bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advances in understanding the leukaemia microenvironment
Authors: Tabe Yoko , Konopleva Marina 
Published: January 2014

SummaryDynamic interactions between leukaemic cells and cells of the bone marrow are a feature of haematological malignancies. Two distinct microenvironmental niches in the bone marrow, the ‘osteoblastic (endosteal)’ and ‘vascular’ niches, provide a sanctuary for subpopulations of leukaemic cells to evade chemotherapy‐induced death and allow acquisition of drug resistance. Key components of the bone marrow microenvironment as a home for normal haematopoietic stem cells and the leukaemia stem cell niches, and the molecular pathways critical for microenvironment/leukaemia interactions via cytokines, chemokines and adhesion molecules as well as hypoxic conditions, are described in this review. Finally, the genetic abnormalities of leukaemia‐associated stroma are discussed. Further understanding of the contribution of the bone marrow niche to the process of leukaemogenesis may provide new targets that allow destruction of leukaemia stem cells without adversely affecting normal stem cell self‐renewal.
Effects of Novel Diarylpentanoid Analogues of Curcumin on Secretory Phospholipase A2, Cyclooxygenases, Lipo‐oxygenase, and Microsomal Prostaglandin E Synthase‐1
Authors: Ahmad Waqas , Kumolosasi Endang , Jantan Ibrahim , Bukhari Syed N. A. , Jasamai Malina 
Published: January 2014

Arachidonic acid and its metabolites have generated a heightened interest due to their significant role in inflammation. Inhibiting the enzymes involved in arachidonic acid metabolism has been considered as the synergistic anti‐inflammatory effect. A series of novel curcumin diarylpentanoid analogues were synthesized and evaluated for their inhibitory effects on activity of secretory phospholipase A2, cyclooxygenases, soybean lipo‐oxygenase as well as microsomal prostaglandin E synthase‐1. Among the curcumin analogues, compounds 3, 6, 9, 12, and 17 exhibited strong inhibition of secretory phospholipase A2 activity, with IC50 values ranging from 5.89 to 11.02 μm. Seven curcumin analogues 1, 3, 6, 7, 9, 11, and 12 showed inhibition of cyclooxygenases‐2 with IC50 values in the range of 46.11 to 94.86 μm, which were lower than that of curcumin. Compounds 3, 6, 7, 12, and 17 showed strong inhibition of lipo‐oxygenase enzyme activity. Preliminary screening of diarylpentanoid curcumin analogues for microsomal prostaglandin E synthase‐1 activity revealed that four diarylpentanoid curcumin analogues 5, 6, 7, and 13 demonstrated higher inhibition of microsomal prostaglandin E synthase‐1 activity with IC50 ranging from 2.41 to 4.48 μm, which was less than that of curcumin. The present results suggest that some of these diarylpentanoid analogues were able to inhibit the activity of these enzymes. This raises the possibility that diarylpentanoid analogues of curcumin might serve as useful starting point for the design of improved anti‐inflammatory agents.
Interactive effects of higher temperature and dissolved organic carbon on planktonic communities in fishless mountain lakes
Authors: Weidman Paul R. , Schindler David W. , Thompson Patrick L. , Vinebrooke Rolf D. 
Published: January 2014

Summary

We tested the hypothesis that higher temperature and dissolved organic carbon (DOC) concentration increase dissolved and particulate carbon (C) relative to phosphorus (P), thereby reducing algal food quality for P‐limited cladocerans while not affecting N‐limited copepods. Also, we expected alpine zooplankton to respond more strongly than those from warmer montane lakes to increased water temperature.

Plankton from two alpine lakes and two montane lakes were incubated in vitro for 30 days at 10 or 17 °C and with ambient or +80% DOC, which was achieved by concentrating humic substances from each lake via reverse osmosis.

