In 2006, Resilience Thinking addressed an essential question: As the natural systems that sustain us are subjected to shock after shock, how much can they take and still deliver the services we need ...from them? This idea caught the attention of both the scientific community and the general public. In Resilience Practice, authors Brian Walker and David Salt take the notion of resilience one step further, applying resilience thinking to real-world situations and exploring how systems can be managed to promote and sustain resilience.
•Testosterone maintains BTB, meiosis, Sertoli–spermatid adhesion and spermiation.•Testosterone acts via classical and non-classical pathways.•Testosterone regulates PTM, Leydig, and Sertoli cells via ...the androgen receptor.•The combined regulation of many genes by testosterone supports spermatogenesis.
Testosterone is essential for maintaining spermatogenesis and male fertility. However, the molecular mechanisms by which testosterone acts have not begun to be revealed until recently. With the advances obtained from the use of transgenic mice lacking or overexpressing the androgen receptor, the cell specific targets of testosterone action as well as the genes and signaling pathways that are regulated by testosterone are being identified. In this review, the critical steps of spermatogenesis that are regulated by testosterone are discussed as well as the intracellular signaling pathways by which testosterone acts. We also review the functional information that has been obtained from the knock out of the androgen receptor from specific cell types in the testis and the genes found to be regulated after altering testosterone levels or androgen receptor expression.
Testosterone is essential to maintain spermatogenesis and male fertility. In the absence of testosterone stimulation, spermatogenesis does not proceed beyond the meiosis stage. After withdrawal of ...testosterone, germ cells that have progressed beyond meiosis detach from supporting Sertoli cells and die, whereas mature sperm cannot be released from Sertoli cells resulting in infertility. The classical mechanism of testosterone action in which testosterone activates gene transcription by causing the androgen receptor to translocate to and bind specific DNA regulatory elements does not appear to fully explain testosterone regulation of spermatogenesis. This review discusses two non-classical testosterone signalling pathways in Sertoli cells and their potential effects on spermatogenesis. Specifically, testosterone-mediated activation of phospholipase C and calcium influx into Sertoli cells is described. Also, testosterone activation of Src, EGF receptor and ERK kinases as well as the activation of the CREB transcription factor and CREB-mediated transcription is reviewed. Regulation of germ cell adhesion to Sertoli cells and release of mature sperm from Sertoli cells by kinases regulated by the non-classical testosterone pathway is discussed. The evidence accumulated suggests that classical and non-classical testosterone signalling contribute to the maintenance of spermatogenesis and male fertility.
We report that, in the rat hippocampus, learning leads to a significant increase in extracellular lactate levels that derive from glycogen, an energy reserve selectively localized in astrocytes. ...Astrocytic glycogen breakdown and lactate release are essential for long-term but not short-term memory formation, and for the maintenance of long-term potentiation (LTP) of synaptic strength elicited in vivo. Disrupting the expression of the astrocytic lactate transporters monocarboxylate transporter 4 (MCT4) or MCT1 causes amnesia, which, like LTP impairment, is rescued by L-lactate but not equicaloric glucose. Disrupting the expression of the neuronal lactate transporter MCT2 also leads to amnesia that is unaffected by either L-lactate or glucose, suggesting that lactate import into neurons is necessary for long-term memory. Glycogenolysis and astrocytic lactate transporters are also critical for the induction of molecular changes required for memory formation, including the induction of phospho-CREB, Arc, and phospho-cofilin. We conclude that astrocyte-neuron lactate transport is required for long-term memory formation.
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► Learning results in glycogenolysis-dependent lactate increase in the hippocampus ► Inhibiting glycogenolysis in the hippocampus blocks long-term memory and LTP ► Knockdown of astrocytic lactate transporters abolishes long-term memory ► Knockdown of neuronal lactate transporter abolishes long-term memory
Circadian rhythm disruption and mental health Walker, 2nd, William H; Walton, James C; DeVries, A Courtney ...
