Computer ranking of the sequence of appearance of 73 features of the brain and related structures in staged human embryos during the sixth week of development

The sequence of events in the development of the brain in human embryos, already published for stages 8-15, is here continued for stages 16 and 17. With the aid of a computerized bubble-sort algorithm, 71 individual embryos were ranked in ascending order of the features present. Whereas these numbered 100 in the previous study, the increasing structural complexity gave 27 new features in the two stages now under investigation. The chief characteristics of stage 16 (approximately 37 postovulatory days) are protruding basal nuclei, the caudal olfactory elevation (olfactory tubercle), the tectobulbar tracts, and ascending fibers to the cerebellum. The main features of stage 17 (approximately 41 postovulatory days) are the cortical nucleus of the amygdaloid body, an intermediate layer in the tectum mesencephali, the posterior commissure, and the habenulo-interpeduncular tract. In addition, a typical feature at stage 17 is the crescentic shape of the lens cavity.     

An ultrahigh-throughput screening assay for estrogen receptor ligands.

Members of the steroid and thyroid hormone receptor superfamily (nuclear receptors) play diverse roles in mammalian physiology, in both normal and pathological states. For this reason, and because nuclear receptors are natural receptors for lipophilic small molecules, they are important therapeutic targets for the pharmaceutical industry. Here we describe a method for screening for ligands for one of these receptors, the estrogen receptor. The method is rapid, robust, and reliable, and has been used in an ultrahigh-throughput robotic screen. The receptor is crosslinked to a scintillant-containing solid support (FlashPlate) via a receptor-specific antibody. Test compounds are assayed for competition with a radiolabeled estrogen for binding to the immobilized receptor. Receptor-ligand complexes are allowed to form and receptor-bound radioactivity is detected in a scintillation counter. The assay has been designed for both isoforms of the estrogen receptor, alpha and beta, using separate antibodies for each. Given a radioactive tracer and an appropriate antibody, many of which are now commercially available, the assay could be established for any nuclear receptor.     

Effects of arterial compliance and non-Newtonian rheology on correlations between intimal thickness and wall shear.

A minimally diseased (mean intimal thickness = 56 microns) human aortic bifurcation was replicated in rigid and compliant flow-through casts. Both casts were perfused with physiological flow waves having the same Reynolds and unsteadiness numbers; the pulse pressure in the compliant cast produced radial strains similar to those expected from post-mortem measurements of the compliance of the original tissue. The compliant cast was perfused with a Newtonian fluid and one whose rheology was closer to that of blood. Wall shear rate histories were estimated from near-wall velocities obtained by laser Doppler velocimetry at identical sites in both casts. Intimal thickness was measured at corresponding sites in the original vessel and linear regressions were performed between these thicknesses and several normalized shear rate measures obtained from the histories. The correlations showed a positive slope--that is, the intima was thicker at sites exposed to higher shear rates--consistent with earlier results for relatively healthy vessels, but their significance was often poor. There was no significant effect of either model compliance or fluid rheology on the slopes of the correlations of intimal thickness against any normalized shear rate measure.     

Changes in the tissue concentration of folate and vitamin B12 during maturation and ageing

Age-dependent changes in folate and vitamin B₁₂ metabolism of mice have been investigated. The concentration of folate in liver plasma and blood showed a postnatal increase to a maximum at approx. 25 weeks. Total folate concentrations then remained constant whereas free folate decreased slowly up to week 98. Conversely both total and free folate of the brain were reduced extensively during the first 10 weeks of life after which time total folate concentration stabilised whilst that of free folate continued to decline slowly. The concentration of vitamin B₁₂ in brain, liver and plasma showed an initial rapid increase. The vitamin continued to accumulate more slowly in the brain and liver from weeks 10 to 98. The concentration of vitamin B₁₂ in the plasma appeared to achieve equilibrium after a period of accumulation lasting 25 weeks. These results suggest that during maturation the characteristics of folate metabolism of the brain are distinct from those of peripheral tissues, and that folate, unlike vitamin B₁₂ metabolism, undergoes continuing change with advancing age.     

The p53-induced lincRNA-p21 derails somatic cell reprogramming by sustaining H3K9me3 and CpG methylation at pluripotency gene promoters

Recent studies have boosted our understanding of long noncoding RNAs (lncRNAs) in numerous biological processes, but few have examined their roles in somatic cell reprogramming. Through expression profiling and functional screening, we have identified that the large intergenic noncoding RNA p21 (lincRNA-p21) impairs reprogramming. Notably, lincRNA-p21 is induced by p53 but does not promote apoptosis or cell senescence in reprogramming. Instead, lincRNA-p21 associates with the H3K9 methyltransferase SETDB1 and the maintenance DNA methyltransferase DNMT1, which is facilitated by the RNA-binding protein HNRNPK. Consequently, lincRNA-p21 prevents reprogramming by sustaining H3K9me3 and/or CpG methylation at pluripotency gene promoters. Our results provide insight into the role of lncRNAs in reprogramming and establish a novel link between p53 and heterochromatin regulation.     

Environmental influences on invertebrate diversity and community composition in the hyporheic zone ecotone in Texas,USA: contrasts between co-occurring epigean taxa and stygobionts

Hydrobiologia - The hyporheic zone (HZ) of streams harbors co-occurring epigean taxa and stygobionts (including HZ specialist taxa and deeper groundwater taxa) that face the same set of local...