bluuebunny/crossref_metadata_2025_split huggingface dataset:
Absence of Mycobacterium intracellulare and Presence of Mycobacterium chimaera in Household Water and Biofilm Samples of Patients in the United States with Mycobacterium avium Complex Respiratory Disease
Authors: Wallace Richard J. , Iakhiaeva Elena , Williams Myra D. , Brown-Elliott Barbara A. , Vasireddy Sruthi , Vasireddy Ravikiran , Lande Leah , Peterson Donald D. , Sawicki Janet , Kwait Rebecca , Tichenor Wellington S. , Turenne Christine , Falkinham Joseph O. 
Published: March 2013

ABSTRACTRecent studies have shown that respiratory isolates from pulmonary disease patients and household water/biofilm isolates ofMycobacterium aviumcould be matched by DNA fingerprinting. To determine if this is true forMycobacterium intracellulare, household water sources for 36 patients withMycobacterium aviumcomplex (MAC) lung disease were evaluated. MAC household water isolates from three published studies that included 37 additional MAC respiratory disease patients were also evaluated. Species identification was done initially using nonsequencing methods with confirmation by internal transcribed spacer (ITS) and/or partial 16S rRNA gene sequencing.M. intracellularewas identified by nonsequencing methods in 54 respiratory cultures and 41 household water/biofilm samples. By ITS sequencing, 49 (90.7%) respiratory isolates wereM. intracellulareand 4 (7.4%) wereMycobacterium chimaera. In contrast, 30 (73%) household water samples wereM. chimaera, 8 (20%) were other MAC X species (i.e., isolates positive with a MAC probe but negative with species-specificM. aviumandM. intracellulareprobes), and 3 (7%) wereM. avium; none wereM. intracellulare. In comparison,M. aviumwas recovered from 141 water/biofilm samples. These results indicate thatM. intracellularelung disease in the United States is acquired from environmental sources other than household water. Nonsequencing methods for identification of nontuberculous mycobacteria (including those of the MAC) might fail to distinguish closely related species (such asM. intracellulareandM. chimaera). This is the first report ofM. chimaerarecovery from household water. The study underscores the importance of taxonomy and distinguishing the many species and subspecies of the MAC.
Comparison of the Vitek 2, MicroScan, and Etest Methods with the Agar Dilution Method in Assessing Colistin Susceptibility of Bloodstream Isolates of Acinetobacter Species from a Korean University Hospital
Authors: Lee Seung Yeob , Shin Jong Hee , Lee Kyungwon , Joo Min Young , Park Kyung Hwa , Shin Myung Geun , Suh Soon Pal , Ryang Dong Wook , Kim Soo Hyun 
Published: March 2013

ABSTRACT

We evaluated three commercial colistin susceptibility testing methods using 213 bloodstream
Acinetobacter
isolates identified by gene sequencing. Compared to the agar dilution reference method, excellent categorical agreements (both 99.1%) were observed using Vitek 2 and Etest, compared to 87.3% (95.7% for
Acinetobacter baumannii
and 80.7% for non-
baumannii Acinetobacter
isolates) using MicroScan.
Prosthetic Valve Endocarditis and Bloodstream Infection Due to Mycobacterium chimaera
Authors: Achermann Yvonne , Rössle Matthias , Hoffmann Matthias , Deggim Vanessa , Kuster Stefan , Zimmermann Dieter R. , Bloemberg Guido , Hombach Michael , Hasse Barbara 
Published: March 2013

ABSTRACT

Prosthetic valve endocarditis (PVE) due to fast-growing nontuberculous mycobacteria (NTM) has been reported anecdotally. Reports of PVE with slowly growing NTM, however, are lacking. We present here one case of PVE and one case of bloodstream infection caused by
Mycobacterium chimaera
. Randomly amplified polymorphic DNA (RAPD)-PCR indicated a relatedness of the two
M. chimaera
strains. Both patients had heart surgery 2 years apart from each other. A nosocomial link was not detected.
Dietzia papillomatosis Bacteremia
Authors: Rammer Paul , Calum Henrik , Moser Claus , Björnsdóttir Maria K. , Smedegaard Heidi , Høiby Niels , Bjarnsholt Thomas 
Published: March 2013

