bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ferric Reduction Is a Potential Iron Acquisition Mechanism forHistoplasma capsulatum
Authors: Timmerman Michelle M. , Woods Jon P. 
Published: April 2020

ABSTRACTFor the fungusHistoplasma capsulatum, and for other microbial pathogens, iron is an essential nutrient. Iron sequestration in response to infection is a demonstrated host defense mechanism; thus, iron acquisition may be considered an important pathogenic determinant.H. capsulatumis known to secrete Fe(III)-binding hydroxamate siderophores, which is one common microbial process for acquiring iron. Here, we reportH. capsulatumferric reduction activities in whole yeast cells and in both high- and low-molecular-weight fractions of culture supernatants. Each of these activities was induced or derepressed by growth under iron-limiting conditions, a phenomenon often associated with specific iron acquisition mechanisms. The high-molecular-weight culture supernatant activity was enhanced by the addition of reduced glutathione, was proteinase K sensitive and heat labile, and could utilize ferric chloride, ferric citrate, and human holotransferrin as substrates. The low-molecular-weight culture supernatant activity was resistant to proteinase K digestion. These results are consistent with the expression byH. capsulatumof both enzymatic ferric reductase and nonproteinaceous ferric reductant, both of which are regulated by iron availability. Such components could be involved in fungal acquisition of iron from inorganic or organic ferric salts, fromH. capsulatumhydroxamate siderophores, or from host Fe(III)-binding proteins, such as transferrin.
Decreased Adherence of Enterohemorrhagic
Escherichia coli
to HEp-2 Cells in the Presence of Antibodies That Recognize the C-Terminal Region of Intimin
Authors: Gansheroff Lisa J. , Wachtel Marian R. , O'Brien Alison D. 
Published: April 2020

ABSTRACT

Antiserum raised against intimin from enterohemorrhagic
Escherichia coli
(EHEC) O157:H7 strain 86-24 has been shown previously by our laboratory to inhibit adherence of this strain to HEp-2 cells. In the present study, we sought to identify the region(s) of intimin important for the effect of anti-intimin antisera on EHEC adherence and to determine whether antisera raised against intimin from an O157:H7 strain could reduce adherence of other strains. Compared to preimmune serum controls, polyclonal sera raised against the histidine-tagged intimin protein RIHisEae (intimin
O157
) or against His-tagged C-terminal fragments of intimin from strain 86-24 reduced adherence of this strain. Furthermore, an antibody fraction purified from the anti-RIHisEae serum that contained antibodies to the C-terminal third of intimin, the putative receptor-binding domain, also reduced adherence of strain 86-24, but a purified fraction containing antibodies to the N-terminal two-thirds of intimin did not inhibit adherence. The polyclonal anti-intimin
O157
serum raised against RIHisEae inhibited, to different degrees, the adherence of another O157:H7 strain, an EHEC O55:H7 strain, one of two independent EHEC O111:NM isolates tested, and one of two EHEC O26:H11 strains tested. Adherence of the other O26:H11 and O111:NM strains and an EPEC O127:H6 strain was not reduced. Finally, immunoblot analysis indicated a correlation between the antigenic divergence in the C-terminal third of intimins from different strains and the capacity of anti-intimin
O157
antiserum to reduce adherence of heterologous strains. Taken together, these data suggest that intimin
O157
could be used as an immunogen to elicit adherence-blocking antibodies against O157:H7 strains and closely-related EHEC.
Optimization of Plasmid Maintenance in the Attenuated Live Vector Vaccine Strain
Salmonella typhi
CVD 908-
htrA
Authors: Galen James E. , Nair Jay , Wang Jin Yuang , Wasserman Steven S. , Tanner Michael K. , Sztein Marcelo B. , Levine Myron M. 
Published: April 2020

