bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Escherichia coli MntR Miniregulon Includes Genes Encoding a Small Protein and an Efflux Pump Required for Manganese Homeostasis
Authors: Waters Lauren S. , Sandoval Melissa , Storz Gisela 
Published: September 2011

ABSTRACT

Manganese is a critical micronutrient for cells, serving as an enzyme cofactor and protecting against oxidative stress. Yet, manganese is toxic in excess and little is known about its distribution in cells. Bacteria control intracellular manganese levels by the transcription regulator MntR. When this work began, the only
Escherichia coli
K-12 gene known to respond to manganese via MntR repression was
mntH
, which encodes a manganese importer. We show that
mntS
(formerly the small RNA gene
rybA
) is repressed by manganese through MntR and encodes an unannotated 42-amino-acid protein. Overproduction of MntS causes manganese sensitivity, while a lack of MntS perturbs proper manganese-dependent repression of
mntH
. We also provide evidence that
mntP
(formerly
yebN
), which encodes a putative efflux pump, is positively regulated by MntR. Deletion of
mntP
leads to profound manganese sensitivity and to elevated intracellular manganese levels. This work thus defines two new proteins involved in manganese homeostasis and suggests mechanisms for their action.
Transfer of R388 Derivatives by a Pathogenesis-Associated Type IV Secretion System into both Bacteria and Human Cells
Authors: Fernández-González Esther , de Paz Héctor D. , Alperi Anabel , Agúndez Leticia , Faustmann Marco , Sangari Félix J. , Dehio Christoph , Llosa Matxalen 
Published: September 2011

ABSTRACT

Bacterial type IV secretion systems (T4SSs) are involved in processes such as bacterial conjugation and protein translocation to animal cells. In this work, we have switched the substrates of T4SSs involved in pathogenicity for DNA transfer. Plasmids containing part of the conjugative machinery of plasmid R388 were transferred by the T4SS of human facultative intracellular pathogen
Bartonella henselae
to both recipient bacteria and human vascular endothelial cells. About 2% of the human cells expressed a green fluorescent protein (GFP) gene from the plasmid. Plasmids of different sizes were transferred with similar efficiencies.
B. henselae
codes for two T4SSs: VirB/VirD4 and Trw. A Δ
virB
mutant strain was transfer deficient, while a Δ
trwE
mutant was only slightly impaired in DNA transfer. DNA transfer was in all cases dependent on protein TrwC of R388, the conjugative relaxase, implying that it occurs by a conjugation-like mechanism. A DNA helicase-deficient mutant of TrwC could not promote DNA transfer. In the absence of TrwB, the coupling protein of R388, DNA transfer efficiency dropped 1 log. The same low efficiency was obtained with a TrwB point mutation in the region involved in interaction with the T4SS. TrwB interacted with VirB10 in a bacterial two-hybrid assay, suggesting that it may act as the recruiter of the R388 substrate for the VirB/VirD4 T4SS. A TrwB ATPase mutant behaved as dominant negative, dropping DNA transfer efficiency to almost null levels.
B. henselae
bacteria recovered from infected human cells could transfer the mobilizable plasmid into recipient
Escherichia coli
under certain conditions, underscoring the versatility of T4SSs.
The Transcript from the σ
28
-Dependent Promoter Is Translationally Inert in the Expression of the σ
28
-Encoding Gene
fliA
in the
fliAZ
Operon of Salmonella enterica Serovar Typhimurium
Authors: Tanabe Yasushi , Wada Takeo , Ono Katsuhiko , Abo Tatsuhiko , Kutsukake Kazuhiro 
Published: September 2011

ABSTRACT

There are three classes of promoters for flagellar operons in
Salmonella
. Class 2 promoters are transcribed by σ
70
RNA polymerase in the presence of an essential activator, FlhD
4
C
2
, and activated by an auxiliary regulator, FliZ. Class 3 promoters are transcribed by σ
28
RNA polymerase and repressed by an anti-σ
28
factor, FlgM. σ
28
(FliA) and FliZ are encoded by the
fliA
and
fliZ
genes, respectively, which together constitute an operon transcribed in this order. This operon is transcribed from both class 2 and class 3 promoters, suggesting that it should be activated by its own product, σ
28
, even in the absence of FlhD
4
C
2
. However, σ
28
-dependent transcription occurs
in vivo
only in the presence of FlhD
4
C
2
, indicating that transcription from the class 2 promoter is a prerequisite to that from the class 3 promoter. In this study, we examined the effects of variously modified versions of the
fliA
regulatory region on transcription and translation of the
fliA
gene. We showed that FliA is not significantly translated from the class 3 transcript. In contrast, the 5′-terminal AU-rich sequence found in the class 2 transcript confers efficient
fliA
translation. Replacement of the Shine-Dalgarno sequence of the
fliA
gene with a better one improved
fliA
translation from the class 3 transcript. These results suggest that the 5′-terminal AU-rich sequence of the class 2 transcript may assist ribosome binding. FliZ was shown to be expressed from both the class 2 and class 3 transcripts.
Improved clinical outcomes and efficacy with a nurse-led colonoscopy surveillance service
Authors: Sarkar Sanchoy , Duffy Una , Haslam Neil 
Published: September 2011

