Predicting the accuracy of multiple sequence alignment algorithms by using computational intelligent techniques

Multiple sequence alignments (MSAs) have become one of the most studied approaches in bioinformatics to perform other outstanding tasks such as structure prediction, biological function analysis or next-generation sequencing. However, current MSA algorithms do not always provide consistent solutions, since alignments become increasingly difficult when dealing with low similarity sequences. As widely known, these algorithms directly depend on specific features of the sequences, causing relevant influence on the alignment accuracy. Many MSA tools have been recently designed but it is not possible to know in advance which one is the most suitable for a particular set of sequences. In this work, we analyze some of the most used algorithms presented in the bibliography and their dependences on several features. A novel intelligent algorithm based on least square support vector machine is then developed to predict how accurate each alignment could be, depending on its analyzed features. This algorithm is performed with a dataset of 2180 MSAs. The proposed system first estimates the accuracy of possible alignments. The most promising methodologies are then selected in order to align each set of sequences. Since only one selected algorithm is run, the computational time is not excessively increased.     

Mosaicism for FMR1 gene full mutation and intermediate allele in a female foetus: A postzygotic retraction event

Fragile X syndrome is caused by the expansion of an unstable CGG repeat in the 5′UTR of FMR1 gene. The occurrence of mosaicism is not uncommon, especially in male patients, whereas in females it is not so often reported. Here we report a female foetus that was subject to prenatal diagnosis, because of her mother being a premutation carrier. The foetus was identified as being a mosaic for an intermediate allele and a full mutation of FMR1 gene, in the presence of a normal allele. The mosaic status was confirmed in three different tissues of the foetus – amniotic fluid, skin biopsy and blood – the last two obtained after pregnancy termination. Karyotype analysis and X-chromosome STR markers analysis do not support the mosaicism as inheritance of both maternal alleles. Oligonucleotide array-CGH excluded an imbalance that could contain the primer binding site with a different repeat size. The obtained results give compelling evidence for a postzygotic expansion mechanism where the foetus mosaic pattern originated from expansion of the mother's premutation into a full mutation and consequent regression to an intermediate allele in a proportion of cells. These events occurred in early embryogenesis before the commitment of cells into the different tissues, as the three tested tissues of the foetus have the same mosaic pattern. The couple has a son with Fragile X mental retardation syndrome and choose to terminate this pregnancy after genetic counselling.     

Sexual dimorphism and intra-populational colour pattern variation in the aposematic frog Dendrobates tinctorius

Despite the predicted purifying role of stabilising selection against variation in warning signals, many aposematic species exhibit high variation in their colour patterns. The maintenance of such variation is not well understood, but it has been suggested to be the result of an interaction between sexual and natural selection. This interaction could also facilitate the evolution of sexual dichromatism. Here we analyse in detail the colour patterns of the poison frog Dendrobates tinctorius and evaluate the possible correlates of the variability in aposematic signals in a natural population. Against the theoretical predictions of aposematism, we found that there is enormous intra-populational variation in colour patterns and that these also differ between the sexes: males have a yellower dorsum and bluer limbs than females. We discuss the possible roles of natural and sexual selection in the maintenance of this sexual dimorphism in coloration and argue that parental care could work synergistically with aposematism to select for yellower males.     

Reproductive cycle of the European clam Ruditapes decussatus from Óbidos Lagoon,Leiria, Portugal

ABSTRACT

In Portugal, the European clam (Ruditapes decussatus) is an important commercial resource. Óbidos Lagoon is a strong candidate as a cultivation area to increase European clam exploitation. However, the reproductive biology of this population has not been described. In this work, the reproductive cycle of R. decussatus was characterized by determining gonadal development stages, gonad index, condition index, and biochemical composition. The relationship between reproduction and environmental parameters (sea surface temperature, chlorophyll a, and particulate organic matter) was assessed. Ruditapes decussatus had an annual reproductive cycle. The gametogenic cycle started in late winter, and the ripe stage in spring was followed by spawning that began at the end of spring/early summer and extended until early autumn. The subsequent period of sexual rest occurred during the winter. Condition index showed seasonal variations related to food availability (chlorophyll a). The European clams in Óbidos Lagoon recovered rapidly after their reproductive period, most likely owing to the availability of food. This study will help to improve sustainable management of this wild stock and is important for future aquaculture development of this species.     

