bluuebunny/crossref_metadata_2025_split huggingface dataset:
MCL1 Enhances the Survival of CD8
+
Memory T Cells after Viral Infection
Authors: Gui Jingang , Hu Zhuting , Tsai Ching-Yi , Ma Tian , Song Yan , Morales Amanda , Huang Li-Hao , Dmitrovsky Ethan , Craig Ruth W. , Usherwood Edward J. 
Published: December 2014

ABSTRACT

Viral infection results in the generation of massive numbers of activated effector CD8
+
T cells that recognize viral components. Most of these are short-lived effector T cells (SLECs) that die after clearance of the virus. However, a small proportion of this population survives and forms antigen-specific memory precursor effector cells (MPECs), which ultimately develop into memory cells. These can participate in a recall response upon reexposure to antigen even at protracted times postinfection. Here, antiapoptotic myeloid cell leukemia 1 (MCL1) was found to prolong survival upon T cell stimulation, and mice expressing human
MCL1
as a transgene exhibited a skewing in the proportion of CD8
+
T cells, away from SLECs toward MPECs, during the acute phase of vaccinia virus infection. A higher frequency and total number of antigen-specific CD8
+
T cells were observed in
MCL1
transgenic mice. These findings show that MCL1 can shape the makeup of the CD8
+
T cell response, promoting the formation of long-term memory.

IMPORTANCE
During an immune response to a virus, CD8
+
T cells kill cells infected by the virus, and most die when the infection resolves. However, a small proportion of cells survives and differentiates into long-lived memory cells that confer protection from reinfection by the same virus. This report shows that transgenic expression of an MCL1 protein enhances survival of memory CD8
+
T cells following infection with vaccinia virus. This is important because it shows that MCL1 expression may be an important determinant of the formation of long-term CD8
+
T cell memory.
Virion-Independent Transfer of Replication-Competent Hepatitis C Virus RNA between Permissive Cells
Authors: Longatti Andrea , Boyd Bryan , Chisari Francis V. 
Published: December 2014

ABSTRACT

In this study, we show that replication-competent subgenomic hepatitis C virus (HCV) RNA can be transferred to permissive Huh7 cells, leading to the establishment of viral RNA replication. Further, we show that these events are mediated by exosomes rather than infectious virus particles. If similar events occur
in vivo
, this could represent a novel, albeit inefficient, mechanism of viral spread and immune escape.
Analysis of the Early Immune Response to Infection by Infectious Bursal Disease Virus in Chickens Differing in Their Resistance to the Disease
Authors: Smith Jacqueline , Sadeyen Jean-Remy , Butter Colin , Kaiser Pete , Burt David W. 
Published: December 2014

ABSTRACT

Chicken whole-genome gene expression arrays were used to analyze the host response to infection by infectious bursal disease virus (IBDV). Spleen and bursal tissue were examined from control and infected birds at 2, 3, and 4 days postinfection from two lines that differ in their resistance to IBDV infection. The host response was evaluated over this period, and differences between susceptible and resistant chicken lines were examined. Antiviral genes, including
IFNA
,
IFNG
,
MX1
,
IFITM1
,
IFITM3
, and
IFITM5
, were upregulated in response to infection. Evaluation of this gene expression data allowed us to predict several genes as candidates for involvement in resistance to IBDV.

IMPORTANCE
Infectious bursal disease (IBD) is of economic importance to the poultry industry and thus is also important for food security. Vaccines are available, but field strains of the virus are of increasing virulence. There is thus an urgent need to explore new control solutions, one of which would be to breed birds with greater resistance to IBD. This goal is perhaps uniquely achievable with poultry, of all farm animal species, since the genetics of 85% of the 60 billion chickens produced worldwide each year is under the control of essentially two breeding companies. In a comprehensive study, we attempt here to identify global transcriptomic differences in the target organ of the virus between chicken lines that differ in resistance and to predict candidate resistance genes.
Epstein-Barr Virus Type 2 Latently Infects T Cells, Inducing an Atypical Activation Characterized by Expression of Lymphotactic Cytokines
Authors: Coleman Carrie B. , Wohlford Eric M. , Smith Nicholas A. , King Christine A. , Ritchie Julie A. , Baresel Paul C. , Kimura Hiroshi , Rochford Rosemary 
Published: December 2014

