Identification of protein and mannoprotein antigens of Candida albicans of relevance for the serodiagnosis of invasive candidiasis

Antigens from Candida albicans blastoconidia and germ tubes were identified by two-dimensional electrophoresis and Western blotting and characterized by microsequencing, reactivity with concanavalin A, and a panel of human sera. Antigens identified included a polydispersed area in the acidic high-molecular-mass regions of blastoconidium and germ-tube extracts, and 16 antigens varying in molecular masses and isoelectric points (pIs). The majority of the detected antigens, especially those in the polydispersed region, showed mannosyl groups, as determined by concanavalin A reactivity. Antibodies present in sera from patients with invasive candidiasis showed high reactivity with a number of antigens not detected with sera from blood donors. Eight of the 16 antigens could be identified by reactivity with monoclonal antibodies or by microsequencing. Five antigens showed homology with five enzymes previously described as antigens in C. albicans: enolase, phosphoglycerate kinase, malate dehydrogenase, and two isoforms of the fructose biphosphate aldolase. However, to our knowledge, this is the first report of the immunogenic activity of a kexin precursor, a mitochondrial complex I chaperone, and a diacylglycerol kinase catalytic domain from C. albicans. Antigens described in this study may be of potential interest for the serodiagnosis of invasive candidiasis. [Int Microbiol 2007; 10(2):103-108

Effective Lagrangians and Light Gravitino Phenomenology

We construct the low-energy effective lagrangian for a light gravitino coupled to the minimal supersymmetric standard model under the assumption that supersymmetry breaking is communicated to the observable sector dominantly through soft terms. Our effective lagrangian is written in terms of the spin-1/2 Goldstino (the longitudinal component of the gravitino) transforming under a non-linear realization of supersymmetry. In this lagrangian, the Goldstino is derivatively coupled and all couplings of the Goldstino to light fields are determined uniquely by the supersymmetry-breaking scale \sqrt{F}. This lagrangian is therefore a useful starting point for further investigation of the light gravitino in gauge-mediated supersymmetry breaking models. We show that the invisible width of the Z into Goldstinos gives the constraint \sqrt{F} > 140 GeV.Comment: 15 pages, LaTeX2e, 1 eps figure. Removed erroneous claim of coupling of photon to gravitino to photons at order M^2 E^2 / F^2. Strongest bound is from invisible Z width, giving F > (140 GeV)^

Clinical factors associated with a Candida albicans Germ Tube Antibody positive test in Intensive Care Unit patients

Background: Poor outcomes of invasive candidiasis (IC) are associated with the difficulty in establishing the microbiological diagnosis at an early stage. New scores and laboratory tests have been developed in order to make an early therapeutic intervention in an attempt to reduce the high mortality associated with invasive fungal infections. Candida albicans IFA IgG has been recently commercialized for germ tube antibody detection (CAGTA). This test provides a rapid and simple diagnosis of IC (84.4% sensitivity and 94.7% specificity). The aim of this study is to identify the patients who could be benefited by the use of CAGTA test in critical care setting. Methods: A prospective, cohort, observational multicentre study was carried out in six medical/surgical Intensive care units (ICU) of tertiary-care Spanish hospitals. Candida albicans Germ Tube Antibody test was performed twice a week if predetermined risk factors were present, and serologically demonstrated candidiasis was considered if the testing serum dilution was >= 1: 160 in at least one sample and no other microbiological evidence of invasive candidiasis was found. Results: Fifty-three critically ill non-neutropenic patients (37.7% post surgery) were included. Twenty-two patients (41.5%) had CAGTA-positive results, none of them with positive blood culture for Candida. Neither corrected colonization index nor antifungal treatment had influence on CAGTA results. This finding could corroborate that the CAGTA may be an important biomarker to distinguish between colonization and infection in these patients. The presence of acute renal failure at the beginning of the study was more frequent in CAGTA-negative patients. Previous surgery was statistically more frequent in CAGTA-positive patients. Conclusions: This study identified previous surgery as the principal clinical factor associated with CAGTA-positive results and emphasises the utility of this promising technique, which was not influenced by high Candida colonization or antifungal treatment. Our results suggest that detection of CAGTA may be important for the diagnosis of invasive candidiasis in surgical patients admitted in ICU.This study has been supported by a Pfizer research gran

