bluuebunny/crossref_metadata_2025_split huggingface dataset:
Src kinase inhibition promotes the chondrocyte phenotype
Authors: Bursell Laura , Woods Anita , James Claudine G , Pala Daphne , Leask Andrew , Beier Frank 
Published: October 2007

AbstractRegulated differentiation of chondrocytes is essential for both normal skeletal development and maintenance of articular cartilage. The intracellular pathways that control these events are incompletely understood, and our ability to modulate the chondrocyte phenotype in vivo or in vitro is therefore limited. Here we examine the role played by one prominent group of intracellular signalling proteins, the Src family kinases, in regulating the chondrocyte phenotype. We show that the Src family kinase Lyn exhibits a dynamic expression pattern in the chondrogenic cell line ATDC5 and in a mixed population of embryonic mouse chondrocytes in high-density monolayer culture. Inhibition of Src kinase activity using the pharmacological compound PP2 (4-Amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo [3,4-d]pyrimidine) strongly reduced the number of primary mouse chondrocytes. In parallel, PP2 treatment increased the expression of both early markers (such as Sox9, collagen type II, aggrecan and xylosyltransferases) and late markers (collagen type X, Indian hedgehog and p57) markers of chondrocyte differentiation. Interestingly, PP2 repressed the expression of the Src family members Lyn, Frk and Hck. It also reversed morphological de-differentiation of chondrocytes in monolayer culture and induced rounding of chondrocytes, and reduced stress fibre formation and focal adhesion kinase phosphorylation. We conclude that the Src kinase inhibitor PP2 promotes chondrogenic gene expression and morphology in monolayer culture. Strategies to block Src activity might therefore be useful both in tissue engineering of cartilage and in the maintenance of the chondrocyte phenotype in diseases such as osteoarthritis.
Differential responsiveness to immunoablative therapy in refractory rheumatoid arthritis is associated with level and avidity of anti-cyclic citrullinated protein autoantibodies: a case study
Authors: Teng YK Onno , Verburg Robert J , Verpoort Kirsten N , Diepenhorst Gwendolyn MP , Bajema Ingeborg M , van Tol Maarten JD , Jol-van der Zijde Els CM , Toes Rene EM , Huizinga Tom WJ , van Laar Jacob M 
Published: October 2007

AbstractIn order to identify pathogenic correlates of refractory rheumatoid arthritis (RA), antibodies against anti-cyclic citrullinated protein (ACPAs) were investigated in RA patients in whom the dysregulated immune system had been ablated by high-dose chemotherapy (HDC) and autologous haematopoietic stem cell transplantation (HSCT). Six patients with refractory RA were extensively characterized in terms of levels of total immunoglobulins, RA-specific autoantibodies (ACPAs and rheumatoid factor) and antibodies against rubella, tetanus toxoid (TT) and phosphorylcholine before and after HDC plus HSCT. Additionally, the avidity of ACPAs was measured before and after treatment and compared with the avidity of TT antibodies following repeated immunizations. Synovial biopsies were obtained by arthroscopy before HDC plus HSCT, and analyzed by immunohistochemistry. In the three patients with clinically long-lasting responses to HDC plus HSCT (median 423 days), significant reductions in ACPA-IgG levels after therapy were observed (median level dropped from 215 to 34 arbitrary units/ml; P = 0.05). In contrast, stable ACPA-IgG levels were observed in three patients who relapsed shortly after HDC plus HSCT (median of 67 days). Clinical responders had ACPA-IgG of lower avidity (r = 0.75; P = 0.08) and higher degree of inflammation histologically (r = 0.73; P = 0.09). Relapse (after 38 to 530 days) in all patients was preceded by rising levels of low avidity ACPA-IgG (after 30 to 388 days), in contrast to the stable titres of high avidity TT antibodies. In conclusion, humoral autoimmune responses were differentially modulated by immunoablative therapy in patients with synovial inflammation and low avidity ACPA-IgG autoantibodies as compared with patients with high levels of high avidity ACPA-IgG. The distinct clinical disease course after immunoablative therapy based on levels and avidity of ACPA-IgG indicates that refractory RA is not a single disease entity.
Mouse mammary tumors display Stat3 activation dependent on leukemia inhibitory factor signaling
Authors: Quaglino Ana , Schere-Levy Carolina , Romorini Leonardo , Meiss Roberto P , Kordon Edith C 
Published: October 2007

Abstract
Introduction
It has been demonstrated that leukemia inhibitory factor (LIF) induces epithelium apoptosis through Stat3 activation during mouse mammary gland involution. In contrast, it has been shown that this transcription factor is commonly activated in breast cancer cells, although what causes this effect remains unknown. Here we have tested the hypothesis that locally produced LIF can be responsible for Stat3 activation in mouse mammary tumors.

