bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure of the DNA-SspC Complex: Implications for DNA Packaging, Protection, and Repair in Bacterial Spores
Authors: Frenkiel-Krispin Daphna , Sack Rinat , Englander Joseph , Shimoni Eyal , Eisenstein Miriam , Bullitt Esther , Horowitz-Scherer Rachel , Hayes Christopher S. , Setlow Peter , Minsky Abraham , Wolf Sharon Grayer 
Published: May 2004

ABSTRACT
Bacterial spores have long been recognized as the sturdiest known life forms on earth, revealing extraordinary resistance to a broad range of environmental assaults. A family of highly conserved spore-specific DNA-binding proteins, termed α/β-type small, acid-soluble spore proteins (SASP), plays a major role in mediating spore resistance. The mechanism by which these proteins exert their protective activity remains poorly understood, in part due to the lack of structural data on the DNA-SASP complex. By using cryoelectron microscopy, we have determined the structure of the helical complex formed between DNA and SspC, a characteristic member of the α/β-type SASP family. The protein is found to fully coat the DNA, forming distinct protruding domains, and to modify DNA structure such that it adopts a 3.2-nm pitch. The protruding SspC motifs allow for interdigitation of adjacent DNA-SspC filaments into a tightly packed assembly of nucleoprotein helices. By effectively sequestering DNA molecules, this dense assembly of filaments is proposed to enhance and complement DNA protection obtained by DNA saturation with the α/β-type SASP.
The Essential Nature of the Ubiquitous 26-Kilobase Circular Replicon ofBorrelia burgdorferi
Authors: Byram Rebecca , Stewart Philip E. , Rosa Patricia 
Published: May 2004

ABSTRACTThe genome of the type strain (B31) ofBorrelia burgdorferi, the causative agent of Lyme disease, is composed of 12 linear and 9 circular plasmids and a linear chromosome. Plasmid content can vary among strains, but one 26-kb circular plasmid (cp26) is always present. The ubiquitous nature of cp26 suggests that it provides functions required for bacterial viability. We tested this hypothesis by attempting to selectively displace cp26 with an incompatible but replication-proficient vector, pBSV26. While pBSV26 transformants contained this incompatible vector, the vector coexisted with cp26, which is consistent with the hypothesis that cp26 carries essential genes. Several cp26 genes with ascribed or predicted functions may be essential. These include the BBB29 gene, which has sequence homology to a gene encoding a glucose-specific phosphotransferase system component, and theresTgene, which encodes a telomere resolvase involved in resolution of the replicated telomeres of the linear chromosome and plasmids. The BBB29 gene was successfully inactivated by allelic exchange, but attempted inactivation ofresTresulted in merodiploid transformants, suggesting thatresTis required forB. burgdorferigrowth. To determine ifresTis the only cp26 gene essential for growth, we introducedresTintoB. burgdorferion pBSV26. This did not result in displacement of cp26, suggesting that additional cp26 genes encode vital functions. We concluded thatB. burgdorferiplasmid cp26 encodes functions critical for survival and thus shares some features with the chromosome.
Methionine Sulfoxide Reductase A (MsrA) Deficiency Affects the Survival ofMycobacterium smegmatiswithin Macrophages
Authors: Douglas T. , Daniel D. S. , Parida B. K. , Jagannath C. , Dhandayuthapani S. 
Published: May 2004

ABSTRACTMethionine sulfoxide reductase A (MsrA) is an antioxidant repair enzyme which reduces oxidized methionine to methionine. Since oxidation of methionine in proteins impairs their function, an absence of MsrA leads to abnormalities in different organisms, including alterations in the adherence patterns and in vivo survival of certain pathogenic bacteria. To understand the role of MsrA in intracellular survival of bacteria, we disrupted the gene encoding MsrA inMycobacterium smegmatisthrough homologous recombination. ThemsrAmutant strain ofM. smegmatisexhibited significantly reduced intracellular survival in murine J774A.1 macrophages compared to the survival of its wild-type counterpart. Furthermore, immunofluorescence and immnunoblotting of phagosomes containingM. smegmatisstrains revealed that the phagosomes with themsrAmutant strain acquired both p67phoxof phagocyte NADPH oxidase and inducible nitric oxide synthase much earlier than the phagosomes with the wild-type strain. In addition, themsrAmutant strain ofM. smegmatiswas observed to be more sensitive to hydroperoxides than the wild-type strain was in vitro. These results suggest that MsrA plays an important role in both extracellular and intracellular survival ofM. smegmatis.
DNA Binding Regions of Q Proteins of Phages λ and φ80
Authors: Guo Jingshu , Roberts Jeffrey W. 
Published: May 2004

