bluuebunny/crossref_metadata_2025_split huggingface dataset:
Seroprevalence of Pertussis among Danish Patients with Cough of Unknown Etiology
Authors: Dalby Tine , Harboe Zitta B. , Krogfelt Karen Angeliki 
Published: October 2010

ABSTRACT

The common perception that pertussis is only a childhood disease is not correct. Vaccination or infection with
Bordetella pertussis
provides only short-lived protection against pertussis—and the majority of the population is consequently at risk of contracting pertussis. We evaluated the seroprevalence of pertussis antibodies (IgG against pertussis toxin) in serum samples from 265 Danish patients, aged 8 years and older, with coughs of unknown etiology. Depending on the cutoff chosen, we found that 2.6% to 10.9% of these patients were seropositive for pertussis. Of 178 patients with a reported duration of cough between 2 weeks and 3 months, 3.4% to 12.4% were seropositive for pertussis, indicating recent infection. Our study indicates that
B. pertussis
infection may be underdiagnosed among older children and adults with coughs in Denmark.
Contributions of Conventional and Heavy-Chain IgG to Immunity in Fetal, Neonatal, and Adult Alpacas
Authors: Daley-Bauer L. P. , Purdy S. R. , Smith M. C. , Gagliardo L. F. , Davis W. C. , Appleton J. A. 
Published: October 2010

ABSTRACTIn addition to conventional immunoglobulins, camelids produce antibodies that do not incorporate light chains into their structures. These so-called heavy-chain (HC) antibodies have incited great interest in the biomedical community, as they have considerable potential for biotechnological and therapeutic application. Recently, we have begun to elucidate the immunological functions of HC antibodies, yet little is known about their significance in maternal immunity or about the B lymphocytes that produce them. This study describes the application of isotype-specific reagents toward physiological assessments of camelid IgGs and the B cells that produce them. We document the specificities of monoclonal antibodies that distinguish two conventional IgG1 isotypes and two HC IgG3 variants produced by alpacas. Next, we report that the relative concentrations of five isotypes are similar in serum, milk, and colostrum; however, following passive transfer, the concentrations of HC IgG2 and IgG3 declined more rapidly than the concentration of conventional IgG1 in the sera of neonates. Finally, we assessed the distribution of B cells of distinct isotypes within lymphoid tissues during fetal and adult life. We detected IgG1, IgG2, and IgG3 in lymphocytes located in lymph node follicles, suggesting that HC B cells affinity mature and/or class switch. One IgG3 isotype was present in B cells located in ileal Peyer's patches, and one conventional IgG1 isotype was detected in splenic marginal zone B cells. Our findings contribute to the growing body of knowledge pertaining to HC antibodies and are compatible with functional specialization among conventional and HC IgGs in the alpaca.
Molecular Cloning of an Immunogenic Protein ofBaylisascaris procyonisand Expression inEscherichia colifor Use in Developing Improved Serodiagnostic Assays
Authors: Dangoudoubiyam Sriveny , Vemulapalli Ramesh , Hancock Kathy , Kazacos Kevin R. 
Published: October 2010

ABSTRACTLarva migrans caused byBaylisascaris procyonisis an important zoonotic disease. Current serological diagnostic assays for this disease depend on the use of the parasite's larval excretory-secretory (ES) antigens. In order to identify genes encoding ES antigens and to generate recombinant antigens for use in diagnostic assays, construction and immunoscreening of aB. procyonisthird-stage larva cDNA expression library was performed and resulted in identification of a partial-length cDNA clone encoding an ES antigen, designated repeat antigen 1 (RAG1). The full-lengthrag1cDNA contained a 753-bp open reading frame that encoded a protein of 250 amino acids with 12 tandem repeats of a 12-amino-acid long sequence. Therag1genomic DNA revealed a single intron of 837 bp that separated the 753-bp coding sequence into two exons delimited by canonical splice sites. No nucleotide or amino acid sequences present in the GenBank databases had significant similarity with those of RAG1. We have cloned, expressed, and purified the recombinant RAG1 (rRAG1) and analyzed its diagnostic potential by enzyme-linked immunosorbent assay. Anti-Baylisascarisspecies-specific rabbit serum showed strong reactivity to rRAG1, while only minimal to no reactivity was observed with sera against the related ascaridsToxocara canisandAscaris suum, strongly suggesting the specificity of rRAG1. On the basis of these results, the identified RAG1 appears to be a promising diagnostic antigen for the development of serological assays for specific detection ofB. procyonislarva migrans.
Improved Detection of
Bartonella
DNA in Mammalian Hosts and Arthropod Vectors by Real-Time PCR Using the NADH Dehydrogenase Gamma Subunit (
nuoG
)
Authors: Colborn James M. , Kosoy Michael Y. , Motin Vladimir L. , Telepnev Maxim V. , Valbuena Gustavo , Myint Khin S. , Fofanov Yuri , Putonti Catherine , Feng Chen , Peruski Leonard 
Published: October 2010

