Challenges for Opioid Receptor Nomenclature

Recent developments in the study of the structure and function of opioid receptors raise significant challenges for the definition of individual receptor types and the development of a nomenclature that precisely describes isoforms that may subserve different functions in vivo. Presentations at the 2013 meeting of the International Narcotics Research Conference in Cairns, Australia, considered some of the new discoveries that are now unravelling the complexities of opioid receptor signalling. Variable processing of opioid receptor messenger RNAs may lead to the presence of several isoforms of the μ receptor. Each opioid receptor type can function either as a monomer or as part of a homo- or heterodimer or higher multimer. Additionally, recent evidence points to the existence of agonist bias in the signal transduction pathways activated through μ receptors, and to the presence of regulatory allosteric sites on the receptors. This brief review summarizes the recent discoveries that raise challenges for receptor definition and the characterization of signal transduction pathways activated by specific receptor forms. LINKED ARTICLES: This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2.NHMRC 104596

Food habits of wintering double-crested cormorants in the Mississippi Delta

Given its ubiquity, it is not surprising that agriculture, including fin fish aquaculture, contributes to food webs worldwide and is used by numerous wildlife for foraging and meeting other needs. Double-crested Cormorants (Phalacrocorax auritus) impact United States commercial aquaculture and are considered the primary avian predator in catfish (Ictalurus spp.) aquaculture facilities in the Mississippi Delta. Recent changes in aquaculture practices, regulatory policies, and decreased overall hectares in production prompted this study that assessed cormorant consumption of catfish in relation to their night roosts through surveys and diet analysis. Cormorants were collected from night roosts from October through April 2016–2018 (n=69 collections). On average, catfish constituted 33% of a cormorant\u27s overall diet, which is less than reported in previous studies. There was no statistical difference between consumption of channel (I. punctatus) and hybrid catfish (I. punctatus x I. furcatus) based on biomass estimates, and the greatest consumption of catfish occurred in the months of February and March. The best fit model for predicting catfish consumption was the cubic polynomial function of the area of catfish aquaculture within a 30.6 km forage buffer of a night roost. Our findings will inform wildlife managers about relationships between cormorant night roost locations and consumption of catfish and aid decision making with respect to cormorant management. Despite cormorants having shifted consumption to naturally occurring fish species associated with changes to aquaculture, aquaculture remains an important part of regional food webs

Potential Biomarkers for Physical Exercise-Induced Brain Health

Physical exercise has long been recognized as an effective and economic strategy to promote brain health in humans. The cellular and structural changes in the brains of exercised animals, including enhancements of neurogenesis and synaptogenesis, dendritic remodeling, and synaptic plasticity, have been considered as the key biological alterations accounting for exercise-elicited benefits to brain health. However, what transduces body movements into the above-mentioned changes remains largely unknown. Emerging theories indicate that physical activity triggers the release of various factors into the circulation from skeletal muscle (neurotrophins, myokines, and cytokines) and/or adipose tissue (adipokines). In this chapter, we review several of these molecules that are potentially implicated in this process, including neurotrophic factors (BDNF, IGF-1, and VEGF), adipokines (adiponectin and irisin), and myokines/cytokines (IL-15). The relationship, either causal or concomitant, between levels of these molecules (particularly in the blood) and brain function after exercise may help to identify biomarkers that can serve as objective indicators to evaluate exercise therapy on diseased or ageing brain. In addition, unmasking biomarkers may be instrumental in elucidating the mechanisms mediating exercise-induced brain health, thereby contributing to novel drug discovery for treatments to maintain brain health

Brain changes: aerobic exercise for traumatic brain injury rehabilitation

IntroductionTraumatic Brain Injury (TBI) accounts for millions of hospitalizations and deaths worldwide. Aerobic exercise is an easily implementable, non-pharmacological intervention to treat TBI, however, there are no clear guidelines for how to best implement aerobic exercise treatment for TBI survivors across age and injury severity.MethodsWe conducted a PRISMA-ScR to examine research on exercise interventions following TBI in children, youth and adults, spanning mild to severe TBI. Three electronic databases (PubMed, PsycInfo, and Web of Science) were searched systematically by two authors, using keywords delineated from “Traumatic Brain Injury,” “Aerobic Exercise,” and “Intervention.”ResultsOf the 415 papers originally identified from the search terms, 54 papers met the inclusion criteria and were included in this review. The papers were first grouped by participants’ injury severity, and subdivided based on age at intervention, and time since injury where appropriate.DiscussionAerobic exercise is a promising intervention for adolescent and adult TBI survivors, regardless of injury severity. However, research examining the benefits of post-injury aerobic exercise for children and older adults is lacking

