bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phylogenomic and Biochemical Characterization of ThreeLegionella pneumophilaPolypeptide Deformylases
Authors: Huang Jianzhong , Van Aller Glenn S. , Taylor Amy N. , Kerrigan John J. , Liu Wu-Schyong , Trulli Janice M. , Lai Zhihong , Holmes David , Aubart Kelly M. , Brown James R. , Zalacain Magdalena 
Published: June 2006

ABSTRACTLegionella pneumophilais a gram-negative facultative intracellular human pathogen that can cause fatal Legionnaires' disease. Polypeptide deformylase (PDF) is a novel broad-spectrum antibacterial target, and reports of inhibitors of PDF with potent activities againstL. pneumophilahave been published previously. Here, we report the identification of not one but three putativepdfgenes,pdfA,pdfB, andpdfC, in the complete genome sequences of three strains ofL. pneumophila. Phylogenetic analysis showed thatL. pneumophilaPdfA is most closely related to the commonly known γ-proteobacterial PDFs encoded by the genedef.PdfB and PdfC are more divergent and do not cluster with any specific bacterial or eukaryotic PDF. All three putativepdfgenes fromL. pneumophilastrain Philadelphia 1 have been cloned, and their encoded products have been overexpressed inEscherichia coliand purified. Enzymatic characterization shows that the purified PDFs with Ni2+substituted are catalytically active and able to remove the N-formyl group from several synthetic polypeptides, although they appear to have different substrate specificities. Surprisingly, while PdfA and PdfB with Zn2+substituted are much less active than the Ni2+forms of each enzyme, PdfC with Zn2+substituted was as active as the Ni2+form for the fMA substrate and exhibited substrate specificity different from that of Ni2+PdfC. Furthermore, the catalytic activities of these enzymes are potently inhibited by a known small-molecule PDF inhibitor, BB-3497, which also inhibits the extracellular growth ofL. pneumophila. These results indicate that even thoughL. pneumophilahas three PDFs, they can be effectively inhibited by PDF inhibitors which can, therefore, have potent anti-L. pneumophilaactivity.
Population Structure of
Francisella tularensis
Authors: Nübel Ulrich , Reissbrodt Rolf , Weller Annette , Grunow Roland , Porsch-Özcürümez Mustafa , Tomaso Herbert , Hofer Erwin , Splettstoesser Wolf , Finke Ernst-Jürgen , Tschäpe Helmut , Witte Wolfgang 
Published: June 2006

ABSTRACT

We have sequenced fragments of five metabolic housekeeping genes and two genes encoding outer membrane proteins from 81 isolates of
Francisella tularensis
, representing all four subspecies. Phylogenetic clustering of gene sequences from
F. tularensis
subsp.
tularensis
and
F. tularensis
subsp.
holarctica
aligned well with subspecies affiliations. In contrast,
F. tularensis
subsp.
novicida
and
F. tularensis
subsp.
mediasiatica
were indicated to be phylogenetically incoherent taxa. Incongruent gene trees and mosaic structures of housekeeping genes provided evidence for genetic recombination in
F. tularensis
.
Holdfast Formation in Motile Swarmer Cells Optimizes Surface Attachment duringCaulobacter crescentusDevelopment
Authors: Levi Assaf , Jenal Urs 
Published: June 2006

ABSTRACTThe adhesive holdfast is required for irreversible surface anchoring ofCaulobacter crescentuscells. The holdfast is synthesized early during swarmer cell development and, together with pili and a functional flagellum, contributes to optimal attachment during cell differentiation. We present evidence that the timing of holdfast formation in swarmer cells is regulated posttranslationally and is dependent on the diguanylate cyclase PleD.
Occurrence of Two 5-Aminolevulinate Biosynthetic Pathways in
Streptomyces nodosus
subsp.
asukaensis
Is Linked with the Production of Asukamycin
Authors: Petříček Miroslav , Petříčková Kateřina , Havlíček Libor , Felsberg Jürgen 
Published: June 2006

