bluuebunny/crossref_metadata_2025_split huggingface dataset:
Islet-Specific Glucose-6-Phosphatase Catalytic Subunit-Related Protein-Reactive CD4+ T Cells in Human Subjects
Authors: Yang Junbao , Danke Nancy A. , Berger DeAnna , Reichstetter Sandra , Reijonen Helena , Greenbaum Carla , Pihoker Catherine , James Eddie A. , Kwok William W. 
Published: April 2014

Abstract
Islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) is recognized as a major autoantigen for autoimmune type 1 diabetes (T1D) in the NOD mouse model. This study was undertaken to examine CD4+ T cell responses toward IGRP in human subjects. The tetramer-guided epitope mapping approach was used to identify IGRP-specific CD4+ T cell epitopes. IGRP23–35 and IGRP247–259 were identified as DRA1*0101/DRB1*0401-restricted epitopes. IGRP13–25 and IGRP226–238 were identified as DRA1*0101/DRB1*0301-restricted epitopes. IGRP-specific tetramers were used to evaluate the prevalence of IGRP-reactive T cells in healthy and T1D subjects. More than 80% of subjects with either DRB1*0401 or DRB1*0301 haplotype have IGRP-specific CD4+ T cell responses for at least one IGRP epitope. IGRP-specific T cells from both healthy and T1D groups produce both γ-IFN and IL-10. DRA1*0101/DRB1*0401 IGRP247–259-restricted T cells also show cross-reactivity to an epitope derived from liver/kidney glucose-6-phosphatase. The detection of IGRP-reactive T cells in both type 1 diabetic subjects and healthy subjects and recent reports of other autoreactive T cells detected in healthy subjects underscore the prevalence of potentially autoreactive T cells in the peripheral immune system of the general population.
C5b-9 Terminal Complex Protects Oligodendrocytes from Apoptotic Cell Death by Inhibiting Caspase-8 Processing and Up-Regulating FLIP
Authors: Cudrici Cornelia , Niculescu Florin , Jensen Timothy , Zafranskaia Ekaterina , Fosbrink Matthew , Rus Violeta , Shin Moon L. , Rus Horea 
Published: April 2014

Abstract
Activation of the terminal complement cascade involving C5 to C9 proteins has a beneficial role for oligodendrocytes (OLG) in experimental allergic encephalomyelitis, an animal model of multiple sclerosis, by protecting them from apoptotic cell death. We have previously shown that sublytic C5b-9 complexes, through posttranslational regulation of Bad, inhibit the mitochondrial pathway of apoptosis induced by serum deprivation. In the present study, we examined the possible involvement of the caspase-8 and Fas pathway in OLG apoptosis and the role of C5b-9 in this process. In a serum-free defined medium, OLG undergo apoptosis and differentiation concomitantly. Under this condition, we found that caspase-8 processing was increased in association with Bid cleavage and markedly reduced expression of cellular FLIP long isoform protein. The caspase-8 inhibitor Z-IETD-FMK inhibited cell death associated with differentiation in a dose-dependent manner. Exposure to C5b-9 induced an inhibition of caspase-8 activation, Bid cleavage, and a significant increase in expression of cellular FLIP long isoform. These C5b-9 effects were reversed by PI3K inhibitor LY294002. C5b-9 also down-regulated the expression of FasL and the Fas-induced apoptosis. These data suggest that C5b-9 through PI3K signaling can rescue OLG from Fas-mediated apoptosis by regulating caspase-8 processing.
TLR6 Modulates First Trimester Trophoblast Responses to Peptidoglycan
Authors: Abrahams Vikki M. , Aldo Paulomi B. , Murphy Shaun P. , Visintin Irene , Koga Kaori , Wilson Gabriella , Romero Roberto , Sharma Surendra , Mor Gil 
Published: April 2014

