Cranial morphometrics of the dire wolf, Canis dirus, at Rancho La Brea: temporal variability and its links to nutrient stress and climate

The tar pits of Rancho La Brea are a unique window onto the biology and ecology of the terminal Pleistocene in southern California. In this study we capitalize on recent advances in understanding of La Brea tar pit chronology to perform the first morphometric study of crania of the dire wolf, Canis dirus, over time. We first present new data on tooth fracture and wear from pits dated older than heretofore analyzed, and demonstrate that fracture and wear events, and the increased competition and heightened carcass utilization they are thought to represent, were of varying intensity across the sampled time intervals. Skull size, and by extension body size, is shown to differ significantly among pits at La Brea, with the strongest single observation being reduction in body size at the last glacial maximum. Skull size variation is shown to be a result of both ontogenetic and evolutionary factors, neither of which is congruent with a temporal version of Bergmann’s rule. Skull shape difference among the pits is also significant, with shape variability attributable to both neotenic effects in populations with high breakage and wear, and evolutionary changes possibly due to climate change. Testing of this hypothesis requires better accuracy and precision in La Brea carbon data, a program that is within the reach of current AMS dating technology

Considerations for best practices in studies of fiber or other dietary components and the intestinal microbiome

Considerations for best practices in studies of fiber or other dietary components and the intestinal microbiome. Am J Physiol Endocrinol Metab 315: E1087–E1097, 2018. First published August 21, 2018; doi:10.1152/ajpendo.00058.2018.—A 2-day workshop organized by the National Institutes of Health and U.S. Department of Agriculture included 16 presentations focused on the role of diet in alterations of the gastrointestinal microbiome, primarily that of the colon. Although thousands of research projects have been funded by U.S. federal agencies to study the intestinal microbiome of humans and a variety of animal models, only a minority addresses dietary effects, and a small subset is described in sufficient detail to allow reproduction of a study. Whereas there are standards being developed for many aspects of microbiome studies, such as sample collection, nucleic acid extraction, data handling, etc., none has been proposed for the dietary component; thus this workshop focused on the latter specific point. It is important to foster rigor in design and reproducibility of published studies to maintain high quality and enable designs that can be compared in systematic reviews. Speakers addressed the influence of the structure of the fermentable carbohydrate on the microbiota and the variables to consider in design of studies using animals, in vitro models, and human subjects. For all types of studies, strengths and weaknesses of various designs were highlighted, and for human studies, comparisons between controlled feeding and observational designs were discussed. Because of the lack of published, best-diet formulations for specific research questions, the main recommendation is to describe dietary ingredients and treatments in as much detail as possible to allow reproduction by other scientists

Complex Collaborative Problem-Solving Processes In Mission Control

ntroduction: NASA\u27s Mission Control Center (MCC) is responsible for control of the International Space Station (ISS), which includes responding to problems that obstruct the functioning of the ISS and that may pose a threat to the health and well-being of the fl ight crew. These problems are often complex, requiring individuals, teams, and multiteam systems, to work collaboratively. Research is warranted to examine individual and collaborative problem-solving processes in this context. Specifi cally, focus is placed on how Mission Control personnel-each with their own skills and responsibilities-exchange information to gain a shared understanding of the problem. The Macrocognition in Teams Model describes the processes that individuals and teams undertake in order to solve problems and may be applicable to Mission Control teams. Method: Semistructured interviews centering on a recent complex problem were conducted with seven MCC professionals. In order to assess collaborative problem-solving processes in MCC with those predicted by the Macrocognition in Teams Model, a coding scheme was developed to analyze the interview transcriptions. Results: Findings are supported with excerpts from participant transcriptions and suggest that team knowledge-building processes accounted for approximately 50% of all coded data and are essential for successful collaborative problem solving in mission control. Support for the internalized and externalized team knowledge was also found (19% and 20%, respectively). Discussion: The Macrocognition in Teams Model was shown to be a useful depiction of collaborative problem solving in mission control and further research with this as a guiding framework is warranted. © by the Aerospace Medical Association. Alexandria, VA

