bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene expression modulation and the molecular mechanisms involved in Nelfinavir resistance in Leishmania donovani axenic amastigotes
Authors: Kumar Pranav , Lodge Robert , Raymond Frédéric , Ritt Jean‐François , Jalaguier Pascal , Corbeil Jacques , Ouellette Marc , Tremblay Michel J. 
Published: June 2013

SummaryDrug resistance is a major public health challenge in leishmaniasis chemotherapy, particularly in the case of emerging Leishmania/HIV‐1 co‐infections. We have delineated the mechanism of cell death induced by the HIV‐1 protease inhibitor, Nelfinavir, in the Leishmania parasite. In order to further study Nelfinavir–Leishmania interactions, we selected Nelfinavir‐resistant axenic amastigotes in vitro and characterized them. RNA expression profiling analyses and comparative genomic hybridizations of closely related Leishmania species were used as a screening tool to compare Nelfinavir‐resistant and ‐sensitive parasites in order to identify candidate genes involved in drug resistance. Microarray analyses of Nelfinavir‐resistant and ‐sensitive Leishmania amastigotes suggest that parasites regulate mRNA levels either by modulating gene copy numbers through chromosome aneuploidy, or gene deletion/duplication by homologous recombination. Interestingly, supernumerary chromosomes 6 and 11 in the resistant parasites lead to upregulation of the ABC class of transporters. Transporter assays using radiolabelled Nelfinavir suggest a greater drug accumulation in the resistant parasites and in a time‐dependent manner. Furthermore, high‐resolution electron microscopy and measurements of intracellular polyphosphate levels showed an increased number of cytoplasmic vesicular compartments known as acidocalcisomes in Nelfinavir‐resistant parasites. Together these results suggest that Nelfinavir is rapidly and dramatically sequestered in drug‐induced intracellular vesicles.
A common pathway for O‐linked protein‐glycosylation and synthesis of capsule in Acinetobacter baumannii
Authors: Lees‐Miller Robert G. , Iwashkiw Jeremy A. , Scott Nichollas E. , Seper Andrea , Vinogradov Evgeny , Schild Stefan , Feldman Mario F. 
Published: June 2013

SummaryMulti‐drug resistant strains of Acinetobacter baumannii are increasingly being isolated in hospitals worldwide. Among the virulence factors identified in this bacterium there is a general O‐glycosylation system that appears to be important for biofilm formation and virulence, and the capsular polysaccharide, which is essential for resistance to complement killing. In this work, we identified a locus that is responsible for the synthesis of the O‐pentasaccharide found on the glycoproteins. Besides the enzymes required for the assembly of the glycan, additional proteins typically involved in polymerization and transport of capsule were identified within or adjacently to the locus. Mutagenesis of PglC, the initiating glycosyltransferase prevented the synthesis of both glycoproteins and capsule, resulting in abnormal biofilm structures and attenuated virulence in mice. These results, together with the structural analysis of A. baumannii 17978 capsular polysaccharide via NMR, demonstrated that the pentasaccharides that decorate the glycoproteins are also the building blocks for capsule biosynthesis. Two linked subunits, but not longer glycan chains, were detected on proteins via MS. The discovery of a bifurcated pathway for O‐glycosylation and capsule synthesis not only provides insight into the biology of A. baumannii but also identifies potential novel candidates for intervention against this emerging pathogen.
Inflation and Inflation Expectations inSouthAfrica: an Attempt at Explanation
Authors: Kabundi Alain , Schaling Eric 
Published: June 2013

AbstractThis paper examines the relationship between inflation and inflation expectations inSouthAfrica. We use inflation expectations derived from the quarterly surveys conducted by the Bureau of Economic Research from 2001Q1 to 2011Q4 . Using these data, we estimate the model assuming that private sector expectations are a linear function of the inflation target and lagged inflation. The results indicate that economic agents' expectations largely depend on lagged inflation. This suggests that theSouthAfrican Reserve Bank (SARB) has not been successful in anchoring expectations of the private sector since the adoption of the inflation targeting (IT) regime in 2000. We also find evidence indicating that theSARB's implicit inflation target lies above the upper bound of the officialITband. Finally, it appears that theSARBhas been more concerned about output stabilisation than inflation stabilisation.
Profile of suicide in rural Cameroon: are health systems doing enough?
Authors: Keugoung Basile , Kongnyu Emmanuel Tabah , Meli Jean , Criel Bart 
Published: June 2013

