bluuebunny/crossref_metadata_2025_split huggingface dataset:
Posttranslational Protein Modification inArchaea
Authors: Eichler Jerry , Adams Michael W. W. 
Published: September 2005

SUMMARYOne of the first hurdles to be negotiated in the postgenomic era involves the description of the entire protein content of the cell, the proteome. Such efforts are presently complicated by the various posttranslational modifications that proteins can experience, including glycosylation, lipid attachment, phosphorylation, methylation, disulfide bond formation, and proteolytic cleavage. Whereas these and other posttranslational protein modifications have been well characterized inEucaryaandBacteria, posttranslational modification inArchaeahas received far less attention. Although archaeal proteins can undergo posttranslational modifications reminiscent of what their eucaryal and bacterial counterparts experience, examination of archaeal posttranslational modification often reveals aspects not previously observed in the other two domains of life. In some cases, posttranslational modification allows a protein to survive the extreme conditions often encountered byArchaea. The various posttranslational modifications experienced by archaeal proteins, the molecular steps leading to these modifications, and the role played by posttranslational modification inArchaeaform the focus of this review.
N
-Ethyl-
N
-Nitrosourea Mutagenesis: Boarding the Mouse Mutant Express
Authors: Cordes Sabine P. 
Published: September 2005

SUMMARY

In the mouse, random mutagenesis with
N
-ethyl-
N
-nitrosourea (ENU) has been used since the 1970s in forward mutagenesis screens. However, only in the last decade has ENU mutagenesis been harnessed to generate a myriad of new mouse mutations in large-scale genetic screens and focused, smaller efforts. The development of additional genetic tools, such as balancer chromosomes, refinements in genetic mapping strategies, and evolution of specialized assays, has allowed these screens to achieve new levels of sophistication. The impressive productivity of these screens has led to a deluge of mouse mutants that wait to be harnessed. Here the basic large- and small-scale strategies are described, as are the basics of screen design. Finally, and importantly, this review describes the mechanisms by which such mutants may be accessed now and in the future. Thus, this review should serve both as an overview of the power of forward mutagenesis in the mouse and as a resource for those interested in developing their own screens, adding onto existing efforts, or obtaining specific mouse mutants that have already been generated.
FRAMED KNOTS IN 3-MANIFOLDS AND AFFINE SELF-LINKING NUMBERS
Authors: CHERNOV TCHERNOV VLADIMIR 
Published: September 2005

The number |K| of non-isotopic framed knots that correspond to a given unframed knot K ⊂ S3 is infinite. This follows from the existence of the self-linking number slk of a zero homologous framed knot. We use the approach of Vassiliev–Goussarov invariants to construct "affine self-linking numbers" that are extensions of slk to the case of nonzero homologous framed knots in 3-manifolds. As a corollary we get that |K| = ∞ for all knots in an oriented (not necessarily compact) 3-manifold M that is not realizable as a connected sum (S1 × S2)# M′. This result for compact manifolds was first stated by Hoste and Przytycki. They referred to the works of McCullough for the idea of the proof, however to the best of our knowledge prior to this work the proof of this fundamental fact was not given in literature or in a preprint form. Our proof is based on different ideas. For M = (S1 × S2)# M′ we construct K in M such that |K| = 2 ≠ ∞.
Molecular profiling of CD34+ cells identifies low expression of CD7, along with high expression of proteinase 3 or elastase, as predictors of longer survival in patients with CML
Authors: Yong Agnes S. M. , Szydlo Richard M. , Goldman John M. , Apperley Jane F. , Melo Junia V. 
Published: September 2005

AbstractAlthough most patients with chronic myeloid leukemia (CML) have the same initial molecular abnormality, the BCR-ABL fusion gene, the duration of chronic phase (CP) varies widely. To identify the possible molecular basis of this heterogeneity, we studied CD34+ cells collected at diagnosis from 68 patients with CML-CP. By using oligonucleotide microarray screening, we performed gene-expression profiling on 2 subsets of patients, one comprising patients with an “aggressive disease” who developed blastic transformation (BT) within 3 years of diagnosis (n = 10) and, at the other extreme, patients with an “indolent disease” whose BT occurred 7 or more years from diagnosis (n = 9). This screening revealed 20 genes differentially expressed in patients with aggressive and indolent disease, which were validated by quantitative reverse transcriptase/polymerase chain reaction (Q-RT/PCR). A multivariate Cox regression model identified the combination of low CD7 expression with high expression of proteinase 3 or elastase as associated with longer survival in the complete cohort of 68 patients. This differential pattern of gene expression probably reflects the intrinsic heterogeneity of the disease; if so, assessing expression levels of selected genes at diagnosis may be valuable in predicting duration of survival in patients treated with imatinib and the newer tyrosine kinase inhibitors.
Impediment in upper airway stabilizing forces assessed by phrenic nerve stimulation in sleep apnea patients
Authors: Sériès F , Vérin E , Similowski T 
Published: September 2005

