Maternal effects on anogenital distance in a wild marmot population

Peer reviewedPublisher PD

T Cells Recognizing a Peptide Contaminant Undetectable by Mass Spectrometry

Synthetic peptides are widely used in immunological research as epitopes to stimulate their cognate T cells. These preparations are never completely pure, but trace contaminants are commonly revealed by mass spectrometry quality controls. In an effort to characterize novel major histocompatibility complex (MHC) Class I-restricted β-cell epitopes in non-obese diabetic (NOD) mice, we identified islet-infiltrating CD8+ T cells recognizing a contaminating peptide. The amount of this contaminant was so small to be undetectable by direct mass spectrometry. Only after concentration by liquid chromatography, we observed a mass peak corresponding to an immunodominant islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)206-214 epitope described in the literature. Generation of CD8+ T-cell clones recognizing IGRP206-214 using a novel method confirmed the identity of the contaminant, further underlining the immunodominance of IGRP206-214. If left undetected, minute impurities in synthetic peptide preparations may thus give spurious results

Evaluation of allelic forms of the erythrocyte binding antigen 175 (EBA-175) in Plasmodium falciparum field isolates from Brazilian endemic area

<p>Abstract</p> <p>Background</p> <p>The <it>Plasmodium falciparum </it>Erythrocyte Binding Antigen-175 (EBA-175) is an antigen considered to be one of the leading malaria vaccine candidates. EBA-175 mediates sialic acid-dependent binding to glycophorin A on the erythrocytes playing a crucial role during invasion of the <it>P. falciparum </it>in the host cell. Dimorphic allele segments, termed C-fragment and F-fragment, have been found in high endemicity malaria areas and associations between the dimorphism and severe malaria have been described. In this study, the genetic dimorphism of EBA-175 was evaluated in <it>P. falciparum </it>field isolates from Brazilian malaria endemic area.</p> <p>Methods</p> <p>The study was carried out in rural villages situated near Porto Velho, Rondonia State in the Brazilian Amazon in three time points between 1993 and 2008. The allelic dimorphism of the EBA-175 was analysed by Nested PCR.</p> <p>Results</p> <p>The classical allelic dimorphism of the EBA-175 was identified in the studied area. Overall, C-fragment was amplified in a higher frequency than F-fragment. The same was observed in the three time points where C-fragment was observed in a higher frequency than F-fragment. Single infections (one fragment amplified) were more frequent than mixed infection (two fragments amplified).</p> <p>Conclusions</p> <p>These findings confirm the dimorphism of EBA175, since only the two types of fragments were amplified, C-fragment and F-fragment. Also, the results show the remarkable predominance of CAMP allele in the studied area. The comparative analysis in three time points indicates that the allelic dimorphism of the EBA-175 is stable over time.</p

Insights from Amphioxus into the Evolution of Vertebrate Cartilage

Central to the story of vertebrate evolution is the origin of the vertebrate head, a problem difficult to approach using paleontology and comparative morphology due to a lack of unambiguous intermediate forms. Embryologically, much of the vertebrate head is derived from two ectodermal tissues, the neural crest and cranial placodes. Recent work in protochordates suggests the first chordates possessed migratory neural tube cells with some features of neural crest cells. However, it is unclear how and when these cells acquired the ability to form cellular cartilage, a cell type unique to vertebrates. It has been variously proposed that the neural crest acquired chondrogenic ability by recruiting proto-chondrogenic gene programs deployed in the neural tube, pharynx, and notochord. To test these hypotheses we examined the expression of 11 amphioxus orthologs of genes involved in neural crest chondrogenesis. Consistent with cellular cartilage as a vertebrate novelty, we find that no single amphioxus tissue co-expresses all or most of these genes. However, most are variously co-expressed in mesodermal derivatives. Our results suggest that neural crest-derived cartilage evolved by serial cooption of genes which functioned primitively in mesoderm

Estimation of the national disease burden of influenza-associated severe acute respiratory illness in Kenya and Guatemala : a novel methodology

