bluuebunny/crossref_metadata_2025_split huggingface dataset:
Switch or Funnel: How RND-Type Transport Systems Control Periplasmic Metal Homeostasis
Authors: Kim Eun-Hae , Nies Dietrich H. , McEvoy Megan M. , Rensing Christopher 
Published: March 2011

ABSTRACT

Bacteria have evolved several transport mechanisms to maintain metal homeostasis and to detoxify the cell. One mechanism involves an RND (
r
esistance-
n
odulation-cell
d
ivision protein family)-driven tripartite protein complex to extrude a variety of toxic substrates to the extracellular milieu. These efflux systems are comprised of a central RND proton-substrate antiporter, a membrane fusion protein, and an outer membrane factor. The mechanism of substrate binding and subsequent efflux has yet to be elucidated. However, the resolution of recent protein crystal structures and genetic analyses of the components of the heavy-metal efflux family of RND proteins have allowed the developments of proposals for a substrate transport pathway. Here two models of substrate extrusion through RND protein complexes of the heavy-metal efflux protein family are described. The funnel model involves the shuttling of periplasmic substrate from the membrane fusion protein to the RND transporter and further on through the outer membrane factor to the extracellular space. Conversely, the switch model requires substrate binding to the membrane fusion protein, inducing a conformational change and creating an open-access state of the tripartite protein complex. The extrusion of periplasmic substrate bypasses the membrane fusion protein, enters the RND-transporter directly via its substrate-binding site, and is ultimately eliminated through the outer membrane channel. Evidence for and against the two models is described, and we propose that current data favor the switch model.
Characterization of the Salmonella enterica Serovar TyphimuriumydcIGene, Which Encodes a Conserved DNA Binding Protein Required for Full Acid Stress Resistance
Authors: Jennings Matthew E. , Quick Laura N. , Soni Anjali , Davis Richard R. , Crosby Kathleen , Ott C. Mark , Nickerson Cheryl A. , Wilson James W. 
Published: March 2011

ABSTRACTSalmonella entericaserovar Typhimurium possesses a stimulon of genes that are differentially regulated in response to conditions of low fluid shear force that increase bacterial virulence and alter other phenotypes. In this study, we show that a previously uncharacterized member of this stimulon,ydcIor STM1625, encodes a highly conserved DNA binding protein with related homologs present in a range of Gram-negative bacterial genera. Gene expression analysis shows thatydcIis expressed in different bacterial genera and is involved in its autoregulation inS. Typhimurium. We demonstrate that purified YdcI protein specifically binds a DNA probe consisting of its own promoter sequence. We constructed anS. Typhimurium ΔydcImutant strain and show that this strain is more sensitive to both organic and inorganic acid stress than is an isogenic WT strain, and this defect is complemented intrans. Moreover, our data indicate thatydcIis part of therpoSregulon related to stress resistance. TheS. Typhimurium ΔydcImutant was able to invade cultured cells to the same degree as the WT strain, but a strain in whichydcIexpression is induced invaded cells at a level 2.8 times higher than that of the WT. In addition, induction ofydcIexpression inS. Typhimurium resulted in the formation of a biofilm in stationary-phase cultures. These data indicate theydcIgene encodes a conserved DNA binding protein involved with aspects of prokaryotic biology related to stress resistance and possibly virulence.
Enzymatic and Functional Analysis of a Protein Phosphatase, Pph3, from Myxococcus xanthus
Authors: Kimura Yoshio , Mori Yumi , Ina Youhei , Takegawa Kaoru 
Published: March 2011

ABSTRACT

A protein phosphatase, designated Pph3, from
Myxococcus xanthus
showed the enzymatic characteristics of PP2C-type serine/threonine protein phosphatases, which are metal ion-dependent, okadaic acid-insensitive protein phosphatases. The
pph3
mutant under starvation conditions formed immature fruiting bodies and reduced sporulation.
Role of the mar-sox-rob Regulon in Regulating Outer Membrane Porin Expression
Authors: Chubiz Lon M. , Rao Christopher V. 
Published: March 2011

