bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conservation and diversity in the immunity regions of wild phages with the immunity specificity of phage λ
Authors: Degnan Patrick H. , Michalowski Christine B. , Babić Andrea C. , Cordes Matthew H. J. , Little John W. 
Published: March 2007

SummaryThe gene regulatory circuitry of phage λ is among the best‐understood circuits. Much of the circuitry centres around the immunity region, which includes genes for two repressors, CI and Cro, and their cis‐acting sites. Related phages, termed lambdoid phages, have different immunity regions, but similar regulatory circuitry and genome organization to that of λ, and show a mosaic organization, arising by recombination between lambdoid phages. We sequenced the immunity regions of several wild phages with the immunity specificity of λ, both to determine whether natural variation exists in regulation, and to analyse conservation and variability in a region rich in well‐studied regulatory elements. CI, Cro and their cis‐acting sites are almost identical to those in λ, implying that regulatory mechanisms controlled by the immunity region are conserved. A segment adjacent to one of the operator regions is also conserved, and may be a novel regulatory element. In most isolates, different alleles of two regulatory proteins (N and CII) flank the immunity region; possibly the lysis‐lysogeny decision is more variable among isolates. Extensive mosaicism was observed for several elements flanking the immunity region. Very short sequence elements or microhomologies were also identified. Our findings suggest mechanisms by which fine‐scale mosaicism arises.
A novel class of mutations that affect DNA replication in E. coli
Authors: Nordman Jared , Skovgaard Ole , Wright Andrew 
Published: March 2007

SummaryOver‐initiation of DNA replication in cells containing the cold‐sensitive dnaA(cos) allele has been shown to lead to extensive DNA damage, potentially due to head‐to‐tail replication fork collisions that ultimately lead to replication fork collapse, growth stasis and/or cell death. Based on the assumption that suppressors of the cold‐sensitive phenotype of the cos mutant should include mutations that affect the efficiency and/or regulation of DNA replication, we subjected a dnaA(cos) mutant strain to transposon mutagenesis and selected mutant derivatives that could form colonies at 30°C. Four suppressors of the dnaA(cos)‐mediated cold sensitivity were identified and further characterized. Based on origin to terminus ratios, chromosome content per cell, measured by flow cytometry, and sensitivity to the replication fork inhibitor hydroxyurea, the suppressors fell into two distinct categories: those that directly inhibit over‐initiation of DNA replication and those that act independently of initiation. Mutations that decrease the cellular level of HolC, the χ subunit of DNA polymerase, or loss of ndk (nucleoside diphosphate kinase) function fall into the latter category. We propose that these novel suppressor mutations function by decreasing the efficiency of replication fork movement in vivo, either by decreasing the dynamic exchange of DNA polymerase subunits in the case of HolC, or by altering the balance between DNA replication and deoxynucleoside triphosphate synthesis in the case of ndk. Additionally, our results indicate a direct correlation between over‐initiation and sensitivity to replication fork inhibition by hydroxyurea, supporting a model of increased head‐to‐tail replication fork collisions due to over‐initiation.
Pharmacokinetics of enteric‐coated mycophenolate sodium in stable liver transplant recipients
Authors: Perry Theodore W. , Christians Uwe , Trotter James F. , Bendrick‐Peart Jamie 
Published: March 2007

Abstract:  Introduction:  Mycophenolate mofetil (MMF) is one of the major immunosuppressive agents used in liver transplantation recipients. In an attempt to mitigate one of the most common side effects of MMF (gastrointestinal symptoms), enteric‐coated mycophenolate sodium (EC‐MPS) was developed. In this study, we report the pharmacokinetic profile of EC‐MPS in stable liver transplantation recipients administered a single 720 mg dose.Methods:  Liver transplantation recipients more than one yr after transplantation were administered a single dose of 720 mg EC‐MPS after which blood levels of MPA were measured at frequent intervals using a specific and validated LC‐MS/MS assay.Results:  The characteristics of the 21 patients studied were: mean age was 55.9 yr, 13 were female, eight had hepatitis C, and 14 were on tacrolimus. The mean apparent half‐life of MPA was 5.3 ± 4.3 h, (1.0–15.7). Mean tmax was 2.4 ± 1.1 h (1.0–5.0). The mean area‐under‐curve was 45.3 ± 23.1 μg‐h/mL (17.3–90.0). Trough level concentrations (C12 h) showed large inter‐individual variability (0–9.2 μg/mL). There was no difference in any of the pharmacokinetic parameters relative to: gender, HCV, administration of tacrolimus vs. cyclosporine or type of biliary anastomosis.Conclusions:  There is a wide variation in pharmacokinetic parameters in stable, long‐term liver transplantation recipients receiving a single dose of EC‐MPS. These data suggest that therapeutic drug monitoring with EC‐MPS may have limited utility in liver transplantation recipients.
Allograft inflammatory factor‐1 and tumor necrosis factor single nucleotide polymorphisms in systemic sclerosis
Authors: Otieno F. G. , Lopez A. M. , Jimenez S. A. , Gentiletti J. , Artlett C. M. 
Published: March 2007

