A Functional Role of RB-Dependent Pathway in the Control of Quiescence in Adult Epidermal Stem Cells Revealed by Genomic Profiling

Continuous cell renewal in mouse epidermis is at the expense of a pool of pluripotent cells that lie in a well defined niche in the hair follicle known as the bulge. To identify mechanisms controlling hair follicle stem cell homeostasis, we developed a strategy to isolate adult bulge stem cells in mice and to define their transcriptional profile. We observed that a large number of transcripts are underexpressed in hair follicle stem cells when compared to non-stem cells. Importantly, the majority of these downregulated genes are involved in cell cycle. Using bioinformatics tools, we identified the E2F transcription factor family as a potential element involved in the regulation of these transcripts. To determine their functional role, we used engineered mice lacking Rb gene in epidermis, which showed increased expression of most E2F family members and increased E2F transcriptional activity. Experiments designed to analyze epidermal stem cell functionality (i.e.: hair regrowth and wound healing) imply a role of the Rb-E2F axis in the control of stem cell quiescence in epidermis

Pb(II) Induces Scramblase Activation and Ceramide-Domain Generation in Red Blood Cells

The mechanisms of Pb(II) toxicity have been studied in human red blood cells using confocal microscopy, immunolabeling, fluorescence-activated cell sorting and atomic force microscopy. The process follows a sequence of events, starting with calcium entry, followed by potassium release, morphological change, generation of ceramide, lipid flip-flop and finally cell lysis. Clotrimazole blocks potassium channels and the whole process is inhibited. Immunolabeling reveals the generation of ceramide-enriched domains linked to a cell morphological change, while the use of a neutral sphingomyelinase inhibitor greatly delays the process after the morphological change, and lipid flip-flop is significantly reduced. These facts point to three major checkpoints in the process: first the upstream exchange of calcium and potassium, then ceramide domain formation, and finally the downstream scramblase activation necessary for cell lysis. In addition, partial non-cytotoxic cholesterol depletion of red blood cells accelerates the process as the morphological change occurs faster. Cholesterol could have a role in modulating the properties of the ceramide-enriched domains. This work is relevant in the context of cell death, heavy metal toxicity and sphingolipid signaling.AGA was a predoctoral student supported by the Basque Government and later by the University of the Basque Country (UPV/EHU). This work was also supported in part by grants from the Spanish Government (FEDER/MINECO BFU 2015-66306-P to F.M.G. and A.A.) and the Basque Government (IT849-13 to F.M.G. and IT838-13 to A.A.), and by the Swiss National Science Foundation

Genomic Characterization of Host Factors Related to SARS-CoV-2 Infection in People with Dementia and Control Populations: The GR@ACE/DEGESCO Study

Emerging studies have suggested several chromosomal regions as potential host genetic factors involved in the susceptibility to SARS-CoV-2 infection and disease outcome. We nested a COVID-19 genome-wide association study using the GR@ACE/DEGESCO study, searching for susceptibility factors associated with COVID-19 disease. To this end, we compared 221 COVID-19 confirmed cases with 17,035 individuals in whom the COVID-19 disease status was unknown. Then, we performed a meta-analysis with the publicly available data from the COVID-19 Host Genetics Initiative. Because the APOE locus has been suggested as a potential modifier of COVID-19 disease, we added sensitivity analyses stratifying by dementia status or by disease severity. We confirmed the existence of the 3p21.31 region (LZTFL1, SLC6A20) implicated in the susceptibility to SARS-CoV-2 infection and TYK2 gene might be involved in COVID-19 severity. Nevertheless, no statistically significant association was observed in the COVID-19 fatal outcome or in the stratified analyses (dementia-only and non-dementia strata) for the APOE locus not supporting its involvement in SARS-CoV-2 pathobiology or COVID-19 prognosis

Monitoring an Alien Invasion: DNA Barcoding and the Identification of Lionfish and Their Prey on Coral Reefs of the Mexican Caribbean

