bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toll-Like Receptor 4 Gene (
TLR4
), but Not
TLR2
, Polymorphisms Modify the Risk of Tonsillar Disease Due to
Streptococcus pyogenes
and
Haemophilus influenzae
Authors: Liadaki Kyriaki , Petinaki Efthimia , Skoulakis Charalampos , Tsirevelou Paraskeui , Klapsa Dimitra , Germenis Anastasios E. , Speletas Matthaios 
Published: December 2010

ABSTRACT

Tonsillar disease (recurrent tonsillitis and/or tonsillar hypertrophy) is one of the most common human disorders, with
Streptococcus pyogenes
(group A beta-hemolytic streptococcus [GAS]) and
Haemophilus influenzae
representing the most common pathogens. Until now, no study has investigated why some individuals are more susceptible to tonsillar infections caused by specific bacteria than others. The aim of this study was to uncover possible associations between common Toll-like receptor gene (
TLR
) polymorphisms and tonsillar disease. The
TLR2
-R753Q,
TLR4
-D299G, and
TLR4
-T399I polymorphisms were determined in a cohort of 327 patients subjected to tonsillectomy due to recurrent tonsillitis (
n
= 245) and tonsillar hypertrophy (
n
= 82) and 245 healthy bone marrow donors. Associations of the aforementioned polymorphisms with the isolated bacterial strains after tonsillectomy were also investigated. Interestingly, carriers of the
TLR4
polymorphisms displayed an approximately 3-fold increased risk for GAS infections (for
TLR4
-D299G, odds ratio [OR] = 2.81, 95% confidence interval [CI] = 1.16 to 6.79,
P
= 0.038; for
TLR4
-T399I, OR = 3.01, 95% CI = 1.29 to 7.02,
P
= 0.023), and this association was more profound in patients with recurrent tonsillitis. On the contrary, the presence of the
TLR4
-T399I polymorphism was associated with a 2-fold decreased risk of
Haemophilus influenzae
carriage (OR = 0.38, 95% CI = 0.15 to 0.96,
P
= 0.038). In the end, no significant differences were observed, considering the genotype and allele frequencies of the above-mentioned polymorphisms, between patients and controls. Our findings indicate that, regarding tonsillar infections,
TLR4
polymorphisms predispose individuals to GAS infection, while they are protective against
Haemophilus influenzae
infection. This result further elucidates the role that host immune genetic variations might play in the susceptibility to common infections and tonsillar disease.
Persistence of
Leishmania donovani
Antibodies in Past Visceral Leishmaniasis Cases in India
Authors: Gidwani Kamlesh , Picado Albert , Ostyn Bart , Singh Shri Prakash , Kumar Rajiv , Khanal Basudha , Lejon Veerle , Chappuis François , Boelaert Marleen , Sundar Shyam 
Published: December 2010

ABSTRACT

The persistence of anti-
Leishmania donovani
antibodies in past visceral leishmaniasis (VL) cases was retrospectively assessed by means of the direct agglutination test (DAT) and the rK39 enzyme-linked immunosorbent assay (ELISA). Antibody titers remained high for an extended period of time in past cases of VL. These results highlight the need to carefully elicit the history of patients with VL symptoms.
Molecular Determination of H Antigens of Salmonella by Use of a Microsphere-Based Liquid Array
Authors: McQuiston John R. , Waters R. Jordan , Dinsmore Blake A. , Mikoleit Matthew L. , Fields Patricia I. 
Published: December 2010