ABSTRACT

The broad objective of the research presented here is to develop a noncatalytic plasmid maintenance system for the stabilization of multicopy expression plasmids encoding foreign antigens in a
Salmonella typhi
live-vector vaccine strain such as CVD 908-
htrA
. We have enhanced the maintenance of expression plasmids at two independent levels. First, we removed dependence upon balanced-lethal maintenance systems that involve catalytic enzymes expressed from multicopy plasmids; we accomplished this through incorporation into expression plasmids of a postsegregational killing system based on the noncatalytic
hok-sok
plasmid addiction system from the antibiotic resistance factor pR1. We also included at least one naturally occurring plasmid partition function in our expression plasmids, which eliminates random segregation of these plasmids, thereby enhancing their inheritance and stability; to accomplish this, we incorporated either the
par
locus from pSC101, the
parA
locus from pR1, or both. We monitored the stability of optimized expression plasmids within CVD 908-
htrA
by quantitating expression of a variant of green fluorescent protein (GFPuv) by using flow cytometry. In this report, we demonstrate the utility of this novel plasmid maintenance system in enhancing the stability of our expression plasmids and go on to show that as the copy number of stabilized plasmids increases, the toxicity of GFPuv synthesis also increases. The implications of these observations for the rational design of immunogenic and protective bacterial live vector vaccines are discussed.
Regulation of Human CD4+αβ T-Cell-Receptor-Positive (TCR+) and γδ TCR+T-Cell Responses toMycobacterium tuberculosisby Interleukin-10 and Transforming Growth Factor β
Authors: Rojas Roxana E. , Balaji Kithiganahalli N. , Subramanian Ahila , Boom W. Henry 
Published: April 2020

ABSTRACTMycobacterium tuberculosisis the etiologic agent of human tuberculosis and is estimated to infect one-third of the world's population. Control ofM. tuberculosisrequires T cells and macrophages. T-cell function is modulated by the cytokine environment, which in mycobacterial infection is a balance of proinflammatory (interleukin-1 [IL-1], IL-6, IL-8, IL-12, and tumor necrosis factor alpha) and inhibitory (IL-10 and transforming growth factor β [TGF-β]) cytokines. IL-10 and TGF-β are produced byM. tuberculosis-infected macrophages. The effect of IL-10 and TGF-β onM. tuberculosis-reactive human CD4+and γδ T cells, the two major human T-cell subsets activated byM. tuberculosis, was investigated. Both IL-10 and TGF-β inhibited proliferation and gamma interferon production by CD4+and γδ T cells. IL-10 was a more potent inhibitor than TGF-β for both T-cell subsets. Combinations of IL-10 and TGF-β did not result in additive or synergistic inhibition. IL-10 inhibited γδ and CD4+T cells directly and inhibited monocyte antigen-presenting cell (APC) function for CD4+T cells and, to a lesser extent, for γδ T cells. TGF-β inhibited both CD4+and γδ T cells directly and had little effect on APC function for γδ and CD4+T cells. IL-10 down-regulated major histocompatibility complex (MHC) class I, MHC class II, CD40, B7-1, and B7-2 expression onM. tuberculosis-infected monocytes to a greater extent than TGF-β. Neither cytokine affected the uptake ofM. tuberculosisby monocytes. Thus, IL-10 and TGF-β both inhibited CD4+and γδ T cells but differed in the mechanism used to inhibit T-cell responses toM. tuberculosis.
Protective Immunity againstStreptococcus mutansInfection in Mice after Intranasal Immunization with the Glucan-Binding Region ofS. mutansGlucosyltransferase
Authors: Jespersgaard Christina , Hajishengallis George , Huang Yan , Russell Michael W. , Smith Daniel J. , Michalek Suzanne M. 
Published: April 2020

ABSTRACTHere we present the construction and characterization of a chimeric vaccine protein combining the glucan-binding domain (GLU) of thegtfB-encoded water-insoluble glucan-synthesizing glucosyltransferase enzyme (GTF-I) fromStreptococcus mutansand thioredoxin fromEscherichia coli, which increases the solubility of coexpressed recombinant proteins and stimulates proliferation of murine T cells. The protective potential of intranasal (i.n.) immunization with this chimeric immunogen was compared to that of the GLU polypeptide alone in a mouse infection model. Both immunogens were able to induce statistically significant mucosal (salivary and vaginal) and serum responses (P< 0.01) which were sustained to the end of the study (experimental day 100). Following infection withS. mutans, sham-immunized mice maintained high levels of this cariogenic organism (∼60% of the total oral streptococci) for at least 5 weeks. In contrast, animals immunized with the thioredoxin-GLU chimeric protein (Thio-GLU) showed significant reduction (>85%) inS. mutanscolonization after 3 weeks (P< 0.05). The animals immunized with GLU alone required 5 weeks to demonstrate significant reduction (>50%) ofS. mutansinfection (P< 0.05). Evaluation of dental caries activity at the end of the study showed that mice immunized with either Thio-GLU or GLU had significantly fewer carious lesions in the buccal enamel or dentinal surfaces than the sham-immunized animals (P< 0.01). The protective effects againstS. mutanscolonization and caries activity following i.n. immunization with GLU or Thio-GLU are attributed to the induced salivary immunoglobulin A (IgA) anti-GLU responses. Although in general Thio-GLU was not significantly better than GLU alone in stimulating salivary IgA responses and in protection against dental caries, the finding that the GLU polypeptide alone, in the absence of any immunoenhancing agents, is protective against disease offers a promising and safe strategy for the development of a vaccine against caries.
Differential Decline inLeishmaniaMembrane Antigen-Specific Immunoglobulin G (IgG), IgM, IgE, and IgG Subclass Antibodies in Indian Kala-Azar Patients after Chemotherapy
Authors: Anam Khairul , Afrin Farhat , Banerjee Dwijadas , Pramanik Netai , Guha Subhasis K. , Goswami Rama P. , Saha Shiben K. , Ali Nahid 
Published: April 2020

