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Biology subjects

Hernandez, J. C.

Publications and source records attributed to Hernandez, J. C..

7 recordsLinked to original sources

Maternal transmission of a plastid structure enhances offspring fitness

Development in the sea has long been thought to be a nutritional gamble that disproportionately ends in starvation. Here, we unexpectedly show that components of plastids are incorporated into sea urchin eggs and that these, in turn, benefit developmental fitness. We find chromoplast-derived carotenoid crystals and chromoplast-specific metabolites inside of sea urchin eggs. The light-dependent activity of these chromoplast components influence the subsequent abundance of phytohormones that, in turn, regulate the use of energetic lipids that promote development and survival. Offspring that benefit from these chromoplast components are predicted to disperse further, over larger geographic areas, and use a wider range of currents, including those that cross ocean basins. Data presented here challenge the long-held assumption that components of non-metazoan organelles are unable to enter the germline and be passed between generations. We hypothesize that sea urchins manipulate plastids solely for their self-interest by a process that we term machioplasty, with the result of this process being a novel and adaptive form of maternal provisioning. SIGNIFICANCEMaking a fertilizable egg is a complex and carefully regulated process. One long-held assumption is that any component of non-animal organelles are unable to cross the evolutionary valley between non-reproductive and reproductive cells. Here, we unexpectedly show that components of plastids are incorporated into sea urchin eggs and that these, in turn, benefit developmental fitness. Offspring benefit from these plastid components by developing more quickly into larvae and having higher survival due to ability to use phytohormones that influence energetic lipids. This allows offspring to use a wider range of ocean currents, including those that cross entire basins. This challenge the long-held assumption that components of non-metazoan organelles are unable to be passed between generations.

developmental biology↗

Foraging specialization and body size in seabirds

Body size affects many biological processes since it predicts traits, timing, and biological rates. Some of these relationships are explained by the metabolic theory of ecology, which predicts that they should scale according to a power law with exponents multiples of [Formula]. Here we study the relationships between foraging specialization, particularly the number of dietary categories and prey capture strategies, and seabird species size, based on a database of 342 species (representing more than 95 % of all species). In our analysis, we found a negative relationship between the number of dietary categories and the number of capture strategies with body size with exponents of -0.83{+/-}0.31 and -0.76{+/-}0.06. To explain these relationships in terms of first principles, we developed a simple model to explain the origin of this scaling based on well-established ecological scaling relationships. Our study suggests that foraging specialization is constrained by the energy used by an organism, providing a basis for future theoretical developments.

ecology↗

Seronegative MSM at high-risk of HIV-1 acquisition show Immune quiescent profile with normal immune response against common antigens

HIV infection still represents a major public health problem worldwide, and a vaccine remains elusive. The study of HIV-exposed seronegative individuals (HESN) brings important information about the natural resistance to HIV, allows a better understanding of the infection and opens doors for new preventive and therapeutic strategies. Among HESN groups there are some men who have sex with men (MSM) with high-risk sexual behaviors, who represent an adequate cohort for the study of HESN because of their major exposure to HIV in the absence of infection. This study aimed to compare the immunological profile of Colombian seronegative MSM with different risk sexual behaviors. Sixty MSM at high-risk (n=16) and low-risk (n=44) of HIV-1 acquisition were included. No sex worker nor homozygous delta 32 mutation subjects were included. All the participants were negative for anti-HIV-1/2 antibodies and HIV-1 proviral DNA. The high-risk MSM presented a higher frequency of sexual partners in the last 3 months previous to the studys enrollment (Median 30 vs. 2), lifetime sexual partners (Median 1708 vs. 26), and unprotected anal intercourse (Median 12.5 vs. 2) than low-risk MSM. This group also showed a quiescent profile of T cells and NK cells, with a significantly lower percentage of CD4+CD38+, CD4+HLADR-CD38+, CD4+Ki67+ T cells, NKG2D+ NK cells (CD3-CD16+CD56+), a significantly higher percentage of CD4+HLADR-CD38- and a tendency to show a higher percentage of CD8+HLADR+CD38-T cells, than the low-risk group. Likewise, they showed higher mRNA levels of Serpin A1 from PBMCs. The results suggest that this cohort of MSM could be HESN individuals and their resistance would be explained by a quiescent profile of T cells and NK cells, and increased expression of Serpin A1. It is necessary to continue the study of MSM at high-risk of exposure to HIV-1 to better understand the natural resistance to HIV.

immunology↗

Atorvastatin effectively inhibits late replicative cycle steps of SARS-CoV-2 in vitro

IntroductionSARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) has caused a pandemic of historic proportions and continues to spread worldwide. Currently, there is no effective therapy against this virus. This article evaluated the in vitro antiviral effect of Atorvastatin against SARS-CoV-2 and also identified the interaction affinity between Atorvastatin and three SARS-CoV-2 proteins, using in silico structure-based molecular docking approach. Materials and methodsThe antiviral activity of Atorvastatin against SARS-CoV-2 was evaluated by three different treatment strategies using a clinical isolate of SARS-CoV-2. The interaction of Atorvastatin with Spike, RNA-dependent RNA polymerase (RdRp) and 3C-like protease (3CLpro) was evaluated by molecular docking. ResultsAtorvastatin showed anti-SARS-CoV-2 activity of 79%, 54.8%, 22.6% and 25% at 31.2, 15.6, 7.9, and 3.9 {micro}M, respectively, by pre-post-treatment strategy. In addition, atorvastatin demonstrated an antiviral effect of 26.9% at 31.2 {micro}M by pre-infection treatment. This compound also inhibited SARS-CoV-2 in 66.9%, 75%, 27.9% and 29.2% at concentrations of 31.2, 15.6, 7.9, and 3.9 {micro}M, respectively, by post-infection treatment. The interaction of atorvastatin with SARS-CoV-2 Spike, RdRp and 3CL protease yielded a binding affinity of -8.5 Kcal/mol, -6.2 Kcal/mol, and -7.5 Kcal/mol, respectively. ConclusionOur study demonstrated the in vitro anti-SARS-CoV-2 activity of Atorvastatin, mainly against the late steps of the viral replicative cycle. A favorable binding affinity with viral proteins by bioinformatics methods was also shown. Due to its low cost, availability, well-established safety and tolerability, and the extensive clinical experience of atorvastatin, it could prove valuable in reducing morbidity and mortality from COVID-19. ImportanceThe COVID-19 pandemic constitutes the largest global public health crisis in a century, with enormous health and socioeconomic challenges. Therefore, it is necessary to search for specific antivirals against its causative agent (SARS-CoV-2). In this sense, the use of existing drugs may represent a useful treatment option in terms of safety, cost-effectiveness, and timeliness. Atorvastatin is widely used to prevent cardiovascular events. This compound modulates the synthesis of cholesterol, a molecule necessary in different stages of the viral replicative cycle. Our study demonstrated the antiviral potential of atorvastatin against SARS-CoV-2, using an in vitro model. Furthermore, the ability of Atorvastatin to directly interfere with three viral targets (Spike, RdRp and 3CL protease) was demonstrated by bioinformatic methods. This compound is a well-studied, low-cost, and generally well-tolerated drug, so it could be a promising antiviral for the treatment of COVID-19.

microbiology↗

PRE-BORDER GENE FOXB1 REGULATES THE DIFFERENTIATION TIMING AND AUTONOMIC NEURONAL POTENTIAL OF HUMAN NEURAL CREST CELLS

What are the factors that are induced during the transitory phases from pluripotent stem cells to lineage specified cells, how are they regulated, and what are their functional contributions are fundamental questions for basic developmental biology and clinical research. Here, we uncover a set of pre-border (pB) gene candidates, including forkhead box B1 (FOXB1), induced during human neural crest (NC) cell development. We characterize their associated enhancers that are bound by pluripotency factors and rapidly activated by {beta}-catenin-mediated signaling during differentiation. Surprisingly, the endogenous transient expression of FOXB1 directly regulates multiple early NC and neural progenitor loci including PAX7, MSX2, SOX1, and ASCL1, controls the timing of NC fate acquisition, and differentially activates autonomic neurogenic versus mesenchymal fates in mature NC cells. Our findings provide further insight into the concept of the less characterized pB state and clearly establishes FOXB1 as a key regulator in early cell fate decisions during human pluripotent stem cell differentiation.

developmental biology↗

WNT/β-CATENIN modulates the axial identity of ES derived human neural crest

The WNT/{beta}-CATENIN pathway is critical for neural crest (NC) formation. However, the effects of the magnitude of the signal remains poorly defined. Here we evaluate the consequences of WNT magnitude variation in a robust model of human NC formation. This model is based on human embryonic stem cells induced by WNT signaling through the small molecule CHIR9902. In addition to its known effect on NC formation, we find that the WNT signal modulates the anterior-posterior axial identity of NCCs in a dose dependent manner, with low WNT leading to anterior OTX+, HOX-NC, and high WNT leading to posterior OTX-, HOX+ NC. Differentiation tests of posterior NC confirm expected derivatives including posterior specific adrenal derivatives, and display partial capacity to generate anterior ectomesenchymal derivatives. Furthermore, unlike anterior NC, posterior NC transit through a TBXT+/SOX2+ neuromesodermal precursor-like intermediate. Finally, we analyze the contributions of other signaling pathways in posterior NC formation, and suggest a critical role for FGF in survival/proliferation, and a requirement of BMP for NC maturation. As expected RA and FGF are able to modulate HOX expression in the posterior NC, but surprisingly, RA supplementation prohibits anterior, but only reduces, posterior NC formation. This work reveals for the first time that the amplitude of WNT signaling can modulate the axial identity of NC cells in humans.

developmental biology↗

Mitogenomes illuminate the origin and migration patterns of the indigenous people of the Canary Islands

The Canary Islands indigenous people have been the subject of substantial archaeological, anthropological, linguistic and genetic research pointing to a most probable North African Berber source. However, neither agreement about the exact point of origin nor a model for the indigenous colonization of the islands has been established. To shed light on these questions, we analyzed 48 ancient mitogenomes from 25 archaeological sites from the seven main islands. Most lineages observed in the ancient samples have a Mediterranean distribution, and belong to lineages associated with the Neolithic expansion in the Near East and Europe (T2c, J2a, X3a...). This phylogeographic analysis of Canarian indigenous mitogenomes, the first of its kind, shows that some lineages are restricted to Central North Africa (H1cf, J2a2d and T2c1d3), while others have a wider distribution, including both West and Central North Africa, and, in some cases, Europe and the Near East (U6a1a1, U6a7a1, U6b, X3a, U6c1). In addition, we identify four new Canarian-specific lineages (H1e1a9, H4a1e, J2a2d1a and L3b1a12) whose coalescence dates correlate with the estimated time for the colonization of the islands (1st millennia CE). Additionally, we observe an asymmetrical distribution of mtDNA haplogroups in the ancient population, with certain haplogroups appearing more frequently in the islands closer to the continent. This reinforces results based on modern mtDNA and Y-chromosome data, and archaeological evidence suggesting the existence of two distinct migrations. Comparisons between insular populations show that some populations had high genetic diversity, while others were probably affected by genetic drift and/or bottlenecks. In spite of observing interinsular differences in the survival of indigenous lineages, modern populations, with the sole exception of La Gomera, are homogenous across the islands, supporting the theory of extensive human mobility after the European conquest.

genetics↗