Bulk Gauge Fields in Warped Space and Localized Supersymmetry Breaking

We consider five dimensional supersymmetric warped scenarios in which the Standard Model quark and lepton fields are localized on the ultraviolet brane, while the Standard Model gauge fields propagate in the bulk. Supersymmetry is assumed to be broken on the infrared brane. The relative sizes of supersymmetry breaking effects are found to depend on the hierarchy between the infrared scale and the weak scale. If the infrared scale is much larger than the weak scale the leading supersymmetry breaking effect on the visible brane is given by gaugino mediation. The gaugino masses at the weak scale are proportional to the square of the corresponding gauge coupling, while the dominant contribution to the scalar masses arises from logarithmically enhanced radiative effects involving the gaugino mass that are cutoff at the infrared scale. While the LSP is the gravitino, the NLSP which is the stau is stable on collider time scales. If however the infrared scale is close to the weak scale then the effects of hard supersymmetry breaking operators on the scalar masses can become comparable to those from gaugino mediation. These operators alter the relative strengths of the couplings of gauge bosons and gauginos to matter, and give loop contributions to the scalar masses that are also cutoff at the infrared scale. The gaugino masses, while exhibiting a more complicated dependence on the corresponding gauge coupling, remain hierarchical and become proportional to the corresponding gauge coupling in the limit of strong supersymmetry breaking. The scalar masses are finite and a loop factor smaller than the gaugino masses. The LSP remains the gravitino.Comment: 36 pages, 2 figure

Sampling multiple life stages significantly increases estimates of marine biodiversity

Biodiversity assessments are critical for setting conservation priorities, understanding ecosystem function and establishing a baseline to monitor change. Surveys of marine biodiversity that rely almost entirely on sampling adult organisms underestimate diversity because they tend to be limited to habitat types and individuals that can be easily surveyed. Many marine animals have planktonic larvae that can be sampled from the water column at shallow depths. This life stage often is overlooked in surveys but can be used to relatively rapidly document diversity, especially for the many species that are rare or live cryptically as adults. Using DNA barcode data from samples of nemertean worms collected in three biogeographical regions—Northeastern Pacific, the Caribbean Sea and Eastern Tropical Pacific—we found that most species were collected as either benthic adults or planktonic larvae but seldom in both stages. Randomization tests show that this deficit of operational taxonomic units collected as both adults and larvae is extremely unlikely if larvae and adults were drawn from the same pool of species. This effect persists even in well-studied faunas. These results suggest that sampling planktonic larvae offers access to a different subset of species and thus significantly increases estimates of biodiversity compared to sampling adults alone. Spanish abstract is available in the electronic supplementary material.Fil: Maslakova, Svetlana A.. University of Oregon; Estados UnidosFil: Ellison, Christina I.. University of Oregon; Estados UnidosFil: Hiebert, Terra C.. University of Oregon; Estados UnidosFil: Conable, Frances. University of Oregon; Estados UnidosFil: Heapy, Maureen C.. University of Oregon; Estados UnidosFil: Venera Pontón, Dagoberto E.. Smithsonian Tropical Research Institute; PanamáFil: Norenburg, Jon L.. National Museum Of Natural History. Departamento de Zoología. Area de Invertebrados; Estados UnidosFil: Schwartz, Megan L.. University of Washington; Estados UnidosFil: Boyle, Michael J.. Smithsonian Tropical Research Institute; PanamáFil: Driskell, Amy C.. National Museum Of Natural History. Departamento de Zoología. Area de Invertebrados; Estados UnidosFil: Macdonald, Kenneth S.. National Museum Of Natural History. Departamento de Zoología. Area de Invertebrados; Estados UnidosFil: Zattara, Eduardo Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; ArgentinaFil: Collin, Rachel. Smithsonian Tropical Research Institute; Panam