ABSTRACT

The clinical significance of
Dietzia papillomatosis
is for the moment limited to the rare skin disease confluent and reticulated papillomatosis. We present a case of infection with
D. papillomatosis
in a 2-year-old boy with known syringomyelia. The microbiological diagnosis was done using 16S rRNA gene sequencing. This is the first report of bacteremia with
D. papillomatosis
.
Griffithsin Protects Mice from Genital Herpes by Preventing Cell-to-Cell Spread
Authors: Nixon Briana , Stefanidou Martha , Mesquita Pedro M. M. , Fakioglu Esra , Segarra Theodore , Rohan Lisa , Halford William , Palmer Kenneth E. , Herold Betsy C. 
Published: March 2013

ABSTRACT

Griffithsin, which binds N-linked glycans on gp120 to prevent HIV entry, has the most potent HIV-1 inhibitory activity described for any antiviral lectin and is being developed for topical preexposure prophylaxis. The current studies were designed to further assess its potential by exploring its activity against herpes simplex virus 2 (HSV-2), a cofactor for HIV acquisition,
in vitro
and in a murine model. Safety was evaluated by examining its impact on epithelial barrier integrity in polarized cultures and testing whether repeated intravaginal dosing potentiates the susceptibility of mice to genital herpes. Griffithsin displayed modest inhibitory activity against HSV-2 if present during viral entry but completely blocked plaque formation if present postentry, reduced plaque size, and prevented cell-to-cell spread. These
in vitro
findings translated to significant protection against genital herpes in mice treated with 0.1% griffithsin gel. Griffithsin, but not placebo gel, prevented viral spread (visualized with a luciferase-expressing virus), significantly reduced disease scores, and resulted in greater survival (
P
< 0.05, log rank test). Protection persisted when HSV-2 was introduced in seminal plasma. Although griffithsin triggered a small decline in transepithelial electrical resistance in polarized cultures, this did not translate to any significant increase in the ability of HIV to migrate from the apical to the basolateral chamber nor to an increase in susceptibility to HSV-2 in mice treated with griffithsin gel for 7 days. These findings demonstrate that griffithsin inhibits HSV-2 by a unique mechanism of blocking cell-to-cell spread and support its further development for HIV and HSV-2 prevention.
Structure-Function Analysis of Severe Acute Respiratory Syndrome Coronavirus RNA Cap Guanine-N7-Methyltransferase
Authors: Chen Yu , Tao Jiali , Sun Ying , Wu Andong , Su Ceyang , Gao Guozhen , Cai Hui , Qiu Su , Wu Yingliang , Ahola Tero , Guo Deyin 
Published: March 2013

ABSTRACT

Coronaviruses possess a cap structure at the 5′ ends of viral genomic RNA and subgenomic RNAs, which is generated through consecutive methylations by virally encoded guanine-N7-methyltransferase (N7-MTase) and 2′-O-methyltransferase (2′-O-MTase). The coronaviral N7-MTase is unique for its physical linkage with an exoribonuclease (ExoN) harbored in nonstructural protein 14 (nsp14) of coronaviruses. In this study, the structure-function relationships of the N7-MTase were analyzed by deletion and site-directed mutagenesis of severe acute respiratory syndrome coronavirus (SARS-CoV) nsp14. The results showed that the ExoN domain is closely involved in the activity of the N7-MTase, suggesting that coronavirus N7-MTase is different from all other viral N7-MTases, which are separable from other structural domains located in the same polypeptide. Two of the 12 critical residues identified to be essential for the N7-MTase were located at the N terminus of the core ExoN domain, reinforcing a role of the ExoN domain in the N7-MTase activity of nsp14. The other 10 critical residues were distributed throughout the N7-MTase domain but localized mainly in the
S
-adenosyl-
l
-methionine (SAM)-binding pocket and key structural elements of the MTase fold of nsp14. The sequence motif DxGxPxA (amino acids [aa] 331 to 338) was identified as the key part of the SAM-binding site. These results provide insights into the structure and functional mechanisms of coronaviral nsp14 N7-MTase.
Epstein-Barr Virus Negativity among Individuals Older than 60 Years Is Associated with HLA-C and HLA-Bw4 Variants and Tonsillectomy
Authors: Durovic Bojana , Gasser Olivier , Gubser Patrick , Sigle Jörg , Hirsch Hans H. , Stern Martin , Buser Andreas , Hess Christoph 
Published: March 2013

