A viral phospholipase A2 is required for parvovirus infectivity.

Sequence analysis revealed phospholipase A2 (PLA2) motifs in capsid proteins of parvoviruses. Although PLA2 activity is not known to exist in viruses, putative PLA2s from divergent parvoviruses, human B19, porcine parvovirus, and insect GmDNV (densovirus from Galleria mellonella), can emulate catalytic properties of secreted PLA2. Mutations of critical amino acids strongly reduce both PLA2 activity and, proportionally, viral infectivity, but cell surface attachment, entry, and endocytosis by PLA2-deficient virions are not affected. PLA2 activity is critical for efficient transfer of the viral genome from late endosomes/lysosomes to the nucleus to initiate replication. These findings offer the prospect of developing PLA2 inhibitors as a new class of antiviral drugs against parvovirus infections and associated diseases.

Topography of the human corpus callosum.

This study was undertaken to determine the topographical organization of fibers coursing through the human corpus callosum. We correlated the distribution of Wallerian degeneration in the corpus callosum with the anatomical sites of focal cortical lesions due to ischemic infarctions or circumscribed contusions. Fibers from the inferior frontal and anterior inferior parietal regions course through the rostrum and genu of the corpus callosum. Callosal connections from the temporo-parieto-occipital junctional region course through the splenium and caudal portion of the body of the corpus callosum. Both the superior parietal lobule and the occipital cortex give rise to interhemispheric fibers that course exclusively through the splenium of the corpus callosum. No callosal degeneration was associated with a cortical lesion in the anterior superior frontal region. The topographical organization of fibers in the human corpus callosum appears to be fairly similar to that found in the rhesus monkey (Macaca mulatta).

Measures of gender differences in the human brain and their relationship to brain weight.

A series of gross brain linear measurements and cross-sectional surface areas were obtained in a sample of 69 postmortem adult human brains. Data indicate that a subset of these measurements are sexually dimorphic and can be used to discriminate between male and female brains. Results further suggest that studies on gender differences in neuromorphometry can be greatly enhanced if they account for sample variance in brain weight. Using 19 of the gross brain measures delineated in this study, it is possible to accurately predict brain weight. It is believed that the measures obtained in this study will facilitate expanded correlative studies of brain morphology and neuropsychological profiles using either postmortem material or in vivo magnetic resonance imaging scans.

The role of cortical connectivity in Alzheimer's disease pathogenesis: a review and model system.

Here we review current evidence in support of the cortical disconnection/cortical connectivity model of Alzheimer disease (AD) pathogenesis, a model which predicts that one of the first events in AD is damage to the entorhinal cortex and/or subiculum resulting in the disconnection of the hippocampal formation and neocortex, and the subsequent progression of the disease in a stepwise fashion along cortico-cortical connections. Much of the evidence for this model has been obtained from studies involving the limbic system where investigators have demonstrated a precise correspondence between established patterns of connectivity and the degenerative changes associated with AD. In addition, some studies of the distribution of neuritic plaques (NP) and neuro-fibrillary tangles (NFT) in the neocortex and subcortical structures have yielded corroborative data. The validity of the cortical disconnection/connectivity model in the neocortex remains to be established or refuted. We propose that testing of this model can be accomplished with systematic studies of the laminar and regional distribution of NP and NFT in a series of sequentially interconnected cytoarchitectural regions that also form part of two functional hierarchies--the paralimbic and occipitotemporal visual systems. To adequately control for variation between brains affected by AD, it is imperative that such studies be conducted in a large but varied population of AD cases exhibiting differences in several variables, including clinical and/or neuropathological severity of the disease, temporal duration of the disease, and clinical/neuropsychological profile. We believe that further understanding of the relationship between characteristic AD pathology and intrinsic anatomico-functional circuits will contribute not only to our comprehension of AD pathogenesis but also to our general knowledge of the human brain.

The corpus callosum in nonhuman primates. Determinants of size.

The relationships between brain weight, sex and various callosal parameters including cross-sectional surface area and maximum splenial width in nonhuman primates are delineated. Overall, brain weight is a good predictor of quantitative aspects of the corpus callosum. However, both pongids and strepsirhines evince sex differences on certain callosal measures. No sex differences were found for either the ceboids or cercopithecoids. We speculate that one aspect of primate brain evolution has involved the modulation of interhemispheric connectivity along the lines of sex.

Sexual dimorphism in the human corpus callosum: an extension and replication study.

Using a new sample of 16 human brains (F = 8, M = 8), it was found that the splenial portion of the corpus callosum was larger and more bulbous in females than in males. In addition, the total area of the corpus callosum was both absolutely and relatively larger in females than in males, with the relative measurements (i.e., to brain weight) differing significantly. This was also true when using exponential values of brain weight commensurate with the areas and linear distances of the corpus callosum. These results, which replicate the findings of earlier work, were found by the two authors using different methods, and working independently of each other. We believe these findings provide a partial anatomical basis for purported gender differences in cognitive task behaviour, and are related to early gonadal steroidal influences during prenatal development.

Possible sex differences in the developing human fetal brain.

Left-right regional volumetric asymmetries in five telencephalic regions were studied in the developing human fetal brain. Complete series of coronal sections of 21 fetal brains were digitized and regional volumes were integrated. Five regional indices of asymmetry and two overall indices of asymmetry were calculated and compared across the fetal sample. The two most asymmetrical regions in the developing fetal brain were region 1, roughly equivalent to prefrontal cortex, and region 5, which includes striate and extrastriate cortices. Region 5 also manifested a statistically significant sex difference (p less than .02) in the degree of volumetric asymmetry. It appears that striate-extrastriate cortices are far more asymmetrical in male brains than in their female counterparts (M = 33%; F = 13%). Overall indices of asymmetry indicated that, on the average, volumetric asymmetries in the male brain favor the right hemisphere. In contrast, the human fetal female is likely to have two hemispheres of the same size or a left hemisphere that is slightly larger than its right counterpart. We believe that these results support the hypothesis that testosterone in utero may lead to a more rapid growth of the right hemisphere or, alternatively, retard the growth of the left hemisphere.

Prosencephalic asymmetries in Lemuridae.

This study was undertaken to determine if regional volumetric asymmetries are a function of sulcal complexity and/or brain size. A complete series of coronal sections of cerebra from six species of Lemuridae, a family of strepsirhines, was digitized. Regional volumes were integrated and indices of asymmetry were calculated. The most significant asymmetries were found in retrocalcarine cortex, suggesting that striate and extrastriate asymmetries emerged early in primate evolution. Results further indicated that the degree of regional volumetric asymmetries, as measured by our indices, does not vary with sulcal complexity and/or brain size.

Sex differences in the fetal human corpus callosum.

Midsagittal sections of fetal cerebra from the Yakovlev collection ranging from 26-41 weeks gestational age were photographed. The photographs were used to obtain areal measurements of the cross-sectional surface of the corpora callosa; and linear measurements of the widths of genu, body and splenium. A significant sex difference, favoring females, was found in the splenial width of the corpus callosum by 26 weeks gestational age. Although other variables, including the overall cross-sectional area of the corpus callosum, were larger in females both absolutely and relative to brain weight, the differences were not statistically significant. These results suggest that the gonadal steroids and/or genetic sex have an important role in utero in the differentiation of neural structures not associated with reproductive functions. Elaboration of sex differences, however, may occur postnatally.