Translational psychiatry,
01/2020, Volume:
10, Issue:
1
Journal Article
Peer reviewed
Open access
Circadian rhythms are internal manifestations of the solar day that permit adaptations to predictable environmental temporal changes. These ~24-h rhythms are controlled by molecular clockworks within ...the brain that are reset daily to precisely 24 h by exposure to the light-dark cycle. Information from the master clock in the mammalian hypothalamus conveys temporal information to the entire body via humoral and neural communication. A bidirectional relationship exists between mood disorders and circadian rhythms. Mood disorders are often associated with disrupted circadian clock-controlled responses, such as sleep and cortisol secretion, whereas disruption of circadian rhythms via jet lag, night-shift work, or exposure to artificial light at night, can precipitate or exacerbate affective symptoms in susceptible individuals. Evidence suggests strong associations between circadian rhythms and mental health, but only recently have studies begun to discover the direct interactions between the circadian system and mood regulation. This review provides an overview of disrupted circadian rhythms and the relationship to behavioral health and psychiatry. The focus of this review is delineating the role of disruption of circadian rhythms on mood disorders using human night shift studies, as well as jet lag studies to identify links. We also review animal models of disrupted circadian rhythms on affective responses. Lastly, we propose low-cost behavioral and lifestyle changes to improve circadian rhythms and presumably behavioral health.
Four families of enveloped RNA viruses, filoviruses, flaviviruses, arenaviruses, and bunyaviruses, cause hemorrhagic fevers. These viruses are maintained in specific natural cycles involving nonhuman ...primates, bats, rodents, domestic ruminants, humans, mosquitoes, and ticks. Vascular instability varies from mild to fatal shock, and hemorrhage ranges from none to life threatening. The pathogenic mechanisms are extremely diverse and include deficiency of hepatic synthesis of coagulation factors owing to hepatocellular necrosis, cytokine storm, increased permeability by vascular endothelial growth factor, complement activation, and disseminated intravascular coagulation in one or more hemorrhagic fevers. The severity of disease caused by these agents varies tremendously; there are extremely high fatality rates in Ebola and Marburg hemorrhagic fevers, and asymptomatic infection predominates in yellow fever and dengue viral infections. Although ineffective immunity and high viral loads are characteristic of several viral hemorrhagic fevers, severe plasma leakage occurs at the time of viral clearance and defervescence in dengue hemorrhagic fever.
Scrub typhus is a serious public health problem in the Asia-Pacific area. It threatens one billion people globally, and causes illness in one million people each year. Caused by Orientia ...tsutsugamushi, scrub typhus can result in severe multiorgan failure with a case fatality rate up to 70% without appropriate treatment. The antigenic heterogeneity of O. tsutsugamushi precludes generic immunity and allows reinfection. As a neglected disease, there is still a large gap in our knowledge of the disease, as evidenced by the sporadic epidemiologic data and other related public health information regarding scrub typhus in its endemic areas. Our objective is to provide a systematic analysis of current epidemiology, prevention and control of scrub typhus in its long-standing endemic areas and recently recognized foci of infection.
Sleep is essential for health. Indeed, poor sleep is consistently linked to the development of systemic disease, including depression, metabolic syndrome, and cognitive impairments. Further evidence ...has accumulated suggesting the role of sleep in cancer initiation and progression (primarily breast cancer). Indeed, patients with cancer and cancer survivors frequently experience poor sleep, manifesting as insomnia, circadian misalignment, hypersomnia, somnolence syndrome, hot flushes, and nightmares. These problems are associated with a reduction in the patients' quality of life and increased mortality. Due to the heterogeneity among cancers, treatment regimens, patient populations and lifestyle factors, the etiology of cancer-induced sleep disruption is largely unknown. Here, we discuss recent advances in understanding the pathways linking cancer and the brain and how this leads to altered sleep patterns. We describe a conceptual framework where tumors disrupt normal homeostatic processes, resulting in aberrant changes in physiology and behavior that are detrimental to health. Finally, we discuss how this knowledge can be leveraged to develop novel therapeutic approaches for cancer-associated sleep disruption, with special emphasis on host-tumor interactions.
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