AbstractBackgroundThe forces developed during inspiration play a key role in determining upper airway stability and the occurrence of nocturnal breathing disorders. Phrenic nerve stimulation applied during wakefulness is a unique tool to assess Upper airway dynamic properties and to measure the overall mechanical effects of the inspiratory process on UA stability.ObjectivesTo compare the flow/pressure responses to inspiratory and expiratory twitches between sleep apnea subjects and normal subjects.MethodsInspiratory and expiratory twitches using magnetic nerve stimulation completed in eleven untreated sleep apnea subjects and ten normal subjects.ResultsIn both groups, higher flow and pressure were reached during inspiratory twitches. The two groups showed no differences in expiratory twitch parameters. During inspiration, the pressure at which flow-limitation occurred was more negative in normals than in apneic subjects, but not reaching significance (p = 0.07). The relationship between pharyngeal pressure and flow adequately fitted with a polynomial regression model providing a measurement of upper airway critical pressure during twitch. This pressure significantly decreased in normals from expiratory to inspiratory twitches (-11.1 ± 1.6 and -15.7 ± 1.0 cm H2O respectively, 95% CI 1.6–7.6, p < 0.01), with no significant difference between the two measurements in apneic subjects. The inspiratory/expiratory difference in critical pressure was significantly correlated with the frequency of nocturnal breathing disorders.ConclusionInspiratory-related upper airway dilating forces are impeded in sleep apnea patients.
Predictors of post-operative mortality following treatment for non-ruptured abdominal aortic aneurysm
Authors: Urbonavicius Sigitas , Vorum Henrik , Urbonaviciene Grazina , Trumpickas Mindaugas , Pavalkis Dainius , Honoré Bent 
Published: September 2005

AbstractThe aim of this prospective study of patients undergoing repair of non-ruptured abdominal aortic aneurysm between 1999 and 2003 was to evaluate and compare risk factors for mortality after surgery, to determine a complex of informative factors for lethal outcome, and to define patient risk groups. Logistic regression analysis revealed a complex of informative factors, including female gender, previous myocardial infarction, age greater than 75 years, and clinical course of abdominal aortic aneurysm as important indicators for lethal outcome. A risk score model identified low-, moderate- and high-risk groups with mortality rates of 2.9%, 8.0% and 44.4%, respectively.
Novel type I interferon IL-28A suppresses hepatitis C viral RNA replication
Authors: Zhu Haizhen , Butera Mike , Nelson David R , Liu Chen 
Published: September 2005

AbstractInterferon alpha (IFN-α)-based therapy is the currently approved treatment for chronic hepatitis C viral infection. The sustained antiviral response rate is approximately 50% for genotype-1 infection. The major challenge to the HCV community is to improve antiviral efficacy and to reduce the side effects typically seen in IFNα-based therapy. One of the strategies is to identify new interferons, which may have better efficacy and less undesirable side effects. In this report, we examined the role of IL-28A (IFN λ2), a novel type I IFN, in suppression of human hepatitis C viral RNA replication. We have cloned both the human genomic DNA and cDNA of IL-28A, and evaluated their biological activity using HCV RNA replicon cell culture system. The results show that IL-28A effectively inhibits HCV subgenomic RNA replication in a dose-dependent manner. Treatment of human hepatoma cells with IL-28A activates the JAK-STAT signaling pathway and induces the expression of some interferon-stimulated genes (ISGs), such as 6–16 and 1–8U. We also demonstrate that IL-28A induces expression of HLA class I antigens in human hepatoma cells. Moreover, IL-28A appears to specifically suppress HCV IRES-mediated translation. Although IL-28A receptor shares one subunit with the IL-10 receptor, IL-10 treatment has no detectable effect on IL-28A-induced antiviral activity. Interestingly, IL-28A can synergistically enhance IFNα antiviral efficacy. Our results suggest that IL-28A antiviral activity is associated with the activation of the JAK-STAT signaling pathway and expression of ISGs. The effectiveness of IL-28A antiviral activity and its synergistic effect on IFN-α indicate that IL-28A may be potentially used to treat HCV chronic infection.
Fludarabine in Combination With Alemtuzumab Is Effective and Feasible in Patients With Relapsed or Refractory B-Cell Chronic Lymphocytic Leukemia: Results of a Phase II Trial
Authors: Elter Thomas , Borchmann Peter , Schulz Holger , Reiser Marcel , Trelle Sven , Schnell Roland , Jensen Markus , Staib Peter , Schinköthe Timo , Stützer Hartmut , Rech Jürgen , Gramatzki Martin , Aulitzky Walter , Hasan Ibrahim , Josting Andreas , Hallek Michael , Engert Andreas 
Published: September 2005

