Sex and age differences in AMPK phosphorylation,mitochondrial homeostasis,and inflammation in hearts from inflammatory cardiomyopathy patients

Linked to exacerbated inflammation, myocarditis is a cardiovascular disease, which may lead to dilated cardiomyopathy. Although sex and age differences in the development of chronic myocarditis have been postulated, underlying cellular mechanisms remain poorly understood. In the current study, we aimed to investigate sex and age differences in mitochondrial homeostasis, inflammation, and cellular senescence. Cardiac tissue samples from younger and older patients with inflammatory dilated cardiomyopathy (DCMI) were used. The expression of Sirt1, phosphorylated AMPK, PGC-1α, Sirt3, acetylated SOD2, catalase, and several mitochondrial genes was analyzed to assess mitochondrial homeostasis. The expression of NF-κB, TLR4, and interleukins was used to examine the inflammatory state in the heart. Finally, several senescence markers and telomere length were investigated. Cardiac AMPK expression and phosphorylation were significantly elevated in male DCMI patients, whereas Sirt1 expression remained unchanged in all groups investigated. AMPK upregulation was accompanied by a preserved expression of all mitochondrial proteins/genes investigated in older male DCMI patients, whereas the expression of TOM40, TIM23, and the mitochondrial oxidative phosphorylation genes was significantly reduced in older female patients. Mitochondrial homeostasis in older male patients was further supported by the reduced acetylation of mitochondrial proteins as indicated by acetylated SOD2. The inflammatory markers NF-κB and TLR4 were downregulated in older male DCMI patients, whereas the expression of IL-18 was increased in older female patients. This was accompanied by progressed senescence in older DCMI hearts. In conclusion, older women experience more dramatic immunometabolic disorders on the cellular level than older men.     

Cardio-respiratory responses in two ecologically distinct erythrinids (Hoplias malabaricus and Hoplias lacerdae) exposed to graded environmental hypoxia

Synopsis Ecologically distinct species of Hoplias were studied as to the cardio-respiratory responses to graded hypoxia. Hoplias malabaricus maintained a constant oxygen uptake down to a PiO₂ of 20 mmHg. Oxygen uptake declined markedly at lower PiO₂ and, concomitantly, cardiac frequency decreased. Concurrent reductions of oxygen uptake and heart rate also occurred in Hoplias lacerdae but at the considerably higher PiO₂ of 35 mmHg. These species-specific differences are consistent with the respective habitats: H. malabaricus occurs in stagnant hypoxic water, whereas H. lacerdae inhabits well-oxygenated rivers.     

Response of xylem parenchyma by suberization in some hardwoods after mechanical injury

Summary Wound responses of xylem parenchyma by suberization were investigated in some hardwoods by light and electron microscopy. Suberized ray and axial parenchyma cells form a distinct boundary around the wound in all investigated species. Vessels and fibres within and close behind the suberized area appeared more or less occluded; vessels in Fagus, Quercus, and Populus contained suberized tyloses, those in Betula and Tilia contained amorphous and fibrillar deposits. A common mechanism for suberin deposition in the parenchyma cells became evident. Cisternae of the endoplasmic reticulum were apparently involved in suberization. Suberin compounds are extruded by cytoplasmic vesicles, which fused with the plasma membrane, in order to release their content. The suberin layer exhibited the typical lamellated structure; cytoplasmic continuity between suberized cells by plasmodesmata was maintained through the suberin layer. Fagus revealed the most intense suberized area as compared with the other species. Within the reaction zone of Fagus and Quercus, some individual ray and axial parenchyma cells exhibited a subdivision into 2 or 3 compartments prior to suberization. Subdivision was achieved by the formation of a primary wall-like layer. Subsequently, the compartments became individually suberized. Wounding during winter did not induce suberization. Also, samples wounded and kept under water during the vegetation period showed no response. The role of suberization in the effectivity of wound-associated compartmentalization is discussed.     

