bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cadence selection affects metabolic responses during cycling and subsequent running time to fatigue
Authors: Vercruyssen F , Suriano R , Bishop D , Hausswirth C , Brisswalter J 
Published: April 2005

Objectives:To investigate the effect of cadence selection during the final minutes of cycling on metabolic responses, stride pattern, and subsequent running time to fatigue.Methods:Eight triathletes performed, in a laboratory setting, two incremental tests (running and cycling) to determine peak oxygen uptake (Vo2peak) and the lactate threshold (LT), and three cycle-run combinations. During the cycle-run sessions, subjects completed a 30 minute cycling bout (90% of LT) at (a) the freely chosen cadence (FCC, 94 (5) rpm), (b) the FCC during the first 20 minutes and FCC−20% during the last 10 minutes (FCC−20%, 74 (3) rpm), or (c) the FCC during the first 20 minutes and FCC+20% during the last 10 minutes (FCC+20%, 109 (5) rpm). After each cycling bout, running time to fatigue (Tmax) was determined at 85% of maximal velocity.Results:A significant increase in Tmaxwas found after FCC−20% (894 (199) seconds) compared with FCC and FCC+20% (651 (212) and 624 (214) seconds respectively). Vo2, ventilation, heart rate, and blood lactate concentrations were significantly reduced after 30 minutes of cycling at FCC−20% compared with FCC+20%. A significant increase in Vo2was reported between the 3rd and 10th minute of all Tmaxsessions, without any significant differences between sessions. Stride pattern and metabolic variables were not significantly different between Tmaxsessions.Conclusions:The increase in Tmaxafter FCC−20% may be associated with the lower metabolic load during the final minutes of cycling compared with the other sessions. However, the lack of significant differences in metabolic responses and stride pattern between the run sessions suggests that other mechanisms, such as changes in muscular activity, probably contribute to the effects of cadence variation on Tmax.
Physiological adaptations to soccer specific endurance training in professional youth soccer players
Authors: McMillan K , Helgerud J , Macdonald R , Hoff J 
Published: April 2005

Background:Improved oxygen uptake improves soccer performance as regards distance covered, involvements with the ball, and number of sprints. Large improvements in oxygen uptake have been shown using interval running. A similar physiological load arising from interval running could be obtained using the soccer ball in training.Objectives:The main aim was to study physiological adaptations to a 10 week high intensity aerobic interval training program performed by professional youth soccer players, using a soccer specific ball dribbling track.Methods:Eleven youth soccer players with a mean (SD) age of 16.9 (0.4) years performed high intensity aerobic interval training sessions twice per week for 10 weeks in addition to normal soccer training. The specific aerobic training consisted of four sets of 4 min work periods dribbling a soccer ball around a specially designed track at 90–95% of maximal heart frequency, with a 3 min recovery jog at 70% of maximal heart frequency between intervals.Results:Mean Vo2maximproved significantly from 63.4 (5.6) to 69.8 (6.6) ml kg−1min−1, or 183.3 (13.2) to 201.5 (16.2) ml kg−0.75min−1(p<0.001). Squat jump and counter movement jump height increased significantly from 37.7 (6.2) to 40.3 (6.1) cm and 52.0 (4.0) to 53.4 (4.2) cm, respectively (p<0.05). No significant changes in body mass, running economy, rate of force development, or 10 m sprint times occurred.Conclusion:Performing high intensity 4 min intervals dribbling a soccer ball around a specially designed track together with regular soccer training is effective for improving the Vo2maxof soccer players, with no negative interference effects on strength, jumping ability, and sprinting performance.
Reliability and validity of a brief physical activity assessment for use by family doctors
Authors: Marshall A L , Smith B J , Bauman A E , Kaur S 
Published: April 2005

