Glutamate and N-Acetylaspartate Alterations Observed in Early Phase Psychosis: A Systematic Review of Proton Magnetic Resonance Spectroscopy Studies.

Glutamate and N-acetylaspartate have been investigated in the neuropathology of chronic schizophrenia, with fewer studies focusing on early phase psychosis. Additionally, there has been little review and synthesis of the literature focused on multiple brain regions. This systematic review aims to provide a clear report of the current state of research on glutamate and n-acetylaspartate concentrations in early phase psychosis (defined as the first five years following psychosis onset) in multiple brain regions. Existing literature was searched systematically to compile reports of glutamate/glutamate+glutamine (Glx) and n-acetylaspartate absolute levels and ratios in both male and female individuals with early phase psychosis. Reports on glutamate/Glx concentrations in the medial prefrontal region and thalamus were varied, but the majority of reports suggested no alterations in EPP. No studies reported glutamate alterations in the hippocampus or cerebellum. There was no evidence for n-acetylaspartate alterations in the caudate, basal ganglia, and medial prefrontal cortex, and minimal evidence for NAA reductions in the thalamus, anterior cingulate cortex, and hippocampus. Future research should focus on the regions that are less commonly reported, and should aim to explore possible confounds, such as medication status and substance use.

High purity single photons entangled with an atomic qubit.

Trapped atomic ions are an ideal candidate for quantum network nodes, with long-lived identical qubit memories that can be locally entangled through their Coulomb interaction and remotely entangled through photonic channels. The integrity of this photonic interface is generally reliant on the purity of single photons produced by the quantum memory. Here, we demonstrate a single-photon source for quantum networking based on a trapped 138Ba+ ion with a single photon purity of g (2)(0)=(8.1±2.3)×10-5 without background subtraction. We further optimize the tradeoff between the photonic generation rate and the memory-photon entanglement fidelity for the case of polarization photonic qubits by tailoring the spatial mode of the collected light.

Multispecies Trapped-Ion Node for Quantum Networking.

Trapped atomic ions are a leading platform for quantum information networks, with long-lived identical qubit memories that can be locally entangled through their Coulomb interaction and remotely entangled through photonic channels. However, performing both local and remote operations in a single node of a quantum network requires extreme isolation between spectator qubit memories and qubits associated with the photonic interface. We achieve this isolation by cotrapping ^{171}Yb^{+} and ^{138}Ba^{+} qubits. We further demonstrate the ingredients of a scalable ion trap network node with two distinct experiments that consist of entangling the mixed species qubit pair through their collective motion and entangling a ^{138}Ba^{+} qubit with an emitted visible photon.

Acute high-caffeine exposure increases autophagic flux and reduces protein synthesis in C2C12 skeletal myotubes.

Caffeine is a highly catabolic dietary stimulant. High caffeine concentrations (1-10 mM) have previously been shown to inhibit protein synthesis and increase protein degradation in various mammalian cell lines. The purpose of this study was to examine the effect of short-term caffeine exposure on cell signaling pathways that regulate protein metabolism in mammalian skeletal muscle cells. Fully differentiated C2C12 skeletal myotubes either received vehicle (DMSO) or 5 mM caffeine for 6 h. Our analysis revealed that caffeine promoted a 40% increase in autolysosome formation and a 25% increase in autophagic flux. In contrast, caffeine treatment did not significantly increase the expression of the skeletal muscle specific ubiquitin ligases MAFbx and MuRF1 or 20S proteasome activity. Caffeine treatment significantly reduced mTORC1 signaling, total protein synthesis and myotube diameter in a CaMKKß/AMPK-dependent manner. Further, caffeine promoted a CaMKII-dependent increase in myostatin mRNA expression that did not significantly contribute to the caffeine-dependent reduction in protein synthesis. Our results indicate that short-term caffeine exposure significantly reduced skeletal myotube diameter by increasing autophagic flux and promoting a CaMKKß/AMPK-dependent reduction in protein synthesis.

The relevance of neuropsychiatric symptoms and cognitive problems in new-onset epilepsy - Current knowledge and understanding.