BackgroundA nurse practitioner-led colonoscopy surveillance service was introduced to improve appropriateness, validation and compliance with the National Patient Safety Agency safety alert and British Society of Gastroenterology consensus guidance for bowel cleansing agents.ObjectiveTo determine the clinical outcomes and efficacy of this new service.Design and patientsA 4-month prospective audit of patients due to attend for surveillance colonoscopy.SettingRoyal Liverpool University Hospital.InterventionA new nurse practitioner-led surveillance service reviewed all patients before listing.OutcomesClinical outcomes, service efficiency and cost effectiveness.Results224 Patients (median age 68 years, 52% male, and median American Society of Anesthesiologists (ASA) 2) were assessed and 34% had medical factors influencing their colonoscopy. 37% patients were discharged without a colonoscopy, 17% deferred (median >2 years), 6% had died while on the register and the remaining (40%) had their procedure at the agreed interval. The 30-day and 6-month all-cause mortality was 0% for those fit for colonoscopy, compared with 5% and 14%, respectively, for those deemed unfit. The did-not-attend (DNA) rate was reduced from 7.6% to <1%. With 95 patients not requiring a colonoscopy a potential £40 000 saving to the primary care trust was made.ConclusionsThe nurse practitioner-led surveillance service has been invaluable for guideline adherence and medical management of patients before colonoscopy. In addition, it potentially avoided procedural all-cause mortality in these patients. It has proved to be efficacious with reduced DNA rates and over one-third of patients assessed did not require a colonoscopy.
A Novel MLL5 Isoform That Is Essential to Activate E6 and E7 Transcription in HPV16/18-Associated Cervical Cancers
Authors: Yew Chow Wenn , Lee Pei , Chan Wai Keong , Lim Vania Kai Jun , Tay Sun Kuie , Tan Theresa M.C. , Deng Lih-Wen 
Published: September 2011

Abstract
Human papillomavirus (HPV) is the primary cause of human cervical cancer. The viral proteins E6 and E7 are essential to transform noncancerous epithelial cells into cancerous carcinomas by targeting key tumor suppressors p53 and retinoblastoma (Rb) proteins, respectively, but the cellular factors involved in E6 and E7 transcription themselves are incompletely understood. In this study, we defined a novel isoform of the mixed lineage leukemia 5 gene (MLL5β) as a specific and critical regulator of E6 and E7 transcription in cervical carcinoma cells. MLL5β is present in HPV16/18-positive cells including human primary cervical carcinoma specimens. Interaction of MLL5β with the AP-1–binding site at the distal region of the HPV18 long control region led to activation of E6/E7 transcription. Conversely, RNA interference–mediated knockdown of MLL5β downregulated both E6 and E7 expression. MLL5β downregulation was sufficient to restore p53 protein levels and reduce Rb phosphorylation, thereby reactivating apoptosis and cell-cycle checkpoints. By defining this novel MLL5β isoform and its specific critical role in activating E6/E7 gene transcription in HPV16/18-induced cervical cancers, our work highlights the potential of MLL5β as a biomarker and new therapeutic target in primary HPV–induced cervical cancers. Cancer Res; 71(21); 6696–707. ©2011 AACR.
Generation of a Mouse Model of Von Hippel–Lindau Kidney Disease Leading to Renal Cancers by Expression of a Constitutively Active Mutant of HIF1α
Authors: Fu Leiping , Wang Gang , Shevchuk Maria M. , Nanus David M. , Gudas Lorraine J. 
Published: September 2011