Objective:To evaluate the reliability and validity of a brief physical activity assessment tool suitable for doctors to use to identify inactive patients in the primary care setting.Methods:Volunteer family doctors (n  =  8) screened consenting patients (n  =  75) for physical activity participation using a brief physical activity assessment tool. Inter-rater reliability was assessed within one week (n  =  71). Validity was assessed against an objective physical activity monitor (computer science and applications accelerometer; n  =  42).Results:The brief physical activity assessment tool produced repeatable estimates of “sufficient total physical activity”, correctly classifying over 76% of cases (κ 0.53, 95% confidence interval (CI) 0.33 to 0.72). The validity coefficient was reasonable (κ 0.40, 95% CI 0.12 to 0.69), with good percentage agreement (71%).Conclusions:The brief physical activity assessment tool is a reliable instrument, with validity similar to that of more detailed self report measures of physical activity. It is a tool that can be used efficiently in routine primary healthcare services to identify insufficiently active patients who may need physical activity advice.
High strain mechanical loading rapidly induces tendon apoptosis: an ex vivo rat tibialis anterior model
Authors: Scott A , Khan K M , Heer J , Cook J L , Lian O , Duronio V 
Published: April 2005

Background:The role of apoptosis, or programmed cell death, has only recently been explored in tendon.Objective:To investigate the development of apoptosis after high strain loading of rat tendon.Methods:The right tibialis anterior tendons of three rats were prepared for mechanical loading, and left tendons were prepared identically as non-loaded controls. Tendon was loaded with 20% strain for six hours using a 1 Hz longitudinal sine wave signal. The following were used to assess apoptosis: (a) a monoclonal mouse antibody (F7-26) to label single stranded DNA breaks; (b) a rabbit polyclonal antibody that specifically recognises the cleaved form of caspase-3.Results:Light microscopy confirmed that the high strain protocol induced a stretch overload injury. Control tendons showed little or no staining with the F7-26 antibody, but the loaded tendons displayed numerous apoptotic cells. The percentage of apoptotic cells (20%) in the loaded tendon was significantly greater than in the control tendon (1%) (p  =  0.000). The labelled cells colocalised with abnormal nuclear morphology, including nuclear fragmentation. The staining against cleaved caspase-3 was positive in loaded tendons only, and localised both to nucleus and cytoplasm.Conclusion:This experiment extends knowledge of human tendon apoptosis by showing that apoptosis can occur in response to short term, high strain mechanical loading. This is the first report of mechanical loading of intact tendon causing excessive apoptosis.
Impaired IL-4 and c-Maf expression and enhanced Th1-cell development in Vav1-deficient mice
Authors: Tanaka Yoshihiko , So Takanori , Lebedeva Svetlana , Croft Michael , Altman Amnon 
Published: April 2005

AbstractAlthough c-Maf is crucial for Th2 differentiation and production of interleukin 4 (IL-4), its regulation is poorly understood. We report that Vav1–/– CD4+ T cells display deficient T-cell receptor (TCR)/CD28-induced IL-4 and c-Maf expression and, conversely, enhanced interferon γ (IFN-γ) production and T-bet expression (even when cultured under Th2-polarizing conditions), but intact expression of other Th2 cytokines and GATA-3. Up-regulation of c-Maf was dependent on Ca2+/nuclear factor of activated T cell (NFAT) and, together with IL-4 production, could be rescued in Vav1–/– T cells by Ca2+ ionophore. Deficient IL-4 production was restored by retrovirus-mediated Vav1 expression, but only partially by retroviral c-Maf expression. Similar IL-4 → IFN-γ skewing was observed in intact, antigen-primed Vav1–/– mice. Thus, Vav1 is selectively required for IL-4 and c-Maf expression, a requirement reflecting, at least in part, the dependence of c-Maf expression on Ca2+/NFAT signaling.
PEP005, a selective small-molecule activator of protein kinase C, has potent antileukemic activity mediated via the delta isoform of PKC
Authors: Hampson Peter , Chahal Hema , Khanim Farhat , Hayden Rachel , Mulder Anneke , Assi Lakhvir Kaur , Bunce Christopher M. , Lord Janet M. 
Published: April 2005

