bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD73-Generated Adenosine Restricts Lymphocyte Migration into Draining Lymph Nodes
Authors: Takedachi Masahide , Qu Dongfeng , Ebisuno Yukihiko , Oohara Hiroyuki , Joachims Michelle L. , McGee Stephanie T. , Maeda Emiko , McEver Rodger P. , Tanaka Toshiyuki , Miyasaka Masayuki , Murakami Shinya , Krahn Thomas , Blackburn Michael R. , Thompson Linda F. 
Published: April 2014

Abstract
After an inflammatory stimulus, lymphocyte migration into draining lymph nodes increases dramatically to facilitate the encounter of naive T cells with Ag-loaded dendritic cells. In this study, we show that CD73 (ecto-5′-nucleotidase) plays an important role in regulating this process. CD73 produces adenosine from AMP and is expressed on high endothelial venules (HEV) and subsets of lymphocytes. Cd73−/− mice have normal sized lymphoid organs in the steady state, but ∼1.5-fold larger draining lymph nodes and 2.5-fold increased rates of L-selectin-dependent lymphocyte migration from the blood through HEV compared with wild-type mice 24 h after LPS administration. Migration rates of cd73+/+ and cd73−/− lymphocytes into lymph nodes of wild-type mice are equal, suggesting that it is CD73 on HEV that regulates lymphocyte migration into draining lymph nodes. The A2B receptor is a likely target of CD73-generated adenosine, because it is the only adenosine receptor expressed on the HEV-like cell line KOP2.16 and it is up-regulated by TNF-α. Furthermore, increased lymphocyte migration into draining lymph nodes of cd73−/− mice is largely normalized by pretreatment with the selective A2B receptor agonist BAY 60-6583. Adenosine receptor signaling to restrict lymphocyte migration across HEV may be an important mechanism to control the magnitude of an inflammatory response.
IL-10 and Natural Regulatory T Cells: Two Independent Anti-Inflammatory Mechanisms in Herpes Simplex Virus-Induced Ocular Immunopathology
Authors: Sarangi Pranita P. , Sehrawat Sharvan , Suvas Susmit , Rouse Barry T. 
Published: April 2014

AbstractTwo prominent anti-inflammatory mechanisms involved in controlling HSV-1-induced corneal immunopathology (stromal keratitis or SK) are the production of the cytokine IL-10 and the activity of natural regulatory T cells (nTregs). It is not known whether, under in vivo conditions, IL-10 and nTregs influence the corneal pathology independently or in concert. In the current study using wild-type and IL-10−/− animals, we have assessed the activity of nTregs in the absence of IL-10 both under in vitro and in vivo conditions. The IL-10−/− animals depleted of nTregs before ocular infection showed more severe SK lesions as compared with the undepleted IL-10−/− animals. In addition, nTregs purified from naive WT and IL-10−/− animals were equally able to suppress the proliferation and the cytokine production from anti-CD3-stimulated CD4+CD25− T cells in vitro. Furthermore, intracellular cytokine staining results indicated that nonregulatory cells expressing B220 and CD25 markers were the major IL-10-producing cell types in the lymphoid tissues of HSV-infected mice. In contrast, in the infected corneas, cells with the CD11b+Gr1+ phenotype along with a minor population of Foxp3−CD4+ and a few F4/80+ cells produced IL-10. Our current investigations indicate that at least two independent anti-inflammatory mechanisms are involved in limiting the corneal lesions in SK, both of which may need to be modulated to control SK therapeutically.
NK but Not CD1-Restricted NKT Cells Facilitate Systemic Inflammation during Polymicrobial Intra-Abdominal Sepsis
Authors: Etogo Anthony O. , Nunez Jesus , Lin Cheng Y. , Toliver-Kinsky Tracy E. , Sherwood Edward R. 
Published: April 2014

