Present‐day shortcomings in the representation of upper tropospheric ice clouds in general circulation models (GCMs) lead to errors in weather and climate forecasts as well as account for a source of ...uncertainty in climate change projections. An ongoing challenge in rectifying these shortcomings has been the availability of adequate, high‐quality, global observations targeting ice clouds and related precipitating hydrometeors. In addition, the inadequacy of the modeled physics and the often disjointed nature between model representation and the characteristics of the retrieved/observed values have hampered GCM development and validation efforts from making effective use of the measurements that have been available. Thus, even though parameterizations in GCMs accounting for cloud ice processes have, in some cases, become more sophisticated in recent years, this development has largely occurred independently of the global‐scale measurements. With the relatively recent addition of satellite‐derived products from Aura/Microwave Limb Sounder (MLS) and CloudSat, there are now considerably more resources with new and unique capabilities to evaluate GCMs. In this article, we illustrate the shortcomings evident in model representations of cloud ice through a comparison of the simulations assessed in the Intergovernmental Panel on Climate Change Fourth Assessment Report, briefly discuss the range of global observational resources that are available, and describe the essential components of the model parameterizations that characterize their “cloud” ice and related fields. Using this information as background, we (1) discuss some of the main considerations and cautions that must be taken into account in making model‐data comparisons related to cloud ice, (2) illustrate present progress and uncertainties in applying satellite cloud ice (namely from MLS and CloudSat) to model diagnosis, (3) show some indications of model improvements, and finally (4) discuss a number of remaining questions and suggestions for pathways forward.
Sensitivity to cocaine and its associated stimuli ("cues") are important factors in the development and maintenance of addiction. Rodent studies suggest that this sensitivity is related, in part, to ...the propensity to attribute incentive salience to food cues, which, in turn, contributes to the maintenance of cocaine self-administration, and cue-induced relapse of drug-seeking. Whereas each of these traits has established links to drug use, the relatedness between the individual traits themselves has not been well characterized in preclinical models. To this end, the propensity to attribute incentive salience to a food cue was first assessed in two distinct cohorts of 2716 outbred heterogeneous stock rats (HS; formerly N:NIH). We then determined whether each cohort was associated with performance in one of two paradigms (cocaine conditioned cue preference and cocaine contextual conditioning). These measure the unconditioned locomotor effects of cocaine, as well as conditioned approach and the locomotor response to a cocaine-paired floor or context. There was large individual variability and sex differences among all traits, but they were largely independent of one another in both males and females. These findings suggest that these traits may contribute to drug-use via independent underlying neuropsychological processes.
The avian “hibernation” enigma Woods, Christopher P.; Czenze, Zenon J.; Brigham, R. Mark
Oecologia,
01/2019, Volume:
189, Issue:
1
Journal Article
Peer reviewed
Compared to mammals, there are relatively few studies examining heterothermy in birds. In 13 bird families known to contain heterothermic species, the common poorwill (Phalaenoptilus nuttallii) is ...the only species that ostensibly hibernates. We used temperature-sensitive radio-transmitters to collect roost and skin temperature (Tskin) data, and winter roost preferences for free-ranging poorwills in southern Arizona. Further, to determine the effect of passive rewarming on torpor bout duration and active rewarming (i.e., the use of metabolic heat to increase Tskin), we experimentally shaded seven birds during winter to prevent them from passively rewarming via solar radiation. Poorwills selected winter roosts that were open to the south or southwest, facilitating passive solar warming in the late afternoon. Shaded birds actively rewarmed following at least 3 days of continuous torpor. Average torpor bout duration by shaded birds was 122 h and ranged from 91 to 164 h. Active rewarming by shaded birds occurred on significantly warmer days than those when poorwills remained torpid. One shaded bird remained inactive for 45 days, during which it spontaneously rewarmed actively on eight occasions. Our findings show that during winter poorwills exhibit physiological patterns and active rewarming similar to hibernating mammals.
Objective
Obesity is influenced by genetic and environmental factors. Despite the success of human genome‐wide association studies, the specific genes that confer obesity remain largely unknown. The ...objective of this study was to use outbred rats to identify the genetic loci underlying obesity and related morphometric and metabolic traits.
Methods
This study measured obesity‐relevant traits, including body weight, body length, BMI, fasting glucose, and retroperitoneal, epididymal, and parametrial fat pad weight in 3,173 male and female adult N/NIH heterogeneous stock (HS) rats across three institutions, providing data for the largest rat genome‐wide association study to date. Genetic loci were identified using a linear mixed model to account for the complex family relationships of the HS and using covariates to account for differences among the three phenotyping centers.
Results
This study identified 32 independent loci, several of which contained only a single gene (e.g., Epha5, Nrg1, Klhl14) or obvious candidate genes (e.g., Adcy3, Prlhr). There were strong phenotypic and genetic correlations among obesity‐related traits, and there was extensive pleiotropy at individual loci.
