855 resultados para biomarker discovery
Sea surface temperatures and Biomarker abundance in the 1-3.5 Ma section of IODP Hole Site 306-U1313
Resumo:
During the Integrated Ocean Drilling Program (IODP) Expedition 307 for the first time a cold-water coral carbonate mound was drilled down through its base into the underlying sediments. In the current study, sample material from within and below Challenger Mound, located in the Belgica carbonate mound province in the Porcupine Basin offshore Ireland, was investigated for its distribution of microbial communities and gas composition using biogeochemical and geochemical approaches to elucidate the question on the initiation of carbonate mounds. Past and living microbial populations are lower in the mound section compared to the underlying sediments or sediments of an upslope reference site. A reason for this might be a reduced substrate feedstock, reflected by low total organic carbon (TOC) contents, in the once coral dominated mound sequence. In contrast, in the reference site a lithostratigraphic sequence with comparatively high TOC contents shows higher abundances of both past and present microbial communities, indicating favourable living conditions from time of sedimentation until today. Composition and isotopic values of gases below the mound base seem to point to a mixed gas of biogenic and thermogenic origin with a higher proportion of biogenic gas. Oil-derived hydrocarbons were not detected at the mound site. This suggests that at least in the investigated part of the mound base the upward flow of fossil hydrocarbons, being one hypothesis for the initiation of the formation of carbonate mounds, seems to be only of minor significance.
Resumo:
Background: Major Depressive Disorder (MDD) is among the most prevalent and disabling medical conditions worldwide. Identification of clinical and biological markers ("biomarkers") of treatment response could personalize clinical decisions and lead to better outcomes. This paper describes the aims, design, and methods of a discovery study of biomarkers in antidepressant treatment response, conducted by the Canadian Biomarker Integration Network in Depression (CAN-BIND). The CAN-BIND research program investigates and identifies biomarkers that help to predict outcomes in patients with MDD treated with antidepressant medication. The primary objective of this initial study (known as CAN-BIND-1) is to identify individual and integrated neuroimaging, electrophysiological, molecular, and clinical predictors of response to sequential antidepressant monotherapy and adjunctive therapy in MDD. Methods: CAN-BIND-1 is a multisite initiative involving 6 academic health centres working collaboratively with other universities and research centres. In the 16-week protocol, patients with MDD are treated with a first-line antidepressant (escitalopram 10-20 mg/d) that, if clinically warranted after eight weeks, is augmented with an evidence-based, add-on medication (aripiprazole 2-10 mg/d). Comprehensive datasets are obtained using clinical rating scales; behavioural, dimensional, and functioning/quality of life measures; neurocognitive testing; genomic, genetic, and proteomic profiling from blood samples; combined structural and functional magnetic resonance imaging; and electroencephalography. De-identified data from all sites are aggregated within a secure neuroinformatics platform for data integration, management, storage, and analyses. Statistical analyses will include multivariate and machine-learning techniques to identify predictors, moderators, and mediators of treatment response. Discussion: From June 2013 to February 2015, a cohort of 134 participants (85 outpatients with MDD and 49 healthy participants) has been evaluated at baseline. The clinical characteristics of this cohort are similar to other studies of MDD. Recruitment at all sites is ongoing to a target sample of 290 participants. CAN-BIND will identify biomarkers of treatment response in MDD through extensive clinical, molecular, and imaging assessments, in order to improve treatment practice and clinical outcomes. It will also create an innovative, robust platform and database for future research. Trial registration: ClinicalTrials.gov identifier NCT01655706. Registered July 27, 2012.
