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Solis, M.

Publications and source records attributed to Solis, M..

3 recordsLinked to original sources

SMARCA2/4-Dependent Chromatin Remodelling Establishes Gene Regulatory Programs in Early Human Embryos and Blastoids

Establishment of cell lineages during development is regulated by transcription factors binding at cis-regulatory elements to activate gene regulatory programs. Many transcription factors require chromatin remodellers for accessibility at their target sites. Although these key principles of gene regulation in mammalian development have emerged, the contribution of chromatin remodellers to early human embryogenesis remains unknown. Here, we show that the SWI/SNF ATPases SMARCA2 and SMARCA4 are required for establishing the epiblast and trophectoderm fates during human pre-implantation development and facilitate accessibility at regulatory elements. We find that degradation of SWI/SNF ATPases disrupts epiblast formation in blastoids and enhances trophectoderm specification, while also showing transcriptional and chromatin misregulation in TE-like cells. In human embryos, SWI/SNF perturbation impaired blastocyst formation and the establishment of the inner cell mass. Single-nucleus chromatin accessibility and transcriptome profiling in blastoids reveals that the SWI/SNF complex safeguards the naive epiblast and trophectoderm programs and facilitates enhancer and transcription factor motif accessibility. These findings identify SWI/SNF chromatin remodellers as critical regulators of embryonic lineage specification during human pre-implantation development.

developmental biology↗

Assembly and phylogeographic analysis of novel Taenia solium mitochondrial genomes reveal further differentiation between and within Asian and African-American genotypes

BackgroundTaenia solium is a parasite that hampers human health, causing taeniasis and cysticercosis. The genetic variability in its mitochondrial genome is related to the geographical origin of the specimen. Two main genotypes have been identified: The Asian and the African-American. The geographic genetic variability is expected to cause different clinical manifestations. Thus, characterizing differences between and within genotypes is crucial for completing the epidemiology of T. solium diseases. Methods/Principal FindingsHere, two Peruvian (one complete and one partial; 7,811X and 42X of coverage, respectively) and one Mexican (complete, 3,395X) T. solium mitochondrial genomes were assembled using the Chinese reference. Variant calling with respect to the reference was performed. Thirteen SNPs that involved a change in the amino acid physicochemical nature were identified. Those were present in all the assembled genomes and might be linked to differences in aerobic respiration efficiency between Latin American (African-American) and Asian genotypes. Then, phylogeographic studies were conducted using Cytochrome C oxidase subunit I and cytochrome B from these genomes and other isolates. The analysis showed that Indonesian samples are the most ancient and related to the modern T. solium ancestor of the Asian genotype. Finally, a consistent subdivision of the African-American genotype into two subgroups was found. One subgroup relates to East African countries, while the other is West Africa. The East African linage suggests a previously unnoticed influence of the Indian Ocean trade in the genetic structure of Latin America T. solium. Conclusions/SignificanceOverall, this study reports novel mitochondrial genomes valuable for further studies. New Latin American SNPs were identified and suggest metabolic differences between parasites of the Asian and African-American genotypes. Moreover, the phylogeographic analysis revealed differences within each genotype that shed light on T. soliums historical spread. Overall, the results represent an important step in completing T. solium genetic epidemiology. Author SummaryTaenia solium is a human parasite that causes taeniasis and cysticercosis. Eradicated from developed countries, they are still a public health problem in developing nations. T. solium differences in the mitochondrial genetic material depend on its geographical origin. This is expected to cause different clinical manifestations. Despite the importance of genetics to the epidemiology of T. solium diseases, few efforts have been made to assemble and compare their genomes. We aimed to help fill this knowledge gap by assembling three mitochondrial genomes from Latin America and comparing them to the Chinese reference. Additionally, two genes from the Latin American genomes and from other isolates were employed to assess T. solium genetic distribution. We found thirteen mutations with respect to the Chinese genome present in all Latin American samples, which involved a change in the amino acid physicochemical nature. Those might be causing metabolic differences between Asian and Latin American parasites that could change their affinity to specific human tissues. Moreover, we determined that Indonesian samples are the most ancient and related to the modern T. solium ancestor. Finally, we identified a previously unnoticed influence of East African countries in T. solium phylogeny, with which our assembled genomes are closely related.

genetics↗

Effects of Topical Antimicrobial Formulations on Pseudomonas aeruginosa Biofilm in an In vivo Porcine Burn Wound Model

Silver has been incorporated into a variety of wound dressings and topical agents to prevent and combat wound infections. Pseudomonas aeruginosa is a common cause of burn wound infections and well-known biofilm producer. The objective of this study was to evaluate the effects of a panel of wound dressings containing different silver formulations on P. aeruginosa biofilms using an in vivo porcine burn wound model. Second-degree burns were created on the skin of specific pathogen-free pigs (n = 3) and inoculated with 2.14 x 105 cfu P. aeruginosa per wound. Biofilms were allowed to develop for 24 h, and then each wound was treated with one of 6 treatments: silver oxynitrate dressing (OXY), silver oxynitrate powder (POWD), nanocrystalline silver dressing (NANO), silver chloride dressing (AGCL), silver sulfadiazine (SSD), or a negative control polyurethane film with no silver-based formulation (NEG). Wounds were cultured at D3 post-infection (n = 3 per pig per treatment) and at D6 post-infection (n = 3 per pig per treatment) for quantification of bacteria. On D6, biopsies (n = 3 per treatment) were taken from POWD, SSD, and NEG wounds and wound healing progress was evaluated histologically. At the time of treatment initiation, 24 h post-infection, 8.71 log cfu P. aeruginosa were present in burn wounds. On D3 and D6, all treatments significantly reduced bacterial counts in wounds as compared to NEG, but POWD caused an approximately 7-log reduction in bacterial counts on both days and was the only treatment to reduce the bacterial counts to below the threshold for detecting bacteria. The OXY, NANO, and SSD treatments had similar reductions in bacterial recovery on D3 and D6 of approximately 2.5-4 log. The histological healing metrics of reepithelialization percentage, epithelial thickness, white cell infiltration, angiogenesis, and granulation tissue formation were similar among wounds from POWD, SSD, and NEG groups at 6 days post-infection. Silver oxynitrate powder reduced P. aeruginosa growth in burn wounds more effectively than other silver-based dressings but did not impact wound healing.

microbiology↗