Abstract
Intrauterine bacterial infections are a well-established cause of pregnancy complications. One key observation in a number of abnormal pregnancies is that placental apoptosis is significantly elevated. First trimester trophoblast cells are known to express TLR1 and TLR2 and to undergo apoptosis following exposure to Gram-positive bacterial peptidoglycan (PDG). Thus, the objectives of this study were to determine whether PDG-induced pregnancy complications are associated with placental apoptosis and to characterize the cellular mechanisms involved. We have demonstrated, using an animal model, that delivery of PDG to pregnant mice early in gestation resulted in highly elevated placental apoptosis, evidenced by trophoblast M-30 and active caspase 3 immunostaining. Using an in vitro model of human first trimester trophoblasts, apoptosis induced by PDG was found to be mediated by both TLR1 and TLR2 and that this could be blocked by the presence of TLR6. Furthermore, in the presence of TLR6, exposure to PDG resulted in trophoblast NF-κB activation and triggered these cells to secrete IL-8 and IL-6. The findings of this study suggest that a Gram-positive bacterial infection, through TLR2 and TLR1, may directly promote the elevated trophoblast cell death and that this may be the underlying mechanism of pregnancy complications, such as preterm delivery. Furthermore, the expression of TLR6 may be a key factor in determining whether the response to PDG would be apoptosis or inflammation.
A DNA Vaccine Prime Followed by a Liposome-Encapsulated Protein Boost Confers Enhanced Mucosal Immune Responses and Protection
Authors: Yang Kejian , Whalen Barbara J. , Tirabassi Rebecca S. , Selin Liisa K. , Levchenko Tatyana S. , Torchilin Vladimir P. , Kislauskis Edward H. , Guberski Dennis L. 
Published: April 2014

Abstract
A variety of DNA vaccine prime and recombinant viral boost immunization strategies have been developed to enhance immune responses in humans, but inherent limitations to these strategies exist. There is still an overwhelming need to develop safe and effective approaches that raise broad humoral and T cell-mediated immune responses systemically and on mucosal surfaces. We have developed a novel mucosal immunization regimen that precludes the use of viral vectors yet induces potent T cell responses. Using hepatitis B surface Ag (HBsAg), we observed that vaccination of BALB/c mice with an i.m. HBsAg-DNA vaccine prime followed by an intranasal boost with HBsAg protein encapsulated in biologically inert liposomes enhanced humoral and T cell immune responses, particularly on mucosal surfaces. Intranasal live virus challenge with a recombinant vaccinia virus expressing HBsAg revealed a correlation between T cell immune responses and protection of immunized mice. A shortened immunization protocol was developed that was successful in both adult and neonatal mice. These results support the conclusion that this new approach is capable of generating a Th-type-1-biased, broad spectrum immune response, specifically at mucosal surfaces. The success of this design may provide a safe and effective vaccination alternative for human use.
Generation of Anaphylatoxins by Human β-Tryptase from C3, C4, and C5
Authors: Fukuoka Yoshihiro , Xia Han-Zhang , Sanchez-Muñoz Laura B. , Dellinger Anthony L. , Escribano Luis , Schwartz Lawrence B. 
Published: April 2014

AbstractBoth mast cells and complement participate in innate and acquired immunity. The current study examines whether β-tryptase, the major protease of human mast cells, can directly generate bioactive complement anaphylatoxins. Important variables included pH, monomeric vs tetrameric forms of β-tryptase, and the β-tryptase-activating polyanion. The B12 mAb was used to stabilize β-tryptase in its monomeric form. C3a and C4a were best generated from C3 and C4, respectively, by monomeric β-tryptase in the presence of low molecular weight dextran sulfate or heparin at acidic pH. High molecular weight polyanions increased degradation of these anaphylatoxins. C5a was optimally generated from C5 at acidic pH by β-tryptase monomers in the presence of high molecular weight dextran sulfate and heparin polyanions, but also was produced by β-tryptase tetramers under these conditions. Mass spectrometry verified that the molecular mass of each anaphylatoxin was correct. Both β-tryptase-generated C5a and C3a (but not C4a) were potent activators of human skin mast cells. These complement anaphylatoxins also could be generated by β-tryptase in releasates of activated skin mast cells. Of further biologic interest, β-tryptase also generated C3a from C3 in human plasma at acidic pH. These results suggest β-tryptase might generate complement anaphylatoxins in vivo at sites of inflammation, such as the airway of active asthma patients where the pH is acidic and where elevated levels of β-tryptase and complement anaphylatoxins are detected.
Cytokine Secretion Depends on Galα(1,3)Gal Expression in a Pig-to-Human Whole Blood Model
Authors: Sæthre Marit , Schneider Mårten K. J. , Lambris John D. , Magotti Paola , Haraldsen Guttorm , Seebach Jörg D. , Mollnes Tom E. 
Published: April 2014