Assessing the Subcellular Dynamics of Alpha-synuclein Using Photoactivation Microscopy

Alpha-synuclein (aSyn) is implicated in Parkinson’s disease and several other neurodegenerative disorders. To date, the function and intracellular dynamics of aSyn are still unclear. Here, we tracked the dynamics of aSyn using photoactivatable green fluorescent protein as a reporter. We found that the availability of the aSyn N terminus modulates its shuttling into the nucleus. Interestingly, familial aSyn mutations altered the dynamics at which the protein distributes throughout the cell. Both the A30P and A53T aSyn mutations increase the speed at which the protein moves between the nucleus and cytoplasm, respectively. We also found that specific kinases potentiate the shuttling of aSyn between nucleus and cytoplasm. A mutant aSyn form that blocks S129 phosphorylation, S129A, results in the formation of cytoplasmic inclusions, suggesting phosphorylation modulates aggregation in addition to modulating aSyn intracellular dynamics. Finally, we found that the molecular chaperone HSP70 accelerates the entry of aSyn into the nuclear compartment.     

Synthetic Condensed 1,4-naphthoquinone Derivative Shifts Neural Stem Cell Differentiation by Regulating Redox State

Naphthoquinones are bioactive compounds widespread in nature that impact on several cellular pathways, including cell proliferation and survival, by acting as prooxidants and electrophiles. We have previously described the role of the synthetic isoxazole condensed 1,4-naphthoquinone derivative 1a in preventing apoptosis induced by distinct stimuli in several cell models. In addition, apoptosis regulators and executioners may control neural stem cell (NSC) fate, without involving cell death per se. Here, we hypothesize that 1a might also play a role in NSC fate decision. We found that exposure to 1a shifts NSC differentiation potential from neurogenic to gliogenic lineage and involves the generation of reactive oxygen species, without increasing cell death. Modulation of caspases and calpains, using cysteine protease inhibitors, failed to mimic 1a effects. In addition, incubation with the naphthoquinone derivative resulted in upregulation and nuclear translocation of antioxidant responsive proteins, Nrf2 and Sirt1, which in turn may mediate 1a-directed shift in NSC differentiation. In fact, antioxidants halted the shift in NSC differentiation potential from neurogenic to gliogenic lineage, while strongly reducing reactive oxygen species generation and Nrf2 and Sirt1 nuclear translocation in NSC exposed to 1a. Collectively, these data support a new role for a specific naphthoquinone derivative in NSC fate decision and underline the importance of redox environment control.     

Distribution,habitat disturbance and pollination of the endangered orchid Broughtonia cubensis (Epidendrae: Laeliinae)

The geographical distribution, population structure and pollination ecology are key aspects in the conservation and management of rare orchids. Here, we address these aspects and the main threats affecting the endangered Cuban orchid Broughtonia cubensis. This rewardless orchid is self‐compatible, but pollinator dependent. However, seed production can be negatively affected by insect‐mediated selfing. Three species of small bee (genera Ceratina and Lasioglossum) act as pollinators. As in the case of other nectarless orchids, we detected two species of plant producing large amounts of nectar in the area, the floral morphology of which closely resembles that of B. cubensis. The simultaneous flowering of these species could positively affect the reproductive success of B. cubensis. Nonetheless, the fitness of this orchid in natural conditions is low, possibly related to strong pollen limitation. To the problems arising from reduced fitness is added the fact that its historical distribution range has been greatly reduced in recent years. Throughout this study, we have detected dramatic reductions in the population sizes, in some cases as a result of human plundering, but also as a consequence of hurricanes. Based on the results of this study, we propose some guidelines to manage and conserve this orchid. © 2013 The Linnean Society of London, Botanical Journal of the Linnean Society, 2013, 172 , 345–357.     

UCP2 and ANT differently modulate proton-leak in brain mitochondria of long-term hyperglycemic and recurrent hypoglycemic rats

A growing body of evidence suggests that mitochondrial proton-leak functions as a regulator of reactive oxygen species production and its modulation may limit oxidative injury to tissues. The main purpose of this work was to characterize the proton-leak of brain cortical mitochondria from long-term hyperglycemic and insulin-induced recurrent hypoglycemic rats through the modulation of the uncoupling protein 2 (UCP2) and adenine nucleotide translocator (ANT). Streptozotocin-induced diabetic rats were treated subcutaneously with twice-daily insulin injections during 2 weeks to induce the hypoglycemic episodes. No differences in the basal proton-leak, UCP2 and ANT protein levels were observed between the experimental groups. Mitochondria from recurrent hypoglycemic rats presented a decrease in proton-leak in the presence of GDP, a specific UCP2 inhibitor, while an increase in proton-leak was observed in the presence of linoleic acid, a proton-leak activator, this effect being reverted by the simultaneous addition of GDP. Mitochondria from long-term hyperglycemic rats showed an enhanced susceptibility to ANT modulation as demonstrated by the complete inhibition of basal and linoleic acid-induced proton-leak caused by the ANT specific inhibitor carboxyatractyloside. Our results show that recurrent-hypoglycemia renders mitochondria more susceptible to UCPs modulation while the proton-leak of long-term hyperglycemic rats is mainly modulated by ANT, which suggest that brain cortical mitochondria have distinct adaptation mechanisms in face of different metabolic insults.