bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Novel Form of Rotavirus NSP2 and Phosphorylation-Dependent NSP2-NSP5 Interactions Are Associated with Viroplasm Assembly
Authors: Criglar Jeanette M. , Hu Liya , Crawford Sue E. , Hyser Joseph M. , Broughman James R. , Prasad B. V. Venkataram , Estes Mary K. 
Published: November 2013

ABSTRACT
Rotavirus (RV) replication occurs in cytoplasmic inclusions called viroplasms whose formation requires the interactions of RV proteins NSP2 and NSP5; however, the specific role(s) of NSP2 in viroplasm assembly remains largely unknown. To study viroplasm formation in the context of infection, we characterized two new monoclonal antibodies (MAbs) specific for NSP2. These MAbs show high-affinity binding to NSP2 and differentially recognize distinct pools of NSP2 in RV-infected cells; a previously unrecognized cytoplasmically dispersed NSP2 (dNSP2) is detected by an N-terminal binding MAb, and previously known viroplasmic NSP2 (vNSP2) is detected by a C-terminal binding MAb. Kinetic experiments in RV-infected cells demonstrate that dNSP2 is associated with NSP5 in nascent viroplasms that lack vNSP2. As viroplasms mature, dNSP2 remains in viroplasms, and the amount of diffuse cytoplasmic dNSP2 increases. vNSP2 is detected in increasing amounts later in infection in the maturing viroplasm, suggesting a conversion of dNSP2 into vNSP2. Immunoprecipitation experiments and reciprocal Western blot analysis confirm that there are two different forms of NSP2 that assemble in complexes with NSP5, VP1, VP2, and tubulin. dNSP2 associates with hypophosphorylated NSP5 and acetylated tubulin, which is correlated with stabilized microtubules, while vNSP2 associates with hyperphosphorylated NSP5. Mass spectroscopy analysis of NSP2 complexes immunoprecipitated from RV-infected cell lysates show both forms of NSP2 are phosphorylated, with a greater proportion of vNSP2 being phosphorylated compared to dNSP2. Together, these data suggest that dNSP2 interacts with viral proteins, including hypophosphorylated NSP5, to initiate viroplasm formation, while viroplasm maturation includes phosphorylation of NSP5 and vNSP2.
New World Simian Foamy Virus Infections
In Vivo
and
In Vitro
Authors: Stenbak Carolyn R. , Craig Karen L. , Ivanov Sergei B. , Wang Xiaoxing , Soliven Khanh C. , Jackson Dana L. , Gutierrez Gustavo A. , Engel Gregory , Jones-Engel Lisa , Linial Maxine L. 
Published: November 2013

ABSTRACT
Foamy viruses (FV) are complex retroviruses that naturally infect all nonhuman primates (NHP) studied to date. Zoonotic transmission of Old World NHP simian foamy viruses (SFV) has been documented, leading to nonpathogenic persistent infections. To date, there have been no reports concerning zoonotic transmission of New World monkey (NWM) SFV to humans and resulting infection. In this study, we developed a Western blot assay to detect antibodies to NWM SFV, a nested PCR assay to detect NWM SFV DNA, and a β-galactosidase-containing indicator cell line to assay replication of NWM SFV. Using these tools, we analyzed the plasma and blood of 116 primatologists, of whom 69 had reported exposures to NWM. While 8 of the primatologists tested were seropositive for SFV from a NWM, the spider monkey, none had detectable levels of viral DNA in their blood. We found that SFV isolated from three different species of NWM replicated in some, but not all, human cell lines. From our data, we conclude that while humans exposed to NWM SFV produce antibodies, there is no evidence for long-term viral persistence.
Lyme disease in the United Kingdom
Authors: Dubrey Simon W , Bhatia Ajay , Woodham Sarah , Rakowicz Wojtek 
Published: November 2013