BACKGROUND: In the Mexican Caribbean, the exotic lionfish Pterois volitans has become a species of great concern because of their predatory habits and rapid expansion onto the Mesoamerican coral reef, the second largest continuous reef system in the world. This is the first report of DNA identification of stomach contents of lionfish using the barcode of life reference database (BOLD). METHODOLOGY/PRINCIPAL FINDINGS: We confirm with barcoding that only Pterois volitans is apparently present in the Mexican Caribbean. We analyzed the stomach contents of 157 specimens of P. volitans from various locations in the region. Based on DNA matches in the Barcode of Life Database (BOLD) and GenBank, we identified fishes from five orders, 14 families, 22 genera and 34 species in the stomach contents. The families with the most species represented were Gobiidae and Apogonidae. Some prey taxa are commercially important species. Seven species were new records for the Mexican Caribbean: Apogon mosavi, Coryphopterus venezuelae, C. thrix, C. tortugae, Lythrypnus minimus, Starksia langi and S. ocellata. DNA matches, as well as the presence of intact lionfish in the stomach contents, indicate some degree of cannibalism, a behavior confirmed in this species by the first time. We obtained 45 distinct crustacean prey sequences, from which only 20 taxa could be identified from the BOLD and GenBank databases. The matches were primarily to Decapoda but only a single taxon could be identified to the species level, Euphausia americana. CONCLUSIONS/SIGNIFICANCE: This technique proved to be an efficient and useful method, especially since prey species could be identified from partially-digested remains. The primary limitation is the lack of comprehensive coverage of potential prey species in the region in the BOLD and GenBank databases, especially among invertebrates

Aurora-A Interacts with AP-2α and Down Regulates Its Transcription Activity

Aurora-A is a serine/threonine protein kinase and plays an important role in the control of mitotic progression. Dysregulated expression of Aurora-A impairs centrosome separation and maturation, which lead to disrupted cell cycle progression and tumorigenesis. However, the molecular mechanism by which Aurora-A causes cell malignant transformation remains to be further defined. In this report, using transcription factors array and mRNA expression profiling array, we found that overexpression of Aurora-A suppressed transcription activity of AP-2α, a tumor suppressor that is often downregulated in variety of tumors, and inhibited expression of AP-2α-regulated downstream genes. These array-based observations were further confirmed by microwell colorimetric TF assay and luciferase reporter assay. Downregulated transcription activity of AP-2α by Aurora-A was found to be associated with reduced AP-2α protein stability, which appeared to be mediated by Aurora-A enhanced ubiquitin-dependent proteasomal degradation of AP-2α protein. Interestingly, Aurora-A-mediated AP-2α degradation was likely dependent Aurora-A kinase activity since inhibition of Aurora-A kinase activity was able to rescue Aurora-A-induced degradation of AP-2α. Moreover, we defined a physical interaction between Aurora-A and AP-2α, and such interaction might bridge the suppressive effect of Aurora-A on AP-2α protein stability. These findings provide new insights into molecular mechanism by which Aurora-A acts as an oncogenic molecule in tumor occurrence and malignant development

Participation in biocultural diversity conservation : insights from five Amazonian examples

Unidad de excelencia María de Maeztu CEX2019-000940-MThe past three decades have seen the emergence of myriads of initiatives focused on conserving, revitalizing, and maintaining Indigenous and Local Knowledge (ILK) as part of biocultural approaches to conservation. However, the extent to which these efforts have been participatory has been often overlooked. In this chapter, we focus on five prominent ILK conservation initiatives in the Amazon Basin to examine the participation of Indigenous Peoples and Local Communities (IPLCs) in ILK conservation. Our review illustrates several examples of ILK conservation initiatives offering substantial opportunities for meaningful IPLC participation over the long term. Overall, our case studies suggest that the development of robust and inclusive decision-making processes is essential to optimize IPLC participation in ILK conservation, thereby increasing the legitimacy of these initiatives. Our review is not an exhaustive account of the breadth and depth of all initiatives promoting participatory biocultural conservation in this region, but it illustrates that there are many strategies that can help foster IPLC engagement and lead the participatory turn in biocultural conservation