ABSTRACT

We used a whole-genome scanning technique to identify the NADH dehydrogenase gamma subunit (
nuoG
) primer set that is sensitive and specific enough to detect a diverse number of
Bartonella
species in a wide range of environmental samples yet maintains minimal cross-reactivity to mammalian host and arthropod vector organisms.
Incidence of and Risk Factors for Community-Associated Methicillin-Resistant
Staphylococcus aureus
Acquired Infection or Colonization in Intensive-Care-Unit Patients
Authors: Wang Jann-Tay , Liao Chun-Hsing , Fang Chi-Tai , Chie Wei-Chu , Lai Mei-Shu , Lauderdale Tsai-Ling , Chang Shan-Chwen 
Published: October 2010

ABSTRACT

The incidence of and risk factors for acquiring community-associated methicillin-resistant
Staphylococcus aureus
(CA-MRSA) among patients staying in intensive care units (ICUs) remain unclear. We enrolled patients staying in two ICUs at the Far Eastern Memorial Hospital during the period of 1 September 2008 to 30 September 2009 to clarify this issue. Surveillance cultures for MRSA were taken from nostril, sputum or throat, axillae, and the inguinal area in all enrolled patients upon admission to the ICU, every 3 days thereafter, and on the day of discharge from the ICU. For each MRSA isolate, we performed multilocus sequence typing, identified the type of staphylococcal cassette chromosome
mec
, detected the presence of the Panton-Valentine leukocidin gene, and conducted drug susceptibility tests. Among the 1,906 patients who were screened, 203 patients were carriers of MRSA before their admission to the ICU; 81 patients acquired MRSA during their stay in the ICU, including 31 who acquired CA-MRSA. The incidence rates of newly acquired MRSA and CA-MRSA during the ICU stay were 7.9 and 3.0 per 1,000 patient-days, respectively. Prior usage of antipseudomonal penicillins and antifungals and the presence of a nasogastric tube were found to be independent risk factors for acquiring CA-MRSA during the ICU stay when data for CA-MRSA carriers and patients without carriage of MRSA were compared (
P
= 0.0035, 0.0330, and 0.0262, respectively). Prior usage of carbapenems was found to be a protective factor against acquiring CA-MRSA when data for patients with CA-MRSA and those with health care-associated MRSA acquired during ICU stay were compared (
P
= 0.0240).
Susceptibility Profiles, Molecular Epidemiology, and Detection of KPC-Producing
Escherichia coli
Isolates from the New York City Vicinity
Authors: Landman David , Urban Carl , Bäcker Martin , Kelly Paul , Shah Neha , Babu Elizabeth , Bratu Simona , Quale John 
Published: October 2010

ABSTRACT

The detection of
Enterobacteriaceae
carrying the carbapenemase KPC has been problematic. Thirty isolates of KPC-possessing
Escherichia coli
were gathered from hospitals in New York City and Connecticut. The imipenem, meropenem, doripenem, and ertapenem MIC
50
values were 4, 2, 1, and 4 μg/ml, respectively. Over half of the isolates belonged to a single ribotype. Using an ertapenem breakpoint of 0.25 μg/ml would efficiently detect these isolates.
HIV-1 Continues To Replicate and Evolve in Patients with Natural Control of HIV Infection
Authors: Mens Helene , Kearney Mary , Wiegand Ann , Shao Wei , Schønning Kristian , Gerstoft Jan , Obel Niels , Maldarelli Frank , Mellors John W. , Benfield Thomas , Coffin John M. 
Published: October 2010