Ascorbic Acid Improves Brachial Artery Vasodilation during Progressive Handgrip Exercise in the Elderly through a Nitric Oxide-Mediated Mechanism

The proposed mechanistic link between the age-related attenuation in vascular function and free radicals is an attractive hypothesis; however, direct evidence of free radical attenuation and a concomitant improvement in vascular function in the elderly is lacking. Therefore, this study sought to test the hypothesis that ascorbic acid (AA), administered intra-arterially during progressive handgrip exercise, improves brachial artery (BA) vasodilation in a nitric oxide (NO)-dependent manner, by mitigating free radical production. BA vasodilation (Doppler ultrasound) and free radical outflow [electron paramagnetic resonance (EPR) spectroscopy] were measured in seven healthy older adults (69 ± 2 yr) during handgrip exercise at 3, 6, 9, and 12 kg (∼13-52% of maximal voluntary contraction) during the control condition and nitric oxide synthase (NOS) inhibition via N(G)-monomethyl-L-arginine (L-NMMA), AA, and coinfusion of l-NMMA + AA. Baseline BA diameter was not altered by any of the treatments, while L-NMMA and L-NMMA + AA diminished baseline BA blood flow and shear rate. AA improved BA dilation compared with control at 9 kg (control: 6.5 ± 2.2%, AA: 10.9 ± 2.5%, P = 0.01) and 12 kg (control: 9.5 ± 2.7%, AA: 15.9 ± 3.7%, P \u3c 0.01). NOS inhibition blunted BA vasodilation compared with control and when combined with AA eliminated the AA-induced improvement in BA vasodilation. Free radical outflow increased with exercise intensity but, interestingly, was not attenuated by AA. Collectively, these results indicate that AA improves BA vasodilation in the elderly during handgrip exercise through an NO-dependent mechanism; however, this improvement appears not to be the direct consequence of attenuated free radical outflow from the forearm

Vascular Function and the Role of Oxidative Stress in Heart Failure, Heart Transplant, and Beyond

Using flow-mediated vasodilation (FMD), reactive hyperemia, and an acute oral antioxidant cocktail (AOC; vitamins C and E and α-lipoic acid), this study aimed to provide greater insight into altered vascular function and the role of oxidative stress in chronic heart failure patients with reduced ejection fraction (HFrEF) and at several time points beyond heart transplantation (HTx). A total of 61 age-matched subjects (12 healthy controls, 14 New York Heart Association class II and III HFrEF, and 35 HTx recipients [\u3c3 years post-HTx, 5-10 years post-HTx, and \u3e14 years post-HTx]) ingested either placebo (PL) or an AOC before FMD and reactive hyperemia testing of the brachial artery. Vascular function, as measured by FMD, was not different among the controls (6.8±1.9%), recent \u3c3-year post-HTx group (8.1±1.2%), and the 5- to 10-year post-HTx group (5.5±1.0%). However, PL FMD was lower in the HFrEF (4.5±0.7%) and in the \u3e14-year post-HTx group (2.9±0.8%). The AOC increased plasma ascorbate levels in all of the groups but only increased FMD in the controls (PL, 6.8±1.9%; AOC, 9.2±1.0%) and \u3e14-year post-HTx recipients (PL, 2.9±0.8%; AOC, 4.5±1.3%). There were no differences in reactive hyperemia in any of the groups with PL or AOC. This cross-sectional study reveals that, compared with controls, vascular function is blunted in HFrEF, is similar soon after HTx, but is decreased with greater time post-HTx with free radicals implicated in this progression

Acute Reversal of Endothelial Dysfunction in the Elderly After Antioxidant Consumption

