Objective

First Place, Essay Division, 1945 Butler Literary Contest Have a purpose! Certainly if one is to get on in life with a degree of success, this seems a practical injunction. To know one\u27s objective is prerequisite to worthwhile living, for the goal determines the course to be pursued, and the nature of the goal influences the method of pursuit

Induction......

Inductive Reasonin

......Deduction

Deductive Reasonin

Global Chromatin Architecture Reflects Pluripotency and Lineage Commitment in the Early Mouse Embryo

An open chromatin architecture devoid of compact chromatin is thought to be associated with pluripotency in embryonic stem cells. Establishing this distinct epigenetic state may also be required for somatic cell reprogramming. However, there has been little direct examination of global structural domains of chromatin during the founding and loss of pluripotency that occurs in preimplantation mouse development. Here, we used electron spectroscopic imaging to examine large-scale chromatin structural changes during the transition from one-cell to early postimplantation stage embryos. In one-cell embryos chromatin was extensively dispersed with no noticeable accumulation at the nuclear envelope. Major changes were observed from one-cell to two-cell stage embryos, where chromatin became confined to discrete blocks of compaction and with an increased concentration at the nuclear envelope. In eight-cell embryos and pluripotent epiblast cells, chromatin was primarily distributed as an extended meshwork of uncompacted fibres and was indistinguishable from chromatin organization in embryonic stem cells. In contrast, lineage-committed trophectoderm and primitive endoderm cells, and the stem cell lines derived from these tissues, displayed higher levels of chromatin compaction, suggesting an association between developmental potential and chromatin organisation. We examined this association in vivo and found that deletion of Oct4, a factor required for pluripotency, caused the formation of large blocks of compact chromatin in putative epiblast cells. Together, these studies show that an open chromatin architecture is established in the embryonic lineages during development and is sufficient to distinguish pluripotent cells from tissue-restricted progenitor cells

Coupling between mechanical and neural behaviour in the human first dorsal interosseous muscle

The neural drive to a muscle and its biomechanical properties determine the force at a joint. These factors may be centrally linked. We studied the relationship between the ability of first dorsal interosseous muscle (FDI) to generate index flexion force around the metacarpophalangeal joint and the neural drive it receives in a voluntary contraction. The role of FDI was assessed in two thumb postures, thumb ‘down’ (thumb abducted) and thumb ‘up’ (thumb extended), and at different thumb carpometacarpal angles. These postures were designed to change acutely the flexion moment arm for FDI. The flexion twitch force evoked by supramaximal stimulation of the ulnar nerve was measured in the two postures and the change in moment arm was assessed by ultrasonography. Subjects also made voluntary flexion contractions of the index finger of ∼5 N in both postures during which neural drive to FDI and the long finger flexor muscles was measured using surface EMG. Recordings of FDI EMG were normalized to the maximal M wave. Five of the 15 subjects also had a radial nerve block to eliminate any co-contraction of the extensor muscles, and extensor muscle EMG was monitored in subjects without radial nerve block. Compared to thumb up, flexion twitch force was ∼60% greater, and the flexion moment arm was ∼50% greater with the thumb down. There was minimal effect of altered carpometacarpal angle on flexion twitch force for either thumb posture. During voluntary flexion contractions, normalized FDI EMG was ∼28% greater with thumb down, compared to thumb up, with no consistent change in neural drive to the long flexors. Hence, the contribution of FDI to index finger flexion can be altered by changes in thumb position. This is linked to changes in neural drive to FDI such that neural drive increases when the mechanical contribution increases, and provides a central mechanism to produce efficient voluntary movements

Characterization of human embryonic stem cell lines by the International Stem Cell Initiative

The International Stem Cell Initiative characterized 59 human embryonic stem cell lines from 17 laboratories worldwide. Despite diverse genotypes and different techniques used for derivation and maintenance, all lines exhibited similar expression patterns for several markers of human embryonic stem cells. They expressed the glycolipid antigens SSEA3 and SSEA4, the keratan sulfate antigens TRA-1-60, TRA-1-81, GCTM2 and GCT343, and the protein antigens CD9, Thy1 (also known as CD90), tissue- nonspecific alkaline phosphatase and class 1 HLA, as well as the strongly developmentally regulated genes NANOG, POU5F1 (formerly known as OCT4), TDGF1, DNMT3B, GABRB3 and GDF3. Nevertheless, the lines were not identical: differences in expression of several lineage markers were evident, and several imprinted genes showed generally similar allele-specific expression patterns, but some gene-dependent variation was observed. Also, some female lines expressed readily detectable levels of XIST whereas others did not. No significant contamination of the lines with mycoplasma, bacteria or cytopathic viruses was detected