Influence of sex, age, pubertal maturation and body mass index on circulating white blood cell counts in healthy European adolescents—the HELENA study

Percentiles 10th, 25th, 50th, 75th and 90th are presented for circulating white blood cells (WBC), neutrophils, lymphocytes, monocytes, eosinophils and basophils in healthy European adolescents (12.5–17.5 years, n = 405, 48.9 % boys), considering age, sex, puberty and body mass index (BMI). CD3+ (mature T cells), CD4+ (T helper), CD8+ (T cytotoxic), CD16+56+ (natural killer), CD19+ (B cells), CD3+CD45RA+, CD4+CD45RA+, CD8+CD45RA+ (naïve), CD3+CD45RO+, CD4+CD45RO+ and CD8+CD45RO+ (memory) lymphocytes were also analysed by immunophenotyping. Girls presented higher WBC, neutrophil, CD3+CD45RO+ and CD4+CD45RO+ cell counts and CD3+/CD19+ ratio, and lower CD3+CD45RA+ and CD4+CD45RA+ counts than boys. Age was associated with higher neutrophil counts and CD3+/CD19+, and lower CD19+ counts; in boys, with lower CD3+CD45RA+, CD4+CD45RA+ and CD8+CD45RA+ counts as well; in girls, with higher WBC, CD3+CD45RO+ and CD4+CD45RO+ counts. Pubertal maturation in boys was associated with lower WBC and lymphocyte counts; in girls, with higher basophil, CD3+CD45RO+ and CD4+CD45RO+ values. BMI was associated with higher WBC counts; in boys, also with higher lymphocyte counts; in girls, with higher neutrophil, CD4+, CD3+CD45RO+ and CD4+CD45RO+ counts. Conclusion: Our study provides normative values for circulating immune cells in adolescents, highlighting the importance of considering sex, age, pubertal maturation and BMI when establishing reference ranges for WBC in paediatric populations

Skewed Exposure to Environmental Antigens Complements Hygiene Hypothesis in Explaining the Rise of Allergy

The Hygiene Hypothesis has been recognized as an important cornerstone to explain the sudden increase in the prevalence of asthma and allergic diseases in modernized culture. The recent epidemic of allergic diseases is in contrast with the gradual implementation of Homo sapiens sapiens to the present-day forms of civilization. This civilization forms a gradual process with cumulative effects on the human immune system, which co-developed with parasitic and commensal Helminths. The clinical manifestation of this epidemic, however, became only visible in the second half of the twentieth century. In order to explain these clinical effects in terms of the underlying IgE-mediated reactions to innocuous environmental antigens, the low biodiversity of antigens in the domestic environment plays a pivotal role. The skewing of antigen exposure as a cumulative effect of reducing biodiversity in the immediate human environment as well as in changing food habits, provides a sufficient and parsimonious explanation for the rise in allergic diseases in a highly developed and helminth-free modernized culture. Socio-economic tendencies that incline towards a further reduction of environmental biodiversity may provide serious concern for future health. This article explains that the “Hygiene Hypothesis”, the “Old Friends Hypothesis”, and the “Skewed Antigen Exposure Hypothesis” are required to more fully explain the rise of allergy in modern societies

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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Enforced PGC-1α expression promotes CD8 T cell fitness, memory formation and antitumor immunity.

Memory CD8 T cells can provide long-term protection against tumors, which depends on their enhanced proliferative capacity, self-renewal and unique metabolic rewiring to sustain cellular fitness. Specifically, memory CD8 T cells engage oxidative phosphorylation and fatty acid oxidation to fulfill their metabolic demands. In contrast, tumor-infiltrating lymphocytes (TILs) display severe metabolic defects, which may underlie their functional decline. Here, we show that overexpression of proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), the master regulator of mitochondrial biogenesis (MB), favors CD8 T cell central memory formation rather than resident memory generation. PGC-1α-overexpressing CD8 T cells persist and mediate more robust recall responses to bacterial infection or peptide vaccination. Importantly, CD8 T cells with enhanced PGC-1α expression provide stronger antitumor immunity in a mouse melanoma model. Moreover, TILs overexpressing PGC-1α maintain higher mitochondrial activity and improved expansion when rechallenged in a tumor-free host. Altogether, our findings indicate that enforcing mitochondrial biogenesis promotes CD8 T cell memory formation, metabolic fitness, and antitumor immunity in vivo

Canonical Quantization, Space-Time Noncommutativity and Deformed Symmetries in Field Theory

Within the spirit of Dirac's canonical quantization, noncommutative spacetime field theories are introduced by making use of the reparametrization invariance of the action and of an arbitrary non-canonical symplectic structure. This construction implies that the constraints need to be deformed, resulting in an automatic Drinfeld twisting of the generators of the symmetries associated with the reparametrized theory. We illustrate our procedure for the case of a scalar field in 1+1- spacetime dimensions, but it can be readily generalized to arbitrary dimensions and arbitrary types of fields.Comment: 16 page