Dissolved organic carbon amendments and warming significantly increase particulate C : P under montane, but not alpine conditions. While higher water temperature and DOC separately reduced phytoplankton abundance, together they increased phytoplankton by stimulating uptake of P. Warming stimulated only Daphnia while suppressing the abundance of the calanoid copepod Hesperodiaptomus when they originated from the three coldest lakes. Particulate C : P was positively correlated with Daphnia abundance and negatively correlated with Hesperodiaptomus, probably due to greater P‐retention by Daphnia.

Our findings highlight the importance of interactions between the ecological effects of higher temperature and increased inputs of terrestrial organic matter to forecasts of the net impact of global warming on mountain lakes. Such predictions may be confounded if they are derived solely from the expected sum of single effects by each climatic factor.
Estimation of the Change in Hydraulic Conductivity Above Mined Longwall Panels
Authors: Tammetta Paul 
Published: January 2014

AbstractThe change in hydraulic conductivity (K) above subsided longwall panels at underground coal mines is determined using a data base of pre‐mining and post‐mining K measurements made at multiple locations down the depth profile at each of a number of sites worldwide. Results show that, following caving of roof strata, there is a clear difference in the magnitude of changes in K above and below the top of the collapsed zone. Within the collapsed zone, relative increases in K are larger, even when taking account of measurements made in potentially unsaturated strata. A generalized conceptual model is presented for K change above subsided longwall panels. These results form a third independent database supporting the height of desaturation reported in an earlier study.
Incidence of group awareness information on students' collaborative learning processes
Authors: Pifarré M. , Cobos R. , Argelagós E. 
Published: January 2014

AbstractThis paper studies how the integration of group awareness tools in the knowledge management system called KnowCat (Knowledge Catalyser), which promotes collaborative knowledge construction, may both foster the students' perception about the meaningfulness of visualization of group awareness information and promote better collaborative processes as well as enhance better task performance. Forty‐seven university students participated in a research study, where one group of 23 students used KnowCat without the awareness console (non‐awareness group); the other 24 students used KnowCat with the awareness console (awareness group). Both groups used KnowCat during one semester. Data analysis revealed that the awareness group means were higher than those of the non‐awareness group in terms of participation, cognitive and metacognitive learning activities, and task performance. Moreover, students revealed that knowing what, where and how much their classmates were contributing acted as positive feedback by encouraging participation and orienting their own behaviour and their contribution to the collaborative work. In this paper, we claim that the visualization group awareness information in KnowCat, a utility allowing students to visualize and track what, where, how much and how often other participants contributed to the KnowCat knowledge area, had a positive impact on the students' collaborative behaviour.
Sex differences in activation of the hypothalamic–pituitary–adrenal axis by methamphetamine
Authors: Zuloaga Damian G. , Johnson Lance A. , Agam Maayan , Raber Jacob 
Published: January 2014

AbstractDysregulation of hypothalamic–pituitary–adrenal (HPA) axis activation is associated with changes in addiction‐related behaviors. In this study, we tested whether sex differences in the acute effects of methamphetamine (MA) exposure involve differential activation of the HPA axis. Male and female mice were injected with MA (1 mg/kg) or saline for comparison of plasma corticosterone and analysis of the immediate early gene c‐Fos in brain. There was a prolonged elevation in corticosterone levels in female compared to male mice. C‐Fos was elevated in both sexes following MA in HPA axis‐associated regions, including the hypothalamic paraventricular nucleus (PVN), central amygdala, cingulate, and CA3 hippocampal region. MA increased the number of c‐Fos and c‐Fos/glucocorticoid receptor (GR) dual‐labeled cells to a greater extent in males than females in the cingulate and CA3 regions. MA also increased the number of c‐fos/vasopressin dual‐labeled cells in the PVN as well as the number and percentage of c‐Fos/GR dual‐labeled cells in the PVN and central amygdala, although no sex differences in dual labeling were found in these regions. Thus, sex differences in MA‐induced plasma corticosterone levels and activation of distinct brain regions and proteins involved in HPA axis regulation may contribute to sex differences in acute effects of MA on the brain.
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Methamphetamine induces a prolonged plasma corticosterone response in females compared to males. This may be mediated by increased neural activation, involving a greater activation of glucocorticoid receptor‐positive cells, in males in the CA3 and cingulate brain regions, which are involved in negative feedback functions. These findings indicate a sex difference in the neural regulation of methamphetamine‐induced plasma corticosterone release.
Muscle Oxygenation Asymmetry in Ice Speed Skaters: Not Compensated by Compression
Authors: Born Dennis-Peter , Zinner Christoph , Herlitz Britta , Richter Katharina , Holmberg Hans-Christer , Sperlich Billy 
Published: January 2014