Vaccination of squirrel monkeys (Saimiri spp.) with nanoparticle-based Toxoplasma gondii antigens: new hope for captive susceptible species

Squirrel monkeys (Saimiri spp.), new world primates from South America, are very susceptible to toxoplasmosis. Numerous outbreaks of fatal toxoplasmosis in zoos have been identified around the world, resulting in acute respiratory distress and sudden death. To date, preventive hygiene measures or available treatments are not able to significantly reduce this mortality in zoos. Therefore, vaccination seems to be the best long-term solution to control acute toxoplasmosis. Recently, we developed a nasal vaccine composed of total extract of soluble proteins of Toxoplasma gondii associated with muco-adhesive maltodextrin-nanoparticles. The vaccine, which generated specific cellular immune responses, demonstrated efficacy against toxoplasmosis in murine and ovine experimental models. In collaboration with six French zoos, our vaccine was used as a last resort in 48 squirrel monkeys to prevent toxoplasmosis. The full protocol of vaccination includes two intranasal sprays followed by combined intranasal and s.c. administration. No local or systemic side-effects were observed irrespective of the route of administration. Blood samples were collected to study systemic humoral and cellular immune responses up to 1 year after the last vaccination. Vaccination induced a strong and lasting systemic cellular immune response mediated by specific IFN-γ secretion by peripheral blood mononuclear cells. Since the introduction of vaccination, no deaths of squirrel monkeys due to T. gondii has been observed for more than 4 years suggesting the promising usage of our vaccine. Moreover, to explain the high susceptibility of naive squirrel monkeys to toxoplasmosis, their innate immune sensors were investigated. It was observed that Toll-like and Nod-like receptors appear to be functional following T. gondii recognition suggesting that the extreme susceptibility to toxoplasmosis may not be linked to innate detection of the parasite.     

Endogenous opiates: 1992

This paper is the fifteenth installment of our annual review of research concerning the opiate system. It includes papers published during 1992 involving the behavioral, nonanalgesic, effects of the endogenous opiate peptides. The specific topics this year include stress; tolerance and dependence; eating; drinking; gastrointestinal and renal function; mental illness and mood; learning, memory, and reward; cardiovascular responses; respiration and thermoregulation; seizures and other neurological disorders; electrical-related activity; general activity and locomotion; sex, pregnancy, and development; immunological responses; and other behaviors.     

Control of development in plants and fungi by far-UV radiation

Far-UV (200–320 nm) radiation regulates development in plants and fungi. Some of these responses are controlled by a chromophore which absorbs strongly near 260 nm, possibly a nucleic acid. Other responses are controlled by a chromophore(s). with maximal in vivo sensitivity near 295 nm. In plants. far-UV induces genes in the phenylpropanoid pathway and the synthesis of phytoalexins and flavonoids. Far-UV also regulates growth rate. controls curvature and taxis, and stimulates sexual and asexual morphogenesis of fungi. Some of these developmental responses may prevent damage by far-UV radiation.     

Role of interleukin-1 in stress responses

Recently, the central roles of interleukin-1 (IL-1) in physical stress responses have been attracting attention. Stress responses have been characterized as central neurohormonal changes, as well as behavioral and physiological changes. Administration of IL-1 has been shown to induce effects comparable to stress-induced changes. IL-1 acts on the brain, especially the hypothalamus, to enhance release of monoamines, such as norepinephrine, dopamine, and serotonin, as well as secretion of corticotropin-releasing hormone (CRH). IL-1-induced activation of the hypothalamo-pituitary-adrenal (HPA) axis in vivo depends on secretion of CRH, an intact pituitary, and the ventral noradrenergic bundle that innervates the CRH-containing neurons in the paraventricular nucleus of the hypothalamus. Recent studies have shown that IL-1 is present within neurons in the brain, suggesting that IL-1 functions in neuronal transmission. We showed that IL-1 in the brain is involved in the stress response, and that stress-induced activation of monoamine release and the HPA axis were inhibited by IL-1 receptor antagonist (IL-1Ra) administration directly into the rat hypothalamus. IL-1Ra has been known to exert a blocking effect on IL-1 by competitively inhibiting the binding of IL-1 to IL-1 receptors. In the latter part of this review, we will attempt to describe the relationship between central nervous system diseases, including psychological disorders, and the functions of IL-1 as a putative neurotransmitter.     

Oral cavity gate of an entry into the Communication Network

For ages naso-oro-pharyngreal cavity was considered as gate of entry toliving organism for air and food. In recent years, however, the thoughtshave changed considerably. Several lines of evidence indicate that the oralcavity with adjacent cavities plays a pivotal role for the recognition ofsignals coming from the surrounding world. These signals in form of food,germs, poisonous substances are initially analyzed in oral cavity andmessages are distributed by a variety of communication pathways intopertinent parts of the body. All these diverse functions are performed byanatomical structures present in the naso-oro-pharyngreal cavity. Thefollowing article describes some of the functions discovered recently.     