Abstract
Lyme disease, while still an uncommon disease in the UK, is on the increase. Case numbers have increased by 3.6-fold since 2001, with over 950 cases reported by the Health Protection Agency (HPA) in 2011, compared with less than 500 cases annually pre-2004. HPA indications of the true incidence are suggested to be closer to 3000 cases/year, of which around 82% of cases are indigenously acquired. Three genospecies, Borrelia burgdorferi sensu stricto, Borrelia afzelli and Borrelia garinii, represent the predominant pathogenic variants in the UK. Erythema migrans is the commonest manifestation, occurring in 60%–91% of cases. In the UK, neuroborelliosis is the most common complication, while myocarditis is unusual, and death from either conduction disease or carditis is extremely rare. The role of Borrelia infection in chronic dilated cardiomyopathy in the UK remains unproven. Controversy over the existence of either ‘chronic Lyme disease’ and/or ‘post-Lyme disease syndrome’ continues unabated. National medical societies, patient advocacy groups, insurance companies, lawyers, doctors, the private health medical sector and scientific journals have all become embroiled in this bitter controversy. New developments include diagnostic tests able to detect Lyme disease at an earlier stage, shorter durations of antibiotic therapy and potential advances in vaccines against Borrelia.
T Lymphocytes Expressing a CD16 Signaling Receptor Exert Antibody-Dependent Cancer Cell Killing
Authors: Kudo Ko , Imai Chihaya , Lorenzini Paolo , Kamiya Takahiro , Kono Koji , Davidoff Andrew M. , Chng Wee Joo , Campana Dario 
Published: November 2013

AbstractTo expand applications for T-cell–based immunotherapy in cancer, we designed a receptor that binds the Fc portion of human immunoglobulins and delivers activation signals. The construct included the high-affinity CD16 (FCGR3A) V158 variant, CD8α hinge, and transmembrane domains, along with signaling domains from CD3ζ and 4-1BB (TNFRSF9), forming a chimeric receptor termed CD16V-BB-ζ. After retrovirus-mediated expression in human T cells, CD16V-BB-ζ bound humanized antibodies with higher affinity than a control receptor containing the more common F158 variant. Engagement of CD16V-BB-ζ provoked T-cell activation, exocytosis of lytic granules, and sustained proliferation, with a mean cell recovery after 4-week coculture with Daudi lymphoma cells and rituximab of nearly 70-fold relative to input cells. In contrast, unbound antibody alone produced no effect. CD16V-BB-ζ T cells specifically killed lymphoma cells and primary chronic lymphocytic leukemia cells in combination with rituximab at a low effector:target ratio, even when assayed on mesenchymal cells. Trastuzumab triggered CD16V-BB-ζ–mediated killing of HER2 (ERBB2)+ breast and gastric cancer cells; similar results were obtained with an anti-GD2 antibody in neuroblastoma and osteosarcoma cells. Furthermore, coadministration of CD16V-BB-ζ T cells with immunotherapeutic antibodies exerted considerable antitumor activity in vivo. Signaling mediated by 4-1BB-CD3ζ induced higher T-cell activation, proliferation, and cytotoxicity than CD3ζ or FcϵRIγ, and the receptor was expressed effectively after mRNA electroporation without viral vectors, facilitating clinical translation. Our results offer preclinical proof of concept for CD16V-BB-ζ as a universal, next-generation chimeric receptor with the potential to augment the efficacy of antibody therapies for cancer. Cancer Res; 74(1); 93–103. ©2013 AACR.
Doxorubicin Eliminates Myeloid-Derived Suppressor Cells and Enhances the Efficacy of Adoptive T-Cell Transfer in Breast Cancer
Authors: Alizadeh Darya , Trad Malika , Hanke Neale T. , Larmonier Claire B. , Janikashvili Nona , Bonnotte Bernard , Katsanis Emmanuel , Larmonier Nicolas 
Published: November 2013

Abstract
Myeloid-derived suppressor cells (MDSC) expand in tumor-bearing hosts and play a central role in cancer immune evasion by inhibiting adaptive and innate immunity. They therefore represent a major obstacle for successful cancer immunotherapy. Different strategies have thus been explored to deplete and/or inactivate MDSC in vivo. Using a murine mammary cancer model, we demonstrated that doxorubicin selectively eliminates MDSC in the spleen, blood, and tumor beds. Furthermore, residual MDSC from doxorubicin-treated mice exhibited impaired suppressive function. Importantly, the frequency of CD4+ and CD8+ T lymphocytes and consequently the effector lymphocytes or natural killer (NK) to suppressive MDSC ratios were significantly increased following doxorubicin treatment of tumor-bearing mice. In addition, the proportion of NK and cytotoxic T cell (CTL) expressing perforin and granzyme B and of CTL producing IFN-γ was augmented by doxorubicin administration. Of therapeutic relevance, this drug efficiently combined with Th1 or Th17 lymphocytes to suppress tumor development and metastatic disease. MDSC isolated from patients with different types of cancer were also sensitive to doxorubicin-mediated cytotoxicity in vitro. These results thus indicate that doxorubicin may be used not only as a direct cytotoxic drug against tumor cells, but also as a potent immunomodulatory agent that selectively impairs MDSC-induced immunosuppression, thereby fostering the efficacy of T-cell–based immunotherapy. Cancer Res; 74(1); 104–18. ©2013 AACR.
USP22 Regulates Oncogenic Signaling Pathways to Drive Lethal Cancer Progression
Authors: Schrecengost Randy S. , Dean Jeffry L. , Goodwin Jonathan F. , Schiewer Matthew J. , Urban Mark W. , Stanek Timothy J. , Sussman Robyn T. , Hicks Jessica L. , Birbe Ruth C. , Draganova-Tacheva Rossitza A. , Visakorpi Tapio , DeMarzo Angelo M. , McMahon Steven B. , Knudsen Karen E. 
Published: November 2013