ABSTRACT
Epstein-Barr virus (EBV) infects ∼95% of the adult population. The factors that confer protection in the remaining ∼5% remain unknown. In an exploratory study, we assessed immunogenetic factors and tonsillectomy in a cohort of 17 EBV-negative and 39 EBV-positive healthy individuals aged >60 years. Analyses of HLA genotypes revealed an association between EBV negativity and the presence of HLA-C-35T/T and/or HLA-Bw4 alleles. In addition, EBV-negative donors presented with a history of tonsillectomy more often than EBV-positive donors.
Rift Valley Fever Virus Clearance and Protection from Neurologic Disease Are Dependent on CD4
+
T Cell and Virus-Specific Antibody Responses
Authors: Dodd Kimberly A. , McElroy Anita K. , Jones Megan E. B. , Nichol Stuart T. , Spiropoulou Christina F. 
Published: March 2013

ABSTRACT

Rift Valley fever virus (RVFV) causes outbreaks of severe disease in people and livestock throughout Africa and the Arabian Peninsula. Human RVFV infections generally manifest as a self-limiting febrile illness, but in some individuals, the disease can progress to a fatal encephalitis or hemorrhagic syndrome. Little is known about the host characteristics that predispose development of more severe disease. Early in infection, interferon-mediated antiviral responses are critical for controlling RVFV replication, but the roles of downstream adaptive immune responses in determining clinical outcome have not been examined. Here, using a C57BL/6 mouse disease model, we evaluated the roles of B cells and T cells in RVFV pathogenesis. Given the profound inhibition of the innate response by the viral NSs protein and rapid course of wild-type infection, we utilized an attenuated RVFV lacking NSs to examine host responses following primary infection. Experiments utilizing B-cell-deficient mice or targeted T cell depletions of wild-type mice demonstrated that B cells and CD4
+
T cells, but not CD8
+
T cells, were critical for mediating viral clearance, even in the presence of a functional innate response. One-third of CD4-depleted mice developed severe neurologic disease following infection, in contrast to virus-infected mock-depleted mice that showed no clinical signs. CD4
+
T cells were required for robust IgG and neutralizing antibody responses that correlated with RVFV clearance from peripheral tissues. Furthermore, CD4-depleted mice demonstrated significantly stronger proinflammatory responses relative to controls, suggesting CD4
+
T cells regulate immune responses to RVFV infection. Together, these results indicate CD4
+
T cells are critical determinants of RVFV pathogenesis and play an important role in preventing onset of neurologic disease.
T Cells Target APOBEC3 Proteins in Human Immunodeficiency Virus Type 1-Infected Humans and Simian Immunodeficiency Virus-Infected Indian Rhesus Macaques
Authors: Champiat Stéphane , Garrison Keith E. , Raposo Rui André Saraiva , Burwitz Benjamin J. , Reed Jason , Tandon Ravi , York Vanessa A. , Newman Laura P. , Nimityongskul Francesca A. , Wilson Nancy A. , Almeida Rafael R. , Martin Jeffrey N. , Deeks Steven G. , Rosenberg Michael G. , Wiznia Andrew A. , Spotts Gerald E. , Pilcher Christopher D. , Hecht Fredrick M. , Ostrowski Mario A. , Sacha Jonah B. , Nixon Douglas F. 
Published: March 2013

ABSTRACT
APOBEC3 proteins mediate potent antiretroviral activity by hypermutating the retroviral genome during reverse transcription. To counteract APOBEC3 and gain a replicative advantage, lentiviruses such as human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) have evolved the Vif protein, which targets APOBEC3 proteins for proteasomal degradation. However, the proteasome plays a critical role in the generation of T cell peptide epitopes. Whether Vif-mediated destruction of APOBEC3 proteins leads to the generation and presentation of APOBEC3-derived T cell epitopes on the surfaces of lentivirus-infected cells remains unknown. Here, using peptides derived from multiple Vif-sensitive APOBEC3 proteins, we identified APOBEC3-specific T cell responses in both HIV-1-infected patients and SIV-infected rhesus macaques. These results raise the possibility that these T cell responses may be part of the larger antiretroviral immune response.
Tyrosine 132 Phosphorylation of Influenza A Virus M1 Protein Is Crucial for Virus Replication by Controlling the Nuclear Import of M1
Authors: Wang Shanshan , Zhao Zhendong , Bi Yuhai , Sun Lei , Liu Xiaoling , Liu Wenjun 
Published: March 2013