EVOLUTIONARY ADAPTATION TO TEMPERATURE. IV. ADAPTATION OF ESCHERICHIA COLI AT A NICHE BOUNDARY

Following an environmental change, the course of a population's adaptive evolution may be influenced by environmental factors, such as the degree of marginality of the new environment relative to the organism's potential range, and by genetic factors, including constraints that may have arisen during its past history. Experimental populations of bacteria were used to address these issues in the context of evolutionary adaptation to the thermal environment. Six replicate lines of Escherichia coli (20°C group), founded from a common ancestor, were propagated for 2000 generations at 20°C, a novel temperature that is very near the lower thermal limit at which it can maintain a stable population size in a daily serial transfer (100-fold dilution) regime. Four additional groups (32/20, 37/20, 42/20, and 32–42/20°C groups) of six lines, each with 2000 generation selection histories at different temperatures (32, 37, 42, and daily alternation of 32 and 42°C), were moved to the same 20°C environment and propagated in parallel to ascertain whether selection histories influence the adaptive response in this novel environment. Adaptation was measured by improvement in fitness relative to the common ancestor in direct competition experiments conducted at 20°C. All five groups showed improvement in relative fitness in this environment; the mean fitness of the 20°C group after 2000 generations increased by about 8%. Selection history had no discernible effect on the rate or final magnitude of the fitness responses of the four groups with different histories after 2000 generations. The correlated fitness responses of the 20°C group were measured across the entire thermal niche. There were significant tradeoffs in fitness at higher temperatures; for example, at 40°C the average fitness of the 20°C group was reduced by almost 20% relative to the common ancestor. We also observed a downward shift of 1–2°C in both the upper and lower thermal niche limits for the 20°C selected group. These observations are contrasted with previous observations of a markedly greater rate of adaptation to growth near the upper thermal limit (42°C) and a lack of trade-off in fitness at lower temperatures for lines adapted to that high temperature. The evolutionary implications of this asymmetry are discussed.     

ECOTYPIC VARIATION IN CYSTOCLONIUM PURPUREUM (RHODOPHYTA) SYNCHRONIZES LIFE HISTORY EVENTS IN DIFFERENT REGIONS1

Temperature and daylength responses were determined in culture for isolates of the red alga Cystoclonium purpureum (Hudson) Batters from Nova Scotia (NS, Canada), Helgoland (HE, Germany), and Roscoff (RO, France). Most isolates survived temperatures of –1.5°/–2° to 23°C, whereas 25°C was lethal. Only the RO-gametophytes died at 23°C. Optimal growth conditions were 10°–20°C in both long and short days for the NS isolates and 8°–15°C and 8°–18°C at daylengths of >12 h for the RO and HE isolates, respectively. Tetrasporophytes and gametophytes of the NS isolate reproduced at 10°–20°C in long and short days within 5 months. At lower temperatures reproduction was limited or slow. The European isolates formed tetrasporangia at 10°–20°C (HE) or 5°–l8°C(RO), spermatangia at 5°–15°C (HE) or 5°–20°C (RO), and carpospores at 5°–15°C(HE) or 10°–15°C (RO). Short days either blocked or delayed reproduction of the European isolates. The phenology of C. purpureum was studied at Helgoland and Roscoff, where similar seasonal patterns were observed. In early spring, growth was rapid and plants started to form reproductive structures. In summer, tetra-and carpospores were shed followed by degeneration of the upright axes while branched holdfasts persisted. New upright axes and juvenile plants were formed in autumn, but these remained small during the winter months. Published data indicate that the seasonal pattern at Nova Scotia is similar, although the onset of growth and reproduction is delayed until the end of spring. These observations correspond well with the results of the experiments. The life history of C. purpureum is regulated by temperature and daylength. In the eastern Atlantic, the limiting effect of short days confines growth and reproduction to spring and summer. In the western Atlantic, low winter temperatures alone bring about the same seasonal pattern. After plants have reproduced, uprights degenerate in spite of continuing favorable conditions.