bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased CXC Ligand 10 Levels and Gene Expression in Type 1 Leprosy Reactions
Authors: Scollard David M. , Chaduvula Meher V. , Martinez Alejandra , Fowlkes Natalie , Nath Indira , Stryjewska Barbara M. , Kearney Michael T. , Williams Diana L. 
Published: April 2011

ABSTRACTType 1 reaction (T1R) is a systemic inflammatory syndrome causing substantial morbidity in leprosy. T1R results from spontaneously enhanced cellular immunity in borderline types of leprosy, but there are no established laboratory markers for the reaction. Preliminary studies have identified elevated circulating CXC ligand 10 (CXCL10) during T1R. Correlation of CXCL10 with clinical T1R was studied in repeated serum specimens obtained before, during, and after T1R. CXCL10 gene expression was assessed in biopsy specimens taken before and during T1R, and sections were stained for the cytokine using monoclonal antibodies. Sequential serum specimens revealed elevation of circulating CXCL10 associated with episodes of T1R (P= 0.0001) but no evidence of an earlier, predictive change in the level of the chemokine. Reverse transcriptase (RT)-PCR revealed elevated expression of CXCL10 transcripts during T1R, but not in patients who did not have T1R. No significant correlation between CXCL10 and gamma interferon (IFN-γ) mRNA levels was observed. Immunohistochemical staining of the skin biopsy specimens suggested an overall increase in CXCL10 but did not identify a particular strongly staining population of leukocytes. Increased CXCL10 in lesions and serum is characteristic of T1R. CXCL10 measurement offers new possibilities for laboratory diagnosis and monitoring of T1R. Studies of the regulation of CXCL10 may provide insight into the mechanisms of T1R and identify potential new drug targets for treatment.
Evaluation of a Novel Chimeric B Cell Epitope-Based Vaccine against Mastitis Induced by Either Streptococcus agalactiae or Staphylococcus aureus in Mice
Authors: Xu Haiyang , Hu Changmin , Gong Rui , Chen Yingyu , Ren Ningning , Xiao Ganwen , Xie Qian , Zhang Minmin , Liu Qin , Guo Aizhen , Chen Huanchun 
Published: April 2011

ABSTRACTTo construct a universal vaccine against mastitis induced by eitherStreptococcus agalactiaeorStaphylococcus aureus, the B cell epitopes of the surface immunogenic protein (Sip) fromS. agalactiaeand clumping factor A (ClfA) fromS. aureuswere analyzed and predicted.sip-clfA, a novel chimeric B cell epitope-based gene, was obtained by overlap PCR, and then the recombinant Sip-ClfA (rSip-ClfA) was expressed and purified. rSip-ClfA and inactivatedS. agalactiaeandS. aureuswere formulated into different vaccines with mineral oil as the adjuvant and evaluated in mouse models. The rSip-ClfA vaccination induced immunoglobulin G (IgG) titers higher than those seen in groups immunized with inactivated bacteria. Furthermore, the response to rSip-ClfA immunization was characterized as having a dominant IgG1 subtype, whereas both bacterial immunizations produced similar levels of IgG1 and IgG2a. The antiserum capacities for opsonizing adhesion and phagocytosis were significantly greater in the rSip-ClfA immunization group than in the killed-bacterium immunization groups (P< 0.05). The immunized lactating mice were challenged with eitherS. agalactiaeorS. aureusvia the intramammary route. At 24 h postinfection, the numbers of bacteria recovered from the mammary glands in the rSip-ClfA group were >5-fold lower than those in both inactivated-bacterium groups (P< 0.01). Histopathological examination of the mammary glands showed that rSip-ClfA immunization provided better protection of mammary gland tissue integrity against bothS. agalactiaeandS. aureuschallenges. Thus, the recombinant protein rSip-ClfA would be a promising vaccine candidate against mastitis induced by eitherS. agalactiaeorS. aureus.
Aspergillus Species and Other Molds in Respiratory Samples from Patients with Cystic Fibrosis: a Laboratory-Based Study with Focus on Aspergillus fumigatus Azole Resistance
Authors: Mortensen Klaus Leth , Jensen Rasmus Hare , Johansen Helle Krogh , Skov Marianne , Pressler Tacjana , Howard Susan Julie , Leatherbarrow Howard , Mellado Emilia , Arendrup Maiken Cavling 
Published: April 2011