AbstractIncreasing evidence links deregulation of the ubiquitin-specific proteases 22 (USP22) deubitiquitylase to cancer development and progression in a select group of tumor types, but its specificity and underlying mechanisms of action are not well defined. Here we show that USP22 is a critical promoter of lethal tumor phenotypes that acts by modulating nuclear receptor and oncogenic signaling. In multiple xenograft models of human cancer, modeling of tumor-associated USP22 deregulation demonstrated that USP22 controls androgen receptor accumulation and signaling, and that it enhances expression of critical target genes coregulated by androgen receptor and MYC. USP22 not only reprogrammed androgen receptor function, but was sufficient to induce the transition to therapeutic resistance. Notably, in vivo depletion experiments revealed that USP22 is critical to maintain phenotypes associated with end-stage disease. This was a significant finding given clinical evidence that USP22 is highly deregulated in tumors, which have achieved therapeutic resistance. Taken together, our findings define USP22 as a critical effector of tumor progression, which drives lethal phenotypes, rationalizing this enzyme as an appealing therapeutic target to treat advanced disease. Cancer Res; 74(1); 272–86. ©2013 AACR.
C-C Chemokine Receptor 5 on Pulmonary Mesenchymal Cells Promotes Experimental Metastasis via the Induction of Erythroid Differentiation Regulator 1
Authors: Mango Robert L. , Wu Qing Ping , West Michelle , McCook Everett C. , Serody Jonathan S. , van Deventer Hendrik W. 
Published: November 2013

Abstract
C-C Chemokine receptor 5 knockout (Ccr5−/−) mice develop fewer experimental pulmonary metastases than wild-type (WT) mice. This phenomenon was explored by applying gene expression profiling to the lungs of mice with these metastases. Consequently, erythroid differentiation regulator 1 (Erdr1) was identified as upregulated in the WT mice. Though commonly associated with bone marrow stroma, Erdr1 was differentially expressed in WT pulmonary mesenchymal cells (PMC) and murine embryonic fibroblasts (MEF). Moreover, the Ccr5 ligand Ccl4 increased its expression by 3.36 ± 0.14–fold. Ccr5 signaling was dependent on the mitogen-activated protein kinase kinase (Map2k) but not the phosphoinositide 3-kinase (Pi3k) pathway because treatment with U0126 inhibited upregulation of Erdr1, but treatment with LY294002 increased the expression by 3.44 ± 0.92–fold (P &lt; 0.05). The effect Erdr1 on B16-F10 melanoma metastasis was verified by the adoptive transfer of WT MEFs into Ccr5−/− mice. In this model, MEFs that had been transduced with Erdr1 short hairpin RNA (shRNA) lowered metastasis by 33% compared with control transduced MEFs. The relevance of ERDR1 on human disease was assessed by coculturing chronic lymphocytic leukemia (CLL) cells with M2-10B4 stromal cells that had been transfected with shRNA or control plasmids. After 96 hours of coculture, the cell counts were higher with control cell lines than with Erdr1 knockdown lines [odds ratio (OR), 1.88 ± 0.27, 2.52 ± 0.66, respectively]. This increase was associated with a decrease in apoptotic cells (OR, 0.69 ± 0.18, 0.58 ± 0.12, respectively).
Implications: Therefore, ERDR1 is a stromal-derived factor that promotes cancer cell survival in vitro and in an experimental metastasis model. Mol Cancer Res; 12(2); 274–82. ©2013 AACR.
Pneumococcal phosphoglycerate kinase interacts with plasminogen and its tissue activator
Authors: Fulde Marcus , Bernardo-García Noelia , Rohde Manfred , Nachtigall Nadine , Frank Ronald , Preissner Klaus T. , Klett Javier , Morreale Antonio , Chhatwal G. Singh , Hermoso Juan A. , Bergmann Simone 
Published: November 2013