Abstract
Renal cancers are highly aggressive and clinically challenging, but a transgenic mouse model to promote pathologic studies and therapeutic advances has yet to be established. Here, we report the generation of a transgenic mouse model of von Hippel–Lindau (VHL) renal cancer termed the TRACK model (transgenic model of cancer of the kidney). TRACK mice specifically express a mutated, constitutively active HIF1α in kidney proximal tubule (PT) cells. Kidney histologies displayed by TRACK mice are highly similar to histologies seen in patients with VHL disease, including areas of distorted tubular structure, cells with clear cytoplasm and increased glycogen and lipid deposition, multiple renal cysts, and early onset of clear cell renal cell carcinoma (ccRCC). Distorted tubules in TRACK mice exhibit higher levels of CA-IX, Glut1, and VEGF than tubules in nontransgenic control mice. Furthermore, these tubules exhibit increased numbers of endothelial cells, increased cell proliferation, and increased expression of the human ccRCC marker CD70(TNFSF7). Moreover, PT cells in kidney tubules from TRACK mice exhibit increased genomic instability, as monitored by elevated levels of γH2AX. Our findings establish that activated HIF1α in murine kidney PT cells is sufficient to promote cell proliferation, angiogenesis, genomic instability, and other phenotypic alterations characteristic of human VHL kidney disease, establishing the TRACK mouse as a valid preclinical model of human renal cell carcinoma. Cancer Res; 71(21); 6848–56. ©2011 AACR.
Breast Cancer Subtype-Specific Interactions with the Microenvironment Dictate Mechanisms of Invasion
Authors: Dang Tuyen T. , Prechtl Amanda M. , Pearson Gray W. 
Published: September 2011

Abstract
Most ductal breast carcinoma cells are weakly invasive in vitro and in vivo, suggesting that components of their microenvironment may facilitate a transition from in situ to invasive stages during progression. Here, we report that coculture of mammary fibroblasts specifically triggers invasive behavior in basal-type breast cancer cells through a ligand independent mechanism. When cultured alone in organotypic culture, both basal- and luminal-type breast cancer cells formed noninvasive spheroids with characteristics of ductal carcinoma in situ (DCIS). In contrast, when cocultured with mammary fibroblasts, basal-type spheroids exhibited invasive character whereas the luminal-type spheroids retained a benign and noninvasive duct-like architecture. Real-time imaging and functional studies revealed that the specificity of invasion was linked to a unique capacity of basal-type breast cancer cells to move within spheroids. Mammary fibroblasts induced invasion by triggering basal-type breast cancer cells to convert from a noninvasive program of mammary epithelial morphogenesis to an invasive program of sprouting endothelial angiogenesis. Contrary to the existing invasion models, soluble ligands produced by the fibroblasts were not sufficient to trigger invasion. Instead, basal-type invasion relied upon a Cdc42-dependent reorganization of collagen fibers in the extracellular matrix by fibroblasts. Inhibiting basal-type cell movement with clinically relevant drugs blocked invasion both in organotypic culture and in animals, suggesting a new treatment strategy for early-stage patients. Together our findings establish that fibroblast recruitment by basal-type breast cancer cells into early-stage tumors is sufficient to trigger their conversion from a benign, noninvasive DCIS-like stage to a malignant invasive stage. Furthermore, our findings suggest that different subtypes of breast cancer may require distinct types of contributions from the microenvironment to undergo malignant progression. Cancer Res; 71(21); 6857–66. ©2011 AACR.
Merkel Cell Polyomavirus-Specific CD8+ and CD4+ T-cell Responses Identified in Merkel Cell Carcinomas and Blood
Authors: Iyer Jayasri G. , Afanasiev Olga K. , McClurkan Christopher , Paulson Kelly , Nagase Kotaro , Jing Lichen , Marshak Joshua O. , Dong Lichun , Carter Joseph , Lai Ivy , Farrar Erik , Byrd David , Galloway Denise , Yee Cassian , Koelle David M. , Nghiem Paul 
Published: September 2011

