bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early HLA-B*57-Restricted CD8+T Lymphocyte Responses Predict HIV-1 Disease Progression
Authors: Brennan Catherine A. , Ibarrondo F. Javier , Sugar Catherine A. , Hausner Mary Ann , Shih Roger , Ng Hwee L. , Detels Roger , Margolick Joseph B. , Rinaldo Charles R. , Phair John , Jacobson Lisa P. , Yang Otto O. , Jamieson Beth D. 
Published: July 2012

ABSTRACTAlthough HLA-B*57 (B57) is associated with slow progression to disease following HIV-1 infection, B57 heterozygotes display a wide spectrum of outcomes, including rapid progression, viremic slow progression, and elite control. Efforts to identify differences between B57-positive (B57+) slow progressors and B57+rapid progressors have largely focused on cytotoxic T lymphocyte (CTL) phenotypes and specificities during chronic stages of infection. Although CTL responses in the early months of infection are likely to be the most important for the long-term rate of HIV-1 disease progression, few data on the early CTL responses of eventual slow progressors have been available. Utilizing the Multicenter AIDS Cohort Study (MACS), we retrospectively examined the early HIV-1-specific CTL responses of 14 B57+individuals whose time to development of disease ranged from 3.5 years to longer than 25 years after infection. In general, a greater breadth of targeting of epitopes from structural proteins, especially Gag, as well as of highly conserved epitopes from any HIV-1 protein, correlated with longer times until disease. The single elite controller in the cohort was an outlier on several correlations of CTL targeting and time until disease, consistent with reports that elite control is typically not achieved solely by protective HLA-mediated CTLs. When targeting of individual epitopes was analyzed, we found that early CTL responses to the IW9 (ISPRTLNAW) epitope of Gag, while generally subdominant, correlated with delayed progression to disease. This is the first study to identify early CTL responses to IW9 as a correlate of protection in persons with HLA-B*57.
Cleavage Activation of the Human-Adapted Influenza Virus Subtypes by Matriptase Reveals both Subtype and Strain Specificities
Authors: Hamilton Brian S. , Gludish David W. J. , Whittaker Gary R. 
Published: July 2012

ABSTRACT

Cleavage activation of the hemagglutinin (HA) precursor is an essential step in the influenza virus replication cycle that is driven by host cell proteases. HA cleavage activation is required for virus-endosome membrane fusion and the subsequent release of the influenza virus genome into the cytoplasm. Previous studies have determined that HA cleavage is most likely driven by either membrane-bound or extracellular trypsin-like proteases that reside in the respiratory tract. However, there is still uncertainty regarding which proteases are critical for HA cleavage
in vivo
. Therefore, further investigation of HA cleavage activation is needed in order to gain insight into the critical proteases involved. Matriptase is a member of the type II transmembrane serine protease family that is highly expressed in a membrane-bound form throughout the respiratory tract. One feature of matriptase is that, once activated, the catalytic domain is secreted into the extracellular space and so serves as a functional extracellular protease. In this study, we have determined that the secreted, catalytic domain of matriptase has the ability to cleave and activate HA from the influenza virus H1 subtype but not the H2 and H3 subtypes. Furthermore, matriptase selectively cleaved the HA of particular strains within the H1 subtype, revealing both subtype and H1 strain specificity. Matriptase was also found to activate thrombolytic zymogens that have been shown to cleave and activate the influenza virus HA. Our data demonstrate that matriptase has the ability to cleave HA directly or indirectly by activating HA-cleaving zymogens.
Risk of Immunodeficiency Virus Infection May Increase with Vaccine-Induced Immune Response
Authors: Tenbusch Matthias , Ignatius Ralf , Temchura Vladimir , Nabi Ghulam , Tippler Bettina , Stewart-Jones Guillaume , Salazar Andres M. , Sauermann Ulrike , Stahl-Hennig Christiane , Überla Klaus 
Published: July 2012