Summary
Streptococcus pneumoniae is not only a commensal of the nasopharyngeal epithelium, but may also cause life-threatening diseases. Immune-electron microscopy studies revealed that the bacterial glycolytic enzyme, phosphoglycerate kinase (PGK), is localised on the pneumococcal surface of both capsulated and non-capsulated strains and colocalises with plasminogen. Since pneumococci may concentrate host plasminogen (PLG) together with its activators on the bacterial cell surface to facilitate the formation of plasmin, the involvement of PGK in this process was studied. Specific binding of human or murine PLG to strain-independent PGK was documented, and surface plasmon resonance analyses indicated a high affinity interaction with the kringle domains 1–4 of PLG. Crystal structure determination of pneumococcal PGK together with peptide array analysis revealed localisation of PLG-binding site in the N-terminal region and provided structural motifs for the interaction with PLG. Based on structural analysis data, a potential interaction of PGK with tissue plasminogen activator (tPA) was proposed and experimentally confirmed by binding studies, plasmin activity assays and thrombus degradation analyses.
Fibrinogen depletion after plasma-dilution: impairment of proteolytic resistance and reversal via clotting factor concentrates
Authors: Johnsson Hans , Zabczyk Michal , Hultenby Kjell , Wallen Håkan , Blombäck Margareta , He Shu 
Published: November 2013

SummaryIn trauma patients, resuscitation treatment of intravascular volume may cause haemodilution including blood cell- and plasma-dilution. After plasma-dilution, fibrinogen is the first factor that decreases to critically low concentrations. Fibrin formed in lowered levels is susceptible to fibrinolysis, a natural forerunner for bleeding. To assess whether a fibrinogen concentrate or a factor XIII (FXIII) concentrate can reverse the impairment of fibrin properties after plasma dilution, different laboratory methods were used to determine thrombin generation and fibrin quantity/quality in a normal plasma sample diluted in vitro. Coagulation and clot lysis by plasmin were triggered with tissue factor and rt-PA, respectively. We found that while the endogenous thrombin potential (ETP) was unaffected after plasma-dilution due to postponement of thrombin decay, levels of fibrinogen and hence fibrin were decreased in dilution degree-dependency. The imbalance between influence of the dilution on thrombin activity and fibrin formation brought unexpected outcomes of fibrin properties: the formed clots favoured the degradation by plasmin but the fibrin networks remained tighter/less permeable. This proteolytic tendency was partly overturned by the fibrinogen concentrate added (total fibrinogen ≥ 2 g/l), and much more affected if used in combination with tranexamic acid (a fibrinolysis inhibitor) at small doses. No reversal effect resulted from the FXIII concentrate added. We conclude that plasma-dilution did reduce the proteolytic resistance of formed clots. The fibrinogen concentrate, better together with small doses of tranexamic acid, may reverse the impairment of fibrin property. The FXIII concentrate is not effective in this regard in our in vitro model using platelet-poor plasma.
Estimation of X-Band Polarimetric Radar Attenuation and Measurement Uncertainty Using a Variational Method
Authors: Chang Wei-Yu , Vivekanandan Jothiram , Chen Wang Tai-Chi 
Published: November 2013

