bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of a
higBA
Toxin-Antitoxin Locus in
Vibrio cholerae
Authors: Budde Priya Prakash , Davis Brigid M. , Yuan Jie , Waldor Matthew K. 
Published: December 2006

ABSTRACT

Toxin-antitoxin (TA) loci, which were initially characterized as plasmid stabilization agents, have in recent years been detected on the chromosomes of numerous free-living bacteria.
Vibrio cholerae
, the causative agent of cholera, contains 13 putative TA loci, all of which are clustered within the superintegron on chromosome II. Here we report the characterization of the
V. cholerae higBA
locus, also known as VCA0391/2. Deletion of
higA
alone was not possible, consistent with predictions that it encodes an antitoxin, and biochemical analyses confirmed that HigA interacts with HigB. Transient exogenous expression of the toxin HigB dramatically slowed growth of
V. cholerae
and
Escherichia coli
and reduced the numbers of CFU by several orders of magnitude. HigB toxicity could be counteracted by simultaneous or delayed production of HigA, although HigA's effect diminished as the delay lengthened. Transcripts from endogenous
higBA
increased following treatment of
V. cholerae
with translational inhibitors, presumably due to reduced levels of HigA, which represses the
higBA
locus. However, no
higBA
-dependent cell death was observed in response to such stimuli. Thus, at least under the conditions tested, activation of endogenous HigB does not appear to be bactericidal.
Inactivation of Lgt Allows Systematic Characterization of Lipoproteins fromListeria monocytogenes
Authors: Baumgärtner Maja , Kärst Uwe , Gerstel Birgit , Loessner Martin , Wehland Jürgen , Jänsch Lothar 
Published: December 2006

ABSTRACTLipoprotein anchoring in bacteria is mediated by the prolipoprotein diacylglyceryl transferase (Lgt), which catalyzes the transfer of a diacylglyceryl moiety to the prospective N-terminal cysteine of the mature lipoprotein. Deletion of thelgtgene in the gram-positive pathogenListeria monocytogenes(i) impairs intracellular growth of the bacterium in different eukaryotic cell lines and (ii) leads to increased release of lipoproteins into the culture supernatant. Comparative extracellular proteome analyses of the EGDe wild-type strain and the Δlgtmutant provided systematic insight into the relative expression of lipoproteins. Twenty-six of the 68 predicted lipoproteins were specifically released into the extracellular proteome of the Δlgtstrain, and this proved that deletion oflgtis an excellent approach for experimental verification of listerial lipoproteins. Consequently, we generated ΔlgtΔprfAdouble mutants to detect lipoproteins belonging to the main virulence regulon that is controlled by PrfA. Overall, we identified three lipoproteins whose extracellular levels are regulated and one lipoprotein that is posttranslationally modified depending on PrfA. It is noteworthy that in contrast to previous studies ofEscherichia coli, we unambiguously demonstrated that lipidation by Lgt is not a prerequisite for activity of the lipoprotein-specific signal peptidase II (Lsp) inListeria.
Mutants, Suppressors, and Wrinkled Colonies: Mutant Alleles of the Cell Division GeneftsQPoint to Functional Domains in FtsQ and a Role for Domain 1C of FtsA in Divisome Assembly
Authors: Goehring Nathan W. , Petrovska Ivana , Boyd Dana , Beckwith Jon 
Published: December 2006

ABSTRACTCell division inEscherichia colirequires the concerted action of at least 10 essential proteins. One of these proteins, FtsQ, is physically associated with multiple essential division proteins, including FtsK, FtsL, FtsB, FtsW, and FtsI. In this work we performed a genetic analysis of theftsQgene. Our studies identified C-terminal residues essential for FtsQ's interaction with two downstream proteins, FtsL and FtsB. Here we also describe a novel screen for cell division mutants based on a wrinkled-colony morphology, which yielded several new point mutations inftsQ. Two of these mutations affect localization of FtsQ to midcell and together define a targeting role for FtsQ's α domain. Further characterization of one localization-defective mutant protein [FtsQ(V92D)] revealed an unexpected role in localization for the first 49 amino acids of FtsQ. Finally, we found a suppressor of FtsQ(V92D) that was due to a point mutation in domain 1C of FtsA, a domain previously implicated in the recruitment of divisome proteins. However, despite reports of a potential interaction between FtsA and FtsQ, suppression by FtsA(I143L) is not mediated via direct contact with FtsQ. Rather, this mutation acts as a general suppressor of division defects, which include deletions of the normally essential geneszipAandftsKand mutations in FtsQ that affect both localization and recruitment. Together, these results reveal increasingly complex connections within the bacterial divisome.
Minimum Length Requirement of the Flexible N-Terminal Translocation Subdomain of Colicin E3
Authors: Sharma Onkar , Cramer William A. 
Published: December 2006