Abstract
Transplants from α1,3-galactosyltransferase (Gal) gene-knockout pigs to nonhuman primates are largely protected from hyperacute but not acute humoral xenograft rejection. The present study investigates the role of Gal in cytokine responses using a novel pig-to-human whole blood in vitro model, developed for species-specific analysis of porcine and human cytokines. Porcine (n = 7) and human (n = 27) cytokines were measured using ELISA or multiplex technology, respectively. Porcine aortic endothelial cells from control (Gal+/+) and Gal-deficient (Gal−/−) pigs were incubated with human lepirudin anticoagulated whole blood from healthy donors. E-selectin expression was measured by flow cytometry. The C3 inhibitor compstatin and a C5aR antagonist were used to study the role of complement. Cytokine species specificity was documented, enabling detection of 2 of 7 porcine cytokines and 13 of 27 human cytokines in one single sample. Gal+/+ porcine aortic endothelial cells incubated with human whole blood showed a marked complement C5b-9 dependent up-regulation of E-selectin and secretion of porcine IL-6 and IL-8. In contrast, Gal−/− cells responded with E-selectin and cytokine expression which was so weak that the role of complement could not be determined. Human IL-6, IL-8, IFN-γ, MIP-1α, MIP-1β, eotaxin, and RANTES were detected in the Gal+/+ system, but virtually no responses were seen in the Gal−/− system (p = 0.03). The increase in human cytokine release was largely complement dependent and, in contrast to the porcine response, mediated through C5a. Species-specific analysis of cytokine release revealed a marked, complement-dependent response when Gal+/+ pig cells were incubated with human whole blood, compared with Gal−/− cells which induced virtually no cytokine release.
Prevalence of bovine tuberculosis in a dairy cattle farm and a research farm in Ghana
Authors: Asante-Poku Adwoa , Aning Kwame G. , Boi-Kikimoto Bashiru , Yeboah-Manu Dorothy 
Published: April 2014

The aim of the study was to estimate the prevalence of bovine tuberculosis (BTB) and to identify the mycobacterial species causing BTB in a dairy farm and research farm. Six hundred and eighty-five cattle were screened for BTB by using the Comparative intradermal tuberculin test (CTT). Positive reactors were slaughtered and carcasses were taken for isolation of mycobacterial species. This was followed by speciation of isolates using both standard conventional and molecular assays. Seventeen of the cattle were positive by CTT, giving a crude BTB prevalence of 2.48% among cattle from the two farms. Six of the 17 samples (35.30%) yielded positive acid-fast bacilli cultures and three of the isolates were identified as Mycobacterium tuberculosis complex (MTBC), which were sub-divided into two Mycobacterium tuberculosis sensu scrito (Mtb) and one Mycobacterium africanum; the remaining three were Mycobacterium other than tuberculoisis (MOTT). Spoligotyping further characterised the two Mtb isolates as Ghana (spoligotype Data Base 4 number 53) and Latin American Mediterranean (LAM), whilst spoligotyping and Single Nucleotide Polymorphism (SNP) analysis typed the M. africanum as West African 1. Microseq 500 analysis identified two of the MOTT as Mycobacterium flavescens and Mycobacterium Moriokaense respectively, whilst the remaining one could not be identified. This study observed the prevalence of bovine TB among cattle from two farms in Ghana as 2.48% and confirms the public health importance of M. africanum as a pathogen in Ghana.
The quest for One Health: Human Resource training aspects
Authors: Kiwara Angwara , Semakafu Ave-Maria , Frumence Gasto 
Published: April 2014