AbstractIngenol 3-angelate (PEP005) is a selective small molecule activator of protein kinase C (PKC) extracted from the plant Euphorbia peplus, whose sap has been used as a traditional medicine for the treatment of skin conditions including warts and cancer. We report here that PEP005 also has potent antileukemic effects, inducing apoptosis in myeloid leukemia cell lines and primary acute myeloid leukemia (AML) cells at nanomolar concentrations. Of importance, PEP005 did not induce apoptosis in normal CD34+ cord blood myeloblasts at up to 2-log concentrations higher than those required to induce cell death in primary AML cells. The effects of PEP005 were PKC dependent, and PEP005 efficacy correlated with expression of PKC-delta. The delta isoform of PKC plays a key role in apoptosis and is therefore a rational potential target for antileukemic therapies. Transfection of KG1a leukemia cells, which did not express PKC-delta or respond to PEP005, with enhanced green fluorescent protein (EGFP)-PKC-delta restored sensitivity to induction of apoptosis by PEP005. Our data therefore suggest that activation of PKC-delta provides a novel approach for treatment of acute myeloid leukemia and that screening for PKC-delta expression may identify patients for potential responsiveness to PEP005. (Blood. 2005;106:1362-1368)
Osteopontin, a key component of the hematopoietic stem cell niche and regulator of primitive hematopoietic progenitor cells
Authors: Nilsson Susan K. , Johnston Hayley M. , Whitty Genevieve A. , Williams Brenda , Webb Ryan J. , Denhardt David T. , Bertoncello Ivan , Bendall Linda J. , Simmons Paul J. , Haylock David N. 
Published: April 2005

AbstractAlthough recent data suggests that osteoblasts play a key role within the hematopoietic stem cell (HSC) niche, the mechanisms underpinning this remain to be fully defined. The studies described herein examine the role in hematopoiesis of Osteopontin (Opn), a multidomain, phosphorylated glycoprotein, synthesized by osteoblasts, with well-described roles in cell adhesion, inflammatory responses, angiogenesis, and tumor metastasis. We demonstrate a previously unrecognized critical role for Opn in regulation of the physical location and proliferation of HSCs. Within marrow, Opn expression is restricted to the endosteal bone surface and contributes to HSC transmarrow migration toward the endosteal region, as demonstrated by the markedly aberrant distribution of HSCs in Opn–/– mice after transplantation. Primitive hematopoietic cells demonstrate specific adhesion to Opn in vitro via β1 integrin. Furthermore, exogenous Opn potently suppresses the proliferation of primitive HPCs in vitro, the physiologic relevance of which is demonstrated by the markedly enhanced cycling of HSC in Opn–/– mice. These data therefore provide strong evidence that Opn is an important component of the HSC niche which participates in HSC location and as a physiologic-negative regulator of HSC proliferation.
PF4/heparin complexes are T cell–dependent antigens
Authors: Suvarna Shayela , Rauova Lubica , McCracken Emily K. E. , Goss Christina M. , Sachais Bruce S. , McKenzie Steven E. , Reilly Michael P. , Gunn Michael Dee , Cines Douglas B. , Poncz Mortimer , Arepally Gowthami 
Published: April 2005

Abstract
Heparin-induced thrombocytopenia (HIT) is a life-threatening, thrombotic disorder associated with development of anti–platelet factor 4 (anti-PF4)/heparin autoantibodies. Little is known about the antigenic and cellular requirements that initiate the immune response to these complexes. To begin to delineate mechanisms of autoantibody formation in HIT, we studied the immunizing effects of murine PF4 (mPF4)/heparin in mice with and without thymic function. Euthymic mice were injected with mPF4/heparin complexes, mPF4, heparin, or buffer. Mice injected with mPF4/heparin, but not mPF4 or heparin alone, developed heparin-dependent autoantibodies that shared serologic and functional characteristics of human HIT antibodies, including preferential binding to mPF4/heparin complexes and causing heparin- and FcRγIIA-dependent platelet activation. In contrast, athymic mice did not develop HIT-like antibodies. Taken together, these studies establish that PF4/heparin complexes are highly immunogenic and elicit self-reacting anti-PF4/heparin antibodies in a T cell–dependent manner.
Direct recognition and lysis of leukemia cells by WT1-specific CD4+ T lymphocytes in an HLA class II-restricted manner
Authors: Guo Yun , Niiya Hironari , Azuma Taichi , Uchida Naoyuki , Yakushijin Yoshihiro , Sakai Ikuya , Hato Takaaki , Takahashi Masuhiro , Senju Satoru , Nishimura Yasuharu , Yasukawa Masaki 
Published: April 2005