Abstract
Evidence suggests that NK and NKT cells contribute to inflammation and mortality during septic shock caused by cecal ligation and puncture (CLP). However, the specific contributions of these cell types to the pathogenesis of CLP-induced septic shock have not been fully defined. The goal of the present study was to determine the mechanisms by which NK and NKT cells mediate the host response to CLP. Control, NK cell-deficient, and NKT cell-deficient mice underwent CLP. Survival, cytokine production, and bacterial clearance were measured. NK cell trafficking and interaction with myeloid cells was also studied. Results show that mice treated with anti-asialoGM1 (NK cell deficient) or anti-NK1.1 (NK/NKT cell deficient) show less systemic inflammation and have improved survival compared with IgG-treated controls. CD1 knockout mice (NKT cell deficient) did not demonstrate decreased cytokine production or improved survival compared with wild type mice. Trafficking studies show migration of NK cells from blood and spleen into the inflamed peritoneal cavity where they appear to facilitate the activation of peritoneal macrophages (F4-80+GR-1−) and F4-80+Gr-1+ myeloid cells. These findings indicate that NK but not CD1-restricted NKT cells contribute to acute CLP-induced inflammation. NK cells appear to mediate their proinflammatory functions during septic shock, in part, by migration into the peritoneal cavity and amplification of the proinflammatory activities of specific myeloid cell populations. These findings provide new insights into the mechanisms used by NK cells to facilitate acute inflammation during septic shock.
An Inducible Caspase 9 Safety Switch Can Halt Cell Therapy-Induced Autoimmune Disease
Authors: de Witte Moniek A. , Jorritsma Annelies , Swart Erwin , Straathof Karin C. , de Punder Karin , Haanen John B. A. G. , Rooney Cliona M. , Schumacher Ton N. M. 
Published: April 2014

AbstractTransfer of either allogeneic or genetically modified T cells as a therapy for malignancies can be accompanied by T cell-mediated tissue destruction. The introduction of an efficient “safety switch” can potentially be used to control the survival of adoptively transferred cell populations and as such reduce the risk of severe graft-vs-host disease. In this study, we have tested the value of an inducible caspase 9-based safety switch to halt an ongoing immune attack in a murine model for cell therapy-induced type I diabetes. The data obtained in this model indicate that self-reactive T cells expressing this conditional safety switch show unimpaired lymphopenia- and vaccine-induced proliferation and effector function in vivo, but can be specifically and rapidly eliminated upon triggering. These data provide strong support for the evaluation of this conditional safety switch in clinical trials of adoptive cell therapy.
A Novel Non-Synonymous Polymorphism (p.Arg240His) in C4b-Binding Protein Is Associated with Atypical Hemolytic Uremic Syndrome and Leads to Impaired Alternative Pathway Cofactor Activity
Authors: Blom Anna M. , Bergström Frida , Edey Matthew , Diaz-Torres Martha , Kavanagh David , Lampe Anne , Goodship Judith A. , Strain Lisa , Moghal Nadeem , McHugh Mary , Inward Carol , Tomson Charles , Frémeaux-Bacchi Véronique , Villoutreix Bruno O. , Goodship Timothy H. J. 
Published: April 2014

Abstract
Atypical hemolytic uremic syndrome (aHUS) is a disorder characterized by hemolytic anemia, thrombocytopenia, and acute renal failure. Mutations, polymorphisms, and copy number variation in complement factors and inhibitors are associated with aHUS. In this study, we report the first functional non-synonymous polymorphism in the complement inhibitor C4b-binding protein (C4BP) α-chain (c.719G&gt;A; p.Arg240His), which is associated with aHUS. This heterozygous change was found in 6/166 aHUS patients compared with 5/542 normal (χ2 = 6.021; p = 0.014), which was replicated in a second cohort of aHUS patients in which we found 5/170 carriers. The polymorphism does not decrease expression efficiency of C4BP. p.Arg240His is equally efficient as the wild type in binding and supporting degradation of C4BP but its ability to bind C3b and act as cofactor to its degradation both in fluid phase and on surfaces is impaired. This observation supports the hypothesis that dysregulation of the alternative pathway of complement is pivotal for aHUS. Three of the patients carry also mutations in membrane cofactor protein and factor H strengthening the hypothesis that individuals may carry multiple susceptibility factors with an additive effect on the risk of developing aHUS.
Natural Naive CD4+CD25+CD127low Regulatory T Cell (Treg) Development and Function Are Disturbed in Multiple Sclerosis Patients: Recovery of Memory Treg Homeostasis during Disease Progression
Authors: Venken Koen , Hellings Niels , Broekmans Tom , Hensen Karen , Rummens Jean-Luc , Stinissen Piet 
Published: April 2014

