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Engineered muscle tissues represent powerful tools for examining tissue level contractile properties of skeletal muscle. However, limitations in the throughput associated with standard analysis methods limit their utility for longitudinal study, high throughput drug screens, and disease modeling. Here we present a method for integrating 3D engineered skeletal muscles with a magnetic sensing system to facilitate non-invasive, longitudinal analysis of developing contraction kinetics. Using this platform, we show that engineered skeletal muscle tissues derived from both induced pluripotent stem cell and primary sources undergo improvements in contractile output over time in culture. We demonstrate how magnetic sensing of contractility can be employed for simultaneous assessment of multiple tissues subjected to different doses of known skeletal muscle inotropes as well as the stratification of healthy versus diseased functional profiles in normal and dystrophic muscle cells. Based on these data, this combined culture system and magnet-based contractility platform greatly broadens the potential for 3D engineered skeletal muscle tissues to impact the translation of novel therapies from the lab to the clinic., Competing Interests: Declaration of conflicting interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: A.S.T.S., N.J.S., and D.L.M. are scientific advisors for Curi Bio, Inc.; the company that commercializes the Mantarray device used in this study. S.M.L, K.G., D.L., J.W.F., N.C., B.J.B., E.C.F., and N.A.G. are employees and equity holders of Curi Bio. All other authors state that they have no conflict of interest (financial or otherwise) associated with this manuscript., (© The Author(s) 2022.)

The study of plant remains in archaeological sites, along with a better understanding of the use of plants by prehistoric populations, can help us shed light on changes in survival strategies of hunter-gatherers and consequent impacts on modern human cognition, social organization, and technology. The archaeological locality of Pinnacle Point (Mossel Bay, South Africa) includes a series of coastal caves, rock-shelters, and open-air sites with human occupations spanning the Acheulian through Middle Stone Age (MSA) and Later Stone Age (LSA). These sites have provided some of the earliest evidence for complex human behaviour and technology during the MSA. We used phytoliths-amorphous silica particles that are deposited in cells of plants-as a proxy for the reconstruction of past human plant foraging strategies on the south coast of South Africa during the Middle and Late Pleistocene, emphasizing the use and control of fire as well as other possible plant uses. We analysed sediment samples from the different occupation periods at the rock shelter Pinnacle Point 5-6 North (PP5-6N). We also present an overview of the taphonomic processes affecting phytolith preservation in this site that will be critical to conduct a more reliable interpretation of the original plant use in the rock shelter. Our study reports the first evidence of the intentional gathering and introduction into living areas of plants from the Restionaceae family by MSA hunter-gatherers inhabiting the south coast of South Africa. We suggest that humans inhabiting Pinnacle Point during short-term occupation events during Marine Isotope Stage (MIS) 5 built fast fires using mainly grasses with some wood from trees and/or shrubs for specific purposes, perhaps for shellfish cooking. With the onset of MIS 4 we observed a change in the plant gathering strategies towards the intentional and intensive exploitation of dry wood to improve, we hypothesise, combustion for heating silcrete. This human behaviour is associated with changes in stone tool technology, site occupation intensity and climate change., Competing Interests: The authors have declared that no competing interests exist.

Approximately 74 thousand years ago (ka), the Toba caldera erupted in Sumatra. Since the magnitude of this eruption was first established, its effects on climate, environment and humans have been debated. Here we describe the discovery of microscopic glass shards characteristic of the Youngest Toba Tuff-ashfall from the Toba eruption-in two archaeological sites on the south coast of South Africa, a region in which there is evidence for early human behavioural complexity. An independently derived dating model supports a date of approximately 74 ka for the sediments containing the Youngest Toba Tuff glass shards. By defining the input of shards at both sites, which are located nine kilometres apart, we are able to establish a close temporal correlation between them. Our high-resolution excavation and sampling technique enable exact comparisons between the input of Youngest Toba Tuff glass shards and the evidence for human occupation. Humans in this region thrived through the Toba event and the ensuing full glacial conditions, perhaps as a combined result of the uniquely rich resource base of the region and fully evolved modern human adaptation.

