Lactate is a critical "sensed" variable in caudal hindbrain monitoring of CNS metabolic stasis

Caudal hindbrain "sensing" of glucoprivation activates central neural mechanisms that enhance systemic glucose availability, but the critical molecular variable(s) linked to detection of local metabolic insufficiency remains unclear. Central neurons and glia are metabolically coupled via intercellular trafficking of the glycolytic product lactate as a substrate for neuronal oxidative respiration. Using complementary in vivo models for experimental manipulation of lactate availability within the caudal hindbrain, we investigated the hypothesis that lactate insufficiency may be monitored by local metabolically "sensitive" neurons as an indicator of central nervous system energy imbalance. The data show that caudal fourth ventricular (CV4) administration of the monocarboxylate transporter inhibitor alpha-cyano-4-hydroxycinnamate (4CIN) resulted in dose-dependent increases in blood glucose in euglycemic animals, whereas the degree and duration of hypoglycemia elicited by insulin administration were exacerbated by exogenous L-lactate delivery to the CV4. Immunocytochemical processing of the hindbrain for the inducible c-fos gene product Fos revealed that 4CIN enhanced Fos immunoreactivity in the dorsal vagal complex (DVC), e.g., the nucleus of the solitary tract and dorsal vagal motor nucleus, and adjacent area postrema, sites where cells characterized by unique sensitivity to diminished glucose and/or glycolytic intermediate/end product levels reside, and in the medial vestibular nucleus (MV), and that CV4 L-lactate infusion increased Fos labeling within the DVC and MV after insulin-induced hypoglycemia. Together, these results support the view that lactate is a critical monitored metabolic variable in caudal hindbrain detection of energy imbalance resulting from glucoprivation and that diminished uptake and/or oxidative catabolism of this fuel activates neural mechanisms that increase systemic glucose availability.     

Counteraction by naltrexone of stress-induced inhibition of TSH release: role of noradrenergic system

The purpose of the present study was to examine the effect of administering an opiate receptor antagonist, naltrexone (NALT) on the decline in pituitary thyrotropin (TSH) release induced by both acute and chronic stress, and to determine whether norepinephrine (NE) is involved in the mechanism by which opiate receptor blockade counteracts inhibition of TSH release during stress. Administration of NALT, a specific opiate receptor antagonist, significantly attenuated the decrease in plasma TSH observed after acute exposure to ether or restraint stress. The ability of NALT to prevent suppression of circulating TSH in ether-stressed rats was blocked by pharmacological suppression of NE activity induced by pretreatment with diethyldithiocarbamate (DDC) or phenoxybenzamine (PB), both NE antagonists. In chronically stressed rats, thrice daily injections of NALT attenuated the sustained decline in circulating TSH, and resulted in a significant elevation in plasma TSH when compared with stressed, saline-treated animals. Pretreatment with DDC prior to NALT injection abolished this stimulatory effect of NALT. These observations indicate that opiate/receptor interaction is prerequisite for the decrease in circulating TSH release during both acute and chronic stress, and support the hypothesis that endogenous opioid peptides (EOPs) mediate the suppressive effect of stress on TSH release. The finding that uninterrupted NE function is necessary for NALT's action on TSH release during stress suggests that the suppressive effect of stress on TSH and its reversal by opiate antagonists involves alterations in hypothalamic NE activity.     

