Retrieving autobiographical memories in autobiographical contexts: are age-related differences in narrated episodic specificity present outside of the laboratory?

The Autobiographical Interview, a method for evaluating detailed memory of real-world events, reliably detects differences in episodic specificity at retrieval between young and older adults in the laboratory. Whether this age-associated reduction in episodic specificity for autobiographical event retrieval is present outside of the laboratory remains poorly understood. We used a videoconference format to administer the Autobiographical Interview to cognitively unimpaired older adults (N = 49, M = 69.5, SD = 5.94) and young adults (N = 54, M = 22.5, SD = 4.19) who were in their homes at the time of retrieval. Relative to young adults, older adults showed reduced episodic specificity in their home environment, as reflected by fewer episodic or "internal" details (t (101) = 3.23, p = 0.009) and more "external" details (i.e., semantic, language-based details) (t (101) = 3.60, p = 0.003). These findings, along with detail subtype profiles in the narratives, bolster the ecological validity of the Autobiographical Interview and add promise to the use of virtual cognitive testing to improve the accessibility, participant diversity, scalability, and ecological validity of memory research.

Protocol to Induce the Temporary Opening of the Blood-Brain Barrier with Short-Time Focused Ultrasound in Rats.

Brain neurodegenerative diseases are central nervous system (CNS) affections typically common in older adults. A new therapeutic approach for them consists of providing specific drugs to the CNS through blood circulation; however, the Blood-Brain Barrier (BBB) prevents almost 100% of neurotherapeutics from reaching the brain. There are indications that Focused Ultrasound (FUS), temporarily placed in the BBB, can achieve a controlled increase in temperature at its focus, allowing temporary, localized, and reversible opening of this barrier, which facilitates the temporary delivery of specific drugs. This work presents a FUS-based protocol for the local, temporary, and reversible opening of the BBB in Wistar rats. The proposed protocol specifies certain power, treatment times, and duty cycle to controllably increase the temperature at the region of interest, i.e., the substantia nigra. Numerical simulations using commercial software based on the finite element method were carried out to determine the optimal size of the craniotomies for nearly full-acoustic transmission. Experiments in rats were performed with the parameters used during computational simulations to determine the adequate opening of the BBB. For this, craniotomies of different sizes were made at coordinates of the substantia nigra, and FUS was applied from the exterior. The opening of the BBB was evaluated using Evans Blue (EB) as an indicator of the crossing of the dye from the blood vessels to brain tissue. Numerical simulations demonstrated a major distance reached by the ultrasound focus with a bigger diameter. Experimental results show the local, temporary, and reversible opening of the BBB through a 10 mm diameter craniotomy, which effectively allowed placing the ultrasound focus over the substantia nigra, unlike a 6 mm diameter craniotomy in which there is a deviation of the focus through that window. Moreover, from these results, it was also determined that the disruption of the BBB was reversible, with an opening duration of 6 h after FUS application. The experimental work developed in this study resulted in a minimally invasive method for the temporary opening of the BBB.

Approaches for the enzymatic synthesis of alkyl hydroxycinnamates and applications thereof.

Alkyl hydroxycinnamates (AHs) is a group of molecules of biotechnological interest due to their cosmetic, food, and pharmaceutical applications. Among their most interesting uses are as UV protectants, skin depigmentation agents, and antioxidant ingredients which are often claimed for their antitumoral potential. Nowadays, many sustainable enzymatic approaches using low-cost starting materials are available and interesting immobilization techniques are helping to increase the reuse of the biocatalysts, allowing the intensification of the processes and increasing AHs accessibility. Here a convenient summary of AHs most interesting biological activities and possible applications is presented. A deeper analysis of the art state to obtain AHs, focusing on most employed enzymatic synthesis approaches, their sustainability, acyl donors relevance, and most interesting enzyme immobilization strategies is provided.Key points• Most interesting alkyl hydroxycinnamates applications are summarized.• Enzymatic approaches to obtain alkyl hydroxycinnamates are critically discussed.• Outlook of enzyme immobilization strategies to attain alkyl hydroxycinnamates.