Neurobehavioral and cognition problems are highly prevalent in epilepsy, but most research studies to date have not adequately addressed the precise nature of the relationship between these comorbidities and seizures. To address this complex issue and to facilitate collaborative, innovative research in the rising field of neurobehavioral comorbidities and cognition disturbances in new-onset epilepsy, international epilepsy experts met at the 3rd Halifax International Epilepsy Conference & Retreat at White Point, South Shore, Nova Scotia, Canada from September 18 to 20, 2014. This Conference Proceedings provides a summary of the conference proceedings. Specifically, the following topics are discussed: (i) role of comorbidities in epilepsy diagnosis and management, (ii) role of antiepileptic medications in understanding the relationship between epilepsy and neurobehavioral and cognition problems, and (iii) animal data and diagnostic approaches. Evidence to date, though limited, strongly suggests a bidirectional relationship between epilepsy and cognitive and psychiatric comorbidities. In fact, it is likely that seizures and neurobehavioral problems represent different symptoms of a common etiology or network-wide disturbance. As a reflection of this shared network, psychiatric comorbidities and/or cognition problems may actually precede the seizure occurrence and likely get often missed if not screened.

Cannabis and the maturing brain: Role in psychosis development.

A common viewpoint has proliferated that cannabis use is mostly harmless. Some argue that by not supporting its use, we are missing a great therapeutic opportunity. The general public view on cannabis may partially be a result of poor knowledge translation. In fact, the "war on drugs" approach has not allowed for basic education on the varied effects of cannabis on the brain, especially at highly critical phases of brain development such as adolescence.

Candidate for laser cooling of a negative ion: observations of bound-bound transitions in La(-).

Despite the tremendous advances in laser cooling of neutral atoms and positive ions, no negatively charged ion has been directly laser cooled. The negative ion of lanthanum, La(-), has been proposed as the best candidate for laser cooling of any atomic anion [ and , Phys. Rev. A 81, 032503 (2010)]. Tunable infrared laser photodetachment spectroscopy is used to measure the bound-state structure of La(-), revealing a spectrum of unprecedented richness with multiple bound-bound electric dipole transitions. The potential laser-cooling transition ((3)F(2)(e)→(3)D(1)(o)) is identified and its excitation energy is measured. The results confirm that La^{-} is a very promising negative ion for laser-cooling applications.

AIT-082 and methylprednisolone singly, but not in combination, enhance functional and histological improvement after acute spinal cord injury in rats.

Extracellular non-adenine based purines are neuroprotective. Preliminary studies indicate that administration of the synthetic purine 4-[[3-(1,6 dihydro-6-oxo-9-purine-9-yl)-1-oxypropyl] amino] benzoic acid (AIT-082, leteprinim potassium) to rats immediately after acute spinal cord injury (SCI), improves functional outcome. The effects of potential new agents are often compared to methylprednisolone (MPSS). We evaluated the effects of AIT-082 and MPSS, separately and in combination, on the functional and morphological outcome of acute SCI in adult rats. After standardized T11-12 spinal cord compression rats were given intraperitoneally one of the following: vehicle (saline); MPSS (30 mg/kg or 60 mg/kg body weight, first dose 15 min after crush); AIT-082 (60 mg/kg body weight daily, first dose 15 min after crush); or AIT-082 plus MPSS. After 1, 3, or 21 days, the rats were perfused for histological analysis. AIT-082 administrations significantly reduced locomotor impairment from 121 days post-operatively. At 1 and 3 days post injury, AIT-082-treatment reduced tissue swelling, tissue loss and astrogliosis at the injured cords but did not alter the extent of hemorrhage and the number of macrophages and/or microglia. MPSS reduced hemorrhage and the number of macrophages and/or microglia, but did not alter astrogliosis. At 21 days, either AIT-082 or MPSS administration improved function and morphology similarly (less tissue loss and astrogliosis). In contrast, administration of AIT-082 and MPSS together abolished the beneficial effects observed when either drug was given individually. These results suggest that MPSS and AIT-082 may exert their beneficial effects through different and potentially antagonistic pathways.