Development and Evaluation of a Sensitive PCR-ELISA System for Detection of Schistosoma Infection in Feces

Schistosomiasis is a neglected disease caused by worms of the genus Schistosoma. The transmission cycle requires contamination of bodies of water by parasite eggs present in excreta, specific snails as intermediate hosts and human contact with water. Fortunately, relatively safe and easily administrable drugs are available and, as the outcome of repeated treatment, a reduction of severe clinical forms and a decrease in the number of infected persons has been reported in endemic areas. The routine method for diagnosis is the microscopic examination but it fails when there are few eggs in the feces, as usually occurs in treated but noncured persons or in areas with low levels of transmission. This study reports the development of the PCR-ELISA system for the detection of Schistosoma DNA in human feces as an alternative approach to diagnose light infections. The system permits the enzymatic amplification of a specific region of the DNA from minute amounts of parasite material. Using the proposed PCR-ELISA approach for the diagnosis of a population in an endemic area in Brazil, 30% were found to be infected, as compared with the 18% found by microscopic fecal examination. Although the technique requires a complex laboratory infrastructure and specific funding it may be used by control programs targeting the elimination of schistosomiasis

Cutoff Scanning Matrix (CSM): structural classification and function prediction by protein inter-residue distance patterns

BACKGROUND: The unforgiving pace of growth of available biological data has increased the demand for efficient and scalable paradigms, models and methodologies for automatic annotation. In this paper, we present a novel structure-based protein function prediction and structural classification method: Cutoff Scanning Matrix (CSM). CSM generates feature vectors that represent distance patterns between protein residues. These feature vectors are then used as evidence for classification. Singular value decomposition is used as a preprocessing step to reduce dimensionality and noise. The aspect of protein function considered in the present work is enzyme activity. A series of experiments was performed on datasets based on Enzyme Commission (EC) numbers and mechanistically different enzyme superfamilies as well as other datasets derived from SCOP release 1.75. RESULTS: CSM was able to achieve a precision of up to 99% after SVD preprocessing for a database derived from manually curated protein superfamilies and up to 95% for a dataset of the 950 most-populated EC numbers. Moreover, we conducted experiments to verify our ability to assign SCOP class, superfamily, family and fold to protein domains. An experiment using the whole set of domains found in last SCOP version yielded high levels of precision and recall (up to 95%). Finally, we compared our structural classification results with those in the literature to place this work into context. Our method was capable of significantly improving the recall of a previous study while preserving a compatible precision level. CONCLUSIONS: We showed that the patterns derived from CSMs could effectively be used to predict protein function and thus help with automatic function annotation. We also demonstrated that our method is effective in structural classification tasks. These facts reinforce the idea that the pattern of inter-residue distances is an important component of family structural signatures. Furthermore, singular value decomposition provided a consistent increase in precision and recall, which makes it an important preprocessing step when dealing with noisy data

An Earthworm Riddle: Systematics and Phylogeography of the Spanish Lumbricid Postandrilus

As currently defined, the genus Postandrilus Qui and Bouché, 1998, (Lumbricidae) includes six earthworm species, five occurring in Majorca (Baleares Islands, western Mediterranean) and another in Galicia (NW Spain). This disjunct and restricted distribution raises some interesting phylogeographic questions: (1) Is Postandrilus distribution the result of the separation of the Baleares-Kabylies (BK) microplate from the proto-Iberian Peninsula in the Late Oligocene (30-28 Mya)--vicariant hypothesis? (2) Did Postandrilus diversify in Spain and then colonize the Baleares during the Messinian salinity crisis (MSC) 5.96-5.33 Mya--dispersal hypothesis? (3) Is the distribution the result of a two-step process--vicariance with subsequent dispersal?To answer these questions and assess Postandrilus evolutionary relationships and systematics, we collected all of the six Postandrilus species (46 specimens - 16 locations) and used Aporrectodea morenoe and three Prosellodrilus and two Cataladrilus species as the outgroup. Regions of the nuclear 28S rDNA and mitochondrial 16S rDNA, 12S rDNA, ND1, COII and tRNA genes (4,666 bp) were sequenced and analyzed using maximum likelihood and Bayesian methods of phylogenetic and divergence time estimation. The resulting trees revealed six new Postandrilus species in Majorca that clustered with the other five species already described. This Majorcan clade was sister to an Iberian clade including A. morenoe (outgroup) and Postandrilus bertae. Our phylogeny and divergence time estimates indicated that the split between the Iberian and Majorcan Postandrilus clades took place 30.1 Mya, in concordance with the break of the BK microplate from the proto-Iberian Peninsula, and that the present Majorcan clade diversified 5.7 Mya, during the MSC.Postandrilus is highly diverse including multiple cryptic species in Majorca. The genus is not monophyletic and invalid as currently defined. Postandrilus is of vicariant origin and its radiation began in the Late Oligocene