Efficacy of Female Rat Models in Translational Cardiovascular Aging Research

Cardiovascular disease is the leading cause of death in women in the United States. Aging is a primary risk factor for the development of cardiovascular disease as well as cardiovascular-related morbidity and mortality. Aging is a universal process that all humans undergo; however, research in aging is limited by cost and time constraints. Therefore, most research in aging has been done in primates and rodents; however it is unknown how well the effects of aging in rat models translate into humans. To compound the complication of aging gender has also been indicated as a risk factor for various cardiovascular diseases. This review addresses the systemic pathophysiology of the cardiovascular system associated with aging and gender for aging research with regard to the applicability of rat derived data for translational application to human aging

Sargassum sp. Act as a Large Regional Source of Marine Dissolved Organic Carbon and Polyphenols

Dissolved organic carbon (DOC) plays critical roles in marine carbon cycling, but its sources and sinks remain uncertain. In this study, we monitored DOC exudation rates of Sargassum natans under visible light (lambda > 390 nm) and solar radiation. DOC release rates ranged from 7 to 10 mu g C g(biomass)(-1) hr(-1) (wet weight) under visible light, but increased to 23 to 41 mu g C g(biomass)(-1) hr(-1) when exposed to natural sunlight. Results indicate that DOC released by Sargassum could amount to 0.3 to 1.2 Tg C/year, potentially contributing significantly to the marine DOC pool in the Gulf of Mexico and Western North Atlantic. We employed the Folin-Ciocalteu phenolic content method, nuclear magnetic resonance (NMR) spectroscopy, and ultrahigh resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) to characterize the diverse pool of organic compounds exuded from Sargassum. Results from these complementary methods showed that Sargassum release large quantities of phlorotannins, a class of polyphenols that have very similar properties to terrestrial DOC. These phlorotannins and their oxygenated phenolic derivatives exhibit a high hydrogen deficiency and functionalization (i.e., 4 to 6 oxygen atoms per aromatic ring), representing 5 to 18% of the released DOC isolated by solid phase extraction. Thus, Sargassum is the largest biological source of open ocean polyphenols recorded to date. The amount of polyphenolic DOC released by Sargassum challenges previous beliefs that all polyphenols found within the oceans are remnants of terrestrial organic matter, although the stability of phlorotannins and their derivatives needs to be further evaluated

Efficacy of Female Rat Models in Translational Cardiovascular Aging Research

Cardiovascular disease is the leading cause of death in women in the United States. Aging is a primary risk factor for the development of cardiovascular disease as well as cardiovascular-related morbidity and mortality. Aging is a universal process that all humans undergo; however, research in aging is limited by cost and time constraints. Therefore, most research in aging has been done in primates and rodents; however it is unknown how well the effects of aging in rat models translate into humans. To compound the complication of aging gender has also been indicated as a risk factor for various cardiovascular diseases. This review addresses the systemic pathophysiology of the cardiovascular system associated with aging and gender for aging research with regard to the applicability of rat derived data for translational application to human aging

Mutations in CIC and IDH1 cooperatively regulate 2-hydroxyglutarate levels and cell clonogenicity

The majority of oligodendrogliomas (ODGs) exhibit combined losses of chromosomes 1p and 19q and mutations of isocitrate dehydrogenase (IDH1-R132H or IDH2-R172K). Approximately 70% of ODGs with 1p19q co-deletions harbor somatic mutations in the Capicua Transcriptional Repressor (CIC) gene on chromosome 19q13.2. Here we show that endogenous long (CIC-L) and short (CIC-S) CIC proteins are predominantly localized to the nucleus or cytoplasm, respectively. Cytoplasmic CIC-S is found in close proximity to the mitochondria. To study wild type and mutant CIC function and motivated by the paucity of 1p19q co-deleted ODG lines, we created HEK293 and HOG stable cell lines ectopically co-expressing CIC and IDH1. Non-mutant lines displayed increased clonogenicity, but cells co-expressing the mutant IDH1-R132H with either CIC-S-R201W or -R1515H showed reduced clonogenicity in an additive manner, demonstrating cooperative effects in our assays. Expression of mutant CIC-R1515H increased cellular 2-Hydroxyglutarate (2HG) levels compared to wild type CIC in IDH1-R132H background. Levels of phosphorylated ATP-citrate Lyase (ACLY) were lower in cell lines expressing mutant CIC-S proteins compared to cells expressing wild type CIC-S, supporting a cytosolic citrate metabolism-related mechanism of reduced clonogenicity in our in vitro model systems. ACLY or phospho-ACLY were similarly reduced in CIC-mutant 1p19q co-deleted oligodendroglioma patient samples

Predicting the Onset of Cavitation in Automotive Torque Converters—Part II: A Generalized Model

