Track analysis of the Mexican species of Buprestidae (Coleoptera): testing the complex nature of the Mexican Transition Zone

Aim  We analysed the geographical distributions of species of Buprestidae (Coleoptera) in Mexico by means of a panbiogeographical analysis, in order to identify their main distributional patterns and test the complex nature of the Mexican Transition Zone, located between the Nearctic and Neotropical regions.
Location  Mexico.
Methods  The geographical distributions of 228 species belonging to 33 genera of Buprestidae were analysed. Localities of the buprestid species were represented on maps and their individual tracks were drawn. Based on a comparison of the individual tracks, generalized tracks were detected and mapped. Nodes were identified as the areas where generalized tracks converged.
Results  Thirteen generalized tracks were obtained: one was restricted to the Mexican Transition Zone and five to the Neotropical region (Antillean and Mesoamerican dominions), a further two occurred in both the Nearctic region (Continental Nearctic dominion) and the Mexican Transition Zone, and a further five in both the Neotropical region (Mesoamerican dominion) and the Mexican Transition Zone. Seven nodes were identified at the intersections of the generalized tracks – in the Mesoamerican dominion (Mexican Pacific Coast, Mexican Gulf and Chiapas biogeographical provinces) and the Mexican Transition Zone (Trans-Mexican Volcanic Belt, Balsas Basin and Sierra Madre Oriental biogeographical provinces).
Main conclusions  We conclude that the geographical distribution of Buprestidae is mainly Neotropical, corresponding to the Mesoamerican dominion and the Antillean dominion of the Neotropical region, and the Mexican Transition Zone. Most of the generalized tracks and nodes correspond to the Mexican Transition Zone, thus confirming its complex nature. We suggest that the nodes we have identified could be particularly important areas to choose for conservation prioritization.     

Towards the identification of the allosteric Phe-binding site in phenylalanine hydroxylase

The enzyme phenylalanine hydroxylase (PAH) is defective in the inherited disorder phenylketonuria. PAH, a tetrameric enzyme, is highly regulated and displays positive cooperativity for its substrate, Phe. Whether Phe binds to an allosteric site is a matter of debate, despite several studies worldwide. To address this issue, we generated a dimeric model for Phe–PAH interactions, by performing molecular docking combined with molecular dynamics simulations on human and rat wild-type sequences and also on a human G46S mutant. Our results suggest that the allosteric Phe-binding site lies at the dimeric interface between the regulatory and the catalytic domains of two adjacent subunits. The structural and dynamical features of the site were characterized in depth and described. Interestingly, our findings provide evidence for lower allosteric Phe-binding ability of the G46S mutant than the human wild-type enzyme. This also explains the disease-causing nature of this mutant.     

SIRT1 is involved in adrenocortical cancer growth and motility

Adrenocortical cancer (ACC) is a rare tumour with unfavourable prognosis, lacking an effective treatment. This tumour is characterized by IGF-II (insulin-like growth factor II) overproduction, aromatase and ERα (oestrogen receptor alpha) up-regulation. Previous reports suggest that ERα expression can be regulated by sirt1 (sirtuin 1), a nicotinamide adenine dinucleotide (NAD+)-dependent class III histone deacetylases that modulates activity of several substrates involved in cellular stress, metabolism, proliferation, senescence, protein degradation and apoptosis. Nevertheless, sirt1 can act as a tumour suppressor or oncogenic protein. In this study, we found that in H295R and SW13 cell lines, sirt1 expression is inhibited by sirtinol, a potent inhibitor of sirt1 activity. In addition, sirtinol is able to decrease ACC cell proliferation, colony and spheroids formation and to activate the intrinsic apoptotic mechanism. Particularly, we observed that sirtinol interferes with E2/ERα and IGF1R (insulin growth factor 1 receptor) pathways by decreasing receptors expression. Sirt1 involvement was confirmed by using a specific sirt1 siRNA. More importantly, we observed that sirtinol can synergize with mitotane, a selective adrenolitic drug, in inhibiting adrenocortical cancer cell growth. Collectively, our data reveal an oncogenic role for sirt1 in ACC and its targeting could implement treatment options for this type of cancer.     

Oh,SNAP! How enteroviruses redirect autophagic traffic away from degradation

Picornaviruses, one of the major causes of human diseases ranging from the common cold to acute flaccid paralysis, have a short cytosolic lifecycle that, in cultured cells, ends in cell lysis. For years, the prevailing model was that these viruses exit from cells exclusively through cell lysis. However, over the last several years it has become apparent that for some picornaviruses, a macroautophagy/autophagy-related pathway can result in release of virus particles wrapped in a membrane containing autophagic markers. It has been proposed that this enveloped release predominates within hosts, allowing cell-to-cell movement of virus while minimizing exposure to the immune system. One reason that picornaviruses induce the autophagy pathway is to provide membrane scaffolds for RNA replication complexes. Perhaps more importantly, acidified autophagosomes (known as amphisomes) provide havens for maturation of new viral particles into infectious viruses. In back-to-back papers recently published in Cell Reports, our labs investigated a basic question: if picornavirus particles are maturing inside amphisomes, then how are they avoiding the typical degradative fate of autophagic cargo and exiting the cell intact?     

Inferior Olive HCN1 Channels Coordinate Synaptic Integration and Complex Spike Timing

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Specific Labeling of Stem Cell Activity in Human Colorectal Organoids Using an ASCL2-Responsive Minigene

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