Catalogues of mammalian long noncoding RNAs: modest conservation and incompleteness

BACKGROUND: Despite increasing interest in the noncoding fraction of transcriptomes, the number, species-conservation and functions, if any, of many non-protein-coding transcripts remain to be discovered. Two extensive long intergenic noncoding RNA (ncRNA) transcript catalogues are now available for mouse: over 3,000 macroRNAs identified by cDNA sequencing, and 1,600 long intergenic noncoding RNA (lincRNA) intervals that are predicted from chromatin-state maps. Previously we showed that macroRNAs tend to be more highly conserved than putatively neutral sequence, although only 5% of bases are predicted as constrained. By contrast, over a thousand lincRNAs were reported as being highly conserved. This apparent difference may account for the surprisingly small fraction (11%) of transcripts that are represented in both catalogues. Here we sought to resolve the reported discrepancy between the evolutionary rates for these two sets. RESULTS: Our analyses reveal lincRNA and macroRNA exon sequences to be subject to the same relatively low degree of sequence constraint. Nonetheless, our observations are consistent with the functionality of a fraction of ncRNA in these sets, with up to a quarter of ncRNA exons having evolved significantly slower than neighboring neutral sequence. The more tissue-specific macroRNAs are enriched in predicted RNA secondary structures and thus may often act in trans, whereas the more highly and broadly expressed lincRNAs appear more likely to act in the cis-regulation of adjacent transcription factor genes. CONCLUSIONS: Taken together, our results indicate that each of the two ncRNA catalogues unevenly and lightly samples the true, much larger, ncRNA repertoire of the mouse

Role of microRNAs in the age-associated decline of pancreatic beta cell function in rat islets

This is a freely-available open access publication. Please cite the published version which is available via the DOI link in this record.AIMS/HYPOTHESIS: Ageing can lead to reduced insulin sensitivity and loss of pancreatic beta cell function, predisposing individuals to the development of diabetes. The aim of this study was to assess the contribution of microRNAs (miRNAs) to age-associated beta cell dysfunction. METHODS: The global mRNA and miRNA profiles of 3- and 12-month-old rat islets were collected by microarray. The functional impact of age-associated differences in miRNA expression was investigated by mimicking the observed changes in primary beta cells from young animals. RESULTS: Beta cells from 12-month-old rats retained normal insulin content and secretion, but failed to proliferate in response to mitotic stimuli. The islets of these animals displayed modifications at the level of several miRNAs, including upregulation of miR-34a, miR-124a and miR-383, and downregulation of miR-130b and miR-181a. Computational analysis of the transcriptomic modifications observed in the islets of 12-month-old rats revealed that the differentially expressed genes were enriched for miR-34a and miR-181a targets. Indeed, the induction of miR-34a and reduction of miR-181a in the islets of young animals mimicked the impaired beta cell proliferation observed in old animals. mRNA coding for alpha-type platelet-derived growth factor receptor, which is critical for compensatory beta cell mass expansion, is directly inhibited by miR34a and is likely to be at least partly responsible for the effects of this miRNA. CONCLUSIONS/INTERPRETATION: Changes in the level of specific miRNAs that occur during ageing affect the proliferative capacity of beta cells. This might reduce their ability to expand under conditions of increased insulin demand, favouring the development of type 2 diabetes.Swiss National Science FoundationFondation Francophone pour la Recherche sur le DiabèteWellcome Trust Senior Investigator AwardMRC Programme GrantRoyal Society Wolfson Research Merit AwardWellcome Trust project gran

Primary Tuberculosis of the Esophagus

Os autores reportam o caso de uma doente de 38 anos de idade com um quadro clínico de odinofagia, dor retroesternal e emagrecimento. Os exames complementares de diagnóstico revelaram a presença de uma lesão ulcerada no esófago, como forma de manifestação de tuberculose primária do esófago. A Tuberculose esofágica é uma doença pouco frequente, sendo responsável por 0,15% da mortalidade por tuberculose. A Tuberculose primária do esófago, sem envolvimento de outros órgãos, como o nosso caso clínico, é ainda mais raro. A maioria dos casos é tratada de forma eficaz com tuberculostáticos, sendo que o atraso no diagnóstico e início da terapêutica dita um mau prognóstico

How equal is equality? Discussions about same-sex marriage in Portugal

In Portugal, public and political discussions about same-sex marriage have been going on since the 1990s. In 2010, same-sex marriage was legalized under intense dispute since it excludes same-sex couples from adoption and reproductive rights. During parliamentary debates, political parties and civil organizations linked to the Catholic Church resorted to conflicting ideas of ‘equality’ and ‘difference’ to advance their claims. In this article, we analyse the contents of petitions, bills and parliamentary proceedings concerning the legal recognition of same-sex unions, highlighting the presence of conflicting notions of equality linked to pervasive beliefs about the inadequacy of homo-erotic desire and practices

Software Phase Correction Technique for Passive Radar

A traditional radar actively transmits pulses and receive the corresponding echoes. By computing the time taken to receive the echoes the system is able to detect targets and estimate their ranges. However, mainly for military applications, an active radar has a major drawback: it can be detected by the enemy since it radiates electromagnetic pulses. As such, there is currently high research and development activity in the field of passive radar systems. In this alternative scenario, the radar does transmit any signal. Instead, it uses signals already present in the environment, such as TV, radio broadcasts and satellite digital video broadcast as transmitters of opportunity. By measuring the time difference between the signal received by the transmitter of opportunity and the signal echoed by the targets, the radar can detect targets and estimate their ranges. In scenarios which use very low power illuminators of opportunity, such as satellite DVB-S or GPS, relatively long integration times are required in order to obtain reasonable values of signal to noise ratio. This implies that, besides frequency correction, the coherency of local oscillators in the receivers need to be maintained during long time intervals, which can be very difficult. The paper presents a novel phase correction technique for passive radar which uses targets of opportunity, already present in the target area, as references to maintain the coherency of the oscillators for all the integration interval. The proposed methodology is quite simple and enables the use of low-cost hardware with independent oscillators for the reference and surveillance channels which can be geographically distributed. The obtained results illustrate the effectiveness and applicability of the method

