Global gene expression analysis provides insight into local adaptation to geothermal streams in tadpoles of the Andean toad Rhinella spinulosa

Indexación: Web of Science; Scopus.The anuran Rhinella spinulosa is distributed along the Andes Range at altitudes that undergo wide daily and seasonal variation in temperature. One of the populations inhabits geothermal streams, a stable environment that influences life history traits such as the timing of metamorphosis. To investigate whether this population has undergone local adaptation to this unique habitat, we carried out transcriptome analyses in animals from two localities in two developmental stages (prometamorphic and metamorphic) and exposed them to two temperatures (20 and 25 degrees C). RNA-Seq, de novo assembly and annotation defined a transcriptome revealing 194,469 high quality SNPs, with 1,507 genes under positive selection. Comparisons among the experimental conditions yielded 1,593 differentially expressed genes. A bioinformatics search for candidates revealed a total of 70 genes that are highly likely to be implicated in the adaptive response of the population living in a stable environment, compared to those living in an environment with variable temperatures. Most importantly, the population inhabiting the geothermal environment showed decreased transcriptional plasticity and reduced genetic variation compared to its counterpart from the non-stable environment. This analysis will help to advance the understanding of the molecular mechanisms that account for the local adaptation to geothermal streams in anurans.https://www.nature.com/articles/s41598-017-01982-

Shared and Distinctive Ultrastructural Abnormalities Expressed by Megakaryocytes in Bone Marrow and Spleen From Patients With Myelofibrosis

Numerous studies have documented ultrastructural abnormalities in malignant megakaryocytes from bone marrow (BM) of myelofibrosis patients but the morphology of these cells in spleen, an important extramedullary site in this disease, was not investigated as yet. By transmission-electron microscopy, we compared the ultrastructural features of megakaryocytes from BM and spleen of myelofibrosis patients and healthy controls. The number of megakaryocytes was markedly increased in both BM and spleen. However, while most of BM megakaryocytes are immature, those from spleen appear mature with well-developed demarcation membrane systems (DMS) and platelet territories and are surrounded by platelets. In BM megakaryocytes, paucity of DMS is associated with plasma (thick with protrusions) and nuclear (dilated with large pores) membrane abnormalities and presence of numerous glycosomes, suggesting a skewed metabolism toward insoluble polyglucosan accumulation. By contrast, the membranes of the megakaryocytes from the spleen were normal but these cells show mitochondria with reduced crests, suggesting deficient aerobic energy-metabolism. These distinctive morphological features suggest that malignant megakaryocytes from BM and spleen express distinctive metabolic impairments that may play different roles in the pathogenesis of myelofibrosis

Is supercomplex organization of the respiratory chain required for optimal electron transfer activity?

AbstractThe supra-molecular assembly of the main respiratory chain enzymatic complexes in the form of “supercomplexes” has been proved by structural and functional experimental evidence. This evidence strongly contrasts the previously accepted Random Diffusion Model stating that the complexes are functionally connected by lateral diffusion of small redox molecules (i.e. Coenzyme Q and cytochrome c).This review critically examines the available evidence and provides an analysis of the functional consequences of the intermolecular association of the respiratory complexes pointing out the role of Coenzyme Q and of cytochrome c as channeled or as freely diffusing intermediates in the electron transfer activity of their partner enzymes

LTA4H and FXR1 Gene and Protein Expression in Canine Oral Melanoma

Introduction: Canine oral melanoma is a common neoplasm that is usually considered malignant, although the correlation between histology and prognosis is still controversial. Therefore, research of new biological markers is ongoing. In this study, LTA4H (an enzyme of the arachidonic acid cascade) and FXR1 (a RNA binding protein) are investigated. Both have been investigated previously for their possible role in metastasis of ocular melanoma, and are studied here in canine oral melanoma. Materials and Methods: Twenty-nine samples of formalin-fixed and paraffin wax-embedded canine oral melanomas were analyzed. Routine HE sections were evaluated on light microscopy and received a histological description, including mitotic activity index (MI). Immunohistochemistry (IHC) for LTA4H, FXR1 and Ki67 was performed. LTA4H and FXR1 were scored semiquantitatively and Ki67 was scored quantitatively. The expression of LTA4H and FXR1 genes was also quantified by RT-PCR. Results: Most of the cases were epithelioid, poorly pigmented melanomas. MI ranged from 0.1 to 9.2 (median 1.1). Ki67 index ranged from 7.9 to 44.4% (median 19%). IHC was positive in 29/29 LTA4H and 28/29 FXR1, with variable intensity and percentage of positivity. RT-PCR relative expression values ranged from 0.49 to 9.11 for LTA4H and 0.15 to 10.33 for FXR1 (in four cases was under the detection limit). Conclusions: LTA4H and FXR1 were detected in all tested melanomas. Marked differences between cases were noted with RT-PCR, although target gene expression levels were not consistent with histological parameters or Ki67 index. Conversely, immunohistochemical positivity was elevated in most cases with negligible expression differences. Further work is ongoing to clarify the prognostic significance of different levels of expression