AbstractWilms tumor gene 1 product (WT1) has been recognized as an attractive target antigen of immunotherapy for various malignancies including leukemia. Because tumor-associated antigen-specific CD4+ T lymphocytes undoubtedly play an important role in the induction of an antitumor immune response, we attempted to generate WT1-specific CD4+ T lymphocytes in vitro and examined their antileukemia functions. A CD4+ T-cell line, designated NIK-1, which proliferated and produced Th1 cytokines specifically in response to stimulation with the WT1-derived peptide, WT1337-347 LSHLQMHSRKH, in an HLA-DP5-restriced manner was established. NIK-1 exhibited cytotoxicity against HLA-DP5-positive, WT1-expressing leukemia cells but did not lyse HLA-DP5-negative, WT1-expressing leukemia cells or HLA-DP5-positive, WT1-negative cells. NIK-1 did not inhibit colony formation by normal bone marrow cells of HLA-DP5-positive individuals. This is the first report to describe WT1-specific and HLA class II-restricted CD4+ T lymphocytes possessing direct cytotoxic activity against leukemia cells. (Blood. 2005;106: 1415-1418)
Oligoclonal expansion of T lymphocytes with multiple second-site mutations leads to Omenn syndrome in a patient with RAG1-deficient severe combined immunodeficiency
Authors: Wada Taizo , Toma Tomoko , Okamoto Hiroyuki , Kasahara Yoshihito , Koizumi Shoichi , Agematsu Kazunaga , Kimura Hirokazu , Shimada Akira , Hayashi Yasuhide , Kato Masahiko , Yachie Akihiro 
Published: April 2005

AbstractOmenn syndrome (OS) is a rare primary immunodeficiency characterized by the presence of activated/oligoclonal T cells, eosinophilia, and the absence of circulating B cells. OS patients carry leaky mutations of recombination activating genes (RAG1 or RAG2) resulting in partial V(D)J recombination activity, whereas null mutations cause severe combined immunodeficiency with absence of mature T and B cells (T-B- SCID). Here we describe somatic mosaicism due to multiple second-site mutations in a patient with RAG1 deficiency. We found that he is homozygous for a single base deletion in the RAG1 gene, which results in frameshift and likely abrogates the protein function. However, the patient showed typical OS features. Molecular analysis revealed that several second-site mutations, all of which restored the RAG1 reading frame and resulted in missense mutations, were demonstrated in his T cells. These findings suggest that his revertant T-cell mosaicism is responsible for OS phenotype switched from T-B- SCID. (Blood. 2005; 106:2099-2101)
Using co-occurrence network structure to extract synonymous gene and protein names from MEDLINE abstracts
Authors: Cohen AM , Hersh WR , Dubay C , Spackman K 
Published: April 2005

Abstract
Background
Text-mining can assist biomedical researchers in reducing information overload by extracting useful knowledge from large collections of text. We developed a novel text-mining method based on analyzing the network structure created by symbol co-occurrences as a way to extend the capabilities of knowledge extraction. The method was applied to the task of automatic gene and protein name synonym extraction.

Results
Performance was measured on a test set consisting of about 50,000 abstracts from one year of MEDLINE. Synonyms retrieved from curated genomics databases were used as a gold standard. The system obtained a maximum F-score of 22.21% (23.18% precision and 21.36% recall), with high efficiency in the use of seed pairs.

Conclusion
The method performs comparably with other studied methods, does not rely on sophisticated named-entity recognition, and requires little initial seed knowledge.
A method for the prediction of GPCRs coupling specificity to G-proteins using refined profile Hidden Markov Models
Authors: Sgourakis Nikolaos G , Bagos Pantelis G , Papasaikas Panagiotis K , Hamodrakas Stavros J 
Published: April 2005

Abstract
Background
G- Protein coupled receptors (GPCRs) comprise the largest group of eukaryotic cell surface receptors with great pharmacological interest. A broad range of native ligands interact and activate GPCRs, leading to signal transduction within cells. Most of these responses are mediated through the interaction of GPCRs with heterotrimeric GTP-binding proteins (G-proteins). Due to the information explosion in biological sequence databases, the development of software algorithms that could predict properties of GPCRs is important. Experimental data reported in the literature suggest that heterotrimeric G-proteins interact with parts of the activated receptor at the transmembrane helix-intracellular loop interface. Utilizing this information and membrane topology information, we have developed an intensive exploratory approach to generate a refined library of statistical models (Hidden Markov Models) that predict the coupling preference of GPCRs to heterotrimeric G-proteins. The method predicts the coupling preferences of GPCRs to Gs, Gi/o and Gq/11, but not G12/13 subfamilies.

