Expression of estrogen receptors in the pelvic floor of pre- and post-menopausal women presenting pelvic organ prolapse

The precise role of estrogen in the pathogenesis of pelvic organ prolapse (POP) is still unclear, while the results concerning the effect of selective estrogen receptor modulators on pelvic organ prolapse are contradictory. Our aim was to test whether alteration in the expression of estrogen receptors in the pelvic floor of pre- and post-menopausal women is related to genital prolapse status. The mRNA levels of ERα and ERβ in 60 biopsy specimens were measured. Significantly higher expression of ERα and higher ERα/ERβ ratio were demonstrated in post-menopausal women compared to pre-menopausal women. Higher expression of ERα and higher ERα/ERβ ratio were detected in all studied groups with POP, thus it did not reach significance in the post-menopausal group. Pre-menopausal and post-menopausal women presenting pelvic organ prolapse had no difference in the ERα expression. Our preliminary study may indicate that pelvic organ prolapse is associated with higher expression of ERα/ERβ in the pelvic floor of both pre- and post-menopausal women; thus not reaching statistical significance in the post-menopausal women was probably due to the group's size. We believe that the inevitable changes in the estrogen receptor expression over women's different lifetimes may affect the risk of genital prolapse progression, and might contribute to the further search for appropriate selective estrogen receptor modulators as a treatment for women with pelvic organ prolapse.     

Scaling of morphogen gradients

Individuals of the same or closely related species can vary substantially in size. Still, the proportions within and between tissues are precisely kept. This adaptation of pattern with size termed scaling, is receiving a growing attention. We review experimental evidence for scaling, and describe theoretical models for mechanisms that scale morphogen gradients. We particularly note the Expansion-Repression mechanism, in which a diffusible molecule that positively regulates the morphogen gradient width is repressed by morphogen signaling. The Expansion-Repression circuit provides scaling in a robust manner and is readily implemented by a host of molecular mechanisms. We suggest means for identifying such a circuit in a system of interest.     

A laminopathic mutation disrupting lamin filament assembly causes disease-like phenotypes in Caenorhabditis elegans

Mutations in the human LMNA gene underlie many laminopathic diseases, including Emery-Dreifuss muscular dystrophy (EDMD); however, a mechanistic link between the effect of mutations on lamin filament assembly and disease phenotypes has not been established. We studied the ΔK46 Caenorhabditis elegans lamin mutant, corresponding to EDMD-linked ΔK32 in human lamins A and C. Cryo-electron tomography of lamin ΔK46 filaments in vitro revealed alterations in the lateral assembly of dimeric head-to-tail polymers, which causes abnormal organization of tetrameric protofilaments. Green fluorescent protein (GFP):ΔK46 lamin expressed in C. elegans was found in nuclear aggregates in postembryonic stages along with LEM-2. GFP:ΔK46 also caused mislocalization of emerin away from the nuclear periphery, consistent with a decreased ability of purified emerin to associate with lamin ΔK46 filaments in vitro. GFP:ΔK46 animals had motility defects and muscle structure abnormalities. These results show that changes in lamin filament structure can translate into disease-like phenotypes via altering the localization of nuclear lamina proteins, and suggest a model for how the ΔK32 lamin mutation may cause EDMD in humans.     

Codon usage bias in prokaryotic pyrimidine-ending codons is associated with the degeneracy of the encoded amino acids

Synonymous codons are unevenly distributed among genes, a phenomenon termed codon usage bias. Understanding the patterns of codon bias and the forces shaping them is a major step towards elucidating the adaptive advantage codon choice can confer at the level of individual genes and organisms. Here, we perform a large-scale analysis to assess codon usage bias pattern of pyrimidine-ending codons in highly expressed genes in prokaryotes. We find a bias pattern linked to the degeneracy of the encoded amino acid. Specifically, we show that codon-pairs that encode two- and three-fold degenerate amino acids are biased towards the C-ending codon while codons encoding four-fold degenerate amino acids are biased towards the U-ending codon. This codon usage pattern is widespread in prokaryotes, and its strength is correlated with translational selection both within and between organisms. We show that this bias is associated with an improved correspondence with the tRNA pool, avoidance of mis-incorporation errors during translation and moderate stability of codon-anticodon interaction, all consistent with more efficient translation.     