The south coast of South Africa provides the earliest evidence for Middle Stone Age (MSA) coastal resource exploitation by early Homo sapiens. In coastal archaeology worldwide, there has been a debate over the general productivity of intertidal foraging, leading to studies that directly measure productivity in some regions, but there have been no such studies in South Africa. Here we present energetic return rate estimates for intertidal foraging along the southern coast of South Africa from Blombos Cave to Pinnacle Point. Foraging experiments were conducted with Khoi-San descendants of the region, and hourly caloric return rates for experienced foragers were measured on 41 days near low tide and through three seasons over two study years. On-site return rates varied as a function of sex, tidal level, marine habitat type and weather conditions. The overall energetic return rate from the entire sample (1492 kcal h(-1)) equals or exceeds intertidal returns reported from other hunter-gatherer studies, as well as measured return rates for activities as diverse as hunting mammals and plant collecting. Returns are projected to be exceptionally high (∼ 3400 kcal h(-1) for men, ∼ 1900 kcal h(-1) for women) under the best combination of conditions. However, because of the monthly tidal cycle, high return foraging is only possible for about 10 days per month and for only 2-3 h on those days. These experiments suggest that while intertidal resources are attractive, women and children could not have subsisted independently, nor met all their protein-lipid needs from marine resources alone, and would have required substantial additional energy and nutrients from plant gathering and/or from males contributing game., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Using fine and coarse resolution geoarchaeological studies at the Middle Stone Age site of PP5-6 at Pinnacle Point, Mossel Bay, South Africa, we discovered different patterns of anthropogenic input and changes in behavior through time. Through the microfacies approach, we documented the various geogenic and anthropogenic processes that formed the deposits of the site. By deciphering large scale rate differences in the production of these microfacies we estimated anthropogenic input rates and therefore gained understanding of occupational duration and intensity. The PP5-6 sediments document occupations characterized by small groups and short visits during Marine Isotope Stage (MIS) 5. This part of the sequence is characterized by numerous single (and mostly intact) hearth structures in a roofspall-rich matrix. During this time the sea was very close to the site and the people were focused on exploiting the rocky shores. With the advent of the glacial conditions of MIS4, the occupation of the site became much more intense. The occurrence of thick palimpsests of burnt remains, sometimes disturbed by small-scale sedimentary gravity processes, supports this conclusion. As sea level dropped and the coastline retreated, the geogenic input shifted to predominately aeolian sediments, implying an exposed shelf probably associated with a rich but more distant coastal environment. The occupants of PP5-6 turned their preference to silcrete as a raw material and they began to make microlithic stone tools. Since sites dating to MIS4 are abundant in the Cape, we suggest that populations during MIS4 responded to glacial conditions with either demographic stability or growth as well as technological change., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Cardiac surgery associated acute kidney injury (CSA-AKI) is associated with poor outcomes including increased mortality, length of hospital stay (LOS) and cost. The incidence of acute kidney injury (AKI) is reported to be between 3 and 30% depending on the definition of AKI. We designed a multicenter randomized controlled trial to test our hypothesis that a perioperative infusion of sodium bicarbonate (SB) during cardiac surgery will attenuate the post-operative rise in creatinine indicating renal injury when compared to a perioperative infusion with normal saline. An interim analysis was performed after data was available on the first 120 participants. A similar number of patients in the two treatment groups developed AKI, defined as an increase in serum creatinine the first 48 h after surgery of 0.3 mg/dl or more. Specifically 14 patients (24%) who received sodium chloride (SC) and 17 patients (27%) who received SB were observed to develop AKI post-surgery, resulting in a relative risk of AKI of 1.1 (95% CI: 0.6-2.1, chi-square p-value = 0.68) for patients receiving SB compared to those who received SC. The data safety monitoring board for the trial recommended closing the study early as there was only a 12% probability that the null hypothesis would be rejected. We therefore concluded that a perioperative infusion of SB failed to attenuate the risk of CSA-AKI.

