Identification of caspase 3 motifs and critical aspartate residues in human Phospholipase D1b and Phopsholipase D2a

Stimulation of mammalian cells frequently initiates phospholipase D-catalysed hydrolysis of phosphatidylcholine in the plasma membrane to yield phosphatidic acid (PA) a novel lipid messenger. PA plays a regulatory role in important cellular processes such as secretion, cellular shape change and movement. A number of studies have highlighted that PLD-based signalling also plays a pro-mitogenic and pro-survival role in cells and therefore anti-apoptotic. We show that human PLD1b and PLD2a contain functional caspase-3 cleavage sites and identify the critical aspartate residues within PLD1b that affect its activation by phorbol esters and attenuate phosphatidylcholine hydrolysis during apoptosis

Adipocytes promote pancreatic cancer cell proliferation via glutamine transfer

AbstractAdipocytes promote progression of multiple cancers, but their role in pancreatic intraepithelial neoplasia (PanIN) and ductal adenocarcinoma (PDAC) is poorly defined. Nutrient transfer is a mechanism underlying stromal cell-cancer crosstalk. We studied the role of adipocytes in regulating in vitro PanIN and PDAC cell proliferation with a focus on glutamine metabolism. Murine 3T3L1 adipocytes were used to model adipocytes. Cell lines derived from PKCY mice were used to model PanIN and PDAC. Co-culture was used to study the effect of adipocytes on PanIN and PDAC cell proliferation in response to manipulation of glutamine metabolism. Glutamine secretion was measured with a bioanalyzer. Western blotting was used to study the effect of PanIN and PDAC cells on expression of glutamine-related enzymes in adipocytes. Adipocytes promote proliferation of PanIN and PDAC cells, an effect that was amplified in nutrient-poor conditions. Adipocytes secrete glutamine and rescue PanIN and PDAC cell proliferation in the absence of glutamine, an effect that was glutamine synthetase-dependent and involved PDAC cell-induced down-regulation of glutaminase expression in adipocytes. These findings suggest glutamine transfer as a potential mechanism underlying adipocyte-induced PanIN and PDAC cell proliferation

Number of prior live births is associated with higher arterial stiffness but not its change in older women: the atherosclerosis risk in communities study

Introduction Although studies have demonstrated a J-shaped association between parity and cardiovascular disease (CVD), the association with arterial stiffness is not fully understood. Methods We examined the association between parity and carotid-femoral pulse wave velocity (cfPWV), a measure of central arterial stiffness. We conducted a longitudinal analysis of 1220 women (mean age 73.7 years) who attended the Atherosclerosis Risk in Communities Study visit 5 (2011-2013). At visit 2 (1990-1992), women self-reported parity (number of prior live births), which we categorized as: 0 (never pregnant or pregnant with no live births); 1-2 (referent); 3-4; and 5+ live births. Technicians measured cfPWV at visit 5 (2011-2013) and visit 6 or 7 (2016-2019). Multivariable linear regression modeled the associations of parity with visit 5 cfPWV and cfPWV change between visit 5 and 6/7 adjusted for demographics and potential confounding factors. Results Participants reported 0 (7.7%), 1-2 (38.7%), 3-4 (40.0%), or 5+ (13.6%) prior live births. In adjusted analyses, women with 5+ live births had a higher visit 5 cfPWV (β=50.6 cm/s, 95% confidence interval: 3.6, 97.7 cm/s) than those with 1-2 live births. No statistically significant associations were observed for other parity groups with visit 5 cfPWV or with cfPWV change. Discussion In later life, women with 5+ live births had higher arterial stiffness than those with 1-2 live births, but cfPWV change did not differ by parity, suggesting women with 5+ live births should be targeted for early primary prevention of CVD given their higher arterial stiffness at later-life

Osseointegration of zirconia implants: an SEM observation of the bone-implant interface

Background The successful use of zirconia ceramics in orthopedic surgery led to a demand for dental zirconium-based implant systems. Because of its excellent biomechanical characteristics, biocompatibility, and bright tooth-like color, zirconia (zirconium dioxide, ZrO2) has the potential to become a substitute for titanium as dental implant material. The present study aimed at investigating the osseointegration of zirconia implants with modified ablative surface at an ultrastructural level. Methods A total of 24 zirconia implants with modified ablative surfaces and 24 titanium implants all of similar shape and surface structure were inserted into the tibia of 12 Gottinger minipigs. Block biopsies were harvested 1 week, 4 weeks or 12 weeks (four animals each) after surgery. Scanning electron microscopy (SEM) analysis was performed at the bone implant interface. Results Remarkable bone attachment was already seen after 1 week which increased further to intimate bone contact after 4 weeks, observed on both zirconia and titanium implant surfaces. After 12 weeks, osseointegration without interposition of an interfacial layer was detected. At the ultrastructural level, there was no obvious difference between the osseointegration of zirconia implants with modified ablative surfaces and titanium implants with a similar surface topography. Conclusion The results of this study indicate similar osseointegration of zirconia and titanium implants at the ultrastructural level