ABSTRACT

Bacteriophage λ gene
Q
protein and the related proteins of other lambdoid phages are transcription antiterminators that interact both with DNA in the late gene promoter segment and with RNA polymerase subunits. Using hybrids between Q of λ and the related Q of phage 80, we characterized elements of both Q and DNA that contribute to the DNA binding function. In particular, we found a C-terminal segment of the protein that is responsible for binding specificity and an ∼15 residue segment on a predicted alpha helix within this segment at which alanine substitutions decrease DNA binding. We identified a six-nucleotide segment located between the −35 and −10 promoter elements that confers binding specificity and is the site of point mutants that impair binding, and we isolated suppressors in λ Q that restore binding function by increasing the overall binding affinity. We also identified putative zinc finger structures in both proteins.
TheSinorhizobium meliloti furGene Regulates, with Dependence on Mn(II), Transcription of thesitABCDOperon, Encoding a Metal-Type Transporter
Authors: Chao Tzu-Chiao , Becker Anke , Buhrmester Jens , Pühler Alfred , Weidner Stefan 
Published: May 2004

ABSTRACTSinorhizobium melilotiis an alpha-proteobacterium able to induce nitrogen-fixing nodules on roots of specific legumes. In order to propagate in the soil and for successful symbiotic interaction the bacterium needs to sequester metals like iron and manganese from its environment. The metal uptake has to be in turn tightly regulated to avoid toxic effects. In this report we describe the characterization of a chromosomal region ofS. melilotiencoding thesitABCDoperon and the putative regulatoryfurgene. It is generally assumed that thesitABCDoperon encodes a metal-type transporter and that thefurgene is involved in iron ion uptake regulation. A constructedS. meliloti sitAdeletion mutant was found to be growth dependent on Mn(II) and to a lesser degree on Fe(II). ThesitApromoter was strongly repressed by Mn(II), with dependence on Fur, and moderately by Fe(II). Applying a genome-wideS. melilotimicroarray it was shown that in thefurdeletion mutant 23 genes were up-regulated and 10 genes were down-regulated when compared to the wild-type strain. Among the up-regulated genes only thesitABCDoperon could be associated with metal uptake. On the other hand, the completerhbABCDEFoperon, which is involved in siderophore synthesis, was identified among the down-regulated genes. Thus, inS. melilotiFur is not a global repressor of iron uptake. Under symbiotic conditions thesitApromoter was strongly expressed and theS. meliloti sitAmutant exhibited an attenuated nitrogen fixation activity resulting in a decreased fresh weight of the host plantMedicago sativa.
A Cytochrome P450 Involved in the Metabolism of Abietane Diterpenoids byPseudomonas abietaniphilaBKME-9
Authors: Smith Daryl J. , Martin Vincent J. J. , Mohn William W. 
Published: May 2004

ABSTRACTDiterpenoids are naturally occurring plant compounds which have pharmaceutical properties. We have sequenced a 10.4-kbp extension of theditcluster inPseudomonas abietaniphilaBKME-9, containing genes involved in abietane diterpenoid biodegradation. TheditQgene was found to encode a cytochrome P450 monooxygenase, P450dit, and to be homologous to thetdtDgene ofPseudomonas diterpeniphilaA19-6a. Knocking outditQhad little effect on growth of BKME-9 on abietic acid but severely impaired growth on dehydroabietic acid (DhA) and palustric acid (PaA), increasing doubling times from 3.8 to 15 h on DhA and from 5.6 to 18.5 h on PaA. AxylEtranscriptional fusion showed that transcription ofditQwas induced by a range of diterpenoids. Substrate binding assays of P450ditexpressed inEscherichia colirevealed that DhA binds to the enzyme and yields a type I binding spectrum with aKdof 0.4 μM. These results indicate that P450ditis involved in the metabolism of DhA and PaA and are consistent with its putative role in converting DhA to 7-hydroxy-DhA. Finally, an amino acid sequence identity of greater than 72% and conserved gene arrangement support the hypothesis that theditgene cluster ofP. abietaniphilaBKME-9 and thetdtcluster ofP. diterpeniphilaA19-6a contain functional homologues.
Dimethylselenide Demethylation Is an Adaptive Response to Selenium Deprivation in the Archaeon
Methanococcus voltae
Authors: Niess Ulf M. , Klein Albrecht 
Published: May 2004