Methods
The studies were performed in different tumorigenic and non-tumorigenic mammary cells. The expression of LIF and LIF receptor was tested by RT-PCR analysis. In tumors, LIF and Stat3 proteins were analyzed by immunohistochemistry, whereas Stat3 and extracellular signal-regulated kinase (ERK)1/2 expression and phosphorylation were studied by Western blot analysis. A LIF-specific blocking antibody was used to determine whether this cytokine was responsible for Stat3 phosphorylation induced by conditioned medium. Specific pharmacological inhibitors (PD98059 and Stat3ip) that affect ERK1/2 and Stat3 activation were used to study their involvement in LIF-induced effects. To analyze cell survival, assays with crystal violet were performed.

Results
High levels of LIF expression and activated Stat3 were found in mammary tumors growing in vivo and in their primary cultures. We found a single mouse mammary tumor cell line, LM3, that showed low levels of activated Stat3. Incidentally, these cells also showed very little expression of LIF receptor. This suggested that autocrine/paracrine LIF would be responsible for Stat3 activation in mouse mammary tumors. This hypothesis was confirmed by the ability of conditioned medium of mammary tumor primary cultures to induce Stat3 phosphorylation, activity that was prevented by pretreatment with LIF-blocking antibody. Besides, we found that LIF increased tumor cell viability. Interestingly, blocking Stat3 activation enhanced this effect in mammary tumor cells.

Conclusion
LIF is overexpressed in mouse mammary tumors, where it acts as the main Stat3 activator. Interestingly, the positive LIF effect on tumor cell viability is not dependent on Stat3 activation, which inhibits tumor cell survival as it does in normal mammary epithelium.
An exploratory study with an adaptive continuous intravenous furosemide regimen in neonates treated with extracorporeal membrane oxygenation
Authors: van der Vorst Maria MJ , den Hartigh Jan , Wildschut Enno , Tibboel Dick , Burggraaf Jacobus 
Published: October 2007

Abstract
Introduction
The objective of the present study was to explore a continuous intravenous furosemide regimen that adapts to urine output in neonates treated with extracorporeal membrane oxygenation (ECMO).

Methods
Seven neonates admitted to a paediatric surgical intensive care unit for ECMO therapy were treated with a furosemide regimen consisting of a loading bolus (1–2 mg/kg) followed by a continuous infusion at 0.2 mg/kg per hour, which was adjusted according to the target urine production of 6 ml/kg per hour. Therapeutic drug monitoring for furosemide concentrations in blood was performed.

Results
The mean ± standard deviation furosemide dose was 0.17 ± 0.06 mg/kg per hour, 0.08 ± 0.04 mg/kg per hour and 0.12 ± 0.07 mg/kg per hour, respectively, on the first day, second day and third day of the study. The median (range of the urine production of the study subjects) urine production over the consecutive study days was 6.8 (0.8–8.4) mg/kg per hour, 6.0 (4.7–8.9) mg/kg per hour and 5.4 (3.4–10.1) ml/kg per hour. The target urine production was reached after a median time of 7 (3–37) hours. The regimen was haemodynamically well tolerated and the median furosemide serum concentration was 3.1 (0.4–12.9) μg/ml, well below the toxic level.

Conclusion
The evaluated furosemide infusion appears an effective means to reduce volume overload in neonates treated with ECMO. The data of this preliminary study suggest that the starting dose of furosemide was too high, however, because the urine output was excessive and required frequent adaptations. The results of this study therefore indicate that a novel pharmacokinetic/pharmacodynamic model needs to be developed for neonates treated with ECMO.
Transcriptional regulatory network for sexual differentiation in fission yeast
Authors: Mata Juan , Wilbrey Anna , Bähler Jürg 
Published: October 2007

Abstract
Background
Changes in gene expression are hallmarks of cellular differentiation. Sexual differentiation in fission yeast (Schizosaccharomyces pombe) provides a model system for gene expression programs accompanying and driving cellular specialization. The expression of hundreds of genes is modulated in successive waves during meiosis and sporulation in S. pombe, and several known transcription factors are critical for these processes.