AbstractObjectivesTo describe the characteristics of suicide and assess the capacity of health services at the district level in Cameroon to deliver quality mental health care.MethodsThe study covered the period between 1999 and 2008 and was carried out in Guidiguis health district which had a population of 145 700 inhabitants in 2008. Data collection was based on psychological autopsy methods. To collect data, we used documentary review of medical archives, semi‐structured interviews of relatives of suicide completers, a focus group discussion of health committee members and a survey to consulting nurses working at the primary health care level.ResultsForty‐seven suicides were recorded from 1999 to 2008: 37 (78.7%) males and 10 (21.3%) females, yielding rates of reported suicides that ranged from 0.89 to 6.54 per 100 000 inhabitants. The most frequently used suicide method was the ingestion of toxic agricultural chemicals (in 76.6% of cases). According to the relatives, the suicides were due to an ongoing chronic illness (31.9%), sexual and marital conflicts (25.5%), witchcraft (14.9%), financial problems (8.5%) or unknown cause (25.5%). In 25 (53.2%) cases, suicide victims exhibited symptoms suggestive of a mental disorder but only six of the suicide committers who presented behavioural symptoms sought health care. Only two of the 15 consulting nurses were able to cite at least three symptoms of depression and were aware that depression can lead to suicide. All of the nurses acknowledged that they had never received any specific training or supervision in mental health care.ConclusionsSuicides are not a rare event in rural settings in Cameroon. The health district capacity to provide quality mental care is almost insignificant. The integration of minimal mental health care services at the community and primary health care levels should be considered a priority in sub‐Saharan Africa.
Small fields output factors measurements and correction factors determination for several detectors for a CyberKnife® and linear accelerators equipped with microMLC and circular cones
Authors: Bassinet C. , Huet C. , Derreumaux S. , Brunet G. , Chéa M. , Baumann M. , Lacornerie T. , Gaudaire‐Josset S. , Trompier F. , Roch P. , Boisserie G. , Clairand I. 
Published: June 2013

Purpose:The use of small photon fields is now an established practice in stereotactic radiosurgery and radiotherapy. However, due to a lack of lateral electron equilibrium and high dose gradients, it is difficult to accurately measure the dosimetric quantities required for the commissioning of such systems. Moreover, there is still no metrological dosimetric reference for this kind of beam today. In this context, the first objective of this work was to determine and to compare small fields output factors (OF) measured with different types of active detectors and passive dosimeters for three types of facilities: a CyberKnife® system, a dedicated medical linear accelerator (Novalis) equipped with m3 microMLC and circular cones, and an adaptive medical linear accelerator (Clinac 2100) equipped with an additional m3 microMLC. The second one was to determine the correction factors introduced in a recently proposed small field dosimetry formalism for different active detectors.Methods:Small field sizes were defined either by microMLC down to 6 × 6 mm2 or by circular cones down to 4 mm in diameter. OF measurements were performed with several commercially available active detectors dedicated to measurements in small fields (high resolution diodes: IBA SFD, Sun Nuclear EDGE, PTW 60016, PTW 60017; ionizing chambers: PTW 31014 PinPoint chamber, PTW 31018 microLion liquid chamber, and PTW 60003 natural diamond). Two types of passive dosimeters were used: LiF microcubes and EBT2 radiochromic films.Results:Significant differences between the results obtained by several dosimetric systems were observed, particularly for the smallest field size for which the difference in the measured OF reaches more than 20%. For passive dosimeters, an excellent agreement was observed (better than 2%) between EBT2 and LiF microcubes for all OF measurements. Moreover, it has been shown that these passive dosimeters do not require correction factors and can then be used as reference dosimeters. Correction factors for the active detectors have then been determined from the mean experimental OF measured by the passive dosimeters.Conclusions:Four sets of correction factors needed to apply the new small field dosimetry formalism are provided for several active detectors. A protocol for small photon beams OF determination based on passive dosimeters measurements has been recently proposed to French radiotherapy treatment centers.
Development and Validation of an Assay To Detect Porcine Reproductive and Respiratory Syndrome Virus-Specific Neutralizing Antibody Titers in Pig Oral Fluid Samples
Authors: Ouyang Kang , Binjawadagi Basavaraj , Kittawornrat Apisit , Olsen Chris , Hiremath Jagadish , Elkalifa Nadia , Schleappi Rose , Wu Jianmin , Zimmerman Jeffrey , Renukaradhya Gourapura J. 
Published: June 2013