Resumo:
The occurrence of microbialites in post-glacial coral reefs has been interpreted to reflect an ecosystem response to environmental change. The greater thickness of microbialites in reefs with a volcanic hinterland compared to thinner microbial crusts in reefs with a non-volcanic hinterland led to the suggestion that fertilization of the reefal environment by chemical weathering of volcanic rocks stimulated primary productivity and microbialite formation. Using a molecular and isotopic approach on reef-microbialites from Tahiti (Pacific Ocean), it was recently shown that sulfate-reducing bacteria favored the formation of microbial carbonates. To test if similar mechanisms induced microbialite formation in other reefs as well, the Tahitian microbialites are compared with similar microbialites from coral reefs off Vanuatu (Pacific Ocean), Belize (Caribbean Sea, Atlantic Ocean), and the Maldives (Indian Ocean) in this study. The selected study sites cover a wide range of geological settings, reflecting variable input and composition of detritus. The new lipid biomarker data and stable sulfur isotope results confirm that sulfate-reducing bacteria played an intrinsic role in the precipitation of microbial carbonate at all study sites, irrespective of the geological setting. Abundant biomarkers indicative of sulfate reducers include a variety of terminally-branched and mid chain-branched fatty acids as well as mono-O-alkyl glycerol ethers. Isotope evidence for bacterial sulfate reduction is represented by low d34S values of pyrite (-43 to -42 per mill) enclosed in the microbialites and, compared to seawater sulfate, slightly elevated d34S and d18O values of carbonate-associated sulfate (21.9 to 22.2 per mill and 11.3 to 12.4 per mill, respectively). Microbialite formation took place in anoxic micro-environments, which presumably developed through the fertilization of the reef environment and the resultant accumulation of organic matter including bacterial extracellular polymeric substances (EPS), coral mucus, and marine snow in cavities within the coral framework. ToF-SIMS analysis reveals that the dark layers of laminated microbialites are enriched in carbohydrates, which are common constituents of EPS and coral mucus. These results support the hypothesis that bacterial degradation of EPS and coral mucus within microbial mats favored carbonate precipitation. Because reefal microbialites formed by similar processes in very different geological settings, this comparative study suggests that a volcanic hinterland is not required for microbialite growth. Yet, detrital input derived from the weathering of volcanic rocks appears to be a natural fertilizer, being conductive for the growth of microbial mats, which fosters the development of particularly abundant and thick microbial crusts.
Resumo:
Background and Objectives: Carotid revascularization to prevent future vascular events is reasonable in patients with high-grade carotid stenosis. Currently, several biomarkers to predict carotid plaque development and progression have been investigated, among which microRNAs (miRs) are promising tools for the diagnosis of atherosclerosis. Methods and Results: A total of 49 participants were included in the study, divided into two main populations: Population 1 comprising symptomatic and asymptomatic inpatients, and Population 2 comprising asymptomatic outpatients. The study consisted of two main phases: a preliminary discovery phase and a validation phase, applying different techniques. MiR-profiles were performed on plasma and plaque tissue samples obtained from 4 symptomatic and 4 asymptomatic inpatients. MiRs emerging from profiling comparisons, i.e. miR-126-5p, miR-134-5p, miR-145-5p, miR-151a-5p, miR-34b, miR-451a, miR-720 and miR-1271-5p, were subjected to validation through RT-qPCR analysis in the total cohort of donors. Comparing asymptomatic and symptomatic inpatients, significant differences were reported in the expression levels of c-miRs for miR-126-5p and miR-1271-5p in blood, being more expressed in symptomatic subjects. In contrast, simultaneous evaluation of the selected miRs in plaque tissue samples did not confirm data obtained by the miR profiling, and no significant differences were observed. Using Receiver-Operating Characteristic (ROC) analysis, a circulating molecular signature (mir-126-5p, miR-1271-5p, albumin, C-reactive protein, and monocytes) was identified, allowing the distinction of the two groups in Population 1 (AUC = 0.795). Conclusions: Data emerging from this thesis suggest that c-miRs (i.e. miR-126-5p, miR-1271-5p) combined with selected haemato-biochemical parameters (albumin, C-reactive protein, and monocytes) produced a good molecular 'signature' to distinguish asymptomatic and symptomatic inpatients. C-miRs in blood do not necessarily reflect the expression levels of the same miRs in carotid plaque tissues since different mechanism can influence their expression.
