Dump the "dimorphism": Comprehensive synthesis of human brain studies reveals few male-female differences beyond size.

With the explosion of neuroimaging, differences between male and female brains have been exhaustively analyzed. Here we synthesize three decades of human MRI and postmortem data, emphasizing meta-analyses and other large studies, which collectively reveal few reliable sex/gender differences and a history of unreplicated claims. Males' brains are larger than females' from birth, stabilizing around 11 % in adults. This size difference accounts for other reproducible findings: higher white/gray matter ratio, intra- versus interhemispheric connectivity, and regional cortical and subcortical volumes in males. But when structural and lateralization differences are present independent of size, sex/gender explains only about 1% of total variance. Connectome differences and multivariate sex/gender prediction are largely based on brain size, and perform poorly across diverse populations. Task-based fMRI has especially failed to find reproducible activation differences between men and women in verbal, spatial or emotion processing due to high rates of false discovery. Overall, male/female brain differences appear trivial and population-specific. The human brain is not "sexually dimorphic."

Palladin is upregulated in kidney disease and contributes to epithelial cell migration after injury.

Recovery from acute kidney injury involving tubular epithelial cells requires proliferation and migration of healthy cells to the area of injury. In this study, we show that palladin, a previously characterized cytoskeletal protein, is upregulated in injured tubules and suggest that one of its functions during repair is to facilitate migration of remaining cells to the affected site. In a mouse model of anti-neutrophilic cytoplasmic antibody involving both tubular and glomerular disease, palladin is upregulated in injured tubular cells, crescents and capillary cells with angiitis. In human biopsies of kidneys from patients with other kidney diseases, palladin is also upregulated in crescents and injured tubules. In LLC-PK1 cells, a porcine proximal tubule cell line, stress induced by transforming growth factor-ß1 (TGF-ß1) leads to palladin upregulation. Knockdown of palladin in LLC-PK1 does not disrupt cell morphology but does lead to a defect in cell migration. Furthermore, TGF-ß1 induced increase in the 75 kDa palladin isoform occurs in both the nucleus and the cytoplasm. These data suggest that palladin expression is induced in injured cells and contributes to proper migration of cells in proximal tubules, possibly by regulation of gene expression as part of the healing process after acute injury.

Chitosan against cutaneous pathogens.

Propionibacterium acnes and Staphylococcus aureus are cutaneous pathogens that have become increasingly resistant to antibiotics. We sought to determine if chitosan, a polymer of deacetylated chitin, could be used as a potential treatment against these bacteria. We found that higher molecular weight chitosan had superior antimicrobial properties compared to lower molecular weights, and that this activity occurred in a pH dependent manner. Electron and fluorescence microscopy revealed that chitosan forms aggregates and binds to the surface of bacteria, causing shrinkage of the bacterial membrane from the cell wall. Of special relevance, clinical isolates of P. acnes were vulnerable to chitosan, which could be combined with benzoyl peroxide for additive antibacterial effect. Chitosan also demonstrated significantly less cytotoxicity to monocytes than benzoyl peroxide. Overall, chitosan demonstrates many promising qualities for treatment of cutaneous pathogens.

Structure and function of palladin's actin binding domain.

Here, we report the NMR structure of the actin-binding domain contained in the cell adhesion protein palladin. Previously, we demonstrated that one of the immunoglobulin domains of palladin (Ig3) is both necessary and sufficient for direct filamentous actin binding in vitro. In this study, we identify two basic patches on opposite faces of Ig3 that are critical for actin binding and cross-linking. Sedimentation equilibrium assays indicate that the Ig3 domain of palladin does not self-associate. These combined data are consistent with an actin cross-linking mechanism that involves concurrent attachment of two actin filaments by a single palladin molecule by an electrostatic mechanism. Palladin mutations that disrupt actin binding show altered cellular distributions and morphology of actin in cells, revealing a functional requirement for the interaction between palladin and actin in vivo.

Treatment of progressive multifocal leukoencephalopathy and idiopathic CD4+ lymphocytopenia.

Progressive multifocal leukoencephalopathy is a neurological disease caused by the human polyoma virus JC virus and can present in patients with known immunodeficiencies. However, when associated with idiopathic CD4+ lymphocytopenia, management of patients can be quite challenging as these are two rare diseases with limited effective treatment options. In conjunction with the case report of a patient diagnosed with both conditions presented within this issue, a discussion of available treatment strategies is detailed.

Inhibitory control of saccadic eye movements and cognitive impairment in Alzheimer's disease.

BACKGROUND: This study examined the relationship of inhibitory control and measures of neuropsychological impairment in patients with early Alzheimer's disease (AD). Four specific questions were addressed: 1) Which error parameters of saccadic inhibition are sensitive to AD? 2) Which inhibitory deficits are related to cognitive measures of impairment? 3) Is the inhibitory impairment in AD dependent on the initiation of a volitional eye movement? 4) How do the effects of saccadic inhibitory control in AD relate to the normal effects of aging? METHODS: Eighteen patients with probable AD and two control groups (seventeen young, and eighteen old participants) completed a battery of neuropsychological tests and four saccadic eye movement paradigms: pro-saccade, NO-GO, GO/NO-GO and anti-saccade. RESULTS: Old controls generated increased inhibition errors in comparison to young controls in the GO/NO-GO paradigm. In comparison to old controls, AD generated normal saccades in the pro-saccade paradigm, but showed a higher proportion of inhibition errors in the NO-GO, GO/NO-GO and anti-paradigms. The frequency of uncorrected errors in the anti-saccade paradigm was positively correlated with cognitive measures of dementia. CONCLUSIONS: AD patients have an impairment of inhibitory control and error-correction that exceeds the effects of normal aging and is related to the severity of dementia. However, the inhibitory impairment is not contingent on the interaction with a volitional saccade.