AbstractTumor necrosis factor (TNF) alleles have been associated with systemic sclerosis (SSc); however, these alleles may be in linkage with other genes. Allograft inflammatory factor‐1 (AIF‐1) is a newly identified gene on the short arm of chromosome 6 in the class III region of the human leukocyte antigen. It appears to be involved in inflammation and was originally identified in rat cardiac allografts undergoing rejection. AIF‐1 has several sequence variations (single nucleotide polymorphisms, SNPs), three of which result in nonsynonymous changes in amino acid coding. We analyzed the linkage of five TNFA and five AIF‐1 SNPs by polymerase chain reaction in 239 Caucasian individuals. The TNFA−1031T/T genotype was found to be associated with SSc (P < 0.0001) and both the DcSSc (diffuse subset of SSc) and the LcSSc (limited subset of SSc) subsets (P= 0.0004 and P= 0.0009, respectively) and the TNFA−237G/G genotype was found to be associated with all SSc (P= 0.0003) and with the DcSSc and LcSSc subsets (P= 0.01 and P= 0.005, respectively). Furthermore, the TNFA−857C/T genotype was associated with LcSSc (P= 0.0003) and TNFA−307A/A genotype associated with DcSSc (P= 0.028). In AIF‐1, RS2269475 exon 4A allele, which generates a nonsynonymous change (tryptophan to arginine), was significantly associated in patients with SSc (P= 0.0009) and was associated with those patients who had DcSSc (P= 0.002). A strong linkage disequilibrium was observed between the AIF‐1 alleles, A allele of RS2269475 and the A allele of RS4711274 (P < 0.0001), and linkage was observed between AIF‐1 and TNFA alleles. Here, we report a novel and significant association of a nonsynonymous change within the AIF‐1 with SSc and identified the linkage with TNFA alleles within 50 kb of this gene. Our study lends support that TNFA may be an important inflammatory modulator in SSc and may play a significant role with AIF‐1 in disease pathogenesis.
Comparison of propofol and isoflurane anesthesia in orthotopic pig‐to‐baboon cardiac xenotransplantation
Authors: Bauer Andreas , Baschnegger Heiko , Renz Vivian , Brandl Ulrike , Brenner Paolo , Thein Eckart , Reichart Bruno , Schmoeckel Michael , Christ Frank 
Published: March 2007

Abstract:Background:  Orthotopic pig‐to‐baboon xenogeneic heart transplantation (oXHTx) is the only accepted preclinical animal model for cardiac xenotransplantation. We compared the hemodynamic stability of a propofol‐ and isoflurane‐based anesthetic regimen during oXHTx.Methods:  Hearts from 12 hDAF or hCD46 transgenic pigs (Sus scrofa; body weight 7 to 32 kg) were transplanted into baboons (Papio anubis and Papio hamadryas; body weight 9 to 26 kg) in the orthotopic life‐supporting position. Animals received a propofol‐based intravenous regimen or inhalation anesthesia with isoflurane. Analgesia was achieved with fentanyl in both groups. Systemic hemodynamic variables were measured before, during and after cardiopulmonary bypass (CPB) and the need for inotropic or vasoactive pharmacological support was compared before and after CPB.Results:  Global hemodynamic variables [i.e. heart rate, mean arterial pressure (MAP) and cardiac output] were not significantly different in propofol‐anesthetized baboons compared to baboons anesthetized with isoflurane. Baboons anesthetized with isoflurane showed a trend towards less pharmacological support required to achieve an adequate MAP of >60 mmHg after CPB (propofol: epinephrine 0.13 [0.05; 0.16] and norepinephrine 0.15 [0.02; 0.16] μg/kg/min vs. isoflurane: epinephrine 0.05 [0.02; 0.08] and norepinephrine 0.06 [0.02; 0.19] μg/kg/min; no significant difference).Conclusions:  Propofol and isoflurane appear to provide equal hemodynamic stability in orthotopic cardiac pig‐to‐baboon xenotransplantation prior to the start of CPB. The trend of a reduced catecholamine support needed after CPB, however, suggests that isoflurane may be the preferred drug for maintenance of anesthesia in this primate model.
Mycophenolate mofetil treatment for therapy‐resistant glomerulopathies
Authors: SAHIN GULIZAR MANGA , SAHIN SEVGI , KANTARCI GULCIN , ERGIN HUIYA 
Published: March 2007