Computational ethics

Technological advances are enabling roles for machines that present novel ethical challenges. The study of 'AI ethics' has emerged to confront these challenges, and connects perspectives from philosophy, computer science, law, and economics. Less represented in these interdisciplinary efforts is the perspective of cognitive science. We propose a framework – computational ethics – that specifies how the ethical challenges of AI can be partially addressed by incorporating the study of human moral decision-making. The driver of this framework is a computational version of reflective equilibrium (RE), an approach that seeks coherence between considered judgments and governing principles. The framework has two goals: (i) to inform the engineering of ethical AI systems, and (ii) to characterize human moral judgment and decision-making in computational terms. Working jointly towards these two goals will create the opportunity to integrate diverse research questions, bring together multiple academic communities, uncover new interdisciplinary research topics, and shed light on centuries-old philosophical questions.publishedVersio

Technology-assisted stroke rehabilitation in Mexico: a pilot randomized trial comparing traditional therapy to circuit training in a Robot/technology-assisted therapy gym

Background Stroke rehabilitation in low- and middle-income countries, such as Mexico, is often hampered by lack of clinical resources and funding. To provide a cost-effective solution for comprehensive post-stroke rehabilitation that can alleviate the need for one-on-one physical or occupational therapy, in lower and upper extremities, we proposed and implemented a technology-assisted rehabilitation gymnasium in Chihuahua, Mexico. The Gymnasium for Robotic Rehabilitation (Robot Gym) consisted of low- and high-tech systems for upper and lower limb rehabilitation. Our hypothesis is that the Robot Gym can provide a cost- and labor-efficient alternative for post-stroke rehabilitation, while being more or as effective as traditional physical and occupational therapy approaches. Methods A typical group of stroke patients was randomly allocated to an intervention (n = 10) or a control group (n = 10). The intervention group received rehabilitation using the devices in the Robot Gym, whereas the control group (n = 10) received time-matched standard care. All of the study subjects were subjected to 24 two-hour therapy sessions over a period of 6 to 8 weeks. Several clinical assessments tests for upper and lower extremities were used to evaluate motor function pre- and post-intervention. A cost analysis was done to compare the cost effectiveness for both therapies. Results No significant differences were observed when comparing the results of the pre-intervention Mini-mental, Brunnstrom Test, and Geriatric Depression Scale Test, showing that both groups were functionally similar prior to the intervention. Although, both training groups were functionally equivalent, they had a significant age difference. The results of all of the upper extremity tests showed an improvement in function in both groups with no statistically significant differences between the groups. The Fugl-Meyer and the 10 Meters Walk lower extremity tests showed greater improvement in the intervention group compared to the control group. On the Time Up and Go Test, no statistically significant differences were observed pre- and post-intervention when comparing the control and the intervention groups. For the 6 Minute Walk Test, both groups presented a statistically significant difference pre- and post-intervention, showing progress in their performance. The robot gym therapy was more cost-effective than the traditional one-to-one therapy used during this study in that it enabled therapist to train up to 1.5 to 6 times more patients for the approximately same cost in the long term. Conclusions The results of this study showed that the patients that received therapy using the Robot Gym had enhanced functionality in the upper extremity tests similar to patients in the control group. In the lower extremity tests, the intervention patients showed more improvement than those subjected to traditional therapy. These results support that the Robot Gym can be as effective as traditional therapy for stroke patients, presenting a more cost- and labor-efficient option for countries with scarce clinical resources and funding. Trial registration ISRCTN98578807

Effects of an intensive behavioral weight loss intervention consisting of caloric restriction with or without physical activity on common carotid artery remodeling in severely obese adults

Obesity increases cardiovascular disease risk and adversely affects vascular structure and function. Few studies have evaluated the vascular effects of non-surgical weight reduction in the severely obese. We hypothesized that weight loss and improvements in cardiometabolic factors would reduce common carotid artery intima-media thickness (CIMT) and inter-adventitial diameter (AD) in severely obese adults

