Trabecular Bone in the Bird Knee Responds with High Sensitivity to Changes in Load Orientation

Wolff’s law of trajectorial orientation proposes that trabecular struts align with the orientation of dominant compressive loads within a joint. Although widely considered in skeletal biology, Wolff’s law has never been experimentally tested while controlling for ontogenetic stage, activity level, and species differences, all factors that may affect trabecular bone growth. Here we report an experimental test of Wolff’s law using a within-species design in age-matched subjects experiencing physiologically normal levels of bone strain. Two age-matched groups of juvenile guinea fowl Numida meleagris ran on a treadmill set at either 0° (Level group) or 20° (Incline group), for 10·min per day over a 45-day treatment period. Birds running on the 20° inclined treadmill used more-flexed knees than those in the Level group at midstance (the point of peak ground reaction force). This difference in joint posture enabled us to test the sensitivity of trabecular alignment to altered load orientation in the knee. Using a new radon transform-based method for measuring trabecular orientation, our analysis shows that the fine trabecular bone in the distal femur has a high degree of correspondence between changes in joint angle and trabecular orientation. The sensitivity of this response supports the prediction that trabecular bone adapts dynamically to the orientation of peak compressive forces.Anthropolog

Thoracic Aortic Calcium Versus Coronary Artery Calcium for the Prediction of Coronary Heart Disease and Cardiovascular Disease Events

ObjectivesThis study compared the ability of coronary artery calcium (CAC) and thoracic aortic calcium (TAC) to predict coronary heart disease (CHD) and cardiovascular disease (CVD) events.BackgroundCoronary artery calcium has been shown to strongly predict CHD and CVD events, but it is unknown whether TAC, also measured within a single cardiac computed tomography (CT) scan, is of further value in predicting events.MethodsA total of 2,303 asymptomatic adults (mean age 55.7 years, 38% female) with CT scans were followed up for 4.4 years for CHD (myocardial infarction, cardiac death, or late revascularizations) and CVD (CHD plus stroke). Cox regression, adjusted for Framingham risk score (FRS), examined the relation of Agatston CAC and TAC categories, and log-transformed CAC and TAC with the incidence of CHD and CVD events and receiver-operator characteristic (ROC) curves tested whether TAC improved prediction of events over CAC and FRS.ResultsA total of 53% of subjects had Agatston CAC scores of 0; 8% 1 to 9; 19% 10 to 99; 12% 100 to 399; and 8% ≥400. For TAC, proportions were 69%, 5%, 12%, 8%, and 7%, respectively; 41 subjects (1.8%) experienced CHD and 47 (2.0%) CVD events. The FRS-adjusted hazard ratios (HR) across increasing CAC groups (relative to <10) ranged from 3.7 (p = 0.04) to 19.6 (p < 0.001) for CHD and from 2.8 (p = 0.07) to 13.1 (p < 0.001) for CVD events; only TAC scores of 100 to 399 predicted CHD and CVD (HR: 3.0, p = 0.008, and HR: 2.3, p = 0.04, respectively); these risks were attenuated after accounting for CAC. Findings were consistent when using log-transformed CAC and TAC Agatston and volume scores. The ROC curve analyses showed CAC predicted CHD and CVD events over FRS alone (p < 0.01); however, TAC did not further add to predicting events over FRS or CAC.ConclusionsThis study found that CAC, but not TAC, is strongly related to CHD and CVD events. Moreover, TAC does not further improve event prediction over CAC

Expertise in research integration and implementation for tackling complex problems: when is it needed, where can it be found and how can it be strengthened?

© 2020, The Author(s). Expertise in research integration and implementation is an essential but often overlooked component of tackling complex societal and environmental problems. We focus on expertise relevant to any complex problem, especially contributory expertise, divided into ‘knowing-that’ and ‘knowing-how.’ We also deal with interactional expertise and the fact that much expertise is tacit. We explore three questions. First, in examining ‘when is expertise in research integration and implementation required?,’ we review tasks essential (a) to developing more comprehensive understandings of complex problems, plus possible ways to address them, and (b) for supporting implementation of those understandings into government policy, community practice, business and social innovation, or other initiatives. Second, in considering ‘where can expertise in research integration and implementation currently be found?,’ we describe three realms: (a) specific approaches, including interdisciplinarity, transdisciplinarity, systems thinking and sustainability science; (b) case-based experience that is independent of these specific approaches; and (c) research examining elements of integration and implementation, specifically considering unknowns and fostering innovation. We highlight examples of expertise in each realm and demonstrate how fragmentation currently precludes clear identification of research integration and implementation expertise. Third, in exploring ‘what is required to strengthen expertise in research integration and implementation?,’ we propose building a knowledge bank. We delve into three key challenges: compiling existing expertise, indexing and organising the expertise to make it widely accessible, and understanding and overcoming the core reasons for the existing fragmentation. A growing knowledge bank of expertise in research integration and implementation on the one hand, and accumulating success in addressing complex societal and environmental problems on the other, will form a virtuous cycle so that each strengthens the other. Building a coalition of researchers and institutions will ensure this expertise and its application are valued and sustained

Michigan Neural Distinctiveness (MiND) study protocol: investigating the scope, causes, and consequences of age-related neural dedifferentiation