Results
We used DNA microarrays to investigate meiotic gene regulation by examining transcriptomes after genetic perturbations (gene deletion and/or overexpression) of rep1, mei4, atf21 and atf31, which encode known transcription factors controlling sexual differentiation. This analysis reveals target genes at a genome-wide scale and uncovers combinatorial control by Atf21p and Atf31p. We also studied two transcription factors not previously implicated in sexual differentiation whose meiotic induction depended on Mei4p: Rsv2p induces stress-related genes during spore formation, while Rsv1p represses glucose-metabolism genes. Our data further reveal negative feedback interactions: both Rep1p and Mei4p not only activate specific gene expression waves (early and middle genes, respectively) but are also required for repression of genes induced in the previous waves (Ste11p-dependent and early genes, respectively).

Conclusion
These data give insight into regulatory principles controlling the extensive gene expression program driving sexual differentiation and highlight sophisticated interactions and combinatorial control among transcription factors. Besides triggering simultaneous expression of gene waves, transcription factors also repress genes in the previous wave and induce other factors that in turn regulate a subsequent wave. These dependencies ensure an ordered and timely succession of transcriptional waves during cellular differentiation.
Impaired ex Vivo Leukotriene B4 Production Characterizes the Metabolic Syndrome and Is Improved after Weight Reduction
Authors: Tsai I. J. , Beilin L. J. , Puddey I. B. , Croft K. D. , Barden A. 
Published: October 2007

AbstractContext: Neutrophil (polymorphonuclear neutrophil) production of leukotriene B4 (LTB4) may be associated with alterations in immune and inflammatory function that characterize the metabolic syndrome (MetS).Objective: We investigated whether polymorphonuclear neutrophil production of LTB4 and its metabolites 20-hydroxy-LTB4 (20-OH-LTB4) and 20-carboxyl-LTB4 were altered in subjects with features of the MetS before and after weight reduction.Design, Setting, Patients, and Intervention: In a case-controlled comparison, men and postmenopausal women with features of the MetS were matched with controls. Subjects with MetS were then matched and randomly assigned to either a 12-wk weight reduction study followed by 4-wk weight stabilization or 16-wk weight maintenance.Main Outcome Measures: Measurements were performed at baseline and at the end of the 16-wk period. Stimulated neutrophil LTB4 and its metabolites were measured by HPLC.Results: In the case-controlled study, body mass index, waist circumference, blood pressure, fasting triglycerides, and glucose were all significantly increased in subjects with features of the MetS (P &lt; 0.05). Production of LTB4 and 20-OH-LTB4 was significantly lower compared with controls (P &lt; 0.005). The weight loss intervention resulted in a 4.6-kg reduction in body weight and 6.6-cm decrease in waist circumference relative to controls and a significant increase in LTB4 and 20-OH-LTB4.Conclusions: Subjects with features of the MetS have lower stimulated LTB4, which is not due to increased metabolism of LTB4. Weight reduction restored the production of neutrophil LTB4, suggesting that in addition to modifying cardiovascular risk, weight loss may also help with the management of perturbed inflammatory responses in overweight subjects.
Low Body Weight Mediates the Relationship between HIV Infection and Low Bone Mineral Density: A Meta-Analysis
Authors: Bolland Mark J. , Grey Andrew B. , Gamble Greg D. , Reid Ian R. 
Published: October 2007

Abstract
Context: HIV infection has been associated with low bone mineral density (BMD) in many cross-sectional studies, although longitudinal studies have not demonstrated accelerated bone loss. The cross-sectional studies may have been confounded by the failure to control for low body weight in HIV-infected patients.
Objective: Our objective was to determine whether low body weight might explain the association of HIV infection with low BMD.
Data Sources: MEDLINE and EMBASE were searched for English language studies published from 1966 to March 2007, and conference abstracts prior to 2007 were hand-searched.
Study Selection: All studies reporting BMD and weight or body mass index in adult patients with HIV and a healthy age- and sex-comparable control group were included. Nine of 40 identified studies and one of 68 identified abstracts were eligible.
Data Synthesis: We adjusted for the between-groups weight differences using regression coefficients from published cohorts of healthy men and women. On average, HIV-infected patients were 5.1 kg [95% confidence interval (CI), −6.8, −3.4; P &lt; 0.001] lighter than controls. At all skeletal sites, unadjusted BMD was lower by 4.4–7.0% in the HIV-infected groups than the controls (P &lt; 0.01). After adjustment for body weight, residual between-groups differences in BMD were small (2.2–4.7%) [lumbar spine, −0.02 (95% CI, −0.05, 0.01) g/cm2; P = 0.12; total hip, −0.02 (95% CI, −0.04, 0.00) g/cm2; P = 0.031; femoral neck, −0.04 (95% CI, −0.07, −0.01) g/cm2; P = 0.013; and total body, −0.03 (95% CI, −0.07, 0.01) g/cm2, P = 0.11].
Conclusion: HIV-infected patients are lighter than controls and low body weight may largely account for the high prevalence of low BMD reported in HIV-infected patients. However, in the setting of current treatment practice, HIV infection per se is not a risk factor for low BMD.
The −374A allele of the receptor for advanced glycation end products (RAGE) gene promoter is a protective factor against cardiovascular lesions in type 2 diabetes mellitus patients
Authors: Picheth Geraldo , Costantini Costantino O. , Pedrosa Fábio O. , Leme da Rocha Martinez Tania , Maltempi de Souza Emanuel 
Published: October 2007

