bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between Helicobacter pylori Virulence Factors and Gastroduodenal Diseases in Okinawa, Japan
Authors: Matsunari Osamu , Shiota Seiji , Suzuki Rumiko , Watada Masahide , Kinjo Nagisa , Murakami Kazunari , Fujioka Toshio , Kinjo Fukunori , Yamaoka Yoshio 
Published: December 2011

ABSTRACT

The incidence of gastric cancer in Okinawa is lowest in Japan. Some previous reports using small number of strains suggested that the high prevalence of
Helicobacter pylori
with Western-type
cagA
in Okinawa compared to other areas in Japan might contribute to the low incidence of gastric cancer. It has still not been confirmed why the prevalence of Western-type
cagA
strains is high in Okinawa. We examined the association between the virulence factors of
H. pylori
and gastroduodenal diseases in Okinawa. The genotypes of
cagA
and
vacA
of 337
H. pylori
strains were determined by PCR and gene sequencing. The genealogy of these Western-type
cagA
strains in Okinawa was analyzed by multilocus sequence typing (MLST). Overall, 86.4% of the strains possessed
cagA
: 70.3% were East-Asian type and 16.0% were Western type. After adjustment by age and sex, the presence of East-Asian-type
cagA
/
vacA
s1m1 genotypes was significantly associated with gastric cancer compared to gastritis (odds ratio = 6.68, 95% confidence interval = 1.73 to 25.8). The structure of Western-type CagA in Okinawa was different from that of typical Western-type CagA found in Western countries. Intriguingly, MLST analysis revealed that the majority of Western-type
cagA
strains formed individual clusters but not hpEurope. Overall, low prevalence of gastric cancer in Okinawa may result from the high prevalence of non-East-Asian-type
cagA
strains. The origin of Western-type
cagA
strains in Okinawa may be different from those of Western countries.
Emergence of Hospital- and Community-Associated Panton-Valentine Leukocidin-Positive Methicillin-Resistant Staphylococcus aureus Genotype ST772-MRSA-V in Ireland and Detailed Investigation of an ST772-MRSA-V Cluster in a Neonatal Intensive Care Unit
Authors: Brennan Gráinne I. , Shore Anna C. , Corcoran Suzanne , Tecklenborg Sarah , Coleman David C. , O'Connell Brian 
Published: December 2011

ABSTRACTSequence type 22 (ST22) methicillin-resistantStaphylococcus aureus(MRSA) harboring staphylococcal cassette chromosomemec(SCCmec) IV (ST22-MRSA-IV) has predominated in Irish hospitals since the late 1990s. Six distinct clones of community-associated MRSA (CA-MRSA) have also been identified in Ireland. A new strain of CA-MRSA, ST772-MRSA-V, has recently emerged and become widespread in India and has spread into hospitals. In the present study, highly similar MRSA isolates were recovered from seven colonized neonates in a neonatal intensive care unit (NICU) in a maternity hospital in Ireland during 2010 and 2011, two colonized NICU staff, one of their colonized children, and a NICU environmental site. The isolates exhibited multiantibiotic resistance,spatype t657, and were assigned to ST772-MRSA-V by DNA microarray profiling. All isolates encoded resistance to macrolides [msr(A) andmpb(BM)] and aminoglycosides (aacA-aphDandaphA3) and harbored the Panton-Valentine leukocidin toxin genes (lukF-PVandlukS-PV), enterotoxin genes (sea,sec,sel, andegc), and one of the immune evasion complex genes (scn). One of the NICU staff colonized by ST772-MRSA-V was identified as the probable index case, based on recent travel to India. Seven additional hospital and CA-ST772-MRSA-V isolates recovered from skin and soft tissue infections in Ireland between 2009 and 2011 exhibiting highly similar phenotypic and genotypic characteristics to the NICU isolates were also identified. The clinical details of four of these patients revealed connections with India through ethnic background or travel. Our study indicates that hospital-acquired and CA-ST772-MRSA-V is currently emerging in Ireland and may have been imported from India on several occasions.
Molecular Characterization of Escherichia coli Strains That Cause Symptomatic and Asymptomatic Urinary Tract Infections
Authors: Abraham Sam , Chapman Toni A. , Zhang Ren , Chin James , Mabbett Amanda N. , Totsika Makrina , Schembri Mark A. 
Published: December 2011