ABSTRACT

Multiple factors control the expression of the outer membrane porins OmpF and OmpC in
Escherichia coli
. In this work, we investigated the role of the
mar-sox-rob
regulon in regulating outer membrane porin expression in response to salicylate. We provide both genetic and physiological evidence that MarA and Rob can independently activate
micF
transcription in response to salicylate, leading to reduced OmpF expression. MarA was also found to repress OmpF expression through a MicF-independent pathway. In the case of OmpC, we found that its transcription was moderately increased in response to salicylate. However, this increase was independent of MarA and Rob. Finally, we found that the reduction in OmpF expression in a
tolC
mutant is due primarily to Rob. Collectively, this work further clarifies the coordinated role of MarA and Rob in regulating the expression of the outer membrane porins.
Non-Identity-Mediated CRISPR-Bacteriophage Interaction Mediated via the Csy and Cas3 Proteins
Authors: Cady Kyle C. , O'Toole George A. 
Published: March 2011

ABSTRACT

Studies of the
Escherichia
,
Neisseria
,
Thermotoga
, and
Mycobacteria
c
lustered
r
egularly
i
nterspaced
s
hort
p
alindromic
r
epeat (CRISPR) subtypes have resulted in a model whereby CRISPRs function as a defense system against bacteriophage infection and conjugative plasmid transfer. In contrast, we previously showed that the
Yersinia
-subtype CRISPR region of
Pseudomonas aeruginosa
strain UCBPP-PA14 plays no detectable role in viral immunity but instead is required for bacteriophage DMS3-dependent inhibition of biofilm formation by
P. aeruginosa
. The goal of this study is to define the components of the
Yersinia
-subtype CRISPR region required to mediate this bacteriophage-host interaction. We show that the
Yersinia
-subtype-specific
C
RISPR-
as
sociated (Cas) proteins Csy4 and Csy2 are essential for small CRISPR RNA (crRNA) production
in vivo
, while the Csy1 and Csy3 proteins are not absolutely required for production of these small RNAs. Further, we present evidence that the core Cas protein Cas3 functions downstream of small crRNA production and that this protein requires functional HD (predicted phosphohydrolase) and DEXD/H (predicted helicase) domains to suppress biofilm formation in DMS3 lysogens. We also determined that only spacer 1, which is not identical to any region of the DMS3 genome, mediates the CRISPR-dependent loss of biofilm formation. Our evidence suggests that gene 42 of phage DMS3 (
DMS3-42
) is targeted by CRISPR2 spacer 1 and that this targeting tolerates multiple point mutations between the spacer and DMS3-42 target sequence. This work demonstrates how the interaction between
P. aeruginosa
strain UCBPP-PA14 and bacteriophage DMS3 can be used to further our understanding of the diverse roles of CRISPR system function in bacteria.
The CRISPR/Cas Immune System Is an Operon Regulated by LeuO, H-NS, and Leucine-Responsive Regulatory Protein in Salmonella enterica Serovar Typhi
Authors: Medina-Aparicio L. , Rebollar-Flores J. E. , Gallego-Hernández A. L. , Vázquez A. , Olvera L. , Gutiérrez-Ríos R. M. , Calva E. , Hernández-Lucas I. 
Published: March 2011

ABSTRACT

Prokaryotes have developed multiple strategies to survive phage attack and invasive DNA. Recently, a novel genetic program denominated the CRISPR/Cas system was demonstrated to have a role in these biological processes providing genetic immunity. This defense mechanism is widespread in the
Archaea
and
Bacteria
, suggesting an ancient origin. In the last few years, progress has been made regarding the functionality of the CRISPR/Cas system; however, many basic aspects of the system remain unknown. For instance, there are few studies about the conditions and regulators involved in its transcriptional control. In this work, we analyzed the transcriptional organization of the CRISPR/Cas system as well as the positive and negative regulators involved in its genetic expression in
Salmonella enterica
serovar Typhi. The results obtained show that in
S
. Typhi the CRISPR/Cas system is a LeuO-dependent operon silenced by the global regulator LRP, in addition to the previously known nucleoid-associated protein H-NS; both LRP and H-NS bind upstream and downstream of the transcriptional start site of
casA.
In this study, relevant nucleotides of the
casA
regulatory region that mediate its LeuO transcriptional activation were identified. Interestingly, specific growth conditions (N-minimal medium) were found for the LeuO-independent expression of the CRISPR/Cas system in
S
. Typhi. Thus, our work provides evidence that there are multiple modulators involved in the genetic expression of this immune system in
S
. Typhi IMSS-1.
Return to sport following anterior cruciate ligament reconstruction surgery: a systematic review and meta-analysis of the state of play
Authors: Ardern Clare L , Webster Kate E , Taylor Nicholas F , Feller Julian A 
Published: March 2011