Terminology of Geological Time: Establishment of a Community Standard

It has been recommended that geological time be described in a single set of terms and according to metric or SI (“Système International d’Unités”) standards, to ensure “worldwide unification of measurement”. While any effort to improve communication in scientific research and writing is to be encouraged, we are also concerned that fundamental differences between date and duration, in the way that our profession expresses geological time, would be lost in such an oversimplified terminology. In addition, no precise value for ‘year’ in the SI base unit of second has been accepted by the international bodies.Under any circumstances, however, it remains the fact that geological dates – as points in time – are not relevant to the SI. Known dates may define durations, just as known durations may define dates, or dates may simply be punctual references that support historical narratives, but dates are not quantities. Furthermore, dates, as datum points, belong to a specific type of guiding information that is in constant use not only by the disciplines that explore the unwritten past, but in the physical sciences and engineering as well. Accordingly, we recommend a new standardization of the distinction between geohistorical date, in years before present expressed in ‘annus’, symbol ‘a’,with the multiples ‘ka’, ‘Ma’, and ‘Ga’ for thousands, millions and billions of years ago, according to a convention that has been very widely adopted during the last 30 years, and geohistorical duration, expressed in ‘year’, symbol ‘yr’, with multiples ‘kyr’, ‘Myr’ and ‘Gyr’, respectively, as the most appropriate among the various formats in the current literature. Agreement on these two sets of terms throughout the wide community that deals with paleochronology would remove a false impression of improvisation and uncertainty as to appropriate terminology, and would lead to more effective communication in areas where a simplified but needlessly SI-conisistent terminology would be less, not more useful

Fragile-X Syndrome Is Associated With NMDA Receptor Hypofunction and Reduced Dendritic Complexity in Mature Dentate Granule Cells

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability. It is caused by the overexpansion of cytosine-guanine-guanine (CGG) trinucleotide in Fmr1 gene, resulting in complete loss of the fragile X mental retardation protein (FMRP). Previous studies using Fmr1 knockout (Fmr1 KO) mice have suggested that a N-methyl-D-aspartate receptors (NMDAR) hypofunction in the hippocampal dentate gyrus may partly contribute to cognitive impairments in FXS. Since activation of NMDAR plays an important role in dendritic arborization during neuronal development, we examined whether deficits in NMDAR function are associated with alterations in dendritic complexity in the hippocampal dentate region. The dentate granule cell layer (GCL) presents active postnatal neurogenesis, and consists of a heterogenous neuronal population with gradient ages from the superficial to its deep layer. Here, we show that neurons with multiple primary dendrites that reside in the outer GCL of Fmr1 KO mice display significantly smaller NMDAR excitatory post-synaptic currents (EPSCs) and a higher α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) to NMDA ratio in comparison to their wild-type counterparts. These deficits were associated with a significant decrease in dendritic complexity, with both dendritic length and number of intersections being significantly reduced. In contrast, although neurons with a single primary dendrite resided in the inner GCL of Fmr1 KO mice had a trend toward a reduction in NMDAR EPSCs and a higher AMPA/NMDA ratio, no alterations were found in dendritic complexity at this developmental stage. Our data indicate that the loss of FMRP causes NMDAR deficits and reduced dendritic complexity in granule neurons with multiple primary dendrites which are thought to be more mature in the GCL

Combined hydration and antibiotics with lisinopril to mitigate acute and delayed high-dose radiation injuries to multiple organs

The NIAID Radiation and Nuclear Countermeasures Program is developing medical agents to mitigate the acute and delayed effects of radiation that may occur from a radionuclear attack or accident. To date, most such medical countermeasures have been developed for single organ injuries. Angiotensin converting enzyme (ACE) inhibitors have been used to mitigate radiation-induced lung, skin, brain and renal injuries in rats. ACE inhibitors have also been reported to decrease normal tissue complication in radiation oncology patients. In the current study we have developed a rat partial-body irradiation (leg-out PBI) model with minimal bone marrow sparing (one leg shielded) that results in acute and late injuries to multiple organs. In this model, the ACE inhibitor lisinopril (at ∼24 mg m-2 day-1 started orally in the drinking water at 7 days after irradiation and continued to ≥150 days) mitigated late effects in the lungs and kidneys after 12.5 Gy leg-out PBI. Also in this model, a short course of saline hydration and antibiotics mitigated acute radiation syndrome following doses as high as 13 Gy. Combining this supportive care with the lisinopril regimen mitigated overall morbidity for up to 150 days after 13 Gy leg-out PBI. Furthermore lisinopril was an effective mitigator in the presence of the growth factor G-CSF (100 μg kg-1 day-1 from days 1-14) which is FDA-approved for use in a radionuclear event. In summary, by combining lisinopril (FDA-approved for other indications) with hydration and antibiotics, we mitigated acute and delayed radiation injuries in multiple organs