ABSTRACT

The differences between
Escherichia coli
strains associated with symptomatic and asymptomatic urinary tract infections (UTIs) remain to be properly determined. Here we examined the prevalence of plasmid types and bacteriocins, as well as genetic relatedness, in a defined collection of
E. coli
strains that cause UTIs. Comparative analysis identified a subgroup of strains with a high number of virulence genes (VGs) and microcins M/H47. We also identified associations between microcin genes, VGs, and specific plasmid types.
The Human Adenovirus Type 5 E1B 55-Kilodalton Protein Is Phosphorylated by Protein Kinase CK2
Authors: Ching Wilhelm , Dobner Thomas , Koyuncu Emre 
Published: December 2011

ABSTRACTThe human adenovirus type 5 (HAdV5) early region 1B 55-kDa protein (E1B-55K) is a multifunctional phosphoprotein playing several critical roles during adenoviral productive infection, e.g., degradation of host cell proteins, viral late mRNA export, and inhibition of p53-mediated transcription. Many of these functions are apparently regulated at least in part by the phosphorylation of E1B-55K occurring at a stretch of amino acids resembling a potential CK2 consensus phosphorylation motif. We therefore investigated the potential role of CK2 phosphorylation upon E1B-55K during adenoviral infection. A phosphonegative E1B-55K mutant showed severely reduced virus progeny production, although viral early, late, and structural protein levels and viral DNA replication were not obviously affected. Binding studies revealed an interaction between the CK2α catalytic subunit and wild-type E1B-55K, which is severely impaired in the phosphonegative E1B mutant. In addition,in situthe α-catalytic subunit is redistributed into ring-like structures surrounding E1B-55K nuclear areas and distinct cytoplasmic accumulations, where a significant amount of CK2α colocalizes with E1B-55K. Furthermore, inin vitrophosphorylation assays, wild-type E1B-55K glutathioneS-transferase fusion proteins were readily phosphorylated by the CK2α subunit but inefficiently phosphorylated by the CK2 holoenzyme. Addition of the CK2-specific inhibitors TBB (4,5,6,7-tetrabromobenzotriazole) and DMAT (2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole) to infected cells confirmed that CK2α binding to E1B-55K is necessary for efficient phosphorylation of E1B-55K. In summary, our data show that CK2α interacts with and phosphorylates HAdV5 E1B-55K at residues S490/491 and T495 and that these posttranslational modifications are essential for E1B-55K lytic functions.
Molecular Signatures Associated with Mx1-Mediated Resistance to Highly Pathogenic Influenza Virus Infection: Mechanisms of Survival
Authors: Cilloniz Cristian , Pantin-Jackwood Mary J. , Ni Chester , Carter Victoria S. , Korth Marcus J. , Swayne David E. , Tumpey Terrence M. , Katze Michael G. 
Published: December 2011

ABSTRACT

Understanding the role of host factors during lethal influenza virus infection is critical to deciphering the events that determine the fate of the host. One such factor is encoded by the Mx1 gene, which confers resistance to influenza virus infection. Here, we compared pathology and global gene expression profiles in lung tissue from BALB/c (Mx1
−
) and BALB · A2G-Mx1 mice (Mx1
+/+
) infected with the fully reconstructed 1918 pandemic influenza virus. Mx1
+/+
mice showed less tissue damage than Mx
−
animals, and pathology and mortality were further reduced by treating the mice with interferon prior to infection. Using global transcriptional profiling, we identified distinct molecular signatures associated with partial protection, complete protection, and the contribution of interferon to the host response. In the absence of interferon treatment, partial protection was characterized by the generation of an acute response with the upregulation of genes associated with apoptosis, reactive oxygen species, and cell migration. Complete protection was characterized by the downregulation of cytokine and chemokine genes previously associated with influenza virus pathogenesis. The contribution of interferon treatment to total protection in virus-infected Mx1
+/+
mice was characterized by the altered regulation of cell cycle genes. These genes were upregulated in Mx1
+/+
mice treated with interferon but downregulated in the absence of interferon treatment. Our results suggest that Mx1
+/+
mice generate a protective antiviral response by controlling the expression of key modulator molecules associated with influenza virus lethality.
Baculovirus-Encoded Protein BV/ODV-E26 Determines Tissue Tropism and Virulence in Lepidopteran Insects
Authors: Katsuma Susumu , Kobayashi Jun , Koyano Yasue , Matsuda-Imai Noriko , Kang WonKyung , Shimada Toru 
Published: December 2011

