Neighborhood Alcohol Environment: Differential Effects on Hazardous Drinking and Mental Health by Sex in Persons Living with HIV (PLWH).

Despite greater mental health co-morbidities and heavier alcohol use among PLWH, few studies have examined the role of the neighborhood alcohol environment on either alcohol consumption or mental health. Utilizing cross-sectional data from a cohort study in a southern U.S. metropolitan area, we examine the association between neighborhood alcohol environments on hazardous drinking and mental health among 358 in-care PLWH (84% African American, 31% female). Multilevel models were utilized to quantify associations between neighborhood alcohol exposure on hazardous drinking and effect modification by sex. Neighborhood alcohol density was associated with hazardous drinking among men but not women. Women living in alcohol dense neighborhoods were nearly two-fold likely to report depression compared to those in less dense neighborhoods, with no association between neighborhood alcohol density and depression among men. Neighborhood alcohol environments may be an important contextual factor to consider in reducing heavy alcohol consumption and improving mental health among PLWH.

Increasing temperature decreases the predatory effect of the intertidal shanny Lipophrys pholis on an amphipod prey.

Interactions between Lipophrys pholis and its amphipod prey Echinogammarus marinus were used to investigate the effect of changing water temperatures, comparing current and predicted mean summer temperatures. Contrary to expectations, predator attack rates significantly decreased with increasing temperature. Handling times were significantly longer at 19° C than at 17 and 15° C and the maximum feeding estimate was significantly lower at 19° C than at 17° C. Functional-response type changed from a destabilizing type II to the more stabilizing type III with a temperature increase to 19° C. This suggests that a temperature increase can mediate refuge for prey at low densities. Predatory pressure by teleosts may be dampened by a large increase in temperature (here from 15 to 19° C), but a short-term and smaller temperature increase (to 17° C) may increase destabilizing resource consumption due to high maximum feeding rates; this has implications for the stability of important intertidal ecosystems during warming events.

Influence of sex and habitat on the size and shape of anal and dorsal fins of the blackstripe topminnow Fundulus notatus.

The size and shape of the anal and dorsal fin in the blackstripe topminnow Fundulus notatus from lake and stream habitats across multiple ages and sexes were examined. Differences in the size and shape of anal and dorsal fins were sex-specific and not related to habitat differences. Males have longer and more pointed anal fins and longer, larger and more pointed dorsal fins than females. These sex differences occur predominantly in the older age class. The angle (i.e. pointedness) of the dorsal and anal fins is tightly correlated suggesting that fins follow a similar growth trajectory as individuals become sexually mature.

Extreme eutrophication and salinisation in the Coorong estuarine-lagoon ecosystem of Australia's largest river basin (Murray-Darling).

Estuaries in rainfall poor regions are highly susceptible to climatic and hydrological changes. The Coorong, a Ramsar-listed estuarine-coastal lagoon at the end of the Murray-Darling Basin (Australia), has experienced declining ecological health over recent decades. Twenty years of environmental data were analysed to assess patterns and drivers of water quality changes. Large areas of the Coorong are now persistently hyper-saline (salinity >80 psu) and hypereutrophic (total nitrogen, TN > 4 mg L-1, total phosphorus, TP > 0.2 mg L-1, chlorophyll a > 50 µg L-1) which coincided with reduced flushing due to diminished freshwater inflows and increasing evapo-concentration. Sediment quality also was related to flushing, with higher concentrations of organic carbon, TN, TP and sulfides as salinity increased. While total nutrient levels are very high, dissolved inorganic nutrients are generally low. Increased lagoonal flushing would be beneficial to reduce the hypersalinisation and hypereutrophication and improve ecosystem health.

Left ventricular dysfunction and intra-ventricular dyssynchrony in idiopathic pulmonary arterial hypertension.

