Early circulating erythroid progenitors (BFU-E) in sickle cell anemia

Sickle cell anemia (SS) patients can be divided into two sub-populations according to peripheral HbF levels. Patients with low (<9%) HbF levels (LFSS) are characterized by an increased number of circulating BFU-E in active DNA synthesis, and release of burst promoting activity (BPA) by unstimulated low density (LD) adherent cells. In contrast, circulating BFU-E from SS patients with high (>9%) HbF levels (HFSS) are normal in number, largely in resting phase, and their LD cells do not release BPA-like activity.More recently further heterogeneity has been found among these two groups. In LFSS patients GM-CSF is constitutively produced by unstimulated monocytes. In contrast, HFSS patients' adherent cell depletion increases cycling of BFU-E in culture. CM from HFSS patients inhibits BFU-E expression in culture. Hence, LD adherent cells from HFSS patients may release an inhibitory factor(s). The nature of this factor has to be determined.In addition, there are distinct subpopulations of BFU-E responsiveness to growth factor (GM-CSF, IL-3): a) LFSS patients have a homogeneous BFU-E population, equally responsive to GM-CSF and IL-3; b) HFSS patients, in addition to this subpopulation, have a subset of BFU-E dependent exclusively on IL-3 which is 20 to 40% of the total number of circulating BFU-E. This is similar to BFU-E from normal individuals. Hence, LFSS BFU-E represent an actively proliferating population, equally responsive to GM-CSF and IL-3, controlled by at least constitutively produced GM-CSF and possibly other factors.These observations suggest a significant modification in BFU-E behavior in the subset of SS patients with low HbF levels and high hemopoietic stress. The heterogenous regulation of BFU-E in SS disease seems to be an epiphenomenon of HbF levels, and not vice-versa.     

Effects of corpora cardiaca extract,furosemide and ion substitution on sodium and chloride flux in perfused Malpighian tubules ofLocusta

Treatment with the co-transport inhibitor, furosemide decreased³⁶Cl^– flux across perfused Malpighian tubules ofLocusta. However, exclusion of³⁶Cl^– from the bathing medium had not effect on²²Na⁺ flux whereas substitution of bathing medium Na⁺ by K⁺ increased³⁶Cl^– flux. Diuretic extract of corpora cardiaca increased²²Na⁺ (by 106%) and³⁶Cl^– (by 335%) fluxes differentially.     

Photoreceptor damage following exposure to excess riboflavin

Flavins generate oxidants during metabolism and when exposed to light. Here we report that the photoreceptor layer of retinas from black-eyed rats is reduced in size by a dietary regime containing excess riboflavin. The effect of excess riboflavin was dose-dependent and was manifested by a decrease in photoreceptor length. This decrease was due in part to a reduction in the thickness of the outer nuclear layer, a structure formed from stacked photoreceptor nuclei. These changes were accompanied by an increase in photoreceptor outer segment autofluorescence following illumination at 328 nm, a wavelength that corresponds to the excitation maxima of oxidized lipopigments of the retinal pigment epithelium.     

Extraordinary levels of cadmium and zinc in a marine sponge,Tedania charcoti Topsent: inorganic chemical defense agents

The Antarctic marine spongeTedania charcoti has been shown to contain extraordinarily high natural concentrations of cadmium and zinc, which have in turn been correlated to the ability of the crude ethanol extract to modulate protein phosphorylation in chicken forebrain and to inhibit the growth of several test bacteria.     

The temporal requirement for endothelin receptor-B signalling during neural crest development

Endothelin receptor B (EDNRB) is a G-protein-coupled receptor with seven transmembrane domains which is required for the development of melanocytes and enteric neurons. Mice that are homozygous for a null mutation in the Ednrb gene are almost completely white and die as juveniles from megacolon. To determine when EDNRB signalling is required during embryogenesis, we have exploited the tetracycline-inducible system to generate strains of mice in which the endogenous Ednrb locus is under the control of the tetracycline-dependant transactivators tTa or rtTA. By using this system to express Ednrb at different stages of embryogenesis, we have determined that EDNRB is required during a restricted period of neural crest development between embryonic days 10 and 12.5. Moreover, our results imply that EDNRB is required for the migration of both melanoblasts and enteric neuroblasts.     

A telomerase component is defective in the human disease dyskeratosis congenita

The X-linked form of the human disease dyskeratosis congenita (DKC) is caused by mutations in the gene encoding dyskerin. Sufferers have defects in highly regenerative tissues such as skin and bone marrow, chromosome instability and a predisposition to develop certain types of malignancy. Dyskerin is a putative pseudouridine synthase, and it has been suggested that DKC may be caused by a defect in ribosomal RNA processing. Here we show that dyskerin is associated not only with H/ACA small nucleolar RNAs, but also with human telomerase RNA, which contains an H/ACA RNA motif. Telomerase adds simple sequence repeats to chromosome ends using an internal region of its RNA as a template, and is required for the indefinite proliferation of primary human cells. We find that primary fibroblasts and lymphoblasts from DKC-affected males are not detectably deficient in conventional H/ACA small nucleolar RNA accumulation or function; however, DKC cells have a lower level of telomerase RNA, produce lower levels of telomerase activity and have shorter telomeres than matched normal cells. The pathology of DKC is consistent with compromised telomerase function leading to a defect in telomere maintenance, which may limit the proliferative capacity of human somatic cells in epithelia and blood.     

Distribution of spatial and nonspatial information in dorsal hippocampus

The hippocampus in the mammalian brain is required for the encoding of current and the retention of past experience. Previous studies have shown that the hippocampus contains neurons that encode information required to perform spatial and nonspatial short-term memory tasks. A more detailed understanding of the functional anatomy of the hippocampus would provide important insight into how such encoding occurs. Here we show that hippocampal neurons in the rat are distributed anatomically in distinct segments along the length of the hippocampus. Each longitudinal segment contains clusters of neurons that become active when the animal performs a task with spatial attributes. Within these same segments are ordered arrangements of neurons that encode the nonspatial aspects of the task appropriate to those spatial features. Thus, anatomical segregation of spatial information, together with the interleaved representation of nonspatial information, represents a structural framework that may help to resolve conflicting views of hippocampal function.     

Periodicity in marine phosphorus burial rate

There have been arguments both for and against a periodicity of 26-33 million years (Myr) in terrestrial and extraterrestrial records. The best way to identify such periodicity is the analysis of geomarine evolutionary records. We have analysed the marine sedimentary phosphorus burial rate (PBR), as fluctuations in this rate are strong indicators of the coupling of climate, continental weathering and ocean primary productivity. We find a statistically significant harmonic component of 33 +/- 3 Myr against the estimated robust background noise spectrum, supporting the idea that geomarine processes are cyclic.