ABSTRACT

Serotyping of
Salmonella
has been an invaluable subtyping method for epidemiologic studies for more than 70 years. The technical difficulties of serotyping, primarily in antiserum production and quality control, can be overcome with modern molecular methods. We developed a DNA-based assay targeting the genes encoding the flagellar antigens (
fliC
and
fljB
) of the Kauffmann-White serotyping scheme. Fifteen H antigens (H:a, -b, -c, -d, -d/j, -e,h, -i, -k, -r, -y, -z, -z
10
, -z
29
, -z
35
, and -z
6
), 5 complex major antigens (H:G, -EN, -Z4, -1, and -L) and 16 complex secondary antigens (H:2, -5, -6, -7, -f, -m/g,m, -m/m,t, -p, -s, -t/m,t, -v, -x, -z
15
, -z
24
, -z
28
, and -z
51
) were targeted in the assay. DNA probes targeting these antigens were designed and evaluated on 500 isolates tested in parallel with traditional serotyping methods. The assay correctly identified 461 (92.2%) isolates based on the 36 antigens detected in the assay. Among the isolates considered correctly identified, 47 (9.4%) were partially serotyped because probes corresponding to some antigens in the strains were not in the assay, and 13 (2.6%) were monophasic or nonmotile strains that possessed flagellar antigen genes that were not expressed but were detected in the assay. The 39 (7.8%) strains that were not correctly identified possessed an antigen that should have been detected by the assay but was not. Apparent false-negative results may be attributed to allelic divergence. The molecular assay provided results that paralleled traditional methods with a much greater throughput, while maintaining the integrity of the Kauffmann-White serotyping scheme, thus providing backwards-compatible epidemiologic data. This assay should greatly enhance the ability of clinical and public health laboratories to serotype
Salmonella
.
Clinically Healthy Skin of Dogs Is a Potential Reservoir for Canine Papillomaviruses
Authors: Lange Christian E. , Zollinger Sabrina , Tobler Kurt , Ackermann Mathias , Favrot Claude 
Published: December 2010

ABSTRACTPapillomaviruses have been linked to several skin disorders in the dog. In order to have a suitable diagnostic tool for canine papillomavirus detection, eight PCRs with published primer combinations were evaluated. The most sensitive PCR was used to demonstrate that papillomavirus DNA can be detected on nonlesional skin of dogs.
Beyond the Consensus: Dissecting Within-Host Viral Population Diversity of Foot-and-Mouth Disease Virus by Using Next-Generation Genome Sequencing
Authors: Wright Caroline F. , Morelli Marco J. , Thébaud Gaël , Knowles Nick J. , Herzyk Pawel , Paton David J. , Haydon Daniel T. , King Donald P. 
Published: December 2010

ABSTRACT

The diverse sequences of viral populations within individual hosts are the starting material for selection and subsequent evolution of RNA viruses such as foot-and-mouth disease virus (FMDV). Using next-generation sequencing (NGS) performed on a Genome Analyzer platform (Illumina), this study compared the viral populations within two bovine epithelial samples (foot lesions) from a single animal with the inoculum used to initiate experimental infection. Genomic sequences were determined in duplicate sequencing runs, and the consensus sequence of the inoculum determined by NGS was identical to that previously determined using the Sanger method. However, NGS revealed the fine polymorphic substructure of the viral population, from nucleotide variants present at just below 50% frequency to those present at fractions of 1%. Some of the higher-frequency polymorphisms identified encoded changes within codons associated with heparan sulfate binding and were present in both foot lesions, revealing intermediate stages in the evolution of a tissue culture-adapted virus replicating within a mammalian host. We identified 2,622, 1,434, and 1,703 polymorphisms in the inoculum and in the two foot lesions, respectively: most of the substitutions occurred in only a small fraction of the population and represented the progeny from recent cellular replication prior to onset of any selective pressures. We estimated the upper limit for the genome-wide mutation rate of the virus within a cell to be 7.8 × 10
−4
per nucleotide. The greater depth of detection achieved by NGS demonstrates that this method is a powerful and valuable tool for the dissection of FMDV populations within hosts.
Serotype-Specific Inactivation of the Cellular DNA Damage Response during Adenovirus Infection
Authors: Forrester Natalie A. , Sedgwick Garry G. , Thomas Anoushka , Blackford Andrew N. , Speiseder Thomas , Dobner Thomas , Byrd Philip J. , Stewart Grant S. , Turnell Andrew S. , Grand Roger J. A. 
Published: December 2010