ABSTRACT

The archaeon
Methanococcus voltae
needs selenium for optimal growth. A gene group most likely involved in the demethylation of dimethylselenide was discovered, the expression of which is induced upon selenium deprivation. The operon comprises open reading frames for a corrinoid protein and two putative methyltransferases. It is shown that the addition of dimethylselenide to selenium-depleted growth medium relieves the lack of selenium, as indicated by the repression of a promoter of a transcription unit encoding selenium-free hydrogenases which is normally active only upon selenium deprivation. Knockout mutants of the corrinoid protein or one of the two methyltransferase genes did not show repression of the hydrogenase promoter in the presence of dimethylselenide. The mutation of the other methyltransferase gene had no effect. Growth rates of the two effective mutants were reduced compared to wild-type cells in selenium-limited medium in the presence of dimethylselenide.
Escherichia coli mazEF
-Mediated Cell Death Is Triggered by Various Stressful Conditions
Authors: Hazan Ronen , Sat Boaz , Engelberg-Kulka Hanna 
Published: May 2004

ABSTRACT

mazEF
is an
Escherichia coli
suicide module specific for a stable toxin and a labile antitoxin. Inhibiting
mazEF
expression appeared to activate the module to cause cell death. Here we show that several stressful conditions, including high temperatures, DNA damage, and oxidative stress, also induce
mazEF
-mediated cell death. We also show that this process takes place only during logarithmic growth and requires an intact
relA
gene.
Professional and medical outcomes for French train drivers after “person under train” accidents: three year follow up study
Authors: Cothereau C , de Beaurepaire C , Payan C , Cambou J P , Rouillon F , Conso F 
Published: May 2004

Aims:To investigate psychiatric disorders, somatic health, and professional effects in French train drivers having experienced a “person under train” accident, and somatic health and professional effects.Methods:A total of 202 train drivers were evaluated several times: immediately after the event, three months later, and one, two, and three years later. These drivers were compared with 186 train drivers not exposed to that psychotraumatic shock. The evaluations relied primarily on the GHQ-28 and MINI questionnaires.Results:In the exposed group, at the first evaluation, the prevalence of post-traumatic stress was 4%; scores ⩾5 on the GHQ-28 were significantly higher than in the non-exposed group (32% versus 6%), for both the overall result and three sub-scores (somatic symptoms, anxiety and sleep, and psychosocial functioning). All these differences disappeared within a year. Vulnerability factors concerned prior traumas, acute and lasting life events, and the particular occupational situation where the driver is not accompanied but drives the train away alone in the aftermath of the accident. Over 95% of subjects had no short, medium, or long term impairment of their occupational fitness.Conclusions:Most of the psycho-behavioural disorders were observed in the immediate aftermath of the accident and disappeared within a year. The driver’s occupational future does not seem to be affected by the “person under train” accident. Consideration of a traumatic accident as a job related risk and close psychological support of drivers after an accident probably increase the subject’s ability to recover from the event.
Enhanced oxidative stress in workers with a standing occupation: Table 1
Authors: Flore R , Gerardino L , Santoliquido A , Pola R , Flex A , Di Campli C , Pola P , Tondi P 
Published: May 2004

Background:Several epidemiological studies have shown a statistically significant association between standing work and chronic venous insufficiency of lower limbs. This condition has been associated with an enhanced oxidative stress that, according to the literature, could represent a risk factor for cardiovascular and other systemic diseases.Aims and Methods:To evaluate venous pressure of the lower limbs and reactive oxygen species (ROS) before and after work in 62 workers with a standing occupation (surgery room nurses) and 65 outpatient department nurses who can walk during their working time.Results:After work, a statistically significant increase of venous pressure of the lower limbs levels was observed in both the study group and controls. Standing workers showed significantly higher mean levels of ROS after work.
Mortality and cancer incidence in New Zealand meat workers
Authors: McLean D , Cheng S , ’t Mannetje A , Woodward A , Pearce N 
Published: May 2004