BACKGROUND: Left ventricular (LV) filling pressures are normal in idiopathic pulmonary arterial hypertension (IPAH). However, direct and indirect interactions between the RV and LV can affect LV performance. We explored LV strain and LV intra-ventricular dyssynchrony in IPAH using feature tracking CMR (CMR-FT). METHODS: Seventy IPAH patients and 40 healthy volunteers were included. Patients underwent CMR and right heart catheterisation. The 4-chamber cine was used to calculate LV longitudinal strain (EllLV). LV circumferential (EccLV) and radial strain (ErrLV) were derived from a short axis cine. LV longitudinal, circumferential and radial intra-ventricular dyssynchrony indices were calculated. RESULTS: There were no differences between the IPAH and healthy volunteer group in LV ejection fraction (66.1% vs 64.2% p = 0.6672). EccLV (-29.1 vs -32.1 p = 0.0323) and EllLV (-16.6 vs -23.7 p < 0.0001) were lower in IPAH. In patients with more severe disease, there was greater impairment of ErrLV compared to mild disease (50.9 vs 87.5 P < 0.0001). LV synchrony was impaired in all directions in IPAH. ErrLV was associated with RV ejection fraction (r = 0.66), RV end-systolic volume index (r = -0.59), pulmonary vascular resistance (PVR)(r = 0.51) and stroke volume index (SVI)(r = 0.44). In a multivariate model with age, SVI and PVR, ErrLV (HR 0.970 p = 002) and radial dyssynchrony (HR 3.759 p < 0.0001) independently predicted survival. CONCLUSION: In IPAH, LV is dyssynchronous with impaired function. Measures of LV strain and intraventricular synchrony were associated with known markers of disease severity. These LV variables which are likely to be related to ventricular interaction, may add incremental value to known prognostic variables in IPAH.

Prevalence of non-tuberculous mycobacteria in HIV-infected patients admitted to hospital with pneumonia.

People living with the human immunodeficiency virus (PLWH) may be particularly vulnerable to the consequences of non-tuberculous mycobacteria (NTM) given their defective T cell-mediated immunity and high rates of structural lung disease. To determine the prevalence of NTM in PLWH hospitalized with pneumonia and to assess the potential predictors of NTM isolation. Secondary data analysis of a prospective cohort study (2007-2011) of early bronchoscopy in PLWH presenting with suspected pneumonia was undertaken. Subjects with any species of NTM, henceforth described as 'NTM of undetermined significance' (NTM-US), isolated from sputum or bronchoalveolar lavage fluid (BALF), were included in the analysis. Potential predictors were chosen a priori. Among 196 HIV-infected subjects hospitalized with pneumonia, 96 had respiratory samples positive for NTM-US, with 91% of all NTM-US isolated from sputum compared with BALF. The overall prevalence of NTM-US was 49% (96/196). More NTM subjects were smokers (P = 0.08), with a history of chronic obstructive pulmonary disease (P = 0.08). Among those with pathogenic NTM, 39% (34/88) would have met American Thoracic Society microbiologic criteria for NTM pulmonary disease (17% of total cohort). Respiratory cultures, predominantly sputum samples, were positive for NTM-US in 45% of HIV-infected subjects admitted to hospital for pneumonia. Further research is needed to characterize the prevalence of NTM in PLWH and help establish specific diagnostic criteria in this population. .

Individual neurons dissociated from rat suprachiasmatic nucleus express independently phased circadian firing rhythms.

Within the mammalian hypothalamus, the suprachiasmatic nucleus (SCN) contains a circadian clock for timing of diverse neuronal, endocrine, and behavioral rhythms. By culturing cells from neonatal rat SCN on fixed microelectrode arrays, we have been able to record spontaneous action potentials from individual SCN neurons for days or weeks, revealing prominent circadian rhythms in firing rate. Despite abundant functional synapses, circadian rhythms expressed by neurons in the same culture are not synchronized. After reversible blockade of neuronal firing lasting 2.5 days, circadian firing rhythms re-emerge with unaltered phases. These data suggest that the SCN contains a large population of autonomous, single-cell circadian oscillators, and that synapses formed in vitro are neither necessary for operation of these oscillators nor sufficient for synchronizing them.

Pneumocystis colonisation is common among hospitalised HIV infected patients with non-Pneumocystis pneumonia.

BACKGROUND: When Pneumocystis DNA is recovered from respiratory specimens of patients without Pneumocystis pneumonia (PCP), patients are said to be colonised with Pneumocystis, although the significance of this state is unknown. Understanding risk factors for and outcomes of colonisation may provide insights into the life cycle and transmission dynamics of Pneumocystis jirovecii. METHODS: We performed a cross sectional study of the prevalence and clinical predictors of Pneumocystis colonisation in 172 HIV infected, PCP negative inpatients undergoing diagnostic evaluation of 183 episodes of pneumonia at either the Medical Center of Louisiana at New Orleans between 2003 and 2005 or San Francisco General Hospital between 2000 and 2005. DNA was extracted from sputum and bronchoalveolar lavage specimens and amplified using a nested PCR assay at the mitochondrial large subunit (18S) ribosomal RNA locus. Colonisation was deemed present if Pneumocystis DNA was identified by both gel electrophoresis and direct DNA sequencing. RESULTS: 68% (117/172) of all patients were colonised with Pneumocystis. No strong associations with colonisation were identified for any demographic factors. Among clinical factors, having a CD4+ T cell count

Differential temperature acclimatization responses in the membrane phospholipids of Posthodiplostomum minimum and its second intermediate host, Lepomis macrochirus.

