A Key Characteristic of Sex Differences in the Developing Brain: Greater Variability in Brain Structure of Boys than Girls.

In many domains, including cognition and personality, greater variability is observed in males than in females in humans. However, little is known about how variability differences between sexes are represented in the brain. The present study tested whether there is a sex difference in variance in brain structure using a cohort of 643 males and 591 females aged between 3 and 21 years. The broad age-range of the sample allowed us to test if variance differences in the brain differ across age. We observed significantly greater male than female variance for several key brain structures, including cerebral white matter and cortex, hippocampus, pallidum, putamen, and cerebellar cortex volumes. The differences were observed at both upper and lower extremities of the distributions and appeared stable across development. These findings move beyond mean levels by showing that sex differences were pronounced for variability, thereby providing a novel perspective on sex differences in the developing brain.

Correction for misclassification of a categorized exposure in binary regression using replication data.

Continuous epidemiologic exposure data are often categorized according to one or more cut points before inclusion in a regression analysis involving some outcome variable. If the original data are subject to measurement error, the categorized data will be afflicted with misclassification, which is differential, and which induces biases in naïve methods that ignore the misclassification. We propose a method for measurement error adjustment in these settings, when there are replicate data available on the original measurements, and when the outcome variable is dichotomous. Working on the continuous measurements, conditional densities of the exposure given the outcome are estimated and used to obtain odds ratios. The estimation of densities is done either parametrically or nonparametrically. The method is compared with the naïve approach of simply categorizing the erroneous mean measurements in simulation studies, and although the nonparametric method is more variable, it has the best overall performance, the greatest differences being observed in settings where the effects and/or the measurement errors are large. The performance of the parametric method is highly dependent on the model fit. Applying the methods to a real-life data set from the Framingham Heart Study produced larger estimated odds ratios for coronary heart disease as a result of elevated systolic blood pressure, as compared with naïve odds ratios. We provide some discussion of alternative procedures that might be considered including regression calibration, SIMEX and the use of estimated misclassification probabilities.

Large-conductance calcium-activated potassium channels in purkinje cell plasma membranes are clustered at sites of hypolemmal microdomains.

Calcium-activated potassium channels have been shown to be critically involved in neuronal function, but an elucidation of their detailed roles awaits identification of the microdomains where they are located. This study was undertaken to unravel the precise subcellular distribution of the large-conductance calcium-activated potassium channels (called BK, KCa1.1, or Slo1) in the somatodendritic compartment of cerebellar Purkinje cells by means of postembedding immunogold cytochemistry and SDS-digested freeze-fracture replica labeling (SDS-FRL). We found BK channels to be unevenly distributed over the Purkinje cell plasma membrane. At distal dendritic compartments, BK channels were scattered over the plasma membrane of dendritic shafts and spines but absent from postsynaptic densities. At the soma and proximal dendrites, BK channels formed two distinct pools. One pool was scattered over the plasma membrane, whereas the other pool was clustered in plasma membrane domains overlying subsurface cisterns. The labeling density ratio of clustered to scattered channels was about 60:1, established in SDS-FRL. Subsurface cisterns, also called hypolemmal cisterns, are subcompartments of the endoplasmic reticulum likely representing calciosomes that unload and refill Ca2+ independently. Purkinje cell subsurface cisterns are enriched in inositol 1,4,5-triphosphate receptors that mediate the effects of several neurotransmitters, hormones, and growth factors by releasing Ca2+ into the cytosol, generating local Ca2+ sparks. Such increases in cytosolic [Ca2+] may be sufficient for BK channel activation. Clustered BK channels in the plasma membrane may thus participate in building a functional unit (plasmerosome) with the underlying calciosome that contributes significantly to local signaling in Purkinje cells.