bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAMHD1 Restricts Herpes Simplex Virus 1 in Macrophages by Limiting DNA Replication
Authors: Kim Eui Tae , White Tommy E. , Brandariz-Núñez Alberto , Diaz-Griffero Felipe , Weitzman Matthew D. 
Published: September 2013

ABSTRACT
Macrophages play important roles in host immune defense against virus infection. During infection by herpes simplex virus 1 (HSV-1), macrophages acquire enhanced antiviral potential. Restriction of HSV-1 replication and progeny production is important to prevent viral spread, but the cellular mechanisms that inhibit the DNA virus in macrophages are unknown. SAMHD1 was recently identified as a retrovirus restriction factor highly expressed in macrophages. The SAMHD1 protein is expressed in both undifferentiated monocytes and differentiated macrophages, but retroviral restriction is limited to differentiated cells by modulation of SAMHD1 phosphorylation. It is proposed to block reverse transcription of retroviral RNA into DNA by depleting cellular deoxynucleotide triphosphates (dNTPs). Viruses with DNA genomes do not employ reverse transcription during infection, but replication of their viral genomes is also dependent on intracellular dNTP concentrations. Here, we demonstrate that SAMHD1 restricts replication of the HSV-1 DNA genome in differentiated macrophage cell lines. Depleting SAMHD1 in THP-1 cells enhanced HSV-1 replication, while ectopic overexpression of SAMHD1 in U937 cells repressed HSV-1 replication. SAMHD1 did not impact viral gene expression from incoming HSV-1 viral genomes. HSV-1 restriction involved the dNTP triphosphohydrolase activity of SAMHD1 and was partially overcome by addition of exogenous deoxynucleosides. Unlike retroviruses, restriction of HSV-1 was not affected by SAMHD1 phosphorylation status. Our results suggest that SAMHD1 functions broadly to inhibit replication of DNA viruses in nondividing macrophages.
Recombination Can Lead to Spurious Results in Retroviral Transduction with Dually Fluorescent Reporter Genes
Authors: Salamango Daniel J. , Evans David A. , Baluyot Mariju F. , Furlong Jackson N. , Johnson Marc C. 
Published: September 2013

ABSTRACT
Fluorescent proteins are routinely employed as reporters in retroviral vectors. Here, we demonstrate that transduction with retroviral vectors carrying a tandem-dimer Tomato (TdTom) reporter produces two distinct fluorescent cell populations following template jumping due to a single nucleotide polymorphism between the first and second Tomato genes. Template jumping also occurs between repeated sequences in the Tomato and green fluorescent protein (GFP) genes. Thus, proper interpretation of the fluorescence intensity of transduced cells requires caution.
Kaposi's Sarcoma-Associated Herpesvirus Transactivator Rta Induces Cell Cycle Arrest in G
0
/G
1
Phase by Stabilizing and Promoting Nuclear Localization of p27
kip
Authors: Kumar Pankaj , Wood Charles 
Published: September 2013

ABSTRACT

The Kaposi's sarcoma-associated herpesvirus (KSHV) immediate-early gene, replication, and transcription activator (K-Rta) is a key viral protein that serves as the master regulator for viral lytic replication. In this study, we investigated the role of K-Rta in cell cycle regulation and found that the expression of K-Rta in doxycycline (Dox)-inducible BJAB cells induced cell cycle arrest in G
0
/G
1
phase. Western blot analysis of key cell cycle regulators revealed that K-Rta-mediated cell cycle arrest was associated with a decrease in cyclin A and phosphorylated Rb (pS807/pS811) protein levels, both markers of S phase progression, and an increase in protein levels for p27, a cyclin-dependent kinase inhibitor. Further, we found that K-Rta does not affect the transcription of p27 but regulates p27 at the posttranslational level by inhibiting its proteosomal degradation. Immunofluorescence staining and cell fractionation experiments revealed largely nuclear compartmentalization of p27 in K-Rta-expressing cells, demonstrating that K-Rta not only stabilizes p27 but also modulates its cellular localization. Finally, short hairpin RNA knockdown of p27 significantly abrogates cell cycle arrest in K-Rta-expressing cells, supporting its key role in K-Rta-mediated cell cycle arrest. Our findings are consistent with previous studies which showed that expression of immediate-early genes of several herpesviruses, including herpes simplex virus, Epstein-Barr virus, and cytomegalovirus, results in cell cycle arrest at the G
0
/G
1
phase, possibly to avoid competition for resources needed for host cell replication during the S phase.
Suppression of PACT-Induced Type I Interferon Production by Herpes Simplex Virus 1 Us11 Protein
Authors: Kew Chun , Lui Pak-Yin , Chan Chi-Ping , Liu Xiang , Au Shannon Wing Ngor , Mohr Ian , Jin Dong-Yan , Kok Kin-Hang 
Published: September 2013