ABSTRACTPathogenesis in kala-azar is associated with depressed cellular immunity and significant elevation of antileishmanial antibodies. Since these antibodies are present even after cure, analysis of the parasite-specific isotypes and immunoglobulin G (IgG) subclasses in kala-azar patients may shed new light on the immune responses during progression and resolution of infection. Using leishmanial membrane antigenic extracts, we investigated the relative levels of specific IgG, IgM, IgA, IgE, and IgG subclasses in Indian kala-azar patient sera during disease, drug resistance, and cure. Acute-phase sera showed strong stimulation of IgG, followed by IgE and IgM and lastly by IgA antibodies. IgG subclass analysis revealed expression of all of the subclasses, with a predominance of IgG1 during disease. Following sodium stibogluconate (SAG) resistance, the levels of IgG, IgM, IgE, and IgG4 remained constant, while there was a decrease in the titers of IgG2 and IgG3. In contrast, a significant (2.2-fold) increase in IgG1 was observed in these individuals. Cure, in both SAG-responsive and unresponsive patients, correlated with a decline in the levels of IgG, IgM, IgE, and all of the IgG subclasses. The stimulation of IgG1 and the persistence, most importantly, of IgE and IgG4 following drug resistance, along with a decline in IgE, IgG4, and IgG1 with cure, demonstrate the potential of these isotypes as possible markers for monitoring effective treatment in kala-azar.
Isogenic Lysogens of Diverse Shiga Toxin 2-Encoding Bacteriophages Produce Markedly Different Amounts of Shiga Toxin
Authors: Wagner Patrick L. , Acheson David W. K. , Waldor Matthew K. 
Published: April 2020

ABSTRACT

We produced isogenic
Escherichia coli
K-12 lysogens of seven different Shiga toxin 2 (Stx2)-encoding bacteriophages derived from clinical Shiga toxin-producing
E. coli
(STEC) isolates of serotypes O157:H7, O145, O111, and O83 to assess the variability among these phages and determine if there were phage-related differences in toxin production. Phage genomic restriction fragment length polymorphisms (RFLP) and superinfection resistance studies revealed significant differences among these phages and allowed the seven phages to be placed into five distinct groups. Experiments revealed striking differences in spontaneous phage and toxin production that were correlated with the groupings derived from the RFLP and resistance studies. These results suggest that the genotype of the Stx2 prophage can influence the level of phage release and toxin expression by host strains and thus may be relevant to STEC pathogenesis.
Effect of a web drama video series on HIV and other sexually transmitted infection testing among gay, bisexual and queer men: study protocol for a community-based, pragmatic randomised controlled trial in Singapore: the People Like Us (PLU) Evaluation Study
Authors: Tan Rayner Kay Jin , Koh Wee Ling , Le Daniel , Tan Avin , Tyler Adrian , Tan Calvin , Banerjee Sumita , Wong Chen Seong , Wong Mee-Lian , Chio Martin Tze-Wei , Chen Mark I-Cheng 
Published: April 2020