AbstractPurpose: Merkel cell polyomavirus (MCPyV) is prevalent in the general population, integrates into most Merkel cell carcinomas (MCC), and encodes oncoproteins required for MCC tumor growth. We sought to characterize T-cell responses directed against viral proteins that drive this cancer as a step toward immunotherapy.Experimental Design: Intracellular cytokine cytometry, IFN-γ enzyme-linked immunospot (ELISPOT) assay, and a novel HLA-A*2402–restricted MCPyV tetramer were used to identify and characterize T-cell responses against MCPyV oncoproteins in tumors and blood of MCC patients and control subjects.Results: We isolated virus-reactive CD8 or CD4 T cells from MCPyV-positive MCC tumors (2 of 6) but not from virus-negative tumors (0 of 4). MCPyV-specific T-cell responses were also detected in the blood of MCC patients (14 of 27) and control subjects (5 of 13). These T cells recognized a broad range of peptides derived from capsid proteins (2 epitopes) and oncoproteins (24 epitopes). HLA-A*2402–restricted MCPyV oncoprotein processing and presentation by mammalian cells led to CD8-mediated cytotoxicity. Virus-specific CD8 T cells were markedly enriched among tumor infiltrating lymphocytes as compared with blood, implying intact T-cell trafficking into the tumor. Although tetramer-positive CD8 T cells were detected in the blood of 2 of 5 HLA-matched MCC patients, these cells failed to produce IFN-γ when challenged ex vivo with peptide.Conclusions: Our findings suggest that MCC tumors often develop despite the presence of T cells specific for MCPyV T-Ag oncoproteins. The identified epitopes may be candidates for peptide-specific vaccines and tumor- or virus-specific adoptive immunotherapies to overcome immune evasion mechanisms in MCC patients. Clin Cancer Res; 17(21); 6671–80. ©2011 AACR.
Prevention of Persistent Human Papillomavirus Infection by an HPV16/18 Vaccine: A Community-Based Randomized Clinical Trial in Guanacaste, Costa Rica
Authors: Herrero Rolando , Wacholder Sholom , Rodríguez Ana C. , Solomon Diane , González Paula , Kreimer Aimee R. , Porras Carolina , Schussler John , Jiménez Silvia , Sherman Mark E. , Quint Wim , Schiller John T. , Lowy Douglas R. , Schiffman Mark , Hildesheim Allan 
Published: September 2011

Abstract
Target groups for human papillomavirus (HPV) vaccination are controversial. We evaluated vaccine efficacy (VE) against 1-year persistent infection, stratified by age and sexual behavior, among young women in Costa Rica. We randomized 7,466 healthy women 18 to 25 years of age to HPV16/18 or hepatitis A vaccine (follow-up, 50.4 months). According-to-protocol (ATP) cohorts included compliant HPV-negative women; intention-to-treat (ITT) included all randomized women. ATP VE was 90.9% (95% CI, 82.0–95.9) against HPV16/18 infections, 44.5% against HPV31/33/45 (95% CI, 17.5–63.1), and 12.4% (95% CI, −3.2 to 25.6) against any oncogenic infection. Overall ITT VE against HPV16/18 infections was 49.0%, but ATP and ITT VE almost reached 100% in year 4 of follow-up. ATP efficacy against HPV16/18 was similar by age, but ITT VE was greatest among youngest women (68.9% among those 18–19 years of age; 21.8% among those 24–25 years of age) and 79.8% among virgins. Among previously unexposed women, vaccination is highly efficacious against HPV16/18 and partially against HPV31/33/45. Vaccination is most effective in women and girls before they initiate sexual activity, with programmatic and individual decision implications.
Significance: In an independent trial of the bivalent ASO4-adjuvanted HPV16/18 vaccine (Cervarix) conducted among young women in Costa Rica, we confirmed the high efficacy against HPV16/18 persistent infection and partial cross-protection against HPV31/33/45. Furthermore, efficacy data suggest that the benefit of HPV vaccination is maximal when the vaccine is given to young women before they initiate sexual activity. Cancer Discovery; 1(5): 408–19. ©2011 AACR.
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Decadal Trends in Evaporation from Global Energy and Water Balances
Authors: Zhang Yongqiang , Leuning Ray , Chiew Francis H. S. , Wang Enli , Zhang Lu , Liu Changming , Sun Fubao , Peel Murray C. , Shen Yanjun , Jung Martin 
Published: September 2011