ABSTRACT

Respiratory tract colonization by molds in patients with cystic fibrosis (CF) were analyzed, with particular focus on the frequency, genotype, and underlying mechanism of azole resistance among
Aspergillus fumigatus
isolates. Clinical and demographic data were also analyzed. A total of 3,336 respiratory samples from 287 CF patients were collected during two 6-month periods in 2007 and 2009. Azole resistance was detected using an itraconazole screening agar (4 mg/liter) and the EUCAST method.
cyp51A
gene sequencing and microsatellite genotyping were performed for isolates from patients harboring azole-resistant
A. fumigatus. Aspergillus
spp. were present in 145 patients (51%), of whom 63 (22%) were persistently colonized. Twelve patients (4%) harbored other molds. Persistently colonized patients were older, provided more samples, and more often had a chronic bacterial infection. Six of 133 patients (4.5%) harbored azole-nonsusceptible or -resistant
A. fumigatus
isolates, and five of those six patients had isolates with Cyp51A alterations (M220K, tandem repeat [TR]/L98H, TR/L98H-S297T-F495I, M220I-V101F, and Y431C). All six patients were previously exposed to azoles. Genotyping revealed (i) microevolution for
A. fumigatus
isolates received consecutively over the 2-year period, (ii) susceptible and resistant isolates (not involving TR/L98H isolates) with identical or very closely related genotypes (two patients), and (iii) two related susceptible isolates and a third unrelated resistant isolate with a unique genotype and the TR/L98H resistance combination (one patient). Aspergilli were frequently found in Danish CF patients, with 4.5% of the
A. fumigatus
isolates being azole nonsusceptible or resistant. Genotyping suggested selection of resistance in the patient as well as resistance being achieved in the environment.
RNA Elements Directing Translation of the Duck Hepatitis B Virus Polymerase via Ribosomal Shunting
Authors: Cao Feng , Tavis John E. 
Published: April 2011

ABSTRACT
The duck hepatitis B virus (DHBV) reverse transcriptase (P) is translated from the downstream position on a bicistronic mRNA, called the pregenomic RNA, through a poorly characterized ribosomal shunt. Here, the positions of the discontinuous ribosomal transfer during shunting were mapped, and RNA elements important for shunting were identified as a prelude to dissecting the shunting mechanism. Mutations were introduced into the DHBV genome, genomic expression vectors were transfected into cells which support reverse transcription, and P translation efficiency was defined as the ratio of P/mRNA. Five observations were made. First, ribosomes departed from sequences that comprise the RNA stem-loop called ε that is key to viral replication, but the known elements of ε were not needed for shunting. Second, at least two landing sites for ribosomes were found on the mRNA. Third, all sequences upstream of ε, most sequences between the cap and the P AUG, and sequences within the P-coding region were dispensable for shunting. Fourth, elements on the mRNA involved in reverse transcription or predicted to be involved in shunting on the basis of mechanisms documented in other viruses, including short open reading frames near the departure site, were not essential for shunting. Finally, two RNA elements in the 5′ portion of the mRNA were found to assist shunting. These observations are most consistent with shunting being directed by signals that act through an uncharacterized RNA secondary structure. Together, these data indicate that DHBV employs either a novel shunting mechanism or a major variation on one of the characterized mechanisms.
A5-Positive Primary Sensory Neurons Are Nonpermissive for Productive Infection with Herpes Simplex Virus 1 In Vitro
Authors: Bertke Andrea S. , Swanson Sophia M. , Chen Jenny , Imai Yumi , Kinchington Paul R. , Margolis Todd P. 
Published: April 2011

ABSTRACT

Herpes simplex viruses 1 and 2 (HSV-1 and HSV-2) establish latency and express the latency-associated transcript (LAT) preferentially in different murine sensory neuron populations, with most HSV-1 LAT expression in A5
+
neurons and most HSV-2 LAT expression in KH10
+
neurons. To study the mechanisms regulating the establishment of HSV latency in specific subtypes of neurons, cultured dissociated adult murine trigeminal ganglion (TG) neurons were assessed for relative permissiveness for productive infection. In contrast to that for neonatal TG, the relative distribution of A5
+
and KH10
+
neurons in cultured adult TG was similar to that seen
in vivo
. Productive infection with HSV was restricted, and only 45% of cultured neurons could be productively infected with either HSV-1 or HSV-2. A5
+
neurons supported productive infection with HSV-2 but were selectively nonpermissive for productive infection with HSV-1, a phenomenon that was not due to restricted viral entry or DNA uncoating, since HSV-1 expressing β-galactosidase under the control of the neurofilament promoter was detected in ∼90% of cultured neurons, with no preference for any neuronal subtype. Infection with HSV-1 reporter viruses expressing enhanced green fluorescent protein (EGFP) from immediate early (IE), early, and late gene promoters indicated that the block to productive infection occurred before IE gene expression. Trichostatin A treatment of quiescently infected neurons induced productive infection preferentially from non-A5
+
neurons, demonstrating that the nonpermissive neuronal subtype is also nonpermissive for reactivation. Thus, HSV-1 is capable of entering the majority of sensory neurons
in vitro
; productive infection occurs within a subset of these neurons; and this differential distribution of productive infection is determined at or before the expression of the viral IE genes.
Human Immunodeficiency Virus Type 1 Modified To Package Simian Immunodeficiency Virus Vpx Efficiently Infects Macrophages and Dendritic Cells
Authors: Sunseri Nicole , O'Brien Meagan , Bhardwaj Nina , Landau Nathaniel R. 
Published: April 2011