Resumo:
A pterosaur bone bed with at least 47 individuals (wing spans: 0.65-2.35 m) of a new species is reported from southern Brazil from an interdunal lake deposit of a Cretaceous desert, shedding new light on several biological aspects of those flying reptiles. The material represents a new pterosaur, Caiuajara dobruskii gen. et sp. nov., that is the southermost occurrence of the edentulous clade Tapejaridae (Tapejarinae, Pterodactyloidea) recovered so far. Caiuajara dobruskii differs from all other members of this clade in several cranial features, including the presence of a ventral sagittal bony expansion projected inside the nasoantorbital fenestra, which is formed by the premaxillae; and features of the lower jaw, like a marked rounded depression in the occlusal concavity of the dentary. Ontogenetic variation of Caiuajara dobruskii is mainly reflected in the size and inclination of the premaxillary crest, changing from small and inclined (∼ 115°) in juveniles to large and steep (∼ 90°) in adults. No particular ontogenetic features are observed in postcranial elements. The available information suggests that this species was gregarious, living in colonies, and most likely precocial, being able to fly at a very young age, which might have been a general trend for at least derived pterosaurs.
Resumo:
Oral squamous cell carcinoma is the most common type of cancer in the oral cavity, representing more than 90% of all oral cancers. The characterization of altered molecules in oral cancer is essential to understand molecular mechanisms underlying tumor progression as well as to contribute to cancer biomarker and therapeutic target discovery. Proteoglycans are key molecular effectors of cell surface and pericellular microenvironments, performing multiple functions in cancer. Two of the major basement membrane proteoglycans, agrin and perlecan, were investigated in this study regarding their role in oral cancer. Using real time quantitative PCR (qRT-PCR), we showed that agrin and perlecan are highly expressed in oral squamous cell carcinoma. Interestingly, cell lines originated from distinct sites showed different expression of agrin and perlecan. Enzymatically targeting chondroitin sulfate modification by chondroitinase, oral squamous carcinoma cell line had a reduced ability to adhere to extracellular matrix proteins and increased sensibility to cisplatin. Additionally, knockdown of agrin and perlecan promoted a decrease on cell migration and adhesion, and on resistance of cells to cisplatin. Our study showed, for the first time, a negative regulation on oral cancer-associated events by either targeting chondroitin sulfate content or agrin and perlecan levels.
Resumo:
Macro- and microarrays are well-established technologies to determine gene functions through repeated measurements of transcript abundance. We constructed a chicken skeletal muscle-associated array based on a muscle-specific EST database, which was used to generate a tissue expression dataset of similar to 4500 chicken genes across 5 adult tissues (skeletal muscle, heart, liver, brain, and skin). Only a small number of ESTs were sufficiently well characterized by BLAST searches to determine their probable cellular functions. Evidence of a particular tissue-characteristic expression can be considered an indication that the transcript is likely to be functionally significant. The skeletal muscle macroarray platform was first used to search for evidence of tissue-specific expression, focusing on the biological function of genes/transcripts, since gene expression profiles generated across tissues were found to be reliable and consistent. Hierarchical clustering analysis revealed consistent clustering among genes assigned to 'developmental growth', such as the ontology genes and germ layers. Accuracy of the expression data was supported by comparing information from known transcripts and tissue from which the transcript was derived with macroarray data. Hybridization assays resulted in consistent tissue expression profile, which will be useful to dissect tissue-regulatory networks and to predict functions of novel genes identified after extensive sequencing of the genomes of model organisms. Screening our skeletal-muscle platform using 5 chicken adult tissues allowed us identifying 43 'tissue-specific' transcripts, and 112 co-expressed uncharacterized transcripts with 62 putative motifs. This platform also represents an important tool for functional investigation of novel genes; to determine expression pattern according to developmental stages; to evaluate differences in muscular growth potential between chicken lines, and to identify tissue-specific genes.