ABSTRACT

We report the results of cloning genes for two key biosynthetic enzymes of different 5-aminolevulinic acid (ALA) biosynthetic routes from
Streptomyces
. The genes encode the glutamyl-tRNA
Glu
reductase (GluTR) of the C
5
pathway and the ALA synthase (ALAS) of the Shemin pathway. While
Streptomyces coelicolor
A3(2) synthesizes ALA via the C
5
route, both pathways are operational in
Streptomyces nodosus
subsp.
asukaensis
, a producer of asukamycin. In this strain, the C
5
route produces ALA for tetrapyrrole biosynthesis; the ALA formed by the Shemin pathway serves as a precursor of the 2-amino-3-hydroxycyclopent-2-enone moiety (C
5
N unit), an antibiotic component. The growth of
S. nodosus
and
S. coelicolor
strains deficient in the GluTR genes (
gtr
) is strictly dependent on ALA or heme supplementation, whereas the defect in the ALAS-encoding gene (
hemA-asuA
) abolishes the asukamycin production in
S. nodosus
. The recombinant
hemA-asuA
gene was expressed in
Escherichia coli
and in
Streptomyces
, and the encoded enzyme activity was demonstrated both in vivo and in vitro. The
hemA-asuA
gene is situated within a putative cluster of asukamycin biosynthetic genes. This is the first report about the cloning of genes for two different ALA biosynthetic routes from a single bacterium.
RecA and RadA Proteins ofBrucella abortusDo Not Perform Overlapping Protective DNA Repair Functions following Oxidative Burst
Authors: Roux Christelle M. , Booth Natha J. , Bellaire Bryan H. , Gee Jason M. , Roop R. Martin , Kovach Michael E. , Tsolis Renée M. , Elzer Philip H. , Ennis Don G. 
Published: June 2006

ABSTRACTVery little is known about the role of DNA repair networks inBrucella abortusand its role in pathogenesis. We investigated the roles of RecA protein, DNA repair, and SOS regulation inB. abortus. WhilerecAmutants in most bacterial species are hypersensitive to UV damage, surprisingly aB. abortus recAnull mutant conferred only modest sensitivity. We considered the presence of a second RecA protein to account for this modest UV sensitivity. Analyses of theBrucellaspp. genomes and our molecular studies documented the presence of only onerecAgene, suggesting a RecA-independent repair process. Searches of the availableBrucellagenomes revealed some homology between RecA and RadA, a protein implicated inE. coliDNA repair. We considered the possibility thatB. abortusRadA might be compensating for the loss of RecA by promoting similar repair activities. We present functional analyses that demonstrated thatB. abortusRadA complements aradAdefect inE. colibut could not act in place of theB. abortusRecA. We show that RecA but not RadA was required for survival in macrophages. We also discovered thatrecAwas expressed at high constitutive levels, due to constitutive LexA cleavage by RecA, with little induction following DNA damage. Higher basal levels of RecA and its SOS-regulated gene products might protect against DNA damage experienced following the oxidative burst within macrophages.
Clinical ethical dilemmas: convergent and divergent views of two scholarly communities
Authors: Stiggelbout A M , Elstein A S , Molewijk B , Otten W , Kievit J 
Published: June 2006

Objective:To survey members of the American Society for Bioethics and Humanities (ASBH; n = 327) and of the Society for Medical Decision Making (SMDM; n = 77) to elicit the similarities and differences in their reasoning about two clinical cases that involved ethical dilemmas.Cases:Case 1 was that of a patient refusing treatment that a surgeon thought would be beneficial. Case 2 dealt with end-of-life care. The argument was whether intensive treatment should be continued of an unconscious patient with multiorgan failure.Method:Four questions, with structured multiple alternatives, were asked about each case: identified core problems, needed additional information, appropriate next steps and who the decision maker should be.Observations and results:Substantial similarities were noticed between the two groups in identifying the core problems, the information needed and the appropriate next steps. SMDM members gave more weight to outcomes and trade-offs and ASBH members had patient autonomy trump other considerations more strongly. In case 1, more than 60% of ASBH respondents identified the patient alone as the decision maker, whereas members of SMDM were almost evenly divided between having the patient as the solo decision maker or preferring a group of some sort as the decision maker, a significant difference (p<0.02). In case 2, both groups agreed that the question of discontinuing treatment should be discussed with the family and that the family alone should not be the decision maker.Conclusion:Despite distinctively different methods of case analysis and little communication between the two professional communities, many similarities were observed in the actual decisions they reached on the two clinical dilemmas.
Who is willing to take the risk? Assessing the readiness for living liver donation in the general German population
Authors: Popp F C , Eggert N , Hoy L , Lang S A , Obed A , Piso P , Schlitt H J , Dahlke M H 
Published: June 2006