Yukawa Deflected Gauge Mediation

We consider models which are natural extensions of those where supersymmetry is broken at low energy scales and transmitted to visible matter by gauge interactions. We investigate the situation where the quark and lepton superfields of the MSSM are localized to a brane in a higher dimensional space while the messenger fields and the sector which breaks supersymmetry dynamically are localized to another brane in the same space. The MSSM gauge and Higgs fields are assumed to propagate in the bulk. If some of the messenger fields and the Higgs fields have the same quantum numbers, this allows the possibility of mixing between these fields so that the physical Higgs and messenger fields are admixtures of the brane and bulk fields. This manifests itself in direct couplings of the quark and lepton fields to the physical messengers that are proportional to the MSSM Yukawa couplings and hence preserve the flavor structure of the CKM matrix. The result is new contributions to the soft supersymmetry breaking parameters that are related to the Yukawa couplings and which therefore naturally satisfy the constraints from FCNC's. For messenger scales greater then 1000 TeV these new contributions are parametrically of the same order of magnitude as gauge mediation. This scenario naturally avoids the cosmological problems associated with stable messengers and admits a simple and natural solution to the $\mu$ problem based on the NMSSM.Comment: 19 pages, expressions for down-type Higgs trilinear terms corrected, conclusions unchange

Electroweak Baryogenesis and Dark Matter with an approximate R-symmetry

It is well known that R-symmetric models dramatically alleviate the SUSY flavor and CP problems. We study particular modifications of existing R-symmetric models which share the solution to the above problems, and have interesting consequences for electroweak baryogenesis and the Dark Matter (DM) content of the universe. In particular, we find that it is naturally possible to have a strongly first-order electroweak phase transition while simultaneously relaxing the tension with EDM experiments. The R-symmetry (and its small breaking) implies that the gauginos (and the neutralino LSP) are pseudo-Dirac fermions, which is relevant for both baryogenesis and DM. The singlet superpartner of the U(1)_Y pseudo-Dirac gaugino plays a prominent role in making the electroweak phase transition strongly first-order. The pseudo-Dirac nature of the LSP allows it to behave similarly to a Dirac particle during freeze-out, but like a Majorana particle for annihilation today and in scattering against nuclei, thus being consistent with current constraints. Assuming a standard cosmology, it is possible to simultaneously have a strongly first-order phase transition conducive to baryogenesis and have the LSP provide the full DM relic abundance, in part of the allowed parameter space. However, other possibilities for DM also exist, which are discussed. It is expected that upcoming direct DM searches as well as neutrino signals from DM annihilation in the Sun will be sensitive to this class of models. Interesting collider and Gravity-wave signals are also briefly discussed.Comment: 50 pages, 10 figure

Warped Universal Extra Dimensions

We consider a 5D warped scenario with a KK-parity symmetry, where the non-trivial warping arises from the dynamics that stabilizes the size of the extra dimension. Generically, the lightest Kaluza-Klein (KK) particle is the first excitation of the radion field, while the next-to-lightest Kaluza-Klein particle is either the first excitation of the (RH) top quark or the first KK-parity odd Higgs. All these masses are expected to be of order the electroweak scale. We present simple analytical expressions for the masses and wavefunctions of the lowest lying KK modes, and derive the Feynman rules necessary for phenomenological applications. The framework allows to interpolate between a strongly warped scenario a la Randall-Sundrum (RS), and a weakly warped scenario that shares properties of both RS and Universal Extra Dimensions models.Comment: 41 pages, 13 figures. Minor comments added. Published versio