ABSTRACT
Phosphorylation of viral proteins plays important roles in the influenza A virus (IAV) life cycle. By using mass spectrometry, we identified tyrosine 132 (Y132) as a phosphorylation site of the matrix protein (M1) of the influenza virus A/WSN/1933(H1N1). Phosphorylation at this site is essential to the process of virus replication by controlling the nuclear import of M1. We further demonstrated that the phosphorylated tyrosine is crucial for the binding of M1 to the nuclear import factor importin-α1, since any substitutions at this site severely reduce this protein-protein interaction and damage the importin-α1-mediated nuclear import of M1. Additionally, the tyrosine phosphorylation which leads to the nuclear import of M1 is blocked by a Janus kinase inhibitor. The present study reveals a pivotal role of this tyrosine phosphorylation in the intracellular transportation of M1, which controls the process of viral replication.
Kaposi's Sarcoma-Associated Herpesvirus Induces Rapid Release of Angiopoietin-2 from Endothelial Cells
Authors: Ye Feng-Chun , Zhou Fu-Chun , Nithianantham Stanley , Chandran Bala , Yu Xiao-Lan , Weinberg Aaron , Gao Shou-Jiang 
Published: March 2013

ABSTRACT

Kaposi sarcoma-associated herpesvirus (KSHV) stimulates proliferation, angiogenesis, and inflammation to promote Kaposi sarcoma (KS) tumor growth, which involves various growth factors and cytokines. Previously, we found that KSHV infection of human umbilical vein endothelial cells (HUVECs) induces a transcriptional induction of the proangiogenic and proinflammatory cytokine angiopoietin-2 (Ang-2). Here, we report that KSHV induces rapid release of Ang-2 that is presynthesized and stored in the Weibel-Palade bodies (WPB) of endothelial cells upon binding to its integrin receptors. Blocking viral binding to integrins inhibits Ang-2 release. KSHV binding activates the integrin tyrosine kinase receptor signaling pathways, leading to tyrosine phosphorylation of focal adhesion kinase (FAK), the tyrosine kinase Src, and the Calα2 subunit of the
l
-type calcium channel to trigger rapid calcium (Ca
2+
) influx. Pretreatment of endothelial cells with specific inhibitors of protein tyrosine kinases inhibits KSHV-induced Ca
2+
influx and Ang-2 release. Inhibition of Ca
2+
mobilization with calcium channel blockers also inhibits Ang-2 release. Thus, the interaction between KSHV and its integrin receptors plays a key role in regulating rapid Ang-2 release from endothelial cells. This finding highlights a novel mechanism of viral induction of angiogenesis and inflammation, which might play important roles in the early event of KS tumor development.
Recombination within the Pandemic Norovirus GII.4 Lineage
Authors: Eden John-Sebastian , Tanaka Mark M. , Boni Maciej F. , Rawlinson William D. , White Peter A. 
Published: March 2013

ABSTRACT
Norovirus (NoV) is the leading cause of viral gastroenteritis globally. Since 1996, NoV variants of a single genetic lineage, GII.4, have been associated with at least six pandemics of acute gastroenteritis and caused between 62 and 80% of all NoV outbreaks. The emergence of these novel GII.4 variants has been attributed to rapid evolution and antigenic variation in response to herd immunity; however, the contribution of recombination as a mechanism facilitating emergence is increasingly evident. In this study, we sought to examine the role that intragenotype recombination has played in the emergence of GII.4 variants. Using a genome-wide approach including 25 complete genome sequences generated as part of this study, 11 breakpoints were identified within the NoV GII.4 lineage. The breakpoints were located at three recombination hot spots: near the open reading frame 1/2 (ORF1/2) and ORF2/3 overlaps, as well as within ORF2, which encodes the viral capsid, at the junction of the shell and protruding domains. Importantly, we show that recombination contributed to the emergence of the recent pandemic GII.4 variant, New Orleans 2009, and a newly identified GII.4 variant, termed Sydney 2012. Reconstructing the evolutionary history of the GII.4 lineage reveals the widespread impact of both inter- and intragenotype recombination on the emergence of many GII.4 variants. Lastly, this study highlights the many challenges in the identification of true recombination events and proposes that guidelines be applied for identifying NoV recombinants.
Acute hamstring injuries in Swedish elite football: a prospective randomised controlled clinical trial comparing two rehabilitation protocols
Authors: Askling Carl M , Tengvar Magnus , Thorstensson Alf 
Published: March 2013

