males (p = 0.213) in sex-specific analysis. Scarlet fever and bronchitis were associated with hearing thresholds at 8 kHz. After adjustment for all significant predictors at each frequency, results remained unchanged.ConclusionsWe found no associations between childhood hearing thresholds and early life growth and socio-economic status. Consistent with other studies, we found associations between childhood infections and hearing thresholds. Current public health strategies aimed at reducing childhood infections may also have a beneficial effect upon childhood hearing.