Genes from the TAS1R and TAS2R families of taste receptors: Looking for signatures of their adaptive role in human evolution

Taste perception is crucial in monitoring food intake and, hence, is thought to play a significant role in human evolution. To gain insights into possible adaptive signatures in genes encoding bitter, sweet, and umami taste receptors, we surveyed the available sequence variation data from the 1000 Genomes Project Phase 3 for TAS1R (TAS1R1-3) and TAS2R (TAS2R16 and TAS2R38) families. Our study demonstrated that genes from these two families have experienced contrasting evolutionary histories: While TAS1R1 and TAS1R3 showed worldwide evidence of positive selection, probably correlated with improved umami and sweet perception, the patterns of variation displayed by TAS2R16 and TAS2R38 were more consistent with scenarios of balancing selection that possibly conferred a heterozygous advantage associated with better capacity to perceive a wide range of bitter compounds. In TAS2R16, such adaptive events appear to have occurred restrictively in mainland Africa, whereas the strongest evidence in TAS2R38 was detected in Europe. Despite plausible associations between taste perception and the TAS1R and TAS2R selective signatures, we cannot discount other biological mechanisms as driving the evolutionary trajectories of those TAS1R and TAS2R members, especially given recent findings of taste receptors behaving as the products of pleiotropic genes involved in many functions outside the gustatory system.IPATIMUP is included in the i3S Consortium, which is partially supported by the Portuguese Foundation for Science and Technology (FCT). This work is also funded by FEDER funds through the Operational Programme Competitiveness Factors (COMPETE) and National Funds through the FCT (projects PEst-C/SAU/LA0003/2013 and POCI-01-0145-FEDER-007274, fellowships SFRH/BD/63343/2009 to C.V., SFRH/ BPD/65000/2009 to L.A., and SFRH/BPD/120777/2016 to P.I.M.), and by Programa Operacional Regional do Norte (Norte 2020), through FEDER funds under the Quadro de Referência Estratégico Nacional (QREN; NORTE-01-0145-FEDER-000029). We thank Jacquelyn Beals for the careful editing of the work. We also thank Sònia Casillas for the helpful instructions about the tracks from the PopHuman browser, and Miguel Arenas and Eduardo Conde Sousa for the aid in extracting data from those tracks

Profiling of lung microbiota discloses differences in adenocarcinoma and squamous cell carcinoma

The lung is a complex ecosystem of host cells and microbes often disrupted in pathological conditions. Although bacteria have been hypothesized as agents of carcinogenesis, little is known about microbiota profile of the most prevalent cancer subtypes: adenocarcinoma (ADC) and squamous cell carcinoma (SCC). To characterize lung cancer (LC) microbiota a first a screening was performed through a pooled sequencing approach of 16S ribosomal RNA gene (V3-V6) using a total of 103 bronchoalveaolar lavage fluid samples. Then, identified taxa were used to inspect 1009 cases from The Cancer Genome Atlas and to annotate tumor unmapped RNAseq reads. Microbial diversity was analyzed per cancer subtype, history of cigarette smoking and airflow obstruction, among other clinical data. We show that LC microbiota is enriched in Proteobacteria and more diverse in SCC than ADC, particularly in males and heavier smokers. High frequencies of Proteobacteria were found to discriminate a major cluster, further subdivided into well-defined communities’ associated with either ADC or SCC. Here, a SCC subcluster differing from other cases by a worse survival was correlated with several Enterobacteriaceae. Overall, this study provides first evidence for a correlation between lung microbiota and cancer subtype and for its influence on patient life expectancy.We would like to thank all patients for donating their samples and for collaborating in this study. IPATIMUP integrates the i3S Research Unit, which is partially supported by the Portuguese Foundation for Science and Technology (FCT). This work was supported by the Portuguese Foundation for Science and Technology (FCT), financed by the European Social Funds (COMPETE-FEDER) and National Funds through the FCT (projects PEstC/SAU/LA0003/2013 and POCI-01-0145-FEDER-007274, fellowships SFRH/BPD/77646/2011 and SFRH/BPD/120777/2016 to S.G. and P.I.M., respectively, grant PTDC/BEXGMG/0242/2012 to S.S. and by Programa Operacional Regional do Norte (ON.2 – O Novo Norte and Norte 2020), through FEDER funds under the Quadro de Referência Estratégico Nacional (QREN; projects NORTE-07-0162-FEDER-00018 and NORTE-070162-FEDER-000067, and NORTE-01-0145-FEDER-000029)

A new insight for monitoring ungulates : density surface modelling of roe deer in a Mediterranean habitat

