Are heart valves from donors over 65 years of age morphologically suitable for transplantation?

Since there is no upper age limit for general organ donation, unlike heart valve donation, and since a quarter of all organ donors are 65 years and older, we examined whether the heart valves from these donors are suitable as allografts. In the period 1999–2004 the aortic valve and pulmonary valve of 100 organ donors above 65 years of age were examined to establish whether they would have been suitable as valve grafts. To compare the valve grafts above and below the age limit of 65 years, we used data on the aortic and pulmonary valves of 380 organ donors below the age limit in the same time period. Examination of the 200 heart valves showed that – just like valves from donors below the age limit – 100 of them would have met the medical quality standards for transplantation, which discriminate among optimal, suitable and unsuitable tissue morphology. The morphological suitability of the aortic valves decreases rapidly during the 4th decade of life and near to the age limit only 6% of them are accepted as grafts. The rate of potentially acceptable aortic valve grafts from organ donors aged over 65 years of 15% is also small. By contrast, the pulmonary valves are not affected by age-related tissue changes that might reduce their transplantability. The predominant majority (85%) of potential pulmonary valve grafts from organ donors over 65 years of age fulfilled the acceptance criteria, half of them (48%) even showing good tissue quality. In light of these results the age limit was raised to 70 years in 2005.     

Localization of acetylcholine receptors and synaptic ultrastructure at nerve-muscle contacts in culture: dependence on nerve type

In cultures of xenopus myotomal muscle cells and spinal cord (SC) some of the nerve-muscle contacts exhibit a high density of acetylcholine receptors (AchRs [Anderson et al., 1977, J. Physiol. (Lond.). 268:731- 756,757-773]) and synaptic ultrastructure (Weldon and Cohen, 1979, J. Neurocytol. 8:239-259). We have examined whether similarly specialized contacts are established when the muscle cells are cultured with explants of xenopus dorsal root ganglia (DRG) or sympathetic ganglia (SG). The outgrowth from the ganglionic explants contained neuronal and non- neuronal cell processes. Although both types of processes approached within 100 A of muscle cells, synaptic ultrastructure was rarely observed at these contacts. Because patches of postsynaptic ultrastructure also develop on noncontacted muscle cells, the very few examples of contacts with such specializations probably occurred by chance. AChRs were stained with fluroscent α-bungarotoxin. More than 70 percent of the SC-contacted muscle cells exhibited a high receptor density along the path of contact. The corresponding values for DRG- and SG- contacted muscle cells were 10 and 6 percent. Similar values were obtained when the ganlionic and SC explants were cultured together in the same chamber. The few examples of high receptor density at ganglionic-muscle contacts resembled the characteristic receptor patches of noncontacted muscle cells rather than the narrow bands of high receptor density seen at SC-muscle contacts. In addition, more than 90 percent of these ganglionic- contacted muscle cells had receptor patches elsewhere, compared to less than 40 percent for the SC-contacted muscle cells. These findings indicate that the SC neurites possess a specific property which is important for the establishment of synaptically specialized contacts with muscle and that this property is lacking in the DRG and SG neurites.     

Nuclear pore biogenesis into an intact nuclear envelope

Nuclear pore complexes (NPCs) serve as transport channels across the nuclear membrane, a double lipid bilayer that physically separates the nucleoplasm and cytoplasm of eukaryotic cells. New evidence suggests that the multiprotein nuclear pores also play a role in chromatin organization and gene expression. Given the importance of NPC function, it is not surprising that a growing list of human diseases and developmental defects have been linked to its malfunction. In order to fully understand the functional repertoire of NPCs and their essential role for nuclear organization, it is critical to determine the sequence of events that lead to the formation of nuclear pores. This is particularly relevant since NPC number, and possibly composition, are tightly linked to metabolic activity. Most of our knowledge is derived from NPC formation that occurs in dividing cells at the end of mitosis when the nuclear envelope (NE) and NPCs reform from disassembled precursors. However, NPC assembly also takes place during interphase into an intact NE. Importantly, this process is not restricted to dividing cells but also occurs during cell differentiation. Here, we will review aspects unique to this process, namely the regulation of nuclear expansion and the mechanisms of fusion between the outer and inner nuclear membranes. We will then discuss conserved and diverging mechanisms between post-mitotic and interphase assembly of the proteinaceous structure in light of recently published data.     