ABSTRACT

The lentiviral accessory protein Vpx is thought to facilitate the infection of macrophages and dendritic cells by counteracting an unidentified host restriction factor. Although human immunodeficiency virus type 1 (HIV-1) does not encode Vpx, the accessory protein can be provided to monocyte-derived macrophages (MDM) and monocyte-derived dendritic cells (MDDC) in virus-like particles, dramatically enhancing their susceptibility to HIV-1. Vpx and the related accessory protein Vpr are packaged into virions through a virus-specific interaction with the p6 carboxy-terminal domain of Gag. We localized the minimal Vpx packaging motif of simian immunodeficiency virus SIVmac
239
p6 to a 10-amino-acid motif and introduced this sequence into an infectious HIV-1 provirus. The chimeric virus packaged Vpx that was provided in
trans
and was substantially more infectious on MDDC and MDM than the wild-type virus. We further modified the virus by introducing the Vpx coding sequence in place of
nef
. The resulting virus produced Vpx and replicated efficiently in MDDC and MDM. The virus also induced a potent type I interferon response in MDDC. In a coculture system, the Vpx-containing HIV-1 was more efficiently transmitted from MDDC to T cells. These findings suggest that
in vivo
, Vpx may facilitate transmission of the virus from dendritic cells to T cells. In addition, the chimeric virus could be used to design dendritic cell vaccines that induce an enhanced innate immune response. This approach could also be useful in the design of lentiviral vectors that transduce these relatively resistant cells.
The Human Cytomegalovirus Gene Products Essential for Late Viral Gene Expression Assemble into Prereplication Complexes before Viral DNA Replication
Authors: Isomura Hiroki , Stinski Mark F. , Murata Takayuki , Yamashita Yoriko , Kanda Teru , Toyokuni Shinya , Tsurumi Tatsuya 
Published: April 2011

ABSTRACT

The regulation of human cytomegalovirus (HCMV) late gene expression by viral proteins is poorly understood, and these viral proteins could be targets for novel antivirals. HCMV open reading frames (ORFs) UL79, -87, and -95 encode proteins with homology to late gene transcription factors of murine gammaherpesvirus 68 ORFs 18, 24, and 34, respectively. To determine whether these HCMV proteins are also essential for late gene transcription of a betaherpesvirus, we mutated HCMV ORFs UL79, -87, and -95. Cells were infected with the recombinant viruses at high and low multiplicities of infection (MOIs). While viral DNA was detected with the recombinant viruses, infectious virus was not detected unless the wild-type viral proteins were expressed in
trans
. At a high MOI, mutation of ORF UL79, -87, or -95 had no effect on the level of major immediate-early (MIE) gene expression or viral DNA replication, but late viral gene expression from the UL44, -75, and -99 ORFs was not detected. At a low MOI, preexpression of UL79 or -87, but not UL95, in human fibroblast cells negatively affected the level of MIE viral gene expression and viral DNA replication. The products of ORFs UL79, -87, and -95 were expressed as early viral proteins and recruited to prereplication complexes (pre-RCs), along with UL44, before the initiation of viral DNA replication. All three HCMV ORFs are indispensable for late viral gene expression and viral growth. The roles of UL79, -87, and -95 in pre-RCs for late viral gene expression are discussed.
Conserved GXXXG- and S/T-Like Motifs in the Transmembrane Domains of NS4B Protein Are Required for Hepatitis C Virus Replication
Authors: Han Qingxia , Aligo Jason , Manna David , Belton Kerry , Chintapalli Sree V. , Hong Yoojin , Patterson Randen L. , van Rossum Damian B. , Konan Kouacou V. 
Published: April 2011