Aims:To ascertain whether there is an increased risk of cancers of the lung and lymphohaematopoietic tissue in workers employed in the New Zealand meat processing industry, and to identify exposures associated with any increased risks.Methods:A cohort of 6647 individuals assembled from personnel records from three plants was followed from 1988 until 2000. The observed number of deaths and cancer registrations was compared with expected numbers using five year age and gender specific rates for the New Zealand population. Subgroup analyses evaluated the effect of duration of exposure to selected agents, based on job titles and departments.Results:Vital status was determined for 84% of the cohort, and 92% of the total possible person-years. Mortality from all causes and all cancers was increased, and there was a significant excess of lung cancer. There were significant trends of increasing risk of lung and lymphohaematopoietic cancer with increasing duration of exposure to biological material.Conclusions:Excess risks were observed for mortality from all causes, all cancers, and lung cancer. Although the increased risk of lung cancer may be partly due to confounding by smoking, it is unlikely to be entirely due to this cause. Furthermore, the dose-response relation observed for lung cancer suggests the effect is related to exposure to biological material contained in animal urine, faeces, and blood. Although numbers were small, the risk of lymphohaematopoietic cancer was also associated with increasing duration and level of exposure to biological material.
Letters to the Editor
Authors: Rothe Carl F. 
Published: May 2004

The following is the abstract of the article discussed in the subsequent letters: The National Research Council-sponsored report, BIO 2010: Transforming Undergraduate Education for Future Research Biologists, describes a number of significant changes that should be made to the undergraduate biology curriculum if we are to adequately train students to become the researchers of the 21st century. What should be of concern to the physiology community is the lack of identifiable physiology in the proposed revisions. This article describes the report and suggests some steps that physiologists can take to enhance our discipline in the undergraduate biology curriculum.
Morphologic Findings of Coronary Atherosclerotic Plaques in Diabetics
Authors: Burke Allen P. , Kolodgie Frank D. , Zieske Arthur , Fowler David R. , Weber Deena K. , Varghese P. Jacob , Farb Andrew , Virmani Renu 
Published: May 2004

Objective—Coronary atherosclerotic plaque composition of diabetic subjects and localization of receptor for advanced glycation end products (RAGE) and its ligands have not been extensively studied.Methods and Results—Hearts from diabetic subjects and age, race, and sex-matched nondiabetic subjects dying suddenly were examined. Coronary arteries were dissected and lesions were evaluated for plaque burden, necrotic core size, and inflammatory infiltrate. The expression of RAGE, the RAGE-binding protein (S100-A12, EN-RAGE), and cell death (apoptosis) were also determined. Lesions from type II diabetic subjects had larger mean necrotic cores (P=0.01) and greater total and distal plaque load (P<0.001) than nondiabetic subjects. Necrotic core size correlated positively with diabetic status, independent of other risk factors. Intimal staining for macrophages, T-cells, and HLA-DR was also significantly greater in diabetic subjects (P=0.03,P=0.003, andP<0.0001), respectively. The association of increased macrophage infiltrate was independent of cholesterol levels and patient age. Expression of RAGE and EN-RAGE was significantly greater in diabetic subjects (P=0.004) and was associated with apoptotic smooth muscle cells and macrophages.Conclusions—In sudden coronary death, inflammation and necrotic core size play a greater role in the progression of atherosclerosis in diabetic subjects. The expression of RAGE and EN-RAGE may further compromise cell survival and promote plaque destabilization.
Sustained correction of B-cell development and function in a murine model of X-linked agammaglobulinemia (XLA) using retroviral-mediated gene transfer
Authors: Yu Phyllis W. , Tabuchi Ruby S. , Kato Roberta M. , Astrakhan Alexander , Humblet-Baron Stephanie , Kipp Kevin , Chae Keun , Ellmeier Wilfried , Witte Owen N. , Rawlings David J. 
Published: May 2004