There is consensus that the modern human lineage appeared in Africa before 100,000 years ago. But there is debate as to when cultural and cognitive characteristics typical of modern humans first appeared, and the role that these had in the expansion of modern humans out of Africa. Scientists rely on symbolically specific proxies, such as artistic expression, to document the origins of complex cognition. Advanced technologies with elaborate chains of production are also proxies, as these often demand high-fidelity transmission and thus language. Some argue that advanced technologies in Africa appear and disappear and thus do not indicate complex cognition exclusive to early modern humans in Africa. The origins of composite tools and advanced projectile weapons figure prominently in modern human evolution research, and the latter have been argued to have been in the exclusive possession of modern humans. Here we describe a previously unrecognized advanced stone tool technology from Pinnacle Point Site 5-6 on the south coast of South Africa, originating approximately 71,000 years ago. This technology is dominated by the production of small bladelets (microliths) primarily from heat-treated stone. There is agreement that microlithic technology was used to create composite tool components as part of advanced projectile weapons. Microliths were common worldwide by the mid-Holocene epoch, but have a patchy pattern of first appearance that is rarely earlier than 40,000 years ago, and were thought to appear briefly between 65,000 and 60,000 years ago in South Africa and then disappear. Our research extends this record to ~71,000 years, shows that microlithic technology originated early in South Africa, evolved over a vast time span (~11,000 years), and was typically coupled to complex heat treatment that persisted for nearly 100,000 years. Advanced technologies in Africa were early and enduring; a small sample of excavated sites in Africa is the best explanation for any perceived 'flickering' pattern.

This paper aims to identify the spatial patterning of burning and occupation within an early Middle Stone Age (MSA) sea cave in the Western Cape Province of South Africa by creating a multidimensional model of archaeomagnetic data recovered from all excavated units. Magnetic susceptibility and other mineral magnetic parameters are shown to provide an excellent proxy for the anthropogenic alteration and spread of burnt material into the surrounding unaltered cave deposits. The identification of combustion features and areas of occupation or different activities within the site can be determined because the movement of people throughout the cave mixes magnetically strong hearth material with magnetically weak unaltered sediments. This is also indicated by micromorphological analysis. The degree of enhancement is also shown to indicate the extent to which a deposit has been altered, and therefore, intensity of occupation, because multiple heatings of deposits are needed to form the concentrations of iron minerals occurring in some layers. This is further supported by a comparison with artifact density for the layers. Variation in the magnetic values between different areas of the site is noted with major occupation or fire building occurring in the front of the cave during earlier MIS 6 periods, while during later MIS 5 periods the entire cave is occupied intensively. The oldest, MIS 11 deposits at the rear of the cave indicate no evidence of enhancement and an apparent absence of any anthropogenic signature., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

The emission of blue-green bioluminescence ({lambda}max = 470 nm) was observed from sucker-like structures arranged along the length of the arms of the cirrate octopod Stauroteuthis syrtensis. Individual photophores either glowed dimly and continuously or flashed on and off more brightly with a period of 1-2 seconds. Examination of the anatomy and ultrastructure of the photophores confirmed that they are modified suckers. During handling, the photophores were unable to attach to surfaces, suggesting that, unlike typical octopod suckers, they have no adhesive function. The oral position of the photophores and the wavelength of peak emission, coupled with the animals' primary postures, suggests that bioluminescence in S. syrtensis may function as a light lure to attract prey.

Cell culture procedures were developed for use with surgical and normal control specimens of the annulus of the human intervertebral disc. Cells were established in monolayer explant culture and seeded into three-dimensional growth environments of alginate or agarose; under these growth conditions cells assumed a rounded phenotype and formed colonies. A novel method of layering suspensions of cells onto cell well inserts proved technically much easier than the microbead culture method. Immunohistochemistry was utilized to demonstrate in vitro production of the following extracellular matrix components: types I, II, III, and VI collagen, 4-S-chondroitin sulfate, and keratan sulfate. Young and old age- and gender-matched cells grown in the presence of TGF-beta1 showed significant enhancement of proliferation after 4 days of exposure to TGF-beta with a lessened mitogenic response present after 10 days. Molecular studies of proteoglycan gene expression showed that at 4 days young normal cells had increased biglycan, but not decorin, message levels. Decorin expression was unchanged at Day 4 and decreased or shut off by Day 10. Results support the use of three-dimensional culture systems for in vitro evaluation of human disc cell function and expand our understanding of the in vitro behavior of these cells.