Purpose To determine the efficacy and safety of a newly developed concomitant administration of fludarabine and alemtuzumab (FluCam) in patients with relapsed or refractory B-cell chronic lymphocytic leukemia (B-CLL). Patients and Methods A total of 36 patients were treated in this phase II study (median age, 61.47 years; mean number of prior chemotherapies, 2.6; Binet stage C, n = 28). After an initial dose escalation of alemtuzumab over 3 days, alemtuzumab 30 mg and fludarabine 30 mg/m2 were administered on 3 consecutive days. Treatment was repeated after 28 days for up to six cycles. Restaging (following National Cancer Institute criteria) was carried out after cycles 2 and 4 and 1 month after the end of treatment. Results The overall response rate was 83% (11 complete responses, 19 partial responses, one stable disease, and five progressive diseases). Two patients with progressive disease developed fungal pneumonias, and one patient died as a result of Escherichia coli sepsis. Two subclinical cytomegalovirus reactivations occurred. Conclusion The new FluCam regimen is effective and feasible in patients with relapsed and refractory B-CLL.
Gene Expression Profiles in Paraffin-Embedded Core Biopsy Tissue Predict Response to Chemotherapy in Women With Locally Advanced Breast Cancer
Authors: Gianni Luca , Zambetti Milvia , Clark Kim , Baker Joffre , Cronin Maureen , Wu Jenny , Mariani Gabriella , Rodriguez Jaime , Carcangiu Marialuisa , Watson Drew , Valagussa Pinuccia , Rouzier Roman , Symmans W. Fraser , Ross Jeffrey S. , Hortobagyi Gabriel N. , Pusztai Lajos , Shak Steven 
Published: September 2005

Purpose We sought to identify gene expression markers that predict the likelihood of chemotherapy response. We also tested whether chemotherapy response is correlated with the 21-gene Recurrence Score assay that quantifies recurrence risk. Methods Patients with locally advanced breast cancer received neoadjuvant paclitaxel and doxorubicin. RNA was extracted from the pretreatment formalin-fixed paraffin-embedded core biopsies. The expression of 384 genes was quantified using reverse transcriptase polymerase chain reaction and correlated with pathologic complete response (pCR). The performance of genes predicting for pCR was tested in patients from an independent neoadjuvant study where gene expression was obtained using DNA microarrays. Results Of 89 assessable patients (mean age, 49.9 years; mean tumor size, 6.4 cm), 11 (12%) had a pCR. Eighty-six genes correlated with pCR (unadjusted P < .05); pCR was more likely with higher expression of proliferation-related genes and immune-related genes, and with lower expression of estrogen receptor (ER) –related genes. In 82 independent patients treated with neoadjuvant paclitaxel and doxorubicin, DNA microarray data were available for 79 of the 86 genes. In univariate analysis, 24 genes correlated with pCR with P < .05 (false discovery, four genes) and 32 genes showed correlation with P < .1 (false discovery, eight genes). The Recurrence Score was positively associated with the likelihood of pCR (P = .005), suggesting that the patients who are at greatest recurrence risk are more likely to have chemotherapy benefit. Conclusion Quantitative expression of ER-related genes, proliferation genes, and immune-related genes are strong predictors of pCR in women with locally advanced breast cancer receiving neoadjuvant anthracyclines and paclitaxel.
Inferring a Tumor Progression Model for Neuroblastoma From Genomic Data
Authors: Bilke Sven , Chen Qing-Rong , Westerman Frank , Schwab Manfred , Catchpoole Daniel , Khan Javed 
Published: September 2005

Purpose The knowledge of the key genomic events that are causal to cancer development and progression not only is invaluable for our understanding of cancer biology but also may have a direct clinical impact. The task of deciphering a model of tumor progression by requiring that it explains (or at least does not contradict) known clinical and molecular evidence can be very demanding, particularly for cancers with complex patterns of clinical and molecular evidence. Materials and Methods We formalize the process of model inference and show how a progression model for neuroblastoma (NB) can be inferred from genomic data. The core idea of our method is to translate the model of clonal cancer evolution to mathematical testable rules of inheritance. Seventy-eight NB samples in stages 1, 4S, and 4 were analyzed with array-based comparative genomic hybridization. Results The pattern of recurrent genomic alterations in NB is strongly stage dependent and it is possible to identify traces of tumor progression in this type of data. Conclusion A tumor progression model for neuroblastoma is inferred, which is in agreement with clinical evidence, explains part of the heterogeneity of the clinical behavior observed for NB, and is compatible with existing empirical models of NB progression.
Connective Tissue Growth Factor Expression in the Human Corpus Luteum: Paracrine Regulation by Human Chorionic Gonadotropin
Authors: Duncan W. Colin , Hillier Stephen G. , Gay Eva , Bell Julie , Fraser Hamish M. 
Published: September 2005