ABSTRACT

Lepidopteran nucleopolyhedroviruses (NPVs) show distinct tissue tropism in host insect larvae. However, the molecular mechanism of this tropism is largely unknown. We quantitatively investigated NPV tissue tropism by measuring mRNA levels of viral genes in 16 tissues from
Bombyx mori
NPV (BmNPV)-infected
B. mori
larvae and found clear tissue tropism, i.e., BmNPV replicates poorly in the silk glands, midgut, and Malpighian tubule compared with other larval tissues. We next identified the viral genes determining tissue tropism in NPV infection by investigating the phenotypes of larvae infected with 44 BmNPV mutants in which one gene was functionally disrupted by a
LacZ
cassette insertion. We found that occlusion body (OB) production was markedly enhanced compared with that of the wild type in the middle silk glands (MSGs) of larvae infected with three mutants in which one of three tandemly arrayed genes (
Bm7
,
Bm8
, and
Bm9
) was disrupted. We generated additional mutants in which one or two genes of this gene cluster were partially deleted and showed that Bm8, also known as BV/ODV-E26, was solely required for the suppression of OB production in the MSGs of BmNPV-infected
B. mori
larvae. Western blotting showed that a
LacZ
cassette insertion in
Bm7
or
Bm9
resulted in aberrant expression of Bm8, presumably leading to abnormal OB production in the MSGs. Larval bioassays also revealed that disruption of
Bm8
accelerated the death of
B. mori
larvae. These results suggest that the group I NPV-specific protein BV/ODV-E26 determines tissue tropism and virulence in host lepidopteran insects.
In Vitro
-Selected Drug-Resistant Varicella-Zoster Virus Mutants in the Thymidine Kinase and DNA Polymerase Genes Yield Novel Phenotype-Genotype Associations and Highlight Differences between Antiherpesvirus Drugs
Authors: Andrei G. , Topalis D. , Fiten P. , McGuigan C. , Balzarini J. , Opdenakker G. , Snoeck R. 
Published: December 2011

ABSTRACT

Varicella zoster virus (VZV) is usually associated with mild to moderate illness in immunocompetent patients. However, older age and immune deficiency are the most important risk factors linked with virus reactivation and severe complications. Treatment of VZV infections is based on nucleoside analogues, such as acyclovir (ACV) and its valyl prodrug valacyclovir, penciclovir (PCV) as its prodrug famciclovir, and bromovinyldeoxyuridine (BVDU; brivudin) in some areas. The use of the pyrophosphate analogue foscarnet (PFA) is restricted to ACV-resistant (ACV
r
) VZV infections. Since antiviral drug resistance is an emerging problem, we attempt to describe the contributions of specific mutations in the viral thymidine kinase (TK) gene identified following selection with ACV, BVDU and its derivative BVaraU (sorivudine), and the bicyclic pyrimidine nucleoside analogues (BCNAs), a new class of potent and specific anti-VZV agents. The string of 6 Cs at nucleotides 493 to 498 of the VZV TK gene appeared to function as a hot spot for nucleotide insertions or deletions. Novel amino acid substitutions (G24R and T86A) in VZV TK were also linked to drug resistance. Six mutations were identified in the “palm domain” of VZV DNA polymerase in viruses selected for resistance to PFA, PCV, and the 2-phophonylmethoxyethyl (PME) purine derivatives. The investigation of the contributions of specific mutations in VZV TK or DNA polymerase to antiviral drug resistance and their impacts on the structures of the viral proteins indicated specific patterns of cross-resistance and highlighted important differences, not only between distinct classes of antivirals, but also between ACV and PCV.
Ultrastructural Characterization of Arterivirus Replication Structures: Reshaping the Endoplasmic Reticulum To Accommodate Viral RNA Synthesis
Authors: Knoops Kèvin , Bárcena Montserrat , Limpens Ronald W. A. L. , Koster Abraham J. , Mommaas A. Mieke , Snijder Eric J. 
Published: December 2011

ABSTRACT

Virus-induced membrane structures support the assembly and function of positive-strand RNA virus replication complexes. The replicase proteins of arteriviruses are associated with double-membrane vesicles (DMVs), which were previously proposed to derive from the endoplasmic reticulum (ER). Using electron tomography, we performed an in-depth ultrastructural analysis of cells infected with the prototypic arterivirus equine arteritis virus (EAV). We established that the outer membranes of EAV-induced DMVs are interconnected with each other and with the ER, thus forming a reticulovesicular network (RVN) resembling that previously described for the distantly related severe acute respiratory syndrome (SARS) coronavirus. Despite significant morphological differences, a striking parallel between the two virus groups, and possibly all members of the order
Nidovirales
, is the accumulation in the DMV interior of double-stranded RNA, the presumed intermediate of viral RNA synthesis. In our electron tomograms, connections between the DMV interior and cytosol could not be unambiguously identified, suggesting that the double-stranded RNA is compartmentalized by the DMV membranes. As a novel approach to visualize and quantify the RNA content of viral replication structures, we explored electron spectroscopic imaging of DMVs, which revealed the presence of phosphorus in amounts equaling on average a few dozen copies of the EAV RNA genome. Finally, our electron tomograms revealed a network of nucleocapsid protein-containing protein tubules that appears to be intertwined with the RVN. This potential intermediate in nucleocapsid formation, which was not observed in coronavirus-infected cells, suggests that arterivirus RNA synthesis and assembly are coordinated in intracellular space.
Baculovirus GP64-Mediated Entry into Mammalian Cells
Authors: Kataoka Chikako , Kaname Yuuki , Taguwa Shuhei , Abe Takayuki , Fukuhara Takasuke , Tani Hideki , Moriishi Kohji , Matsuura Yoshiharu 
Published: December 2011