ABSTRACT
The 315-residue N-terminal T domain of colicin E3 functions in translocation of the colicin across the outer membrane through its interaction with outer membrane proteins including the OmpF porin. The first 83 residues of the T domain are known from structure studies to be disordered. This flexible translocation subdomain contains the TolB box (residues 34 to 46) that must cross the outer membrane in an early translocation event, allowing the colicin to bind to the TolB protein in the periplasm. In the present study, it was found that cytotoxicity of the colicin requires a minimum length of 19 to 23 residues between the C terminus (residue 46) of the TolB box and the end of the flexible subdomain (residue 83). Colicin E3 molecules of sufficient length display normal binding to TolB and occlusion of OmpF channels in vitro. The length of the N-terminal subdomain is critical because it allows the TolB box to cross the outer membrane and interact with TolB. It is proposed that the length constraint is a consequence of ordered structure in the downstream segment of the T domain (residues 84 to 315) that prevents its insertion through the outer membrane via a translocation pore that includes OmpF.
Distinct Antimicrobial Resistance Patterns and Antimicrobial Resistance-Harboring Genes According to Genomic Species of
Acinetobacter
Isolates
Authors: Lim Yu Mi , Shin Kyeong Seob , Kim Jungmin 
Published: December 2006

ABSTRACT

Using 58 isolates of
Acinetobacter
species recovered from a university hospital between August 2004 and March 2005, we performed genomic identification by amplified rRNA gene restriction analysis (ARDRA) and investigated the existence of metallo-β-lactamase (MBL) producers and extended-spectrum β-lactamase (ESBL) producers. Genomic species identification of
Acinetobacter
strains using ARDRA showed that 40 strains were genomic species 2 (
Acinetobacter baumannii
), 9 were 13 sensu Tjernberg and Ursing (13TU), 5 were
Acinetobacter
phenon 6/ct 13TU, and 4 were
Acinetobacter
genospecies 3. Among 58 strains, 13 isolates were MBL producers carrying
bla
IMP-1
or
bla
VIM-2
and 13 isolates were ESBL producers carrying
bla
PER-1
. Notably, the MBL producers were mostly 13TU,
Acinetobacter
phenon 6/ct 13TU, and
Acinetobacter
genospecies 3, which showed susceptibility to ciprofloxacin and ampicillin-sulbactam. However, 12 of 13 strains carrying
bla
PER-1
were
A. baumannii
, showing multidrug resistance. The data revealed that the antimicrobial resistance patterns and resistance-harboring genes of
Acinetobacter
species are remarkably distinct according to the genomic species of
Acinetobacter
isolates.
Tropism Modification of Adenovirus Vectors by Peptide Ligand Insertion into Various Positions of the Adenovirus Serotype 41 Short-Fiber Knob Domain
Authors: Hesse Andrea , Kosmides Daniela , Kontermann Roland E. , Nettelbeck Dirk M. 
Published: December 2006

ABSTRACTRecombinant adenoviruses have emerged as promising agents in therapeutic gene transfer, genetic vaccination, and viral oncolysis. Therapeutic applications of adenoviruses, however, would benefit substantially from targeted virus cell entry, for example, into cancer or immune cells, as opposed to the broad tropism that adenoviruses naturally possess. Such tropism modification of adenoviruses requires the deletion of their natural cell binding properties and the incorporation of cell binding ligands. The short fibers of subgroup F adenoviruses have recently been suggested as a tool for genetic adenovirus detargeting based on the reduced infectivity of corresponding adenovectors with chimeric fibers in vitro and in vivo. The goal of our study was to determine functional insertion sites for peptide ligands in the adenovirus serotype 41 (Ad41) short fiber knob. With a model peptide, CDCRGDCFC, we could demonstrate that ligand incorporation into three of five analyzed loops of the knob, namely, EG, HI, and IJ, is feasible without a loss of fiber trimerization. The resulting adenovectors showed enhanced infectivity for various cell types, which was superior to that of viruses with the same peptide fused to the fiber C terminus. Strategies to further augment gene transfer efficacy by extension of the fiber shaft, insertion of tandem copies of the ligand peptide, or extension of the ligand-flanking linkers failed, indicating that precise ligand positioning is pivotal. Our study establishes that internal ligand incorporation into a short-shafted adenovirus fiber is feasible and suggests the Ad41 short fiber with ligand insertion into the top (IJ loop) or side (EG and HI loops) of the knob domain as a novel platform for genetic targeting of therapeutic adenoviruses.
GENERIC q-MARKOV SEMIGROUPS AND SPEED OF CONVERGENCE OF q-ALGORITHMS
Authors: ACCARDI LUIGI , FAGNOLA FRANCO , HACHICHA SKANDER 
Published: December 2006