Abstract
Context: The molecular mechanisms of luteolysis and its inhibition during maternal recognition of pregnancy remain unclear.
Objective: The objective of this study was to investigate the differential regulation of connective tissue growth factor (CTGF) expression in human corpora lutea using in vivo and in vitro models.
Design: Corpora lutea from different stages of the luteal phase and after luteal rescue with human chorionic gonadotropin (hCG) were studied. Primary cultures and cocultures of luteinized granulosa cells and luteal fibroblast-like cells were performed.
Setting: This study was performed at the research center of a university teaching hospital.
Patients: Women with regular cycles having hysterectomy for nonmalignant conditions and women undergoing oocyte collection for assisted conception were studied.
Interventions: CTGF localization was determined by in situ hybridization, and expression by quantitative RT-PCR.
Outcomes: The outcome measures were the effect of hCG on the expression and localization of CTGF mRNA in human corpora lutea and the effect of hCG on CTGF expression in primary cultures of luteinized granulosa cells and luteal fibroblast-like cells.
Results: Luteal rescue reduced CTGF expression compared with that in the late luteal phase (P &lt; 0.05). CTGF expression was localized to fibroblast-like cells and endothelial cells of larger blood vessels, not to steroidogenic cells. The expression of CTGF by fibroblast-like cells in vitro was not regulated by hCG. When cocultured with luteinized granulosa cells, fibroblast-like cell CTGF expression was inhibited by hCG (P &lt; 0.001). This effect was independent of stimulated progesterone concentrations and was not blocked by follistatin or indomethacin. Both IL-1α (P &lt; 0.05) and cAMP (P &lt; 0.001) inhibited CTGF expression in fibroblast-like cells.
Conclusions: These results provide evidence for negative regulation of CTGF by hCG during luteal rescue mediated by paracrine signals.
Depression in Anorexia Nervosa: A Risk Factor for Osteoporosis
Authors: Konstantynowicz Jerzy , Kadziela-Olech Halina , Kaczmarski Maciej , Zebaze Roger M. D. , Iuliano-Burns Sandra , Piotrowska-Jastrzebska Janina , Seeman Ego 
Published: September 2005

AbstractContext: Both anorexia nervosa (AN) and depression are associated with osteoporosis. We hypothesized that adolescent girls with AN and depression will have lower bone mineral density (BMD) than anorexic girls without depression.Objective: The objective of this study was to investigate whether depression is an independent risk factor for osteoporosis in anorexic adolescent girls.Design: This study was cross-sectional.Setting: This study was conducted at the University Children’s Hospital (Bialystok, Poland) from October 2002 through September 2003.Participants: Forty-five Caucasian anorexic girls aged 13–23 yr, matched by age, Tanner stage, weight, height, calcium intake, and duration of AN, were studied, including 14 with comorbid depression (based on Hamilton Depression Rating Scale and Montgomery-Asberg Depression Rating Scale) and 31 anorexic girls without depression.Main Outcome Measures: Total body and lumbar spine (LS) BMD, fat mass, and lean mass assessed using dual-energy x-ray absorptiometry were compared between AN girls with and without depression.Results: BMD was reduced in both groups, relative to reference data, but girls with AN and depression had lower BMD than those with AN alone (LS Z-scores, −2.6 ± 0.3 vs. −1.7 ± 0.3; P = 0.02) (mean ± sem). Quantitative assessment of depression correlated independently with total body BMD (r = −0.4; P &lt; 0.05) and LS BMD (r = −0.6; P &lt; 0.001).Conclusion: Anorexic girls with depression are at higher risk of osteoporosis than those without depression. The mechanisms responsible for decreased BMD in depression are not known. Independent treatment of the depressive disorder in AN may partly alleviate the bone fragility.
Association of Mitochondrial Deoxyribonucleic Acid 16189 Variant (T→C Transition) with Metabolic Syndrome in Chinese Adults
Authors: Weng Shao-Wen , Liou Chia-Wei , Lin Tsu-Kung , Wei Yau-Huei , Lee Cheng-Feng , Eng Hock-Liew , Chen Shang-Der , Liu Rue-Tsuan , Chen Jung-Fu , Chen I-Ya , Chen Ming-Hong , Wang Pei-Wen 
Published: September 2005

