Calcium ion binding to blood cell surfaces

Zusammenfassung Neue Erkenntnisse über die quantitativen Zusammenhänge von fixierten, negativen Ladungen an Zellmembranen und ihren Interaktionen mit Kalzium-Ionen. Die elektrophoretische Analyse der Bindung von Ca-Ionen an menschliche polymorphkernige Leukozyten und rote Blutkörperchen deutet die Anwesenheit von mindestens 3 verschiedenen anionischen Ladungskonfigurationen in der peripheren Zone der Zellen an. Die zwischen den Ca-Ionen und den Oberflächen-Anionen existierenden elektrochemischen freien Bindungsenergien sind relativ schwach; daraus folgert, dass die Ca-Ionen nur schlechte Komponenten für eine direkte interzelluläre überbrückung darstellen.     

Heterozygous missense mutations in BSCL2 are associated with distal hereditary motor neuropathy and Silver syndrome

Distal hereditary motor neuropathy (dHMN) or distal spinal muscular atrophy (OMIM #182960) is a heterogeneous group of disorders characterized by an almost exclusive degeneration of motor nerve fibers, predominantly in the distal part of the limbs. Silver syndrome (OMIM #270685) is a rare form of hereditary spastic paraparesis mapped to chromosome 11q12-q14 (SPG17) in which spasticity of the legs is accompanied by amyotrophy of the hands and occasionally also the lower limbs. Silver syndrome and most forms of dHMN are autosomal dominantly inherited with incomplete penetrance and a broad variability in clinical expression. A genome-wide scan in an Austrian family with dHMN-V (ref. 4) showed linkage to the locus SPG17, which was confirmed in 16 additional families with a phenotype characteristic of dHMN or Silver syndrome. After refining the critical region to 1 Mb, we sequenced the gene Berardinelli-Seip congenital lipodystrophy (BSCL2) and identified two heterozygous missense mutations resulting in the amino acid substitutions N88S and S90L. Null mutations in BSCL2, which encodes the protein seipin, were previously shown to be associated with autosomal recessive Berardinelli-Seip congenital lipodystrophy (OMIM #269700). We show that seipin is an integral membrane protein of the endoplasmic reticulum (ER). The amino acid substitutions N88S and S90L affect glycosylation of seipin and result in aggregate formation leading to neurodegeneration.     

Mid-mantle deformation inferred from seismic anisotropy

With time, convective processes in the Earth's mantle will tend to align crystals, grains and inclusions. This mantle fabric is detectable seismologically, as it produces an anisotropy in material properties--in particular, a directional dependence in seismic-wave velocity. This alignment is enhanced at the boundaries of the mantle where there are rapid changes in the direction and magnitude of mantle flow, and therefore most observations of anisotropy are confined to the uppermost mantle or lithosphere and the lowermost-mantle analogue of the lithosphere, the D" region. Here we present evidence from shear-wave splitting measurements for mid-mantle anisotropy in the vicinity of the 660-km discontinuity, the boundary between the upper and lower mantle. Deep-focus earthquakes in the Tonga-Kermadec and New Hebrides subduction zones recorded at Australian seismograph stations record some of the largest values of shear-wave splitting hitherto reported. The results suggest that, at least locally, there may exist a mid-mantle boundary layer, which could indicate the impediment of flow between the upper and lower mantle in this region.     

Histone H3 lysine 9 methylation is an epigenetic imprint of facultative heterochromatin.

Post-translational modifications of histone amino termini are an important regulatory mechanism that induce transitions in chromatin structure, thereby contributing to epigenetic gene control and the assembly of specialized chromosomal subdomains. Methylation of histone H3 at lysine 9 (H3-Lys9) by site-specific histone methyltransferases (Suv39h HMTases) marks constitutive heterochromatin. Here, we show that H3-Lys9 methylation also occurs in facultative heterochromatin of the inactive X chromosome (Xi) in female mammals. H3-Lys9 methylation is retained through mitosis, indicating that it might provide an epigenetic imprint for the maintenance of the inactive state. Disruption of the two mouse Suv39h HMTases abolishes H3-Lys9 methylation of constitutive heterochromatin but not that of the Xi. In addition, HP1 proteins, which normally associate with heterochromatin, do not accumulate with the Xi. These observations suggest the existence of an Suv39h-HP1-independent pathway regulating H3-Lys9 methylation of facultative heterochromatin.     

PAX6 haploinsufficiency causes cerebral malformation and olfactory dysfunction in humans.

PAX6 is widely expressed in the central nervous system. Heterozygous PAX6 mutations in human aniridia cause defects that would seem to be confined to the eye. Magnetic resonance imaging (MRI) and smell testing reveal the absence or hypoplasia of the anterior commissure and reduced olfaction in a large proportion of aniridia cases, which shows that PAX6 haploinsuffiency causes more widespread human neuro developmental anomalies.     

Have we underestimated the importance of the thymus in man?

Summary Recent immunological research has concentrated on the complex and subtle interactions between T cells, B cells and accessory cells. In these studies, little attention has been given to the adult thymus gland. Modern textbooks of disease and anatomy all stress that the gland undergoes fatty involution with age in man but omit reference to the statements here and there in the literature that the gland is active and produces lymphocytes throughout life. To suggest that the bone marrow, which also builds up fat throughout life, is atrophic and not important to adult man would deny all modern hematological concepts. Yet few people today take a parallel view of the thymus except perhaps those investigating aging and thymic hormones. In both of these areas of research it is obvious that the thymus must be active throughout life for continued good health. This brief review urges that a thorough understanding of the vital importance of the thymus in adult life is now needed. From it could emerge a new philosophy on the treatment of immune diseases in both the young (SCID and AIDS patients) and in the aged (autoimmune conditions and cancers) and it would aid our treatment of patients recovering from illnesses and from many drug treatments.