Carrier-bound and carrier-free immobilization of type A feruloyl esterase from Aspergillus niger: Searching for an operationally stable heterogeneous biocatalyst for the synthesis of butyl hydroxycinnamates.

Feruloyl esterases synthesize butyl hydroxycinnamates, molecules possessing interesting biological properties, nonetheless, they exhibit a low stability under synthesis conditions in organic solvents, restricting its use. To enhance its operational stability in synthesis, we immobilized type A feruloyl esterase from Aspergillus niger (AnFAEA) using several carrier-bound and carrier-free strategies. The most active biocatalysts were: 1) AnFAEA immobilized on epoxy-activated carriers (protein load of 0.6 mgenzyme x mg-1carrier) that recovered 91 % of the initial hydrolytic activity, and 2) AnFAEA aggregated and cross-linked in the presence of 5 mg of BSA and 15 mM of glutaraldehyde (AnFAEA-amino-CLEAs), which exhibited 385 % of its initial hydrolytic activity; both using 4-nitrophenyl butyrate as substrate. The AnFAEA-amino-CLEAs were 12.7 times more thermostable at 60 °C than the AnFAEA immobilized on epoxy-activated carrier, thus AnFAEA-amino-CLEAs were selected for further characterization. Interestingly, during methyl sinapate hydrolysis (pH 7.2 and 30 °C), AnFAEA-amino-CLEAs KM was 15 % higher, while during butyl sinapate synthesis the KM was reduced in 63 %, both compared with the soluble enzyme. The direct esterification of butyl sinapate at solvent free conditions using sinapic acid 50 mM, reached 95 % conversion after 24 h employing AnFAEA-amino-CLEAs, which could be used for 10 cycles without significant activity losses, demonstrating their outstanding operational stability.

Nebulette is a powerful cytolinker organizing desmin and actin in mouse hearts.

In the hearts of patients bearing nebulette mutations, a severe general disorganization in cardiomyocytes of the extrasarcomeric desmin intermediate filament system is frequently observed. However, the molecular and functional relationship between the desmin cytoskeleton and nebulette-containing sarcomeres is still unclear. Here we report a high-affinity in vitro interaction between nebulette and desmin filaments. A major interaction site has been mapped to the desmin α-helical rod domain, indicating that the filament core is directly involved in the binding of nebulette. The disease-mutant desmin variants E245D and T453I exhibited increased binding affinity for nebulette, delayed filament assembly kinetics, and caused significant weakening of networks. In isolated chick cardiomyocytes and sections from canine heart, we revealed by ground-state depletion and confocal microscopies that module 5 of nebulette extends outward from Z-disk-associated desmin filaments toward the center of the sarcomere. Accordingly, in the myocardium of Des-/- mice, elevated levels of cardiac actin correlated with alterations in the distribution of nebulette. Our data suggest that a well-organized desmin network is required to accommodate an optimal conformation of nebulette on sarcomeres to bind and recruit cardiac α-actin. Hence we propose that nebulette acts in synergy with nebulin to reinforce and temporally fine-tune striated muscle relaxation-contraction cycles.

Metabolic responses to the seated calf press exercise performed against inertial resistance.