We study a special class of generic quantum Markov semigroups, on the algebra of all bounded operators on a Hilbert space [Formula: see text], arising in the stochastic limit of a generic system interacting with a boson–Fock reservoir. This class depends on an orthonormal basis of [Formula: see text]. We obtain a new estimate for the trace distance of a state from a pure state and use this estimate to prove that, under the action of a semigroup of this class, states with finite support with respect to the given basis converge to equilibrium with a speed which is exponential, but with a polynomial correction which makes the convergence increasingly worse as the dimension of the support increases (Theorem 5.1). We interpret the semigroup as an algorithm, its initial state as input and, following Belavkin and Ohya,10 the dimension of the support of a state as a measure of complexity of the input. With this interpretation, the above results mean that the complexity of the input "slows down" the convergence of the algorithm. Even if the convergence is exponential and the slow down the polynomial, the constants involved may be such that the convergence times become unacceptable from a computational standpoint. This suggests that, in the absence of estimates of the constants involved, distinctions such as "exponentially fast" and "polynomially slow" may become meaningless from a constructive point of view. We also show that, for arbitray states, the speed of convergence to equilibrium is controlled by the rate of decoherence and the rate of purification (i.e. of concentration of the probability on a single pure state). We construct examples showing that the order of magnitude of these two decays can be quite different.
A Psychological Autopsy of the Suicide of an Academically Gifted Student: Researchers' and Parents' Perspectives
Authors: Cross Tracy L. , Gust-Brey Karyn , Ball P. Bonny 
Published: January 2007

This study uses the methods and procedures of psychological autopsy to portray the life of an academically gifted college student who completed suicide. The study is unique in that it follows the subject across his 21 years of life, highlighting relevant milestones and significant stages and events. A comprehensive view of the life and death of a gifted student is offered through both researchers' and parents' perspectives, along with multiple theoretical explanations, including a developmental explanation. This psychological autopsy yielded three sets of findings: those that reflected exclusively on the subject's life, those that compare his life with 3 previous psychological autopsies conducted, and those that reflect the parents' observations and experiences of his life. Two important findings of this study include a depiction of the psychological makeup of a subject in interaction with his environment and the fact that many of the factors contributing to suicidal behavior identified for the general population of adolescents and young adults existed in this case, as well. Consequently, as Cross, Cook, and Dixon (1996) fund, certain types of aberrant behavior, belief systems, or both should not be considered a typical part of being a gifted person; they should be recognized as potential indicators of suicidal behavior.
Trapping and apoptosis of novel subsets of memory T lymphocytes expressing CCR6 in the spleen of HIV-infected patients
Authors: Lécureuil Cédric , Combadière Béhazine , Mazoyer Elodie , Bonduelle Olivia , Samri Assia , Autran Brigitte , Debré Patrice , Combadière Christophe 
Published: December 2006

AbstractCCR6, a homeostatic chemokine receptor, is shown here to characterize subsets of both central and effector memory T cells that secrete high levels of IL-2 and TNF-α in response to polyclonal and antigen-specific stimulation. CCR6+ T lymphocytes disappeared dramatically from the peripheral blood of HIV-infected patients as HIV disease progressed. The capacity of CD4+CCR6+ to secrete multiple cytokines remained intact among HIV-infected long-term nonprogressors but was partially lost from subjects with standard disease progression. CCR6+ T lymphocytes, regardless of their CCR7 expression, accumulated in the spleen of HIV-infected patients, where they died by apoptosis. Assessment of CCR6 expression allowed us to describe novel memory T-cell subpopulations capable of high cytokine production and provided evidence of a pathologic CCR6-dependent pathway of memory T-cell homing that may participate in the loss of memory response against infections.
Polymorphisms in DNA repair genes and therapeutic outcomes of AML patients from SWOG clinical trials
Authors: Kuptsova Nataliya , Kopecky Kenneth J. , Godwin John , Anderson Jeanne , Hoque Ashraful , Willman Cheryl L. , Slovak Marilyn L. , Ambrosone Christine B. 
Published: December 2006