Purpose:The current investigation assessed tissue oxygenation and local blood volume in both vastus lateralis muscles during 3000-m race simulations in elite speed skaters on ice and the effects of leg compression on physiological, perceptual, and performance measures.Methods:Ten (6 female) elite ice speed skaters completed 2 on-ice trials with and without leg compression. Tissue oxygenation and local blood volume in both vastus lateralis muscles were assessed with near-infrared spectroscopy. Continuous measures of oxygen uptake, ventilation, heart rate, and velocity were conducted throughout the race simulations, as well as blood lactate concentration and ratings of perceived exertion before and after the trials. In addition, lap times were assessed.Results:The investigation of tissue oxygenation in both vastus lateralis muscles revealed an asymmetry (P < .00; effect size = 1.81) throughout the 3000-m race simulation. The application of leg compression did not affect oxygenation asymmetry (smallest P = .99; largest effect size = 0.31) or local blood volume (P = .33; 0.95). Lap times (P = .88; 0.43), velocity (P = .24; 0.84), oxygen uptake (P = .79; 0.10), ventilation (P = .11; 0.59), heart rate (P = .21; 0.89), blood lactate concentration (P = .82; 0.59), and ratings of perceived exertion (P = .19; 1.01) were also unaffected by the different types of clothing.Conclusion:Elite ice speed skaters show an asymmetry in tissue oxygenation of both vastus lateralis muscles during 3000-m events remaining during the long gliding phases along the straight sections of the track. Based on the data, the authors conclude that there are no performance-enhancing benefits from wearing leg compression under a normal racing suit.
Repeated-Sprint Ability and Team Selection in Australian Football League Players
Authors: Rossignol Peter Le , Gabbett Tim J. , Comerford Dan , Stanton Warren R. 
Published: January 2014

Purpose:To investigate the relationship between selected physical capacities and repeated-sprint performance of Australian Football League (AFL) players and to determine which physical capacities contributed to being selected for the first competition game.Methods:Sum of skinfolds, 40-m sprint (with 10-, 20-, 30-, and 40-m splits), repeated-sprint ability (6 × 30-m sprints), and 3-km-run time were measured during the preseason in 20 AFL players. The physical qualities of players selected to play the first match of the season and those not selected were compared. Pearson correlation coefficients were used to determine the relationship among variables, and a regression analysis identified variables significantly related to repeated-sprint performance.Results:In the regression analysis, maximum velocity was the best predictor of repeated-sprint time, with 3-km-run time also contributing significantly to the predictive model. Sum of skinfolds was significantly correlated with 10-m (r = .61, P < .01) and 30-m (r = .53, P < .05) sprint times. A 2.6% ± 2.1% difference in repeated-sprint time (P < .05, ES = 0.88 ± 0.72) was observed between those selected (25.26 ± 0.55 s) and not selected (25.82 ± 0.80 s) for the first game of the season.Conclusions:The findings indicate that maximum-velocity training using intervals of 30–40 m may contribute more to improving repeated-sprint performance in AFL players than short 10- to 20-m intervals from standing starts. Further research is warranted to establish the relative importance of endurance training for improving repeated-sprint performance in AFL football.
Thirty-Eight Years of Training Distribution in Olympic Speed Skaters
Authors: Orie Jac , Hofman Nico , de Koning Jos J. , Foster Carl 
Published: January 2014