Induction of osteogenic markers in differentially treated cultures of embryonic stem cells

<p>Abstract</p> <p>Background</p> <p>Facial trauma or tumor surgery in the head and face area often lead to massive destruction of the facial skeleton. Cell-based bone reconstruction therapies promise to offer new therapeutic opportunities for the repair of bone damaged by disease or injury. Currently, embryonic stem cells (ESCs) are discussed to be a potential cell source for bone tissue engineering. The purpose of this study was to investigate various supplements in culture media with respect to the induction of osteogenic differentiation.</p> <p>Methods</p> <p>Murine ESCs were cultured in the presence of LIF (leukemia inhibitory factor), DAG (dexamethasone, ascorbic acid and β-glycerophosphate) or bone morphogenetic protein-2 (BMP-2). Microscopical analyses were performed using von Kossa staining, and expression of osteogenic marker genes was determined by real time PCR.</p> <p>Results</p> <p>ESCs cultured with DAG showed by far the largest deposition of calcium phosphate-containing minerals. Starting at day 9 of culture, a strong increase in collagen I mRNA expression was detected in the DAG-treated cells. In BMP-2-treated ESCs the collagen I mRNA induction was less increased. Expression of osteocalcin, a highly specific marker for osteogentic differentiation, showed a double-peaked curve in DAG-treated cells. ESCs cultured in the presence of DAG showed a strong increase in osteocalcin mRNA at day 9 followed by a second peak starting at day 17.</p> <p>Conclusion</p> <p>Supplementation of ESC cell cultures with DAG is effective in inducing osteogenic differentiation and appears to be more potent than stimulation with BMP-2 alone. Thus, DAG treatment can be recommended for generating ESC populations with osteogenic differentiation that are intended for use in bone tissue engineering.</p

Galaxy And Mass Assembly (GAMA) : trends in galaxy colours, morphology, and stellar populations with large-scale structure, group, and pair environments

We explore trends in galaxy properties with Mpc-scale structures using catalogues of environment and large-scale structure from the Galaxy And Mass Assembly (GAMA) survey. Existing GAMA catalogues of large-scale structure, group, and pair membership allow us to construct galaxy stellar mass functions for different environmental types. To avoid simply extracting the known underlying correlations between galaxy properties and stellar mass, we create a mass matched sample of galaxies with stellar masses within 9.5 ≤ log M*/h−2 M⊙ ≤ 11 for each environmental population. Using these samples, we show that mass normalized galaxies in different large-scale environments have similar energy outputs, u − r colours, luminosities, and morphologies. Extending our analysis to group and pair environments, we show that galaxies that are not in groups or pairs exhibit similar characteristics to each other regardless of broader environment. For our mass controlled sample, we fail to see a strong dependence of Sérsic index or galaxy luminosity on halo mass, but do find that it correlates very strongly with colour. Repeating our analysis for galaxies that have not been mass controlled introduces and amplifies trends in the properties of galaxies in pairs, groups, and large-scale structure, indicating that stellar mass is the most important predictor of the galaxy properties we examine, as opposed to environmental classifications.Publisher PDFPeer reviewe

Galaxy And Mass Assembly (GAMA): trends in galaxy colours, morphology, and stellar populations with large-scale structure, group, and pair environments

We explore trends in galaxy properties with Mpc-scale structures using catalogues of environment and large-scale structure from the Galaxy And Mass Assembly (GAMA) survey. Existing GAMA catalogues of large-scale structure, group, and pair membership allow us to construct galaxy stellar mass functions for different environmental types. To avoid simply extracting the known underlying correlations between galaxy properties and stellar mass, we create a mass matched sample of galaxies with stellar masses within 9.5 ≤ log M*/h−2 M⊙ ≤ 11 for each environmental population. Using these samples, we show that mass normalized galaxies in different large-scale environments have similar energy outputs, u − r colours, luminosities, and morphologies. Extending our analysis to group and pair environments, we show that galaxies that are not in groups or pairs exhibit similar characteristics to each other regardless of broader environment. For our mass controlled sample, we fail to see a strong dependence of Sérsic index or galaxy luminosity on halo mass, but do find that it correlates very strongly with colour. Repeating our analysis for galaxies that have not been mass controlled introduces and amplifies trends in the properties of galaxies in pairs, groups, and large-scale structure, indicating that stellar mass is the most important predictor of the galaxy properties we examine, as opposed to environmental classifications