The effects of temperature change on phospholipid content in metacercariae of Posthodiplostomum minimum and their second intermediate hosts, Lepomis macrochirus, were examined to gauge similarities in the homeoviscous adaptation of host and parasite membranes to environmental thermal change. Heart, liver, and muscle tissues from individual L. macrochirus responded to environmental temperature declines with a decrease in the ratio of phosphatidylethanolamine (PE) to phosphatidylcholine (PC). Increases in membrane PE concentration increase membrane fluidity, maintaining fish membrane function as environmental temperature declines. However, the metacercariae of P. minimum exhibit changes in cholesterol levels, total lipid levels, and lipid composition (PE/PC) that contrast the normal changes for homeoviscous membrane adaptation exhibited by their fish intermediate hosts. The parasites seem to rely on their hosts for homeoviscous adaptation within normal developmental temperature ranges, pooling both cholesterol and PE as energetic stores for development and ontological transitions signaled by elevated temperatures.

Ecological significance of compatible solute accumulation by micro-organisms: from single cells to global climate.

The osmoadaptation of most micro-organisms involves the accumulation of K(+) ions and one or more of a restricted range of low molecular mass organic solutes, collectively termed 'compatible solutes'. These solutes are accumulated to high intracellular concentrations, in order to balance the osmotic pressure of the growth medium and maintain cell turgor pressure, which provides the driving force for cell extension growth. In this review, I discuss the alternative roles which compatible solutes may also play as intracellular reserves of carbon, energy and nitrogen, and as more general stress metabolites involved in protection of cells against other environmental stresses including heat, desiccation and freezing. Thus, the evolutionary selection for the accumulation of a specific compatible solute may not depend solely upon its function during osmoadaptation, but also upon the secondary benefits its accumulation provides, such as increased tolerance of other environmental stresses prevalent in the organism's niche or even anti-herbivory or dispersal functions in the case of dimethylsulfoniopropionate (DMSP). In the second part of the review, I discuss the ecological consequences of the release of compatible solutes to the environment, where they can provide sources of compatible solutes, carbon, nitrogen and energy for other members of the micro-flora. Finally, at the global scale the metabolism of specific compatible solutes (betaines and DMSP) in brackish water, marine and hypersaline environments may influence global climate, due to the production of the trace gases, methane and dimethylsulfide (DMS) and in the case of DMS, also couple the marine and terrestrial sulfur cycles.

Intravascular ultrasound study of angiographically mildly diseased coronary arteries.

OBJECTIVES: We hypothesized that intravascular ultrasound may identify significant coronary artery narrowing in the mildly diseased coronary artery of patients with insignificant or one- or two-vessel coronary artery disease. BACKGROUND: Necropsy studies have revealed that coronary angiography may underestimate stenosis severity in vessels that appear mildly diseased. Intravascular ultrasound has been shown to detect atherosclerotic changes in angiographically normal coronary arteries and to correlate better with histologic findings. METHODS: In 20 patients, we performed intravascular ultrasound imaging (3.5F catheter, 30-MHz transducer) in 37 coronary arteries that were considered mildly diseased (<50% diameter narrowing) by qualitative angiography. The angiographic diagnosis was no significant coronary artery disease in eight patients, one-vessel disease in seven and two-vessel disease in five. Each vessel, except for the left main coronary artery, was divided into proximal, mid and distal segments. Percent area narrowing and minimal lumen diameter were subsequently quantified by both ultrasound and quantitative angiography. RESULTS: Mean maximal arterial area narrowing by ultrasound in the 67 segments studied was 36 +/- 20% (range 0% to 80.2%) and 19 +/- 23% (range 0% to 82%) by quantitative angiography of these same segments (p < 0.001, paired t test). Mean minimal lumen diameter of the segment was 3.3 +/- 0.9 mm by ultrasound and 2.7 +/- 0.8 mm by quantitative angiography. In 10 patients there were 19 angiographically mildly diseased segments where the percent arterial area narrowing by ultrasound was > or = 50%. Intravascular ultrasound revealed that the more proximal (reference) segment had > 25% intimal thickening in 12 of the 19 underestimated segments. In six stenosed segments (32%), total vessel area increased compared with that of the adjacent proximal vessel segment because of compensatory dilation. CONCLUSIONS: Intravascular ultrasound identifies potentially significant coronary artery disease in vessels that appear to be only mildly diseased by angiography.

