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Mitohormesis defines the increase in fitness mediated by adaptive responses to mild mitochondrial stress. Tetracyclines inhibit not only bacterial but also mitochondrial translation, thus imposing a low level of mitochondrial stress on eukaryotic cells. We demonstrate in cell and germ-free mouse models that tetracyclines induce a mild adaptive mitochondrial stress response (MSR), involving both the ATF4-mediated integrative stress response and type I interferon (IFN) signaling. To overcome the interferences of tetracyclines with the host microbiome, we identify tetracycline derivatives that have minimal antimicrobial activity, yet retain full capacity to induce the MSR, such as the lead compound, 9-tert-butyl doxycycline (9-TB). The MSR induced by doxycycline (Dox) and 9-TB improves survival and disease tolerance against lethal influenza virus (IFV) infection when given preventively. 9-TB, unlike Dox, did not affect the gut microbiome and also showed encouraging results against IFV when given in a therapeutic setting. Tolerance to IFV infection is associated with the induction of genes involved in lung epithelial cell and cilia function, and with downregulation of inflammatory and immune gene sets in lungs, liver, and kidneys. Mitohormesis induced by non-antimicrobial tetracyclines and the ensuing IFN response may dampen excessive inflammation and tissue damage during viral infections, opening innovative therapeutic avenues., Introduction Cells constantly monitor the function of their mitochondria and activate adaptive mitochondrial stress responses (MSRs) to maintain or restore mitochondrial homeostasis upon stress. Mitohormesis is the phenomenon that ensues [...]

With increasing resistance to existing antimalarials, there is an urgent need to discover new drugs at affordable prices for countries in which malaria is endemic. One approach to the development of new antimalarial drugs is to improve upon existing antimalarial agents, such as the tetracyclines. Tetracyclines exhibit potent, albeit relatively slow, action against malaria parasites, and doxycycline is used for both treatment (with other agents) and prevention of malaria. We synthesized 18 novel 7-position modified tetracycline derivatives and screened them for activity against cultured malaria parasites. Compounds with potent in vitro activity and other favorable drug properties were further tested in a rodent malaria model. Ten compounds inhibited the development of cultured Plasmodium falciparum with a 50% inhibitory concentration (IC50) after 96 h of incubation of

Microbial infections of the brain can lead to dementia, and for many decades microbial infections have been implicated in Alzheimer's disease (AD) pathology. However, a causal role for infection in AD remains contentious, and the lack of standardized detection methodologies has led to inconsistent detection/identification of microbes in AD brains. There is a need for a consensus methodology; the Alzheimer's Pathobiome Initiative aims to perform comparative molecular analyses of microbes in post mortem brains versus cerebrospinal fluid, blood, olfactory neuroepithelium, oral/nasopharyngeal tissue, bronchoalveolar, urinary, and gut/stool samples. Diverse extraction methodologies, polymerase chain reaction and sequencing techniques, and bioinformatic tools will be evaluated, in addition to direct microbial culture and metabolomic techniques. The goal is to provide a roadmap for detecting infectious agents in patients with mild cognitive impairment or AD. Positive findings would then prompt tailoring of antimicrobial treatments that might attenuate or remit mounting clinical deficits in a subset of patients. [ABSTRACT FROM AUTHOR]

Histological evidence of tetracycline use has been reported in an ancient X-Group population (350-550 CE) from Sudanese Nubia (Bassett et al., 1980). When bone samples were examined by fluorescent microscopy under UV light at 490 A yellow-green fluorophore deposition bands, similar to those produced by tetracycline, were observed, suggesting significant exposure of the population to the antibiotic. These reports were met skeptically with claims that the fluorescence was the result of postmortem taphonomic infiltration of bacteria and fungi. Herein, we report the acid extraction and mass spectroscopic characterization of the antibiotic tetracycline from these samples. The bone samples were demineralized in anhydrous hydrogen fluoride which dissolved the bone-complexed tetracycline, followed by isolation by solid phase extraction on reverse-phase media. Chemical characterization by high pressure liquid chromatography mass-spectroscopic procedures showed that the retention times and mass spectra of the bone extract were identical to tetracycline when treated similarly. These results indicate that a natural product tetracycline was detectable within the sampled bone and was converted to the acid-stable form, anhydrotetracycline, with a mass + H of 427.1 amu. Our findings show that the bone sampled is labeled by the antibiotic tetracycline, and that the NAX population ingested and were exposed to tetracycline-containing materials in their dietary regime. Am J Phys Anthropol 143:151-154, 2010. KEY WORDS antibiotic; prehistory; chemical extraction DOI 10.1002/ajpa.21340

Research suggests dopamine may significantly affect the tendency to smoke cigarettes. Allele 9 of a dopamine transporter gene, also known as SLC6A3-9, alters dopamine transmission to reduce the need for novelty and reward, behaviors associated with smoking.

Research has been conducted on tetracycline derivatives. The authors report the synthesis of these derivatives which utilizes Suzuki, Heck and other palladium-coupling reactions by means of tetracycline iodoarene and arenediazonium salts.

Discusses the working relationship between librarians and architects in handling feasibility studies, site evaluations, budget considerations, time line predictions, and the architectural programing involved in library building projects, whether it be replacing, expanding, remodeling, or relocating. (EJS)