ABSTRACTEpstein-Barr virus (EBV) is a well-established B-cell-tropic virus associated with various lymphoproliferative diseases of both B-cell and non-B-cell origin. EBV is associated with a number of T-cell lymphomas; however,in vitrostudies utilizing prototypical EBV type 1 (EBV-1) laboratory strains have generally failed to readily infect mature T cells in culture. The difficulties in performingin vitroT-cell experiments have left questions regarding the role of EBV in the pathogenesis of EBV-positive T-cell lymphoproliferative diseases largely unresolved. We report here that the EBV type 2 (EBV-2) strain displays a unique cell tropism for T cells. In remarkable contrast to EBV-1, EBV-2 readily infects primary T cellsin vitro, demonstrating a propensity for CD8+T cells. EBV-2 infection of purified T cells results in expression of latency genes and ultimately leads to T-cell activation, substantial proliferation, and profound alteration of cytokine expression. The pattern of cytokine production is strikingly skewed toward chemokines with roles in lymphocyte migration, demonstrating that EBV-2 has the ability to modulate normal T-cell processes. Collectively, these novel findings identify a previously unknown cell population potentially utilized by EBV-2 to establish latency and lay the foundation for further studies to elucidate the role of EBV in the pathogenesis of T-cell lymphoproliferative diseases.IMPORTANCEThe ability of EBV to infect T cells is made apparent by its association with a variety of T-cell lymphoproliferative disorders. However, studies to elucidate the pathogenic role of EBV in these diseases have been limited by the inability to conductin vitroT-cell infection experiments. Here, we report that EBV-2 isolates, compromised in the capacity to immortalize B cells, infect CD3+T cellsex vivoand propose a working model of EBV-2 persistence where alteration of T-cell functions resulting from EBV-2 infection enhances the establishment of latency in B cells. If indeed EBV-2 utilizes T cells to establish a persistent infection, this could provide one mechanism for the association of EBV with T-cell lymphomas. The novel finding that EBV-2 infects T cells in culture will provide a model to understand the role EBV plays in the development of T-cell lymphomas.
Herpes Simplex Virus 1 gN Partners with gM To Modulate the Viral Fusion Machinery
Authors: El Kasmi Imane , Lippé Roger 
Published: December 2014

ABSTRACT
Herpes simplex virus 1 (HSV-1) capsids are assembled in the nucleus, where they incorporate the viral genome. They then transit through the two nuclear membranes and are wrapped by a host-derived envelope. In the process, several HSV-1 proteins are targeted to the nuclear membranes, but their roles in viral nuclear egress are unclear. Among them, glycoprotein M (gM), a known modulator of virus-induced membrane fusion, is distributed on both the inner and outer nuclear membranes at the early stages of the infection, when no other viral glycoproteins are yet present there. Later on, it is found on perinuclear virions and ultimately redirected to the trans-Golgi network (TGN), where it cycles with the cell surface. In contrast, transfected gM is found only at the TGN and cell surface, hinting at an interaction with other viral proteins. Interestingly, many herpesvirus gM analogs interact with their gN counterparts, which typically alters their intracellular localization. To better understand how HSV-1 gM localization is regulated, we evaluated its ability to bind gN and discovered it does so in both transfected and infected cells, an interaction strongly weakened by the deletion of the gM amino terminus. Functionally, while gN had no impact on gM localization, gM redirected gN from the endoplasmic reticulum (ER) to the TGN. Most interestingly, gN overexpression stimulated the formation of syncytia in the context of an infection by a nonsyncytial strain, indicating that gM and gN not only physically but also functionally interact and that gN modulates gM's activity on membrane fusion.

IMPORTANCE
HSV-1 gM is an important modulator of virally induced cell-cell fusion and viral entry, a process that is likely finely modulated in time and space. Until now, little was known of the proteins that regulate gM's activity. In parallel, gM is found in various intracellular locations at different moments, ranging from nuclear membranes, perinuclear virions, the TGN, cell surface, and mature extracellular virions. In transfected cells, however, it is found only on the TGN and cell surface, hinting that its localization is modulated by other viral proteins. The present study identifies HSV-1 gN as a binding partner for gM, in agreement with their analogs in other herpesviruses, but most excitingly shows that gN modulates gM's impact on HSV-1-induced membrane fusion. These findings open up new research avenues on the viral fusion machinery.
Opposite trends in the consumption of manufactured and roll-your-own cigarettes in Spain (1991–2020)
Authors: Fu Marcela , Martínez-Sánchez Jose M , Clèries Ramon , Villalbí Joan R , Daynard Richard A , Connolly Gregory N , Fernández Esteve 
Published: December 2014