Appropriately trained Human Resources for Health (HRH) are key inputs into One Health. ‘… more than 50% of all infectious diseases of humans originate from animals and that, of the emerging diseases about 75% could be traced back to animal origin’ (Rweyemamu et al. 2006). A comprehensive understanding of the social determinants of health, through an appropriate training model for HRH, is a key input. This study aimed to explore if human and veterinary medical schools were using such a model or providing time for this model in their curricula. Specific objectives were to: determine the time that human and veterinary medical schools’ curricula provide for subjects or courses related to the social determinants of health; analyse the curricula contents to establish how they relate to the social determinants of health; and explore how a bio-medical model may influence the graduates’ understanding and practice of One Health. A review of human and veterinary graduate-level medical schools’ curricula in East Africa was performed in April 2013 and May 2013. The findings were: in the curricula, SDH contents for knowledge enhancement about One Health are minimal and that teaching is Germ Theory model-driven and partisan. Out of the total training time for physicians and veterinarians, less than 10% was provided for the social determinants of health-related courses. In conclusion, the curricula and training times provided are inadequate for graduates to fully understand the social determinants of health and their role in One Health. Furthermore, the Germ Theory model that has been adopted addresses secondary causes and is inappropriate. There is a need for more in-depth model. This article suggests that a vicious cycle of ill-health model must be taught.
Investigation of foot-and-mouth disease outbreaks in the Mbala and Kazungula districts of Zambia
Authors: Banda Frank , Kasanga Christopher J. , Sallu Raphael , Sinkala Yona , Sinkombe Tingiya W. , Mulumba Misheck , Rweyemamu Mark M. , Wambura Philemon N. 
Published: April 2014

Foot-and-mouth disease (FMD) is an acute, highly contagious viral infection of domestic and wild cloven-hoofed animals. It is known to be endemic in Zambia, with periodic outbreaks occurring in different geographical areas of the country. This study was conducted to investigate the presence of FMD virus (FMDV) in reported FMD-suspected cases in cattle from the Kazungula and Mbala districts of Zambia. Sixty epithelial tissues or oesophageal-pharyngeal (OP) scrapings (probang samples) were collected from Mbala (n = 51) and Kazungula (n = 9) and examined for FMDV. The FMDV viral RNA and serotypes were examined by realtime reverse transcription polymerase chain reaction (qRT-PCR) and antigen Enzyme- linked immunosorbent assay (ELISA), respectively. Twenty-two samples (36.7%) were positive for the FMDV genome by qRT-PCR with Cycle threshold (Ct) values ranging from 13 to 31. The FMDV-positive samples from epithelial tissues showed relatively higher Ct values compared to those obtained from OP scrapings, irrespective of geographical location. Forty percent (40%; n = 4) of epithelial tissues from Mbala were serotyped into SAT 2 serotype by antigen ELISA. Kazungula samples were serotyped into SAT 1. These findings indicated that Mbala and Kazungula districts had FMD outbreaks in 2012 that were ascribed to at least FMDV serotype SAT 2 and SAT 1 field strains. Furthermore, regular interaction between buffalos from the Mosi-o Tunya Park and domestic animals from surrounding areas could contribute to the occurrence of regular FMD outbreaks in Kazungula, whilst the uncontrolled animal movements across borders between Mbala and Nsumbawanga could be responsible for disease outbreaks in Mbala. In-depth molecular biological studies, including sequencing and phylogeny of the viruses, should be conducted to elucidate the complex epidemiology of FMD in Zambia, thereby providing valuable information needed for the rational control strategy of FMD in Zambia and neighbouring countries.
Drivers of disease emergence and spread: Is wildlife to blame?
Authors: Kock Richard 
Published: April 2014

The global focus on wildlife as a major contributor to emerging pathogens and infectious diseases (EIDs) in humans and domestic animals is not based on field, experimental or dedicated research, but mostly on limited surveys of literature, opinion and the assumption that biodiversity harbours pathogens. The perceived and direct impacts of wildlife, from being a reservoir of certain human and livestock pathogens and as a risk to health, are frequently overstated when compared to the Global burden of disease statistics available from WHO, OIE and FAO. However organisms that evolve in wildlife species can and do spill-over into human landscapes and humans and domestic animal population and, where these organisms adapt to surviving and spreading amongst livestock and humans, these emerging infections can have significant consequences. Drivers for the spill-over of pathogens or evolution of organisms from wildlife reservoirs to become pathogens of humans and domestic animals are varied but almost without exception poorly researched. The changing demographics, spatial distribution and movements, associated landscape modifications (especially agricultural) and behavioural changes involving human and domestic animal populations are probably the core drivers of the apparent increasing trend in emergence of new pathogens and infectious diseases over recent decades.
ADVANZ: Establishing a Pan-African platform for neglected zoonotic disease control through a One Health approach
Authors: Saarnak Christopher F.L. , Johansen Maria V. , Mukaratirwa Samson 
Published: April 2014

