Catecholamine metabolism via monoamine oxidase (MAO) within myocardium of individuals with type 2 diabetes

The primary comorbidity and cause of mortality in type 2 diabetes is cardiovascular disease. The structural and the functional cardiac remodeling observed in patients with type 2 diabetes has been shown to be driven by a plethora of mechanisms including mitochondrial dysfunction and oxidative stress. Monoamine oxidase (MAO), an enzyme located on the outer mitochondrial membrane, catabolizes catecholamines to produce two reactive byproducts upon substrate deamination: catechol-aldehyde and H2O2. We hypothesized that within environments of decreased redox buffering capacity like type 2 diabetes, these byproducts of MAO metabolism disrupt mitochondrial respiration and further drive redox imbalance. Furthermore, we hypothesized that the antioxidant and aldehyde scavenging capacity of carnosine could mitigate the reactivity of MAO-derived byproducts. A comprehensive analysis of catecholamine metabolism was performed in atrial myocardium from individuals with and without type 2 diabetes. MAO-A and-B maximal activity and expression were significantly increased within myocardium from individuals with diabetes and correlated with BMI. MAO-dependent metabolism of norepinephrine decreased ATP production within myocardium from individuals with type 2 diabetes. In addition, decreased aldehyde dehydrogenase and increased basal levels of catechol-protein adducts were observed within this metabolic group. Metabolomic analysis of atrial tissue from individuals with diabetes showed decreased catecholamine levels in the myocardium, supporting an increased flux through MAOs. As a proof of concept of our second hypothesis we showed that carnosine was able to sequester DOPAL, the dopamine-derived catecholaldehyde. Carnosine also attenuated DOPAL-dependent decrease in state 3 respiration in permeabilized fibers isolated from atria. Furthermore, the production of catechol-modified proteins was mitigated by carnosine in a concentration dependent manner. In conclusion, these findings illustrate a pathogenic mechanism for MAO within type 2 diabetes, and suggest that MAO-derived byproducts, especially catecholaldehydes, contribute to redox imbalance and altered mitochondrial bioenergetics observed in myocardium of individuals with type 2 diabetes. In addition, this translational study provides a mechanistic framework for the study of carnosine or related aldehyde scavengers as therapeutic approach for the prevention of cardiac dysfunction in patients with type 2 diabetes

Innervation of Gill Lateral Cells in the Bivalve Mollusc Crassostrea virginica Affects Cellular Membrane Potential and Cilia Activity

Gill lateral cells of Crassostrea virginica are innervated by the branchial nerve, which contains serotonergic and dopaminergic fibers that regulate cilia beating rate. Terminal release of serotonin or dopamine results in an increase or decrease, respectively, of cilia beating rate in lateral gill cells. In this study we used the voltage sensitive fluorescent probe DiBAC4(3) to quantify changes in gill lateral cell membrane potential in response to electrical stimulation of the branchial nerve or to applications of serotonin and dopamine, and correlate these changes to cilia beating rates. Application of serotonin to gill lateral cells caused prolonged membrane depolarization, similar to plateau potentials, while increasing cilia beating rate. Application of dopamine hyperpolarized the resting membrane while decreasing cilia beating rate. Low frequency (5 Hz) electrical stimulations of the branchial nerve, which cause terminal release of endogenous serotonin, or high frequency (20 Hz) stimulations, which cause terminal release of endogenous dopamine, had the same effects on gill lateral cell membrane potentials and cilia beating rate as the respective applications of serotonin or dopamine. The study shows that innervation of gill lateral cells by the branchial nerve affects membrane potential as well as cilia beating rate, and demonstrates a strong correlation between changes in membrane potential and regulation of cilia beating rate. The study furthers the understanding of serotonin and dopamine signaling in the innervation and regulation of gill cilia in bivalves. The study also shows that voltage sensitive fluorescent probes like DiBAC 4(3) can be successfully used as an alternative to microelectrodes to measure changes in membrane potential of ciliated gill cells and other small cells with fast moving cilia

The Use of Thermal Capacity in Measuring the Effectiveness of Meals on Wheels Transport Containers