ObjectiveThe aim of this study is to describe trends in the consumption of manufactured and roll-your-own cigarettes between 1991 and 2012 in Spain, and to project these trends up to 2020.MethodsWe estimated daily consumption per capita during 1991–2012 using data on sales of manufactured cigarettes (20-packs) and rolling tobacco (kg) from the Tobacco Market Commission, and using data of the Spanish adult population from the National Statistics Institute. We considered different weights (0.5, 0.8 and 1 g) to compute the number of rolled cigarettes per capita. We computed the annual per cent of change and assessed possible changes in trends using joinpoint regression, and projected the consumption up to 2020 using Bayesian methods.ResultsDaily consumption per capita of manufactured cigarettes decreased on average by 3.0% per year in 1991–2012, from 7.6 to 3.8 units, with three trend changes. However, daily consumption per capita of roll-your-own cigarettes increased on average by 14.1% per year, from 0.07 to 0.92 units of 0.5 g, with unchanged trends. Together, daily consumption per capita decreased between 2.9% and 2.5%, depending on the weight of the roll-your-own cigarettes. Projections up to 2020 indicate a decrease of manufactured cigarettes (1.75 units per capita) but an increase of roll-your-own cigarettes (1.25 units per capita).ConclusionsWhile the consumption per capita of manufactured cigarettes has decreased in the past years in Spain, the consumption of roll-your-own cigarettes has increased at an annual rate around 14% over the past years. Whereas a net decrease in cigarette consumption is expected in the future, use of roll-your-own cigarettes will continue to increase.
A clinico-ethical framework for multidisciplinary review of medication in nursing homes
Authors: Baqir Wasim , Barrett Steven , Desai Nisha , Copeland Richard , Hughes Julian 
Published: December 2014

AbstractResidents in care homes are more likely to be prescribed multiple medicines yet often have little involvement in these prescribing decisions. Reviewing and stopping inappropriate medicines is not currently adopted across the health economy. This Health Foundation funded Shine project developed a pragmatic approach to optimising medicines in care homes while involving all residents in decision making.The pharmacist undertook a detailed medication review using primary care records. The results were discussed at a multidisciplinary team (MDT) meeting involving the care home nurse and the resident’s general practitioner (GP), with input from the local psychiatry of old age service (POAS) where appropriate.Suggestions for medicines which should be stopped, changed or started, and other interventions (eg monitoring) were discussed with the resident and/or their family.Over 12 months 422 residents were reviewed, and 1346 interventions were made in 91% of residents reviewed with 15 different types of interventions. The most common intervention (52.3%) was to stop medicines; 704 medicines stopped in 298 residents (70.6%). On average, 1.7 medicines were stopped for every resident reviewed (range zero to nine medicines; SD=1.7), with a 17.4% reduction in medicines prescribed (3602 medicines prescribed before and 2975 after review). The main reasons for stopping medicines were: no current indication (401 medicines; 57%), resident not wanting medicine after risks and benefits were explained (120 medicines; 17%), and safety concerns (42 medicines; 6%).The net annualised savings against the medicines budget were £77,703 or £184 per person reviewed. The cost of delivering the intervention was £32,670 (pharmacist, GP, POAS consultant, and care home nurse time) for 422 residents; for every £1 invested, £2.38 could be released from the medicines budget.This project demonstrated that a multidisciplinary medication review with a pharmacist, doctor, and care home nurse can safely reduce inappropriate medication in elderly care home residents.
Improving acute eye consultations in general practice: a practical approach
Authors: Teo Michelle Ai Ling 
Published: December 2014