ABSTRACT
Herpes simplex virus 1 (HSV-1) Us11 protein is a double-stranded RNA-binding protein that suppresses type I interferon production through the inhibition of the cytoplasmic RNA sensor RIG-I. Whether additional cellular mediators are involved in this suppression remains to be determined. In this study, we report on the requirement of cellular double-stranded RNA-binding protein PACT for Us11-mediated perturbation of type I interferon production. Us11 associates with PACT tightly to prevent it from binding with and activating RIG-I. The Us11-deficient HSV-1 was indistinguishable from the Us11-proficient virus in the suppression of interferon production when PACT was compromised. More importantly, HSV-1-induced activation of interferon production was abrogated in PACT knockout murine embryonic fibroblasts. Our findings suggest a new mechanism for viral evasion of innate immunity through which a viral double-stranded RNA-binding protein interacts with PACT to circumvent type I interferon production. This mechanism might also be used by other PACT-binding viral interferon-antagonizing proteins such as Ebola virus VP35 and influenza A virus NS1.
Visual analogue scales in stroke: what can they tell us about health-related quality of life?
Authors: Hilari Katerina , Boreham Lois-Danielle 
Published: September 2013

Objectives Contrasting accounts exist on whether people with stroke are able to self-report on outcomes using visual analogue scales (VASs). We explored correlations between multi-item scale-rated health-related quality of life (HRQL) and VAS-rated HRQL after stroke, and compared those with versus without aphasia.DesignCross-sectional survey.SettingCommunity dwelling stroke patients living in London.ParticipantsPeople with first stroke were recruited during their hospital stay and were assessed 3 months later.MeasuresThe Frenchay Aphasia Screening Test, the Stroke and Aphasia Quality of Life Scale (SAQOL-39g) and a single vertical VAS.Results73 people took part, 14 with aphasia. VAS scores were significantly correlated with the overall SAQOL-39g (r=0.69, p<0.01). SAQOL-39g subdomain scores were also correlated with VAS scores, with the psychosocial domain most highly correlated (r=0.67, p<0.01) and the communication least correlated (ρ=0.30, p<0.05). SAQOL-39g—VAS difference scores were higher for people with aphasia and the difference was significant (t (71)=2.02, p<0.05).ConclusionsDespite the significant correlation of the overall SAQOL-39g and the VAS-rated HRQL, subdomain results suggested that people considered mostly psychosocial aspects when rating their HRQL on a single VAS. Agreement was poorer for people with aphasia, raising issues for the use of VASs with people with aphasia.
The association between patients’ beliefs about medicines and adherence to drug treatment after stroke: a cross-sectional questionnaire survey
Authors: Sjölander Maria , Eriksson Marie , Glader Eva-Lotta 
Published: September 2013

ObjectivesAdherence to preventive drug treatment is a clinical problem and we hypothesised that patients’ beliefs about medicines and stroke are associated with adherence. The objective was to examine associations between beliefs of patients with stroke about stroke and drug treatment and their adherence to drug treatment.DesignCross-sectional questionnaire survey.SettingPatients with stroke from 25 Swedish hospitals were included.MeasurementsQuestionnaires were sent to 989 patients to assess their perceptions about stroke (Brief Illness Perception Questionnaire, Brief IPQ), beliefs about medicines (Beliefs about Medicines Questionnaires, BMQ) and adherence to treatment (Medication Adherence Report Scale, MARS) 3 months after stroke onset. Only patients living at home were included in the analysis. The primary outcome was self-reported adherence as measured on MARS. MARS scores were dichotomised into adherent/non-adherent. Background and clinical data from the Swedish Stroke register were included.Results811 patients were still living at home and 595 answered the questionnaire. Complete MARS data were available for 578 patients and 72 (12.5%) of these were classified as non-adherent. Non-adherent patients scored lower on positive beliefs as measured on BMQ-necessity (OR = 0.90, 95% CI 0.83 to 0.98) and BMQ-benefit (OR=0.77, 95% CI 0.68 to 0.87), and higher on negative beliefs as measured on BMQ-concern (OR=1.12, 95% CI 1.05 to 1.21), BMQ-overuse (OR=1.29, 95% CI 1.14 to 1.45), and BMQ-harm (OR=1.12, 95% CI 1.01 to 1.24). The Brief IPQ showed that non-adherent patients believed their current treatment to be less useful (p=0.001).ConclusionsThis study showed associations between beliefs of Swedish patients with stroke about medicines and adherence. Positive beliefs were less common and negative more common among non-adherent. To improve adherence, patients’ beliefs about medicines should be considered.
Concordant Effects of Aromatase Inhibitors on Gene Expression in ER+ Rat and Human Mammary Cancers and Modulation of the Proteins Coded by These Genes
Authors: Lu Yan , You Ming , Ghazoui Zara , Liu Pengyuan , Vedell Peter T. , Wen Weidong , Bode Ann M. , Grubbs Clinton J. , Lubet Ronald A. 
Published: September 2013