We would like to thank the University of Aveiro (Department of Biology) and FCT/MEC for the financial support to CESAM RU (UID/AMB/50017) through national funds and, where applicable, co-financed by the FEDER, within the PT2020 Partnership Agreement. TAM is partially funded by FCT, Fundação para a Ciência e a Tecnologia, Portugal, through the project UID/MAT/00006/2013.Ungulates are especially difficult to monitor, and population estimates are challenging to obtain; nevertheless, such information is fundamental for effective management. This is particularly important for expanding species such as roe deer (Capreolus capreolus), whose populations dramatically increased in number and geographic distribution over the last decades. In an attempt to follow population trends and assess species ecology, important methodological advances were recently achieved by combining line or point sampling with geographic information systems (GIS). In this study, we combined density surface modelling (DSM) with line transect survey to predict roe deer density in northeastern Portugal. This was based on modelling pellet group counts as a function of environmental factors while taking into account the probability of detecting pellets and conversion factors to relate pellet density to animal density. We estimated a global density of 3.01 animals/100 ha (95 % CI 0.37–3.51) with a 32.82 % CV. Roe deer densities increased with increasing distance to roads as well as with higher percentage of cover areas and decreased with increasing distance to human populations. This recently developed spatial method can be advantageous to predict density over space through the identification of key factors influencing species abundance. Furthermore, surface maps for subset areas will enable to visually depict abundance distribution of wild populations. This will enable the assessment of areas where ungulate impacts should be minimized, allowing an adaptive management through time.PostprintPeer reviewe

The clinical relevance of PCL index on the reconstruction of anterior cruciate ligament with hamstring tendon autograft

The posterior cruciate ligament index (PCL index) has been reported as a diagnostic and prognostic marker for anterior cruciate ligament (ACL) reconstruction. The clinical relevance of PCL index on the reconstruction of ACL with hamstring tendon autograft has not been described in the literature. The objective of this study is to evaluate the importance of the PCL index as a marker of anatomic reconstruction and of functional improvement of patients undergoing ACL reconstruction with HT autograft. Twenty-four patients were submitted to ACL reconstruction with HT autograft. The PCL index was assessed by magnetic resonance imaging before and after surgery. The functional evaluation was performed through the International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Form© and Knee Society Knee Scoring System© (IKS). Patients presented a significant positive variation of the PCL index, IKDC and IKS scores. There is no significant correlation between PCL index variation and IKDC and IKS scores (p > 0.05). Unlike other studies reporting a relationship between the PCL index, control of rotational kinematics, and functional improvement in patients undergoing ACL reconstruction with bone-patellar tendon-bone autograft, this study does not demonstrate this association. There is evidence in this study to show that the PCL index may be used as an anatomic reconstructive marker of ACL but not to predict the clinical outcome in this type of reconstruction.(undefined

Portuguese Ministers, 1851-1999: Social Background and Paths to Power

Disponível em: http://193.136.113.6/Opac/Pages/Search/Results.aspx?SearchText=UID=bb8aa8d5-c6b6-466a-81bb-fe8a67693cee&DataBase=10449_UNLFCSHThis paper provides an empirical analysis of the impact of regime changes in the composition and patterns of recruitment of the Portuguese ministerial elite throughout the last 150 years. The ‘out-of-type’, violent nature of most regime transformations accounts for the purges in and the extensive replacements of the political personnel, namely of the uppermost officeholders. In the case of Cabinet members, such discontinuities did not imply, however, radical changes in their social profile. Although there were some significant variations, a series of salient characteristics have persisted over time. The typical Portuguese minister is a male in his midforties, of middle-class origin and predominantly urban-born, highly educated and with a state servant background. The two main occupational contingents have been university professors - except for the First Republic (1910-26) - and the military, the latter having only recently been eclipsed with the consolidation of contemporary democracy. As regards career pathways, the most striking feature is the secular trend for the declining role of parliamentary experience, which the democratic regime did not clearly reverse. In this period, a technocratic background rather than political experience has been indeed the privileged credential for a significant proportion of minister

Inhibition of the Mitochondrial Enzyme ABAD Restores the Amyloid-β-Mediated Deregulation of Estradiol

Alzheimer's disease (AD) is a conformational disease that is characterized by amyloid-β (Aβ) deposition in the brain. Aβ exerts its toxicity in part by receptor-mediated interactions that cause down-stream protein misfolding and aggregation, as well as mitochondrial dysfunction. Recent reports indicate that Aβ may also interact directly with intracellular proteins such as the mitochondrial enzyme ABAD (Aβ binding alcohol dehydrogenase) in executing its toxic effects. Mitochondrial dysfunction occurs early in AD, and Aβ's toxicity is in part mediated by inhibition of ABAD as shown previously with an ABAD decoy peptide. Here, we employed AG18051, a novel small ABAD-specific compound inhibitor, to investigate the role of ABAD in Aβ toxicity. Using SH-SY5Y neuroblastoma cells, we found that AG18051 partially blocked the Aβ-ABAD interaction in a pull-down assay while it also prevented the Aβ42-induced down-regulation of ABAD activity, as measured by levels of estradiol, a known hormone and product of ABAD activity. Furthermore, AG18051 is protective against Aβ42 toxicity, as measured by LDH release and MTT absorbance. Specifically, AG18051 reduced Aβ42-induced impairment of mitochondrial respiration and oxidative stress as shown by reduced ROS (reactive oxygen species) levels. Guided by our previous finding of shared aspects of the toxicity of Aβ and human amylin (HA), with the latter forming aggregates in Type 2 diabetes mellitus (T2DM) pancreas, we determined whether AG18051 would also confer protection from HA toxicity. We found that the inhibitor conferred only partial protection from HA toxicity indicating distinct pathomechanisms of the two amyloidogenic agents. Taken together, our results present the inhibition of ABAD by compounds such as AG18051 as a promising therapeutic strategy for the prevention and treatment of AD, and suggest levels of estradiol as a suitable read-out