ABSTRACTPorcine reproductive and respiratory syndrome virus (PRRSV)-specific neutralizing antibodies (NA) are important for clearing the virus. Pen-based pig oral fluid samples for disease surveillance are gaining in importance due to the ease of collection and low cost. The aim of this study was to develop a PRRSV-specific NA assay to determine NA titers in pig oral fluid samples. At first, we standardized the PRRSV NA assay using pen-based pig oral fluid samples collected over a period of 3 months from a herd of swine that received a PRRSV modified live vaccine (PRRS-MLV), and we also used oral fluid and serum samples collected from individual boars that were vaccinated with PRRS-MLV or infected with a virulent PRRSV strain. Our results suggest that a PRRSV NA titer of >8 in oral fluid samples is virus specific and can be detected beginning at 28 days after vaccination or infection. To validate the assay, we used 104 pen-based pig oral fluid and five representative serum samples from each pen of unknown history, as well as 100 serum samples from repeatedly vaccinated sows and oral fluid samples of their respective litters belonging to four different swine-breeding farms. Our results demonstrated that PRRSV NA titers in oral fluid samples are correlated with serum sample titers, and maternally derived PRRSV-specific NA titers could be detected in litters at the time of weaning. In conclusion, we have standardized and validated the pig oral fluid-based PRRSV NA assay, which has 94.3% specificity and 90.5% repeatability. The assay can be used to monitor herd immunity against PRRSV in vaccinated and infected herds of swine.
Geographical Differences Associated with Single-Nucleotide Polymorphisms (SNPs) in Nine Gene Targets among Resistant Clinical Isolates of Mycobacterium tuberculosis
Authors: Hoshide Matt , Qian Lishi , Rodrigues Camilla , Warren Rob , Victor Tommie , Evasco Henry B. , Tupasi Thelma , Crudu Valeriu , Douglas James T. 
Published: June 2013

ABSTRACT

Alternative diagnostic methods, such as sequence-based techniques, are necessary for increasing the proportion of tuberculosis cases tested for drug resistance. Despite the abundance of data on drug resistance, isolates can display phenotypic resistance but lack any distinguishable markers. Furthermore, because resistance-conferring mutations develop under antibiotic pressure, different drug regimens could favor unique single-nucleotide polymorphisms (SNPs) in different geographical regions. A total of 407 isolates were collected from four geographical regions with a high prevalence of drug-resistant tuberculosis (India, Moldova, the Philippines, and South Africa). The “hot spot” or promoter sequences of nine genes (
rpoB
,
gyrA
,
gyrB
,
katG
,
inhA
promoter,
ahpC
promoter,
eis
promoter,
rrs
, and
tlyA
) associated with resistance to four types of antibiotics (rifampin, isoniazid, fluoroquinolones, and aminoglycosides) were analyzed for markers. Four genes contributed largely to resistance (
rpoB
,
gyrA
,
rrs
, and
katG
), two genes contributed moderately to resistance (the
eis
and
inhA
promoters), and three genes contributed little or no resistance (
gyrB
,
tlyA
, and the
ahpC
promoter) in clinical isolates. Several geographical differences were found, including a double mutation in
rpoB
found in 37.1% of isolates from South Africa, the C→T mutation at position −12 of the
eis
promoter found exclusively in 60.6% of isolates from Moldova, and the G→A mutation at position −46 of the
ahpC
promoter found only in India. These differences in polymorphism frequencies emphasize the uniqueness of isolates found in different geographical regions. The inclusion of several genes provided a moderate increase in sensitivity, and elimination of the examination of other genes might increase efficiency.
First Report of Liver Abscess Caused by Salmonella enterica Serovar Dublin
Authors: Qu Fen , Fan Zhenping , Cui Enbo , Zhang Wenjin , Bao Chunmei , Chen Suming , Mao Yuanli , Zhou Dongsheng 
Published: June 2013

ABSTRACT

This is the first reported case of liver abscess attributable to
Salmonella
serovar Dublin infection and also the fourth case of
Salmonella
liver abscess complicated with hepatocellular carcinoma reported since 1990. Drainage combined with intravenous antibiotics resulted in improvement, but recovery regressed again. Subsequent hepatic left lobectomy led to full recovery.
New Tetratrichomonas Species in Two Patients with Pleural Empyema
Authors: Lopez-Escamilla Eduardo , Sanchez-Aguillon Fabiola , Alatorre-Fernandez Cynthia Pamela , Aguilar-Zapata Daniel , Arroyo-Escalante Sara , Arellano Teresa , Moncada-Barron David , Romero-Valdovinos Mirza , Martinez-Hernandez Fernando , Rodriguez-Zulueta Patricia , Maravilla Pablo 
Published: June 2013