Abstract
Aromatase inhibitors are effective in therapy/prevention of estrogen receptor–positive (ER+) breast cancers. Rats bearing methylnitrosourea (MNU)-induced ER+ mammary cancers were treated with the aromatase inhibitor vorozole (1.25 mg/kg BW/day) for five days. RNA expression showed 162 downregulated and 180 upregulated (P &lt; 0.05 and fold change &gt;1.5) genes. Genes modulated by vorozole were compared with published data from four clinical neoadjuvant trials using aromatase inhibitors (anastrozole or letrozole). More than 30 genes and multiple pathways exhibited synchronous changes in animal and human datasets. Cell-cycle genes related to chromosome condensation in prometaphase [anaphase-prometaphase complex (APC) pathway, including Aurora-A kinase, BUBR1B, TOP2, cyclin A, cyclin B CDC2, and TPX-2)] were downregulated in animal and human studies reflecting the strong antiproliferative effects of aromatase inhibitors. Comparisons of rat arrays with a cell culture study where estrogen was removed from MCF-7 cells showed decreased expression of E2F1-modulated genes as a major altered pathway. Alterations of the cell cycle and E2F-related genes were confirmed in a large independent set of human samples (81 pairs baseline and two weeks anastrozole treatment). Decreases in proliferation-related genes were confirmed at the protein level for cyclin A2, BuRB1, cdc2, Pttg, and TPX-2. Interestingly, the proteins downregulated in tumors were similarly downregulated in vorozole-treated normal rat mammary epithelium. Finally, decreased expression of known estrogen-responsive genes (including TFF, 1,3, progesterone receptor, etc.) were decreased in the animal model. These studies demonstrate that gene expression changes (pathways and individual genes) are similar in humans and the rat model. Cancer Prev Res; 6(11); 1151–61. ©2013 AACR.
Glycosylation of autoantibodies: Insights into the mechanisms of immune thrombocytopenia
Authors: Bakchoul Tamam , Walek Kathrin , Krautwurst Annika , Rummel Mathias , Bein Gregor , Santoso Sentot , Sachs Ulrich J. 
Published: September 2013

SummaryImmune thrombocytopenia (ITP) is a bleeding disorder caused by IgG autoantibodies (AAbs) directed against platelets (PLTs). IgG effector functions depend on their Fc-constant region which undergoes post-translational glycosylation. We investigated the role of Asn279-linked N-glycan of AAbs in vitro and in vivo. AAbs were purified from ITP patients (n=15) and N-glycans were enzymatically cleaved by endoglycosidase F. The effects of native AAbs and deglycosylated AAbs were compared in vitro on enhancement of phagocytosis of platelets by monocytes and complement fixation and activation applying flow cytometry, laser scanning microscopy, and a complement consumption assay. AAb-induced platelet phagocytosis was inhibited by N-glycan cleavage (median phagocytic activity: 8% vs 0.8%, p=0.004). Seven out of 15 native AAbs bound C1q and activated complement. N-glycan cleavage significantly reduced both effects. In vivo survival of human PLTs was assessed after co-transfusion with native or N-glycan cleaved AAbs in a NOD/SCID mouse model. Injection of AAbs resulted in rapid clearance of human platelets compared to control (platelet clearance after 5h (CL5h) 75% vs 30%, p<0.001). AAbs that were able to activate complement induced more pronounced platelet clearance in the presence of complement compared to the clearance in the absence of complement (CL5h 82% vs 62%, p=0.003). AAbs lost their ability to destroy platelets in vivo after deglycosylation (CL5h 42%, p<0.001). N-glycosylation of human ITP AAbs appears to be required for platelet phagocytosis and complement activation, reducing platelet survival in vivo. Posttranslational modification of AAbs may constitute an important determinant for the clinical manifestation of ITP.
Life and Times of the Samson Box
Authors: Loy D. Gareth 
Published: September 2013