ABSTRACTHepatitis C virus (HCV) nonstructural protein 4B (NS4B) is an integral membrane protein, which plays an important role in the organization and function of the HCV replication complex (RC). Although much is understood about its amphipathic N-terminal and C-terminal domains, we know very little about the role of the transmembrane domains (TMDs) in NS4B function. We hypothesized that in addition to anchoring NS4B into host membranes, the TMDs are engaged in intra- and intermolecular interactions required for NS4B structure/function. To test this hypothesis, we have engineered a chimeric JFH1 genome containing the Con1 NS4B TMD region. The resulting virus titers were greatly reduced from those of JFH1, and further analysis indicated a defect in genome replication. We have mapped this incompatibility to NS4B TMD1 and TMD2 sequences, and we have defined putative TMD dimerization motifs (GXXXG in TMD2 and TMD3; the S/T cluster in TMD1) as key structural/functional determinants. Mutations in each of the putative motifs led to significant decreases in JFH1 replication. Like most of the NS4B chimeras, mutant proteins had no negative impact on NS4B membrane association. However, some mutations led to disruption of NS4B foci, implying that the TMDs play a role in HCV RC formation. Further examination indicated that the loss of NS4B foci correlates with the destabilization of NS4B protein. Finally, we have identified an adaptive mutation in the NS4B TMD2 sequence that has compensatory effects on JFH1 chimera replication. Taken together, these data underscore the functional importance of NS4B TMDs in the HCV life cycle.
The SUMOylation of Matrix Protein M1 Modulates the Assembly and Morphogenesis of Influenza A Virus
Authors: Wu Chung-Yi , Jeng King-Song , Lai Michael M.-C. 
Published: April 2011

ABSTRACT
SUMOylation is an important posttranslational modification for regulation of cellular functions and viral replication. Here, we report that protein SUMOylation regulates the replication of influenza A virus at the steps of viral maturation and assembly. Knocking down the SUMO-conjugating enzyme Ubc9 resulted in the reduction of virus production. Dissection of the virus life cycle revealed that SUMOylation is involved in the processes of virus maturation and assembly. The viral matrix protein M1 is SUMOylated at K242. A virus carrying the SUMO-defective M1 produced a lower titer of virus, while its viral proteins and viral RNA (vRNA) accumulated in the cells. Furthermore, the mechanistic studies showed that the SUMOylation of M1 is required for the interaction between M1 and viral RNP (vRNP) to form the M1-vRNP complex. The lack of M1 SUMOylation prevented the nuclear export of vRNP and subsequent viral morphogenesis. Taken together, our findings elucidate that the maturation and assembly of influenza A virus is controlled by the SUMO modification of M1 protein. Therefore, we suggest that M1 can serve as a target for developing a new generation of drugs for flu therapy.
NF-κB-Mediated Modulation of Inducible Nitric Oxide Synthase Activity Controls Induction of the Epstein-Barr Virus Productive Cycle by Transforming Growth Factor Beta 1
Authors: Oussaief Lassad , Ramírez Vanessa , Hippocrate Aurélie , Arbach Hratch , Cochet Chantal , Proust Alexis , Raphaël Martine , Khelifa Ridha , Joab Irène 
Published: April 2011

ABSTRACT
Transforming growth factor beta 1 (TGF-β1) signal transduction has been implicated in many second-messenger pathways, including the NF-κB pathway. We provide evidence of a novel TGF-β1-mediated pathway that leads to extracellular signal-regulated kinase (ERK) 1/2 phosphorylation, which in turn induces expression of an Epstein-Barr virus (EBV) protein, ZEBRA, that is responsible for the induction of the viral lytic cycle. This pathway includes two unexpected steps, both of which are required to control ERK 1/2 phosphorylation: first, a quick and transient activation of NF-κB, and second, downregulation of inducible nitric oxide synthase (iNOS) activity that requires the participation of NF-κB activity. Although necessary, NF-κB alone is not sufficient to produce downregulation of iNOS, suggesting that another uncharacterized event(s) is involved in this pathway. Dissection of the steps involved in the switch from the EBV latent cycle to the lytic cycle will be important to understand how virus-host relationships modulate the innate immune system.
The Single RBP-Jκ Site within the LANA Promoter Is Crucial for Establishing Kaposi's Sarcoma-Associated Herpesvirus Latency during Primary Infection
Authors: Lu Jie , Verma Subhash C. , Cai Qiliang , Robertson Erle S. 
Published: April 2011