The physiology of hibernation in common map turtles (Graptemys geographica).

Map turtles from Wisconsin were submerged at 3 degrees C in normoxic and anoxic water to simulate extremes of potential respiratory microenvironments while hibernating under ice. In predive turtles, and in turtles submerged for up to 150 days, plasma PO2, PCO2) pH, [Cl-], [Na+], [K+], total Mg, total Ca, lactate, glucose, and osmolality were measured; hematocrit and body mass were determined, and plasma [HCO3-] was calculated. Turtles in anoxic water developed a severe metabolic acidosis, accumulating lactate from a predive value of 1.7 to 116 mmol/l at 50 days, associated with a fall in pH from 8.010 to 7.128. To buffer lactate increase, total calcium and magnesium rose from 3.5 and 2.0 to 25.7 and 7.6 mmol/l, respectively. Plasma [HCO3-] was titrated from 44.7 to 4.3 mmol/l in turtles in anoxic water. Turtles in normoxic water had only minor disturbances of their acid-base status and ionic statuses; there was a marked increase in hematocrit from 31.1 to 51.9%. This study and field studies suggest that map turtles have an obligatory requirement for a hibernaculum that provides well-oxygenated water (e.g. rivers and large lakes rather than small ponds and swamps) and that this requirement is a major factor in determining their microdistribution.

Gut blood flow in fish during exercise and severe hypercapnia.

This paper reviews the effects of exercise and hypercapnia on blood flow to the splanchnic circulation. Brief struggling behaviours are known to decrease blood flow to the gut (GBF). Likewise, prolonged swimming in unfed fish has been shown to reduce GBF in proportion to the increased oxygen uptake. Therefore, the normal postprandial increase in GBF theoretically should be impaired whenever fish are active. However, indirect evidence suggests that GBF is spared to some degree when fed fish swim continuously but at a cost (10-15%) to their critical swimming speed. Severe respiratory acidosis can be created by the new intensive aquaculture settings that use oxygen injection into re-circulated water. The only study so far to examine the effects of severe hypercapnia on GBF and its regulation showed that routine GBF and alpha-adrenergic control of GBF remained normal in unfed white sturgeon (Acipenser transmontanus). However, severe hypercapnia produced a hyperactive state and increased sensitivity of GBF to struggling. As a result, routine GBF was maintained for a short period of time. Thus, environmental changes such as severe hypercapnia can indirectly impact GBF through altered struggling behaviour, but the implications of the overall reduction in GBF to food assimilation have yet to be established.

The physiology of hibernation among painted turtles: the midland painted turtle (Chrysemys picta marginata).

Midland painted turtles from Michigan were submerged at 3 degrees C in normoxic and anoxic water. In predive, and in turtles submerged for up to 150 days, plasma PO2, PCO2, pH, [Cl-], [Na+], [K+], total Mg, total Ca, lactate, glucose, and osmolality were measured; hematocrit and mass were determined, and plasma [HCO3-] was calculated. Anoxic turtles developed a severe metabolic acidosis, accumulating lactate from a predive value of 4.4 mmol/L to a 150-day value of 185 mmol/L, associated with a fall in pH from 7.983 to 7.189. To buffer lactate increase, total calcium and magnesium rose from 3.7 and 2.6 to 58.9 and 11.8 mmol/L, respectively. Plasma [HCO3-] was titrated from 39.2 to 4.8 mmol/L in anoxic turtles. Turtles in normoxic water had only minor disturbances of their acid-base and ionic statuses, associated with a much smaller increase of lactate to 23 mmol/L; there was a marked increase in hematocrit from 29.1% to 42.1%. We suggest that it is ecologic, rather than phylogenetic, relationships that determine the responses of painted turtles to prolonged submergence associated with hibernation.

Providing continuity of care for patients transferred from ICU.

Patients requiring treatments previously only undertaken in critical care units are now being nursed in other ward areas. A study was carried out to determine the difficulties that are faced by ward nurses caring for this highly dependent patient group. Staff and patient stress were problems experienced and there was a call for closer liaison between ICU and ward staff.

Cardiorespiratory responses of white sturgeon to environmental hypercapnia.