Statistical properties of the variation at linked microsatellite loci: implications for the history of human Y chromosomes [published erratum appears in Mol Biol Evol 1997 Mar;14(3):354]

It has recently been suggested that observed levels of variation at microsatellite loci can be used to infer patterns of selection in genomes and to assess demographic history. In order to evaluate the feasibility of these suggestions it is necessary to know something about how levels of variation at microsatellite loci are expected to fluctuate due simply to stochasticity in the processes of mutation and inheritance (genetic sampling). Here we use recently derived properties of the stepwise mutation model to place confidence intervals around the variance in repeat score that is expected at mutation-drift equilibrium and outline a statistical test for whether an observed value differs significantly from expectation. We also develop confidence intervals for the time course of the buildup of variation following a complete elimination of variation, such as might be caused by a selective sweep or an extreme population bottleneck. We apply these methods to the variation observed at human Y-specific microsatellites. Although a number of authors have suggested the possibility of a very recent sweep, our analyses suggest that a sweep or extreme bottleneck is unlikely to have occurred anytime during the last approximately 74,000 years. To generate this result we use a recently estimated mutation rate for microsatellite loci of 5.6 x 10(-4) along with the variation observed at autosomal microsatellite loci to estimate the human effective population size. This estimate is 18,000, implying an effective number of 4,500 Y chromosomes. One important general conclusion to emerge from this study is that in order to reject mutation-drift equilibrium at a set of linked microsatellite loci it is necessary to have an unreasonably large number of loci unless the observed variance is far below that expected at mutation-drift equilibrium.      

High-resolution climatic analysis of wood anatomical features in Corsican pine from Corsica (France) using latewood tracheid profiles

Key message

We propose a new methodology to identify intra-annual density fluctuations in latewood using cell features and relative radial position within the latewood of pine trees growing on Corsica, France. Climatic forcing of latewood wood anatomical anomalies was analyzed.

Abstract

We analyzed latewood anatomical features from Corsican pine (Pinus nigra ssp. laricio) of high-elevation sites in Corsica (France) derived from digital images of the wood surface. Latewood of each ring during the period 1950–2008 was partitioned into ten equal parts P1–P10. Mean values of the cell parameters cell lumen area (CLA), radial cell width (RCW), radial cell wall thickness (CWT), and modeled latewood density (MLD) were calculated for P1–P10. The cellular profiles for each cell parameter were subjected to principal component analyses. It was possible to quantify macroscopically visible variations of wood anatomy like intra-annual density fluctuations (IADFs) by latewood profiles of different cell parameters. A combination of cell parameter characteristics including their relative radial position within latewood provides a quantification of the cell anatomical variations in an IADF. Individual cell parameter chronologies and principal components of cell parameter profiles were correlated with climate data to determine the climatic forcing on latewood formation. Average cell parameter profiles and deviations from the long-term means are able to describe “normal” and “anomalous” environmental conditions during latewood formation. Cell feature anomalies throughout the latewood during individual years allow the reconstruction of past weather conditions with a high temporal resolution.     

Differences in methylation profiles between HPV-positive and HPV-negative oropharynx squamous cell carcinoma: A systematic review

Oropharyngeal squamous cell carcinoma (OPSCC) is associated with human papillomavirus (HPV). HPV-positive OPSCC is considered a distinct molecular entity with a better prognosis than HPV-negative cases of OPSCC. However, the exact pathogenic mechanisms underlying the differences in clinical and molecular behavior between HPV-positive and HPV-negative OPSCC remain poorly understood. Epigenetic events play an important role in the development of cancer. Hypermethylation of DNA in promoter regions and global hypomethylation are 2 epigenetic changes that have been frequently observed in human cancers. It is suggested that heterogeneous epigenetic changes play a role in the clinical and biological differences between HPV-positive and HPV-negative tumors. Unraveling the differences in methylation profiles of HPV-associated OPSCC may provide for promising clinical applications and may pave the road for personalized cancer treatment. This systematic review aims to assess the current state of knowledge regarding differences in promoter hypermethylation and global methylation between HPV-positive and HPV-negative OPSCC.