Relevance of the Diversity among Members of the Trypanosoma Cruzi Trans-Sialidase Family Analyzed with Camelids Single-Domain Antibodies

The sialic acid present in the protective surface mucin coat of Trypanosoma cruzi is added by a membrane anchored trans-sialidase (TcTS), a modified sialidase that is expressed from a large gene family. In this work, we analyzed single domain camelid antibodies produced against trans-sialidase. Llamas were immunized with a recombinant trans-sialidase and inhibitory single-domain antibody fragments were obtained by phage display selection, taking advantage of a screening strategy using an inhibition test instead of the classic binding assay. Four single domain antibodies displaying strong trans-sialidase inhibition activity against the recombinant enzyme were identified. They share the same complementarity-determining region 3 length (17 residues) and have very similar sequences. This result indicates that they likely derived from a unique clone. Probably there is only one structural solution for tight binding inhibitory antibodies against the TcTS used for immunization. To our surprise, this single domain antibody that inhibits the recombinant TcTS, failed to inhibit the enzymatic activity present in parasite extracts. Analysis of individual recombinant trans-sialidases showed that enzymes expressed from different genes were inhibited to different extents (from 8 to 98%) by the llama antibodies. Amino acid changes at key positions are likely to be responsible for the differences in inhibition found among the recombinant enzymes. These results suggest that the presence of a large and diverse trans-sialidase family might be required to prevent the inhibitory response against this essential enzyme and might thus constitute a novel strategy of T. cruzi to evade the host immune system

Associations of airway inflammation and responsiveness markers in non asthmatic subjects at start of apprenticeship

<p>Abstract</p> <p>Background</p> <p>Bronchial Hyperresponsiveness (BHR) is considered a hallmark of asthma. Other methods are helpful in epidemiological respiratory health studies including Fractional Exhaled Nitric Oxide (FENO) and Eosinophils Percentage (EP) in nasal lavage fluid measuring markers for airway inflammation along with the Forced Oscillatory Technique measuring Airway resistance (AR). Can their outcomes discriminate profiles of respiratory health in healthy subjects starting apprenticeship in occupations with a risk of asthma?</p> <p>Methods</p> <p>Rhinoconjunctivitis, asthma-like symptoms, FEV1 and AR post-Methacholine Bronchial Challenge (MBC) test results, FENO measurements and EP were all investigated in apprentice bakers, pastry-makers and hairdressers not suffering from asthma. Multiple Correspondence Analysis (MCA) was simultaneously conducted in relation to these groups and this generated a synthetic partition (EI). Associations between groups of subjects based on BHR and EI respectively, as well as risk factors, symptoms and investigations were also assessed.</p> <p>Results</p> <p>Among the 441 apprentice subjects, 45 (10%) declared rhinoconjunctivitis-like symptoms, 18 (4%) declared asthma-like symptoms and 26 (6%) suffered from BHR. The mean increase in AR post-MBC test was 21% (sd = 20.8%). The median of FENO values was 12.6 ppb (2.6-132 range). Twenty-six subjects (6.7%) had EP exceeding 14%. BHR was associated with atopy (p < 0.01) and highest FENO values (p = 0.09). EI identified 39 subjects with eosinophilic inflammation (highest values of FENO and eosinophils), which was associated with BHR and atopy.</p> <p>Conclusions</p> <p>Are any of the identified markers predictive of increased inflammatory responsiveness or of development of symptoms caused by occupational exposures? Analysis of population follow-up will attempt to answer this question.</p

A Study of D0 --> K0(S) K0(S) X Decay Channels

Using data from the FOCUS experiment (FNAL-E831), we report on the decay of $D^0$ mesons into final states containing more than one $K^0_S$. We present evidence for two Cabibbo favored decay modes, $D^0\to K^0_SK^0_S K^- \pi^+$ and $D^0\to K^0_SK^0_S K^+ \pi^-$, and measure their combined branching fraction relative to $D^0\to \bar{K} ^0\pi^+\pi^-$ to be $\frac{\Gamma(D^0\to K^0_SK^0_SK^{\pm}\pi^{\mp})}{\Gamma(D^0\to \bar{K} ^0\pi^+\pi^-)}$ = 0.0106 $\pm$ 0.0019 $\pm$ 0.0010. Further, we report new measurements of $\frac{\Gamma(D^0\to K^0_SK^0_SK^0_S)}{\Gamma(D^0\to \bar{K} ^0\pi^+\pi^-)}$ = 0.0179 $\pm$ 0.0027 $\pm$ 0.0026, $\frac{\Gamma(D^0\to K^0\bar{K} ^0)}{\Gamma(D^0\to \bar{K} ^0\pi^+\pi^-)}$ = 0.0144 $\pm$ 0.0032 $\pm$ 0.0016, and $\frac{\Gamma(D^0\to K^0_SK^0_S\pi^+\pi^-)}{\Gamma(D^0\to \bar{K} ^0\pi^+\pi^-)}$ = 0.0208 $\pm$ 0.0035 $\pm$ 0.0021 where the first error is statistical and the second is systematic.Comment: 11 pages, 3 figures, typos correcte

Prospective study comparing skin impedance with EEG parameters during the induction of anaesthesia with fentanyl and etomidate

