Identification of biomarker panels as predictors of severity in coronary artery disease

Matrix metalloproteinases (MMPs) are implicated in atherosclerotic plaque rupture and recondition. Specific tissue inhibitors (TIMPs) control MMP functions. Both MMPs and TIMPs are potential biomarkers of plaque instability. Elevated Apo-CII and CIII and Apo-E levels are recognized as cardiovascular disease risk factors. We aimed to establish the best blood biomarker panel to evaluate the coronary artery disease (CAD) severity. Plasma levels of MMP-3 and MMP-9, TIMP-1 and TIMP-2, Apo-CII, Apo-CIII and Apo-E were measured in 472 patients with CAD evaluated by coronary angiography and electrocardiography, and in 285 healthy controls. MMP-3 and MMP-9 plasma levels in CAD patients were significantly increased (P < 0.001) compared to controls (3.54- and 3.81-fold, respectively). Furthermore, these increments are modulated by CAD severity as well as for Apo-CII and Apo-CIII levels (P < 0.001). TIMPs levels were decreased in CAD versus controls (P < 0.001) and in inverse correlation to MMPs. Standard ROC curve approach showed the importance of panels of biomarkers, including MMP-3, MMP-9, TIMP-1, TIMP-2, Apo-CII and Apo-CIII, for disease aggravation diagnosis. A high area under curve (AUC) value (0.995) was reached for the association of MMP-9, TIMP-2 and Apo-CIII. The unbalance between MMPs and TIMPs in vascular wall and dyslipidaemia creates favourable conditions for plaque disruption. Our study suggests that the combination of MMP-9, TIMP-2 and Apo-CIII values (‘CAD aggravation panel’) characterizes the severity of CAD, that is electrophysiological state, number of involved vessels, stent disposal and type of stent.     

The microbiota of intertidal macroalgae Fucus distichus is site-specific and resistant to change following transplant

It is unclear how host-associated microbial communities will be affected by future environmental change. Characterizing how microbiota differ across sites with varying environmental conditions and assessing the stability of the microbiota in response to abiotic variation are critical steps towards predicting outcomes of environmental change. Intertidal organisms are valuable study systems because they experience extreme variation in environmental conditions on tractable timescales such as tide cycles and across small spatial gradients in the intertidal zone. Here we show a widespread intertidal macroalgae, Fucus distichus, hosts site-specific microbiota over small (meters to kilometres) spatial scales. We demonstrate stability of site-specific microbial associations by manipulating the host environment and microbial species pool with common garden and reciprocal transplant experiments. We hypothesized that F. distichus microbiota would readily shift to reflect the contemporary environment due to selective filtering by abiotic conditions and/or colonization by microbes from the new environment or nearby hosts. Instead, F. distichus microbiota was stable for days after transplantation in both the laboratory and field. Our findings expand the current understanding of microbiota dynamics on an intertidal foundation species. These results may also point to adaptations for withstanding short-term environmental variation, in hosts and/or microbes, facilitating stable host–microbial associations.     

How threatened are large branchiopods (Crustacea,Branchiopoda) in the Iberian Peninsula?

Aquatic macroinvertebrates in drainage ditches may alter rates of nutrient cycling and decomposition of organic matter but have not been accounted for in studies of ditch biogeochemistry. We collected sediment cores from four pairs of field (intermittent) and collection (perennial) ditches on Maryland’s Eastern Shore monthly from March 2011 to February 2012 to determine how taxonomic and functional group composition varies among different ditch types. We identified 138 taxa and assigned them to functional groups according to trophic position and modes of burrowing. There was no difference in mean abundance of invertebrates (5821 ind./m²) between seasons or types of ditches, and species richness peaked in winter (20 taxa/site) compared to other seasons (15 taxa/site), but did not vary between ditch types. Assemblage composition differed between field and collection ditches, but functional group composition did not. Field ditches flow intermittently which may limit the assemblage to early colonists and taxa adapted to survive desiccation. The benthic macroinvertebrate assemblage was dominated by the collector–gatherer functional feeding group (83.6%) and burrowing taxa (97.1%). Bioturbation by burrowing macroinvertebrates is likely an important process contributing to ecosystem-scale functions of drainage ditches, including regulation of biogeochemical processes occurring at the sediment–water interface.     