BackgroundAn athlete's intention to return to sport following anterior cruciate ligament (ACL) injury is a major indication for surgical intervention.PurposeThe purpose of this review was to determine postoperative return-to-sport outcomes after ACL reconstruction surgery.Study designMeta-analysis and systematic reviewMethodsElectronic databases including Medline, Embase, SPORTDiscus and CINAHL were searched from the earliest possible entry to April 2010. Studies were included that reported the number of patients returning to sports participation following ACL reconstruction surgery. The results were presented using the World Health Organization's International Classification of Functioning, Disability and Health as a framework and combined using proportion meta-analyses.ResultsForty-eight studies evaluating 5770 participants at a mean follow-up of 41.5 months were included for review. Overall, 82% of participants had returned to some kind of sports participation, 63% had returned to their preinjury level of participation, and 44% had returned to competitive sport at final follow-up. Approximately 90% of participants achieved normal or nearly normal knee function when assessed postoperatively using impairment-based outcomes such as laxity and strength, and 85% when using activity-based outcomes such as the International Knee Documentation Committee knee evaluation form. Fear of reinjury was the most common reason cited for a postoperative reduction in or cessation of sports participation.ConclusionThe relatively low rate of return to competitive sport despite the high rates of successful outcome in terms of knee impairment-based function suggests that other factors such as psychological factors may be contributing to return-to-sport outcomes.
Unusual morphological features of uterine leiomyomas treated with progestogens
Authors: Boyd Clinton , McCluggage W Glenn 
Published: March 2011

BackgroundUterine leiomyomas are extremely common in surgical pathology practice and in the vast majority there are no issues in diagnosis. Progestogens are widely prescribed drugs for a variety of indications, including abnormal uterine bleeding, and are often given to women with leiomyomas but the pathological features of leiomyomas treated with progestogens are poorly described.MethodsWe report the pathological features in eight cases of uterine leiomyomas in women who had been treated with oral progestogens or a progestogen-containing intrauterine device; all cases were received in consultation because the features raised concern for leiomyosarcoma, smooth muscle tumour of uncertain malignant potential or a benign leiomyoma with unusual features. Additionally, we reviewed a series of cases of uterine leiomyomas (n=99) in women who exhibited progestogenic effects in the endometrium.ResultsThe morphological features in the consult cases, which were widespread and marked and which varied somewhat from case to case, included small and/or large areas of infarct-type necrosis (sometimes mimicking coagulative tumour cell necrosis) with surrounding increased cellularity, mitotic activity, nuclear pyknosis, cytoplasmic eosinophilia, epithelioid morphology, stromal oedema, haemorrhage, and myxoid change and infiltration by CD56 positive granulated lymphocytes. Sometimes the features resulted in an almost deciduoid appearance. Similar features were present to a minor degree in significant numbers of the additional series of cases.ConclusionsPathologists should be aware of these progestogen-associated features when reporting uterine leiomyomas whether or not the clinician has indicated that the woman is taking progestogens since otherwise a diagnosis of leiomyosarcoma or smooth muscle tumour of uncertain malignant potential may be rendered. Useful features in suggesting a benign leiomyoma, in addition to recognition of the morphological features described which, in combination, are characteristic of progestogens, are the lack of true nuclear atypia and the low mitotic activity away from the abnormal areas.
Examining the decline in lost-time claim rates across age groups in Ontario between 1991 and 2007
Authors: Breslin F Curtis , Smith Peter M , Moore Ian 
Published: March 2011

ObjectivesGiven the tendency for young people to show elevated work injury rates, this study sought to examine trends in young worker and adult compensation claim rates in a Canadian province.MethodsWorkers' compensation records and labour force survey data from 1991 to 2007 were used to compute claim rates by age group. To examine the contribution of work-related factors to claim rates by age group, multivariate analyses included industry and job tenure.ResultsDescriptive analysis showed that age groups had different rates of declines over the time period. Multivariate analyses showed that claim rate declines for older adults were greatest prior to 1999. Young workers showed the largest declines after 1999. There was no indication that changes in industry or job tenure accounted for the trends in claim rates among older or younger workers.ConclusionsThis study is one of the first to show a convergence in youth and adult workers' compensation claims in a North American jurisdiction. Ruling out work-related factors increases the possibility that systemic interventions may have contributed to the convergence. This provides policy makers in occupational health and safety with empirical data to guide targeting of resources.
A NOVEL IMAGE SEGMENTATION APPROACH BASED ON NEUTROSOPHIC SET AND IMPROVED FUZZY C-MEANS ALGORITHM
Authors: CHENG H. D. , GUO YANHUI , ZHANG YINGTAO 
Published: March 2011