Conclusions
This study demonstrates the utility of HS rats for investigating the genetics of obesity‐related traits across institutions and identify several candidate genes for future functional testing.
Organisms must regulate their behavior flexibly in the face of environmental challenges. Failure can lead to a host of maladaptive behavioral traits associated with a range of neuropsychiatric ...disorders, including attention deficit hyperactivity disorder, autism, and substance use disorders. This maladaptive dysregulation of behavior is influenced by genetic and environmental factors. For example, environmental enrichment produces beneficial neurobehavioral effects in animal models of such disorders. The present study determined the effects of environmental enrichment on a range of measures related to behavioral regulation using a large cohort of male, outbred heterogeneous stock (HS) rats as subjects. Subjects were reared from late adolescence onwards either in pairs in standard housing with minimal enrichment (n = 200) or in groups of 16 in a highly enriched environment consisting of a large multi-level cage filled with toys, running wheels, and shelters (n = 64). Rats were subjected to a battery of tests, including: (i) locomotor response to novelty, (ii) light reinforcement, (iii) social reinforcement, (iv) reaction time, (v) a patch-depletion foraging test, (vi) Pavlovian conditioned approach, (vii) conditioned reinforcement, and (viii) cocaine conditioned cue preference. Results indicated that rats housed in the enriched environment were able to filter out irrelevant stimuli more effectively and thereby regulate their behavior more efficiently than standard-housing rats. The dramatic impact of environmental enrichment suggests that behavioral studies using standard housing conditions may not generalize to more complex environments that may be more ethologically relevant.
Rationale
Disorders of behavioral regulation, including attention deficit hyperactivity disorder (ADHD) and drug addiction, are in part due to poor inhibitory control, attentional deficits, and ...hyper-responsivity to reward-associated cues.
Objectives
To determine whether these traits are related, we tested genetically variable male and female heterogeneous stock rats in the choice reaction time (CRT) task and Pavlovian conditioned approach (PavCA). Sex differences in the response to methylphenidate during the CRT were also assessed.
Methods
In the CRT task, rats were required to withhold responding until one of two lights indicated whether responses into a left or right port would be reinforced with water. Reaction time on correct trials and premature responses were the operational definitions of attention and response inhibition, respectively. Rats were also pretreated with oral methylphenidate (0, 2, 4 mg/kg) during the CRT task to determine whether this drug would improve performance. Subsequently, during PavCA, presentation of an illuminated lever predicted the delivery of a food pellet into a food-cup. Lever-directed approach (sign-tracking) and food-cup approach (goal-tracking) were the primary measures, and rats were categorized as “sign-trackers” and “goal-trackers” using an index based on these measures.
Results
Sign-trackers made more premature responses than goal-trackers but showed no differences in reaction time. There were sex differences in both tasks, with females having higher sign-tracking, completing more CRT trials, and making more premature responses after methylphenidate administration.
Conclusions
These results indicate that response inhibition is related to reward-cue responsivity, suggesting that these traits are influenced by common genetic factors.
According to the National Survey on Drug Use and Health (NSDUH), approximately 808,000 Americans reported using heroin in the past year in 2018, but use declined overall between 2016 and 2018 and ...especially in individuals aged 18 to 25 years. According to the Centers for Disease Control and Prevention (CDC), while heroin-related fatalities increased significantly between 1999 and 2016, they remained stable between 2016 and 2018, with heroin-related deaths exceeding 15,000 in 2018 (Han et al., 2020). ...timely surveillance of heroin overdoses as well as a greater understanding of the characteristics of such cases is key to developing response efforts. Independent risk markers of heroin exposures with severe medical outcomes reported to the U.S. Poison Center Centers Characteristic, N (%) Adjusted odds ratios (AOR) 95% confidence intervals (95% CI) Age 20–29 years Reference Reference 0–5 years 0.54 0.32–0.93 6–19 years 0.92 0.84–1.01 30–39 years 1.02 0.96–1.09 40–49 years 1.15 1.07–1.25 50–59 years 1.31 1.20–1.44 ≥ 60 years 1.29 1.10–1.51 Gender Female Reference Reference Male 1.10 1.04–1.16 Reason1 Unintentional Reference Reference Suspected suicide 1.25 1.02–1.53 Abuse 2.04 1.68–2.47 Misuse 0.47 0.37–0.60 Number of products Single substance exposures Reference Reference Multiple substance exposures 1.54 1.45–1.64 Number of opioids involved in exposure 1 Reference Reference 2 1.37 1.27–1.49 3 or more 1.84 1.50–2.25 Route of exposure2 Ingestion Reference Reference Inhalation/nasal 2.28 2.10–2.49 Parenteral 2.51 2.31–2.70 Others 2.79 2.58–3.01 Chronicity3 Acute Reference Reference Others 0.97 0.92–1.02 Region Northeast Reference Reference Midwest 1.37 1.27–1.49 South 1.84 1.50–2.25 West 1.37 1.28–1.47 1Unintentional include unknown, contamination/tampering, malicious, withdrawal, bite/sting, environmental, food poisoning, unintentional–misuse, occupational, therapeutic error 2Others include aspiration, ocular, dermal, bite/sting, unknown, otic, rectal, and vaginal 3Others include acute-on-chronic, chronic, and unknown Discussion Our study comprehensively identified the most recent trends and characteristics of the heroin exposures reported to a national poison database, a near real-time, validated surveillance system that has been extensively utilized for tracking opioid overdoses (Allen et al., 2017; Patel et al., 2019; Rege et al., 2018).
