Jornal de Biomarcadores Moleculares e Diagnóstico

Sabe-se que as células humanas são incapazes de sintetizar o ácido N-glicolil neuramínico (NeuGc) devido à inativação da citidina monofosfo-N-acetil-ácido neuramínico hidroxilase, a enzima responsável pela síntese deste ácido siálico. Por outro lado, a expressão aberrante de NeuGc-sialoconjugados foi detectada em humanos, embora preferencialmente em tecidos malignos. A hipótese mais aceita para a presença de NeuGc em malignidades humanas está associada à sua incorporação de fontes alimentares ao metabolismo alterado de células malignas, que também é favorecido pelas condições hipóxicas dos tumores. No entanto, a importância dos conjugados contendo NeuGc na biologia tumoral, bem como suas implicações clínicas, ainda está sob investigação. Uma dessas moléculas é o gangliosídeo Nglicolil GM3 (NeuGcGM3).

Nutrientes são parcialmente bioacessíveis para serem extraídos de sua matriz. Eles podem ser parcialmente perdidos pelo processamento em uma refeição e pelo metabolismo após a absorção do trato gastrointestinal. Várias etapas nesta cascata têm um impacto na quantidade de nutrientes que finalmente estará biodisponível para um efeito. As doses diárias são definidas e amplamente recomendadas para obter tal efeito. No entanto, essas necessidades são derivadas da observação de populações saudáveis ??e são aumentadas para cobrir as necessidades de grupos especiais de consumidores e pacientes ou para gravidez. As doses diárias estão sujeitas a mudanças frequentes sempre que surgem novas evidências científicas, como é o caso da vitamina D. Este artigo descreve as razões pelas quais recomendações geralmente razoáveis ??podem falhar ocasionalmente são encontradas entre a variação de genes, idade, gênero ou raça, bem como epigenética, que contribuem para a expressão individual da capacidade metabólica e, portanto, para diferenças na biodisponibilidade individual.

On the basis of this axioms we are proposing that consciousness is the result of a global workspace in the brain, which distributes information to the huge number of paralell unconscious processors forming a rest of the brain. Our theory is founded on the view that the brain is composed of many different paralell processors, or moduls, each capable of performing some task on the symbolic representations that it receives as input. The moduls are flexible in that they can combine to form new processors capable of performing novel tasks, and can decompose into a smaller component processors. Axiom A: The consciousness is a mathematical structure, with neurobiological semantics. Axiom B: The higher mental processes all correspond to well-defined but, at present, poorly understood information processing functions that are carried out by physical systems, our brains.

Many targeted therapies have been developed to treat lung cancer. Unfortunately, however statistical data over the past two decades suggest only a slight improvement in a patient's survival rate after diagnosis. Clonal evolution and tumor heterogeneity are the major obstacles in designing effective targeted treatments against cancer. To create more comprehensive treatments, emerging therapies target bioenergetic pathways of cancer cells. Like normal cells, cancer cells can generate energy only through glycolysis and oxidative phosphorylation. Notably, a number of studies have shown that many types of cancer cells rely heavily on mitochondrial respiration. Importantly, research carried out in the authors’ laboratory showed that non-small cell lung cancer cells exhibit increased levels of mitochondrial and heme function. Hence, limiting heme availability interferes with bioenergetics of cancer cells. Evidently, targeting heme function may provide an effective way for treating lung cancer.

A novel two-photon fluorescence probe for Hg2+ derived from bis(styryl)terephthalonitrile as a two-photon fluorophore and bis [2-(2-hydroxyethyl sulfanyl) ethyl] amino group (ionophore) as a novel Hg2+ ligand was developed. The probe possesses small molecule size, large two-photon absorption cross-section (1067 GM) in H2O, noncytotoxic effect, long-wavelength emission at 588 nm, large Stokes shift (121 nm), excellent photostability, high water-solubility, good cell-permeability, and pH-insensitivity in the biologically relevant range. The probe can selectively detect Hg2+ ions in live cells and living tissues without interference from other metal ions and the membrane-bound probes, and its quenching constant (Ksv TP) is 8.73 × 105 M-1.

Particular MYBPC3. A 25-basepair deletion variant of MYBPC3 occurs at high frequency in individuals of South Asian descent and is estimated to affect 55 million people worldwide, carrying an increased likelihood of cardiomyopathy. Since this variant is prevalent and severe in this subpopulation, quick and affordable screening to provide risk-assessment to guide treatment for these patients is critical. An RNaseH qPCR assay was developed to quickly and specifically diagnose the presence of the 25-basepair deletion variant in MYBPC3. RNAseH-blocked nucleotide primers were designed to identify the presence or absence of the wild type MYBPC3 allele or the genomic sequence containing the 25-basepair deletion. Using this assay, three blinded operators were able to accurately determine the genotype from human genomic DNA samples from blood and saliva using a qPCR thermocycler. Furthermore, positive variant subjects were examined by both electrocardiography and echocardiography for the presence of cardiomyopathy. A simple, robust assay was established, verified and validated that can be automated to detect the presence of the highly prevalent 25-basepair deletion MYBPC3 variant using both blood and saliva samples. The assay will provide quick and accurate prescreening of individuals at high risk for cardiomyopathies and allow for better clinical identification of 25-basepair deletion MYBPC3 carriers in large cohort epidemiological studies.

We have designed a standardized protocol with multiplex-primer sets capable of detecting majority IG kappa (IGK) and IG lambda (IGL) light chain rearrangements in plasma cell neoplasms (PCN). Thirty primers were combined in three multiplexed PCR reactions to target IGK, KDE and IGL rearrangements. Variable region (V) primers were designed to prevent “primer dimers”, provide matching melting temperatures (Tm), minimize amplicon size, and optimize sequencing time. Amplicons were subjected to capillary gel electrophoresis for analysis. In a discovery series, we tested 37 plasma cells neoplasms PCN (28 PCNs at diagnosis and 9 PCNs post-treatment). The assay investigated an additional 52 prospective PCN cases in the validation series. Results were compared to bone marrow morphology, immunohistochemical (IHC), flow cytometry data, and standard IGH FRIII gene rearrangement assay. In the discovery series, the following sensitivities/specificities were obtained for mature B-cell neoplasms: IGH FRIII: 29.7%/100%, IGK: 80.4%/100%, KDE: 25.0%/100%, and IGL: 35.1%/96.8%. The combination of IGH FRIII, IGK, and KDE detected 83.8% (31/37) vs 67.3% (35/52) in the discovery vs validation series, respectively, for the PCN population. Interestingly, 21.2% (11/52) of the validation samples positive by IG clonality, were negative by IHC and flow cytometry. In IHC/flow cytometry positive cases with a PCN representing a tumor burden of >50%, 10% to 50%, 1% to 10%, 0% to 1% of cells, the combined sensitivity of the IG clonality assay was 100% (20/20), 72% (23/32), 53% (10/19) and 20% (1/5) respectively. This IGK/IGL clonality assay has good sensitivity at diagnosis.