Notes

Cooperation among liver-specific versions of pten and also tp53 genetically causes hepatocarcinogenesis throughout zebrafish.
Two types of domestic water buffalo are currently recognized the river buffalo from the Indian subcontinent and Mediterranean countries and the swamp buffalo from China and Southeast Asia. To test the hypothesis of two separate species of water buffalo, we sequenced the genome of the lowland anoa, Bubalus depressicornis, which is a dwarf wild buffalo endemic to Sulawesi, and two genomes of swamp buffalo, and made comparisons with 12 additional genomes. Three genomic data sets were constructed to infer phylogenetic relationships the mitochondrial genome (15,468 bp; maternal transmission), two concatenated Y-chromosomal genes, AMELY and DDX3Y (20,036 bp; paternal transmission), and a selection of 30 nuclear genes representing all cattle chromosomes (364,887 bp; biparental transmission). The comparisons between our 30 nuclear gene sequences obtained by read mapping and those directly extracted from Bos taurus and Bubalus bubalis genome assemblies show that the mapping approach revealed higher levels of heterozygosity at both nucleotide sites and indels (insertions and deletions) (0.09-0.15%), as well as several sequence errors (0.07%). Our phylogenetic and molecular dating analyses provide strong evidence that the lowland anoa, river buffalo, and swamp buffalo are three distinct taxa which separated rapidly from each other during the Pleistocene epoch. Necrostatin-1 We therefore conclude that two species of domestic water buffalo should be distinguished Bubalus bubalis for the river buffalo and Bubalus kerabau for the swamp buffalo. The new classification can have deep implications for understanding the evolution and selection of domesticated forms and for the conservation and management of wild buffalo populations in South and Southeast Asia.Climbing mice in the genus Dendromus (sensu lato) are widely distributed in Africa, south of the Saharan Desert. The 17 currently recognized species in the genus range from widespread taxa to single-mountain endemics, and there is considerable variation across species with respect to habitats occupied. These habitats range from arid grasslands and savannahs to sub-alpine and alpine vegetation. Using the most comprehensive geographic and genetic survey to date and after reviewing many type specimens, we assess the systematics and biogeography of Dendromus. Given the structure of our molecular phylogenetic hypotheses, in which we recover six major clades, we propose the recognition of three genera within the Dendromus group (sensu lato) in addition to Dendromus (26 lineages), we suggest the retention of Megadendromus (monotypic) and the resurrection of the genus Poemys (six lineages). From our model-based molecular phylogenetic results and morphological comparisons, we suggest that six formerly synonymized taxaSouth Africa or Western Africa. None of the four Dendromus clades are reciprocally monophyletic with respect to distributional area.In less than one year since the outbreak of the COVID-19 pandemic, two mRNA-based vaccines, BNT162b2 and mRNA-1273, were granted the first historic authorization for emergency use, while another mRNA vaccine, CVnCoV, progressed to phase 3 clinical testing. The COVID-19 mRNA vaccines represent a new class of vaccine products, which consist of synthetic mRNA strands encoding the SARS-CoV-2 Spike glycoprotein, packaged in lipid nanoparticles to deliver mRNA to cells. This review digs deeper into the scientific breakthroughs of the last decades that laid the foundations for the rapid rise of mRNA vaccines during the COVID-19 pandemic. As well as providing momentum for mRNA vaccines, SARS-CoV-2 represents an ideal case study allowing to compare design-activity differences between the different mRNA vaccine candidates. Therefore, a detailed overview of the composition and (pre)clinical performance of the three most advanced mRNA vaccines is provided and the influence of choices in their structural design on to their immunogenicity and reactogenicity profile is discussed in depth. In addition to the new fundamental insights in the mRNA vaccines' mode of action highlighted here, we also point out which unknowns remain that require further investigation and possibly, optimization in future mRNA vaccine development.Breast cancer metastasis and recurrence accounts for vast majority of breast cancer-induced mortality. Tumor microenvironment (TME) plays an important role at each step of metastasis, evasion of immunosurveillance, and therapeutic resistance. Consequently, TME-targeting alternatives to traditional therapies focused on breast cancer cells are gaining increasing attention. These new therapies involve the use of tumor cells, and key TME components or secreted bioactive molecules as therapeutic targets, alone or in combination. Recently, TME-related nanoparticles have been developed to deliver various agents, such as bioactive ingredients extracted from natural sources or chemotherapeutic agents, genes, proteins, small interfering RNAs, and vaccines; they have shown great therapeutic potential against breast cancer metastasis. Among various types of nanoparticles, biomimetic nanovesicles are a promising means of addressing the limitations of conventional nanocarriers. This review highlights various nanoparticles related to or mediated by TME according to the key TME components responsible for metastasis. Furthermore, TME-related biomimetic nanoparticles against breast cancer metastasis have garnered attention owing to their promising efficiency, especially in payload delivery and therapeutic action. Here, we summarize recent representative studies on nanoparticles related to cancer-associated fibroblasts, extracellular matrix, endothelial cells, angiogenesis, and immune cells, as well as advanced biomimetic nanoparticles. Future challenges and opportunities in the field are also discussed.Tacrolimus has shown efficacy in eye inflammatory diseases. However, due to the drug lability, its formulation into a stable ophthalmic product remains a challenge. Tacrolimus-loaded nanocapsules (NCs) were designed for ocular instillation. Further, the stability and effects of the formulation were analyzed under different experimental conditions. Physicochemical characterization of the NCs revealed suitable homogeneous size and high encapsulation efficiency. Moreover, the lyophilized formulation was stable at ICH long term and accelerated storage conditions, for at least 18 and 3 months, respectively. The tacrolimus NCs did not elicit any eye irritation in rabbits after single- and multiple-dose applications. Additionally, ex vivo penetration assays on isolated porcine cornea and pharmacokinetics analyses in various rabbit eye compartments demonstrated the superiority of the NCs in retention and permeation into the anterior chamber of the eye compared to the free drug dissolved in oil. Moreover, multiple dose ocular instillation of the NCs in rats allowed high tacrolimus levels in the eye with very low plasma concentrations.
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