Marija Heffer-Lauc

c-pathway polysialogangliosides are transiently expressed in the human cerebrum during fetal development

Gangliosides are assumed to play a crucial role in processes of cellular recognition and interaction important for neural development. They are designated as cytochemical markers of neuronal maturation, as striking changes in the ganglioside pattern parallel the nervous system development. Of particular interest to us are numerous studies that reported during migration of postmitotic neurons and axon formation in developing avian and mammalian brains a transient accumulation of highly sialylated c-pathway gangliosides. However, it has thus far been thought that c-pathway gangliosides do not appear in the human cerebrum; their absence could be somehow interpreted in the light of an evolutionary trend in the pattern of brain gangliosides: by increasing the phylogenetic scale this pattern changes by an accretion of less sialylated gangliosides and switches from c- via b- to a-series, respectively. The present study presents both biochemical and immunocytochemical evidence for the existence of c-pathway gangliosides in the human cerebrum during prenatal life, and their localization in discrete neuronal populations and growing axonal pathways.

Complex patterns and simple architects: molecular guidance cues for developing axonal pathways in the telencephalon

The aim of this review is to discuss the current research on the spatio-temporal distribution and function of the four major classes of axonal guidance cues (netrins, semaphorins, slits, and ephrins) and their receptors in the developing mammalian telencephalon. In the first part, we briefly describe guidance molecules and their receptors. In the second part, we review their overlapping distribution in the specific architectonic zones of the cerebral wall during the embryonic and early postnatal period. In the third part, we describe complementary and/or overlapping functions of these molecules in the development of all major classes of telencephalic axon pathways: subcortical (thalamic and extrathalamic) afferent systems, corticofugal (projection) systems, and cortico-cortical (commissural and ipsilateral) fiber systems. To conclude, we discuss several general themes which emerge from the current research, and point out that most axonal guidance cues have other developmental roles as well, including possible involvement in synaptic plasticity in the adult brain.

C-series polysialogangliosides are expressed on stellate neurons of adult human cerebellum

Until now ‘c-series’ polysialogangliosides were known to exist in human brain only during development and in some pathological conditions like Alzheimer’s disease. Using thin-layer chromatography (TLC) and immunostaining with Q211 antibody (TLC-overlay technique) we have analysed ‘c-series’ gangliosides in four human cerebella (age 20, 47, 52 and 54 years). Four distinct ganglioside bands, most probably corresponding to GT1c, GQ1c, GP1c and GH1c were found to exist in the analysed brains, which is convincing demonstration of the existence of ‘c-series’ gangliosides in normal adult human brain. Immunohistochemical analysis was performed to locate polysialogangliosides in the analysed tissue. Q211 antibody was found to bind specifically to a single subpopulation of neurons in the molecular layer of adult cerebellum. According to their position and morphology these cells correspond to stellate neurons.

Anti-GM3 (II3Neu5Ac-lactosylceramide) ganglioside antibody labels human fetal Purkinje neurons during the critical stage of cerebellar development

The ganglioside GM3 (II3Neu5Ac-lactosylceramide) represents a minor ganglioside in normal human brain compared to major gangliosides with gangliotetraose-backbone. In this study the presence of GM3 in three 23 and 24 weeks of gestation old human cerebella was demonstrated by immunostaining extracted gangliosides on thin-layer chromatography plate as well as by immunohistochemical analysis of cerebellar cryosections. During this stage of brain development GM3 was found to be dominantly expressed on cells corresponding to Purkinje neurons. Delipidation of histological sections with chloroform/methanol caused significant reduction of anti-GM3 immunostaining, thus confirming the prevalent ganglioside nature of this antigen. These results give evidence that (1) GM3 ganglioside is associated with a specific subset of human fetal cerebellar neurons during the critical development stage, and (2) a definite ganglioside in general is distributed to a specific subset of cells in normal human brain.

Entropies of coding and noncoding sequences of DNA and proteins

The entropies of protein coding genes from Escherichia coli were calculated according to Boltzmanns formula. Entropies of the coding regions were compared to the entropies of noncoding or miscoding ones. With nucleotides as code units, the entropies of the coding regions, when compared to the entropies of complete sequences (leader and coding region as well as trailer), were seen to be lower but with a marginal statistical significance. With triplets of nucleotides as code units, the entropies of correct reading frames were significantly lower than the entropies of frameshifts +1 and -1. With amino acids as code units, the results were opposite: Biologically functional proteins had significantly higher entropies than proteins translated from the frameshifted sequences. We attempt to explain this paradox with the hypothesis that the genetic code may have the ability of lowering information content (increasing entropy) of proteins while translating them from DNA. This ability might be beneficial to bacteria because it would make the functional proteins more probable (having a higher entropy) than nonfunctional proteins translated from frameshifted sequences.

Glycoprotein and ganglioside changes in human trophoblasts after exposure to pulsed Doppler ultrasound

Changes in glycoprotein and ganglioside composition in human trophoblasts (eighth week of gestation) after in vitro exposure to pulsed Doppler ultrasound (pulse duration 1.22 microseconds; repetition frequency 11.1 kHz; center frequency 4 MHz; ISPPA = 175.5 W/cm2; ISPTA = 0.59 W/cm2) were investigated. Evacuated trophoblasts were divided in two halves and insonated for 10 min on top of a 6-cm layer of 5% gelatin in 50-mL tubes (Falcon) at 37 degrees C. One half of each trophoblast was sham insonated and served as an internal control. After insonation trophoblasts were maintained at 37 degrees C for 24 h. Glycoproteins were detected using alpha-D-mannose specific lectins from Galanthus nivalis and Narcissus pseudonarcissus. A decrease in the expression of mannose containing glycoprotein mgp47 and an increase in expression of mgp54 were observed. Ganglioside composition was also significantly altered. Concentrations of two gangliosides migrating similarly to GM2, and one similarly to GQ1, decreased by more than 75%. At the same time, concentrations of one ganglioside migrating similarly to GM3, and two other unidentified gangliosides increased two- to fourfold.