SUMMARY:Background:  The management of steroid‐resistant glomerulopathies remains a clinical problem. In this trial, we report a clinical observation of 43 patients treated with mycophenolate mofetil (MMF) for steroid‐resistant glomerulopathies.Methods:  All patients underwent renal biopsies, and immunofluorescence and light microscopy examinations were conducted in all cases. All patients had been treated with prednisone at a dose of 1 mg/kg per day for at least 8 weeks. Of the 43 patients, 16 were treated with cyclophosphamide and five were treated with cyclosporine A before MMF started. The primary study outcomes were the change in the urinary protein excretion, serum creatinine, comparing the levels at the start of MMF treatment with those at the end of the MMF treatment period. Changes in renal function were also estimated with Modification of Diet in Renal Failure calculation. Wilcoxon signed‐ranks test was used as appropriate to compare data from the start with data at the end of the treatment period.Results:  The primary glomerular diseases represented included membranoproliferative glomerulonephritis in 23.2%, membranous glomerulonephritis in 18.6%, IgA nephropathy in 13.9%, focal segmental glomerulosclerosis in 9.3%, lupus nephritis (systemic lupus erythematosus) in 25.6% and pauci‐immune glomerulopathy in 9.3% of patients. The mean follow‐up time was 28.9 ± 12 months. Before MMF treatment, 16 patients (37%) had nephrotic range proteinuria and 11 (26%) had renal insufficiency. The urinary protein before MMF treatment was 3.3 ± 2.6 g/dL (0.6–9.6) and decreased significantly to 0.87 ± 1.1 g/dL (0–5.5) at the end of the MMF treatment period (P = 0.02). During treatment, complete remission was seen in 27 patients, partial remission in 10 patients and MMF failure in six patients. The serum creatinine level decreased significantly from 1.29 ± 0.55 mg/dL (0.6–3.0) to 1.14 ± 0.38 mg/dL (0.5–2.4) post MMF therapy (P = 0.046). Using the four‐variable Modification of Diet in Renal Failure formula, the glomerular filtration rate increased from 71.5 ± 28 mL/min per 1.73 m2 to 78.1 ± 27 mL/min per 1.73 m2 (P = 0.021). Renal insufficiency resolved in seven of the 11 (63.6%) patients with renal insufficiency initially, two with membranoproliferative glomerulonephritis, two with membranous glomerulonephritis, one with focal segmental glomerulosclerosis, four with pauci‐immune glomerulopathy, two with systemic lupus erythematosus nephritis, and in two patients de novo renal insufficiency developed.Conclusion:  In general, MMF was well tolerated, and most of the patients achieved remission and improvement of renal functions. MMF treatment appeared to offer benefits to problematic patients refractory to conventional therapies for glomerulopathies.
Dengue has a benign presentation in renal transplant patients: A case series
Authors: RENAUD CLAUDE JEFFREY , MANJIT KAUR , PARY SIVARAMAN 
Published: March 2007