Inhibitor sensitivity of respiratory complex I in human platelets: A possible biomarker of ageing

AbstractNADH-Coenzyme Q reductase was assayed in platelet mitochondrial membranes obtained from 19 pools of two venous blood samples from female young (19–30 years) individuals and 18 pools from aged ones (66–107 years). The enzyme activities were not significantly changed in the two groups, but a decrease of sensitivity to the specific inhibitor, rotenone, occurred in a substantial number of aged individuals. The results are in agreement with the predictions of the mitochondrial theory of ageing and may be used to develop a sensitive biomarker of the ageing process

Rho GTPase function in flies: insights from a developmental and organismal perspective.

Morphogenesis is a key event in the development of a multicellular organism and is reliant on coordinated transcriptional and signal transduction events. To establish the segmented body plan that underlies much of metazoan development, individual cells and groups of cells must respond to exogenous signals with complex movements and shape changes. One class of proteins that plays a pivotal role in the interpretation of extracellular cues into cellular behavior is the Rho family of small GTPases. These molecular switches are essential components of a growing number of signaling pathways, many of which regulate actin cytoskeletal remodeling. Much of our understanding of Rho biology has come from work done in cell culture. More recently, the fruit fly Drosophila melanogaster has emerged as an excellent genetic system for the study of these proteins in a developmental and organismal context. Studies in flies have greatly enhanced our understanding of pathways involving Rho GTPases and their roles in development

Planck early results. IX. XMM-Newton follow-up for validation of Planck cluster candidates

We present the XMM-Newton follow-up for confirmation of Planck cluster candidates. Twenty-five candidates have been observed to date using snapshot (∼10 ks) exposures, ten as part of a pilot programme to sample a low range of signal-to-noise ratios (4 < S/N < 6), and a further 15 in a programme to observe a sample of S/N > 5 candidates. The sensitivity and spatial resolution of XMM-Newton allows unambiguous discrimination between clusters and false candidates. The 4 false candidates have S/N ≤ 4.1. A total of 21 candidates are confirmed as extended X-ray sources. Seventeen are single clusters, the majority of which are found to have highly irregular and disturbed morphologies (about ∼70%). The remaining four sources are multiple systems, including the unexpected discovery of a supercluster at z = 0.45. For 20 sources we are able to derive a redshift estimate from the X-ray Fe K line (albeit of variable quality). The new clusters span the redshift range 0.09 <∼ z <∼ 0.54, with a median redshift of z ∼ 0.37. A first determination is made of their X-ray properties including the characteristic size, which is used to improve the estimate of the SZ Compton parameter, Y500. The follow-up validation programme has helped to optimise the Planck candidate selection process. It has also provided a preview of the X-ray properties of these newly-discovered clusters, allowing comparison with their SZ properties, and to the X-ray and SZ properties of known clusters observed in the Planck survey. Our results suggest that Planck may have started to reveal a non-negligible population of massive dynamically perturbed objects that is under-represented in X-ray surveys. However, despite their particular properties, these new clusters appear to follow the Y500–YX relation established for X-ray selected objects, where YX is the product of the gas mass and temperature