Systems microscopy approaches to understand cancer cell migration and metastasis

Cell migration is essential in a number of processes, including wound healing, angiogenesis and cancer metastasis. Especially, invasion of cancer cells in the surrounding tissue is a crucial step that requires increased cell motility. Cell migration is a well-orchestrated process that involves the continuous formation and disassembly of matrix adhesions. Those structural anchor points interact with the extra-cellular matrix and also participate in adhesion-dependent signalling. Although these processes are essential for cancer metastasis, little is known about the molecular mechanisms that regulate adhesion dynamics during tumour cell migration. In this review, we provide an overview of recent advanced imaging strategies together with quantitative image analysis that can be implemented to understand the dynamics of matrix adhesions and its molecular components in relation to tumour cell migration. This dynamic cell imaging together with multiparametric image analysis will help in understanding the molecular mechanisms that define cancer cell migration

The PLATO 2.0 mission

PLATO 2.0 has recently been selected for ESA's M3 launch opportunity (2022/24). Providing accurate key planet parameters (radius, mass, density and age) in statistical numbers, it addresses fundamental questions such as: How do planetary systems form and evolve? Are there other systems with planets like ours, including potentially habitable planets? The PLATO 2.0 instrument consists of 34 small aperture telescopes (32 with 25 s readout cadence and 2 with 2.5 s candence) providing a wide field-of-view (2232 deg 2) and a large photometric magnitude range (4-16 mag). It focusses on bright (4-11 mag) stars in wide fields to detect and characterize planets down to Earth-size by photometric transits, whose masses can then be determined by ground-based radial-velocity follow-up measurements. Asteroseismology will be performed for these bright stars to obtain highly accurate stellar parameters, including masses and ages. The combination of bright targets and asteroseismology results in high accuracy for the bulk planet parameters: 2 %, 4-10 % and 10 % for planet radii, masses and ages, respectively. The planned baseline observing strategy includes two long pointings (2-3 years) to detect and bulk characterize planets reaching into the habitable zone (HZ) of solar-like stars and an additional step-and-stare phase to cover in total about 50 % of the sky. PLATO 2.0 will observe up to 1,000,000 stars and detect and characterize hundreds of small planets, and thousands of planets in the Neptune to gas giant regime out to the HZ. It will therefore provide the first large-scale catalogue of bulk characterized planets with accurate radii, masses, mean densities and ages. This catalogue will include terrestrial planets at intermediate orbital distances, where surface temperatures are moderate. Coverage of this parameter range with statistical numbers of bulk characterized planets is unique to PLATO 2.0. The PLATO 2.0 catalogue allows us to e.g.: - complete our knowledge of planet diversity for low-mass objects, - correlate the planet mean density-orbital distance distribution with predictions from planet formation theories,- constrain the influence of planet migration and scattering on the architecture of multiple systems, and - specify how planet and system parameters change with host star characteristics, such as type, metallicity and age. The catalogue will allow us to study planets and planetary systems at different evolutionary phases. It will further provide a census for small, low-mass planets. This will serve to identify objects which retained their primordial hydrogen atmosphere and in general the typical characteristics of planets in such low-mass, low-density range. Planets detected by PLATO 2.0 will orbit bright stars and many of them will be targets for future atmosphere spectroscopy exploring their atmosphere. Furthermore, the mission has the potential to detect exomoons, planetary rings, binary and Trojan planets. The planetary science possible with PLATO 2.0 is complemented by its impact on stellar and galactic science via asteroseismology as well as light curves of all kinds of variable stars, together with observations of stellar clusters of different ages. This will allow us to improve stellar models and study stellar activity. A large number of well-known ages from red giant stars will probe the structure and evolution of our Galaxy. Asteroseismic ages of bright stars for different phases of stellar evolution allow calibrating stellar age-rotation relationships. Together with the results of ESA's Gaia mission, the results of PLATO 2.0 will provide a huge legacy to planetary, stellar and galactic science

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field