Lithium lengthens circadian period in a diurnal primate, Saimiri sciureus.

Lithium lengthens the period of free-running circadian rhythms in a variety of species, but this effect has not been demonstrated unequivocally in primates. Because of the possible link between lithium's action on the circadian clock and its therapeutic action in human mood disorders, we tested the ability of lithium to lengthen circadian period in a diurnal primate with circadian properties similar to those of humans. Lithium carbonate was administered in food pellets to 8 adult male squirrel monkeys (Saimiri sciureus) for at least 27 consecutive days. Serum lithium levels on the last day of lithium administration ranged from 0.76 to 2.02 mEq/liter, comparable to the therapeutic range for treatment of bipolar disorder in humans (0.6-1.2 mEq/liter). Circadian periods of perch-hopping activity were longer during lithium treatment than during baseline in 7 of the 8 monkeys (changes of -0.08 to +1.41 hr, mean +0.55 hr, p = 0.01), and returned toward baseline values when lithium was discontinued. In most cases, the period change was evident within a few days after beginning full lithium dose, and was not accompanied by changes in level or pattern of activity, nor in amplitude of the circadian rhythm. Food consumption and body weight were reduced during lithium treatment, and rebounded on return to lithium-free diet. Period change was related to lithium dose (p less than 0.05), but did not correlate with food consumption, body weight, or baseline circadian period. These results, by establishing that lithium lengthens circadian period in primates, suggest that studying the cellular mechanisms of this circadian effect may be relevant to understanding lithium's therapeutic effect on mood in humans.

Rapid rise and subsequent decline in prostate cancer incidence rates for New Mexico, 1989-1993.

Beginning in the late 1980s, a large increase in incidence rates for prostate cancer occurred in association with increased prostate-specific antigen (PSA) screening. In New Mexico, the increased screening was associated with earlier detection of cancers and decreased prostate cancer mortality, suggesting that PSA screening may be effective. PSA screening has become a controversial topic of public debate, and anecdotal reports from physicians indicated that prostate cancer screening practice patterns were changing in New Mexico. To assess whether PSA-associated trends in prostate cancer incidence were continuing, we examined incidence rates from 1989 to 1993 among men in New Mexico. From 1989 to 1992, age-adjusted rates increased substantially for non-Hispanic whites (77%), Hispanics (50%), and American Indians (27%). Although rates increased for all stages combined, incidence rates decreased for distant-stage disease, especially for non-Hispanic whites, indicating a continuing trend toward earlier detection. In 1993, incidence rates unexpectedly decreased from 203 to 158/100,000 in non-Hispanic whites, largely as a result of changes in rates in men over age 65 years. Although incidence rates decreased, the trend toward earlier detection was maintained for non-Hispanic whites. In contrast, among Hispanic and American Indians, rates did not change substantially between 1992 and 1993. Because the epidemic in prostate cancer was associated with increased PSA screening, it is likely that the trends for non-Hispanic whites are also related to PSA screening. We suggest that the decrease in rates and the continued stage shift are consistent with repeated screening of men in the population at risk.

An electrophysiological study of the action of N-methyl-D-aspartate on excitatory synaptic transmission in the optic tectum of the frog in vitro.

Excitatory synaptic field potentials, induced by stimulating optic nerve fibers, were recorded from in vitro preparations of the optic tectum of the frog. Bath-applied N-methyl-D-aspartate (NMDA), glutamate or quisqualate elicited transient enhancement in these field potentials, followed by a sustained depression reversible on washout. Responses to glutamate or quisqualate and the amplitude of control synaptic potentials, were not affected by the NMDA receptor antagonists aminophosphonovalerate (APV), 3(2-carboxypiperazin-4-yl)propyl-1-phosphonate (CPP), ketamine, magnesium ions or dizocipiline (MK 801) which, on the other hand, blocked the effects of NMDA. The antagonist dinitroquinoxaline-2,3-dione (DNQX), which is preferential for non-NMDA receptors, blocked the action of glutamate and synaptic transmission. In the presence of strychnine, glycine reversed the block of NMDA-mediated responses caused by magnesium. It is suggested that in the optic tectum of the frog, glutamate is the excitatory transmitter of at least one class of optic nerve fibers and that it acts through non-NMDA receptors. Although this area of the brain contains a well-developed NMDA receptor system, its function in physiological synaptic transmission remains to be elucidated.

