Mathiesen Falk (pinkbrown0)

It has been firmly observed that replicative DNA polymerases of bacteria, archaea and eukaryotes are not homologous proteins. This lack of homology in the replication apparatus among the domains of life is not only compatible with but would seem to imply the view that the emergence of DNA occurred in the fundamental cellular lineages. In consequence, this diversity of DNA polymerase would go back to the level of ancestors of the domains of life and to the evolutionary time in which the DNA emerged. Therefore, the presumed evolutionary stage linked to the RNA- > DNA transition would have occurred only at the level of ancestors of the main lineages of the tree of life. Thus, the high noise associated with this major evolutionary transition and the impossibility for a cellular stage to generate different fundamental genetically profound traits - such as the different replication apparatuses of bacteria, archaea and eukaryotes - would imply not only that the last universal common ancestor (LUCA) was a progenote but that the ancestors of the domains of life were also at this evolutionary stage. So, I criticize the hypotheses which want, instead, that completely different cells - such as, bacteria and archaea - could have originated from a cellular LUCA.Alpha-synuclein (a-syn) can aggregate and form toxic oligomers and insoluble fibrils which are the main component of Lewy bodies. Intra-neuronal Lewy bodies are a major pathological characteristic of Parkinson's disease (PD). These fibrillar structures can act as seeds and accelerate the aggregation of monomeric a-syn. Indeed, recent studies show that injection of preformed a-syn fibrils (PFF) into the rodent brain can induce aggregation of the endogenous monomeric a-syn resulting in neuronal dysfunction and eventual cell death. We injected 8 μg of murine a-syn PFF, or soluble monomeric a-syn into the right striatum of rats. #link# The animals were monitored behaviourally using the cylinder test, which measures paw asymmetry, and the corridor task that measures lateralized sensorimotor response to sugar treats. In vivo PET imaging was performed after 6, 13 and 22 weeks using [11C]DTBZ, a marker of the vesicular monoamine 2 transporter (VMAT2), and after 15 and 22 weeks using [11C]UCB-J, a marker of synaptic SV2A pronfirm that intrastriatal injection of a-syn PFFs provides a model of progressive a-syn pathology with loss of dopaminergic and synaptic function accompanied by neuroinflammation, as found in human PD.Baicalin has been widely investigated against different types of malignancies both at the cellular and molecular levels over the past few years. Due to its remarkable anti-proliferative potential in numerous cancer cell lines, it has created immense interest as a potential chemotherapeutic modality compared to other flavonoids. Thus, this review focuses on the recent accomplishments of baicalin and its limitations in cancer prevention and treatment. Further, combination studies and nanoformulations using baicalin to treat cancer along with the metabolism, bioavailability, toxicity, and pharmacokinetics have been discussed. The present review explains biological source, and anti-proliferative potential of baicalin against cancers including breast, colon, hepatic, leukemia, lung, and skin, as well as the relevant mechanism of action to modulate diverse signaling pathways including apoptosis, cell cycle, invasion, and migration, angiogenesis, and autophagy. The anticancer mechanism of baicalin in orthotropic and xenograft mice models have been deliberated. The combination studies of baicalin in novel therapies as chemotherapeutic adjuvants have also been summarized. The low bioavailability, fast metabolism, and poor solubility, and other significant factors that limit the clinical use of baicalin have been examined as a challenge. The improvement in the pharmacokinetics and pharmacodynamics of baicalin with newer approaches and the gaps are highlighted, which could establish