Peter Samson designed and built a real-time signal-processing computer for music applications in the 1970s. The Systems Concepts Digital Synthesizer (“Samson Box” for short) was installed at the Center for Computer Research in Music and Acoustics (CCRMA) at Stanford University in 1977, where it served for over a decade as the principal music generation system. It was an important landmark in the transition from general-purpose computers to real-time systems for music and audio, and helped set the stage for the sea change in the music industry from analog to digital technologies that began in the 1980s and continues at a rapid pace today. This article focuses on the historical context of the Samson Box, its development, its impact on the culture of CCRMA and the Stanford Artificial Intelligence Laboratory, its use for music research and composition at Stanford, and its role in the transformation of the music and audio industries from analog to digital practices. A list of compositions realized on the Samson Box is included, which shows that from 1978 to its decommissioning in 1992 it was used to create over 100 finished works, many of which were widely performed and were awarded prizes. A companion article provides a detailed architectural review and an interview with Pete Samson.
A Large-Eddy Simulation Study of Scalar Dissimilarity in the Convective Atmospheric Boundary Layer
Authors: Cancelli Diana M. , Chamecki Marcelo , Dias Nelson L. 
Published: September 2013

Abstract
A numerical study of the effect of entrainment fluxes at the top of the atmospheric boundary layer (ABL) on dissimilarity between scalars within the mixed and surface layers is conducted. Simulation results clearly show that entrainment fluxes of opposite sign cause decorrelation between the scalars throughout the entire ABL. In the upper part of the mixed layer, this decorrelation is caused by changes in the covariance between the scalars and the scalar variance as well, and is distributed over the entire range of scales resolved in the simulation. Near the surface, the reduction in correlation coefficient originates from an increasing scalar variance, which is present exclusively in the large scales. These effects are noticeable on time scales of about 24 min or longer, and could be interpreted as nonstationarity for the typical 30-min periods used in surface-layer data processing. In addition, it is shown that, for the conditions studied here, the scalar correlation coefficient within the surface layer scales with the measurement height normalized by the ABL depth and not by the Obukhov length.
A walking intervention to reduce inflammation in patients with diabetes and peripheral arterial/artery disease: A pilot study
Authors: Collins Tracie C , Twumasi-Ankrah Philip 
Published: September 2013

Objectives: In this pilot study, we sought to determine whether walking reduces inflammation in patients with diabetes mellitus and peripheral arterial/artery disease. Methods: We obtained blood samples from patients with diabetes mellitus and peripheral arterial/artery disease. Intervention participants were advised to walk for 50 min 3 days per week for 6 months. Participants completed assessments of comorbidities and walking ability. Difference-in-difference analyses were used to assess the relationship between group assignment and each biomarker over time. Results: We randomized 55 participants (control = 25 and intervention = 30). At 6 months and based on p values of <0.20, vascular cellular adhesion molecule, beta-2 microglobulin, total cholesterol, and triglycerides demonstrated a greater decrease among participants randomized to the intervention compared to the control. Conclusions: Walking may reduce inflammation in persons with diabetes mellitus and peripheral arterial/artery disease. Further research is needed to determine the impact of walking on inflammation in persons with vascular disease.
Compartment syndrome of the testicle: a case report and review of the literature
Authors: Sharifi LK , Patten DK , Thomas R , Alchikhali T , Vig S 
Published: September 2013

In this case report we describe a patient presenting with symptoms of right sided testicular torsion who, upon surgical exploration, was noted to no longer have a torsion of the spermatic cord but persisted in having an ischaemic testicle refractory to reperfusion. A testicular compartment syndrome was suspected and the patient underwent fasciotomy of the tunica albuginea, leading to full reperfusion and good clinical outcome at three weeks and 10 months. This case raises the question of the value of performing such fasciotomies in patients who would otherwise undergo orchidectomy. Following a review of the literature, we feel the technique may well have a place in the management of torsion, pending further study. Databases searched were Medline, Embase, Cochrane, Trip and NHS Evidence. Search criteria included ‘compartment’, ‘testicle’, ‘testicular’, ‘syndrome’, ‘compartment syndrome’ and testis’ and combinations of these key words.
JAK2 p.V617F detection and allele burden measurement in peripheral blood and bone marrow aspirates in patients with myeloproliferative neoplasms
Authors: Takahashi Koichi , Patel Keyur P. , Kantarjian Hagop , Luthra Rajyalakshmi , Pierce Sherry , Cortes Jorge , Verstovsek Srdan 
Published: September 2013