ABSTRACT

To explore the efficacy of novel complementary prime-boost immunization regimens in a nonhuman primate model for HIV infection, rhesus monkeys primed by different DNA vaccines were boosted with virus-like particles (VLP) and then challenged by repeated low-dose rectal exposure to simian immunodeficiency virus (SIV). Characteristic of the cellular immune response after the VLP booster immunization were high numbers of SIV-specific, gamma interferon-secreting cells after stimulation with inactivated SIV particles, but not SIV peptides, and the absence of detectable levels of CD8
+
T cell responses. Antibodies specific to SIV Gag and SIV Env could be induced in all animals, but, consistent with a poor neutralizing activity at the time of challenge, vaccinated monkeys were not protected from acquisition of infection and did not control viremia. Surprisingly, vaccinees with high numbers of SIV-specific, gamma interferon-secreting cells were infected fastest during the repeated low-dose exposures and the numbers of these immune cells in vaccinated macaques correlated with susceptibility to infection. Thus, in the absence of protective antibodies or cytotoxic T cell responses, vaccine-induced immune responses may increase the susceptibility to acquisition of immunodeficiency virus infection. The results are consistent with the hypothesis that virus-specific T helper cells mediate this detrimental effect and contribute to the inefficacy of past HIV vaccination attempts (e.g., STEP study).
Spread of a Distinct Stx2-Encoding Phage Prototype among Escherichia coli O104:H4 Strains from Outbreaks in Germany, Norway, and Georgia
Authors: Beutin Lothar , Hammerl Jens Andre , Strauch Eckhard , Reetz Jochen , Dieckmann Ralf , Kelner-Burgos Ylanna , Martin Annett , Miko Angelika , Strockbine Nancy A. , Lindstedt Björn Arne , Horn Detlef , Monse Hella , Huettel Bruno , Müller Ines , Stüber Kurt , Reinhardt Richard 
Published: July 2012

ABSTRACT

Shiga toxin 2 (Stx2)-producing
Escherichia coli
(STEC) O104:H4 caused one of the world's largest outbreaks of hemorrhagic colitis and hemolytic uremic syndrome in Germany in 2011. These strains have evolved from enteroaggregative
E. coli
(EAEC) by the acquisition of the Stx2 genes and have been designated enteroaggregative hemorrhagic
E. coli
. Nucleotide sequencing has shown that the Stx2 gene is carried by prophages integrated into the chromosome of STEC O104:H4. We studied the properties of Stx2-encoding bacteriophages which are responsible for the emergence of this new type of
E. coli
pathogen. For this, we analyzed Stx bacteriophages from STEC O104:H4 strains from Germany (in 2001 and 2011), Norway (2006), and the Republic of Georgia (2009). Viable Stx2-encoding bacteriophages could be isolated from all STEC strains except for the Norwegian strain. The Stx2 phages formed lysogens on
E. coli
K-12 by integration into the
wrbA
locus, resulting in Stx2 production. The nucleotide sequence of the Stx2 phage P13374 of a German STEC O104:H4 outbreak was determined. From the bioinformatic analyses of the prophage sequence of 60,894 bp, 79 open reading frames were inferred. Interestingly, the Stx2 phages from the German 2001 and 2011 outbreak strains were found to be identical and closely related to the Stx2 phages from the Georgian 2009 isolates. Major proteins of the virion particles were analyzed by mass spectrometry. Stx2 production in STEC O104:H4 strains was inducible by mitomycin C and was compared to Stx2 production of
E. coli
K-12 lysogens.
Preexposure to CpG Protects against the Delayed Effects of Neonatal Respiratory Syncytial Virus Infection
Authors: Yamaguchi Yuko , Harker James A. , Wang Belinda , Openshaw Peter J. , Tregoning John S. , Culley Fiona J. 
Published: July 2012

ABSTRACTSevere respiratory viral infection in early life is associated with recurrent wheeze and asthma in later childhood. Neonatal immune responses tend to be skewed toward T helper 2 (Th2) responses, which may contribute to the development of a pathogenic recall response to respiratory infection. Since neonatal Th2 skewing can be modified by stimulation with Toll-like receptor (TLR) ligands, we investigated the effect of exposure to CpG oligodeoxynucleotides (TLR9 ligands) prior to neonatal respiratory syncytial virus (RSV) infection in mice. CpG preexposure was protective against enhanced disease during secondary adult RSV challenge, with a reduction in viral load and an increase in Th1 responses. A similar Th1 switch and reduction in disease were observed if CpG was administered in the interval between neonatal infection and challenge. In neonates, CpG pretreatment led to a transient increase in expression of major histocompatibility complex class II (MHCII) and CD80 on CD11c-positive cells and gamma interferon (IFN-γ) production by NK cells after RSV infection, suggesting that the protective effects may be mediated by antigen-presenting cells (APC) and NK cells. We conclude that the adverse effects of early-life respiratory viral infection on later lung health might be mitigated by conditions that promote TLR activation in the infant lung.
Optimum Length and Flexibility of Reovirus Attachment Protein σ1 Are Required for Efficient Viral Infection
Authors: Bokiej Magdalena , Ogden Kristen M. , Ikizler Mine , Reiter Dirk M. , Stehle Thilo , Dermody Terence S. 
Published: July 2012