The objective of this investigation was to develop a dimensionless model for predicting the onset of cavitation in torque converters applicable to general converter designs. Dimensional analysis was applied to test results from a matrix of torque converters that ranged from populations comprised of strict geometric similitude to those with more relaxed similarities onto inclusion of all the torque converters tested. Stator torque thresholds at the onset of cavitation for the stall operating condition were experimentally determined with a dynamometer test cell using nearfield acoustical measurements. Cavitation torques, design parameters, and operating conditions were resolved into a set of dimensionless quantities for use in the development of dimensionless empirical models. A systematic relaxation of the fundamental principle of dimensional analysis, geometric similitude, was undertaken to present empirical models applicable to torque converter designs of increasingly diverse design parameters. A stepwise linear regression technique coupled with response surface methodology was utilized to produce an empirical model capable of predicting stator torque at the onset of cavitation with less than 7% error for general automotive torque converter designs

Generalization Mediates Sensitivity to Complex Odor Features in the Honeybee

Animals use odors as signals for mate, kin, and food recognition, a strategy which appears ubiquitous and successful despite the high intrinsic variability of naturally-occurring odor quantities. Stimulus generalization, or the ability to decide that two objects, though readily distinguishable, are similar enough to afford the same consequence [1], could help animals adjust to variation in odor signals without losing sensitivity to key inter-stimulus differences. The present study was designed to investigate whether an animal's ability to generalize learned associations to novel odors can be influenced by the nature of the associated outcome. We use a classical conditioning paradigm for studying olfactory learning in honeybees [2] to show that honeybees conditioned on either a fixed- or variable-proportion binary odor mixture generalize learned responses to novel proportions of the same mixture even when inter-odor differences are substantial. We also show that the resulting olfactory generalization gradients depend critically on both the nature of the stimulus-reward paradigm and the intrinsic variability of the conditioned stimulus. The reward dependency we observe must be cognitive rather than perceptual in nature, and we argue that outcome-dependent generalization is necessary for maintaining sensitivity to inter-odor differences in complex olfactory scenes

Choice biases in no-sample and delay testing in pigeons (Columba livia)

In experimental tasks that involve stimuli that vary along a quantitative continuum, some choice biases are commonly found. Take, for instance, a matching-to-sample task where animals must, following the presentation of sample stimuli (that differ in duration), choose between two or more comparison stimuli. In tests where no sample is presented there is usually a bias towards the comparison that is correct following the shortest sample. To examine some aspects of these choice biases, pigeons were trained in a symbolic matching-to-sample task with two durations of keylight as samples, where key pecking had to be maintained during sample presentation. Firstly, even though animals were required to attend to the sample, a preference for the "short" comparison in no-sample testing was found. This result disproves an account where this effect was hypothesized to happen due to non-programmed learning resulting from the animals failing to attend to some trials. Secondly, even though a bias for "short" was found in both no-sample and delay testing, the extent of the biases differed between tasks, thus suggesting that forgetting the sample presented during a delay does not necessarily land the animal in a state similar to presenting no sample at all to begin with.The present study was supported by the Portuguese Foundation for Science and Technology and the Portuguese Ministry of Science, Technology and Higher Education through national funds. It was also co-financed by the European Regional Development Fund (FEDER)-through COMPETE2020-under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-007653)

Comparison of the clinical and economic outcomes between open and minimally invasive appendectomy and colectomy: evidence from a large commercial payer database

Background: Appendectomy and colectomy are commonly performed surgical procedures. Despite evidence demonstrating advantages with the minimally invasive surgical (MIS) approach, open procedures occur with greater prevalence. Therefore, there is still controversy as to whether the MIS approach is safer or more cost effective. Methods: A retrospective analysis was performed using a large commercial payer database. The data included information on 7,532 appendectomies and 2,745 colectomies. Data on the distribution of patient demographic and comorbidity characteristics associated with the MIS and open approaches were reviewed. The corresponding complication rates and expenditures were analyzed. Summary statistics were compared using chi-square tests, and generalized linear models were constructed to estimate expenditures while controlling for patient characteristics. Results: The patients undergoing MIS and open colectomy showed no significant variations in age distribution or marginal age differences for appendectomy. Significantly more patients experienced an infection postoperatively, and procedure-specific complications were more common in the open group for both procedures (P < 0.05). The postsurgical hospital stay was longer for the patients treated using the open techniques, differing an average of half a day for appendectomies and significantly more (4 days) for colectomy (P < 0.05). Readmission rates differed little between the two approaches. Procedures performed through an MIS approach were associated with lower expenditures than for the open technique, with differences ranging from $700 for appendectomy patients (P < 0.05) to$15,200 for colectomy patients (P < 0.05). Conclusions: Minimally invasive appendectomy and colectomy were associated with lower infection rates, fewer complications, shorter hospital stays, and lower expenditures than open surgery