The Meals on Wheels (MOW) program is designed to help combat hunger in persons needing assistance. MOW has a duty not only to provide food but also to ensure that it reaches eligible clients safely. Given the population that MOW serves, transporting food safely takes on increased importance. This experiment focused on the major food safety issue of maintaining temperature integrity through the use of transport containers. For containers that did not contain electric heating elements, several factors influenced how fast the food temperature fell. Those factors included the U-value and size of the container as well as how many meals were in the container. As predicted, the smaller the U-value, the longer it took the temperature to fall. Larger containers did better at maintaining food temperatures, provided they were fully loaded. In general, fully loaded small and medium containers were better at maintaining food temperatures than larger containers loaded with the same number of meals

General anesthesia does not have persistent effects on attention in rodents

Background: Studies in animals have shown that general anesthesia can cause persistent spatial memory impairment, but the influence of anesthetics on other cognitive functions is unclear. This study tested whether exposure to general anesthesia without surgery caused a persistent deficit in attention in rodents.Methods: To evaluate whether anesthesia has persistent effects on attention, rats were randomized to three groups. Group A was exposed for 2 h to isoflurane anesthesia, and tested the following seven days for attentional deficits. Group B was used as a control and received room air before attentional testing. Since there is some evidence that a subanesthetic dose of ketamine can improve cognition and reduce disorders of attention after surgery, rats in group C were exposed to isoflurane anesthesia in combination with a ketamine injection before cognitive assessment. Attention was measured in rats using the 5-Choice Serial Reaction Time Task, for which animals were trained to respond with a nose poke on a touchscreen to a brief, unpredictable visual stimulus in one of five possible grid locations to receive a food reward. Attention was analyzed as % accuracy, % omission, and premature responses.Results: Evaluating acute attention by comparing baseline values with data from the day after intervention did not reveal any differences in attentional measurements. No significant differences were seen in % accuracy, % omission, and premature responses for the three groups tested for 7 consecutive days.Conclusion: These data in healthy rodents suggest that general anesthesia without surgery has no persistent effect on attention and the addition of ketamine does not alter the outcome

Variation in neural development as a result of exposure to institutionalization early in childhood

We used structural MRI and EEG to examine brain structure and function in typically developing children in Romania (n = 20), children exposed to institutional rearing (n = 29), and children previously exposed to institutional rearing but then randomized to a high-quality foster care intervention (n = 25). In so doing, we provide a unique evaluation of whether placement in an improved environment mitigates the effects of institutional rearing on neural structure, using data from the only existing randomized controlled trial of foster care for institutionalized children. Children enrolled in the Bucharest Early Intervention Project underwent a T1-weighted MRI protocol. Children with histories of institutional rearing had significantly smaller cortical gray matter volume than never-institutionalized children. Cortical white matter was no different for children placed in foster care than never-institutionalized children but was significantly smaller for children not randomized to foster care. We were also able to explain previously reported reductions in EEG α-power among institutionally reared children compared with children raised in families using these MRI data. As hypothesized, the association between institutionalization and EEG α-power was partially mediated by cortical white matter volume for children not randomized to foster care. The increase in white matter among children randomized to an improved rearing environment relative to children who remained in institutional care suggests the potential for developmental “catch up” in white matter growth, even following extreme environmental deprivation

Public Awareness of the Nebraska Regional Poison Control Center

A Poison Control Center needs to continually update its impact on the community it serves. At the Nebraska Regional Poison Control Center, a telephone survey was performed to ascertain baseline data for ongoing poison awareness programs. Our data shows that 36.6% of the population would call the PCC in the case of acute poisoning. There is a need to stress that the PCC is not only a center for information but also for treatment at home. Distribution of the PCC phone number to be attached to the phone needs to be increased. Many people obtained the phone number through time consuming methods which would increase the anxiety of the caller. Despite past programs, 63.9% of the respondents were not familiar with Syrup of Ipecac, and overall out of 608, people, 91.1% did not have Syrup of Ipecac at home in case of poisoning. In distributing poison information to the public, the pre-school and other school programs seem to be very effective. Newspapers and television also are an integral part in distributing poison information. With the help of the networks and newspapers in devoting time and space to poison prevention more households can be reached. There is a need to involve the pharmacist in distribution of poison information. Being the major supplier of Syrup of Ipecac, pharmacists can take a more active role by always carrying Syrup of Ipecac, and displaying it so that patrons may be reminded that they should have it at home

The beneficial effects of a positive attention bias amongst children with a history of psychosocial deprivation