AbstractClin Chem Lab Med 2007;45:1268–72.
Combined androgen blockade therapy can convert RT-PCR detection of prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) transcripts from positive to negative in the peripheral blood of patients with clinically localized prostate cancer and increase biochemical failure-free survival after curative therapy
Authors: Lembessis Peter , Msaouel Pavlos , Halapas Antonis , Sourla Antigone , Panteleakou Zacharoula , Pissimissis Nikolaos , Milathianakis Constantine , Bogdanos John , Papaioannou Andreas , Maragoudakis Evangelos , Dardoufas Constantine , Dimopoulos Theodoros , Koutsilieris Michael 
Published: October 2007

AbstractClin Chem Leb Med 2007;45:1488–94.
A polymorphism in the resistin gene promoter is related to increased C-reactive protein levels in patients with coronary artery disease
Authors: Tang Na-Ping , Wang Lian-Sheng , Yang Li , Zhou Bo , Gu Hai-Juan , Sun Qing-Min , Cong Ri-Hong , Zhu Huai-Jun , Wang Bin 
Published: October 2007

AbstractClin Chem Lab Med 2007;45:1471–5.
Validation study of Axis-Shield carbohydrate-deficient transferrin (CDT) on ARCHITECT® chemistry analyzer
Authors: Janssen Marcel J.W. , De Gruyter Heidi L.M. , Stappers Peter M.G. , Velmans Mathieu H. , van den Ouweland Johannes M.W. , van Daal Henny , Hampsink Rene M. 
Published: October 2007

AbstractClin Chem Lab Med 2007;45:1555–8.
Huntingtin-Interacting Protein 1 Influences Worm and Mouse Presynaptic Function and ProtectsCaenorhabditis elegansNeurons against Mutant Polyglutamine Toxicity
Authors: Parker J. Alex , Metzler Martina , Georgiou John , Mage Marilyne , Roder John C. , Rose Ann M. , Hayden Michael R. , Néri Christian 
Published: October 2007

Huntingtin-interacting protein 1 (HIP1) was identified through its interaction with htt (huntingtin), the Huntington's disease (HD) protein. HIP1 is an endocytic protein that influences transport and function of AMPA and NMDA receptors in the brain. However, little is known about its contribution to neuronal dysfunction in HD.We report that theCaenorhabditis elegansHIP1 homologhipr-1modulates presynaptic activity and the abundance of synaptobrevin, a protein involved in synaptic vesicle fusion. Presynaptic function was also altered in hippocampal brain slices of HIP1−/−mice demonstrating delayed recovery from synaptic depression and a reduction in paired-pulse facilitation, a form of presynaptic plasticity. Interestingly, neuronal dysfunction in transgenic nematodes expressing mutant N-terminal huntingtin was specifically enhanced byhipr-1loss of function. A similar effect was observed with several other mutant proteins that are expressed at the synapse and involved in endocytosis, such asunc-11/AP180,unc-26/synaptojanin, andunc-57/endophilin.Thus, HIP1 is involved in presynaptic nerve terminal activity and modulation of mutant polyglutamine-induced neuronal dysfunction. Moreover, synaptic proteins involved in endocytosis may protect neurons against amino acid homopolymer expansion.
3D Micro‐ and Nanostructures via Interference Lithography
Authors: Jang J.‐H. , Ullal C. K. , Maldovan M. , Gorishnyy T. , Kooi S. , Koh C. , Thomas E. L. 
Published: October 2007