Effects of ultra-wideband electromagnetic pulses on pre-neoplastic mammary epithelial cell proliferation

Electromagnetic ultra-wideband pulses (UWB) or nanopulses, are generated by a wide range of electronic devices used in communications and radar technology. However, the specific effects of nanopulse exposure on cell growth and function have not been extensively investigated. Here, studies have been conducted to determine the effects of prolonged exposure to non-ionizing, low to moderate intensity nanopulses on the growth of pre-neoplastic CL-S1 mammary epithelial cells in vitro. Cells were grown in culture and maintained in serum-free defined medium containing 10 ng/ml EGF and 10 microg/ml insulin as comitogens. Studies showed that 0.25-3.0 h exposure to nanopulses of 18 kV/m field intensity, 1 kHz repetition rate and 10 ns pulse width had no effect on CL-S1 cell growth or viability during the subsequent 72-h culture period. However, exposure to similar nanopulses for prolonged periods of time (4-6 h) resulted in a significant increase in cell proliferation, as compared to untreated controls. Additional studies showed that nanopulse exposure enhanced CL-S1 cell growth when cells were maintained in media containing only EGF, but had no effect on cells maintained in defined media that were mitogen-free or containing only insulin. Studies also showed that the growth-promoting effects of nanopulse exposure were associated with a relatively large increase in intracellular levels of phospho-MEK1 (active) and phospho-ERK1/2 (active) in these cells. These findings demonstrate that prolonged exposure to moderate levels of UWB enhanced EGF-dependent mitogenesis, and that this growth-promoting effect appears to be mediated by enhanced activation of the mitogen-activated protein kinase (MAPK) signalling pathway in pre-neoplastic CL-S1 mammary epithelial cells.     

Heat waves and their significance for a temperate benthic community: A near‐natural experimental approach

Climate change will not only shift environmental means but will also increase the intensity of extreme events, exerting additional stress on ecosystems. While field observations on the ecological consequences of heat waves are emerging, experimental evidence is rare, and lacking at the community level. Using a novel “near‐natural” outdoor mesocosms approach, this study tested whether marine summer heat waves have detrimental consequences for macrofauna of a temperate coastal community, and whether sequential heat waves provoke an increase or decrease of sensitivity to thermal stress. Three treatments were applied, defined and characterized through a statistical analysis of 15 years of temperature records from the experimental site: (1) no heat wave, (2) two heat waves in June and July followed by a summer heat wave in August and (3) the summer heat wave only. Overall, 50% of the species showed positive, negative or positive/negative responses in either abundance and/or biomass. We highlight four possible ways in which single species responded to either three subsequent heat waves or one summer heat wave: (1) absence of a response (tolerance, 50% of species), (2) negative accumulative effects by three subsequent heat waves (tellinid bivalve), (3) buffering by proceeding heat waves due to acclimation and/or shifts in phenology (spionid polychaete) and (4) an accumulative positive effect by subsequent heat waves (amphipod). The differential responses to single or sequential heat waves at the species level entailed shifts at the community level. Community‐level differences between single and triple heat waves were more pronounced than those between regimes with vs. without heat waves. Detritivory was reduced by the single heat wave while suspension feeding was less common in the triple heat wave regime. Critical extreme events occur already today and will occur more frequently in a changing climate, thus, leading to detrimental impacts on coastal marine systems.     

Diversity and distribution of genetic variation in gammarids: Comparing patterns between invasive and non‐invasive species

Biological invasions are worldwide phenomena that have reached alarming levels among aquatic species. There are key challenges to understand the factors behind invasion propensity of non‐native populations in invasion biology. Interestingly, interpretations cannot be expanded to higher taxonomic levels due to the fact that in the same genus, there are species that are notorious invaders and those that never spread outside their native range. Such variation in invasion propensity offers the possibility to explore, at fine‐scale taxonomic level, the existence of specific characteristics that might predict the variability in invasion success. In this work, we explored this possibility from a molecular perspective. The objective was to provide a better understanding of the genetic diversity distribution in the native range of species that exhibit contrasting invasive propensities. For this purpose, we used a total of 784 sequences of the cytochrome c oxidase subunit I of mitochondrial DNA (mtDNA‐COI) collected from seven Gammaroidea, a superfamily of Amphipoda that includes species that are both successful invaders (Gammarus tigrinus, Pontogammarus maeoticus, and Obesogammarus crassus) and strictly restricted to their native regions (Gammarus locusta, Gammarus salinus, Gammarus zaddachi, and Gammarus oceanicus). Despite that genetic diversity did not differ between invasive and non‐invasive species, we observed that populations of non‐invasive species showed a higher degree of genetic differentiation. Furthermore, we found that both geographic and evolutionary distances might explain genetic differentiation in both non‐native and native ranges. This suggests that the lack of population genetic structure may facilitate the distribution of mutations that despite arising in the native range may be beneficial in invasive ranges. The fact that evolutionary distances explained genetic differentiation more often than geographic distances points toward that deep lineage divergence holds an important role in the distribution of neutral genetic diversity.     