Abstract
Patients with relapsing-remitting multiple sclerosis (RR-MS) show a suboptimal CD4+CD25+ regulatory T cell (Treg) function, whereas no Treg alterations are observed in secondary progressive MS (SP-MS) patients. To clarify the difference in Treg activity between early and chronic disease stages in MS, we analyzed the functional capacity and homeostatic parameters of naive CD4+CD25+CD127lowCD45RA+ Tregs (nTregs) and their memory counterparts CD4+CD25+CD127lowCD45RO+ Tregs (mTregs) in untreated MS patients and healthy controls. Interestingly, whereas the suppressive capacity of FACS-sorted nTregs was impaired in both early and chronic MS patients, only the latter group showed a restored mTreg function. Consistent with this observation, chronic MS patients had increased numbers of mTregs as compared with age-matched early MS patients, whereas nTreg frequencies did not differ significantly. TCR excision circle numbers were reduced in nTregs of early MS patients, suggestive of a diminished nTreg thymic output. Moreover, a decreased number of CD31+ mTregs were observed in early vs chronic MS patients, indicating that inflammatory processes drive the homeostatic turnover of mTregs during the early disease stage. Additionally, early MS patients showed a more restricted nTreg and mTreg TCR BV gene profile as compared with healthy controls and chronic MS patients. Finally, analysis of IFN-β and glatiramer acetate-treated MS patients showed that these immunomodulatory drugs modify nTreg homeostasis. Taken together, this study provides strong evidence for a disturbed thymic nTreg development and function in MS patients. Moreover, memory Treg but not naive Treg homeostasis recovers during disease progression.
Decreased Expression of the Fractalkine Receptor CX3CR1 on Circulating Monocytes as New Feature of Sepsis-Induced Immunosuppression
Authors: Pachot Alexandre , Cazalis Marie-Angélique , Venet Fabienne , Turrel Fanny , Faudot Caroline , Voirin Nicolas , Diasparra Jennifer , Bourgoin Naïck , Poitevin Françoise , Mougin Bruno , Lepape Alain , Monneret Guillaume 
Published: April 2014

Abstract
Although it is known that septic shock rapidly induces immune dysfunctions, which contribute to the impaired clearance of microorganisms observed in patients, the mechanisms for this phenomenon remain incompletely understood. We recently observed, in a microarray study, an altered circulating leukocyte CX3CR1 mRNA expression associated with patients’ mortality. As monocytes play a central role in septic shock pathophysiology and express high levels of CX3CR1, we therefore further investigated the alteration of CX3CR1 expression and of its ligand fractalkine (CX3CL1) on those cells in this clinical condition. We observed that CX3CR1 expression (both mRNA and protein) was severely down-regulated in monocytes and consequently associated with a lack of functionality upon fractalkine challenge. Importantly, nonsurvivors presented with significantly sustained lower expression in comparison with survivors. This down-regulation was reproduced by incubation of cells from healthy individuals with LPS, whole bacteria (Escherichia coli and Staphylococcus aureus), and, to a lower extent, with corticosteroids–in accordance with the concept of LPS-induced monocyte deactivation. In addition, CX3CL1 serum concentrations were elevated in patients supporting the hypothesis of increased cleavage of the membrane-anchored form expressed by endothelial cells. As CX3CR1/CX3CL1 interaction preferentially mediates arrest and migration of proinflammatory cells, the present observations may contribute to patients’ inability to kill invading microorganisms. This could represent an important new feature of sepsis-induced immunosuppression.
Epidemiologic Comparison of Injured High School Basketball Athletes Reporting to Emergency Departments and the Athletic Training Setting
Authors: Fletcher Erica N. , McKenzie Lara B. , Comstock R. Dawn 
Published: April 2014

Context:
Basketball is a popular US high school sport with more than 1 million participants annually.

Objective:
To compare patterns of athletes with basketball-related injuries presenting to US emergency departments from 2005 through 2010 and the high school athletic training setting from the 2005–2011 seasons.

Design:
Descriptive epidemiology study.

Setting:
Data from the National Electronic Injury Surveillance System of the US Consumer Product Safety Commission and the High School Reporting Information Online database.

Main Outcome Measure(s):
Complex sample weights were used to calculate national estimates of basketball-related injuries for comparison.

Patients or Other Participants:
Adolescents from 13 to 19 years of age treated in US emergency departments for basketball-related injuries and athletes from 13 to 19 years of age from schools participating in High School Reporting Information Online who were injured while playing basketball.