Aging is associated with a pro-oxidant state and a decline in endothelial function. Whether acute, enteral antioxidant treatment can reverse this decrement in vascular function is not well known. Flow-mediated vasodilation and reactive hyperemia were evaluated after consumption of either placebo or an oral antioxidant cocktail (vitamin C, 1000 mg; vitamin E, 600 IU; α-lipoic acid, 600 mg) in 87 healthy volunteers (42 young: 25±1 years; 45 older: 71±1 years) using a double-blind, crossover design. Blood velocity and brachial artery diameter (ultrasound Doppler) were assessed before and after 5-minute forearm circulatory arrest. Serum markers of lipid peroxidation, total antioxidant capacity, endogenous antioxidant activity, and vitamin C were assayed, and plasma nitrate, nitrite, and 3-nitrotyrosine were determined. In the placebo trial, an age-related reduction in brachial artery vasodilation was evident (young: 7.4±0.6%; older: 5.2±0.4%). After antioxidant consumption, flow-mediated vasodilation improved in older subjects (placebo: 5.2±0.4%; antioxidant: 8.2±0.6%) but declined in the young (placebo: 7.4±0.6%; antioxidant: 5.8±0.6%). Reactive hyperemia was reduced with age, but antioxidant administration did not alter the response in either group. Together, these data demonstrate that antioxidant consumption acutely restores endothelial function in the elderly while disrupting normal endothelium-dependent vasodilation in the young and suggest that this age-related impairment is attributed, at least in part, to free radicals

Taming the Sleeping Giant : The Role of Endothelin-1 in the Regulation of Skeletal Muscle Blood Flow and Arterial Blood Pressure during Exercise

The cardiovascular response to exercise is governed by a combination of vasodilating and vasoconstricting influences that optimize exercising muscle perfusion while protecting mean arterial pressure (MAP). The degree to which endogenous endothelin (ET)-1, the body\u27s most potent vasoconstrictor, participates in this response is unknown. Thus, in eight young (24 ± 2 yr), healthy volunteers, we examined leg blood flow, MAP, tissue oxygenation, heart rate, leg arterial-venous O2 difference, leg O2 consumption, pH, and net ET-1 and lactate release at rest and during knee extensor exercise (0, 5, 10, 15, 20, and 30 W) before and after an intra-arterial infusion of BQ-123 [ET subtype A (ETA) receptor antagonist]. At rest, BQ-123 did not evoke a change in leg blood flow or MAP. During exercise, net ET-1 release across the exercising leg increased approximately threefold. BQ-123 increased leg blood flow by ∼20% across all work rates (changes of 113 ± 76, 176 ± 83, 304 ± 108, 364 ± 130, 502 ± 117, and 570 ± 178 ml/min at 0, 5, 10, 15, 20, and 30 W, respectively) and attenuated the exercise-induced increase in MAP by ∼6%. The increase in leg blood flow was accompanied by a ∼9% increase in leg O2 consumption with an unchanged arterial-venous O2 difference and deoxyhemoglobin, suggesting a decline in intramuscular efficiency after ETA receptor blockade. Together, these findings identify a significant role of the ET-1 pathway in the cardiovascular response to exercise, implicating vasoconstriction via the ETA receptor as an important mechanism for both the restraint of blood flow in the exercising limb and maintenance of MAP in healthy, young adults

Endogenous Endothelin-1 and Femoral Artery Shear Rate: Impact of Age and Implications for Atherosclerosis

Background: Both altered shear rate and endothelin-1 (ET-1) are associated with the age-related development of atherosclerosis. However, the role of ET-1, a potent endogenous vasoconstrictor, in altering shear rate in humans, especially in the atherosclerotic-prone vasculature of the leg, is unknown. Therefore, this study examined the contribution of ET-1 to the age-related alterations in common femoral artery (CFA) shear rate. Method: BQ-123, a specific endothelin type A (ETA) receptor antagonist, was infused into the CFA, and diameter and blood velocity were measured by Doppler ultrasound in young (n = 8, 24 ± 2 years) and old (n = 9, 70 ± 2 years) study participants. Results and conclusion: The old had greater intima–media thickening in the CFA, indicative of a preatherogenic phenotype. Prior to infusion, the old study participants exhibited reduced mean shear rate (27 ± 3/s) compared with the young study participants (62 ± 9/s). This difference was likely driven by attenuated antegrade shear rate in the old as retrograde shear rate was similar in the young and old. Inhibition of ETA receptors, by BQ-123, increased leg blood flow in the old, but not in the young, abolishing age-related differences. Older study participants had a larger CFA (young: 0.82 ± 0.03 cm, old: 0.99 ± 0.03 cm) in which BQ-123 induced significant vasodilation (5.1 ± 1.0%), but had no such effect in the young (−0.8 ± 0.8%). Interestingly, despite the age-specific, BQ-123-induced increase in leg blood flow and CFA diameter, shear rate patterns remained largely unchanged. Therefore, ET-1, acting through the ETA receptors, exerts a powerful age-specific vasoconstriction. However, removal of this vasoconstrictor stimulus does not augment mean shear rate in the old