Background:Shortage of donor organs is one of the major problems for liver transplant programmes. Living liver donation is a possible alternative, which could increase the amount of donor organs available in the short term.Objective:To assess the attitude towards living organ donation in the general population to have an overview of the overall attitude within Germany.Methods:A representative quota of people was evaluated by a mail questionnaire (n = 250). This questionnaire had 24 questions assessing the willingness to be a living liver donor for different potential recipients. Factors for and against living liver donation were assessed.Results:Donating a part of the liver was almost as accepted as donating a kidney. The readiness to donate was highest when participants were asked to donate for children. In an urgent life-threatening situation the will to donate was especially high, whereas it was lower in the case of recipient substance misuse. More women than men expressed a higher disposition to donate for their children. Sex, religion, state of health and age of the donor, however, did not influence other questions on the readiness to consider living organ donation. The will for postmortem organ donation positively correlated with the will to be a living organ donor.Conclusions:The motivation in different demographic subgroups to participate in living liver transplantation is described. Differences in donation readiness resulting from the situation of every donor and recipient are thoroughly outlined. The acceptance for a living liver donation was found to be high – and comparable to that of living kidney donation.
Can patients be sure they are fully informed when representatives of surgical equipment manufacturers attend their operations?: Table 1
Authors: Sillender M 
Published: June 2006

Objective:To determine the practice in UK hospitals regarding the level of patient involvement and consent when representatives of commercial surgical device manufacturers attend and advise during operations.Methods:An anonymous postal questionnaire was sent to the senior nurse in charge in all 236 UK gynaecology theatres in 2004. 79/236 (33%) replies were received.Results:Operating departments were visited every 2 weeks on average by a representative of the surgical device manufacturer. Actual operations were attended every 10 weeks, although there was much variation. 33/79 (42%) units consistently obtained patient consent for visits, usually orally, whereas 40/79 (51%) units did not. 65/79 (82%) units had no guidelines for surgical device representative visits. 91% of nurses in charge believed that there should be guidelines to protect both patients and staff. 6/79 (8%) units were preparing local guidelines at the time of the survey.Conclusions:Currently, patient safety, confidentiality and autonomy are being protected by a minority of NHS operating theatres when surgical device representatives attend surgery. National guidelines would hopefully ensure that fully informed patient consent is obtained and that representatives are fully trained and supervised.
New Teachers' Experiences of Hiring: Late, Rushed, and Information-Poor
Authors: Liu Edward , Johnson Susan Moore 
Published: June 2006

Purpose: Teacher hiring decisions have far-reaching consequences for a school, its students, and faculty. This article examines how new teachers in four states are hired and explores whether the process leads to good matches between these individuals and their schools. The authors conceive of hiring as a two-way process and examine the extent to which the hiring process provides opportunities for prospective teachers and schools to collect rich information about, and form accurate impressions of, one another. Research Methods: This study surveyed a representative random sample of 486 first-year and second-year teachers in California, Florida, Massachusetts, and Michigan. Participants were chosen using two-stage stratified cluster sampling, and the study achieved a response rate of 65%. Statistical methods used in the analysis include principal components analysis, chi-square analysis, and t tests. Findings: The data reveal that the majority of new teachers in these states are hired through a decentralized, school-based process. Despite the opportunity this provides schools and prospective teachers to explore the potential match between them, most new teachers actually have limited interactions with school-based personnel during the hiring process, and the process is relatively information-poor. Many new teachers are also hired quite late—more than one third of new teachers in California and Florida are hired after the school year has already started. Implications: The results of our analysis suggest that shifting hiring decisions to the school level is not sufficient to guarantee information-rich hiring. They also suggest that schools may need help removing barriers to conducting more information-rich hiring.
Accessing Internal Leadership Positions at School: Testing the Similarity-Attraction Approach Regarding Gender in Three Educational Systems in Israel
Authors: Addi-Raccah Audrey 
Published: June 2006