The use of measured genotype information in the analysis of quantitative phenotypes in man. II. The role of the apolipoprotein E polymorphism in determining levels, variability, and covariability of cholesterol, betalipoprotein, and triglycerides in a sample of unrelated individuals.

Recent advances in molecular biology provide measures of genotypes at loci involved in lipid metabolism. Genotypes for apolipoprotein E (apo E) and quantitative levels of total plasma cholesterol, betalipoprotein, and triglycerides were measured in a sample of 223 unrelated individuals from Nancy, France. The frequencies of the epsilon 2, epsilon 3, and epsilon 4 alleles are 0.13, 0.74, and 0.13, respectively, in this sample. Significant differences among apo E genotypes were detected for these lipoprotein phenotypes. The average effect of the epsilon 2 allele was to reduce total plasma cholesterol and betalipoprotein levels by 0.52 mmol/L and 0.98, respectively, while the epsilon 4 allele raised these levels by 0.26 mmol/L and 0.61, respectively. Apo E genotype specific correlations suggest that this locus also has an effect on the coordinated metabolism between cholesterol and triglycerides. We infer that approximately 17% of the genetic variability in total plasma cholesterol may be attributable to this apo E polymorphism. No other single locus has been identified with such a large contribution to cardiovascular disease risk factors in the general population.

Do physicians judge a study by its cover? An investigation of journal attribution bias.

The effect of a journal's prestige on readers' impressions of an article is unknown. Two hypotheses were tested: first, that attribution of a study to a "high" prestige journal would be associated with improved impressions and attribution to a "low" prestige journal would be associated with diminished impressions; and second, that formal training in epidemiology and biostatistics would mitigate the effects of this journal attribution bias. The study was designed as a trial among a random sample of 264 internists. Participants were asked to read an article and an abstract from either the Southern Medical Journal (SMJ) or the New England Journal of Medicine (NEJM). Questionnaires were constructed that either attributed the article or abstract to its source or presented it as unattributed. After each article or abstract, respondents were asked to rate the quality of the study, the appropriateness of the methodology employed, the significance of the findings, and its likely effects on their practice. A 20-point impression score was created based on responses to these statements. The effect of attribution to a specific journal and formal epidemiology training on impression scores were assessed using linear regression. Of the 399 eligible participants, 264 questionnaires were returned (response rate 66%). Differences in impression scores associated with attribution of an article or abstract to the NEJM were.71 [95% C.I. (-.44-1.87)] and.50 [95% C.I. (-.87-1.87)] respectively; differences in impression scores associated with attribution of an article or abstract to the SMJ were -.12 [95% C.I. (-1.53-1.30)] and -.95 [95% C.I. (-2.41-.52)]. A stratified analysis demonstrated that epidemiology training did not meaningfully alter the effect of journal attribution on participants' impression scores. If journal attribution bias exists, it is likely to exert small and clinically insignificant effects when physicians read articles carefully. Formal training in epidemiology and biostatistics does not appear to alter these results.

L-type Ca2+ channel and Na+/Ca2+ exchange inhibitors reduce Ca2+ accumulation in reperfused skeletal muscle.

It is known that extracellular Ca2+ accumulates within skeletal muscle after prolonged periods of ischemia and reperfusion. In this study, we determined whether the L-type Ca2+ channel and the Na+/Ca2+ exchanger mediated Ca2+ influx and whether Ca2+ accumulation limited the metabolic and contractile recovery of reperfused skeletal muscle. Contracting rat hindlimbs (1-Hz twitch) exposed to 40 min of no-flow ischemia were reperfused with diltiazem (500 microM) or 3,4-dichlorobenzamil (300 microM) to block the Na+/Ca2+ exchanger and/or the L-type Ca2+ channel. High inhibitor concentrations were used to counter the binding of diltiazem and 3,4-dichlorobenzamil to albumin and red blood cells. Muscle Ca2+ accumulation, contractile function, and energy metabolism were assessed by measuring intracellular Ca2+ concentration ([Ca2+]i), Ca2+ influx, twitch tension, and high-energy phosphagens [ATP, total adenine nucleotides (TAN) and phosphocreatine (PCr)]. Compared with control reperfusion, diltiazem and 3,4-dichlorobenzamil reduced Ca2+ influx and attenuated the rise in [Ca2+]i in the fast-oxidative glycolytic plantaris (Pl) and the fast-glycolytic white gastrocnemius (WG). The inhibitor-induced decrease in Ca2+ influx was 1.5- to 2-fold greater with 3,4-dichlorobenzamil than with diltiazem. Coinciding with the reduced Ca2+ accumulation, diltiazem and 3,4-dichlorobenzamil enhanced the resynthesis of ATP (Pl and WG), PCr (Pl and WG), and TAN (Pl) compared with control reperfusion. 3,4-Dichlorobenzamil also augmented twitch-tension recovery. We conclude that Ca2+ accumulation during reperfusion 1) arises from L-type Ca2+ channel and Na+/Ca2+ exchange activation; and 2) impairs the metabolic and contractile recovery of skeletal muscle.