Angiotensin II Potentiates α-adrenergic Vasoconstriction in the Elderly

Aging is characterized by increased sympatho-excitation, expressed through both the α-adrenergic and RAAS (renin-angiotensin-aldosterone) pathways. Although the independent contribution of these two pathways to elevated vasoconstriction with age may be substantial, significant cross-talk exists that could produce potentiating effects. To examine this interaction, 14 subjects (n=8 young, n=6 old) underwent brachial artery catheterization for administration of AngII (angiotensin II; 0.8-25.6 ng/dl per min), NE [noradrenaline (norepinephrine); 2.5-80 ng/dl per min] and AngII with concomitant α-adrenergic antagonism [PHEN (phentolamine); 10 μg/dl per min]. Ultrasound Doppler was utilized to determine blood flow, and therefore vasoconstriction, in both infused and contralateral (control) limbs. Arterial blood pressure was measured directly, and sympathetic nervous system activity was assessed via microneurography and plasma NE analysis. AngII sensitivity was significantly greater in the old, indicated by both greater maximal vasoconstriction (-59±4% in old against -48±3% in young) and a decreased EC50 (half-maximal effective concentration) (1.4±0.2 ng/dl per min in old against 2.6±0.7 μg/dl per min in young), whereas the maximal NE-mediated vasoconstriction was similar between these groups (-58±9% in old and -62±5% in young). AngII also increased venous NE in the old group, but was unchanged in the young group. In the presence of α-adrenergic blockade (PHEN), maximal AngII-mediated vasoconstriction in the old was restored to that of the young (-43±8% in old and -39±6% in young). These findings indicate that, with healthy aging, the increased AngII-mediated vasoconstriction may be attributed, in part, to potentiation of the α-adrenergic pathway, and suggest that cross-talk between the RAAS and adrenergic systems may be an important consideration in therapeutic strategies targeting these two pathways

Oral Antioxidants Improve Leg Blood Flow during Exercise in Patients with Chronic Obstructive Pulmonary Disease

The consequence of elevated oxidative stress on exercising skeletal muscle blood flow as well as the transport and utilization of O2 in patients with chronic obstructive pulmonary disease (COPD) is not well understood. The present study examined the impact of an oral antioxidant cocktail (AOC) on leg blood flow (LBF) and O2 consumption during dynamic exercise in 16 patients with COPD and 16 healthy subjects. Subjects performed submaximal (3, 6, and 9 W) single-leg knee extensor exercise while LBF (Doppler ultrasound), mean arterial blood pressure, leg vascular conductance, arterial O2 saturation, leg arterial-venous O2 difference, and leg O2 consumption (direct Fick) were evaluated under control conditions and after AOC administration. AOC administration increased LBF (3 W: 1,604 ± 100 vs. 1,798 ± 128 ml/min, 6 W: 1,832 ± 109 vs. 1,992 ± 120 ml/min, and 9W: 2,035 ± 114 vs. 2,187 ± 136 ml/min, P \u3c 0.05, control vs. AOC, respectively), leg vascular conductance, and leg O2 consumption (3 W: 173 ± 12 vs. 210 ± 15 ml O2/min, 6 W: 217 ± 14 vs. 237 ± 15 ml O2/min, and 9 W: 244 ± 16 vs 260 ± 18 ml O2/min, P \u3c 0.05, control vs. AOC, respectively) during exercise in COPD, whereas no effect was observed in healthy subjects. In addition, the AOC afforded a small, but significant, improvement in arterial O2 saturation only in patients with COPD. Thus, these data demonstrate a novel beneficial role of AOC administration on exercising LBF, O2 consumption, and arterial O2 saturation in patients with COPD, implicating oxidative stress as a potential therapeutic target for impaired exercise capacity in this population