Evolution of genetic networks for human creativity

The genetic basis for the emergence of creativity in modern humans remains a mystery despite sequencing the genomes of chimpanzees and Neanderthals, our closest hominid relatives. Data-driven methods allowed us to uncover networks of genes distinguishing the three major systems of modern human personality and adaptability: emotional reactivity, self-control, and self-awareness. Now we have identified which of these genes are present in chimpanzees and Neanderthals. We replicated our findings in separate analyses of three high-coverage genomes of Neanderthals. We found that Neanderthals had nearly the same genes for emotional reactivity as chimpanzees, and they were intermediate between modern humans and chimpanzees in their numbers of genes for both self-control and self-awareness. 95% of the 267 genes we found only in modern humans were not protein-coding, including many long-non-coding RNAs in the self-awareness network. These genes may have arisen by positive selection for the characteristics of human well-being and behavioral modernity, including creativity, prosocial behavior, and healthy longevity. The genes that cluster in association with those found only in modern humans are over-expressed in brain regions involved in human self-awareness and creativity, including late-myelinating and phylogenetically recent regions of neocortex for autobiographical memory in frontal, parietal, and temporal regions, as well as related components of cortico-thalamo-ponto-cerebellar-cortical and cortico-striato-cortical loops. We conclude that modern humans have more than 200 unique non-protein-coding genes regulating co-expression of many more protein-coding genes in coordinated networks that underlie their capacities for self-awareness, creativity, prosocial behavior, and healthy longevity, which are not found in chimpanzees or Neanderthals.Peer reviewe

Positive Psychosocial Factors in Childhood Predicting Lower Risk for Adult Type 2 Diabetes : The Cardiovascular Risk in Young Finns Study, 1980-2012

Introduction: Type 2 diabetes is a public health concern, but psychosocial factors that may protect against the disease are unknown. This study examines whether a positive psychosocial environment in childhood is associated with lower risk for Type 2 diabetes in adulthood or healthier glucose trajectories over the life course, and whether BMI mediates the associations. Methods: A cohort of 3,596 Finnish children was followed into adulthood over 32 years. An overall positive psychosocial score, consisting of six subdomains, was measured at study baseline (1980). Relative risk ratios and multilevel growth curve modeling were used to examine associations of the psychosocial score with Type 2 diabetes (2012) and glucose trajectories (1986-2012). The mediating effect by BMI was examined using mediation analysis. The analyses were conducted between June 2015 and January 2016. Results: There was a 21% decrease in the rate of Type 2 diabetes (relative risk ratio, 0.79; 95% CI = 0.66, 0.94) for each 1-SD increase in the positive psychosocial score after adjustment for childhood cardiovascular risk factors and dietary behaviors. Adult BMI mediated 52% and weight gain mediated 25% of the association. The growth curve model showed healthier glucose trajectories (age X psychosocial score interaction, b = -0.01; p = 0.010) for participants with higher versus lower positive psychosocial score in childhood. Conclusions: Positive psychosocial environment in childhood seems to have beneficial influences on the risk for Type 2 diabetes over the life span. RCTs will be required to see if interventions directed at early-life circumstances are warranted. (C) 2017 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.Peer reviewe

Corrigendum to "Translating big data to better treatment in bipolar disorder - a manifesto for coordinated action [European Neuropsychopharmacology (2020) 36, 121-136]"

The authors regret that there was an error in the author list, this should appear as above. The authors apologise for any inconvenience caused

Large Asymmetric Hypertrophy of Rectus Abdominis Muscle in Professional Tennis Players

Purpose: To determine the volume and degree of asymmetry of the musculus rectus abdominis (RA) in professional tennis players. Methods: The volume of the RA was determined using magnetic resonance imaging (MRI) in 8 professional male tennis players and 6 non-active male control subjects. Results: Tennis players had 58 % greater RA volume than controls (P = 0.01), due to hypertrophy of both the dominant (34% greater volume, P = 0.02) and non-dominant (82 % greater volume, P = 0.01) sides, after accounting for age, the length of the RA muscle and body mass index (BMI) as covariates. In tennis players, there was a marked asymmetry in the development of the RA, which volume was 35 % greater in the non-dominant compared to the dominant side (P,0.001). In contrast, no sideto-side difference in RA volume was observed in the controls (P = 0.75). The degree of side-to-side asymmetry increased linearly from the first lumbar disc to the pubic symphysis (r = 0.97, P,0.001). Conclusions: Professional tennis is associated with marked hypertrophy of the musculus rectus abdominis, which achieves a volume that is 58 % greater than in non-active controls. Rectus abdominis hypertrophy is more marked in the non-dominant than in the dominant side, particularly in the more distal regions. Our study supports the concept that humans can differentially recruit both rectus abdominis but also the upper and lower regions of each muscle. It remains to b

Is Symptomatic Long QT Syndrome Associated with Depression in Women and Men?