BackgroundHamstring injury is the single most common injury in European professional football and, therefore, time to return and secondary prevention are of particular concern.ObjectiveTo compare the effectiveness of two rehabilitation protocols after acute hamstring injury in Swedish elite football players by evaluating time needed to return to full participation in football team-training and availability for match selection.Study designProspective randomised comparison of two rehabilitation protocols.MethodsSeventy-five football players with an acute hamstring injury, verified by MRI, were randomly assigned to one of two rehabilitation protocols. Thirty-seven players were assigned to a protocol emphasising lengthening exercises, L-protocol and 38 players to a protocol consisting of conventional exercises, C-protocol. The outcome measure was the number of days to return to full-team training and availability for match selection. Reinjuries were registered during a period of 12 months after return.ResultsTime to return was significantly shorter for the players in the L-protocol, mean 28 days (1SD±15, range 8–58 days), compared with the C-protocol, mean 51 days (1SD±21, range 12–94 days). Irrespective of protocol, stretching-type of hamstring injury took significantly longer time to return than sprinting-type, L-protocol: mean 43 vs 23 days and C-protocol: mean 74 vs 41 days, respectively. The L-protocol was significantly more effective than the C-protocol in both injury types. One reinjury was registered, in the C-protocol.ConclusionsA rehabilitation protocol emphasising lengthening type of exercises is more effective than a protocol containing conventional exercises in promoting time to return in Swedish elite football.
Endovascular treatment for aneurysmal subarachnoid hemorrhage in the ninth decade of life and beyond
Authors: Wilson Thomas J , Davis Matthew C , Stetler William R , Giles David A , Chaudhary Neeraj , Gemmete Joseph J , Thompson B Gregory , Pandey Aditya S 
Published: March 2013

ObjectiveAs the population ages, clinicians will be faced with difficult decisions regarding treatment of elderly patients presenting with aneurysmal subarachnoid hemorrhage (aSAH). Previous data have led to continued pessimism by some clinicians treating elderly and very elderly patients presenting with aSAH. The aim of this study was to present our experience in the very elderly treated with endovascular coiling after presentation with aSAH.MethodsRetrospective review of all patients 80 years of age or older presenting with aSAH who underwent coil embolization. Primary outcomes of interest were functional outcome, as assessed by the Glasgow Outcome Scale score, and inhospital mortality.ResultsDuring the study period, 16 patients aged 80 years or older presenting with aSAH underwent coil embolization; nine (56%) had a poor outcome at the 6 month follow-up while seven (44%) had a good outcome. The inhospital mortality rate was 50%. Of those patients alive at discharge, seven out of eight (88%) patients had a good outcome. Variables associated with poor outcome included higher Hunt and Hess score (p=0.010), use of balloon assistance/remodeling (p=0.025), and presence of coronary artery disease (p=0.006).ConclusionsNot surprisingly, we found that very elderly patients presenting with aSAH have a high inhospital mortality rate. However, those patients who survive to discharge have a surprisingly robust chance at good functional recovery when treated with coil embolization. We believe these results support offering endovascular coil embolization, when feasible, to very elderly patients presenting with aSAH.
Bazedoxifene Exhibits Antiestrogenic Activity in Animal Models of Tamoxifen-Resistant Breast Cancer: Implications for Treatment of Advanced Disease
Authors: Wardell Suzanne E. , Nelson Erik R. , Chao Christina A. , McDonnell Donald P. 
Published: March 2013

Abstract
Purpose: There is compelling evidence to suggest that drugs that function as pure estrogen receptor (ER-α) antagonists, or that downregulate the expression of ER-α, would have clinical use in the treatment of advanced tamoxifen- and aromatase-resistant breast cancer. Although such compounds are currently in development, we reasoned, based on our understanding of ER-α pharmacology, that there may already exist among the most recently developed selective estrogen receptor modulators (SERM) compounds that would have usage as breast cancer therapeutics. Thus, our objective was to identify among available SERMs those with unique pharmacologic activities and to evaluate their potential clinical use with predictive models of advanced breast cancer.
Experimental Design: A validated molecular profiling technology was used to classify clinically relevant SERMs based on their impact on ER-α conformation. The functional consequences of these observed mechanistic differences on (i) gene expression, (ii) receptor stability, and (iii) activity in cellular and animal models of advanced endocrine-resistant breast cancer were assessed.
Results: The high-affinity SERM bazedoxifene was shown to function as a pure ER-α antagonist in cellular models of breast cancer and effectively inhibited the growth of both tamoxifen-sensitive and -resistant breast tumor xenografts. Interestingly, bazedoxifene induced a unique conformational change in ER-α that resulted in its proteasomal degradation, although the latter activity was dispensable for its antagonist efficacy.
Conclusion: Bazedoxifene was recently approved for use in the European Union for the treatment of osteoporosis and thus may represent a near-term therapeutic option for patients with advanced breast cancer. Clin Cancer Res; 19(9); 2420–31. ©2013 AACR.