Results:
Nationally, an estimated 1 514 957 (95% confidence interval = 1 337 441, 1 692 474) athletes with basketball-related injuries reported to the emergency department and 1 064 551 (95% confidence interval = 1 055 482, 1 073 620) presented to the athletic training setting. Overall, the most frequent injuries seen in the emergency department were lacerations and fractures (injury proportion ratios [IPRs] = 3.45 and 1.72, respectively), whereas those seen in the athletic training setting were more commonly concussions and strains/sprains (IPRs = 2.23 and 1.19, respectively; all P values &lt; .0001). Comparisons of body site and diagnosis combinations revealed additional differences. For example, athletes with lower leg fractures more often presented to the emergency department (IPR = 6.53), whereas those with hand fractures more frequently presented to the athletic training setting (IPR = 1.18; all P values &lt; .0001).

Conclusions:
Patterns of injury differed among high school basketball players presenting for treatment in the emergency department and the athletic training setting. Understanding differences specific to clinical settings is crucial to grasping the full epidemiologic and clinical picture of sport-related injuries. Certified athletic trainers play an important role in identifying, assessing, and treating athletes with sport-related injuries who might otherwise present to clinical settings with higher costs, such as the emergency department.
Serosurveillance of foot-and-mouth disease virus in selected livestock-wildlife interface areas of Tanzania
Authors: Mkama Mathias , Kasanga Christopher J. , Sallu Raphael , Ranga Ezekia , Yongolo Mmeta , Mulumba Misheck , Rweyemamu Mark , Wambura Philemon 
Published: April 2014

Foot-and-mouth disease (FMD) is caused by a virus of the genus Aphthorvirus of the family Picornaviridae. There is great scientific need for determining the transmission dynamics of FMD virus (FMDV) by drawing more attention to the livestock-wildlife interface areas. A variety of literature suggests that buffalo could serve as reservoir of FMDV in wildlife and cattle. However, many FMDV research studies conducted on experimentally infected cattle as carriers and groups of animal highly susceptible to FMDV (i.e. bovine calves) have shown lower chances of transmission of the virus between carriers and the susceptible groups. These findings underscore the importance of continued research on the role played by carrier animals on FMDV transmission dynamics under natural conditions. The aim of this research study was to determine FMDV infection status among buffalo and cattle herds in selected livestock-wildlife interface areas. The sampled areas included Mikumi, Mkomazi and Ruaha national parks, where a total of 330 buffalo and bovine sera samples were collected. Laboratory analysis of the samples was done through the NSP ELISA technique using the PrioCHECK® FMDV NS Kit for detection of antibodies directed against 3ABC non-structural proteins and confirming natural infections. Results showed that 76.3% of tested sera samples were positive for FMDV. However, serotyping of NSP ELISA seroreactors with LPBE is yet to be done. This information is important for further epidemiological studies towards developing effective FMD control strategies.
Rapid, sensitive and effective diagnostic tools for foot-and-mouth disease virus in Africa
Authors: Kasanga Christopher J. , Yamazaki Wataru , Mioulet Valerie , King Donald P. , Mulumba Misheck , Ranga Ezekia , Deve Jimis , Mundia Cornelius , Chikungwa Patrick , Joao Laureta , Wambura Philemon N. , Rweyemamu Mark M. 
Published: April 2014

Speed is paramount in the diagnosis of highly infectious diseases, such as foot-and-mouth disease (FMD), as well as for emerging diseases; however, simplicity is required if a test is to be deployed in the field. Recent developments in molecular biology have enabled the specific detection of FMD virus (FMDV) by reverse-transcription loop-mediated isothermal amplification (RT-LAMP), real-time reverse-transcription polymerase chain reaction (RT-qPCR) and sequencing. RT-LAMP enables amplification of the FMDV RNA-dependent RNA polymerase 3D(pol) gene at 63 °C (in the presence of a primer mixture and both reverse transcriptase and Bst DNA polymerase) for 1 h, whilst RT-qPCR amplifies the same gene in approximately 2 h 30 min. In this study, we compared the sensitivity and effectiveness of RT-LAMP against RT-qPCR for the detection of the FMDV 3D(pol) gene in 179 oesophageal-pharyngeal scraping samples (collected by probang) obtained from clinically healthy cattle and buffalo in Malawi, Mozambique and Tanzania in 2010. The FMDV detection rate was higher with RT-LAMP (30.2%; n = 54) than with RT-qPCR (17.3%; n = 31). All samples positive by RT-qPCR (Cq ≤ 32.0) were also positive for the RT-LAMP assay; and both assays proved to be highly specific for the FMDV target sequence. In addition, the VP1 sequences of 10 viruses isolated from positive samples corresponded to the respective FMDV serotypes and genotypes. Our findings indicate that the performance of RT-LAMP is superior to RT-qPCR. Accordingly, we consider this test to have great potential with regard to the specific detection and surveillance of infectious diseases of humans and animals in resource-compromised developing countries.
The changing landscape of rabies epidemiology and control
Authors: Cleaveland Sarah , Beyer Hawthorne , Hampson Katie , Haydon Daniel , Lankester Felix , Lembo Tiziana , Meslin Francois-Xavier , Morters Michelle , Mtema Zacharia , Sambo Maganga , Townsend Sunny 
Published: April 2014