We examined whether long QT syndrome (LQTS) mutation carrier status or symptomatic LQTS are associated with depression, and whether there are sex differences in these potential relationships. The sample comprised 782 participants (252 men). Of the 369 genetically defined LQTS mutation carriers, 169 were symptomatic and 200 were asymptomatic. The control group consisted of 413 unaffected relatives. Depression was assessed using the Beck Depression Inventory-II (BDI-II). No association was found for LQTS mutation carrier status with depression. The multinomial logistic regression showed that LQTS mutation carrier men with arrhythmic events scored higher on depression compared with the control group, even when adjusting for age, beta-blockers, antidepressants, and social support (OR = 1.09, 95 % CI [1.02, 1.15], p = .007). The binary logistic regression comparing symptomatic and asymptomatic LQTS mutation carriers showed that symptomatic LQTS was associated with depression in men (OR = 1.10, 95 % CI [1.03, 1.19], p = .009). The results were unchanged when additionally adjusted for education. These findings suggest that symptomatic LQTS is associated with depression in men but not in women. Overall, however, depression is more frequent in women than men. Thus, regular screening for depression in LQTS mutation carriers and their unaffected family members can be important.Peer reviewe

STAT3 Activation in Skeletal Muscle Links Muscle Wasting and the Acute Phase Response in Cancer Cachexia

Cachexia, or weight loss despite adequate nutrition, significantly impairs quality of life and response to therapy in cancer patients. In cancer patients, skeletal muscle wasting, weight loss and mortality are all positively associated with increased serum cytokines, particularly Interleukin-6 (IL-6), and the presence of the acute phase response. Acute phase proteins, including fibrinogen and serum amyloid A (SAA) are synthesized by hepatocytes in response to IL-6 as part of the innate immune response. To gain insight into the relationships among these observations, we studied mice with moderate and severe Colon-26 (C26)-carcinoma cachexia.Moderate and severe C26 cachexia was associated with high serum IL-6 and IL-6 family cytokines and highly similar patterns of skeletal muscle gene expression. The top canonical pathways up-regulated in both were the complement/coagulation cascade, proteasome, MAPK signaling, and the IL-6 and STAT3 pathways. Cachexia was associated with increased muscle pY705-STAT3 and increased STAT3 localization in myonuclei. STAT3 target genes, including SOCS3 mRNA and acute phase response proteins, were highly induced in cachectic muscle. IL-6 treatment and STAT3 activation both also induced fibrinogen in cultured C2C12 myotubes. Quantitation of muscle versus liver fibrinogen and SAA protein levels indicates that muscle contributes a large fraction of serum acute phase proteins in cancer.These results suggest that the STAT3 transcriptome is a major mechanism for wasting in cancer. Through IL-6/STAT3 activation, skeletal muscle is induced to synthesize acute phase proteins, thus establishing a molecular link between the observations of high IL-6, increased acute phase response proteins and muscle wasting in cancer. These results suggest a mechanism by which STAT3 might causally influence muscle wasting by altering the profile of genes expressed and translated in muscle such that amino acids liberated by increased proteolysis in cachexia are synthesized into acute phase proteins and exported into the blood

A Probabilistic Model of Glenohumeral External Rotation Strength for Healthy Normals and Rotator Cuff Tear Cases

The reigning paradigm of musculoskeletal modeling is to construct deterministic models from parameters of an “average” subject and make predictions for muscle forces and joint torques with this model. This approach is limited because it does not perform well for outliers, and it does not model the effects of population parameter variability. The purpose of this study was to simulate variability in musculoskeletal parameters on glenohumeral external rotation strength in healthy normals, and in rotator cuff tear case using a Monte Carlo model. The goal was to determine if variability in musculoskeletal parameters could quantifiably explain variability in glenohumeral external rotation strength. Multivariate Gamma distributions for musculoskeletal architecture and moment arm were constructed from empirical data. Gamma distributions of measured joint strength were constructed. Parameters were sampled from the distributions and input to the model to predict muscle forces and joint torques. The model predicted measured joint torques for healthy normals, subjects with supraspinatus tears, and subjects with infraspinatus–supraspinatus tears with small error. Muscle forces for the three conditions were predicted and compared. Variability in measured torques can be explained by differences in parameter variability.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44005/1/10439_2005_Article_9045.pd

Down-regulation of protein kinase Cdelta inhibits inducible nitric oxide synthase expression through IRF1

Peer reviewe

Viscoelastic responses of the lumbar spine during prolonged stooping

There is considerable evidence that awkward postures of the low back are related to the incidence of low back disorders (LBDs), but the specific biomechanics/physiology of this link is not fully developed. This study combined empirical work with finite element analyses to explore this relationship. The empirical work focused on quantifying the time-dependent responses of the lumbar spine during a prolonged stooped posture by assessing the changes in the sagittal plane range of motion and the electromyographic activity of the back extensor musculature during and after prolonged stooping. Ten healthy participants performed a regimen of a 10 minute stooping period followed by a 10 minute upright standing recovery period, with an isokinetic lift at every 2.5 minutes. Results showed significant creep effects of the flexion angle and the increased activity of extensor muscles in stooping to compensate for the reduced extensor moment producing capability of the passive tissues. The 10 minute upright standing did not produce a full recovery of the lumbar spine tissues but a 30 second rest break in the middle of the stooping moderated these viscoelastic responses. A nonlinear viscoelastic 3D finite element (FE) model of the lumbar spine was developed to predict the responses of the passive and active tissues of the low back. Validation of the FE model by comparing its predicted results (range of motion, muscle activation levels, etc.) with experimental results indicated good agreement in terms of mechanical behaviors in stooping, confirming the capability of the FE model as a potential tool for risk assessment of the prolonged stooping tasks