A decline in insulin sensitivity is associated with aging, inactivity, and obesity. The effects of exercise training on glucose homeostasis independent of weight loss in older glucose-intolerant individuals are not well established. We examined the effects of exercise training on oral glucose tolerance, insulin action, and concentration of the GLUT-4 glucose transporters in skeletal muscle. Exercise training at 50 and 75% of heart rate reserve was performed for 12 wk in 18 individuals (age = 64 +/- 2, body fat = 37.0 +/- 1.5%). Peripheral insulin action was determined 96 h after the last exercise bout using a two-step hyperinsulinemic-euglycemic glucose clamp (insulin = 192 and 708 pmol/l). Percent body fat and fat-free mass (FFM) were unchanged with training. Diet composition, assessed by diet record, did not change over the 12 wk. Improved oral glucose tolerance was observed, as exhibited by lower plasma glucose concentrations after training (P < 0.05), whereas plasma insulin response remained unchanged. The rate of glucose disposal was unchanged during the low insulin concentration but increased 11.0% at the high insulin concentration (P < 0.05) after training (54.4 +/- 4.4 vs. 60.4 +/- 5.5 mumol.kg FFM-1.min-1). Skeletal muscle glycogen and GLUT-4 concentration increased 24 and 60%, respectively, with training. There was no direct relationship between the change in GLUT-4 protein and the change in glucose disposal rate. These findings demonstrate that chronic exercise training without changes in body composition improves peripheral insulin action in subjects with impaired glucose tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of 12 wk of endurance training at 70% peak O2 consumption (VO2) were studied in 10 elderly (65.1 +/- 2.9 yr) and 10 young (23.6 +/- 1.8 yr) healthy men and women. Training had no effect on weight or body composition in either group. The elderly had more adipose tissue and less muscle mass than the young. Initial peak VO2 was lower in the elderly, but the absolute increase of 5.5-6.0 ml.kg-1.min-1 after training was similar for both groups. Muscle biopsies taken at rest showed that, before training, muscle glycogen stores were 61% higher in the young. Before training, glycogen utilization per joule during submaximal exercise was higher in the elderly. Glycogen stores and muscle O2 consumption increased significantly in response to training in the elderly only. After training, the proportion of energy derived from whole body carbohydrate oxidation during submaximal exercise declined in the young only. The absolute changes that training produced in peak VO2 were similar in both age groups, but the 128% increase in muscle oxidative capacity was greater in the elderly, suggesting that peripheral factors play an important role in the response of the elderly to endurance exercise.

Substrate utilization after fructose, glucose, or water ingestion was examined in four male and four female subjects during three treadmill runs at approximately 75% of maximal O2 uptake. Each test was preceded by three days of a carbohydrate-rich diet. The runs were 30 min long and were spaced at least 1 wk apart. Exercise began 45 min after ingestion of 300 ml of randomly assigned 75 g fructose (F), 75 g glucose (G), or control (C). Muscle glycogen depletion determined by pre- and postexercise biopsies (gastrocnemius muscle) was significantly (P less than 0.05) less during the F trial than during C or G. Venous blood samples revealed a significant increase in serum glucose (P less than 0.05) and insulin (P less than 0.01) within 45 min after the G drink, followed by a decrease (P less than 0.05) in serum glucose during the first 15 min of exercise, changes not observed in the C or F trials. Respiratory exchange ratio was higher (P less than 0.05) during the G than C or F trials for the first 5 min of exercise and lower (P less than 0.05) during the C trial compared with G or F for the last 15 min of exercise. These data suggest that fructose ingested before 30 min of submaximal exercise maintains stable blood glucose and insulin concentrations, which may lead to the observed sparing of muscle glycogen.

