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The existence of exoplanets orbiting low mass-stars is one of the most significant discoveries of our time. Especially intriguing to us is the possibility that Earth-sized exoplanets within a habitable zone might harbor life-forms that resemble our own RNA/DNA-based species. We further narrow this theoretical possibility with the following question: if alien life does indeed exist elsewhere, would extraterrestrial life be burdened with earthly diseases? Given that the chemistry of the universe is subject to specific rules, restraints, and predictable outcomes, we argue that cancer-signaling pathways might be programmed into the life cycle of habitable exoplanets. This hypothetical prediction is also based on evolutionary convergence, the repeated emergence of biological similarity that occurs when disparate life-forms adapt to comparable selection pressures. The possibility that mutations and nucleotide base rearrangements that drive cancer growth might be fixed in the chemical hardware of alien life provides us with the opportunity to wonder and consider the origins, evolution, and ubiquity of disease beyond Earth., Competing Interests: The authors have declared that no competing interests exist.

Patients who harbor brain arteriovenous malformations are at risk for intracranial hemorrhage. These malformations are often seen in inherited vascular diseases such as hereditary hemorrhagic telangiectasia. However, malformations within the brain also sporadically occur without a hereditary-coding component. Here, we review recent insights into the pathophysiology of arteriovenous malformations, in particular, certain signaling pathways that might underlie endothelial cell pathology. To better interpret the origins, determinants and consequences of brain arteriovenous malformations, we present a clinical case to illustrate the phenotypic landscape of the disease. We also propose that brain arteriovenous malformations might share certain signaling dimensions with those of anorectal hemorrhoids. This working hypothesis provides casual anchors from which to understand vascular diseases characterized by arteriovenous lesions with a hemorrhagic- or bleeding-risk component. Anat Rec, 2017. © The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists. Anat Rec, 300:1973-1980, 2017. © 2017 The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists., (© 2017 The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists.)

Ketamine exerts powerful anesthetic, psychotic, and antidepressant effects in both healthy volunteers and clinically depressed patients. Although ketamine targets particular glutamate receptors, there is a dearth of evidence for additional, alternative molecular substrates for the behavioral actions of this N-methyl-D-aspartate (NMDA) receptor antagonist drug. Here, we provide behavioral and molecular evidence for the actions of ketamine using a new vertebrate model for psychiatric disorders: the zebrafish. Subanesthetic doses of ketamine produced a variety of abnormal behaviors in zebrafish that were qualitatively analogous to those previously measured in humans and rodents treated with drugs that produce transient psychosis. In addition, we revealed that the transcription factor Phox2b is a molecular substrate for the actions of ketamine, particularly during periods of hypoxic stress. Finally, we also show that SIRT1, a histone deacetylase widely recognized for its link to cell survival is also affected by hypoxia crises. These results establish a relevant assay system in which the effects of psychotomimetic drugs can rapidly be assessed, and provide a plausible and novel neuronal mechanism through which ketamine affects critical sensory circuits that monitor breathing behavior., (Copyright © 2010 Wiley-Liss, Inc.)

Sirtuins function with other biogenic molecules to promote adaptation to caloric restriction in a broad spectrum of eukaryotic species. Sirtuin pathways also converge in the mammalian brain where they appear to protect neurons from nutrient stress. However, few anatomical studies on sirtuins (e.g., SIRT1) are available, particularly those detailing the spatial distribution and subcellular localization pattern of SIRT1 in the brain parenchyma. Here, we report the characterization of a panel of SIRT1-specific antibodies within rodent (i.e., rat and mouse) and human central nervous systems. Immunocytochemical and Western blot analyses indicate that the subcellular localization of SIRT1 is predominantly nuclear throughout the rodent brain and spinal cord. A similar subcellular distribution pattern of SIRT1 was detected in human central nervous system material. SIRT1 is ubiquitously present in areas of the brain especially susceptible to age-related neurodegenerative states (e.g., the prefrontal cortex, hippocampus and basal ganglia). Further, we show no apparent species-specific differences in the subcellular localization pattern of rodent versus human SIRT1. Finally, we identify the chemical phenotype of SIRT1-containing neurons in a number of brain sites that are strongly compromised by aging. These data provide additional and important anatomical findings for the role of SIRT1 in the mammalian brain and suggest that SIRT1 pathways are broadly distributed in neurons most susceptible to senescence injury. Activating endogenous sirtuin pathways may, therefore, offer a therapeutic approach to delay and/or treat human age-related diseases.

The mammalian protein deacetylase SIRT1 (sirtuin1) is widely recognized for its link to calorie restriction and longevity. SIRT1 not only modulates the function of protein targets such as p53 or NFkappaB, but it also affects gene transcription by causing hypoacetylation of associated nucleosomal histones. However, the identification of SIRT1-specific DNA targets that confer chromosomal stability and cell longevity have remained elusive. Here, we report the usefulness of a ChIP-cloning approach for the identification of an endogenous DNA target intimately linked with SIRT1 activity. Using the aforementioned technique, we identified a gene encoding the neuro-oncological ventral antigen2 (nova2) as a SIRT1 target. Nova2 regulates the alternative splicing of scn1a, which encodes the alpha-subunit of a neuronal sodium channel targeted by antiepileptic drugs. This finding demonstrates that ChIP-cloning is an innovative approach for the identification of SIRT1-specific DNA targets.