Background: Women school leaders may act as social agents who promote gender equality, but evidence is inconclusive regarding the effect of women's leadership on gender stratification in the workplace. Purpose: Based on the similarity-attraction perspective, this study examined male and female school leaders' relations to similar others in three educational systems: Jewish secular public schools, Jewish religious public schools, and Arab schools. As these school systems represent distinct sociocultural contexts regarding women's status, the study tested for differences among them in women's sponsorship of other women. Data Collection and Analysis: The study was based on a survey conducted by the Israel Central Bureau of Statistics in 2000 that included ( N = 63, 886) teachers and school administrators. The data were analyzed by conducting several multinomial logistic regression analyses in which the dependent variable was holding an internal leadership position within the school. Findings: The findings indicated that female school leaders have more diversified behavior to other women than male school leaders show in regard to men. The extent to which women promoted other women depended on their relative social power within each educational system. Conclusions: The study supports the claim that sponsoring similar others tends to be context bound, as gender inequality in holding internal administrative positions differed according to school principals'gender and to educational system. The implications of the study are discussed.
Going Beyond Role Expectations: Toward an Understanding of the Determinants and Components of Teacher Organizational Citizenship Behavior
Authors: Oplatka Izhar 
Published: June 2006

Purpose: To fill the gap in theoretical and empirical knowledge on the patterns of organizational citizenship behavior (OCB) in school, the aim of this study was to explore the components of teacher OCB as well as its personal and contextual determinants. Research Design: Semistructured interviews were conductedwith 50 schoolteachers, 10 principals, and 10 supervisors, all from the elementary and secondary educational systems of Israel. The analysis followed the principles of qualitative research. Findings: The article presents an initial conceptualization of the components of teacher OCB. Among these components are supportive behaviors toward students and colleagues, initiation of changes and innovations in teaching, strong orientation toward the organization, and strong loyalty to the teaching profession. In addition, the study identified a variety of determinants of teacher OCB, such as the school principal, the teacher's character, and the school's climate. Conclusions: Empirical and practical implications for the educational system and the educational research are suggested. Principals are strongly encouraged to establish a school environment that promotes OCB-oriented teachers and to create workshops to help him or her in this task. Researchers of educationalsystems are provided with new directions for research on the teacher's role and behavior.
Rac1 links leading edge and uropod events through Rho and myosin activation during chemotaxis
Authors: Pestonjamasp Kersi N. , Forster Carol , Sun Chunxiang , Gardiner Elisabeth M. , Bohl Ben , Weiner Orion , Bokoch Gary M. , Glogauer Michael 
Published: June 2006

Abstract
Chemotactic responsiveness is crucial to neutrophil recruitment to sites of infection. During chemotaxis, highly divergent cytoskeletal programs are executed at the leading and trailing edge of motile neutrophils. The Rho family of small GTPases plays a critical role in cell migration, and recent work has focused on elucidating the specific roles played by Rac1, Rac2, Cdc42, and Rho during cellular chemotaxis. Rac GTPases regulate actin polymerization and extension of the leading edge, whereas Rho GTPases control myosin-based contraction of the trailing edge. Rac and Rho signaling are thought to crosstalk with one another, and previous research has focused on mutual inhibition of Rac and Rho signaling during chemotaxis. Indeed, polarization of neutrophils has been proposed to involve the activity of a negative feedback system where Rac activation at the front of the cell inhibits local Rho activation, and vice versa. Using primary human neutrophils and neutrophils derived from a Rac1/Rac2-null transgenic mouse model, we demonstrate here that Rac1 (and not Rac2) is essential for Rho and myosin activation at the trailing edge to regulate uropod function. We conclude that Rac plays both positive and negative roles in the organization of the Rhomyosin “backness” program, thereby promoting stable polarity in chemotaxing neutrophils.
B-chronic lymphocytic leukemia cells and other B cells can produce granzyme B and gain cytotoxic potential after interleukin-21-based activation
Authors: Jahrsdörfer Bernd , Blackwell Sue E. , Wooldridge James E. , Huang Jian , Andreski Melinda W. , Jacobus Laura S. , Taylor Christiana M. , Weiner George J. 
Published: June 2006