AbstractInterference lithography (IL) holds the promise of fabricating large‐area, defect‐free 3D structures on the submicrometer scale both rapidly and cheaply. A stationary spatial variation of intensity is created by the interference of two or more beams of light. The pattern that emerges out of the intensity distribution is transferred to a light sensitive medium, such as a photoresist, and after development yields a 3D bicontinuous photoresist/air structure. Importantly, by a proper choice of beam parameters one can control the geometrical elements and volume fraction of the structures. This article provides an overview of the fabrication of 3D structures via IL (e.g., the formation of interference patterns, their dependence on beam parameters and several requirements for the photoresist) and highlights some of our recent efforts in the applications of these 3D structures in photonic crystals, phononic crystals and as microframes, and for the synthesis of highly non spherical polymer particles. Our discussion concludes with perspectives on the future directions in which this technique could be pursued.
A possible link between the pubertal growth of girls and breast cancer in their daughters
Authors: Barker David J.P. , Osmond Clive , Thornburg Kent L. , Kajantie Eero , Forsen Tom J. , Eriksson Johan G. 
Published: October 2007

AbstractOne hypothesis for the origins of breast cancer is that it is initiated by exposure of developing breast tissue in utero to maternal sex hormones. The sex hormone profile is established at puberty, when it regulates growth of the pelvic bones. The pubertal growth of girls is characterized by broadening and rounding of the pelvis. The maximal width between their iliac crests, the intercristal width, increases more rapidly than in boys. We hypothesized that higher sex hormone concentrations at puberty produce larger intercristal widths, and these are markers of increased breast cancer risk in the next generation. We followed up 6,370 women who were born in Helsinki during 1934–1944, and whose mothers' pelvic bones were measured during routine antenatal care. Women whose mothers had large intercristal widths had higher rates of breast cancer. In those born at or after 40 weeks gestation, the hazard ratio for breast cancer was 3.7 (95% CI: 2.1–6.6) if their mother's intercristal width was greater than 30 cm. Among women born to multiparous mothers this hazard ratio rose to 7.2 (3.4–15.4). Hazard ratios for breast cancer were also higher in the daughters of mothers with round iliac crests. Pelvic bone measurements which increase similarly in girls and boys at puberty did not predict breast cancer. We conclude that the intercristal width, and the roundness of the iliac crests, are markers of mothers' sex hormones, and postulate that high concentrations cause genetic instability in differentiating breast cells in their daughters in utero. Am. J. Hum. Biol., 2008. © 2007 Wiley‐Liss, Inc.
Note on drill (Mandrillus leucophaeus) ecology and conservation status in Korup National Park, Southwest Cameroon
Authors: Astaras Christos , Mühlenberg Michael , Waltert Matthias 
Published: October 2007

AbstractWe report preliminary findings on drill population ecology, feeding ecology, primate associations and conservation status in Korup National Park, Cameroon, based on analysis of data collected during 1,346 km (620 field hours) of trail patrols from February to June 2006. We encountered drills on 25 occasions and collected 304 fecal samples. Group size was estimated on four occasions (≥25, ≥40, ≥67, ≥77), and multiple males were heard emitting the characteristic two‐phase grunt of mature male drills in two of these groups. We saw a solitary male drill once. Examination of fecal samples indicated a seasonally variable diet consisting mainly of seeds, fruit pith, leaves and insects (especially ants and termites). Irvingia gabonensis and Musanga cecropioides fruits showed the highest percentage of occurrence in May (96%) and March (75%) samples, respectively, and could be a major food source for drills at that time. Drills were in association with at least one additional primate species during 57.9% of observations. These associations involved all of the diurnal primates found in Korup (Cercopithecus mona, Cercopithecus nictitans, Cercopithecus erythrotis, Cercopithecus pogonias, Piliocolobus preussi and Cercocebus torquatus) except chimpanzees (Pan troglodytes). We discuss our findings in terms of existing knowledge about drill ecology and highlight the urgent need for the protection of the significant drill population in Korup National Park. Am. J. Primatol. 70:306–310, 2008. © 2007 Wiley‐Liss, Inc.
Simple machine‐assisted protocol for solid‐phase synthesis of depsipeptides
Authors: Spengler Jan , Koksch Beate , Albericio Fernando 
Published: October 2007

AbstractA straightforward machine‐assisted protocol for the synthesis of linear depsipeptides is reported. The synthesis was performed on a 433A Peptide Synthesizer (Applied Biosystems) using preprogrammed and optimized modules for Boc chemistry and without any need for hardware modification. The robustness of the protocol was demonstrated with 12 examples of 26‐membered depsipeptides with single and multiple (up to 6) ester backbone substitutions. © 2007 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 88: 823–828, 2007.This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com