ABSTRACT

Two unusual occurrences of pleural trichomonosis due to a new
Tetratrichomonas
species previously reported but not named were confirmed. In one patient,
Trichomonas tenax
and a
Tetratrichomonas
species were also detected in the oral cavity by molecular methods. We suggest that this new
Tetratrichomonas
species be named
Tetratrichomonas empyemagena
.
Human T Lymphotropic Virus Type 1 SU Residue 195 Plays a Role in Determining the Preferential CD4+T Cell Immortalization/Transformation Tropism
Authors: Kannian Priya , Fernandez Soledad , Jones Kathryn S. , Green Patrick L. 
Published: June 2013

ABSTRACTHuman T lymphotropic virus type 1 (HTLV-1) mainly causes adult T cell leukemia and predominantly immortalizes/transforms CD4+T cells in culture. HTLV-2 is aleukemic and predominantly immortalizes/transforms CD8+T cells in culture. We have shown previously that the viral envelope is the genetic determinant of the differential T cell tropism in culture. The surface component (SU) of the HTLV-1 envelope is responsible for binding to the cellular receptors for entry. Here, we dissect the HTLV-1 SU further to identify key domains that are involved in determining the immortalization tropism. We generated HTLV-1 envelope recombinant virus containing the HTLV-2 SU domain. HTLV-1/SU2 was capable of infecting and immortalizing freshly isolated peripheral blood mononuclear cells in culture. HTLV-1/SU2 shifted the CD4+T cell immortalization tropism of wild-type HTLV-1 (wtHTLV-1) to a CD8+T cell preference. Furthermore, a single amino acid substitution, N195D, in HTLV-1 SU (Ach.195) resulted in a shift to a CD8+T cell immortalization tropism preference. Longitudinal phenotyping analyses of thein vitrotransformation process revealed that CD4+T cells emerged as the predominant population by week 5 in wtHTLV-1 cultures, while CD8+T cells emerged as the predominant population by weeks 4 and 7 in wtHTLV-2 and Ach.195 cultures, respectively. Our results indicate that SU domain independently influences the preferential T cell immortalization tropism irrespective of the envelope counterpart transmembrane (TM) domain. We further showed that asparagine at position 195 in HTLV-1 SU is involved in determining this CD4+T cell immortalization tropism. The slower emergence of the CD8+T cell predominance in Ach.195-infected cultures suggests that other residues/domains contribute to this tropism preference.
Molecular Basis for Broad Neuraminidase Immunity: Conserved Epitopes in Seasonal and Pandemic H1N1 as Well as H5N1 Influenza Viruses
Authors: Wan Hongquan , Gao Jin , Xu Kemin , Chen Hongjun , Couzens Laura K. , Rivers Katie H. , Easterbrook Judy D. , Yang Kevin , Zhong Lei , Rajabi Mohsen , Ye Jianqiang , Sultana Ishrat , Wan Xiu-Feng , Liu Xiufan , Perez Daniel R. , Taubenberger Jeffery K. , Eichelberger Maryna C. 
Published: June 2013

ABSTRACT
Influenza A viruses, including H1N1 and H5N1 subtypes, pose a serious threat to public health. Neuraminidase (NA)-related immunity contributes to protection against influenza virus infection. Antibodies to the N1 subtype provide protection against homologous and heterologous H1N1 as well as H5N1 virus challenge. Since neither the strain-specific nor conserved epitopes of N1 have been identified, we generated a panel of mouse monoclonal antibodies (MAbs) that exhibit different reactivity spectra with H1N1 and H5N1 viruses and used these MAbs to map N1 antigenic domains. We identified 12 amino acids essential for MAb binding to the NA of a recent seasonal H1N1 virus, A/Brisbane/59/2007. Of these, residues 248, 249, 250, 341, and 343 are recognized by strain-specific group A MAbs, while residues 273, 338, and 339 are within conserved epitope(s), which allows cross-reactive group B MAbs to bind the NAs of seasonal H1N1 and the 1918 and 2009 pandemic (09pdm) H1N1 as well as H5N1 viruses. A single dose of group B MAbs administered prophylactically fully protected mice against lethal challenge with seasonal and 09pdm H1N1 viruses and resulted in significant protection against the highly pathogenic wild-type H5N1 virus. Another three N1 residues (at positions 396, 397, and 456) are essential for binding of cross-reactive group E MAbs, which differ from group B MAbs in that they do not bind 09pdm H1N1 viruses. The identification of conserved N1 epitopes reveals the molecular basis for NA-mediated immunity between H1N1 and H5N1 viruses and demonstrates the potential for developing broadly protective NA-specific antibody treatments for influenza.
Development of Norwalk Virus-Specific Monoclonal Antibodies with Therapeutic Potential for the Treatment of Norwalk Virus Gastroenteritis
Authors: Chen Zhaochun , Sosnovtsev Stanislav V. , Bok Karin , Parra Gabriel I. , Makiya Michelle , Agulto Liane , Green Kim Y. , Purcell Robert H. 
Published: June 2013