ABSTRACT
Reovirus attachment protein σ1 is an elongated trimer with head-and-tail morphology that engages cell-surface carbohydrate and junctional adhesion molecule A (JAM-A). The σ1 protein is comprised of three domains partitioned by two flexible linkers termed interdomain regions (IDRs). To determine the importance of σ1 length and flexibility at different stages of reovirus infection, we generated viruses with mutant σ1 molecules of altered length and flexibility and tested these viruses for the capacity to bind the cell surface, internalize, uncoat, induce protein synthesis, assemble, and replicate. We reduced the length of the α-helical σ1 tail to engineer mutants L1 and L2 and deleted midpoint and head-proximal σ1 IDRs to generate ΔIDR1 and ΔIDR2 mutant viruses, respectively. Decreasing length or flexibility of σ1 resulted in delayed reovirus infection and reduced viral titers. L1, L2, and ΔIDR1 viruses but not ΔIDR2 virus displayed reduced cell attachment, but altering σ1 length or flexibility did not diminish the efficiency of virion internalization. Replication of ΔIDR2 virus was hindered at a postdisassembly step. Differences between wild-type and σ1 mutant viruses were not attributable to alterations in σ1 folding, as determined by experiments assessing engagement of cell-surface carbohydrate and JAM-A by the length and IDR mutant viruses. However, ΔIDR1 virus harbored substantially less σ1 on the outer capsid. Taken together, these data suggest that σ1 length is required for reovirus binding to cells. In contrast, IDR1 is required for stable σ1 encapsidation, and IDR2 is required for a postuncoating replication step. Thus, the structural architecture of σ1 is required for efficient reovirus infection of host cells.
Live Attenuated Influenza Vaccine Provides Superior Protection from Heterologous Infection in Pigs with Maternal Antibodies without Inducing Vaccine-Associated Enhanced Respiratory Disease
Authors: Vincent Amy L. , Ma Wenjun , Lager Kelly M. , Richt Jürgen A. , Janke Bruce H. , Sandbulte Matthew R. , Gauger Philip C. , Loving Crystal L. , Webby Richard J. , García-Sastre Adolfo 
Published: July 2012

ABSTRACT
Control of swine influenza A virus (IAV) in the United States is hindered because inactivated vaccines do not provide robust cross-protection against the multiple antigenic variants cocirculating in the field. Vaccine efficacy can be limited further for vaccines administered to young pigs that possess maternally derived immunity. We previously demonstrated that a recombinant A/sw/Texas/4199-2/1998 (TX98) (H3N2) virus expressing a truncated NS1 protein is attenuated in swine and has potential for use as an intranasal live attenuated influenza virus (LAIV) vaccine. In the present study, we compared 1 dose of intranasal LAIV with 2 intramuscular doses of TX98 whole inactivated virus (WIV) with adjuvant in weanling pigs with and without TX98-specific maternally derived antibodies (MDA). Pigs were subsequently challenged with wild-type homologous TX98 H3N2 virus or with an antigenic variant, A/sw/Colorado/23619/1999 (CO99) (H3N2). In the absence of MDA, both vaccines protected against homologous TX98 and heterologous CO99 shedding, although the LAIV elicited lower hemagglutination inhibition (HI) antibody titers in serum. The efficacy of both vaccines was reduced by the presence of MDA; however, WIV vaccination of MDA-positive pigs led to dramatically enhanced pneumonia following heterologous challenge, a phenomenon known as vaccine-associated enhanced respiratory disease (VAERD). A single dose of LAIV administered to MDA-positive pigs still provided partial protection from CO99 and may be a safer vaccine for young pigs under field conditions, where dams are routinely vaccinated and diverse IAV strains are in circulation. These results have implications not only for pigs but also for other influenza virus host species.
Body mass index, fitness and physical activity from childhood through adolescence
Authors: Pahkala Katja , Hernelahti Miika , Heinonen Olli J , Raittinen Päivi , Hakanen Maarit , Lagström Hanna , Viikari Jorma S A , Rönnemaa Tapani , Raitakari Olli T , Simell Olli 
Published: July 2012