INTRODUCTION: Future in-flight strength training devices may use inertial resistance to abate mass and strength losses to muscle groups such as the triceps surae, which incurs pronounced deficits from space travel. Yet little data exist regarding physiological outcomes to triceps surae exercise performed against inertial resistance. Two sets of subjects were employed to note either blood lactate (La-) or net caloric cost responses to seated calf presses done on an inertial resistance ergometer. METHODS: Both sets of subjects performed 3 identical 3-set 10-repetition workouts. Blood La- measurements were made pre- and 5 min post-exercise. During workouts, breath-by-breath O2 uptake values were also recorded to help determine the net caloric cost of exercise. RESULTS: Compared to pre-exercise (mean +/- SEM) blood La- (2.01 +/- 0.08 mmol x L(-1)) values, post-exercise (4.73 +/- 0.24 mmol x L(-1)) measurements showed a significant increase. Delta (post/pre differences) La- correlated significantly (r = 0.31-0.34) to several workout performance measures. Net caloric cost averaged 52.82 +/- 3.26 kcals for workouts; multivariate regression showed a subject's height, body mass, and body surface area described the variance associated with energy expenditure. CONCLUSIONS: Workouts evoked minimal energy expenditure, though anaerobic glycolysis likely played a major role in ATP resynthesis. Metabolic and exercise performance measures were likely influenced by series elastic element involvement of the triceps surae-Achilles tendon complex. Ergometer calf presses provided a high-intensity workout stimulus with a minimal metabolic cost.

A comparison of isoload and isoinertial leg press training on bone and muscle outcomes.

The subjects of this study (n = 20; 16 women, 4 men) performed 10 weeks of leg press training using one of two exercise modes (isoload or isotonic) with no crossover. Their workouts, which were performed 3 times per week, involved 4 sets of 8 repetitions with maximal voluntary effort. Testing was performed pre- and posttraining to examine bone and muscle changes. Posttraining, both groups incurred significant concentric knee extensor strength and leg muscle mass gains, while the percentage of body fat and total body fat mass each decreased. Leg and total body bone mineral densities showed group-by-time interactions, as isoload exercise caused posttraining gains, while isoinertial values were unchanged. Bone resorption assays showed insignificant changes. Isoload training likely involved greater strain magnitudes and rates to evoke higher peak forces and osteogenesis. Transduction of the training stimulus may have involved (a) formation in response to microdamage, and (b) piezoelectric-induced potentials that stimulated site-specific osteoblast activity and osteogenesis.

Inclusion of eccentric actions on net caloric cost resulting from isoinertial resistance exercise.

Net O(2) uptake was measured from maximal-effort 3-set, 8-repetition seated leg press protocols on an isoinertial ergometer. Subjects (25 women, 9 men) did 2 workouts each exerting concentric-eccentric (CE) and concentric-only (CO) knee extensor forces to measure work and net caloric cost. Significant (p < 0.05) relationships between work and net caloric cost resulted from CE and CO workouts for the male, female, and total subject sample. Two-way repeated-measures analyses of variance showed CE workouts resulted in significantly higher work but not net caloric cost and values. CE workouts likely relied on the knee extensors series elastic element to perform an additional approximately 3,600 J of eccentric work at no additional net caloric cost. Unlike other exercise modes, maximal-effort eccentric actions on the isoinertial ergometer, as done in the current study, provide no additional net caloric cost and is thus safe to administer to populations in whom metabolic cost is a concern.

A multivariate approach to predicting knee extensor performance.

The impact of two predictor variables (estimated knee extensor fast-twitch fiber percentage, body mass) on performance measures (vertical jump power output, leg press peak angular velocity) were examined. Subjects (25 men, 27 women) performed 5 workouts involving 2 vertical jump, leg press, and 50-repetition isokinetic tests (to estimate knee extensor fast-twitch fiber percentage). Multivariate regression determined the following significant (p < 0.05) vertical jump equations: predicted male power output = -59.3464 + 1.566 (estimated knee extensor fast-twitch muscle fiber percent) + 15.7884 (body mass), predicted female power output = 36.1574 + 3.4248 (estimated knee extensor fast-twitch muscle fiber percent) + 9.8633 (body mass). Leg press peak angular velocity equations were insignificant by gender; thus, pooled data yielded the following: predicted leg press peak angular velocity = 18.6187 + 0.235 (estimated knee extensor fast-twitch muscle fiber percent) + 0.3801 (body mass). Body mass explained more variance for each performance measure.