AbstractThere is significant evidence that patients with acute eye symptoms are poorly assessed in primary care. There is a tendency to diagnose viral or bacterial conjunctivitis in any acutely red eye. This has led to delays in treatment and in some cases, permanent loss of sight.The aim of this project was to improve acute eye consultations within the Birchwood Medical Practice. The project focused on the "red flag" findings that would identify patients who require referral for same-day ophthalmology assessment.A retrospective baseline audit was carried out on all cases read-coded "conjunctivitis" over the period of one year. Initially, only 2.8% of consultations had documented all four findings.By considering the main factors that lead to poor eye assessments, two main areas for improvement were identified. These were education (reinforced with memory aids) and improving the availability of eye examination equipment within each consultation room. An "eye examination kit" was developed with the needs of the general practitioner in mind.The practice was re-audited six weeks following the intervention. Consultations where all four red flag findings were documented rose from 2.8% to 50%. This was found to be a statistically significant difference (p < 0.01). Pain was checked 63% of the time, compared to 26% prior to intervention. Visual acuity screening had increased to from 35% to 69%. Photophobia was the most significantly increased metric, from being documented only 6% of the time to now 63% of the time. Documentation of whether the symptoms were unilateral or bilateral had also increased from 88% to 94% of consultations.The initial audit indicated that general practitioners often diagnosed conjunctivitis without screening for symptoms of sight-threatening disease. However, it was clear from the results that the doctors had made a significant change to their approach to acute eye consultations. This shows that doctors are willing to make changes to their behaviour when given the right tools and information. It was felt that a first-hand understanding of the problem and an open discussion regarding the changes required was key to the success of this project.This project has shown that significant improvements can be achieved with practical and inexpensive interventions. Therefore, general practices throughout the UK are encouraged to adopt similar strategies to improve the identification of patients needing same-day Ophthalmology assessment.
Trends in the incidence and prevalence of cardiac pacemaker insertions in an ageing population
Authors: Bradshaw Pamela J , Stobie Paul , Knuiman Matthew W , Briffa Thomas G , Hobbs Michael S T 
Published: December 2014

ObjectivesTo determine contemporary population estimates of the prevalence of cardiac permanent pacemaker (PPM) insertions.MethodsA population-based observational study using linked hospital morbidity and death registry data from Western Australia (WA) to identify all incident cases of PPM insertion for adults aged 18 years or older. Prevalence rates were calculated by age and sex for the years 1995–2009 for the WA population.ResultsThere were 9782 PPMs inserted during 1995–2009. Prevalence rose across the study period, exceeding 1 in 50 among people aged 75 or older from 2005. This was underpinned by incidence rates which rose with age, being highest in those 85 years or older; over 500/100 000 for men throughout, and over 200/100 000 for women. Rates for patients over 75 were more than double the rates for those aged 65–74 years. Women were around 40% of cases overall. The use of dual-chamber and triple-chamber pacing increased across the study period. A cardiac resynchronisation defibrillator was implanted for 58% of patients treated with cardiac resynchronisation therapy.ConclusionsRates of insertion and prevalence of PPM continue to rise with the ageing population in WA. As equilibrium has probably not been reached, the demand for pacing services in similarly well-developed economies is likely to continue to grow.
The development of the Betton Farm Coral Bed within the Malton Oolite Member (Upper Jurassic, Middle Oxfordian) of the Scarborough District, North Yorkshire, UK
Authors: Wright John K. , Rawson Peter F. 
Published: December 2014

Summary

Betton Farm quarries contain, within a small area, a remarkable range of facies associated with the development of a Jurassic coral reef. A NW–SE-trending barrier reef protected the whole area containing the two quarries. Betton Farm North Quarry displays
Thamnasteria
patch reefs. These consist of scattered, 1 m high masses of colonial coral surrounded by reef debris that were situated behind the barrier within a large reef platform area. In Betton Farm South Quarry, bioclastic sand, consisting largely of coral and bivalve debris, interdigitates with the development of a small ribbon reef made up of the massive colonial coral
Thamnasteria
. This ribbon reef, only 3 to 4 m wide, sheltered a lagoonal area that accumulated lime mud and was colonized by large gastropods and burrowing bivalves. A fauna of reef-specializing bivalves and echinoids occupied these areas of patch/ribbon reef development, which were periodically swept by nutrient-bearing currents. Competition between the growth of the ribbon of
Thamnasteria
and the accumulation of fringing sediments saw periods when the
Thamnasteria
expanded over the coral-shell sand, and periods when the encroaching sediment cut back the growth of the
Thamnasteria
considerably. Considered initially to represent the Coral Rag Member of the Coralline Oolite Formation, the Betton Farm Coral Bed is now seen to represent localized coral reef developments situated near the base of the Malton Oolite Member, and growing upon antecedent bedrock features such as hard-ground surfaces that formed during pauses in sedimentation of the Malton Oolite.
Echinoid remains preserved in a Derbyshire screwstone (Mississippian, Visean, Brigantian), UK
Authors: Donovan Stephen K. , Lewis David N. , Bouman Roderick W. 
Published: December 2014