ABSTRACT

Elucidating mechanisms leading to the natural control of HIV-1 infection is of great importance for vaccine design and for understanding viral pathogenesis. Rare HIV-1-infected individuals, termed HIV-1 controllers, have plasma HIV-1 RNA levels below the limit of detection by standard clinical assays (<50 to 75 copies/ml) without antiretroviral therapy. Although several recent studies have documented persistent low-grade viremia in HIV-1 controllers at a level not significantly different from that in HIV-1-infected individuals undergoing treatment with combination antiretroviral therapy (cART), it is unclear if plasma viruses are undergoing full cycles of replication
in vivo
or if the infection of new cells is completely blocked by host immune mechanisms. We studied a cohort of 21 HIV-1 controllers with a median level of viremia below 1 copy/ml, followed for a median of 11 years. Less than half of the cohort carried known protective HLA types (B*57/27). By isolating HIV-1 RNA from large volumes of plasma, we amplified single genome sequences of both
pro-rt
and
env
longitudinally. This study is the first to document that HIV-1
pro-rt
and
env
evolve in this patient group, albeit at rates somewhat lower than in HIV-1 noncontrollers, in HLA B*57/27-positive, as well as HLA B*57/27-negative, individuals. Viral diversity and adaptive events associated with immune escape were found to be restricted in HIV-1 controllers, suggesting that replication occurs in the face of less overall immune selection.
Glycine 184 in Nonstructural Protein NS1 Determines the Virulence of Influenza A Virus Strain PR8 without Affecting the Host Interferon Response
Authors: Steidle Sabine , Martínez-Sobrido Luis , Mordstein Markus , Lienenklaus Stefan , García-Sastre Adolfo , Stäheli Peter , Kochs Georg 
Published: October 2010

ABSTRACT
The nonstructural protein NS1 of influenza A virus counteracts the interferon (IFN) system and thereby promotes viral replication. NS1 has acquired different mechanisms to limit induction of IFN. It prevents double-stranded RNA (dsRNA) and RIG-I-mediated activation of interferon regulatory factor 3 (IRF3), and it blocks posttranscriptional processing of cellular mRNAs by binding to the cleavage and polyadenylation specificity factor (CPSF). Using a mouse-adapted A/PR/8/34 virus and reverse genetics to introduce specific mutations in NS1 which eliminate one or both functions, we determined the relative contributions of these two activities of NS1 to viral virulence in mice. We found that a functional RNA-binding motif was required for IFN suppression and virulence. Restoration of CPSF binding in the NS1 protein of wild-type A/PR/8/34 virus, which cannot bind CPSF due to mutations in the central binding motif at positions 103 and 106, resulted in enhanced virulence. Surprisingly, if CPSF binding was abolished by substituting glycine for arginine at position 184 in the classical NS1-CPSF binding motif, the mutant virus replicated much more slowly in mice, although the mutated NS1 protein continued to repress the IFN response very efficiently. Our results show that a functional RNA-binding motif is decisive for NS1 of A/PR/8/34 virus to suppress IFN induction. They further demonstrate that in addition to its contribution to CPSF binding, glycine 184 strongly influences viral virulence by an unknown mechanism which does not involve the IFN system.
Multiple Functions of
Rice Dwarf Phytoreovirus
Pns10 in Suppressing Systemic RNA Silencing
Authors: Ren Bo , Guo Yuanyuan , Gao Feng , Zhou Peng , Wu Feng , Meng Zheng , Wei Chunhong , Li Yi 
Published: October 2010

ABSTRACT

RNA silencing is a potent mechanism of antiviral defense response in plants and other organisms. For counterdefense, viruses have evolved a variety of suppressors of RNA silencing (VSRs) that can inhibit distinct steps of a silencing pathway. We previously identified Pns10 encoded by
Rice dwarf phytoreovirus
(RDV) as a VSR, the first of its kind from double-stranded RNA (dsRNA) viruses. In this study we investigated the mechanisms of Pns10 function in suppressing systemic RNA silencing in the widely used
Nicotiana benthamiana
model plant. We report that Pns10 suppresses local and systemic RNA silencing triggered by sense mRNA, enhances viral replication and/or viral RNA stability in inoculated leaves, accelerates the systemic spread of viral infection, and enables viral invasion of shoot apices. Mechanistically, Pns10 interferes with the perception of silencing signals in recipient tissues, binds double-stranded small interfering RNA (siRNAs) with two-nucleotide 3′ overhangs, and causes the downregulated expression of RDR6. These results significantly deepen our mechanistic understanding of the VSR functions encoded by a dsRNA virus and contribute additional evidence that binding siRNAs and interfering with RDR6 expression are broad mechanisms of VSR functions encoded by diverse groups of viruses.
Human T-Lymphotropic Virus Type 1 Tax Protein Complexes with P-TEFb and Competes for Brd4 and 7SK snRNP/HEXIM1 Binding
Authors: Cho Won-Kyung , Jang Moon Kyoo , Huang Keven , Pise-Masison Cynthia A. , Brady John N. 
Published: October 2010