ABSTRACT
Passive immunoprophylaxis or immunotherapy with norovirus-neutralizing monoclonal antibodies (MAbs) could be a useful treatment for high-risk populations, including infants and young children, the elderly, and certain patients who are debilitated or immunocompromised. In order to obtain antinorovirus MAbs with therapeutic potential, we stimulated a strong adaptive immune response in chimpanzees to the prototype norovirus strain Norwalk virus (NV) (genogroup I.1). A combinatorial phage Fab display library derived from mRNA of the chimpanzees' bone marrow was prepared, and four distinct Fabs reactive with Norwalk recombinant virus-like particles (rVLPs) were recovered, with estimated binding affinities in the subnanomolar range. Mapping studies showed that the four Fabs recognized three different conformational epitopes in the protruding (P) domain of NV VP1, the major capsid protein. The epitope of one of the Fabs, G4, was further mapped to a specific site involving a key amino acid residue, Gly365. One additional specific Fab (F11) was recovered months later from immortalized memory B cells and partially characterized. The anti-NV Fabs were converted into full-length IgG (MAbs) with human γ1 heavy chain constant regions. The anti-NV MAbs were tested in the two available surrogate assays for Norwalk virus neutralization, which showed that the MAbs could block carbohydrate binding and inhibit hemagglutination by NV rVLP. By mixing a single MAb with live Norwalk virus prior to challenge, MAbs D8 and B7 neutralized the virus and prevented infection in a chimpanzee. Because chimpanzee immunoglobulins are virtually identical to human immunoglobulins, these chimpanzee anticapsid MAbs may have a clinical application.
Introduction to Leonhard Lapin's “Objective
Art”
Authors: Kurg Andres 
Published: June 2013

Abstract
Leonhard Lapin's “Objective Art” was written for “Event Harku '75. Objects, Concepts” – an exhibtion and an accompanying symposium on the premises of the Institute of Experimental Biology in Harku, near Tallinn, Estonia, in December 1975. Objective art, in the artist's mind, answered to the industrialization and urbanization of the late 20th century, to the growing significance of not only mechanical but also electronic machines in everyday life, and to the emergence of the so-called artificial environment. Rather than representing this environment, new art had to intervene in it or even produce it. Lapin's call was quite different from other reactions to the changing postindustrial environment in the mid 1970s in the Soviet Union in that instead of active intervention many of them proposed withdrawal as the most appropriate tactics to resist the grim surrounding reality.
Do Crises Catalyze Creative Destruction? Firm-level Evidence from Indonesia
Authors: Hallward-Driemeier Mary , Rijkers Bob 
Published: June 2013

AbstractUsing Indonesian manufacturing census data (1991–2001), this paper rejects the hypothesis that the East Asian crisis unequivocally improved the reallocative process. The correlation between productivity and employment growth did not strengthen, and the crisis induced the exit of relatively productive firms. The attenuation of the relationship between productivity and survival was stronger in provinces with comparatively lower reductions in minimum wages, but not due to reduced entry, changing loan conditions, or firms connected to the Suharto regime suffering disproportionately. On the bright side, firms that entered during the crisis were relatively more productive, which helped mitigate the reduction in aggregate productivity.
Biblical Perspectives on Migration and Mission: Contributions from the Old Testament
Authors: Carroll R. M. Daniel 
Published: June 2013

Abstract
The growing interest in diaspora mission requires consideration of the pertinent biblical material. This essay focuses on two parts of the Old Testament: the patriarchal narratives of Genesis and Israel’s Law. The former introduces the reader to migrant experiences of the people of God and then connects these to their call to be a blessing to all the earth. The latter contends that Old Testament Law can serve as a paradigm for diaspora mission today in the form of tangible initiatives on behalf of diaspora peoples, both within the Christian community and beyond.