AbstractA variational algorithm for estimating measurement error covariance and the attenuation of X-band polarimetric radar measurements is described. It concurrently uses both the differential reflectivity ZDR and propagation phase ΦDP. The majority of the current attenuation estimation techniques use only ΦDP. A few of the ΦDP-based methods use ZDR as a constraint for verifying estimated attenuation. In this paper, a detailed observing system simulation experiment was used for evaluating the performance of the variational algorithm. The results were compared with a single-coefficient ΦDP-based method. Retrieved attenuation from the variational method is more accurate than the results from a single coefficient ΦDP-based method. Moreover, the variational method is less sensitive to measurement noise in radar observations. The variational method requires an accurate description of error covariance matrices. Relative weights between measurements and background values (i.e., mean value based on long-term DSD measurements in the variational method) are determined by their respective error covariances. Instead of using ad hoc values, error covariance matrices of background and radar measurement are statistically estimated and their spatial characteristics are studied. The estimated error covariance shows higher values in convective regions than in stratiform regions, as expected. The practical utility of the variational attenuation correction method is demonstrated using radar field measurements from the Taiwan Experimental Atmospheric Mobile-Radar (TEAM-R) during 2008’s Southwest Monsoon Experiment/Terrain-Influenced Monsoon Rainfall Experiment (SoWMEX/TiMREX). The accuracy of attenuation-corrected X-band radar measurements is evaluated by comparing them with collocated S-band radar measurements.
EMG-triggered electrical stimulation is a feasible intervention to apply to multiple arm muscles in people early after stroke, but does not improve strength and activity more than usual therapy: a randomized feasibility trial
Authors: Dorsch Simone , Ada Louise , Canning Colleen G 
Published: November 2013

Objective: To determine whether EMG-triggered electrical stimulation applied to multiple muscles daily is a feasible intervention and to determine its effect on strength and activity in very weak stroke patients. Design: A prospective, randomized trial with blinded assessment. Setting: Metropolitan mixed acute and rehabilitation units. Participants: Thirty-three people within four weeks of a stroke with less than Grade 3 strength in three out of four muscle groups (shoulder flexors, elbow extensors, wrist and finger extensors and thumb abductors) of the affected arm. Interventions: Participants were randomly allocated to receive EMG-triggered electrical stimulation to the four muscle groups of the affected arm plus usual therapy five times a week for four weeks, or usual therapy only. Main measures: Feasibility of the intervention was measured by examining compliance with the trial protocol. Strength was measured using manual muscle testing summed across muscle groups (0–20). Activity was measured using the Motor Assessment Scale, summed upper limb items (0–18). Results: The experimental group received 87% of the intervention. Following the intervention period, there was no difference between the groups for strength (mean between-group difference, 0 out of 20, 95% confidence interval (CI) −3 to 3, p = 0.91) or activity (mean between-group difference 1 out of 18, 95% CI −2 to 4, p = 0.44). Conclusions: It is feasible to apply EMG-triggered electrical stimulation to multiple muscles of the upper limb in very weak people early after stroke. However, it does not appear to improve strength or activity beyond usual arm therapy that contains strengthening.
Life Expectancy and Economic Well-being: A Within-country Regional-level Analysis Using the Micro-data of Bangladesh
Authors: Husain Muhammad Jami 
Published: November 2013

A frequent empirical approach toward examining the impact of health on economic growth has been to focus on data for a cross-section of countries and to regress the income indicator on the health indicator controlling for the initial level of income and for other factors believed to influence steady-state income levels. From the methodological perspective, such a growth regression approach has mainly offered evidence for the relationship between health and income, using cross-country macro-level data. This article contributes to existing empirical research by introducing within-country regional-level analysis using three rounds of the Demographic and Health Surveys of Bangladesh, combined with corresponding geo-referenced global positioning system (GPS) data, to estimate the contribution of life expectancy to economic well-being. The joint evolution of the regional-level longevity and wealth indicator obtained from the micro-data corroborates Preston’s cross-country macro-level findings. Also, the finding that a 1 per cent increase in life expectancy leads to about 3 per cent increase in the wealth index corroborates the findings of several macro-regression studies and promotes the concept of direct investments in health. JEL Classification: I10, O40, R10
From a court orientation to a victim orientation: The paradigm shift in Israel’s Juvenile Probation Service
Authors: Yanay Uri , Borowski Allan 
Published: November 2013

During the course of the last decade, Israel’s Juvenile Probation Service (JPS) added Victim Offender Mediation (VOM), an important example of restorative justice, to its repertoire of diagnostic, therapeutic and caring practices for young offenders. The introduction of VOM represented a major shift from its traditional service orientation. When first established by the British Mandate over Palestine in the 1930s, the primary beneficiaries of the probation services were His Majesty’s Courts and their British judges. Later, after the establishment of the State of Israel in 1948, the JPS specialized in assessing and supervising young offenders. The introduction of VOM meant the acknowledgement by the JPS of the victims of its young clientele. This acknowledgement blurred the boundaries of the JPS’s traditional mission, operations and clientele. This paper describes how this new orientation in the work of the JPS came about. In doing so it draws on some of the findings of a qualitative research study, findings that serve to highlight some of the main issues that arose along the way.