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

Sexual Relationships in Hispanic Countries: a Literature Review

This is a pre-print of an article published in Current Sexual Health Reports. The final authenticated version is available online at: https://doi.org/10.1007/s11930-020-00272-6Purpose of Review: Sexuality is a complex dimension for which culture seems to play an important role, particularly in countries that are more traditional. This review summarizes the knowledge about sexual relationships in Hispanic countries, considering sexual debut, attitudes, behaviors, and satisfaction. Recent Findings: In line with the literature reviewed, the sexual double standard seems to be continuing to influence sexual relationships. Some countries show more open expressions of sexuality based on the level of gender inequality or sexualized context, and within countries, variables such as religious commitment, family characteristics, and access to resources may play important roles in sexuality. Summary: Future research, policies, and interventions should consider these specific characteristics, including these forms of expression of sexuality, in the adjustment of cross-cultural and cross-national strategies

The effect of perceived discrimination on the health of immigrant workers in Spain

Background: Discrimination is an important determinant of health inequalities, and immigrants may be more vulnerable to certain types of discrimination than the native-born. This study analyses the relationship between immigrants' perceived discrimination and various self-reported health indicators. Methods: A cross-sectional survey was conducted (2008) amongst a non-random sample of 2434 immigrants from Ecuador, Morocco, Romania and Colombia in four Spanish cities: Barcelona, Huelva, Madrid and Valencia. A factorial analysis of variables revealed three dimensions of perceived discrimination (due to immigrant status, due to physical appearance, and workplace-related). The association of these dimensions with self-rated health, mental health (GHQ-12), change in self-rated health between origin and host country, and other self-reported health outcomes was analysed. Logistic regression was used adjusting for potential confounders (aOR-95%CI). Subjects with worsening self-reported health status potentially attributable to perceived discrimination was estimated (population attributable proportion, PAP %). Results: 73.3% of men and 69.3% of women immigrants reported discrimination due to immigrant status. Moroccans showed the highest prevalence of perceived discrimination. Immigrants reporting discrimination were at significantly higher risk of reporting health problems than those not reporting discrimination. Workplace-related discrimination was associated with poor mental health (aOR 2.97 95%CI 2.45-3.60), and the worsening of self-rated health (aOR 2.20 95%CI 1.73- 2.80). 40% (95% CI 24-53) PAP of those reporting worse self-rated health could be attributable to discrimination due to immigrant status. Conclusions: Discrimination may constitute a risk factor for health in immigrant workers in Spain and could explain some health inequalities among immigrant populations in Spanish society.This work was supported by the following sources: Carolina Foundation (Spain), Healthcare Research Fund of the Spanish Ministry of Health and Consumption (references PI050497, PI052202, PI052334, PI061701, and PI0790470

Parkinson Phenotype in Aged PINK1-Deficient Mice Is Accompanied by Progressive Mitochondrial Dysfunction in Absence of Neurodegeneration

Background Parkinson's disease (PD) is an adult-onset movement disorder of largely unknown etiology. We have previously shown that loss-of-function mutations of the mitochondrial protein kinase PINK1 (PTEN induced putative kinase 1) cause the recessive PARK6 variant of PD. Methodology/Principal Findings Now we generated a PINK1 deficient mouse and observed several novel phenotypes: A progressive reduction of weight and of locomotor activity selectively for spontaneous movements occurred at old age. As in PD, abnormal dopamine levels in the aged nigrostriatal projection accompanied the reduced movements. Possibly in line with the PARK6 syndrome but in contrast to sporadic PD, a reduced lifespan, dysfunction of brainstem and sympathetic nerves, visible aggregates of alpha-synuclein within Lewy bodies or nigrostriatal neurodegeneration were not present in aged PINK1-deficient mice. However, we demonstrate PINK1 mutant mice to exhibit a progressive reduction in mitochondrial preprotein import correlating with defects of core mitochondrial functions like ATP-generation and respiration. In contrast to the strong effect of PINK1 on mitochondrial dynamics in Drosophila melanogaster and in spite of reduced expression of fission factor Mtp18, we show reduced fission and increased aggregation of mitochondria only under stress in PINK1-deficient mouse neurons. Conclusion Thus, aging Pink1 -/- mice show increasing mitochondrial dysfunction resulting in impaired neural activity similar to PD, in absence of overt neuronal death