Background: Knowing the national disease burden of severe influenza in low-income countries can inform policy decisions around influenza treatment and prevention. We present a novel methodology using locally generated data for estimating this burden. Methods and Findings: This method begins with calculating the hospitalized severe acute respiratory illness (SARI) incidence for children <5 years old and persons ≥5 years old from population-based surveillance in one province. This base rate of SARI is then adjusted for each province based on the prevalence of risk factors and healthcare-seeking behavior. The percentage of SARI with influenza virus detected is determined from provincial-level sentinel surveillance and applied to the adjusted provincial rates of hospitalized SARI. Healthcare-seeking data from healthcare utilization surveys is used to estimate non-hospitalized influenza-associated SARI. Rates of hospitalized and non-hospitalized influenza-associated SARI are applied to census data to calculate the national number of cases. The method was field-tested in Kenya, and validated in Guatemala, using data from August 2009–July 2011. In Kenya (2009 population 38.6 million persons), the annual number of hospitalized influenza-associated SARI cases ranged from 17,129–27,659 for children <5 years old (2.9–4.7 per 1,000 persons) and 6,882–7,836 for persons ≥5 years old (0.21–0.24 per 1,000 persons), depending on year and base rate used. In Guatemala (2011 population 14.7 million persons), the annual number of hospitalized cases of influenza-associated pneumonia ranged from 1,065–2,259 (0.5–1.0 per 1,000 persons) among children <5 years old and 779–2,252 cases (0.1–0.2 per 1,000 persons) for persons ≥5 years old, depending on year and base rate used. In both countries, the number of non-hospitalized influenza-associated cases was several-fold higher than the hospitalized cases. Conclusions: Influenza virus was associated with a substantial amount of severe disease in Kenya and Guatemala. This method can be performed in most low and lower-middle income countries

Combination therapy: the next opportunity and challenge of medicine

From an historical point of view, combination therapy was the basis for the care of important diseases like infection diseases or cancer. Today the "cocktail drug" of the Highly Active Anti Retroviral Therapy (HAART) has reduced the death for HIV infection changing the outcome of such disease. Moreover, the combination of different strategies changed the course of transplants (both in haematology and surgical transplant). Different diseases with high social impact including cardiovascular, metabolic (obesity, hypercholesterolaemia and diabetes) and autoimmune diseases, have better results with combinations of different drug classes of drugs. After recent successes in the immunotherapy field (Sepuleucel-T, ipilimumab) and the new promising small molecule therapies, cancer should be the next challenge for combination strategies

Near fatal posterior reversible encephalopathy syndrome complicating chronic liver failure and treated by induced hypothermia and dialysis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Posterior reversible encephalopathy syndrome is a clinico-neuroradiological entity characterized by headache, vomiting, altered mental status, blurred vision and seizures with neuroimaging studies demonstrating white-gray matter edema involving predominantly the posterior region of the brain.</p> <p>Case presentation</p> <p>We report a 47-year-old Caucasian man with liver cirrhosis who developed posterior reversible encephalopathy syndrome following an upper gastrointestinal hemorrhage and who was managed with induced hypothermia for control of intracranial hypertension and continuous veno-venous hemodiafiltration for severe hyperammonemia.</p> <p>Conclusion</p> <p>We believe this is the first documented case report of posterior reversible encephalopathy syndrome associated with cirrhosis as well as the first report of the use of induced hypothermia and continuous veno-venous hemodiafiltration in this setting.</p

A Discrete Time Model for the Analysis of Medium-Throughput C. elegans Growth Data

BACKGROUND: As part of a program to predict the toxicity of environmental agents on human health using alternative methods, several in vivo high- and medium-throughput assays are being developed that use C. elegans as a model organism. C. elegans-based toxicological assays utilize the COPAS Biosort flow sorting system that can rapidly measure size, extinction (EXT) and time-of-flight (TOF), of individual nematodes. The use of this technology requires the development of mathematical and statistical tools to properly analyze the large volumes of biological data. METHODOLOGY/PRINCIPAL FINDINGS: Findings A Markov model was developed that predicts the growth of populations of C. elegans. The model was developed using observations from a 60 h growth study in which five cohorts of 300 nematodes each were aspirated and measured every 12 h. Frequency distributions of log(EXT) measurements that were made when loading C. elegans L1 larvae into 96 well plates (t = 0 h) were used by the model to predict the frequency distributions of the same set of nematodes when measured at 12 h intervals. The model prediction coincided well with the biological observations confirming the validity of the model. The model was also applied to log(TOF) measurements following an adaptation. The adaptation accounted for variability in TOF measurements associated with potential curling or shortening of the nematodes as they passed through the flow cell of the Biosort. By providing accurate estimates of frequencies of EXT or TOF measurements following varying growth periods, the model was able to estimate growth rates. Best model fits showed that C. elegans did not grow at a constant exponential rate. Growth was best described with three different rates. Microscopic observations indicated that the points where the growth rates changed corresponded to specific developmental events: the L1/L2 molt and the start of oogenesis in young adult C. elegans. CONCLUSIONS: Quantitative analysis of COPAS Biosort measurements of C. elegans growth has been hampered by the lack of a mathematical model. In addition, extraneous matter and the inability to assign specific measurements to specific nematodes made it difficult to estimate growth rates. The present model addresses these problems through a population-based Markov model