Effects of intracerebroventricular administration of the NPY-Y1 receptor antagonist, 1229U91, on hyperphagic and glycemic responses to acute and chronic intermediate insulin-induced hypoglycemia in female rats

Neuropeptide Y (NPY) Y1 receptors are implicated in CNS regulation of food intake, but their role in hypoglycemic hyperphagia remains unclear. The present studies utilized a pharmacological approach to investigate the hypothesis that NPY acts via Y1 receptor-dependent mechanisms to regulate feeding and blood glucose profiles during intermediate insulin-induced hypoglycemia. Groups of ovariectomized, estradiol benzoate-treated female rats were injected subcutaneously with one or four doses of neutral protamine Hagedorn insulin (NPH), on as many days, or with diluent alone. Before final treatments on day four, the animals were pretreated by intracerebroventricular (icv) delivery of the NPY Y1 receptor antagonist, 1229U91, or the vehicle, artificial cerebrospinal fluid (acsf). Food intake during acute hypoglycemia was significantly diminished between t_o and + 2 h in animals pretreated with the Y1 receptor antagonist versus vehicle. Administration of 1229U91 prior to the fourth of four NPH doses suppressed hypoglycemic hyperphagia over a relatively longer interval, e.g. 4 h, after t_o relative to the acute insulin group. Blood glucose levels after a single NPH injection were similar in acsf- and antagonist-pretreated rats at + 2, + 4, and + 6 h, but were lower at + 9 h in the latter group. Pretreatment with 1229U91 did not modify glucose profiles between + 2 and + 9 h after multiple dosing with NPH, but prevented recovery from hypoglycemia at + 12 h. The present results show that central NPY Y1 receptor antagonism inhibits hypoglycemic hyperphagia, and that this suppressive effect on feeding was of greater duration during recurring hypoglycemia. The data also show that Y1 receptor blockade decreases glycemic responses to both single and serial NPH dosing, albeit at different post-injection time points. The current studies support the view that NPY Y1 receptors function within central neural pathways that govern feeding and glycemic responses to intermediate-acting insulin, and that Y1 receptor-mediated stimulation of food intake may habituate in a positive manner to repetitive insulin-induced hypoglycemia. Further research is needed to evaluate the impact of chronic insulin-induced hypoglycemia on neuropeptide Y neurotransmission and Y1 receptor expression within regulatory circuitries that control food intake and glucostasis.     

High nitrate removal from synthetic wastewater with the mixed bacterial culture

The applicability of the mixed bacterial culture, originated from two-stage anaerobic-aerobic industrial yeasts production wastewater treatment plant for high rate denitrification processes was investigated. After acclimation to nitrate, the dominant strains were Pseudomonas and Paracoccus sp. Complete denitrification with low accumulation of nitrite-N (0.1 mg/l) was found in synthetic wastewater, obeying a zero-order reaction with respect to nitrate and a first-order reaction with respect to biomass concentration. Denitrification was then monitored in the continuous-flow stirred reactor at different hydraulic retention time, HRT (62-28 h) in order to achieve the optimal HRT. Nitrate was completely removed during following 45 days, at 25 degrees C with HRT, which we reduced from 62 to 28 h. Yet still, at 28 h HRT, high average specific denitrification rate of 142 mg NO3- -N/g VSS h was obtained.