Summary

Fossil echinoids are moderately common in the Mississippian (Lower Carboniferous) limestones of the White Peak of Derbyshire and Staffordshire, but are invariably disarticulated; in consequence, they have received little attention. Herein, we record echinoid radioles (spines) from the chert of a Derbyshire screwstone for the first time. These specimens come from the Monsal Dale Limestone Formation (Brigantian, Visean) of Bradford Dale, near Youlgrave, Derbyshire. Radioles are slender, smooth, rounded in section, straight to slightly curved, but incomplete. We refer these specimens to
Lepidocidaris
sp., a genus previously recorded from the Preston area of Lancashire and Iowa, USA. The radioles are accumulated in a near-linear bedding plane assemblage, indicating a unidirectional current flow at the time of deposition.
PDGFRα and β Play Critical Roles in Mediating Foxq1-Driven Breast Cancer Stemness and Chemoresistance
Authors: Meng Fanyan , Speyer Cecilia L. , Zhang Bin , Zhao Yongzhong , Chen Wei , Gorski David H. , Miller Fred R. , Wu Guojun 
Published: December 2014

Abstract
Many epithelial–mesenchymal transition (EMT)–promoting transcription factors have been implicated in tumorigenesis and metastasis as well as chemoresistance of cancer. However, the underlying mechanisms mediating these processes are unclear. Here, we report that Foxq1, a forkhead box-containing transcription factor and EMT-inducing gene, promotes stemness traits and chemoresistance in mammary epithelial cells. Using an expression profiling assay, we identified Twist1, Zeb2, and PDGFRα and β as Foxq1 downstream targets. We further show that PDGFRα and β can be directly regulated by Foxq1 or indirectly regulated through the Foxq1/Twist1 axis. Knockdown of both PDGFRα and β results in more significant effects on reversing Foxq1-promoted oncogenesis in vitro and in vivo than knockdown of either PDGFRα or β alone. In addition, PDGFRβ is a more potent mediator of Foxq1-promoted stemness traits than PDGFRα. Finally, pharmacologic inhibition or gene silencing of PDGFRs sensitizes mammary epithelial cells to chemotherapeutic agents in vitro and in vivo. These findings collectively implicate PDGFRs as critical mediators of breast cancer oncogenesis and chemoresistance driven by Foxq1, with potential implications for developing novel therapeutic combinations to treat breast cancer. Cancer Res; 75(3); 584–93. ©2014 AACR.
Host miR155 Promotes Tumor Growth through a Myeloid-Derived Suppressor Cell–Dependent Mechanism
Authors: Chen Siqi , Wang Long , Fan Jie , Ye Cong , Dominguez Donye , Zhang Yi , Curiel Tyler J. , Fang Deyu , Kuzel Timothy M. , Zhang Bin 
Published: December 2014

Abstract
miR155 is a regulator of immune cell development and function that is generally thought to be immunostimulatory. However, we report here that genetic ablation of miR155 renders mice resistant to chemical carcinogenesis and the growth of several transplanted tumors, suggesting that miR155 functions in immunosuppression and tumor promotion. Host miR155 deficiency promoted overall antitumor immunity despite the finding of defective responses of miR155-deficient dendritic cells and antitumor T cells. Further analysis of immune cell compartments revealed that miR155 regulated the accumulation of functional myeloid-derived suppressive cells (MDSC) in the tumor microenvironment. Specifically, miR155 mediated MDSC suppressor activity through at least two mechanisms, including SOCS1 repression and a reduced ability to license the generation of CD4+Foxp3+ regulatory T cells. Importantly, we demonstrated that miR155 expression was required for MDSC to facilitate tumor growth. Thus, our results revealed a contextual function for miR155 in antitumor immunity, with a role in MDSC support that appears to dominate in tumor-bearing hosts. Overall, the balance of these cellular effects appears to be a root determinant of whether miR155 promotes or inhibits tumor growth. Cancer Res; 75(3); 519–31. ©2014 AACR.