AbstractSatellite and gridded meteorological data can be used to estimate evaporation (E) from land surfaces using simple diagnostic models. Two satellite datasets indicate a positive trend (first time derivative) in global available energy from 1983 to 2006, suggesting that positive trends in evaporation may occur in “wet” regions where energy supply limits evaporation. However, decadal trends in evaporation estimated from water balances of 110 wet catchments do not match trends in evaporation estimated using three alternative methods: 1) , a model-tree ensemble approach that uses statistical relationships between E measured across the global network of flux stations, meteorological drivers, and remotely sensed fraction of absorbed photosynthetically active radiation; 2) , a Budyko-style hydrometeorological model; and 3) , the Penman–Monteith energy-balance equation coupled with a simple biophysical model for surface conductance. Key model inputs for the estimation of and are remotely sensed radiation and gridded meteorological fields and it is concluded that these data are, as yet, not sufficiently accurate to explain trends in E for wet regions. This provides a significant challenge for satellite-based energy-balance methods. Trends in for 87 “dry” catchments are strongly correlated to trends in precipitation (R2 = 0.85). These trends were best captured by , which explicitly includes precipitation and available energy as model inputs.
Markov Chain Models for Hydrological Drought Characteristics
Authors: Akyuz Dilek Eren , Bayazit Mehmetcik , Onoz Bihrat 
Published: September 2011

Abstract
Estimation of drought characteristics such as probabilities and return periods of droughts of various lengths is of major importance in drought forecast and management and in solving water resources problems related to water quality and navigation. This study aims at applying first- and second-order Markov chain models to dry and wet periods of annual streamflow series to reproduce the stochastic structure of hydrological droughts. Statistical evaluation of drought duration and intensity is usually carried out using runs analysis. First-order Markov chain model (MC1) for dry and wet periods is not adequate when autocorrelation of the original hydrological series is high. A second-order Markov chain model (MC2) is proposed to estimate the probabilities and return periods of droughts. Results of these models are compared with those of a simulation study assuming a lag-1 autoregressive [AR(1)] process widely used to model annual streamflows. Probability distribution and return periods of droughts of various lengths are estimated and compared with the results of MC1 and MC2 models using efficacy evaluation statistics. It is found that the MC2 model in general gives results that are in better agreement with simulation results as compared with the MC1 model. Skewness is found to have little effect on return periods except when autocorrelation is very high. MC1 and MC2 models are applied to droughts observed in some annual streamflow series, with the result that the MC2 model has a relatively good agreement considering the limited duration of the records.
Changes in Intense Precipitation over the Central United States
Authors: Groisman Pavel Ya. , Knight Richard W. , Karl Thomas R. 
Published: September 2011

Abstract
In examining intense precipitation over the central United States, the authors consider only days with precipitation when the daily total is above 12.7 mm and focus only on these days and multiday events constructed from such consecutive precipitation days. Analyses show that over the central United States, a statistically significant redistribution in the spectra of intense precipitation days/events during the past decades has occurred. Moderately heavy precipitation events (within a 12.7–25.4 mm day−1 range) became less frequent compared to days and events with precipitation totals above 25.4 mm. During the past 31 yr (compared to the 1948–78 period), significant increases occurred in the frequency of “very heavy” (the daily rain events above 76.2 mm) and extreme precipitation events (defined as daily and multiday rain events with totals above 154.9 mm or 6 in.), with up to 40% increases in the frequency of days and multiday extreme rain events. Tropical cyclones associated with extreme precipitation do not significantly contribute to the changes reported in this study. With time, the internal precipitation structure (e.g., mean and maximum hourly precipitation rates within each preselected range of daily or multiday event totals) did not noticeably change. Several possible causes of observed changes in intense precipitation over the central United States are discussed and/or tested.
Self-reinforced nanocomposite by partial dissolution of cellulose microfibrils in ionic liquid
Authors: Shakeri Alireza , Mathew Aji P , Oksman Kristiina 
Published: September 2011

All-cellulose nanocomposite films with different ratios of cellulose I and II were produced by partial dissolution of microfibrillated cellulose using ionic liquid and subsequent film casting. The films were isotropic, transparent to visible light, highly crystalline, and contained different amounts of undissolved cellulose I crystallites in a matrix of dissolved cellulose. X-ray diffraction confirmed that cellulose I, i.e., the major polymorphic modification of cellulose in these nanocomposites, is rearranged to cellulose II crystal packing after the partial dissolution. The all-cellulose nanocomposite showed enhanced thermal properties, with thermal degradation temperature increased by 22% compared with thedissolved cellulose. The SEM and AFM studies verified that the nano-sized cellulose crystallites were well dispersed in the matrix. Results from DMA showed that the storage modulus was increased from 270 MPa for the dissolved cellulose to 1104 MPa for the nanocomposite with lower dissolution grade. This indicates that the all-cellulose nanocomposite films contained undissolved cellulose fragments – possibly cellulose I crystallites or aggregates of crystallites in a matrix of regenerated cellulose.