ABSTRACT

The baculovirus
Autographa californica
multiple nucleopolyhedrovirus (AcMNPV) serves as an efficient viral vector, not only for abundant gene expression in insect cells, but also for gene delivery into mammalian cells. Lentivirus vectors pseudotyped with the baculovirus envelope glycoprotein GP64 have been shown to acquire more potent gene transduction than those with vesicular stomatitis virus (VSV) envelope glycoprotein G. However, there are conflicting hypotheses about the molecular mechanisms of the entry of AcMNPV. Moreover, the mechanisms of the entry of pseudotyped viruses bearing GP64 into mammalian cells are not well characterized. Determination of the entry mechanisms of AcMNPV and the pseudotyped viruses bearing GP64 is important for future development of viral vectors that can deliver genes into mammalian cells with greater efficiency and specificity. In this study, we generated three pseudotyped VSVs, NPVpv, VSVpv, and MLVpv, bearing envelope proteins of AcMNPV, VSV, and murine leukemia virus, respectively. Depletion of membrane cholesterol by treatment with methyl-β-cyclodextrin, which removes cholesterol from cellular membranes, inhibited GP64-mediated internalization in a dose-dependent manner but did not inhibit attachment to the cell surface. Treatment of cells with inhibitors or the expression of dominant-negative mutants for dynamin- and clathrin-mediated endocytosis abrogated the internalization of AcMNPV and NPVpv into mammalian cells, whereas inhibition of caveolin-mediated endocytosis did not. Furthermore, inhibition of macropinocytosis reduced GP64-mediated internalization. These results suggest that cholesterol in the plasma membrane, dynamin- and clathrin-dependent endocytosis, and macropinocytosis play crucial roles in the entry of viruses bearing baculovirus GP64 into mammalian cells.
Risk factors for injury in rugby union football in New Zealand: a cohort study
Authors: Chalmers David J , Samaranayaka Ari , Gulliver Pauline , McNoe Bronwen 
Published: December 2011

ObjectiveTo identify risk factors for injury in amateur club rugby.DesignProspective cohort design; with follow-up over the 2004 season.SettingAmateur club rugby in New Zealand.ParticipantsSeven hundred and four male rugby players, aged 13 years and over.Assessment of risk factorsThe study investigated the independent effect on injury incidence of age, ethnicity, rugby experience, height, weight, body mass index, physical activity, cigarette smoking, previous injury, playing while injured, grade, position, training, time of season, warm-up, foul play, weather conditions, ground conditions and protective equipment. Generalised Poisson regression was used to estimate the effect of each factor after adjusting for all other factors.Main outcome measuresGame injury, defined as ‘any event that resulted in an injury requiring medical attention or causing a player to miss at least one scheduled game or team practice’.ResultsA total of 704 players, representing 6263 player-games, contributed information on injury and exposure. Evidence was obtained of the effect on injury incidence of increasing age, Pacific Island versus Maori ethnicity (injury rate ratio (IRR)=1.48, 1.03–2.13), ≥40 h strenuous physical activity per week (IRR=1.54, 1.11–2.15), playing while injured (IRR=1.46, 1.20–1.79), very hard ground condition (IRR=1.50, 1.13–2.00), foul-play (IRR=1.87, 1.54–2.27) and use of headgear (IRR=1.23, 1.00–1.50).ConclusionsOpportunities for injury prevention might include promoting injury-prevention measures more vigorously among players of Pacific Island ethnicity, ensuring injured players are fully rehabilitated before returning to play, reducing the effects of ground hardness through ground preparation and stricter enforcement of the laws relating to foul play.
APPLICATION OF 25 NM QUANTUM DOT GATE FETs TO THE DESIGN OF ADC AND DAC CIRCUITS
Authors: KARMAKAR SUPRIYA , CHANDY JOHN A , JAIN FAQUIR C. 
Published: December 2011