AbstractRepair of damage to DNA resulting from chemotherapy may influence drug toxicity and survival in response to treatment. We evaluated the role of polymorphisms in DNA repair genes APE1, XRCC1, ERCC1, XPD, and XRCC3 in predicting therapeutic outcomes of older adults with acute myeloid leukemia (AML) from 2 Southwest Oncology Group (SWOG) clinical trials. All patients received standard chemotherapy induction regimens. Using logistic and proportional hazards regression models, relationships between genotypes, haplotypes, and toxicities, response to induction therapy, and overall survival were evaluated. Patients with XPD Gln751C/Asp312G (‘D’) haplotype were more likely to have complete response (OR = 3.06; 95% CI, 1.44-6.70) and less likely to have resistant disease (OR = 0.32; 95%CI, 0.14-0.72) than patients with other haplotypes. ERCC1 polymorphisms were significantly associated with lung (P = .037) and metabolic (P = .041) toxicities, and patients with the XRCC3 241Met variant had reduced risk of liver toxicity (OR = 0.32; 95%CI, 0.11-0.95). Significant associations with other toxicities were also found for variant XPD genotypes/haplotypes. These data from clinical trials of older patients treated for AML indicate that variants in DNA repair pathways may have an impact on both outcomes of patients and toxicities associated with treatments. With validation of results in larger samples, these findings could lead to optimizing individual chemotherapy options.
MALT lymphoma and extranodal diffuse large B-cell lymphoma are targeted by aberrant somatic hypermutation
Authors: Deutsch Alexander J. A. , Aigelsreiter Ariane , Staber Philipp B. , Beham Alfred , Linkesch Werner , Guelly Christian , Brezinschek Ruth I. , Fruhwirth Margareta , Emberger Werner , Buettner Maike , Beham-Schmid Christine , Neumeister Peter 
Published: December 2006

AbstractRecently, a novel mechanism introducing genetic instability, termed aberrant somatic hypermutation (ASHM), has been described in diffuse large B-cell lymphoma. To further investigate whether ASHM also occurs in mucosa-associated lymphoid tissue type (MALT) lymphoma, we studied the mutation profile of PIM1, PAX5, RhoH/TTF, and c-MYC in 17 MALT lymphomas and 17 extranodal diffuse large B-cell lymphomas (DLBCLs) still exhibiting a low-grade MALT lymphoma component (transformed MALT lymphoma). Mutations in one or more genes were detected in 13 (76.5%) of 17 cases of MALT lymphomas and in all of 17 (100%) cases of extranodal DLBCL. A total of 100 sequence variants were found in 30 of 34 cases, 28 in the MALT lymphomas and 72 in extranodal DLBCL. Further, in PIM1 and c-MYC some of the mutations were found to affect coding exons, leading to amino acid exchanges, thus potentially altering gene function. Expression levels of activation-induced cytidine deaminase (AID), an enzyme essential for somatic hypermutation (SHM), was associated with the mutational load. These data indicate that aberrant SHM is associated with extranodal DLBCL and MALT lymphoma, likewise. By mutating regulatory and coding sequences of the targeted genes, ASHM may represent a major contributor to their pathogenesis.
Oridonin, a diterpenoid extracted from medicinal herbs, targets AML1-ETO fusion protein and shows potent antitumor activity with low adverse effects on t(8;21) leukemia in vitro and in vivo
Authors: Zhou Guang-Biao , Kang Hui , Wang Lan , Gao Li , Liu Ping , Xie Jun , Zhang Feng-Xiang , Weng Xiang-Qin , Shen Zhi-Xiang , Chen Jue , Gu Long-Jun , Yan Ming , Zhang Dong-Er , Chen Sai-Juan , Wang Zhen-Yi , Chen Zhu 
Published: December 2006

AbstractStudies have documented the potential antitumor activities of oridonin, a compound extracted from medicinal herbs. However, whether oridonin can be used in the selected setting of hematology/oncology remains obscure. Here, we reported that oridonin induced apoptosis of t(8;21) acute myeloid leukemic (AML) cells. Intriguingly, the t(8;21) product AML1-ETO (AE) fusion protein, which plays a critical role in leukemogenesis, was degraded with generation of a catabolic fragment, while the expression pattern of AE target genes investigated could be reprogrammed. The ectopic expression of AE enhanced the apoptotic effect of oridonin in U937 cells. Preincubation with caspase inhibitors blocked oridonin-triggered cleavage of AE, while substitution of Ala for Asp at residues 188 in ETO moiety of the fusion abrogated AE degradation. Furthermore, oridonin prolonged lifespan of C57 mice bearing truncated AE-expressing leukemic cells without suppression of bone marrow or reduction of body weight of animals, and exerted synergic effects while combined with cytosine arabinoside. Oridonin also inhibited tumor growth in nude mice inoculated with t(8;21)-harboring Kasumi-1 cells. These results suggest that oridonin may be a potential antileukemia agent that targets AE oncoprotein at residue D188 with low adverse effect, and may be helpful for the treatment of patients with t(8;21) AML.
Endorepellin, the C-terminal angiostatic module of perlecan, enhances collagen-platelet responses via the α2β1-integrin receptor
Authors: Bix Gregory , Iozzo Rex A. , Woodall Ben , Burrows Michelle , McQuillan Angela , Campbell Shelly , Fields Gregg B. , Iozzo Renato V. 
Published: December 2006