ABSTRACT
Adenovirus type 5 (Ad5) inactivates the host cell DNA damage response by facilitating the degradation of Mre11, DNA ligase IV, and p53. In the case of p53, this is achieved through polyubiquitylation by Ad5E1B55K and Ad5E4orf6, which recruit a Cul5-based E3 ubiquitin ligase. Recent evidence indicates that this paradigm does not apply to other adenovirus serotypes, since Ad12, but not Ad5, causes the degradation of TOPBP1 through the action of E4orf6 alone and a Cul2-based E3 ubiquitin ligase. We now have extended these studies to adenovirus groups A to E. While infection by Ad4, Ad5, and Ad12 (groups E, C, and A, respectively) cause the degradation of Mre11, DNA ligase IV, and p53, infection with Ad3, Ad7, Ad9, and Ad11 (groups B1, B1, D, and B2, respectively) only affects DNA ligase IV levels. Indeed, Ad3, Ad7, and Ad11 cause the marked accumulation of p53. Despite this, MDM2 levels were very low following infection with all of the viruses examined here, regardless of whether they increase p53 expression. In addition, we found that only Ad12 causes the degradation of TOPBP1, and, like Ad5, Ad4 recruits a Cul5-based E3 ubiquitin ligase to degrade p53. Surprisingly, Mre11 and DNA ligase IV degradation do not appear to be significantly affected in Ad4-, Ad5-, or Ad12-infected cells depleted of Cul2 or Cul5, indicating that E1B55K and E4orf6 recruit multiple ubiquitin ligases to target cellular proteins. Finally, although Mre11 is not degraded by Ad3, Ad7, Ad9, and Ad11, no viral DNA concatemers could be detected. We suggest that group B and D adenoviruses have evolved mechanisms based on the loss of DNA ligase IV and perhaps other unknown molecules to disable the host cell DNA damage response to promote viral replication.
Deerpox Virus Encodes an Inhibitor of Apoptosis That Regulates Bak and Bax
Authors: Banadyga Logan , Lam Sing-Chi , Okamoto Toru , Kvansakul Marc , Huang David C. , Barry Michele 
Published: December 2010

ABSTRACT

Poxviruses encode numerous proteins that inhibit apoptosis, a form of cell death critical to the elimination of virally infected cells. Sequencing of the deerpox virus genome revealed DPV022, a protein that lacks obvious homology to cellular members of the Bcl-2 family but shares limited regions of amino acid identity with two unique poxviral inhibitors of apoptosis, M11L and F1L. Given the limited homology, we sought to determine whether DPV022 could inhibit apoptosis. Here we show that DPV022 localized to the mitochondria, where it inhibited apoptosis. We used a
Saccharomyces cerevisiae
model system to demonstrate that in the absence of all other Bcl-2 family proteins, DPV022 interacted directly with Bak and Bax. We confirmed the ability of DPV022 to interact with Bak and Bax by immunoprecipitation and showed that DPV022 prevented apoptosis induced by Bak and Bax overexpression. Moreover, we showed that DPV022 blocked apoptosis even when all the endogenous mammalian antiapoptotic proteins were neutralized by a combination of selective BH3 ligands. During virus infection, DPV022 interacted with endogenous Bak and Bax and prevented the conformational activation of both of them. Thus, we have characterized a novel poxviral inhibitor of apoptosis with intriguing amino acid differences from the well-studied proteins M11L and F1L.
Palmitoylation of MIR2 Is Required for Its Function
Authors: Anania Veronica G. , Coscoy Laurent 
Published: December 2010

ABSTRACT

Kaposi's sarcoma-associated herpesvirus (KSHV) encodes two RING finger E3 ubiquitin ligases (MIR1 and MIR2) that mediate ubiquitination and degradation of cellular proteins important for the establishment of an efficient antiviral immune response. MIR1 and MIR2 share 30% sequence identity; however, their substrate preferences are varied. MIR1 has been shown to primarily downregulate major histocompatibility complex class I (MHC-I), whereas MIR2 can downregulate a wide range of cell surface proteins. Many of the MIR substrates are thought to be present in lipid raft microdomains, a subregion of the plasma membrane known to be important for a wide range of signal transduction events. Palmitoylation is a posttranslational modification that increases recruitment of transmembrane proteins to lipid rafts. In this study, we investigated the importance of palmitoylation for MIR function. We present evidence that MIR2-mediated downregulation of MHC-I and platelet endothelial cell adhesion molecule 1 (PECAM-1) but not other substrates is inhibited in the presence of the drug 2-bromohexadecanoic acid (2-Br), a chemical inhibitor of palmitoylation. Biochemical analysis indicates that MIR2 is directly palmitoylated on cysteine 146. Mutation of this cysteine to a phenylalanine prevents MIR2 palmitoylation and blocks the ability of MIR2 to downregulate MHC-I and PECAM-I but not B7.2 and intercellular adhesion molecule 1 (ICAM-I), consistent with the phenotype observed after 2-Br treatment. Unpalmitoylated MIR2 does not interact with MHC-I and is thus unable to ubiquitinate and downregulate MHC-I from the cell surface. Furthermore, we observed that MIR2 is palmitoylated
in vivo
during lytic infection. Palmitoylation may act to regulate MIR2 function and localization during viral infection by allowing MIR2 to properly interact with and downregulate multiple substrates known to play an important role in the host immune response.
A Conserved Determinant in the V1 Loop of HIV-1 Modulates the V3 Loop To Prime Low CD4 Use and Macrophage Infection
Authors: Musich Thomas , Peters Paul J. , Duenas-Decamp Maria José , Gonzalez-Perez Maria Paz , Robinson James , Zolla-Pazner Susan , Ball Jonathan K. , Luzuriaga Katherine , Clapham Paul R. 
Published: December 2010