Results
Using a dataset of 282 GPCR sequences of known coupling preference to G-proteins and adopting a five-fold cross-validation procedure, the method yielded an 89.7% correct classification rate. In a validation set comprised of all receptor sequences that are species homologues to GPCRs with known coupling preferences, excluding the sequences used to train the models, our method yields a correct classification rate of 91.0%. Furthermore, promiscuous coupling properties were correctly predicted for 6 of the 24 GPCRs that are known to interact with more than one subfamily of G-proteins.

Conclusion
Our method demonstrates high correct classification rate. Unlike previously published methods performing the same task, it does not require any transmembrane topology prediction in a preceding step. A web-server for the prediction of GPCRs coupling specificity to G-proteins available for non-commercial users is located at http://bioinformatics.biol.uoa.gr/PRED-COUPLE.
Crosstalk regulation among group 2- Sigma factors in Synechocystis PCC6803
Authors: Lemeille Sylvain , Geiselmann Johannes , Latifi Amel 
Published: April 2005

Abstract
Background
The cyanobacterium Synechocystis PCC6803 contains one group 1 (sigA) and four group 2 (sigB, sigC, sigD and sigE) sigma factors. The activity of these multiple sigma factors determines the transcriptional program of this bacterium. We wanted to study the role of the group 2 sigma factors in Synechocystis. We have therefore constructed mutants of each of the group 2 sigma factors and investigated their crosstalk.

Results
We used quantitative RT-PCR analysis to measure the relative abundance of the sig mRNAs in the four sigma mutants. Our data indicate that a network of mutual transcriptional regulation links the expression of the sigma genes. Accordingly, an environmental stress acting on only one of the sigma factors will indirectly modify the expression of most of the other sigma factors. This was confirmed by the transcriptional analysis of the sig mRNAs as a function of nitrogen starvation.

Conclusion
Taken together, our observations suggest that the crosstalk regulation between all group 1 and group 2 genes could be important for the adaptation of the bacterium to different environmental and physiological conditions.
Sequence determinants of protein aggregation: tools to increase protein solubility
Authors: Ventura Salvador 
Published: April 2005

AbstractEscherichia coliis one of the most widely used hosts for the production of recombinant proteins. However, very often the target protein accumulates into insoluble aggregates in a misfolded and biologically inactive form. Bacterial inclusion bodies are major bottlenecks in protein production and are hampering the development of top priority research areas such structural genomics. Inclusion body formation was formerly considered to occur via non-specific association of hydrophobic surfaces in folding intermediates. Increasing evidence, however, indicates that protein aggregation in bacteria resembles to the well-studied process of amyloid fibril formation. Both processes appear to rely on the formation of specific, sequence-dependent, intermolecular interactions driving the formation of structured protein aggregates. This similarity in the mechanisms of aggregation will probably allow applying anti-aggregational strategies already tested in the amyloid context to the less explored area of protein aggregation inside bacteria. Specifically, new sequence-based approaches appear as promising tools to tune protein aggregation in biotechnological processes.
GIDEON: a comprehensive Web-based resource for geographic medicine
Authors: Berger Stephen A 
Published: April 2005

Abstract
GIDEON (Global Infectious Diseases and Epidemiology Network) is a web-based computer program designed for decision support and informatics in the field of Geographic Medicine. The first of four interactive modules generates a ranked differential diagnosis based on patient signs, symptoms, exposure history and country of disease acquisition. Additional options include syndromic disease surveillance capability and simulation of bioterrorism scenarios. The second module accesses detailed and current information regarding the status of 338 individual diseases in each of 220 countries. Over 50,000 disease images, maps and user-designed graphs may be downloaded for use in teaching and preparation of written materials. The third module is a comprehensive source on the use of 328 anti-infective drugs and vaccines, including a listing of over 9,500 international trade names. The fourth module can be used to characterize or identify any bacterium or yeast, based on laboratory phenotype. GIDEON is an up-to-date and comprehensive resource for Geographic Medicine.