Cardioventilatory variables and blood-gas, acid-base status were measured in cannulated white sturgeon (Acipenser transmontanus) maintained at 19 degrees C during normocapnic and hypercapnic (Pw(CO(2)) approximately 20 Torr) water conditions and after the injection of adrenergic analogs. Hypercapnia produced significant increases in arterial PCO(2), ventilatory frequency, and plasma concentration of cortisol and epinephrine, and it produced significant decreases in arterial pH and plasma concentration of glucose but no change in arterial PO(2), hematocrit, and concentration of lactate or norepinephrine. Hypercapnia significantly increased cardiac output (Q) by 22%, mean arterial pressure (MAP) by 8%, and heart rate (HR) by 8%. However, gut blood flow (GBF) remained constant. In normocapnic fish, phenylephrine significantly constricted the splanchnic circulation, whereas isoproterenol significantly increased Q and produced a systemic vasodilation. During hypercapnia, propranolol significantly decreased Q, GBF, MAP, and HR, whereas phentolamine significantly decreased MAP and increased GBF. These changes suggest that cardiovascular function in the white sturgeon is sensitive to both alpha- and beta-adrenergic modulation. We found microspheres to be unreliable in predicting GBF on the basis of our comparisons with simultaneous direct measurements of GBF. Overall, our results demonstrate that environmental hypercapnia (e.g., as is experienced in high-intensity culture situations) elicits stress responses in white sturgeon that significantly elevate steady-state cardiovascular and ventilatory activity levels.

The effect of coal combustion flue gas components on low-level chlorine speciation using EPA method 26A.

U.S. Environmental Protection Agency (EPA) Method 26A is the recommended procedure for capturing and speciating halogen (X2) and hydrogen halide (HX) stack emissions from combustion sources. Previous evaluation studies of Method 26A have focused primarily on hydrogen chloride (HCl) speciation. Capture efficiency, bias, and the potential interference of Cl2 at high levels (> 20 ppm [microgram/m3]) and NH4Cl in the flue gas stream have been investigated. It has been suggested that precise Cl2 measurement and accuracy in quantifying HX or X2 using Method 26A are difficult to achieve at Cl2 concentrations < 5 ppm; however, no performance data exist to support this. Coal contains low levels of Cl, in the range of 5-2000 ppmw, which results in the presence of HCl and Cl2 in the products of combustion. HCl is the predominant Cl compound formed in the high-temperature combustion process, and it persists in the gas as the products of combustion cool. Concentrations of Cl2 in coal combustion flue gas at stack temperatures typically do not exceed 5 ppm. For this research, bench-scale experiments using simulated combustion flue gas were designed to validate the ability of Method 26A to speciate low levels of Cl2 accurately. This paper presents the results of the bench-scale tests. The effect of various flue gas components is discussed. The results indicate that SO2 is the only component in coal combustion flue gas that has an appreciable effect on Cl2 distribution in Method 26A impingers, and that Method 26A cannot accurately speciate HCl and Cl2 in coal combustion flue gas without modification.

Lactic acid buffering by bone and shell in anoxic softshell and painted turtles.

We tested two hypotheses: first, that the inferior anoxia tolerance of the softshell turtle, Apalone spinifera, compared to the western painted turtle, Chrysemys picta bellii, is related to its less mineralized shell, and second, that turtle bone, like its shell, stores lactate during prolonged anoxia. Lactate concentrations of blood, hindlimb bone, and shell were measured on normoxic Apalone and Chrysemys and after anoxic submergence at 10 degrees C for 2 and 9 d, respectively. Blood and shell concentrations of Ca(2+), Mg(2+), Na(+), K(+), and inorganic phosphate (P(i); for shell only) were also measured. Because a preliminary study indicated lactate distribution in Chrysemys throughout its skeleton during anoxia at 20 degrees C, we used hindlimb bones as representative skeletal samples. Apalone shell, though a similar percentage of body mass as Chrysemys shell, had higher water content (76.9% vs. 27.9%) and only 20%-25% as much Ca(2+), Mg(2+), CO(2), and P(i). When incubated at constant pH of 6.0 or 6.5, Apalone shell powder released only 25% as much buffer per gram wet weight as Chrysemys shell. In addition, plasma [Ca(2+)] and [Mg(2+)] increased less in Apalone during anoxia at an equivalent plasma lactate concentration. Lactate concentrations increased in the shell and skeletal bone in both species. Despite less mineralization, Apalone shell took up lactate comparably to Chrysemys. In conclusion, a weaker compensatory response to lactic acidosis in Apalone correlates with lower shell mineralization and buffer release and may partially account for the poorer anoxia tolerance of this species.

