Multipotent blood progenitor cells enter the thymus and begin a protracted differentiation process in which they gradually acquire T-cell characteristics while shedding their legacy of developmental plasticity. Notch signalling and basic helix-loop-helix E-protein transcription factors collaborate repeatedly to trigger and sustain this process throughout the period leading up to T-cell lineage commitment. Nevertheless, the process is discontinuous with separately regulated steps that demand roles for additional collaborating factors. This Review discusses new evidence on the coordination of specification and commitment in the early T-cell pathway; effects of microenvironmental signals; the inheritance of stem-cell regulatory factors; and the ensemble of transcription factors that modulate the effects of Notch and E proteins, to distinguish individual stages and to polarize T-cell-lineage fate determination.

Analyses of complete genomes indicate that a massive prokaryotic gene transfer (or transfers) preceded the formation of the eukaryotic cell. In comparisons of the entire set of Methanococcus jannaschii genes with their orthologs from Escherichia coli, Synechocystis 6803, and the yeast Saccharomyces cerevisiae, it is shown that prokaryotic genomes consist of two different groups of genes. The deeper, diverging informational lineage codes for genes which function in translation, transcription, and replication, and also includes GTPases, vacuolar ATPase homologs, and most tRNA synthetases. The more recently diverging operational lineage codes for amino acid synthesis, the biosynthesis of cofactors, the cell envelope, energy metabolism, intermediary metabolism, fatty acid and phospholipid biosynthesis, nucleotide biosynthesis, and regulatory functions. In eukaryotes, the informational genes are most closely related to those of Methanococcus, whereas the majority of operational genes are most closely related to those of Escherichia, but some are closest to Methanococcus or to Synechocystis.Prokaryotic and eukaryotic evolution has long been viewed primarily through the perspective of a single molecule, rRNA. Emphasis on this perspective has led to the simplified view that prokaryotes and eukaryotes have evolved as pure lineages relatively uncorrupted by horizontal gene transfer. This view has been contradicted by some puzzling phylogenetic relationships. Recent publications demonstrate that a number of proteins such as heat shock protein HSP70, glutamate dehydrogenase, L-malate dehydrogenase, aspartate amino transferase, and others do not fit the rRNA pattern. These, and other observations, have prompted fusion, or chimeric, theories for the origin of eukaryotes (1-6). Some also indicate an intricate assortment of prokaryotic relationships (6-9). The availability of complete genomes (10-13), including the first eukaryotic genome, now provides an opportunity to reconstruct a more complete picture of eukaryotic and prokaryotic evolution through the analysis of entire functional classes.By using complete genomes from Saccharomyces cerevisiae (10), a eukaryote, Synechocystis 6803 (11), a cyanobacterium, Escherichia coli (12), a proteobacterium, and Methanococcus jannaschii (13), a methanogen, we have reconstructed the broad outlines of eukaryotic and prokaryotic evolution. Borrowing many of the comparative tools and techniques of molecular evolution (14) and having sufficiently large numbers of genes, we have followed the evolution of functional classes of genes (15) and have found two strikingly different inheritance patterns. METHODSDistances from BLASTP. Approximate distances were calculated from the ''sum probabilities'' of BLASTP (16,17) by using the distance to likelihood approximation of Kruskal (18). To assure that distances satisfied the ''symmetry'' property of distance metrics (18), P-values were symmetrized by the following procedure. If a and b are homologous genes in genomes A and B, respectively, an...

Horizontal gene transfer (HGT) spreads genetic diversity by moving genes across species boundaries. By rapidly introducing newly evolved genes into existing genomes, HGT circumvents the slow step of ab initio gene creation and accelerates genome innovation. However, HGT can only affect organisms that readily exchange genes (exchange communities). In order to define exchange communities and understand the internal and external environmental factors that regulate HGT, we analyzed approximately 20,000 genes contained in eight free-living prokaryotic genomes. These analyses indicate that HGT occurs among organisms that share similar factors. The most significant are genome size, genome G/C composition, carbon utilization, and oxygen tolerance.

The QoV Questionnaire consists of a Rasch-tested, linear-scaled, 30-item instrument on three scales providing a QoV score in terms of symptom frequency, severity, and bothersome. It is suitable for measuring QoV in patients with all types of refractive correction, eye surgery, and eye disease that cause QoV problems.

BackgroundNon-tuberculous mycobacteria have long been identified as capable of causing human disease and the number at risk, due to immune-suppression, is rising. Several reports have suggested incidence to be increasing, yet routine surveillance-based evidence is lacking. We investigated recent trends in, and the epidemiology of, non-tuberculous mycobacterial infections in England, Wales and Northern Ireland, 1995-2006.MethodsHospital laboratories voluntarily report non-tuberculous mycobacterial infections to the Health Protection Agency Centre for Infections. Details reported include age and sex of the patient, species, specimen type and source laboratory. All reports were analysed.ResultsThe rate of non-tuberculous mycobacteria reports rose from 0.9 per 100,000 population in 1995 to 2.9 per 100,000 in 2006 (1608 reports). Increases were mainly in pulmonary specimens and people aged 60+ years. The most commonly reported species was Mycobacterium avium-intracellulare (43%); M. malmoense and M. kansasii were also commonly reported. M. gordonae showed the biggest increase over the study period rising from one report in 1995 to 153 in 2006. Clinical information was rarely reported.ConclusionsThe number and rate of reports increased considerably between 1995 and 2006, primarily in older age groups and pulmonary specimens. Increases in some species are likely to be artefacts but real changes in more pathogenic species, some of which will require clinical care, should not be excluded. Enhanced surveillance is needed to understand the true epidemiology of these infections and their impact on human health.

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Aims Foreign materials used in ocular surface surgery may lead to local complications such as discomfort, scarring, or infection. Plasma-derived products such as fibrin glue may produce possible hypersensitivity reactions whereas the risk of viral transmission remains. We describe a simple method of achieving conjunctival autograft adherence during pterygium surgery avoiding potential complications associated with the use of fibrin glue or sutures. Methods After pterygium excision and fashioning of the autologous conjunctival graft, the recipient bed is encouraged to achieve natural haemostasis and relative dessication before graft placement. Excessive haemorrhage in the graft bed is tamponaded. Graft adherence and positioning is examined 20 min after surgery. Results A total of 15 eyes of 12 patients (mean (SD) age 73.7 (11.2) years), 8 females underwent SGF autologous conjunctival graft post-pterygium excision. Mean graft area was 24(1.5) mm 2 . Mean follow-up time was 9.2 (2.2) months. Cosmesis was excellent in all cases and visual acuity improved in one patient. There were no intra-or post-operative complications requiring further treatment. Conclusion This simple technique for pterygium surgery may prevent potential adverse reactions encountered with the use of foreign materials and in this small series provided safe and comparable results to current methods.

Postoperative visual acuity was good with high-level contrast sensitivity, producing significant improvement in quality of life.