Key Points
The sensitivity and specificity of detecting the JAK2 p.V617F mutation in PB are both 100% compared with BM. The JAK2 p.V617F allele burden measured in PB is equivalent to that in BM aspirate (R2 = 0.991; P < .0001).
Regulatory T cells and natural killer T cells for modulation of GVHD following allogeneic hematopoietic cell transplantation
Authors: Schneidawind Dominik , Pierini Antonio , Negrin Robert S. 
Published: September 2013

AbstractAlloreactivity of donor lymphocytes leads to graft-versus-host disease (GVHD) contributing to significant morbidity and mortality following allogeneic hematopoietic cell transplantation (HCT). Within the past decade, significant progress has been made in elucidating the mechanisms underlying the immunologic dysregulation characteristic of GVHD. The recent discoveries of different cell subpopulations with immune regulatory function has led to a number of studies aimed at understanding their role in allogeneic HCT and possible application for the prevention and treatment of GVHD and a host of other immune-mediated diseases. Preclinical animal modeling has helped define the potential roles of distinct populations of regulatory cells that have progressed to clinical translation with promising early results.
Small ruminant macrophage polarization may play a pivotal role on lentiviral infection
Authors: Crespo Helena , Bertolotti Luigi , Juganaru Magda , Glaria Idoia , de Andrés Damián , Amorena Beatriz , Rosati Sergio , Reina Ramsés 
Published: September 2013

AbstractSmall ruminant lentiviruses (SRLV) infect the monocyte/macrophage lineage inducing a long-lasting infection affecting body condition, production and welfare of sheep and goats all over the world. Macrophages play a pivotal role on the host’s innate and adaptative immune responses against parasites by becoming differentially activated. Macrophage heterogeneity can tentatively be classified into classically differentiated macrophages (M1) through stimulation with IFN-γ displaying an inflammatory profile, or can be alternatively differentiated by stimulation with IL-4/IL-13 into M2 macrophages with homeostatic functions. Since infection by SRLV can modulate macrophage functions we explored here whether ovine and caprine macrophages can be segregated into M1 and M2 populations and whether this differential polarization represents differential susceptibility to SRLV infection. We found that like in human and mouse systems, ovine and caprine macrophages can be differentiated with particular stimuli into M1/M2 subpopulations displaying specific markers. In addition, small ruminant macrophages are plastic since M1 differentiated macrophages can express M2 markers when the stimulus changes from IFN-γ to IL-4. SRLV replication was restricted in M1 macrophages and increased in M2 differentiated macrophages respectively according to viral production. Identification of the infection pathways in macrophage populations may provide new targets for eliciting appropriate immune responses against SRLV infection.
Post-transplantation encapsulating peritoneal sclerosis without inflammation or radiological abnormalities
Authors: Habib Sayed Meelad , Dor Frank Johan Marinus Frederik , Korte Mario Richard , Hagen Sander Martijn , Betjes Michiel Gerardus Henricus 
Published: September 2013

Abstract

Background
Post-transplantation encapsulating peritoneal sclerosis (EPS) causing bowel obstruction has been identified as a serious complication after kidney transplantation in patients previously treated with peritoneal dialysis. Systemic inflammation and abnormalities on an abdominal computed tomography (CT) scan are important hallmarks of EPS. To our knowledge, this is the first report of a case being diagnosed with late-onset post-transplantation EPS without systemic inflammation or abnormalities on a CT scan which could only be diagnosed by laparotomy.

Case presentation
A 59-year old female presented because of symptoms of bowel obstruction 33 months after kidney transplantation. The patient had a 26-month history of peritoneal dialysis before her first kidney transplantation and was treated with peritoneal dialysis for 4 years before undergoing a second kidney transplantation. Physical examination was unremarkable and laboratory tests showed no signs of systemic inflammation (C-reactive protein <1 mg/L). An abdominal CT scan did not reveal any abnormalities fitting the diagnosis of EPS, except a “feces sign”. Given the severity of the progressive symptoms, a diagnostic laparotomy was performed, visualizing a classical EPS. Total peritonectomy and enterolysis were performed, leading to restoration of peristalsis.

Conclusion
EPS may occur several years after kidney transplantation in the absence of inflammation and typical radiological abnormalities. Obtaining a diagnosis of post-transplantation EPS is challenging, however, a low threshold for surgical exploration in case of high clinical suspicion and negative findings on the CT scan is mandatory.