Phenomenology of Non-Custodial Warped Models

We study the effect of bulk fermions on electroweak precision observables in a recently proposed model with warped extra dimensions and no custodial symmetry. We find that the top-quark mass, together with the corrections to the Zbb vertex and the one-loop contribution to the T parameter, which is finite, impose important constraints that single out a well defined region of parameter space. New massive vector bosons can be as light as 1.5 TeV and have large couplings to the t_R quark, and suppressed couplings to the t_L, b_L and lighter quarks. We discuss the implications for searches of models with warped extra dimensions at the LHC.Comment: Most relevant one-loop contributions to EWP observables included, physics results partially changed. References added. 29 pages, 14 Figure

Antibody Complementarity-Determining Regions (CDRs) Can Display Differential Antimicrobial, Antiviral and Antitumor Activities

Background: Complementarity-determining regions (CDRs) are immunoglobulin (Ig) hypervariable domains that determine specific antibody (Ab) binding. We have shown that synthetic CDR-related peptides and many decapeptides spanning the variable region of a recombinant yeast killer toxin-like antiidiotypic Ab are candidacidal in vitro. An alanine-substituted decapeptide from the variable region of this Ab displayed increased cytotoxicity in vitro and/or therapeutic effects in vivo against various bacteria, fungi, protozoa and viruses. the possibility that isolated CDRs, represented by short synthetic peptides, may display antimicrobial, antiviral and antitumor activities irrespective of Ab specificity for a given antigen is addressed here.Methodology/Principal Findings: CDR-based synthetic peptides of murine and human monoclonal Abs directed to: a) a protein epitope of Candida albicans cell wall stress mannoprotein; b) a synthetic peptide containing well-characterized B-cell and T-cell epitopes; c) a carbohydrate blood group A substance, showed differential inhibitory activities in vitro, ex vivo and/or in vivo against C. albicans, HIV-1 and B16F10-Nex2 melanoma cells, conceivably involving different mechanisms of action. Antitumor activities involved peptide-induced caspase-dependent apoptosis. Engineered peptides, obtained by alanine substitution of Ig CDR sequences, and used as surrogates of natural point mutations, showed further differential increased/unaltered/decreased antimicrobial, antiviral and/or antitumor activities. the inhibitory effects observed were largely independent of the specificity of the native Ab and involved chiefly germline encoded CDR1 and CDR2 of light and heavy chains.Conclusions/Significance: the high frequency of bioactive peptides based on CDRs suggests that Ig molecules are sources of an unlimited number of sequences potentially active against infectious agents and tumor cells. the easy production and low cost of small sized synthetic peptides representing Ig CDRs and the possibility of peptide engineering and chemical optimization associated to new delivery mechanisms are expected to give rise to a new generation of therapeutic agents.Department of Education, Universities and Research, Basque GovermentFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Istituto Superiore di Sanita, National Research Project on A.I.D.S.Cariparma Banking FoundationBrazilian National Research CouncilUniv Parma, Sez Microbiol, Dipartimento Patol, I-43100 Parma, ItalyUniv Basque Country, Fac Med Odontol, Dept Inmunol, Microbiol Parasitol, Bilbao, SpainUniv Basque Country, Dept Enfermeria I, Bilbao, SpainUniv Milan, Dipartimento Sci Cliniche L Sacco, Sez Malattie Infettive Immunopatol, Milan, ItalyUniv Studi Parma, Dipartimento Clin Med, Nefrol Sci Prev, Parma, ItalyUniversidade Federal de São Paulo, Departamento Microbiol, Imunol Parasitol, Unidade Oncol Expt, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biofis, São Paulo, BrazilUniversidade Federal de São Paulo, Departamento Microbiol, Imunol Parasitol, Unidade Oncol Expt, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biofis, São Paulo, BrazilDepartment of Education, Universities and Research, Basque Goverment: IT-264-07FAPESP: 06/50634-2Istituto Superiore di Sanita, National Research Project on A.I.D.S.: 50G.30Istituto Superiore di Sanita, National Research Project on A.I.D.S.: 40D.14Cariparma Banking Foundation: 2004.0190Brazilian National Research Council: research fellowshipWeb of Scienc