SUMMARY:Aim:  Dengue fever and its complications are a poorly described entity in the renal transplant population. Previous reports in renal transplant patients suggest a high mortality rate.Methods:  We undertook a retrospective study of six cases of dengue fever in renal transplant patients during a dengue outbreak in Singapore in 2005 which involved a total of 1400 cases in the city state.Results:  Mean thrombocytopenia was 130 000/μL on presentation and 80 000/μL at deffervescence. No dengue haemorrhagic fever, dengue shock syndrome, deaths or abnormal graft function were observed. Mean hospital stay was 8.6 days. Four of six patients also had simultaneous CMV reactivation.Conclusion:  In common with the majority of adults, dengue fever follows a benign course in the renal transplant population and dengue haemorrhagic fever is rare. This may be related to the relative immunosuppression reducing the risk for antibody‐enhanced complications.
Benazepril slows progression of renal dysfunction in patients with non‐diabetic renal disease
Authors: ISHIMITSU TOSHIHIKO , AKASHIBA AKIRA , KAMEDA TOMOKO , TAKAHASHI TOSHIAKI , OHTA SATOSHI , YOSHII MASAYOSHI , MINAMI JUNICHI , ONO HIDEHIKO , NUMABE ATSUSHI , MATSUOKA HIROAKI 
Published: March 2007

SUMMARY:Aim:  The present study examined the effects of benazepril, an angiotensin‐converting enzyme inhibitor, on the progression of renal insufficiency in patients with non‐diabetic renal disease.Methods:  Fifteen patients with non‐diabetic renal disease whose serum creatinine (Cr) ranged from 1.5 to 3.0 mg/dL were given either benazepril (2.5–5 mg) or placebo once daily for 1 year in a random crossover manner. In both periods, antihypertensive medications were increased if blood pressure was greater than 130/85 mmHg. Blood sampling and urinalysis were performed bimonthly throughout the study period.Results:  Blood pressure was similar when comparing the benazepril and the placebo periods (128 ± 12/83 ± 6 vs 129 ± 10/83 ± 7 mmHg). Serum Cr significantly increased from 1.62 ± 0.18 to 1.72 ± 0.30 mg/dL (P = 0.036) during the placebo period, while there was no statistically significant increase in serum Cr during the benazepril period (from 1.67 ± 0.17 to 1.71 ± 0.27 mg/dL). The slope of decrease of the reciprocal of serum Cr was steeper in the placebo period than in the benazepril period (−0.073 ± 0.067 vs−0.025 ± 0.096/year, P = 0.014). Urinary protein excretion was lower during the benazepril period than during the placebo period (0.57 ± 0.60 vs 1.00 ± 0.85 g/gCr, P = 0.006). Serum K was significantly higher in the benazepril period than in the placebo period (4.4 ± 0.5 vs 4.2 ± 0.5 mEq/L, P < 0.001), but no patient discontinued benazepril therapy as a result of hyperkalemia.Conclusion:  Long‐term benazepril treatment decreased the progression of renal dysfunction in patients with non‐diabetic renal disease by a mechanism that is independent of blood pressure reduction.
Impacts of forest fragmentation on species composition and forest structure in the temperate landscape of southern Chile
Authors: Echeverría Cristian , Newton Adrian C. , Lara Antonio , Benayas José María Rey , Coomes David A. 
Published: March 2007

ABSTRACTAim  Few studies have explicitly examined the influence of spatial attributes of forest fragments when examining the impacts of fragmentation on woody species. The aim of this study was to assess the diverse impacts of fragmentation on forest habitats by integrating landscape‐level and species‐level approaches.Location  The investigation was undertaken in temperate rain forests located in southern Chile. This ecosystem is characterized by high endemism and by intensive recent changes in land use.Method  Measures of diversity, richness, species composition, forest structure and anthropogenic disturbances were related to spatial attributes of the landscape (size, shape, connectivity, isolation and interior forest area) of forest fragments using generalized linear models. A total of 63 sampling plots distributed in 51 forest fragments with different spatial attributes were sampled.Results  Patch size was the most important attribute influencing different measures of species composition, stand structure and anthropogenic disturbances. The abundance of tree and shrub species associated with interior and edge habitats was significantly related to variation in patch size. Basal area, a measure of forest structure, significantly declined with decreasing patch size, suggesting that fragmentation is affecting successional processes in the remaining forests. Small patches also displayed a greater number of stumps, animal trails and cow pats, and lower values of canopy cover as a result of selective logging and livestock grazing in relatively accessible fragments. However, tree richness and β‐diversity of tree species were not significantly related to fragmentation.Main conclusions  This study demonstrates that progressive fragmentation by logging and clearance is associated with dramatic changes in the structure and composition of the temperate forests in southern Chile. If this fragmentation process continues, the ability of the remnant forests to maintain their original biodiversity and ecological processes will be significantly reduced.
Does size matter for dispersal distance?
Authors: Jenkins David G. , Brescacin Camille R. , Duxbury Craig V. , Elliott Jennifer A. , Evans Jennafer A. , Grablow Katherine R. , Hillegass Melissa , Lyon Boyd N. , Metzger Genevieve A. , Olandese Michelle L. , Pepe Diana , Silvers Greg A. , Suresch Hiliary N. , Thompson Tracy N. , Trexler Christina M. , Williams Graham E. , Williams Natalie C. , Williams Sara E. 
Published: March 2007