During the last decade discussion about training-intensity distribution has been an important issue in sports science. Training-intensity distribution has not been adequately investigated in speed skating, a unique activity requiring both high power and high endurance.Purpose:To quantify the training-intensity distribution and training hours of successful Olympic speed skaters over 10 Olympiads.Methods:Olympic-medal-winning trainers/coaches and speed skaters were interviewed and their training programs were analyzed. Each program was qualified and quantified: workout type (specific and nonspecific) and training zones (zone 1 ≤2 mMol/L lactate, zone 2 2–4 mMol/L lactate, zone 3 lactate >4 mMol/L). Net training times were calculated.Results:The relation between total training hours and time (successive Olympiads) was not progressive (r = .51, P > .5). A strong positive linear relation (r = .96, P < .01) was found between training distribution in zone 1 and time. Zones 2 and 3 both showed a strong negative linear relation to time (r = –.94, P < .01; r = –.97, P < .01). No significant relation was found between speed skating hours and time (r = –.11, P > .05). This was also the case for inline skating and time (r = –.86, P > .05).Conclusions:These data indicate that in speed skating there was a shift toward polarized training over the last 38 y. This shift seems to be the most important factor in the development of Olympic speed skaters. Surprisingly there was no relation found between training hours, skating hours, and time.
Performance of a Redesigned HIV Selectest Enzyme-Linked Immunosorbent Assay Optimized To Minimize Vaccine-Induced Seropositivity in HIV Vaccine Trial Participants
Authors: Penezina Oksana , Krueger Neil X. , Rodriguez-Chavez Isaac R. , Busch Michael P. , Hural John , Kim Jerome H. , O'Connell Robert J. , Hunter Eric , Aboud Said , Higgins Keith , Kovalenko Victor , Clapham David , Crane David , Levin Andrew E. ,   the HIV Selectest Study Group
Published: January 2014

ABSTRACTVaccine-induced seropositivity (VISP) or seroreactivity (VISR), defined as the reaction of antibodies elicited by HIV vaccines with antigens used in HIV diagnostic immunoassays, can result in reactive assay results for vaccinated but uninfected individuals, with subsequent misclassification of their infection status. The eventual licensure of a vaccine will magnify this issue and calls for the development of mitigating solutions in advance. An immunoassay that discriminates between antibodies elicited by vaccine antigens and those elicited by infection has been developed to address this laboratory testing need. The HIV Selectest is based on consensus and clade-specific HIV peptides that are omitted in many HIV vaccine constructs. The assay was redesigned to enhance performance across worldwide clades and to simplify routine use via a standard kit format. The redesigned assay was evaluated with sera from vaccine trial participants, HIV-infected and uninfected individuals, and healthy controls. The HIV Selectest exhibited specificities of 99.5% with sera from uninfected recipients of 6 different HIV vaccines and 100% with sera from normal donors, while detecting HIV-1 infections, including intercurrent infections, with 95 to 100% sensitivity depending on the clade, with the highest sensitivities for clades A and C. HIV Selectest sensitivity decreased in very early seroconversion specimens, which possibly explains the slightly lower sensitivity observed for asymptomatic blood donors than for clinical HIV cases. Thus, the HIV Selectest provides a new laboratory tool for use in vaccine settings to distinguish the immune response to HIV vaccine antigens from that due to true infection.
Specific Residues of PB2 and PA Influenza Virus Polymerase Subunits Confer the Ability for RNA Polymerase II Degradation and Virus Pathogenicity in Mice
Authors: Llompart C. M. , Nieto A. , Rodriguez-Frandsen A. 
Published: January 2014