ABSTRACT
The CD4 binding site (CD4bs) on the HIV-1 envelope plays a major role in determining the capacity of R5 viruses to infect primary macrophages. Thus, envelope determinants within or proximal to the CD4bs have been shown to control the use of low CD4 levels on macrophages for infection. These residues affect the affinity for CD4 either directly or indirectly by altering the exposure of CD4 contact residues. Here, we describe a single amino acid determinant in the V1 loop that also modulates macrophage tropism. Thus, we identified an E153G substitution that conferred high levels of macrophage infectivity for several heterologous R5 envelopes, while the reciprocal G153E substitution abrogated infection. Shifts in macrophage tropism were associated with dramatic shifts in sensitivity to the V3 loop monoclonal antibody (MAb), 447-52D and soluble CD4, as well as more modest changes in sensitivity to the CD4bs MAb, b12. These observations are consistent with an altered conformation or exposure of the V3 loop that enables the envelope to use low CD4 levels for infection. The modest shifts in b12 sensitivity suggest that residue 153 impacts on the exposure of the CD4bs. However, the more intense shifts in sCD4 sensitivity suggest additional mechanisms that likely include an increased ability of the envelope to undergo conformational changes following binding to suboptimal levels of cell surface CD4. In summary, we show that a conserved determinant in the V1 loop modulates the V3 loop to prime low CD4 use and macrophage infection.
Facebook activity of residents and fellows and its impact on the doctor–patient relationship
Authors: Moubarak Ghassan , Guiot Aurélie , Benhamou Ygal , Benhamou Alexandra , Hariri Sarah 
Published: December 2010

AimFacebook is an increasingly popular online social networking site. The purpose of this study was to describe the Facebook activity of residents and fellows and their opinions regarding the impact of Facebook on the doctor–patient relationship.MethodsAn anonymous questionnaire was emailed to 405 residents and fellows at the Rouen University Hospital, France, in October 2009.ResultsOf the 202 participants who returned the questionnaire (50%), 147 (73%) had a Facebook profile. Among responders, 138 (99%) displayed their real name on their profile, 136 (97%) their birthdates, 128 (91%) a personal photograph, 83 (59%) their current university and 76 (55%) their current position. Default privacy settings were changed by 61% of users, more frequently if they were registered for >1 year (p=0.02). If a patient requested them as a ‘friend’, 152 (85%) participants would automatically decline the request, 26 (15%) would decide on an individual basis and none would automatically accept the request. Eighty-eight participants (48%) believed that the doctor–patient relationship would be altered if patients discovered that their doctor had a Facebook account, but 139 (76%) considered that it would change only if the patient had open access to their doctor's profile, independent of its content.ConclusionsResidents and fellows frequently use Facebook and display personal information on their profiles. Insufficient privacy protection might have an impact the doctor–patient relationship.
Electrocardiography of the normal domestic pet rabbit
Authors: Lord B. , Boswood A. , Petrie A. 
Published: December 2010