ABSTRACT

Positive transcription elongation factor b (P-TEFb) plays an important role in stimulating RNA polymerase II elongation for viral and cellular gene expression. P-TEFb is found in cells in either an active, low-molecular-weight (LMW) form or an inactive, high-molecular-weight (HMW) form. We report here that human T-lymphotropic virus type 1 (HTLV-1) Tax interacts with the cyclin T1 subunit of P-TEFb, forming a distinct Tax/P-TEFb LMW complex. We demonstrate that Tax can play a role in regulating the amount of HMW complex present in the cell by decreasing the binding of 7SK snRNP/HEXIM1 to P-TEFb. This is seen both
in vitro
using purified Tax protein and
in vivo
in cells transduced with Tax expression constructs. Further, we find that a peptide of cyclin T1 spanning the Tax binding domain inhibits the ability of Tax to disrupt HMW P-TEFb complexes. These results suggest that the direct interaction of Tax with cyclin T1 can dissociate P-TEFb from the P-TEFb/7SK snRNP/HEXIM1 complex for activation of the viral long terminal repeat (LTR). We also show that Tax competes with Brd4 for P-TEFb binding. Chromatin immunoprecipitation (ChIP) assays demonstrated that Brd4 and P-TEFb are associated with the basal HTLV-1 LTR, while Tax and P-TEFb are associated with the activated template. Furthermore, the knockdown of Brd4 by small interfering RNA (siRNA) activates the HTLV-1 LTR promoter, which results in an increase in viral expression and production. Our studies have identified Tax as a regulator of P-TEFb that is capable of affecting the balance between its association with the large inactive complex and the small active complex.
Tetrameric Ring Formation of Epstein-Barr Virus Polymerase Processivity Factor Is Crucial for Viral Replication
Authors: Nakayama Sanae , Murata Takayuki , Yasui Yoshihiro , Murayama Kazutaka , Isomura Hiroki , Kanda Teru , Tsurumi Tatsuya 
Published: October 2010

ABSTRACT

The Epstein-Barr virus BMRF1 DNA polymerase processivity factor, which is essential for viral genome replication, exists mainly as a C-shaped head-to-head homodimer but partly forms a ring-shaped tetramer through tail-to-tail association. Based on its molecular structure, several BMRF1 mutant viruses were constructed to examine their influence on viral replication. The R256E virus, which has a severely impaired capacity for DNA binding and polymerase processivity, failed to form replication compartments, resulting in interference of viral replication, while the C95E mutation, which impairs head-to-head contact
in vitro
, unexpectedly hardly affected the viral replication. Also, surprisingly, replication of the C206E virus, which is expected to have impairment of tail-to-tail contact, was severely restricted, although the mutant protein possesses the same
in vitro
biochemical activities as the wild type. Since the tail-to-tail contact surface is smaller than that of the head-to-head contact area, its contribution to ring formation might be essential for viral replication.
Immature and Transitional B Cells Are Latency Reservoirs for a Gammaherpesvirus
Authors: Coleman Carrie B. , Nealy Michael S. , Tibbetts Scott A. 
Published: October 2010

ABSTRACTGammaherpesviruses, including Kaposi's sarcoma-associated herpesvirus (KSHV; also known as human herpesvirus 8 [HHV-8]), Epstein-Barr virus (EBV), and murine gammaherpesvirus 68 (MHV68; also known as gammaherpesvirus 68 [γHV68] or murine herpesvirus 4 [MuHV-4]), establish lifelong latency in the resting memory B cell compartment. However, little is known about how this reservoir of infected mature B cells is maintained for the life of the host. In the context of a normal immune system, the mature B cell pool is naturally maintained by the renewable populations of developing B cells that arise from hematopoiesis. Thus, recurrent infection of these developing B cell populations could allow the virus continual access to the B cell lineage and, subsequent to differentiation, the memory B cell compartment. To begin to address this hypothesis, we examined whether MHV68 establishes latency in developing B cells during a normal course of infection. In work described here, we demonstrate the presence of viral genome in bone marrow pro-pre-B cells and immature B cells during early latency and immature B cells during long-term latency. Further, we show that transitional B cells in the spleen are latently infected and express the latency-associated nuclear antigen (LANA) throughout chronic infection. Because developing B cells normally exhibit a short life span and a high rate of turnover, these findings suggest a model in which gammaherpesviruses may gain access to the mature B cell compartment by recurrent seeding of developing B cells.
A New Wave of Cellular Imaging
Authors: Toomre Derek , Bewersdorf Joerg 
Published: October 2010