CpGH89 is a large multimodular enzyme produced by the human and animal pathogen Clostridium perfringens. The catalytic activity of this exo-α-D-N-acetylglucosaminidase is directed towards a rare ...carbohydrate motif, N-acetyl-β-D-glucosamine-α-1,4-D-galactose, which is displayed on the class III mucins deep within the gastric mucosa. In addition to the family 89 glycoside hydrolase catalytic module this enzyme has six modules that share sequence similarity to the family 32 carbohydrate-binding modules (CBM32s), suggesting the enzyme has considerable capacity to adhere to carbohydrates. Here we suggest that two of the modules, CBM32-1 and CBM32-6, are not functional as carbohydrate-binding modules (CBMs) and demonstrate that three of the CBMs, CBM32-3, CBM32-4, and CBM32-5, are indeed capable of binding carbohydrates. CBM32-3 and CBM32-4 have a novel binding specificity for N-acetyl-β-D-glucosamine-α-1,4-D-galactose, which thus complements the specificity of the catalytic module. The X-ray crystal structure of CBM32-4 in complex with this disaccharide reveals a mode of recognition that is based primarily on accommodation of the unique bent shape of this sugar. In contrast, as revealed by a series of X-ray crystal structures and quantitative binding studies, CBM32-5 displays the structural and functional features of galactose binding that is commonly associated with CBM family 32. The functional CBM32s that CpGH89 contains suggest the possibility for multivalent binding events and the partitioning of this enzyme to highly specific regions within the gastrointestinal tract.
Power analyses are often used to determine the number of animals required for a genome-wide association study (GWAS). These analyses are typically intended to estimate the sample size needed for at ...least 1 locus to exceed a genome-wide significance threshold. A related question that is less commonly considered is the number of significant loci that will be discovered with a given sample size. We used simulations based on a real data set that consisted of 3,173 male and female adult N/NIH heterogeneous stock rats to explore the relationship between sample size and the number of significant loci discovered. Our simulations examined the number of loci identified in subsamples of the full data set. The subsampling analysis was conducted for 4 traits with low (0.15 ± 0.03), medium (0.31 ± 0.03 and 0.36 ± 0.03), and high (0.46 ± 0.03) SNP-based heritabilities. For each trait, we subsampled the data 100 times at different sample sizes (500, 1,000, 1,500, 2,000, and 2,500). We observed an exponential increase in the number of significant loci with larger sample sizes. Our results are consistent with similar observations in human GWAS and imply that future rodent GWAS should use sample sizes that are significantly larger than those needed to obtain a single significant result.
Obesity is a growing health problem worldwide. The renin-angiotensin system (RAS) is present in adipose tissue, and evidence suggests that it is involved in both diet-induced obesity and the ...inflammation associated with obesity. The present experiments determined the effect of (1) different angiotensin-converting enzyme (ACE) inhibitors (captopril, perindopril, enalapril) and angiotensin receptor blockers (ARBs: telmisartan, losartan) on adiposity of mice fed a high-fat diet for 28 days (2); acute treatment with the ACE-inhibitor captopril on gene expression of inflammatory markers in mice fed a high-fat diet (HFD); and (3) short-term (2 days) and chronic (28 days) treatment of ACE-inhibition on energy expenditure (EE) and energy balance in mice fed HFD
(AL), as well as receiving HFD limited to the amount of calories eaten by controls (pair-fed (PF) group). Body weight, food intake, adiposity and plasma leptin were lower in ACE inhibitor or ARB-treated groups over 28 days compared with HFD untreated mice. Short-term treatment with captopril led to increased EE relative to the level in the PF group. After 28 days, EE was lower in both captopril-treated and PF mice compared with AL, but the effect was greater in the captopril-treated group. Adiponectin was elevated in captopril-treated mice, but not in PF mice, after both 2 and 28 days. Additionally, acute RAS blockade in HFD-fed mice reduced mRNA expression for MCP-1, IL-6, TLR4, and leptin in adipose tissue relative to values in untreated groups. These data demonstrate that ACE inhibition and angiotensin receptor blockade reduce food intake to produce weight loss and suggest that the anti-inflammatory effects of ACE inhibition may be independent of weight loss.
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