Serum gonadotropin and estrogen levels and their relationship to bone mineral content in exercise-related amenorrhea were studied in 11 amenorrheic women and 24 eumenorrheic women, all of whom were runners. Serum estradiol, LH, FSH, estrone, and testosterone were measured in serial blood samples obtained at 15-min intervals for 4 h. The amenorrheic women had lower estradiol, LH, FSH; and estrone levels as well as a higher estrone-estradiol ratio than did the eumenorrheic women. There was no difference in testosterone levels. The amenorrheic women had lower LH pulse amplitudes, whereas no differences were found in FSH pulse amplitudes. LH and FSH pulse frequencies did not differ between the two groups. Bone mineral content of the lumbar spine was lower in amenorrheic women and was positively correlated with estradiol levels in all women. There was no difference in bone mineral content of the radius. These data suggest that, in exercise-related amenorrhea, low serum LH, FSH, and estrogen levels reflect an alteration in the hypothalamic control of gonadotropin release. Reduced circulating estrogen levels in amenorrheic running women may be a cause of low mineral content of the spine.

Habitual physical exercise has been reported to have beneficial effects on plasma lipoproteins. To examine this question in women, plasma cholesterol, triglyceride, and apolipoprotein (apo) A-I and B levels, and low density lipoprotein (LDL) particle size were determined in 25 women runners (9 of whom had exercise-related secondary amenorrhea) and 36 age-matched nonexercising women (controls). The eumenorrheic runners had significantly lower apo B levels and significantly greater mean apo A-I/apo B ratios and LDL particle sizes than did the control women (P less than 0.05). Lower apo B levels were correlated with decreased body mass index, a known exercise effect (P less than 0.0001). In addition, normally menstruating runners had cholesterol and triglyceride levels that were 7.6% and 25.4% lower, respectively, and apo A-I levels that were 6.4% higher than control women (P = NS). In amenorrheic runners all parameters were similar to values in control women, except that apo B levels were 20% lower (P less than 0.05). Amenorrheic runners had lower plasma apo A-I levels (13%) and significantly lower apo A-I/apo B ratios and estradiol levels than eumenorrheic runners, and serum estradiol values in the runners were correlated with apo A-I levels (P less than 0.01). These data indicate that the beneficial effects of strenuous exercise on plasma apo A-I levels and apo A-I/apo B ratios in women runners can be reversed by exercise-induced amenorrhea and decreased serum estradiol levels, and that women runners have lower apo B levels than nonexercising women, regardless of menstrual status.

The influence of short-term high-altitude (HA) residence on intramuscular pH and skeletal muscle enzyme activity of sea-level (SL) residents was investigated. Vastus lateralis muscle samples were obtained by biopsy from rested subjects (n = 5) at SL (50 m) and on the 18th day of HA residence (4,300 m) for determination of glycogen phosphorylase, hexokinase, malate dehydrogenase, and total lactate dehydrogenase activities. A second group of subjects (n = 6) performed cycle exercise of the same absolute intensity (mean +/- SE = 195 +/- 5 W) at SL and on the 15th day of residence at HA. Before and immediately after exercise, vastus lateralis muscle samples were obtained for the determination of intramuscular pH, and venous blood was obtained for determination of lactate concentration. The first group of subjects showed no significant changes in skeletal muscle enzyme activity after 18 days at HA. The second group of subjects were instructed to exercise for exactly 30 min, and all but one could complete the entire bout at SL. However, at HA, none could continue 30 min, and time to exhaustion (mean +/- SE) was 11.9 +/- 1.6 min. Resting intramuscular pH was not significantly different after HA residence as compared to SL. The fall in intramuscular pH was less with exercise on day 15 at HA than during SL exercise. Likewise, the increase in blood lactate concentration with exercise at HA was less than at SL. These data indicate that, after 15-18 days of HA residence, limitations in exercise performance are not due to inordinate intramuscular acidosis or to changes in the activity of glycolytic and oxidative enzymes.