Planck early results. VIII. The all-sky early Sunyaev-Zeldovich cluster sample

We present the first all-sky sample of galaxy clusters detected blindly by the Planck satellite through the Sunyaev-Zeldovich (SZ) effect from its six highest frequencies. This early SZ (ESZ) sample is comprised of 189 candidates, which have a high signal-to-noise ratio ranging from 6 to 29. Its high reliability (purity above 95%) is further ensured by an extensive validation process based on Planck internal quality assessments and by external cross-identification and follow-up observations. Planck provides the first measured SZ signal for about 80% of the 169 previouslyknown ESZ clusters. Planck furthermore releases 30 new cluster candidates, amongst which 20 meet the ESZ signal-to-noise selection criterion. At the submission date, twelve of the 20 ESZ candidates were confirmed as new clusters, with eleven confirmed using XMM-Newton snapshot observations, most of them with disturbed morphologies and low luminosities. The ESZ clusters are mostly at moderate redshifts (86% with z below 0.3) and span more than a decade in mass, up to the rarest and most massive clusters with masses above 1 × 1015 M

Global, regional, and national age-sex-specific mortality and life expectancy, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017

BACKGROUND: Assessments of age-specific mortality and life expectancy have been done by the UN Population Division, Department of Economics and Social Affairs (UNPOP), the United States Census Bureau, WHO, and as part of previous iterations of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD). Previous iterations of the GBD used population estimates from UNPOP, which were not derived in a way that was internally consistent with the estimates of the numbers of deaths in the GBD. The present iteration of the GBD, GBD 2017, improves on previous assessments and provides timely estimates of the mortality experience of populations globally. METHODS: The GBD uses all available data to produce estimates of mortality rates between 1950 and 2017 for 23 age groups, both sexes, and 918 locations, including 195 countries and territories and subnational locations for 16 countries. Data used include vital registration systems, sample registration systems, household surveys (complete birth histories, summary birth histories, sibling histories), censuses (summary birth histories, household deaths), and Demographic Surveillance Sites. In total, this analysis used 8259 data sources. Estimates of the probability of death between birth and the age of 5 years and between ages 15 and 60 years are generated and then input into a model life table system to produce complete life tables for all locations and years. Fatal discontinuities and mortality due to HIV/AIDS are analysed separately and then incorporated into the estimation. We analyse the relationship between age-specific mortality and development status using the Socio-demographic Index, a composite measure based on fertility under the age of 25 years, education, and income. There are four main methodological improvements in GBD 2017 compared with GBD 2016: 622 additional data sources have been incorporated; new estimates of population, generated by the GBD study, are used; statistical methods used in different components of the analysis have been further standardised and improved; and the analysis has been extended backwards in time by two decades to start in 1950. FINDINGS: Globally, 18·7% (95% uncertainty interval 18·4–19·0) of deaths were registered in 1950 and that proportion has been steadily increasing since, with 58·8% (58·2–59·3) of all deaths being registered in 2015. At the global level, between 1950 and 2017, life expectancy increased from 48·1 years (46·5–49·6) to 70·5 years (70·1–70·8) for men and from 52·9 years (51·7–54·0) to 75·6 years (75·3–75·9) for women. Despite this overall progress, there remains substantial variation in life expectancy at birth in 2017, which ranges from 49·1 years (46·5–51·7) for men in the Central African Republic to 87·6 years (86·9–88·1) among women in Singapore. The greatest progress across age groups was for children younger than 5 years; under-5 mortality dropped from 216·0 deaths (196·3–238·1) per 1000 livebirths in 1950 to 38·9 deaths (35·6–42·83) per 1000 livebirths in 2017, with huge reductions across countries. Nevertheless, there were still 5·4 million (5·2–5·6) deaths among children younger than 5 years in the world in 2017. Progress has been less pronounced and more variable for adults, especially for adult males, who had stagnant or increasing mortality rates in several countries. The gap between male and female life expectancy between 1950 and 2017, while relatively stable at the global level, shows distinctive patterns across super-regions and has consistently been the largest in central Europe, eastern Europe, and central Asia, and smallest in south Asia. Performance was also variable across countries and time in observed mortality rates compared with those expected on the basis of development. INTERPRETATION: This analysis of age-sex-specific mortality shows that there are remarkably complex patterns in population mortality across countries. The findings of this study highlight global successes, such as the large decline in under-5 mortality, which reflects significant local, national, and global commitment and investment over several decades. However, they also bring attention to mortality patterns that are a cause for concern, particularly among adult men and, to a lesser extent, women, whose mortality rates have stagnated in many countries over the time period of this study, and in some cases are increasing