Image segmentation is an important component in image processing, pattern recognition and computer vision. Many segmentation algorithms have been proposed. However, segmentation methods for both noisy and noise-free images have not been studied in much detail. Neutrosophic set (NS), a part of neutrosophy theory, studies the origin, nature, and scope of neutralities, as well as their interaction with different ideational spectra. However, neutrosophic set needs to be specified and clarified from a technical point of view for a given application or field to demonstrate its usefulness. In this paper, we apply neutrosophic set and define some operations. Neutrosphic set is integrated with an improved fuzzy c-means method and employed for image segmentation. A new operation, α-mean operation, is proposed to reduce the set indeterminacy. An improved fuzzy c-means (IFCM) is proposed based on neutrosophic set. The computation of membership and the convergence criterion of clustering are redefined accordingly. We have conducted experiments on a variety of images. The experimental results demonstrate that the proposed approach can segment images accurately and effectively. Especially, it can segment the clean images and the images having different gray levels and complex objects, which is the most difficult task for image segmentation.
Convergence of Iterative Sequences for Common Zero Points of a Family of "Equation missing" -Accretive Mappings in Banach Spaces
Authors: Qing Yuan , Cho SunYoung , Qin Xiaolong 
Published: March 2011

AbstractWe introduce implicit and explicit viscosity iterative algorithms for a finite family of "Equation missing"-accretive operators. Strong convergence theorems of the iterative algorithms are established in a reflexive Banach space which has a weakly continuous duality map.
Strong Convergence Theorems for an Infinite Family of Equilibrium Problems and Fixed Point Problems for an Infinite Family of Asymptotically Strict Pseudocontractions
Authors: Wang Shenghua , Kang ShinMin , Kwun YoungChel 
Published: March 2011

AbstractWe prove a strong convergence theorem for an infinite family of asymptotically strict pseudo-contractions and an infinite family of equilibrium problems in a Hilbert space. Our proof is simple and different from those of others, and the main results extend and improve those of many others.
Approximating Fixed Points of Non-Lipschitzian Mappings by Metric Projections
Authors: Dehghan Hossein , Gharajelo Amir , Afkhamitaba Davood 
Published: March 2011

AbstractWe define and study a new iterative algorithm inspired by Matsushita and Takahashi (2008). We establish a strong convergence theorem of the proposed algorithm for asymptotically nonexpansive in the intermediate sense mappings in uniformly convex and smooth Banach spaces by using metric projections. This theorem generalizes and refines Matsushita and Takahashi's strong convergence theorem which was established for nonexpansive mappings.
Shmt1 Heterozygosity Impairs Folate-Dependent Thymidylate Synthesis Capacity and Modifies Risk of Apcmin-Mediated Intestinal Cancer Risk
Authors: MacFarlane Amanda J. , Perry Cheryll A. , McEntee Michael F. , Lin David M. , Stover Patrick J. 
Published: March 2011

Abstract
Folate-mediated one-carbon metabolism is required for the de novo synthesis of purines, thymidylate, and S-adenosylmethionine, the primary cellular methyl donor. Impairments in folate metabolism diminish cellular methylation potential and genome stability, which are risk factors for colorectal cancer (CRC). Cytoplasmic serine hydroxymethyltransferase (SHMT1) regulates the partitioning of folate-activated one-carbons between thymidylate and S-adenosylmethionine biosynthesis. Therefore, changes in SHMT1 expression enable the determination of the specific contributions made by thymidylate and S-adenosylmethionine biosynthesis to CRC risk. Shmt1 hemizygosity was associated with a decreased capacity for thymidylate synthesis due to downregulation of enzymes in its biosynthetic pathway, namely thymidylate synthase and cytoplasmic thymidine kinase. Significant Shmt1-dependent changes to methylation capacity, gene expression, and purine synthesis were not observed. Shmt1 hemizygosity was associated with increased risk for intestinal cancer in Apcmin/+ mice through a gene-by-diet interaction, indicating that the capacity for thymidylate synthesis modifies susceptibility to intestinal cancer in Apcmin/+ mice. Cancer Res; 71(6); 2098–107. ©2011 AACR.
The IL-8–Regulated Chemokine Receptor CXCR7 Stimulates EGFR Signaling to Promote Prostate Cancer Growth
Authors: Singh Rajendra Kumar , Lokeshwar Bal L. 
Published: March 2011

