Effect of early adversity and childhood internalizing symptoms on brain structure in young men

- Importance: Early adversity is an important risk factor that relates to internalizing symptoms and altered brain structure. - Objective: To assess the direct effects of early adversity and child internalizing symptoms (ie, depression, anxiety) on cortical gray matter (GM) volume, as well as the extent to which early adversity associates with variation in cortical GM volume indirectly via increased levels of internalizing symptoms. - Design, Setting, and Participants: A prospective investigation of associations between adversity within the first 6 years of life, internalizing symptoms during childhood and early adolescence, and altered brain structure in late adolescence (age, 18-21 years) was conducted in a community-based birth cohort in England (Avon Longitudinal Study of Parents and Children). Participants from the cohort included 494 mother-son pairs monitored since the mothers were pregnant (estimated date of delivery between April 1, 1991, and December 31, 1992). Data collection for the present study was conducted between April 1, 1991, and November 30, 2010; the neuroimaging data were collected between September 1, 2010, and November 30, 2012, and data analyses for the present study occurred between January 25, 2013, and February 15, 2015. Risk factors were adversity within the first 6 years of the child’s life (including prenatal exposure) and the child’s internalizing symptoms between age 7 and 13 years. - Exposures: Early childhood adversity. - Main Outcomes and Measures: The main outcome was GM volume of cortical regions previously associated with major depression measured through T1-weighted magnetic resonance images collected in late adolescence. - Results: Among 494 young men included in this analysis, early adversity was directly associated with lower GM volumes in the anterior cingulate cortex (β = −.18; P = .01) and higher GM volume in the precuneus (β = .18; P = .009). Childhood internalizing symptoms were associated with lower GM volume in the right superior frontal gyrus (β = −.20; P = .002). Early adversity was also associated with higher levels of internalizing symptoms (β = .37; P < .001), which, in turn, were associated with lower superior frontal gyrus volume (ie, an indirect effect) (β = −.08; 95% CI, −0.14 to −0.01; P = .02). - Conclusions and Relevance: Adversity early in life was associated with higher levels of internalizing symptoms as well as with altered brain structure. Early adversity was related to variation in brain structure both directly and via increased levels of internalizing symptoms. These findings may suggest that some of the structural variation often attributed to depression might be associated with early adversity in addition to the effect of depression

Erythropoietin Modulates the Structure of Bone Morphogenetic Protein 2–Engineered Cranial Bone

The ideally engineered bone should have similar structural and functional properties to the native tissue. Although structural integrity is critical for functional bone regeneration, we know less about modulating the structural properties of the engineered bone elicited by bone morphogenetic protein (BMP) than efficacy and safety. Erythropoietin (Epo), a primary erythropoietic hormone, has been used to augment blood transfusion in orthopedic surgery. However, the effects of Epo on bone regeneration are not well known. Here, we determined the role of Epo in BMP2-induced bone regeneration using a cranial defect model. Epo administration improved the quality of BMP2-induced bone and more closely resembled natural cranial bone with a higher bone volume (BV) fraction and lower marrow fraction when compared with BMP2 treatment alone. Epo increased red blood cells (RBCs) in peripheral blood and also increased hematopoietic and mesenchymal stem cell (MSC) populations in bone marrow. Consistent with our previous work, Epo increased osteoclastogenesis both in vitro and in vivo. Results from a metatarsal organ culture assay suggested that Epo-promoted osteoclastogenesis contributed to angiogenesis because angiogenesis was blunted when osteoclastogenesis was blocked by alendronate (ALN) or osteoprotegerin (OPG). Earlier calcification of BMP2-induced temporary chondroid tissue was observed in the Epo+BMP group compared to BMP2 alone. We conclude that Epo significantly enhanced the outcomes of BMP2-induced cranial bone regeneration in part through its actions on osteoclastogenesis and angiogenesis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98479/1/ten%2Etea%2E2011%2E0742.pd

Center or Limit Cycle: Renormalization Group as a Probe

Based on our studies done on two-dimensional autonomous systems, forced non-autonomous systems and time-delayed systems, we propose a unified methodology - that uses renormalization group theory - for finding out existence of periodic solutions in a plethora of nonlinear dynamical systems appearing across disciplines. The technique will be shown to have a non-trivial ability of classifying the solutions into limit cycles and periodic orbits surrounding a center. Moreover, the methodology has a definite advantage over linear stability analysis in analyzing centers

On observability of Renyi's entropy

Despite recent claims we argue that Renyi's entropy is an observable quantity. It is shown that, contrary to popular belief, the reported domain of instability for Renyi entropies has zero measure (Bhattacharyya measure). In addition, we show the instabilities can be easily emended by introducing a coarse graining into an actual measurement. We also clear up doubts regarding the observability of Renyi's entropy in (multi--)fractal systems and in systems with absolutely continuous PDF's.Comment: 18 pages, 1 EPS figure, REVTeX, minor changes, accepted to Phys. Rev.

Combined deletion of Glut1 and Glut3 impairs lung adenocarcinoma growth.

Glucose utilization increases in tumors, a metabolic process that is observed clinically by &lt;sup&gt;18&lt;/sup&gt; F-fluorodeoxyglucose positron emission tomography ( &lt;sup&gt;18&lt;/sup&gt; F-FDG-PET). However, is increased glucose uptake important for tumor cells, and which transporters are implicated in vivo? In a genetically-engineered mouse model of lung adenocarcinoma, we show that the deletion of only one highly expressed glucose transporter, Glut1 or Glut3, in cancer cells does not impair tumor growth, whereas their combined loss diminishes tumor development. &lt;sup&gt;18&lt;/sup&gt; F-FDG-PET analyses of tumors demonstrate that Glut1 and Glut3 loss decreases glucose uptake, which is mainly dependent on Glut1. Using &lt;sup&gt;13&lt;/sup&gt; C-glucose tracing with correlated nanoscale secondary ion mass spectrometry (NanoSIMS) and electron microscopy, we also report the presence of lamellar body-like organelles in tumor cells accumulating glucose-derived biomass, depending partially on Glut1. Our results demonstrate the requirement for two glucose transporters in lung adenocarcinoma, the dual blockade of which could reach therapeutic responses not achieved by individual targeting