This paper describes design of analog-to-digital converters (ADCs) and digital-to-analog onverters (DACs) using field-effect transistors that exhibit three states in their transfer characteristics. An intermediate state " i " has been observed in the transfer characteristics (drain current-gate voltage) of FETs when two layers of cladded quantum dots (e.g. SiO x - Si and GeO x - Ge ) are introduced in the gate region above the tunnel insulator between the source and drain regions. Three states in such a transistor, defined as quantum dot gate field-effect transistor (QDG-FET) include two stable states (ON and OFF) and a low-current saturation state " i " in its transfer characteristics. QDG-FETs are quite different in construction than nanodot based nonvolatile memories, reported in the literature, where the quantum dots are sandwiched between a tunnel gate insulator and a relatively thick control gate dielectric. In this paper we present analog-to-digital converters (ADCs) using comparators based on QDG-FETs. A comparator is designed with fewer three-state QDG-FETs. Designs of 3-bit ADC, using 25 nm QDG-FETs, are simulated showing a signal-to-noise ratio (SNR) of ~18. In addition, the R-2R ladder problem, encountered in conventional analog-to digital converters (ADCs), is absent in QDG-FET based architecture.
Sorafenib Sensitizes (−)-Gossypol-Induced Growth Suppression in Androgen-Independent Prostate Cancer Cells via Mcl-1 Inhibition and Bak Activation
Authors: Lian Jiqin , Ni Zhenhong , Dai Xufang , Su Chang , Smith Amber Rae , Xu Liang , He Fengtian 
Published: December 2011

AbstractThe natural BH3-mimetic (−)-gossypol shows promising efficacy in ongoing phase II/III clinical trials for human prostate cancer. Here, we show for the first time, that treatment with (−)-gossypol and multikinase inhibitor sorafenib synergistically suppresses the growth of androgen-independent prostate cancer cells (AI-PC) in vitro and in vivo. Our data suggest that sorafenib attenuates (−)-gossypol-induced Mcl-1 upregulation in AI-PCs. In this way, it serves as a potent chemosensitizer to affect cell death. Interestingly, (−)-gossypol and sorafenib induce cell death via two distinct pathways among different AI-PCs; DU145 cells via apoptosis and PC-3 via autophagy. The appointed death pathway may depend on the level of proapoptotic protein Bak, although the level of antiapoptotic protein Bcl-2 plays some role in it. DU145 cells with high Bak level prefer apoptosis induction, whereas PC-3 cells with low Bak prefer the induction of autophagy. Furthermore, inhibiting nondominant death pathways, that is, autophagy in DU145 and apoptosis in PC-3, enhances cell killing by (−)-gossypol/sorafenib combination therapy. Ultimately, our data expose a new action for sorafenib as an enhancer of (−)-gossypol-induced cell growth suppression and reveal a novel cell death mode by Bak activation manners in AI-PCs. These new insights may facilitate the rational design of clinical trials by selecting patients most likely to benefit from the Bcl-2–targeted molecular therapy. Mol Cancer Ther; 11(2); 416–26. ©2011 AACR.
Computing and Partitioning Cloud Feedbacks Using Cloud Property Histograms. Part II: Attribution to Changes in Cloud Amount, Altitude, and Optical Depth
Authors: Zelinka Mark D. , Klein Stephen A. , Hartmann Dennis L. 
Published: December 2011

Cloud radiative kernels and histograms of cloud fraction, both as functions of cloud-top pressure and optical depth, are used to quantify cloud amount, altitude, and optical depth feedbacks. The analysis is applied to doubled-CO2 simulations from 11 global climate models in the Cloud Feedback Model Intercomparison Project. Global, annual, and ensemble mean longwave (LW) and shortwave (SW) cloud feedbacks are positive, with the latter nearly twice as large as the former. The robust increase in cloud-top altitude in both the tropics and extratropics is the dominant contributor to the positive LW cloud feedback. The negative impact of reductions in cloud amount offsets more than half of the positive impact of rising clouds on LW cloud feedback, but the magnitude of compensation varies considerably across the models. In contrast, robust reductions in cloud amount make a large and virtually unopposed positive contribution to SW cloud feedback, though the intermodel spread is greater than for any other individual feedback component. Overall reductions in cloud amount have twice as large an impact on SW fluxes as on LW fluxes, such that the net cloud amount feedback is moderately positive, with no models exhibiting a negative value. As a consequence of large but partially offsetting effects of cloud amount reductions on LW and SW feedbacks, both the mean and intermodel spread in net cloud amount feedback are smaller than those of the net cloud altitude feedback. Finally, the study finds that the large negative cloud feedback at high latitudes results from robust increases in cloud optical depth, not from increases in total cloud amount as is commonly assumed.