Abstract
The proinflammatory chemokine receptor CXCR7 that binds the ligands CXCL11 and CXCL12 (SDF-1a) is elevated in a variety of human cancers, but its functions are not understood as it does not elicit classical chemokine receptor signaling. Here we report that the procancerous cytokine IL-8 (interleukin-8) upregulates CXCR7 expression along with ligand-independent functions of CXCR7 that promote the growth and proliferation of human prostate cancer cells (CaP cells). In cell culture, ectopic expression or addition of IL-8 selectively increased expression of CXCR7 at the level of mRNA and protein production. Conversely, suppressing IL-8 signaling abolished the ability of IL-8 to upregulate CXCR7. RNAi-mediated knockdown of CXCR7 in CaP cells caused multiple antitumor effects, including decreased cell proliferation, cell-cycle arrest in G1 phase, and decreased expression of proteins involved in G1 to S phase progression. In contrast, addition of the CXCR7 ligand SDF-1a and CXCL11 to CaP cells did not affect cell proliferation. Over expression of CXCR7 in normal prostate cells increased their proliferation in a manner associated with increased levels of phospho-EGFR (epidermal growth factor receptor; pY1110) and phospho-ERK1/2. Notably, coimmunoprecipitation studies established a physical association of CXCR7 with EGFR, linking CXCR7-mediated cell proliferation to EGFR activation. Consistent with these findings, CXCR7-depleted CaP tumors grew more slowly than control tumors, expressing decreased tumor-associated expression of VEGF, cyclin D1, and p-EGFR. Together, these results reveal a novel mechanism of ligand-independent growth promotion by CXCR7 and its coregulation by the proinflammatory factor IL-8 in prostate cancer. Cancer Res; 71(9); 3268–77. ©2011 AACR.
Enigmol: A Novel Sphingolipid Analogue with Anticancer Activity against Cancer Cell Lines and In vivo Models for Intestinal and Prostate Cancer
Authors: Symolon Holly , Bushnev Anatoliy , Peng Qiong , Ramaraju Harsha , Mays Suzanne G. , Allegood Jeremy C. , Pruett Sarah T. , Sullards M. Cameron , Dillehay Dirck L. , Liotta Dennis C. , Merrill Alfred H. 
Published: March 2011

Abstract
Sphingoid bases are cytotoxic for many cancer cell lines and are thought to contribute to suppression of intestinal tumorigenesis in vivo by ingested sphingolipids. This study explored the behavior of a sphingoid base analogue, (2S,3S,5S)-2-amino-3,5-dihydroxyoctadecane (Enigmol), that cannot be phosphorylated by sphingosine kinases and is slowly N-acylated and therefore is more persistent than natural sphingoid bases. Enigmol had potential anticancer activity in a National Cancer Institute (NCI-60) cell line screen and was confirmed to be more cytotoxic and persistent than naturally occurring sphingoid bases using HT29 cells, a colon cancer cell line. Although the molecular targets of sphingoid bases are not well delineated, Enigmol shared one of the mechanisms that has been found for naturally occurring sphingoid bases: normalization of the aberrant accumulation of β-catenin in the nucleus and cytoplasm of colon cancer cells due to defect(s) in the adenomatous polyposis coli (APC)/β-catenin regulatory system. Enigmol also had antitumor efficacy when administered orally to Min mice, a mouse model with a truncated APC gene product (C57Bl/6JMin/+ mice), decreasing the number of intestinal tumors by half at 0.025% of the diet (w/w), with no evidence of host toxicity until higher dosages. Enigmol was also tested against the prostate cancer cell lines DU145 and PC-3 in nude mouse xenografts and suppressed tumor growth in both. Thus, Enigmol represents a novel category of sphingoid base analogue that is orally bioavailable and has the potential to be effective against multiple types of cancer. Mol Cancer Ther; 10(4); 648–57. ©2011 AACR.