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  1. Article ; Online: Tetracycline-induced mitohormesis mediates disease tolerance against influenza

    Adrienne Mottis / Terytty Y. Li / Gaby El Alam / Alexis Rapin / Elena Katsyuba / David Liaskos / Davide D’Amico / Nicola L. Harris / Mark C. Grier / Laurent Mouchiroud / Mark L. Nelson / Johan Auwerx

    The Journal of Clinical Investigation, Vol 132, Iss

    2022  Volume 17

    Abstract: 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. ... ...

    Abstract 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.
    Keywords Infectious disease ; Medicine ; R
    Subject code 610
    Language English
    Publishing date 2022-09-01T00:00:00Z
    Publisher American Society for Clinical Investigation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Vitamin A administration at birth promotes calf growth and intramuscular fat development in Angus beef cattle

    Corrine L. Harris / Bo Wang / Jeneane M. Deavila / Jan R. Busboom / Martin Maquivar / Steven M. Parish / Brent McCann / Mark L. Nelson / Min Du

    Journal of Animal Science and Biotechnology, Vol 9, Iss 1, Pp 1-

    2018  Volume 9

    Abstract: Abstract Background Marbling, or intramuscular fat, is an important factor contributing to the palatability of beef. Vitamin A, through its active metabolite, retinoic acid, promotes the formation of new fat cells (adipogenesis). As intramuscular ... ...

    Abstract Abstract Background Marbling, or intramuscular fat, is an important factor contributing to the palatability of beef. Vitamin A, through its active metabolite, retinoic acid, promotes the formation of new fat cells (adipogenesis). As intramuscular adipogenesis is active during the neonatal stage, we hypothesized that vitamin A administration during the neonatal stage would enhance intramuscular adipogenesis and marbling. Methods Angus steer calves (n = 30), in a completely randomized design, were randomly allotted to three treatment groups at birth, receiving 0, 150,000, or 300,000 IU of vitamin A at both birth and one month of age. A biopsy of the biceps femoris muscle was collected at two months of age. After weaning at 210 d of age, steers were fed a backgrounding diet in a feedlot until 308 d of age, when they were transitioned to a high concentrate finishing diet and implanted with trenbolone/estradiol/tylosin mixture. Steers were harvested at an average of 438 d of age. All diets were formulated to meet nutrient requirements. Results Weaning weight and weight during the backgrounding phase were linearly increased (P < 0.05) by vitamin A level, though no difference in body weight was observed at harvest. Intramuscular fat of steers at 308 d of age, measured by ultrasound, quadratically increased (P < 0.05) with vitamin A level from 4.0±0.26 % to 4.9±0.26 %. Similarly, carcass marbling score in the ribeye quadratically increased (P < 0.05). Conclusion Administration of vitamin A at birth increased weaning weight and enhanced marbling fat development. Thus, vitamin A administration provides a practical method for increasing marbling and early growth of beef cattle.
    Keywords Beef ; Calf ; Cattle ; Marbling fat ; Quality ; Vitamin A ; Animal culture ; SF1-1100 ; Veterinary medicine ; SF600-1100
    Language English
    Publishing date 2018-07-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Airway epithelial NF-κB activation promotes Mycoplasma pneumoniae clearance in mice.

    Di Jiang / Mark L Nelson / Fabienne Gally / Sean Smith / Qun Wu / Maisha Minor / Stephanie Case / Jyoti Thaikoottathil / Hong Wei Chu

    PLoS ONE, Vol 7, Iss 12, p e

    2012  Volume 52969

    Abstract: Respiratory infections including atypical bacteria Mycoplasma pneumoniae (Mp) contribute to the pathobiology of asthma and chronic obstructive pulmonary disease (COPD). Mp infection mainly targets airway epithelium and activates various signaling ... ...

    Abstract Respiratory infections including atypical bacteria Mycoplasma pneumoniae (Mp) contribute to the pathobiology of asthma and chronic obstructive pulmonary disease (COPD). Mp infection mainly targets airway epithelium and activates various signaling pathways such as nuclear factor κB (NF-κB). We have shown that short palate, lung, and nasal epithelium clone 1 (SPLUNC1) serves as a novel host defense protein and is up-regulated upon Mp infection through NF-κB activation in cultured human and mouse primary airway epithelial cells. However, the in vivo role of airway epithelial NF-κB activation in host defense against Mp infection has not been investigated. In the current study, we investigated the effects of in vivo airway epithelial NF-κB activation on lung Mp clearance and its association with airway epithelial SPLUNC1 expression.Non-antimicrobial tetracycline analog 9-t-butyl doxycycline (9-TB) was initially optimized in mouse primary tracheal epithelial cell culture, and then utilized to induce in vivo airway epithelial specific NF-κB activation in conditional NF-κB transgenic mice (CC10-(CA)IKKβ) with or without Mp infection. Lung Mp load and inflammation were evaluated, and airway epithelial SPLUNC1 protein was examined by immunohistochemistry. We found that 9-TB treatment in NF-κB transgene positive (Tg+), but not transgene negative (Tg-) mice significantly reduced lung Mp load. Moreover, 9-TB increased airway epithelial SPLUNC1 protein expression in NF-κB Tg+ mice.By using the non-antimicrobial 9-TB, our study demonstrates that in vivo airway epithelial NF-κB activation promotes lung bacterial clearance, which is accompanied by increased epithelial SPLUNC1 expression.
    Keywords Medicine ; R ; Science ; Q
    Subject code 570
    Language English
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Silencing and un-silencing of tetracycline-controlled genes in neurons.

    Peixin Zhu / M Isabel Aller / Udo Baron / Sidney Cambridge / Melanie Bausen / Jan Herb / Jürgen Sawinski / Ali Cetin / Pavel Osten / Mark L Nelson / Sebastian Kügler / Peter H Seeburg / Rolf Sprengel / Mazahir T Hasan

    PLoS ONE, Vol 2, Iss 6, p e

    2007  Volume 533

    Abstract: To identify the underlying reason for the controversial performance of tetracycline (Tet)-controlled regulated gene expression in mammalian neurons, we investigated each of the three components that comprise the Tet inducible systems, namely ... ...

    Abstract To identify the underlying reason for the controversial performance of tetracycline (Tet)-controlled regulated gene expression in mammalian neurons, we investigated each of the three components that comprise the Tet inducible systems, namely tetracyclines as inducers, tetracycline-transactivator (tTA) and reverse tTA (rtTA), and tTA-responsive promoters (P(tets)). We have discovered that stably integrated P(tet) becomes functionally silenced in the majority of neurons when it is inactive during development. P(tet) silencing can be avoided when it is either not integrated in the genome or stably-integrated with basal activity. Moreover, long-term, high transactivator levels in neurons can often overcome integration-induced P(tet) gene silencing, possibly by inducing promoter accessibility.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2007-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

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