Abstract Background Aging is often associated with behavioral impairments, but some people age more gracefully than others. Why? One factor that may play a role is individual differences in the distinctiveness of neural representations. Previous research has found that neural activation patterns in visual cortex in response to different visual stimuli are often more similar (i.e., less distinctive) in older vs. young participants, a phenomenon referred to as age-related neural dedifferentiation. Furthermore, older people whose neural representations are less distinctive tend to perform worse on a wide range of behavioral tasks. The Michigan Neural Distinctiveness (MiND) project aims to investigate the scope of neural dedifferentiation (e.g., does it also occur in auditory, motor, and somatosensory cortex?), one potential cause (age-related reductions in the inhibitory neurotransmitter gamma-aminobutyric acid (GABA)), and the behavioral consequences of neural dedifferentiation. This protocol paper describes the study rationale and methods being used in complete detail, but not the results (data collection is currently underway). Methods The MiND project consists of two studies: the main study and a drug study. In the main study, we are recruiting 60 young and 100 older adults to perform behavioral tasks that measure sensory and cognitive function. They also participate in functional MRI (fMRI), MR spectroscopy, and diffusion weighted imaging sessions, providing data on neural distinctiveness and GABA concentrations. In the drug study, we are recruiting 25 young and 25 older adults to compare neural distinctiveness, measured with fMRI, after participants take a placebo or a benzodiazepine (lorazepam) that should increase GABA activity. Discussion By collecting multimodal imaging measures along with extensive behavioral measures from the same subjects, we are linking individual differences in neurochemistry, neural representation, and behavioral performance, rather than focusing solely on group differences between young and old participants. Our findings have the potential to inform new interventions for age-related declines. Trial registration This study was retrospectively registered with the ISRCTN registry on March 4, 2019. The registration number is ISRCTN17266136 .https://deepblue.lib.umich.edu/bitstream/2027.42/148569/1/12883_2019_Article_1294.pd

Transglutaminase 2 facilitates the distant hematogenous metastasis of breast cancer by modulating interleukin-6 in cancer cells

This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Abstract Introduction Inflammation has been implicated in cancer aggressiveness. As transglutaminase 2 (TG2), which has been associated with inflammatory signaling, has been suggested to play a role in tumor behavior, we propose that TG2 may be an important linker inducing interleukin (IL)-6-mediated cancer-cell aggressiveness, including distant hematogenous metastasis. Methods To investigate the role for TG2 and IL-6, TG2-knocked-down and IL-6-knocked-down cancer cells were generated by using shRNA. Human breast cancer cell xenograft model in highly immunocompromised mice and human advanced breast cancer primary tumor tissue microarrays were used in this study. Results IL-6 production in human breast cancer cells was dependent on their TG2 expression level. In vitro tumor-sphere formation was dependent on TG2 and downstream IL-6 production from cancer cells. Primary tumor growth in the mammary fat pads and distant hematogenous metastasis into the lung was also dependent on TG2 and downstream IL-6 expression levels. The effect of TG2 expression on human breast cancer distant metastasis was investigated by analyzing a tissue microarray of primary tumors from 412 patients with their clinical data after 7 years. TG2 expression in primary tumor tissue was inversely correlated with recurrence-free survival (P = 0.019) and distant metastasis-free survival (DMFS) (P = 0.006) in patients with advanced breast cancer. Furthermore, by using public datasets that included a total of 684 breast cancer patients, we found that the combined high expression of TG2 and IL-6 was associated with shorter DMFS, compared with the high expression of IL-6 only (P = 0.013). Conclusions We provide evidence that TG2 is an important link in IL-6-mediated tumor aggressiveness, and that TG2 could be an important mediator of distant metastasis, both in a xenograft animal model and in patients with advanced breast cancer

How Can Selection of Biologically Inspired Features Improve the Performance of a Robust Object Recognition Model?

Humans can effectively and swiftly recognize objects in complex natural scenes. This outstanding ability has motivated many computational object recognition models. Most of these models try to emulate the behavior of this remarkable system. The human visual system hierarchically recognizes objects in several processing stages. Along these stages a set of features with increasing complexity is extracted by different parts of visual system. Elementary features like bars and edges are processed in earlier levels of visual pathway and as far as one goes upper in this pathway more complex features will be spotted. It is an important interrogation in the field of visual processing to see which features of an object are selected and represented by the visual cortex. To address this issue, we extended a hierarchical model, which is motivated by biology, for different object recognition tasks. In this model, a set of object parts, named patches, extracted in the intermediate stages. These object parts are used for training procedure in the model and have an important role in object recognition. These patches are selected indiscriminately from different positions of an image and this can lead to the extraction of non-discriminating patches which eventually may reduce the performance. In the proposed model we used an evolutionary algorithm approach to select a set of informative patches. Our reported results indicate that these patches are more informative than usual random patches. We demonstrate the strength of the proposed model on a range of object recognition tasks. The proposed model outperforms the original model in diverse object recognition tasks. It can be seen from the experiments that selected features are generally particular parts of target images. Our results suggest that selected features which are parts of target objects provide an efficient set for robust object recognition

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Preterm lung function after retreatment with antenatal betamethasone in preterm lambs

OBJECTIVE: We hypothesized that two doses of betamethasone administered 1 week apart would further enhance postnatal pulmonary function in preterm lambs (compared with a single dose)