Children raised in institutions experience psychosocial deprivation that has detrimental influences on attention and mental health. The current study examined patterns of attention biases in children from institutions who were randomized at approximately 21.6 months to receive either a high-quality foster care intervention or care-as-usual. At age 12, children performed a dot-probe task and indices of attention bias were calculated. Additionally, children completed a social stress paradigm and cortisol reactivity was computed. Children randomized into foster care (N=40) exhibited an attention bias toward positive stimuli but not threat, whereas children who received care-as-usual (N=40) and a never-institutionalized comparison group (N=47) showed no bias. Stability of foster care placement was related to positive bias, while instability of foster care placement was related to threat bias. The magnitude of the positive bias was associated with fewer internalizing problems and better coping mechanisms. Within the foster care group, positive attention bias was related to less blunted cortisol reactivity

NASA ESDIS Employs the Latest Generation Web Analytics Tool

Under the auspices of NASA's Earth Observing System Data and Information System (EOSDIS), The Earth Science Data and Information System (ESDIS) Project distributes science data to a wide community of users through its Distributed Active Archive Centers (DAACs). Much of this data is made available via interactive websites - which involve links, downloads, on page interaction, and referrals to additional online pages. To meet the earth science data and information needs of many data users representing numerous different science domains, over 80 specialized websites are supported by multiple distributed organizations under the ESDIS umbrella

A Pilot Study of the Effects of Mycoplasma ovipneumoniae Exposure on Domestic Lamb Growth and Performance

Mycoplasma ovipneumoniae is a globally distributed pathogen that has been associated with pneumonia in both domestic and wild Caprinae. It is closely related to M. hyopneumoniae, a respiratory pathogen of swine that is associated with decreased growth rates of pigs as well as clinical respiratory disease. In order to assess the effects of M. ovipneumoniae on lamb performance, we generated a cohort of lambs free of M. ovipneumoniae by segregation of test negative ewes after lambing, then compared the growth and carcass quality traits of M. ovipneumoniae-free and -colonized lambs from weaning to harvest. Some signs of respiratory disease were observed during the feeding trial in both lamb groups, but the M. ovipneumoniae-exposed group included more affected lambs and higher average disease scores. At harvest, lungs of lambs in both groups showed few grossly visible lesions, although the M. ovipneumoniae-exposed group did exhibit increased microscopic lung lesions (P\u3c0.05). In addition, M. ovipneumoniae exposed lambs produced lower average daily gains (P\u3c0.05), and lower yield grade carcasses (P\u3c0.05) compared to those of non-exposed lambs. The results demonstrated the feasibility of test and segregation for elimination of M. ovipneumoniae from groups of sheep and suggested that this pathogen may impair lamb growth and productivity even in the absence of overt respiratory disease

Decoupling of net community and export production on submesoscales in the Sargasso Sea

Author Posting. © American Geophysical Union, 2015. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Global Biogeochemical Cycles 29 (2015): 1266–1282, doi:10.1002/2014GB004913.Determinations of the net community production (NCP) in the upper ocean and the particle export production (EP) should balance over long time and large spatial scales. However, recent modeling studies suggest that a horizontal decoupling of flux-regulating processes on submesoscales (≤10 km) could lead to imbalances between individual determinations of NCP and EP. Here we sampled mixed-layer biogeochemical parameters and proxies for NCP and EP during 10, high-spatial resolution (~2 km) surface transects across strong physical gradients in the Sargasso Sea. We observed strong biogeochemical and carbon flux variability in nearly all transects. Spatial coherence among measured biogeochemical parameters within transects was common but rarely did the same parameters covary consistently across transects. Spatial variability was greater in parameters associated with higher trophic levels, such as chlorophyll in >5.0 µm particles, and variability in EP exceeded that of NCP in nearly all cases. Within sampling transects, coincident EP and NCP determinations were uncorrelated. However, when averaged over each transect (30 to 40 km in length), we found NCP and EP to be significantly and positively correlated (R = 0.72, p = 0.04). Transect-averaged EP determinations were slightly smaller than similar NCP values (Type-II regression slope of 0.93, standard deviation = 0.32) but not significantly different from a 1:1 relationship. The results show the importance of appropriate sampling scales when deriving carbon flux budgets from upper ocean observations.NASA Ocean Carbon and Biogeochemistry program Grant Number: NNX11AL94G; WHOI Postdoctoral Scholar fellowship; NASA ACE Grant Number: NNX12AJ25G; NSF Grant Number: OCE-07523662016-02-2