IntroductionGay, bisexual and queer (GBQ) men are at disproportionately higher risk of acquiring HIV and other sexually transmitted infections (STI). While HIV/STI testing rates among GBQ men are increasing worldwide, they remain suboptimal in a variety of settings.Methods and analysisThe study is a pragmatic randomised controlled trial designed to evaluate an online video series developed by a community-based organisation in Singapore for GBQ men. A total of 300 HIV-negative GBQ men in Singapore aged 18–29 years old will be recruited for this study. Participants will subsequently be randomised into the intervention arm (n=150) and the control arm (n=150). The intervention arm (n=150) will be assigned the intervention along with sexual health information via a pamphlet, while the control group (n=150) will be assigned only the sexual health information via a pamphlet. Participants should also not have watched the video prior to their participation in this study, which will be ascertained through a questionnaire. Primary outcomes for this evaluation are changes in self-reported intention to test for, actual testing for and regularity of testing for HIV, syphilis, chlamydia and gonorrhoea at the 3 and 6 months after intervention. Secondary outcomes include changes in self-reported risk perception for HIV and other STIs, knowledge of HIV, knowledge of risks associated with acquiring STIs, knowledge of HIV pre-exposure prophylaxis, consistent condom use for anal sex with casual partners, incidence of STIs, connectedness to the lesbian, gay, bisexual and transgender community, self-concealment of sexual orientation, perceived homophobia, internalised homophobia, HIV testing self-efficacy and HIV testing social norms.Ethics and disseminationThe study has been approved by the National University of Singapore Institutional Review Board (S-19-059) and registered at ClinicalTrials.gov. The results will be published in peer-reviewed academic journals and disseminated to community-based organisations and policymakers.Trial registration numberNCT04021953
Phenomenology at the LHC of composite particles from strongly interacting Standard Model fermions via four-fermion operators of NJL type
Authors: Leonardi R. , Panella O. , Romeo F. , Gurrola A. , Sun H. , Xue S.-S. 
Published: April 2020

AbstractA new physics scenario shows that four-fermion operators of Nambu-Jona-Lasinio (NJL) type have a strong-coupling UV fixed point, where composite fermions F (bosons $$\Pi $$Π) form as bound states of three (two) SM elementary fermions and they couple to their constituents via effective contact interactions at the composite scale $$\Lambda \approx {{{\mathcal {O}}}} $$Λ≈O(TeV). We present a phenomenological study to investigate such composite particles at the LHC by computing the production cross sections and decay widths of composite fermions in the context of the relevant experiments at the LHC with pp collisions at $$\sqrt{s}=13$$s=13 TeV and $$\sqrt{s}=14$$s=14 TeV. Systematically examining all the different composite particles F and the signatures with which they can manifest, we found a vast spectrum of composite particles F that has not yet been explored at the LHC. Recasting the recent CMS results of the resonant channel $$pp\rightarrow e^+F \rightarrow e^+e^- q\bar{q}'$$pp→e+F→e+e-qq¯′ (as $$F=E$$F=E), we find that the composite fermion mass $$m_F$$mF below 4.25 TeV is excluded for $$\Lambda $$Λ/$$m_F$$mF = 1. We further highlight the region of parameter space where this specific composite particle F can appear using 3 $$\hbox {ab}^{-1}$$ab-1, expected by the High-Luminosity LHC, computing 3 and 5 $$\sigma $$σ contour plots of its statistical significance.
The Palatini star: exact solutions of the modified Lane–Emden equation
Authors: Sergyeyev Artur , Wojnar Aneta 
Published: April 2020

AbstractTwo exact solutions for $$n=0$$n=0 and $$n=1$$n=1 of the Palatini-modified Lane–Emden equation are found. We have employed these solutions to describe a Palatini–Newtonian neutron or low mass brown dwarf star and compared the result with the pure Newtonian counterpart. It turned out that for the negative parameter of the Starobinsky model the star is heavier and larger.
Hispanic/Latino Patients with Gastric Adenocarcinoma Have Distinct Molecular Profiles Including a High Rate of GermlineCDH1Variants
Authors: Wang Sam C. , Yeu Yunku , Hammer Suntrea T.G. , Xiao Shu , Zhu Min , Hong Changjin , Clemenceau Jean R. , Yoon Lynn Y. , Nassour Ibrahim , Shen Jeanne , Agarwal Deepak , Reznik Scott I. , Mansour John C. , Yopp Adam C. , Zhu Hao , Hwang Tae Hyun , Porembka Matthew R. 
Published: April 2020