To establish a well‐tolerated technique for recording electrocardiograms (ECGs) and a reference range for the normal pet rabbit ECG, 46 healthy pet rabbits were studied. The following reference ranges were calculated. Heart rate was 198 to 330 bpm. P waves had a duration of 0.01 to 0.05 seconds and an amplitude of 0.04 to 0.12 mV. The P‐R interval was 0.04 to 0.08 seconds and the duration of the QRS complex was 0.02 to 0.06 seconds. The amplitude of the R wave was 0.03 to 0.39 mV. The Q‐T interval was 0.08 to 0.16 seconds. The amplitude of the T wave was 0.05 to 0.17 mV. Mean electrical axis was found to be −43° to +80°. Evidence of variation due to breed or bodyweight was not found to be significant, except for a quadratic relationship between R wave amplitude and bodyweight. The ECG recording technique used in this study for pet rabbits was well tolerated and shown to be both reliable and repeatable.
Field investigation of a suction break designed to control slope-induced desaturation in an oxygen barrier
Authors: Maqsoud Abdelkabir , Bussière Bruno , Aubertin Michel , Chouteau Michel , Mbonimpa Mamert 
Published: December 2010

Covers with capillary barrier effects (CCBEs) can be used as oxygen barriers to limit gas flux into waste disposal sites. Laboratory and field measurements show that the hydraulic behaviour of such a layered cover system is influenced by its slope geometry and gravity drainage, which can result in local desaturation that may be detrimental to cover performance. Such desaturation can be minimized by placing a suction break in the moisture-retaining layer of the inclined cover. This novel approach was applied in the field to an existing inclined CCBE. The three-layer cover was then subjected to different boundary conditions to evaluate the influence of the suction break on hydraulic behaviour. Volumetric water content and suction measurements demonstrated that a zone of water saturation and low suction was created upslope of the suction break under natural climatic conditions. The hydrological behaviour close to the suction break was not significantly affected by a forced drought of 78 days (without water infiltration). The results also reveal that the suction break had a relatively limited upslope zone of influence (typically less than 10 m). The monitoring results are confirmed by geophysical measurements used to characterize water distribution in the inclined CCBE.
EXTENSION OF THE POINCARÉ GROUP AND NON-ABELIAN TENSOR GAUGE FIELDS
Authors: SAVVIDY GEORGE 
Published: December 2010

In the recently proposed generalization of the Yang–Mills theory, the group of gauge transformation gets essentially enlarged. This enlargement involves a mixture of the internal and space–time symmetries. The resulting group is an extension of the Poincaré group with infinitely many generators which carry internal and space–time indices. The matrix representations of the extended Poincaré generators are expressible in terms of Pauli–Lubanski vector in one case and in terms of its invariant derivative in another. In the later case the generators of the gauge group are transversal to the momentum and are projecting the non-Abelian tensor gauge fields into the transversal plane, keeping only their positively definite spacelike components.
The Impact of Insurance on Access to Cancer Clinical Trials at a Comprehensive Cancer Center
Authors: Klamerus Justin F. , Bruinooge Suanna S. , Ye Xiaobu , Klamerus Mandi L. , Damron Dorothy , Lansey Dina , Lowery John C. , Diaz Luis A. , Ford Jean G. , Kanarek Norma , Rudin Charles M. 
Published: December 2010

Abstract
Purpose: Cancer patients at Johns Hopkins undergo insurance clearance to verify coverage for enrollment to interventional clinical trials. We sought to explore the impact of insurance clearance on disparities in access to cancer clinical trials at this urban comprehensive cancer center.
Experimental Design: We evaluated the frequency of insurance-based denial of access to cancer clinical trials over a 5-year period after initiation of a formal insurance clearance process. We used a case-control design to compare demographic and clinical parameters of patients denied or approved for clinical trials participation by their insurance company in a 3-year interval.
Results: From July 2003 to July 2008, insurance requests for clinical trial participation were submitted on 4,617 consented cancer patients at Johns Hopkins. A total of 628 patients (13.6%) with health insurance were denied therapeutic trial enrollment owing to lack of insurance coverage for participation. A total of 254 patients denied enrollment from 2005 to 2007 were selected for further analysis. Two-hundred sixty randomly selected patients approved for clinical trial participation served as controls. Patients approved were on average older (59.2 versus 54.9 years) than patients denied (P = 0.0001). Residents of Pennsylvania, which lacks a state law mandating cancer clinical trial coverage for residents, were overrepresented among the denied patients (P = 0.0009). No statistically significant variance in the likelihood of insurance denial was found on the basis of sex, race, stage of disease, or presence of comorbidities.
Conclusions: Denial of access to therapeutic clinical trials, even among insured patients, is a significant barrier to clinical cancer research. This barrier spans racial, ethnic, and gender categories. Clin Cancer Res; 16(24); 5997–6003. ©2010 AACR.