AbstractX-linked agammaglobulinemia (XLA) is a human immunodeficiency caused by mutations in Bruton tyrosine kinase (Btk) and characterized by an arrest in early B-cell development, near absence of serum immunoglobulin, and recurrent bacterial infections. Using Btk- and Tec-deficient mice (BtkTec–/–) as a model for XLA, we determined if Btk gene therapy could correct this disorder. Bone marrow (BM) from 5-fluorouracil (5FU)–treated BtkTec–/– mice was transduced with a retroviral vector expressing human Btk and transplanted into BtkTec–/– recipients. Mice engrafted with transduced hematopoietic cells exhibited rescue of both primary and peripheral B-lineage development, recovery of peritoneal B1 B cells, and correction of serum immunoglobulin M (IgM) and IgG3 levels. Gene transfer also restored T-independent type II immune responses, and B-cell antigen receptor (BCR) proliferative responses. B-cell progenitors derived from Btk-transduced stem cells exhibited higher levels of Btk expression than non-B cells; and marking studies demonstrated a selective advantage for Btk-transduced B-lineage cells. BM derived from primary recipients also rescued Btk-dependent function in secondary hosts that had received a transplant. Together, these data demonstrate that gene transfer into hematopoietic stem cells can reconstitute Btk-dependent B-cell development and function in vivo, and strongly support the feasibility of pursuing Btk gene transfer for XLA.
Glutathione S-transferase M1 polymorphism: a risk factor for hepatic venoocclusive disease in bone marrow transplantation
Authors: Srivastava Alok , Poonkuzhali Balasubramanian , Shaji Ramachandran V. , George Biju , Mathews Vikram , Chandy Mammen , Krishnamoorthy Rajagopal 
Published: May 2004

Abstract
Hepatic venoocclusive disease (HVOD) in bone marrow transplantation (BMT) is attributed to toxicity of cytoreductive agents, especially busulfan and cyclophosphamide, in the conditioning therapy. Busulfan, as well as the metabolites of cyclophosphamide, are conjugated with glutathione (GSH), catalyzed by enzymes of the glutathione S-transferase (GST) family. To assess the impact of polymorphisms of the GST genes, GSTM1 and GSTT1, on the risk of HVOD, we evaluated 114 consecutive patients with β-thalassemia major undergoing BMT. There was a significantly increased incidence of HVOD in patients with the GSTM1-null genotype compared with those with the GSTM1-positive genotype (46.5% vs 18.3%; P = .001). Pharmacokinetic analysis in these patients showed that the clearance of busulfan was higher and first-dose steady-state concentration was lower among those with HVOD (0.403 ± 0.06 vs 0.33 ± 0.071 L/h/kg, Student t test P value = .000 01; and 508 ± 125 vs 656 ± 255 ng/mL, t test P value = .001, respectively). We conclude that the GSTM1-null genotype predisposes to HVOD, and the sinusoidal endothelial cells and hepatocyte damage may be mediated by metabolites of busulfan through depletion of the cellular GSH pool.
Acute lymphoblastic leukemia with TEL-AML1 fusion has lower expression of genes involved in purine metabolism and lower de novo purine synthesis
Authors: Zaza Gianluigi , Yang Wenjian , Kager Leo , Cheok Meyling , Downing James , Pui Ching-Hon , Cheng Cheng , Relling Mary V. , Evans William E. 
Published: May 2004

AbstractBecause de novo purine synthesis (DNPS) is a target of widely used antileukemic agents (eg, methotrexate, mercaptopurine), we determined the rate of DNPS and the expression of genes involved in purine metabolism in different subtypes of acute lymphoblastic leukemia (ALL). Among 113 children with newly diagnosed ALL, lymphoblasts with the TEL-AML1 translocation had significantly lower DNPS than all other genetic subtypes of B-lineage ALL or T-lineage ALL (352 ± 57 versus 1001 ± 31 or versus 1315 ± 76 fmol/nmol/h, P &lt; .0001). By assessing the expression of 82 genes involved in purine metabolism (KEGG pathway database) in ALL blasts from 38 patients with B-lineage ALL (14 with TEL-AML1, 24 without), we identified 16 genes that were differentially expressed in TEL-AML1–positive and TEL-AML1–negative ALL (P &lt; .001, false discovery rate [FDR] = 5%). The pattern of expression of these 16 genes discriminated TEL-AML1–positive ALL with a true accuracy of 84% in an independent test set (n = 17, confidence interval 70% to 94%, P &lt; .001). Western blots of selected genes documented corresponding levels of the proteins encoded. Differentially expressed genes included HPRT, IMPDH, PAICS, and GART, all of which were expressed at a significantly lower level in TEL-AML1 ALL. These findings have established that TEL-AML1 ALL has significantly lower de novo purine synthesis and differential expression of genes involved in purine metabolism.