BackgroundObesity, sedentary lifestyle and poor cardiorespiratory fitness in childhood may increase the risk of health problems later in life.PurposeThe authors studied the association of early childhood weight status with cardiorespiratory fitness and leisure-time physical activity (LTPA) in adolescence. The stability and associations of LTPA and fitness from childhood through adolescence were also studied.MethodsBody mass index (BMI) was assessed annually since birth in a prospective, longitudinal study. The mean BMI between ages 2 and 7 years indicated weight status at preschool age. Fitness was studied with a shuttle run test at age 9 and with a maximal cycle ergometer test at age 17. The same questionnaire was used to assess LTPA at age 9, 13 and 17. Complete data on preschool BMI, LTPA at ages 13 and 17 and fitness at age 17 years was provided by 351 children, while fitness and LTPA data were available for 74 children at ages 9 and 17.ResultsPreschool BMI was inversely associated with fitness in adolescence independently of adolescent LTPA (p=0.0001). Children who had a high preschool BMI but whose weight status was reduced in adolescence had similar fitness in adolescence as the children with a persistently low BMI. Regardless of the fitness level in childhood, the children whose LTPA increased between age 9 and 17 had a similar adolescent fitness level as persistently active subjects.ConclusionsIt is important to maintain a healthy body weight and a physically active lifestyle from very childhood through adolescence to improve fitness during adolescence.
A novel 28-bp insertion–deletion polymorphism within goat PRNP gene and its association with production traits in Chinese native breeds
Authors: Lan X.Y. , Zhao H.Y. , Li Z.J. , Li A.M. , Lei C.Z. , Chen H. , Pan C.Y. 
Published: July 2012

In this study, a novel 28-bp insertion–deletion (indel) polymorphism (AJ298878:g.47836–47853insCCTCAGACACTGAGTCTCCCCAACAGCA) was found in goat prion protein (PRNP) gene in 2373 goats from 13 Chinese native breeds. The frequencies of allele “ins” varied from 0.500 to 1.000 in different breeds. The establishment of association of the 28-bp indel polymorphism with production traits was performed in Inner Mongolia white cashmere (IMWC) and Xinong Sannen dairy (XNSN) breeds. Two significant associations between this polymorphism and 1-year-old body mass (P = 0.011) and average body mass (P = 0.024) were observed in IMWC breed, as well as wool thickness of 3-year-olds (P < 0.001). Furthermore, the novel 28-bp indel polymorphism was significantly associated with total solids in the evening (%) (P = 0.009) and milk yield (P = 0.016) in XNSN breed. These findings suggested that the 28-bp indel polymorphism was a potential DNA marker for eliminating or selecting preferred individuals in relation to production traits in goat marker-assisted selection breeding while carrying out preventing scrapie project.
Effect of chronic ammonium nitrate addition on the ectomycorrhizal community in a black spruce stand1This article is one of a selection of papers from the 7th International Conference on Disturbance Dynamics in Boreal Forests.
Authors: Rossi Sergio , Bordeleau Adam , Houle Daniel , Morin Hubert 
Published: July 2012