AbstractB cells currently are not viewed as being capable of producing granzyme B or being cytotoxic. We found that B-chronic lymphocytic leukemia (B-CLL) cells treated with interleukin-21 (IL-21) produce low levels of granzyme B. The addition of either CpG oligodeoxynucleotide (ODN) or anti-B-cell-receptor antibody (anti-BCR) to IL-21 results in enhanced production of functional granzyme B by B-CLL cells. B-CLL cells treated with IL-21 and CpG ODN undergo apoptosis and are able to induce apoptosis of untreated bystander B-CLL cells. This effect can be inhibited by anti-granzyme B antibody. Benign human B cells, Epstein-Barr virus (EBV)-transformed lymphoblasts, and many standard lymphoma cell lines produce high levels of granzyme B in response to IL-21 and anti-BCR. Our results suggest that the ability to induce production of functional granzyme B by B cells could open new approaches to the therapy of B-CLL and other B-cell malignancies. Our findings also have significant implications for our understanding of the role of B cells for immune regulation and for a variety of immune phenomena, including cancer immunity, autoimmunity, and infectious immunity.
Specific killing of multiple myeloma cells by (-)-epigallocatechin-3-gallate extracted from green tea: biologic activity and therapeutic implications
Authors: Shammas Masood A. , Neri Paola , Koley Hemanta , Batchu Ramesh B. , Bertheau Robert C. , Munshi Vidit , Prabhala Rao , Fulciniti Mariateresa , Tai Yu tzu , Treon Steven P. , Goyal Raj K. , Anderson Kenneth C. , Munshi Nikhil C. 
Published: June 2006

AbstractEpigallocatechin-3-gallate (EGCG), a polyphenol extracted from green tea, is an antioxidant with chemopreventive and chemotherapeutic actions. Based on its ability to modulate growth factor-mediated cell proliferation, we evaluated its efficacy in multiple myeloma (MM). EGCG induced both dose- and time-dependent growth arrest and subsequent apoptotic cell death in MM cell lines including IL-6-dependent cells and primary patient cells, without significant effect on the growth of peripheral blood mononuclear cells (PBMCs) and normal fibroblasts. Treatment with EGCG also led to significant apoptosis in human myeloma cells grown as tumors in SCID mice. EGCG interacts with the 67-kDa laminin receptor 1 (LR1), which is significantly elevated in myeloma cell lines and patient samples relative to normal PBMCs. RNAi-mediated inhibition of LR1 resulted in abrogation of EGCG-induced apoptosis in myeloma cells, indicating that LR1 plays an important role in mediating EGCG activity in MM while sparing PBMCs. Evaluation of changes in gene expression profile indicates that EGCG treatment activates distinct pathways of growth arrest and apoptosis in MM cells by inducing the expression of death-associated protein kinase 2, the initiators and mediators of death receptor-dependent apoptosis (Fas ligand, Fas, and caspase 4), p53-like proteins (p73, p63), positive regulators of apoptosis and NF-κB activation (CARD10, CARD14), and cyclin-dependent kinase inhibitors (p16 and p18). Expression of related genes at the protein level were also confirmed by Western blot analysis. These data demonstrate potent and specific antimyeloma activity of EGCG and provide the rationale for its clinical evaluation.
Coordination between CCR7- and CCR9-mediated chemokine signals in prevascular fetal thymus colonization
Authors: Liu Cunlan , Saito Fumi , Liu Zhijie , Lei Yu , Uehara Shoji , Love Paul , Lipp Martin , Kondo Shunzo , Manley Nancy , Takahama Yousuke 
Published: June 2006

AbstractThymus seeding by T-lymphoid progenitor cells is a prerequisite for T-cell development. However, molecules guiding thymus colonization and their roles before and after thymus vascularization are unclear. Here we show that mice doubly deficient for chemokine receptors CCR7 and CCR9 were defective specifically in fetal thymus colonization before, but not after, thymus vascularization. The defective prevascular fetal thymus colonization was followed by selective loss of the first wave of T-cell development generating epidermal Vγ3+ γδ T cells. Unexpectedly, CCL21, a CCR7 ligand, was expressed not by Foxn1-dependent thymic primordium but by Gcm2-dependent parathyroid primordium, whereas CCL25, a CCR9 ligand, was predominantly expressed by Foxn1-dependent thymic primordium, revealing the role of the adjacent parathyroid in guiding fetal thymus colonization. These results indicate coordination between Gcm2-dependent parathyroid and Foxn1-dependent thymic primordia in establishing CCL21/CCR7- and CCL25/CCR9-mediated chemokine guidance essential for prevascular fetal thymus colonization.