ABSTRACT

Influenza virus transcription requires functional coupling with cellular transcription for the cap-snatching process. Despite this fact, RNA polymerase II (RNAP II) is degraded during infection in a process triggered by the viral polymerase. Reassortant viruses from the A/PR/8/34 (PR8) strain that induce (hvPR8) or do not induce (lvPR8) RNAP II degradation led to the identification of PA and PB2 subunits as responsible for the degradation process. Three changes in the PB2 sequence (I105M, N456D, and I504V) and two in PA (Q193H and I550L) differentiate PA and PB2 of lvPR8 from those of hvPR8. Using recombinant viruses, we observed that changes at position 504 of PB2, together with 550 of PA, confer the ability on lvPR8 for RNAP II degradation and, conversely, abolish hvPR8 degradation capacity. Since hvPR8 is more pathogenic than lvPR8 in mice, we tested the potential contribution of RNAP II degradation in a distant viral strain, the 2009 pandemic A/California/04/09 (CAL) virus, whose PA and PB2 subunits are of avian origin. As in the hvPR8 virus, mutations at positions 504 of PB2 and 550 of PA in CAL virus abolished its RNAP II degradation capacity. Moreover, in an
in vivo
model, the CAL-infected mice lost more body weight, and 75% lethality was observed in this situation compared with 100% survival in mutant-CAL- or mock-infected animals. These results confirm the involvement of specific PB2 and PA residues in RNAP II degradation, which correlates with pathogenicity in mice of viruses containing human or avian polymerase PB2 and PA subunits.

IMPORTANCE
The influenza virus polymerase induces the degradation of RNAP II, which probably cooperates to avoid the antiviral response. Here, we have characterized two specific residues located in the PA and PB2 polymerase subunits that mediate this degradation in different influenza viruses. Moreover, a clear correlation between RNAP II degradation and
in vivo
pathogenicity in mice was observed, indicating that the degradative process constitutes a viral pathogenicity factor.
Amino Acid Substitutions in Polymerase Basic Protein 2 Gene Contribute to the Pathogenicity of the Novel A/H7N9 Influenza Virus in Mammalian Hosts
Authors: Mok Chris Ka Pun , Lee Horace Hok Yeung , Lestra Maxime , Nicholls John Malcolm , Chan Michael Chi Wai , Sia Sin Fun , Zhu Huachen , Poon Leo Lit Man , Guan Yi , Peiris Joseph Sriyal Malik 
Published: January 2014

ABSTRACT

A novel avian-origin influenza A/H7N9 virus emerged in 2013 to cause more than 130 cases of zoonotic human disease, with an overall case fatality rate of around 30% in cases detected. It has been shown that an E-to-K amino acid change at residue 627 of polymerase basic protein 2 (PB2) occurred frequently in the H7N9 isolates obtained from humans but not in viruses isolated from poultry. Although this mutation has been reported to confer increased mammalian pathogenicity in other avian influenza subtypes, it has not been experimentally investigated in the H7N9 virus. In this study, we determined the contribution of PB2-E627K in H7N9 virus to its pathogenicity in mammalian hosts. In addition, the compensatory role of the PB2 mutations T271A, Q591K, and D701N in H7N9 virus was investigated. We characterized the activity of polymerase complexes with these PB2 mutations and found that they enhance the polymerase activity in human 293T cells. The rescued mutants enhanced growth in mammalian cells
in vitro
. Mice infected with the H7N9 mutant containing the avian signature protein PB2-627E showed a marked decrease in disease severity (weight loss) and pathology compared to mice infected with the wild-type strain (PB2-627K) or other PB2 mutants. Also, mutants with PB2-627E showed lower virus replication and proinflammatory cytokine responses in the lungs of the virus-infected mice, which may contribute to pathogenicity. Our results suggest that these amino acid substitutions contribute to mouse pathogenicity and mammalian adaptation.

IMPORTANCE
A novel avian H7N9 influenza A virus emerged in east China in 2013 to cause zoonotic human disease associated with significant mortality. It is important to understand the viral genetic markers of mammalian adaptation and disease severity in this H7N9 virus. Since many human (but not avian) H7N9 virus isolates have an amino acid substitution at position E627K in the polymerase basic protein 2 (PB2) gene, we investigated the role of this and other functionally related mutations for polymerase activity
in vitro
, virus replication competence, and pathogenicity in the mouse model. We found that E627K and functionally related mutations are associated with increased polymerase activity, increased viral replication competence, and increased disease severity in mice.