Observed modifications of ectomycorrhizal (ECM) communities have been connected to the increased N depositions of the 20th century. Because of their narrow niche width, small disturbances of soil conditions can produce greater effects on the fungal species than on their host trees. This study investigated the ECM community in a black spruce ( Picea mariana (Mill.) BSP) stand subjected to long-term additions of 9 and 30 kg N·ha–1·year–1 of ammonium nitrate, representing 3 and 10 times the atmospheric N deposition at the site, respectively. Root tip vitality and ECM presence were detected on samples collected from the organic horizon and ECM were classified into morphotypes according to their morphological and anatomical characters. In the control, 80.6% of the root tips were vital, 76.5% of them showing ECM colonization. Higher root tip vitality and mycorrhization were observed in the treated plots. Forty-one morphotypes were identified, most of them detected at the higher N inputs. Results diverging from the expectations of a reduction in ECM presence and diversity could be related to a higher growth rate of the trees following fertilization. The repeated application of small N doses could have been a better imitation of natural inputs from atmospheric deposition and could have provided more reliable responses of ECM to treatment.
Effects of canopy N uptake on foliar CO2 assimilation rates and biomass production and allocation in Japanese red pine seedlings
Authors: Chiwa Masaaki , Matsuda Toshihide , Nakatani Nobutake , Kobayashi Tsuyoshi , Kume Atsushi , Sakugawa Hiroshi 
Published: July 2012

To investigate the direct physiological effects of CNU (canopy nitrogen uptake), three mist solutions (control, N1, and N2 with 0.03, 13.1, and 32.7 kg NH4+-N·ha–1, respectively) were sprayed on Japanese red pine (Pinus densiflora Sieb. et Zucc.) seedlings three times a week for three months. Waterproof sheets protected the surface soil during misting to avoid adding N to the soil. The results show N mist treatments to foliage increased needle N availability in proportion to N dose, which was large enough to cause greater N and chlorophyll content in the needles. This suggests that N is rapidly absorbed, is directly assimilated by the needles, and is used in photosynthesis. These increases resulted in higher maximum net CO2 assimilation rates (Amax) and maximum quantum yield of PSII photochemistry (Fv/Fm) of pine seedlings and subsequently increased bud and root biomass. Increased root biomass reduced the sensitivity of the shoot-to-root ratio to increased N availability in the foliage. In conclusion, our study supported the idea that CNU should be taken into consideration when evaluating the impacts of elevated atmospheric N deposition on forest C sequestration and biomass allocation.
RB-Pathway Disruption Is Associated with Improved Response to Neoadjuvant Chemotherapy in Breast Cancer
Authors: Witkiewicz Agnieszka K. , Ertel Adam , McFalls Jeanne , Valsecchi Matias E. , Schwartz Gordon , Knudsen Erik S. 
Published: July 2012

Abstract
Purpose: We sought to determine whether dysregulation of the retinoblastoma (RB) tumor suppressor pathway was associated with improved response to neoadjuvant chemotherapy in breast cancer.
Experimental Design: An RB-loss signature was used to analyze the association between pathway status and pathologic complete response in gene expression datasets encompassing three different neoadjuvant regimens. Parallel immunohistochemical analysis of the RB pathway was conducted on pretreatment biopsies to determine the association with pathologic response to neoadjuvant chemotherapy.
Results: An RB-loss gene expression signature was associated with increased pathologic complete response in datasets from breast cancer patients treated with 5-fluorouracil/adriamycin/cytoxan (FAC; P &lt; 0.001), T/FAC (P &lt; 0.001), and Taxane/Adriaymcin (P &lt; 0.001) neoadjuvant therapy encompassing approximately 1,000 patients. The association with improved response to neoadjuvant chemotherapy was true in both estrogen receptor (ER)–positive and ER-negative breast cancer. Elevated expression of p16ink4a is associated with the RB-loss signature (R = 0.493–0.5982), and correspondingly p16ink4a mRNA levels were strongly associated with pathologic complete response in the same datasets analyzed. In an independent cohort, immunohistochemical analyses of RB and p16ink4a revealed an association of RB loss (P = 0.0018) or elevated p16ink4a (P = 0.0253) with pathologic complete response. In addition, by Miller–Payne and clinicopathologic scoring analyses, RB-deficient tumors experienced an overall improved response to neoadjuvant chemotherapy.
Conclusion: Disruption of the RB pathway as measured by several independent methods was associated with improved response to neoadjuvant chemotherapy. The RB-pathway status was relevant for pathologic response in both ER-positive and ER-negative breast cancer with similar results observed with multiple chemotherapy regimens. Combined, these data indicate that RB status is associated with the response to neoadjuvant chemotherapy in breast cancer and could be used to inform treatment. Clin Cancer Res; 18(18); 5110–22. ©2012 AACR.