ABSTRACT
Kaposi's sarcoma-associated herpesvirus (KSHV; or human herpesvirus 8 [HHV8]) is implicated in the pathogenesis of many human malignancies including Kaposi's sarcoma (KS), multicentric Castleman's disease (MCD), and primary effusion lymphoma (PEL). KSHV infection displays two alternative life cycles, referred to as the latent and lytic or productive cycle. Previously, we have reported that the replication and transcription activator (RTA), a major lytic cycle transactivator, contributes to the development of KSHV latency by inducing latency-associated nuclear antigen (LANA) expression during early stages of infection by targeting RBP-Jκ, the master regulator of the Notch signaling pathway. Here, we generated a bacterial artificial chromosome (BAC) KSHV recombinant virus with a deletion of the RBP-Jκ site within the LANA promoter to evaluate the function of the RBP-Jκ cognate site in establishing primary latent infection. The results showed that genetic disruption of the RBP-Jκ binding site within the KSHV LANA promoter led to enhanced expression of the KSHV-encoded immediate early RTA, resulting in an increase in lytic replication during primary infection of human peripheral blood mononuclear cells (PBMCs). This system provides a powerful tool for use in indentifying additional cellular and viral molecules involved in LANA-mediated latency maintenance during the early stages of KSHV infection.
Prevention of sports injury I: a systematic review of applied biomechanics and physiology outcomes research
Authors: McBain Kellen , Shrier Ian , Shultz Rebecca , Meeuwisse Willem H , Klügl Martin , Garza Daniel , Matheson Gordon O 
Published: April 2011

ObjectiveTo analyse published articles that used interventions aimed at investigating biomechanical/physiological outcomes (ie, intermediate risk factors) for sport injury prevention in order to characterise the state of the field and identify important areas not covered in the literature.Data sourcesPubMed, Cinahl, Web of Science and Embase were searched using a broad search strategy.Main resultsOnly 144 of 2525 articles retrieved by the search strategy met the inclusion criteria. Crossover study designs increased by 175% in the late 1980s until 2005 but have declined 32% since then. Randomised controlled trial (RCT) study designs increased by 650% since the early 1980s. Protective equipment studies (61.8% of all studies) declined by 35% since 2000, and training studies (35.4% of all studies) increased by 213%. Equipment research studied stability devices (83.1%) and attenuating devices (13.5%) whereas training research studied balance and coordination (54.9%), strength and power (43.1%) and stretching (15.7%). Almost all (92.1%) studies investigated the lower extremity and 78.1% were of the joint (non-bone)-ligament type. Finally, 57.5% of the reports studied contact sports, 24.2% collision and 25.8% non-contact sports.ConclusionThe decrease in crossover study design and increase in RCTs over time suggest a shift in study design for injury prevention articles. Another notable finding was the change in research focus from equipment interventions, which have been decreasing since 2000 (35% decline), to training interventions, which have been increasing (213% increase). Finally, there is very little research on overuse or upper extremity injuries.
A new VO2maxprotocol allowing self-pacing in maximal incremental exercise
Authors: Mauger Alexis R , Sculthorpe Nick 
Published: April 2011

Introduction The traditional maximal oxygen uptake (VO2max) protocol has received criticism for being an unnatural form of exercise, lacking ecological validity and producing different VO2maxresponses depending on protocol duration and work rate increments.Purpose The purpose of this investigation was to design and test a new VO2maxprotocol allowing subjects to self-pace their work rate while maintaining an incremental test structure.Methods16 untrained subjects completed a self-paced VO2maxprotocol (SPV) and a traditional VO2maxtest in a counter-balanced, crossover design. The SPV used incremental ‘clamps’ of ratings of perceived exertion (RPE) over 5 × 2-min stages (10-min duration) while allowing subjects to vary their power output (PO) according to the required RPE.ResultsSubjects achieved significantly higher (p < 0.05) VO2maxvalues (40 ± 10 ml/kg/min vs 37 ± 8 ml/kg/min) and peak POs (273 ± 58 W vs 238 ± 55 W) in the SPV. Higher VO2maxvalues were observed in the SPV even when a plateau (VO2–time slope <0.05 l/min) occurred in the traditional test. No differences were found between any other measured physiological variable (minute ventilation, heart rate and respiratory exchange ratio).ConclusionsAs SPV is a closed-loop test (10-min duration) that allows subjects to self-pace their work rate, it disregards the need for experimenters to estimate starting work rates, stage lengths and increments in order to bring about volitional exhaustion in 8–10 min. The observation that the SPV may also elicit higher VO2maxvalues than a traditional test warrants further research in this area and its consideration as standard measure to elicit VO2max.