NaHCO(3) and KHCO(3) ingestion rapidly increases renal electrolyte excretion in humans.

This paper describes and quantifies acute responses of the kidneys in correcting plasma volume, acid-base, and ion disturbances resulting from NaHCO(3) and KHCO(3) ingestion. Renal excretion of ions and water was studied in five men after ingestion of 3.57 mmol/kg body mass of sodium bicarbonate (NaHCO(3)) and, in a separate trial, potassium bicarbonate (KHCO(3)). Subjects had a Foley catheter inserted into the bladder and indwelling catheters placed into an antecubital vein and a brachial artery. Blood and urine were sampled in the 30-min period before, the 60-min period during, and the 210-min period after ingestion of the solutions. NaHCO(3) ingestion resulted in a rapid, transient diuresis and natriuresis. Cumulative urine output was 44 +/- 11% of ingested volume, resulting in a 555 +/- 119 ml increase in total body water at the end of the experiment. The cumulative increase (above basal levels) in renal Na(+) excretion accounted for 24 +/- 2% of ingested Na(+). In the KHCO(3) trial, arterial plasma K(+) concentration rapidly increased from 4.25 +/- 0.10 to a peak of 7.17 +/- 0.13 meq/l 140 min after the beginning of ingestion. This increase resulted in a pronounced, transient diuresis, with cumulative urine output at 270 min similar to the volume ingested, natriuresis, and a pronounced kaliuresis that was maintained until the end of the experiment. Cumulative (above basal) renal K(+) excretion at 270 min accounted for 26 +/- 5% of ingested K(+). The kidneys were important in mediating rapid corrections of substantial portions of the fluid and electrolyte disturbances resulting from ingestion of KHCO(3) and NaHCO(3) solutions.

Osmotically induced intracellular trehalose, but not glycine betaine accumulation promotes desiccation tolerance in Escherichia coli.

Trehalose considerably increased the tolerance of Escherichia coli to air drying, whether added as an excipient prior to drying or accumulated as a compatible solute in response to osmotic stress. The protective effect of exogenously added trehalose was concentration dependent, up to a threshold value of 350 mM. However, trehalose alone cannot explain the intrinsically greater desiccation tolerance of stationary compared to exponential phase E. coli cells, although their tolerance was also enhanced by exogenous or endogenously accumulated trehalose. In contrast, glycine betaine whether added as an excipient or accumulated intracellularly had no influence on desiccation tolerance. These data demonstrate that the protection provided by compatible solutes to cells subjected to desiccation differs from that during osmotic stress, due to the much greater reduction in available cell water. The protective effects of trehalose during desiccation appear to be due to its stabilising influence on membrane structure, its chemically inert nature and the propensity of trehalose solutions to form glasses upon drying, properties which are not shared by glycine betaine.

Gap junctions couple astrocytes but not neurons in dissociated cultures of rat suprachiasmatic nucleus.

Individual neurons dissociated from rat suprachiasmatic nucleus can express independently phased circadian firing rhythms in culture. The phases of these rhythms are unperturbed by reversible blockade of neuronal firing lasting 2.5 days, indicating that multiple circadian clocks continue to operate in the absence of conventional synaptic transmission. The possibility remains, however, that these circadian rhythms might depend on some other form of intercellular communication. In the present study, a potential role for gap junctional coupling in SCN cultures was evaluated by introduction of the tracer molecule Neurobiotin into both neurons (n = 98) and astrocytes (n = 10), as well as by immunolabeling for specific connexins, the molecular components of gap junctions. Astrocytes were extensively coupled to each other by connexin 43-positive gap junctions, but no evidence was found for coupling of neurons to each other or to astrocytes. These data support the hypothesis that neurons expressing independently phased circadian rhythms in SCN cultures ('clock cells') are autonomous, single cell circadian oscillators, but do not exclude a role for glia in synchronizing neuronal clock cells in vivo.