Bone and shell contribution to lactic acid buffering of submerged turtles Chrysemys picta bellii at 3 degrees C.

To evaluate shell and bone buffering of lactic acid during acidosis at 3 degrees C, turtles were submerged in anoxic or aerated water and tested at intervals for blood acid-base status and plasma ions and for bone and shell percent water, percent ash, and concentrations of lactate, Ca(2+), Mg(2+), P(i), Na(+), and K(+). After 125 days, plasma lactate concentration rose from 1.6 +/- 0.2 mM (mean +/- SE) to 155.2 +/- 10.8 mM in the anoxic group but only to 25.2 +/- 6.4 mM in the aerated group. The acid-base state of the normoxic animals was stable after 25 days of submergence. Plasma calcium concentration (¿Ca(2+)) rose during anoxia from 3.2 +/- 0.2 to 46.0 +/- 0.6 mM and ¿Mg(2+) from 2.7 +/- 0.2 to 12.2 +/- 0.6 mM. Both shell and bone accumulated lactate to concentrations of 135.6 +/- 35.2 and 163.6 +/- 5.1 mmol/kg wet wt, respectively, after 125 days anoxia. Shell and bone ¿Na(+) both fell during anoxia but the fate of this Na(+) is uncertain because plasma ¿Na(+) also fell. No other shell ions changed significantly in concentration, although the concentrations of both bone calcium and bone potassium changed significantly. Control shell water (27.8 +/- 0.6%) was less than bone water (33.6 +/- 1.1%), but neither changed during submergence. Shell ash (44.7 +/- 0.8%) remained unchanged, but bone ash (41.0 +/- 1.0%) fell significantly. We conclude that bone, as well as shell, accumulate lactate when plasma lactate is elevated, and that both export sodium carbonate, as well as calcium and magnesium carbonates, to supplement ECF buffering.

Physiology of common map turtles (Graptemys geographica) hibernating in the Lamoille river, Vermont.

Common map turtles (Graptemys geographica) were collected from a natural underwater hibernaculum in Vermont at monthly intervals during the winter of 1997-1998. Blood was sampled by cardiac puncture and analyzed for pH, PCO(2), PO(2), and hematocrit; separated plasma was tested for Na(+), K(+), Cl(-), total [Ca], total [Mg], [lactate], and osmolality (mOsm kg(-1) H(2)O). Control (eupneic; 1 degrees C) values for pH, PO(2), PCO(2), [HCO(3)(-)], and [lactate] were 7.98 +/- 0.03, 47.4 +/- 18.7, 10.1 +/- 0.7 (mm Hg), 36.1 +/- 0.2 (mmol liter(-1)), and 2.1 +/- 0.1 (mmol liter(-1)), respectively. Between November 1997 and March 1998, ice covered the river and the turtles rested on the substratum, fully exposed to the water, and were apneic. Blood PO(2) was maintained at less than 3 mm Hg (range 0.9 +/- 0.2 to 2.1 +/- 0.7 mm Hg), PCO(2) decreased slightly, plasma [lactate] was <5 mmol liter(-1), and plasma [HCO(3)(-)] decreased significantly. In March [lactate] rose to 7.5 +/- 1.5 mmol liter(-l), but there was no acidemia. Map turtles meet most of their metabolic demand for O(2) via aquatic respiration and tolerate prolonged submergence at 1 degrees C with little change in acid-base or ionic status. The adaptive significance of remaining essentially aerobic during winter is to avoid the life-threatening progressive acidosis that results from anaerobic metabolism. J. Exp. Zool. 286:143-148, 2000.