Abstract
Objective: A common variant in mitochondrial DNA (mtDNA) at bp 16189 (T→C transition) has been associated with small birth size, adulthood hyperglycemia, and insulin resistance in Caucasians. In this study, we investigated whether mtDNA 16189 variant is associated with metabolic syndrome in Chinese subjects.
Methods: Six hundred fifteen Chinese adults, aged 40 yr or older, were recruited in this study. The 16189 variant of mtDNA was detected using PCR and restriction enzyme digestion. Metabolic syndrome was diagnosed on modified National Cholesterol Education Program Adult Treatment Panel III guidelines, using body mass index (BMI) instead of waist circumference. An association study was performed with χ2 test and logistic regression analysis.
Results: The prevalence of the 16189 variant was higher in patients with metabolic syndrome than in those without: 44% (125 of 284) vs. 33.2% (110 of 331) (P = 0.006). The association between this 16189 variant of mtDNA and metabolic syndrome (P = 0.021) remained significant even after correcting for age and BMI. As to the individual traits, the prevalence of fasting plasma glucose of at least 110 mg/dl (≥6.1 mmol/liter) [(51.5% (121 of 235) vs. 42.1% (160 of 380); P = 0.023], type 2 diabetes mellitus [48.1% (113 of 235) vs. 39.2% (149 of 380); P = 0.031], and hypertriglyceridemia [44.3% (104 of 235) vs. 35.8% (136 of 380); P = 0.037] were significantly higher in subjects harboring the 16189 variant of mtDNA than those with the wild type. However, the prevalence of hypertension [53.2% (125 of 235) vs. 47.6% (181 of 380); P = 0.180], BMI greater than 25 kg/m2 [48.5% (114 of 235) vs. 43.9% (167 of 380); P = 0.270], and low high-density lipoprotein cholesterol [61.3% (144 of 235) vs. 54.7% (208 of 380); P = 0.111] did not reach a significant difference between the two groups. Furthermore, there was a trend of increasing frequency of occurrence of the 16189 variant in individuals having an increasing number of components of metabolic syndrome (Ptrend &lt; 0.005).
Conclusion: Our data strongly suggest that mtDNA 16189 variant underlies susceptibility to metabolic syndrome in the Chinese population.
Hyperglycemia Alters Tumor Necrosis Factor-α Release from Mononuclear Cells in Women with Polycystic Ovary Syndrome
Authors: González Frank , Minium Judi , Rote Neal S. , Kirwan John P. 
Published: September 2005

AbstractContext: Women with polycystic ovary syndrome (PCOS) are often insulin resistant and have chronic low-level inflammation.Objective: The purpose of this study was to determine the effects of hyperglycemia on lipopolysaccharide (LPS)-stimulated TNFα release from mononuclear cells (MNC) in PCOS.Design: The study was designed as a prospective controlled study.Setting: The study was carried out at an academic medical center.Patients: Sixteen reproductive age women with PCOS (eight lean, eight obese) and 14 age-matched controls (eight lean, six obese) participated in the study.Main Outcome Measures: Insulin sensitivity (IS) was derived from a 2-h 75-g oral glucose tolerance test (ISOGTT). Percentage of truncal fat was determined by dual-energy absorptiometry. TNFα release was measured from MNC cultured in the presence of LPS from blood samples drawn fasting and 2 h after glucose ingestion.Results: ISOGTT was lower in women with PCOS compared with controls (3.9 ± 0.4 vs. 6.3 ± 1.0; P &lt; 0.03) and was negatively correlated with percentage of truncal fat (r = 0.56; P &lt; 0.002). Truncal fat was greater in lean women with PCOS compared with lean controls (29.8 ± 2.6 vs. 23.8 ± 2.5%; P &lt; 0.04). The TNFα response was different between obese and lean controls (−96.9 ± 21.2 vs. 24.4 ± 21.6 pg/ml; P &lt; 0.03) and obese and lean women with PCOS (−94.1 ± 34.5 vs. 30.4 ± 17.6 pg/ml; P &lt; 0.002). Fasting plasma C-reactive protein was elevated (P &lt; 0.003) in obese PCOS and obese controls compared with lean controls.Conclusion: An increase in abdominal adiposity and increased TNFα release from MNC after hyperglycemia may contribute to insulin resistance in lean PCOS patients. In contrast, obese PCOS patients have more profound chronic inflammation, and thus may have LPS tolerance that protects them from relatively mild excursions in blood glucose.