Self-organized shuttling: generating sharp dorsoventral polarity in the early Drosophila embryo

Morphogen gradients pattern tissues and organs during development. When morphogen production is spatially restricted, diffusion and degradation are sufficient to generate sharp concentration gradients. It is less clear how sharp gradients can arise within the source of a broadly expressed morphogen. A recent solution relies on localized production of an inhibitor outside the domain of morphogen production, which effectively redistributes (shuttles) and concentrates the morphogen within its expression domain. Here, we study how a sharp gradient is established without a localized inhibitor, focusing on early dorsoventral patterning of the Drosophila embryo, where an active ligand and its inhibitor are concomitantly generated in a broad ventral domain. Using theory and experiments, we show that?a sharp?Toll activation gradient is produced through "self-organized shuttling," which dynamically relocalizes inhibitor production to lateral regions, followed by inhibitor-dependent ventral shuttling of the activating ligand Sp?tzle. Shuttling may represent?a general paradigm for patterning early embryos. PAPERFLICK:     

The influence of mechanical stretching on mitosis, growth, and adipose conversion in adipocyte cultures

The mechanotransduction of adipocytes is not well characterized in the literature. In this study, we employ stochastic modeling fitted to experiments for characterizing the influence of mechanical stretching delivered to adipocyte monolayers on the probabilities of commitment to the adipocyte lineage, mitosis, and growth after mitosis in 3T3-L1 adipocytes. We found that the probability of a cell to become committed to the adipocyte lineage in a single division when cultured on an elastic substrate was 0.025, which was indistinguishable between cultures that were radially stretched (to 12% strain) and control cultures. The probability of undergoing mitosis however was different between the groups, being 0.4 in the stretched cultures and 0.6 in the controls. The probability of growing after mitosis was affected by the stretching as well and was 0.9 and 0.8 in the stretched and control groups, respectively. We conclude that static stretching of the substrate of adipocyte cultures influences the mitotic potential of the cells as well as the growth potential post-mitosis. The present work provides better understanding of the mechanotransduction of adipocytes and in particular quantify how stretching influences the likelihood of cell proliferation and differentiation and, consequently, adipogenesis in the adipocyte cultures.     

Promoting organ donation registration with the priority incentive: Israeli transplantation surgeons' and other medical practitioners' views and ethical concerns

Because the number of organs available for transplantation does not meet the needs of potential recipients, some have proposed that a potentially effective way to increase registration is to offer a self-benefit incentive that grants a 'preferred status' or some degree of prioritization to those who register as potential donors, in case they might need organs. This proposal has elicited an ethical debate on the appropriateness of such a benefit in the context of a life-saving medical procedure. In this paper we review arguments and ethical concerns raised by scholars, and studies of views of members of the public regarding the prioritization incentive system. We also report on our study of the views of those involved in organ transplant and of other medical professionals in Israel, as over half a decade ago Israel implemented a prioritization incentive system. Bioethicists propose that key stakeholders' views can provide additional arguments and perspectives on controversial issues. Proponents justify the prioritization incentive drawing mainly on arguments related to its potential effectiveness, reciprocity and fairness. Opponents point to the fact that registering is not binding and not an actual donation, and raise concerns regarding equity, autonomy and gaming the system. Ethical concerns raised by the practitioners in the study were examined in light of scholars' arguments and actual registration and donation data. Practitioners involved in transplantation raised ethical concerns corresponding to those raised by scholars as well as additional concerns. They also challenged proponents' assumptions regarding the utility of the incentive system from their own experience and argued that proponents obscure the meaning of reciprocity.