The physiology of diving in a north-temperate and three tropical turtle species.

We examined changes in blood gases, plasma ions, and acid-base status during prolonged submergence (6 h) of four aquatic turtle species in aerated water at 20 degrees C. Our objective was to determine whether the temperate species, Chrysemys picta bellii, exhibits greater tolerance to submergence apnea than the tropical species, Pelomedusa subrufa, Elseya novaeguineae, and Emydura subglobosa. Blood was sampled from indwelling arterial catheters for measurements of blood PO2, PCO2, pH, and hematocrit and for plasma concentrations of lactate, glucose, Na+, K+, Cl-, total Ca, and total Mg. The pattern of change was similar in all species: a combined respiratory and metabolic acidosis associated with a marked decrease of blood PO2. The severity of the acidosis developed in the temperate species, however, was significantly less than that of the tropical turtles. Lactate rose significantly and HCO3- fell proportionately in all turtles; changes in other plasma ion concentrations were small but were generally in the directions consistent with compensatory exchanges with other body compartments; i.e., cations (K+, Ca, and Mg increased) and anions (Cl- decreased). The results indicate that hypoxia tolerance is a conserved trait in turtles, even in those that do not experience enforced winter submergence, and that the temperate species may be superior in this capacity because of reduced metabolic rate.

The physiology of hibernation among painted turtles: the Eastern painted turtle Chrysemys picta picta.

Eastern painted turtles (Chrysemys picta picta) from Connecticut were submerged at 3 degrees C in normoxic and anoxic water to simulate potential respiratory environments within their hibernacula. Those in normoxic water could survive submergence for at least 150 d, while those in anoxic water could survive for a maximum of about 125 d. Turtles in normoxic water developed a slight metabolic acidosis as plasma lactate accumulated to about 50 mM in 150 d, while anoxic turtles developed a severe lactic acidosis as plasma lactate reached about 200 mM in 125 d; there was no respiratory acidosis in either group. Plasma [Na+] changed little in either group, [Cl-] fell by about one-third in both, and [K+] increased by about fourfold in anoxic turtles but only slightly in those in normoxic water. Total plasma magnesium and calcium increased profoundly in anoxic turtles but moderately in those in normoxic water. Consideration of charge balance indicates that all major ions were measured in both groups. Plasma glucose remained unchanged in anoxic turtles until after about 75 d of submergence, when it increased and continued to increase with the duration of anoxia, with much variation among individuals; glucose remained unchanged throughout in turtles in normoxic water. Hematocrit doubled in 150 d in turtles in normoxic water; in anoxic turtles, an initial increase was no longer significant by day 100. Plasma osmolality increased markedly in anoxic turtles, largely because of accumulation of lactate, but anoxic turtles only gained about half the mass of turtles in normoxic water, who showed no increase in osmolality. The higher weight gain in the latter group is attributed to selective perfusion and ventilation of extrapulmonary gas exchange surfaces, resulting in a greater osmotic influx of water. The physiologic responses to simulated hibernation of C. picta picta are intermediate between those of Chrysemys picta bellii and Chrysemys picta dorsalis, which correlates with the severity of the winter each subspecies would be expected to encounter.

AIT-082 as a potential neuroprotective and regenerative agent in stroke and central nervous system injury.

The synthetic purine 4-[[3-(1,6 dihydro-6-oxo-9-purin-9-yl)-1-oxypropyl] amino] benzoic acid (AIT-082, Neotrofin, leteprinim potassium) possesses several biological properties of note: it stimulates outgrowth of neurites from PC12 cells and neurones, stimulates synthesis and/or release of neurotrophic factors from astrocytes, enhances nerve fibre regeneration in vivo and enhances of memory in animals and humans. AIT-082 also protects against glutamate neurotoxicity in vitro and in vivo, which has led to successful tests of AIT-082 in animal models of acute central nervous system injury. In such cases, AIT-082 probably functions by both acutely reducing glutamate excitotoxicity and, over a longer period, by enhancing neuronal sprouting and functional recovery.