Defining the importance of landscape metrics for large branchiopod biodiversity and conservation: the case of the Iberian Peninsula and Balearic Islands

The deficiency in the distributional data of invertebrate taxa is one of the major impediments acting on the bias towards the low awareness of its conservation status. The present study sets a basic framework to understand the large branchiopods distribution in the Iberian Peninsula and Balearic Islands. Since the extensive surveys performed in the late 1980s, no more studies existed updating the information for the whole studied area. The present study fills the gap, gathering together all available information on large branchiopods distribution since 1995, and analysing the effect of human population density and several landscape characteristics on their distribution, taking into consideration different spatial scales (100 m, 1 km and 10 km). In overall, 28 large branchiopod taxa (17 anostracans, 7 notostracans and 4 spinicaudatans) are known to occur in the area. Approximately 30% of the sites hosted multiple species, with a maximum of 6 species. Significant positive co-occurring species pairs were found clustered together, forming 4 different associations of large branchiopod species. In general, species clustered in the same group showed similar responses to analysed landscape characteristics, usually showing a better fit at higher spatial scales.     

Structural Features of Single-Stranded Integron Cassette attC Sites and Their Role in Strand Selection

We recently showed that cassette integration and deletion in integron platforms were occurring through unconventional site-specific recombination reactions involving only the bottom strand of attC sites. The lack of sequence conservation among attC sites led us to hypothesize that sequence-independent structural recognition determinants must exist within attC sites. The structural data obtained from a synaptic complex of the Vibrio cholerae integrase with the bottom strand of an attC site has shown the importance of extra helical bases (EHB) inside the stem-loop structure formed from the bottom strand. Here, we systematically determined the contribution of three structural elements common to all known single-stranded attC site recombination substrates (the EHBs, the unpaired central spacer (UCS), and the variable terminal structure (VTS)) to strand choice and recombination. Their roles have been evaluated in vivo in the attI×attC reaction context using the suicide conjugation assay we previously developed, but also in an attC×attC reaction using a deletion assay. Conjugation was used to deliver the attC sites in single-stranded form. Our results show that strand choice is primarily directed by the first EHB, but the presence of the two other EHBs also serves to increase this strand selection. We found that the structure of the central spacer is essential to achieve high level recombination of the bottom strand, suggesting a dual role for this structure in active site exclusion and for hindering the reverse reaction after the first strand exchange. Moreover, we have shown that the VTS has apparently no role in strand selectivity.     

The Human Proteins MBD5 and MBD6 Associate with Heterochromatin but They Do Not Bind Methylated DNA

Background

MBD5 and MBD6 are two uncharacterized mammalian proteins that contain a putative Methyl-Binding Domain (MBD). In the proteins MBD1, MBD2, MBD4, and MeCP2, this domain allows the specific recognition of DNA containing methylated cytosine; as a consequence, the proteins serve as interpreters of DNA methylation, an essential epigenetic mark. It is unknown whether MBD5 or MBD6 also bind methylated DNA; this question has interest for basic research, but also practical consequences for human health, as MBD5 deletions are the likely cause of certain cases of mental retardation.

Principal Findings

Here we report the first functional characterization of MBD5 and MBD6. We have observed that the proteins colocalize with heterochromatin in cultured cells, and that this localization requires the integrity of their MBD. However, heterochromatic localization is maintained in cells with severely decreased levels of DNA methylation. In vitro, neither MBD5 nor MBD6 binds any of the methylated sequences DNA that were tested.

Conclusions

Our data suggest that MBD5 and MBD6 are unlikely to be methyl-binding proteins, yet they may contribute to the formation or function of heterochromatin. One isoform of MBD5 is highly expressed in oocytes, which suggests a possible role in epigenetic reprogramming after fertilization.     

Discovering significant evolution patterns from satellite image time series

Satellite Image Time Series (SITS) provide us with precious information on land cover evolution. By studying these series of images we can both understand the changes of specific areas and discover global phenomena that spread over larger areas. Changes that can occur throughout the sensing time can spread over very long periods and may have different start time and end time depending on the location, which complicates the mining and the analysis of series of images. This work focuses on frequent sequential pattern mining (FSPM) methods, since this family of methods fits the above-mentioned issues. This family of methods consists of finding the most frequent evolution behaviors, and is actually able to extract long-term changes as well as short term ones, whenever the change may start and end. However, applying FSPM methods to SITS implies confronting two main challenges, related to the characteristics of SITS and the domain's constraints. First, satellite images associate multiple measures with a single pixel (the radiometric levels of different wavelengths corresponding to infra-red, red, etc.), which makes the search space multi-dimensional and thus requires specific mining algorithms. Furthermore, the non evolving regions, which are the vast majority and overwhelm the evolving ones, challenge the discovery of these patterns. We propose a SITS mining framework that enables discovery of these patterns despite these constraints and characteristics. Our proposal is inspired from FSPM and provides a relevant visualization principle. Experiments carried out on 35 images sensed over 20 years show the proposed approach makes it possible to extract relevant evolution behaviors.