AbstractHispanic/Latino patients have a higher incidence of gastric cancer and worse cancer-related outcomes compared with patients of other backgrounds. Whether there is a molecular basis for these disparities is unknown, as very few Hispanic/Latino patients have been included in previous studies. To determine the genomic landscape of gastric cancer in Hispanic/Latino patients, we performed whole-exome sequencing (WES) and RNA sequencing on tumor samples from 57 patients; germline analysis was conducted on 83 patients. The results were compared with data from Asian and White patients published by The Cancer Genome Atlas. Hispanic/Latino patients had a significantly larger proportion of genomically stable subtype tumors compared with Asian and White patients (65% vs. 21% vs. 20%, P &lt; 0.001). Transcriptomic analysis identified molecular signatures that were prognostic. Of the 43 Hispanic/Latino patients with diffuse-type cancer, 7 (16%) had germline variants in CDH1. Variant carriers were significantly younger than noncarriers (41 vs. 50 years, P &lt; 0.05). In silico algorithms predicted five variants to be deleterious. For two variants that were predicted to be benign, in vitro modeling demonstrated that these mutations conferred increased migratory capability, suggesting pathogenicity. Hispanic/Latino patients with gastric cancer possess unique genomic landscapes, including a high rate of CDH1 germline variants that may partially explain their aggressive clinical phenotypes. Individualized screening, genetic counseling, and treatment protocols based on patient ethnicity and race may be necessary.Significance:Gastric cancer in Hispanic/Latino patients has unique genomic profiles that may contribute to the aggressive clinical phenotypes seen in these patients.
LATIN PHRASEOLOGICAL FUND AS A SOURCE OF DEVELOPING FUTURE PHYSICIANS’ LEXICAL COMPETENCE
Authors: Kolodnytska O. D. , Palasiuk H. B. , Vorona I. I. 
Published: April 2020

The article reviews Latin proverbs and sayings, short quotes, statements of historical figures as a means of aphorism; it summarizes the importance of learning Latin aphorisms, quotes, proverbs and sayings and their corresponding equivalents in English and Ukrainian by medical students on Latin classes.
According to historical conditions, Latin has lost its communicative function, but it has gained great historical and educational significance and has become an inexhaustible source of universal human culture and a link between antiquity and modernity. Learning Latin helps the deeper acquisition of knowledge from many specialties, and plays an important role in the artistic and aesthetic education of future physicians.
Phraseological funds of many modern languages have been replenished by Latin and Greek aphorisms borrowed by new languages mainly through Latin. The Latin phraseological fund contains numerous proverbs and sayings borrowed by world’s languages in the translated form.
Many Latin words were borrowed by Ukrainian, and it is not only the international terminological vocabulary used by scholars in various branches of knowledge but also everyday words (forum – форум (forum), colleague – колега (collega), professor – професор (professor), etc.).
Latin is a basis of all medical terminology facilitating professional communication between languages. The study of Latin obviously helps future physicians to better understand and learn the medical terminology of Greek-Latin origin. Learning Latin not only introduces folk wisdom (learning of aphorisms, proverbs, and sayings), but also lays the foundations of scientific knowledge, promotes the formation of a professional language, which allows to carry out communicative tasks of medical staff.
Blood lactate concentrations following maximal incremental test in male runners with different ages
Authors: Peserico Cecília Segabinazi , Mezzaroba Paulo Victor , Silva Danilo Fernandes da , Kravchychyn Ana Claudia Pelissari , Alves Júlio César Camargo , Machado Fabiana Andrade 
Published: April 2020

The aim of this study was to investigate the effect of age on peak blood lactate concentration following a maximal incremental treadmill test in male recreational runners. Seventy runners from four age groups, ≤25 years; 26-35 years; 36-45 years; >45 years, performed an incremental treadmill test starting at 8 km·h-1, and increasing by 1 km·h-1 every three minutes until volitional exhaustion. Blood samples were collected at baseline and at the zero, third, fifth and seventh minutes after test to determine lactate concentrations. Peak lactate concentration (LApeak) was defined for each participant as the highest value among the four samples. The lactate concentrations were influenced by the participants’ age (r = -0.47), with LApeak of the younger runners (10.8 ± 2.6 mmol·L) being higher than the values for the older age categories (8.1 ± 3.1, 7.0 ± 1.1 and 6.9 ± 2.8 mmol·L for those 26-35, 36-45 and >45 years, respectively). The LApeak occurred more frequently at the third and fifth minute after the initiation of the test. In conclusion, the lactate concentrations were higher in the younger group (< 25) and reached peak more frequently at the third and fifth minute after the incremental test.