<p>Abstract</p> <p>Objective</p> <p>Sympathetic stimulation leads to a change in electrical skin impedance. So far it is unclear whether this effect can be used to measure the effects of anaesthetics during general anaesthesia. The aim of this prospective study is to determine the electrical skin impedance during induction of anaesthesia for coronary artery bypass surgery with fentanyl and etomidate.</p> <p>Methods</p> <p>The electrical skin impedance was measured with the help of an electro-sympathicograph (ESG). In 47 patients scheduled for elective cardiac surgery, anaesthesia was induced with intravenous fentanyl 10 μg/kg and etomidate 0.3 mg/kg. During induction, the ESG (Electrosympathicograph), BIS (Bispectral IndeX), BP (arterial blood pressure) and HR (heart rate) values of each patient were recorded every 20 seconds. The observation period from administration of fentanyl to intubation for surgery lasted 4 min.</p> <p>Results</p> <p>The ESG recorded significant changes in the electrical skin impedance after administration of fentanyl and etomidate(p < 0.05). During induction of anaesthesia, significant changes of BIS, HR and blood pressure were observed as well (p < 0.05).</p> <p>Conclusions</p> <p>The electrical skin impedance measurement may be used to monitor the effects of anesthetics during general anaesthesia.</p

A Research Agenda to Underpin Malaria Eradication

Pedro Alonso and colleagues introduce the Malaria Eradication Research Agenda (malERA) initiative and the set of articles published in this PLoS Medicine Supplement that distill the research questions key to malaria eradication

How a slow-ovipositing parasitoid can succed as a biological control agent of the invasive mealybug Phenacoccus peruvianus: implications for future classical and conservation biological control programs

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Suppression of Radiation-Induced Salivary Gland Dysfunction by IGF-1

Radiation is a primary or secondary therapeutic modality for treatment of head and neck cancer. A common side effect of irradiation to the neck and neck region is xerostomia caused by salivary gland dysfunction. Approximately 40,000 new cases of xerostomia result from radiation treatment in the United States each year. The ensuing salivary gland hypofunction results in significant morbidity and diminishes the effectiveness of anti-cancer therapies as well as the quality of life for these patients. Previous studies in a rat model have shown no correlation between induction of apoptosis in the salivary gland and either the immediate or chronic decrease in salivary function following gamma-radiation treatment.A significant level of apoptosis can be detected in the salivary glands of FVB mice following gamma-radiation treatment of the head and neck and this apoptosis is suppressed in transgenic mice expressing an activated mutant of Akt (myr-Akt1). Importantly, this suppression of apoptosis in myr-Akt1 mice preserves salivary function, as measured by saliva output, three and thirty days after gamma-radiation treatment. In order to translate these studies into a preclinal model we found that intravenous injection of IGF1 stimulated activation of endogenous Akt in the salivary glands in vivo. A single injection of IGF1 prior to exposure to gamma-radiation diminishes salivary acinar cell apoptosis and completely preserves salivary gland function three and thirty days following irradiation.These studies suggest that apoptosis of salivary acinar cells underlies salivary gland hypofunction occurring secondary to radiation of the head and neck region. Targeted delivery of IGF1 to the salivary gland of patients receiving head and neck irradiation may be useful in reducing or eliminating xerostomia and restoring quality of life to these patients

Neutralising antibodies for West Nile virus in horses from Brazilian Pantanal

Despite evidence of West Nile virus (WNV) activity in Colombia, Venezuela and Argentina, this virus has not been reported in most South American countries. In February 2009, we commenced an investigation for WNV in mosquitoes, horses and caimans from the Pantanal, Central-West Brazil. The sera of 168 horses and 30 caimans were initially tested using a flaviviruses-specific epitope-blocking enzyme-linked immunosorbent assay (blocking ELISA) for the detection of flavivirus-reactive antibodies. The seropositive samples were further tested using a plaque-reduction neutralisation test (PRNT90) for WNV and its most closely-related flaviviruses that circulate in Brazil to confirm the detection of specific virus-neutralising antibodies. Of the 93 (55.4%) blocking ELISA-seropositive horse serum samples, five (3%) were seropositive for WNV, nine (5.4%) were seropositive for St. Louis encephalitis virus, 18 (10.7%) were seropositive for Ilheus virus, three (1.8%) were seropositive for Cacipacore virus and none were seropositive for Rocio virus using PRNT90, with a criteria of > four-fold antibody titre difference. All caimans were negative for flaviviruses-specific antibodies using the blocking ELISA. No virus genome was detected from caiman blood or mosquito samples. The present study is the first report of confirmed serological evidence of WNV activity in Brazil

Ultracool dwarfs candidates based on 6 yr of the Dark Energy Survey data

We present a sample of 19 583 ultracool dwarf candidates brighter than z ≤23 selected from the Dark Energy Survey DR2 coadd data matched to VHS DR6, VIKING DR5, and AllWISE covering ∼ 480 deg2. The ultracool candidates were first pre-selected based on their (i–z), (z–Y), and (Y–J) colours. They were further classified using a method that compares their optical, near-infrared, and mid-infrared colours against templates of M, L, and T dwarfs. 14 099 objects are presented as new L and T candidates and the remaining objects are from the literature, including 5342 candidates from our previous work. Using this new and deeper sample of ultracool dwarf candidates we also present: 20 new candidate members to nearby young moving groups and associations, variable candidate sources and four new wide binary systems composed of two ultracool dwarfs. Finally, we also show the spectra of 12 new ultracool dwarfs discovered by our group and presented here for the first time. These spectroscopically confirmed objects are a sanity check of our selection of ultracool dwarfs and photometric classification method