Abstract
Endorepellin, a C-terminal fragment of the vascular basement membrane proteoglycan perlecan, inhibits angiogenesis via the α2β1-integrin receptor. Because this integrin is also implicated in platelet-collagen responses and because endorepellin or its fragments are generated in response to injury and inflammation, we hypothesized that endorepellin could also affect platelet biology. We discovered that endorepellin supported α2β1-dependent platelet adhesion, without appreciably activating or aggregating platelets. Notably, endorepellin enhanced collagen-evoked responses in platelets, in a src kinase-dependent fashion, and enhanced the collagen-inhibitory effect of an α2β1-integrin function-blocking antibody. Collectively, these results suggest that endorepellin/α2β1-integrin interaction and effects are specific and dependent on cell type, differ from those emanated by exposure to collagen, and may be due to cellular differences in α2β1-integrin activation/ligand affinity state. These studies also suggest a heretofore unrecognized role for angiostatic basement membrane fragments in platelet biology.
RNA silencing of the mitochondrial ABCB7 transporter in HeLa cells causes an iron-deficient phenotype with mitochondrial iron overload
Authors: Cavadini Patrizia , Biasiotto Giorgio , Poli Maura , Levi Sonia , Verardi Rosanna , Zanella Isabella , Derosas Manuela , Ingrassia Rosaria , Corrado Marcella , Arosio Paolo 
Published: December 2006

Abstract
X-linked sideroblastic anemia with ataxia (XLSA/A) is caused by defects of the transporter ABCB7 and is characterized by mitochondrial iron deposition and excess of protoporphyrin in erythroid cells. We describe ABCB7 silencing in HeLa cells by performing sequential transfections with siRNAs. The phenotype of the ABCB7-deficient cells was characterized by a strong reduction in proliferation rate that was not rescued by iron supplementation, by evident signs of iron deficiency, and by a large approximately 6-fold increase of iron accumulation in the mitochondria that was poorly available to mitochondrial ferritin. The cells showed an increase of protoporphyrin IX, a higher sensitivity to H2O2 toxicity, and a reduced activity of mitochondrial superoxide dismutase 2 (SOD2), while the activity of mitochondrial enzymes, such as citrate synthase or succinate dehydrogenase, and ATP content were not decreased. In contrast, aconitase activity, particularly that of the cytosolic, IRP1 form, was reduced. The results support the hypothesis that ABCB7 is involved in the transfer of iron from mitochondria to cytosol, and in the maturation of cytosolic Fe/S enzymes. In addition, the results indicate that anemia in XLSA/A is caused by the accumulation of iron in a form that is not readily usable for heme synthesis.
A leukemia fusion protein attenuates the spindle checkpoint and promotes aneuploidy
Authors: Boyapati Anita , Yan Ming , Peterson Luke F. , Biggs Joseph R. , Le Beau Michelle M. , Zhang Dong-Er 
Published: December 2006

AbstractThe 8;21 chromosomal translocation occurs in 15% to 40% of patients with the FAB M2 subtype of acute myeloid leukemia (AML). This chromosomal abnormality fuses part of the AML1/RUNX1 gene to the ETO/MTG8 gene and generates the AML1-ETO protein. We previously identified a C-terminal truncated AML1-ETO protein (AEtr) in a mouse leukemia model. AEtr is almost identical to the AML1-ETO exon 9a isoform expressed in leukemia patients. Here, we describe a novel function of AEtr in the development of aneuploidy through spindle checkpoint attenuation. AEtr cells had a reduced mitotic index following nocodazole treatment, suggesting a failure in a subset of cells to arrest in mitosis with a functional spindle checkpoint. Additionally, primary leukemia cells and cell lines expressing AEtr were aneuploid. Moreover, AEtr cells had reduced levels of several spindle checkpoint proteins including BubR1 and securin following treatment with the spindle poison nocodazole. These results suggest that inactivation of the spindle checkpoint may contribute to the development of aneuploidy described in t(8;21) leukemia patients.