Genetic assessment of a bighorn sheep population expansion in the Silver Bell Mountains, Arizona

Background The isolated population of desert bighorn sheep in the Silver Bell Mountains of southern Arizona underwent an unprecedented expansion in merely four years. We hypothesized that immigration from neighboring bighorn sheep populations could have caused the increase in numbers as detected by Arizona Game and Fish Department annual aerial counts. Methods We applied a multilocus genetic approach using mitochondrial DNA and nuclear microsatellite markers for genetic analyses to find evidence of immigration. We sampled the Silver Bell Mountains bighorn sheep before (2003) and during (2015) the population expansion, and a small number of available samples from the Gila Mountains (southwestern Arizona) and the Morenci Mine (Rocky Mountain bighorn) in an attempt to identify the source of putative immigrants and, more importantly, to serve as comparisons for genetic diversity metrics. Results We did not find evidence of substantial gene flow into the Silver Bell Mountains population. We did not detect any new mitochondrial haplotypes in the 2015 bighorn sheep samples. The microsatellite analyses detected only one new allele, in one individual from the 2015 population that was not detected in the 2003 samples. Overall, the genetic diversity of the Silver Bell Mountains population was lower than that seen in either the Gila population or the Morenci Mine population. Discussion Even though the results of this study did not help elucidate the precise reason for the recent population expansion, continued monitoring and genetic sampling could provide more clarity on the genetic demographics of this population

Ideal Cardiovascular Health During Adult Life and Cardiovascular Structure and Function Among the Elderly.

BACKGROUND: A higher American Heart Association cardiovascular health score (CVHS) predicts a lower incidence of cardiovascular disease (CVD). However, the relationship of CVHS attainment through midlife to late life with CVD prevalence and cardiovascular structure and function in late life is not well described. METHODS AND RESULTS: The following 6 ideal cardiovascular health metrics were assessed in the Atherosclerosis Risk in Communities (ARIC) study participants at 5 examination visits between 1987 and 2013: nonsmoking, body mass index <25 kg/m(2), untreated total cholesterol <200 mg/dL, untreated blood pressure <120/<80 mm Hg, fasting blood glucose <100 mg/dL, and ideal physical activity. Attainment over time was assessed as the percentage of maximum possible CVHS metrics achieved at visits 1 through 5, the slope of change in CVHS per decade of follow-up, and CVHS trajectory through follow-up. At visit 5, participant groups were characterized with respect to CVD prevalence (n=6520) and echocardiographic measures of cardiac structure and function (n=5903 free of CVD). CVHS was low at baseline and declined with age. Both greater CVHS attainment and improvement in CVHS during follow-up were associated with a lower prevalence of CVD and better left ventricular structure and systolic and diastolic function at visit 5. CONCLUSIONS: Greater attainment of, and improvements in, ideal cardiovascular health through midlife to late life are associated with lower CVD prevalence and better cardiovascular structure and function when elderly. These findings highlight the importance of consistent primordial and primary prevention efforts throughout midlife to late life as a potential intervention to decrease the burden of CVD among the elderly

Larval Connectivity in an Effective Network of Marine Protected Areas

Acceptance of marine protected areas (MPAs) as fishery and conservation tools has been hampered by lack of direct evidence that MPAs successfully seed unprotected areas with larvae of targeted species. For the first time, we present direct evidence of large-scale population connectivity within an existing and effective network of MPAs. A new parentage analysis identified four parent-offspring pairs from a large, exploited population of the coral-reef fish Zebrasoma flavescens in Hawai'i, revealing larval dispersal distances ranging from 15 to 184 km. In two cases, successful dispersal was from an MPA to unprotected sites. Given high adult abundances, the documentation of any parent-offspring pairs demonstrates that ecologically-relevant larval connectivity between reefs is substantial. All offspring settled at sites to the north of where they were spawned. Satellite altimetry and oceanographic models from relevant time periods indicated a cyclonic eddy that created prevailing northward currents between sites where parents and offspring were found. These findings empirically demonstrate the effectiveness of MPAs as useful conservation and management tools and further highlight the importance of coupling oceanographic, genetic, and ecological data to predict, validate and quantify larval connectivity among marine populations