ABSTRACTAim  The aim of this study is to answer the questions: (1) do small organisms disperse farther than large, or vice versa; and (2) does the observed pattern differ for passive and active dispersers? These questions are central to several themes in biogeography (including microbial biogeography), macroecology, metacommunity ecology and conservation biology.Location  The meta‐analysis was conducted using published data collected worldwide.Methods  We collected and analysed 795 data values in the peer‐reviewed literature for direct observations of both maximal dispersal distance and mass of the dispersing organisms (e.g. seeds, not trees). Analysed taxa ranged in size from bacteria to whales. We applied macroecology analyses based on null models (using Monte Carlo randomizations) to test patterns relative to specific hypotheses.Results  Collected dispersal distance and mass data spanned 9 and 21 orders of magnitude, respectively. Active dispersers dispersed significantly farther (P < 0.001) and were significantly greater in mass (P < 0.001) than passive dispersers. Overall, size matters: larger active dispersers attained greater maximum observed dispersal distances than smaller active dispersers. In contrast, passive‐disperser distances were random with respect to propagule mass, but not uniformly random, in part due to sparse data available for tiny propagules.Conclusions  Size is important to maximal dispersal distance for active dispersers, but not for passive dispersers. Claims that microbes disperse widely cannot be tested by current data based on direct observations of dispersal: indirect approaches will need to be applied. Distance–mass relationships should contribute to a resolution of neutral and niche‐based metacommunity theories by helping scale expectations for dispersal limitation. Also, distance–mass relationships should inform analyses of latitudinal species richness and conservation biology topics such as fragmentation, umbrella species and taxonomic homogenization.
Stakeholder appraisal of policy options for responding to obesity in Finland
Authors: Borg P. , Fogelholm M. 
Published: March 2007

SummaryThe aim of the Finnish Policy Options for Responding to the Growing Challenge of Obesity Research Project study was to use a multi‐criteria mapping method to assess stakeholder opinions on policies that might have relevance when planning policies targeting obesity prevention. When evaluating policies, criteria relating to ‘Positive societal benefits’ and ‘Additional health benefits’ were often considered important, along with the more obvious ‘Efficacy in addressing obesity’. Other criteria (like economic factors) were of less importance. All policy options targeting at ‘Educational and Research Initiatives’ were highly ranked in the analysis by all stakeholders. Policies aimed at improving ‘Food‐Related Informational Initiatives’ were also ranked well on average, although more variation between stakeholders existed. Policies targeting increased physical activity and easier access/provision to healthy foods received also relatively good rankings but with wide variation and doubts in the appraisals. Policies encouraging new technological innovations and institutional reforms were mostly ranked poorly and were not seen as solutions to obesity problem. Irrespective of the stakeholder group, it seems that while traditional educational policies were most highly ranked, several other policies are also viable options in the policy portfolio of obesity prevention.
Stakeholder views on policy options for responding to the growing challenge from obesity in France: findings from the PorGrow project
Authors: Holdsworth M. , Kameli Y. , Delpeuch F. 
Published: March 2007

SummaryTo explore the perspectives of key stakeholders towards a range of policy options to prevent obesity in France, a multi‐criteria mapping method was used to gather quantitative and qualitative data from 21 types of stakeholder groups. During structured interviews, stakeholders appraised a set of pre‐defined options by reference to criteria of their own choosing and provided relative weights to their criteria, and overall rankings of the policy options. Efficacy, feasibility and societal benefits were the groups of criteria given most importance by stakeholders. There was most consensus and preference for options related to health education, particularly in schools, compared with options that aimed at changing the environment to prevent obesity, i.e. options around physical activity; options that modified food supply and demand; and information‐related options. There was little support for technological solutions or institutional reforms. While there was broad interest in a range of different options, those related to behaviour change through education were the most valued by stakeholders. Raising awareness among policymakers about the convincing scientific evidence for the effectiveness of environmental level policy options will be a crucial first step.