Fluorescence imaging methods that push or break the diffraction limit of resolution (approximately 200 nm) have grown explosively. These super-resolution nanoscopy techniques include: stimulated emission depletion (STED), Pointillism microscopy [(fluorescence) photoactivation localization microscopy/stochastic optical reconstruction microscopy, or (F)PALM/STORM], structured illumination, total internal reflection fluorescence microscopy (TIRFM), and those that combine multiple modalities. Each affords unique strengths in lateral and axial resolution, speed, sensitivity, and fluorophore compatibility. We examine the optical principles and design of these new instruments and their ability to see more detail with greater sensitivity—down to single molecules with tens of nanometers resolution. Nanoscopes have revealed transient intermediate states of organelles and molecules in living cells and have led to new discoveries but also biological controversies. We highlight common unifying principles behind nanoscopy such as the conversion of a subset of probes between states (ground or excited) and the use of scanning (ordered or stochastic). We emphasize major advances, biological applications, and promising new developments.
Conditional Regulatory T-Cell Depletion Releases Adaptive Immunity Preventing Carcinogenesis and Suppressing Established Tumor Growth
Authors: Teng Michele W.L. , Ngiow Shin Foong , von Scheidt Bianca , McLaughlin Nicole , Sparwasser Tim , Smyth Mark J. 
Published: October 2010

Abstract
Foxp3 is a central control element in the development and function of regulatory T cells (Treg), and mice expressing a diphtheria toxin (DT) receptor–enhanced green fluorescent protein fusion protein under the control of the foxp3 gene locus (DEREG mice) allow conditional and efficient depletion of Foxp3+ Treg by DT injection. Herein, we use DEREG mice and a mouse model of carcinogenesis to show that conditional and effective Treg depletion can both protect mice from carcinogenesis by innate control, yet permanently eradicate a proportion of de novo–established tumors in mice in a largely CD8+ T-cell– and IFN-γ–dependent manner. Tumors displayed a heterogeneous response to Treg depletion, and suppression of established tumors was accompanied by an increase in the tumor-infiltrating CD8+ T-cell/B-cell ratio. Tumor rejection occurred in the absence of overt autoimmunity, suggesting that effective transient Treg depletion strategies may be therapeutic in at least a proportion of spontaneous tumors developing in the host. Cancer Res; 70(20); 7800–9. ©2010 AACR.
Optical Detection of Buccal Epithelial Nanoarchitectural Alterations in Patients Harboring Lung Cancer: Implications for Screening
Authors: Roy Hemant K. , Subramanian Hariharan , Damania Dhwanil , Hensing Thomas A. , Rom William N. , Pass Harvey I. , Ray Daniel , Rogers Jeremy D. , Bogojevic Andrej , Shah Maitri , Kuzniar Tomasz , Pradhan Prabhakar , Backman Vadim 
Published: October 2010

Abstract
We have recently developed a novel optical technology, partial wave spectroscopic (PWS) microscopy, which is exquisitely sensitive to the nanoarchitectural manifestation of the genetic/epigenetic alterations of field carcinogenesis. Our approach was to screen for lung cancer by assessing the cheek cells based on emerging genetic/epigenetic data which suggests that the buccal epithelium is altered in lung field carcinogenesis. We performed PWS analysis from microscopically normal buccal epithelial brushings from smokers with and without lung cancer (n = 135). The PWS parameter, disorder strength of cell nanoarchitecture (Ld), was markedly (&gt;50%) elevated in patients harboring lung cancer compared with neoplasia-free smokers. The performance characteristic was excellent with an area under the receiver operator characteristic curve of &gt;0.80 and was equivalent for both disease stage (early versus late) and histologies (small cell versus non–small cell lung cancers). An independent data set validated the findings with only a minimal degradation of performance characteristics. Our results offer proof of concept that buccal PWS may potentially herald a minimally intrusive prescreening test that could be integral to the success of lung cancer population screening programs. Cancer Res; 70(20); 7748–54. ©2010 AACR.