Advocacy for neglected zoonotic diseases (ADVANZ) is a One Health Neglected Zoonotic Diseases (NZDs) project, funded by the European Commission through its 7th framework programme. The initiative aims at persuading decision makers and empowering stakeholders at local, regional, and international levels towards a coordinated fight against NZDs. ADVANZ is establishing an African platform to share experiences in the prevention and control of NZDs. The platform will compile and package existing knowledge or data on NZDs and generate evidence-based algorithms for improving surveillance and control with the ultimate aim of eliminating and eradicating these diseases. The platform will serve as a forum for African and international stakeholders, as well as existing One Health and NZD networks and harness and consolidate their efforts in the control and prevention of NZDs. The platform had its first meeting in Johannesburg, South Africa in March 2013.
Technical Efficiency of Sugar Cane (Saccharum officinarum) Production in Niger State, Nigeria.
Authors: Omotesho OA , Muhammad-Lawal A , Olatinwo KB , Adenuga AH , Bello AJ 
Published: April 2014

Sugar cane (Saccharum officinarum) is grown by thousands of local farmers in Nigeria, yet the level of production has not kept pace with the level of consumption. This study was therefore carried out to examine the efficiency of sugar cane production in Niger State, Nigeria. The study sample comprised of 105 sugar cane producers selected across three Local Government Areas in Niger State. Major tools of analysis used for the study were the gross margin analysis and the stochastic frontiers model. Results of the study showed that a gross margin of N401606/ha was realized per farmer from sugar cane production. Also, the result of the stochastic frontier model shows that experience of the farmer and household size had significant effect on the efficiency of sugar cane production. A mean technical efficiency of 69.5% was obtained from the Maximum Likelihood Estimation (MLE) of the Stochastic Production Frontier. The study recommends that the government should make inputs such as fertilizers and sugarcane cuttings available to farmers at a subsidized rate. Also, given the significant and negative relationship of herbicide usage and farmers’ output, it is important that the government organize trainings on the appropriate use of agricultural inputs for farmers to ensure increased production and profitabilityKey words: Efficiency; Extension Services; Gross Margin; Niger State; Stochastic Production Frontier; Sugar cane
Survey Results: Characterization of Direct Thrombin Inhibitor Use in Pediatric Patients
Authors: Oschman Alexandra 
Published: April 2014

OBJECTIVES
The objective of this multicenter survey is to characterize the use of direct thrombin inhibitors (DTIs) in the pediatric population. The results of this survey may be used to design a prospective multicenter study with the ultimate goal of developing a dosing/titration recommendation for the use of DTIs in the pediatric population.

METHODS
This is a multicenter, descriptive study to survey hospitals around the country regarding the use of DTIs (argatroban, bivalirudin, and lepirudin) in the pediatic population. Institutional review board approval was obtained. The survey consisted of 42 questions and was designed utilizing Survey Monkey. The survey was emailed to members of the Pediatric Pharmacy Advocacy Group. Listserv members who responded to the survey within 4 weeks of when the survey was emailed were included in the study. Descriptive statistics were performed utilizing Microsoft Excel 2007.

RESULTS
Responses were obtained from 56 institutions from 29 states in the United States. Multiple agents are available on formulary with argatroban being the most common (~80%). The large majority of institutions (41.1%) utilize DTIs 2 to 4 times a year with an additional 33.9% utilizing them less than twice a year. There is no consistent approach to dosing and titration amongst pediatric institutions.

CONCLUSIONS
There are a wide variety of methods used by pediatric institutions with regard to dosing and titration of DTIs. Recently published prospective studies and package insert updates should help guide practitioners toward a more consistent approach to dosing of these high-risk medications.