Determinants on an efficient cellulase recycling process for the production of bioethanol from recycled paper sludge under high solid loadings

Background: In spite of the continuous efforts and investments in the last decades, lignocellulosic ethanol is still not economically competitive with fossil fuels. Optimization is still required in different parts of the process. Namely, the cost effective usage of enzymes has been pursued by different strategies, one of them being recycling. Results: Cellulase recycling was analyzed on Recycled Paper Sludge (RPS) conversion into bioethanol under intensified conditions. Different cocktails were studied regarding thermostability, hydrolysis efficiency, distribution in the multiphasic system and recovery from solid. Celluclast showed inferior stability at higher temperatures (45-55 ºC), nevertheless its performance at moderate temperatures (40ºC) was slightly superior to other cocktails (ACCELLERASE®1500 and Cellic®CTec2). Celluclast distribution in the solid-liquid medium was also more favorable, enabling to recover 88 % of final activity at the end of the process. A Central Composite Design studied the influence of solids concentration and enzyme dosage on RPS conversion by Celluclast. Solids concentration showed a significant positive effect on glucose production, no major limitations being found from utilizing high amounts of solids under the studied conditions. Increasing enzyme loading from 20 to 30 FPU/ gcellulose had no significant effect on sugars production, suggesting that 22 % solids and 20 FPU/gcellulose are the best operational conditions towards an intensified process. Applying these, a system of multiple rounds of hydrolysis with enzyme recycling was implemented, allowing to maintain steady levels of enzyme activity with only 50 % of enzyme on each recycling stage. Additionally, interesting levels of solid conversion (70-81 %) were also achieved, leading to considerable improvements on glucose and ethanol production comparatively with the reports available so far (3.4 and 3.8 fold, respectively). Conclusions: Enzyme recycling viability depends on enzyme distribution between the solid and liquid phases at the end of hydrolysis, as well as enzymes thermostability. Both are critical features to be observed for a judicious choice of enzyme cocktail. This work demonstrates that enzyme recycling in intensified biomass degradation can be achieved through simple means. The process is possibly much more effective at larger scale, hence novel enzyme formulations favoring this possibility should be developed for industrial usage.This work had the fnancial support of the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/ BIO/04469/2013 unit, COMPETE 2020 (POCI-01-0145-FEDER-006684) and the MultiBiorefnery project (POCI-01-0145-FEDER-016403). Furthermore, FCT equally supported the Ph.D. grant to DG (SFRH/BD/88623/2012).info:eu-repo/semantics/publishedVersio

Influences on gum feeding in primates

This chapter reviews the factors that may affect patterns of gum feeding by primates. These are then examined for mixed-species troops of saddleback (S. fuscicollis) and mustached (S. mystax) tamarins. An important distinction is made between gums produced by tree trunks and branches as a result of damage and those produced by seed pods as part of a dispersal strategy as these may be expected to differ in their biochemistry. Feeding on fruit and Parkia seed pod exudates was more prevalent in the morning whereas other exudates were eaten in the afternoon. This itinerary may represent a deliberate strategy to retain trunk gums in the gut overnight, thus maximising the potential for microbial fermentation of their β-linked oligosaccharides. Both types of exudates were eaten more in the dry than the wet season. Consumption was linked to seasonal changes in resource availability and not the tamarins’ reproductive status pro-viding no support for the suggestion that gums are eaten as a pri-mary calcium source in the later stages of gestation and lactation. The role of availability in determining patterns of consumption is further supported by the finding that dietary overlap for the trunk gums eaten was greater between species within mixed-species troops within years than it was within species between years. These data and those for pygmy marmosets (Cebuella pygmaea) suggest that patterns of primate gummivory may reflect the interaction of prefer-ence and availability for both those able to stimulate gum production and those not

Development of ligament tissue biodegradable devices: A review

This bibliographic review is focused on ligament tissue rehabilitation, its anatomy-physiology, and, mainly, on the dimensioning considerations of a composite material solution. The suture strength is problematic during the tissue recovering, implying reduction of mobility for several months. However, early postoperative active mobilization may enable a faster and more effective recovering of tissue biomechanical functions. As the risk of tendon rupture becomes a significant concern, a repair technique must be used to withstand the tensile forces generated by active mobilization. However, to avoid stress shielding effect on ligament tissue, an augmentation device must be designed on stiffness basis, that preferably will decrease. Absorbable biocomposite reinforcements have been used to allow early postoperative active mobilization and avoid the shortcomings of current repair solutions. Tensile strength decrease of the repair, during the initial inflammatory phase, is expected, derived from oedema and tendon degradation. In the fibroblastic phase, stiffness and strength will increase, which will stabilize during the remodeling phase. The reinforcement should be able to carry the dynamic load due to locomotion with a mechanical behavior similar to the undamaged natural tissue, during all rehabilitation process. Moreover, the degradation rate Must also be compatible with the ligament tissue recovering. The selection and combination of different biodegradable materials, in order to make the biocomposite reinforcement functionally compatible to the damaged sutured tissue, in terms of mechanical properties and degradation rate, is a major step on the design process. Modelling techniques allow pre-clinical evaluation of the reinforcement functional compatibility, and the optimization by comparison of different composite solutions in terms of biomechanical behavior