Over the past 20 years, major progress has been made in our understanding of critical aspects of rabies epidemiology and control. This paper presents results of recent research, highlighting methodological advances that have been applied to burden of disease studies, rabies epidemiological modelling and rabies surveillance. These results contribute new insights and understanding with regard to the epidemiology of rabies and help to counteract misperceptions that currently hamper rabies control efforts in Africa. The conclusion of these analyses is that the elimination of canine rabies in Africa is feasible, even in wildlife-rich areas, through mass vaccination of domestic dogs and without the need for indiscriminate culling to reduce dog population density. Furthermore, the research provides valuable practical insights that support the operational planning and design of dog vaccination campaigns and rabies surveillance measures.
Preliminary investigation on presence of peste des petits ruminants in Dakawa, Mvomero district, Morogoro region, Tanzania
Authors: Kgotlele Tebogo , Kasanga Christopher J. , Kusiluka Lughano J.M. , Misinzo Gerald 
Published: April 2014

Peste des petits ruminants (PPR) is an acute viral disease of small ruminants characterised by the sudden onset of depression, fever, oculonasal discharges, sores in the mouth, foul-smelling diarrhoea and death. For many years, in Africa, the disease was mainly confined to West and Central Africa but it has now spread southwards to previously PPR-free countries including Tanzania, Democratic Republic of Congo and Angola. The disease was first reported in Tanzania in 2008 when it was confined to the Northern Zone districts bordering Kenya. Presence of the disease has also been confirmed in southern Tanzania especially Mtwara region. Recently, a suspected outbreak of PPR in Dakawa area, Mvomero district, Morogoro region was reported. Clinical samples (lungs, intestines, lymph nodes, whole blood and sera) from suspected goats (n = 8) and sheep (n = 1) were submitted to Sokoine University of Agriculture for analysis. Molecular diagnosis by amplification of the nucleoprotein gene and the fusion gene of PPR virus (PPRV) using PPRV specific primers was done. Five goats and the sheep were positive for PPRV after performing RT-PCR. To our knowledge, this is the first report confirming the presence of PPR in the Mvomero district of the Morogoro region, Tanzania. Hence, more efforts should be put in place to prevent the spread of PPR in Tanzania.
The changing landscape of public health in sub-Saharan Africa: Control and prevention of communicable diseases needs rethinking
Authors: Mboera Leonard E.G. , Mfinanga Sayoki G. , Karimuribo Esron D. , Rumisha Susan F. , Sindato Calvin 
Published: April 2014

In sub-Saharan Africa, communicable diseases (CDs) are the leading public health problems and major causes of morbidity and mortality. CDs result in significant individual suffering, disrupting daily life, threatening livelihoods and causing one-third of the years lost to illness or death worldwide. This paper aims to analyse the current strategies in the control and prevention of CDs in sub-Saharan Africa and proposes an ecohealth approach in relation to current changing epidemiological profiles. Whilst in recent years the burden of HIV and AIDS, tuberculosis and malaria have helped to mobilise large amounts of funding and expertise to help address them, many CDs, particularly those affecting the poor, have been neglected. People living in rural areas are also likely to be politically marginalised and living in degraded environments. They often lack assets, knowledge and opportunities to gain access to health care or protect themselves from infections. New diseases are also emerging at unprecedented rates and require attention. Many CDs are rooted in environmental and livelihood conditions and mediated by social and individual determinants. It is now increasingly recognised that a much broader, coordinated and multi-sectoral ecohealth approach is required to address CDs in sub-Saharan Africa. An ecohealth approach has been shown to be more robust in public health interventions than the traditional medical approach. The approach helps to generate an understanding of ecosystem factors that influence the emergence and spread of both old and new diseases, considers temporal and spatial dimensions of disease infection and allows systems thinking. In conclusion, establishing intersectoral and multisectoral linkages is important to facilitate joint efforts to address CDs at the national, district and community levels.