Mitochondrial point mutations do not limit the natural lifespan of mice

Whether mitochondrial mutations cause mammalian aging, or are merely correlated with it, is an area of intense debate. Here, we use a new, highly sensitive assay to redefine the relationship between mitochondrial mutations and age. We measured the in vivo rate of change of the mitochondrial genome at a single-base pair level in mice, and we demonstrate that the mutation frequency in mouse mitochondria is more than ten times lower than previously reported. Although we observed an 11-fold increase in mitochondrial point mutations with age, we report that a mitochondrial mutator mouse was able to sustain a 500-fold higher mutation burden than normal mice, without any obvious features of rapidly accelerated aging. Thus, our results strongly indicate that mitochondrial mutations do not limit the lifespan of wild-type mice.     

A high-resolution map of human evolutionary constraint using 29 mammals

The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering ～4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for ～60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate- and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease.     

GLOBAL MANUFACTURING VIRTUAL NETWORK （GMVN）：A REVISITING OF THE CONCEPT AFTER THREE YEARS FIELDWORK

The idea of the global manufacturing virtual network (GMVN) was introduced in 2000 in order to highlight an emerging as well as an alternative manufacturing system which will have strong impacts on industry and implications to management theory. During the last three years, more than thirty companies - based in the electronics, bio-pharmaceuticals, garment, and home electronics appliance industries - have been studied in the UK and China. The research project addresses the emergence of the collaborative manufacturing phenomenon at three levels - sector, system and enabling technology. This paper summarises preliminary research findings from fieldwork conducted over the last three years. It seeks to clarify the characteristics and functionality of GMVN through the case studies and to contrast it to other types of business model, such as the multinational corporations (MNC) and international strategic alliances (ISAs). It also raises some new research questions and themes for further research into GMVN.     

Continuous Communication Control Disruptors During Systems Development

This paper presents an open-ended, exploratory study of formal and informal communication and control subprocesses during information systems development (ISD) over an extended period in a large bureaucracy. Using a participant action research strategy, the case study explores the continuous unintended disruptions and barriers to the effective implementation of the ISD project and suggests major variables associated with them. Based on an inductive analysis of the data, the authors suggest some tentatively hypothesized action stages for future research and a broad conceptual model incorporating the process variables. Implications for MIS research, management, and MIS professionals are discussed.     

Regional and strain variation in brain 3':5' cyclic adenosine monophosphate of inbred mice.

Regional variations were found in cAMP levels in flash frozen mouse brains with the pons and cerebellum having higher levels than the cerebrum. There were also strain variations with CBA/J and BALB/cJ having higher levels than C57B1/6J in the pons and cerebellum.     

Designing CD4 immunoadhesins for AIDS therapy

A newly-constructed antibody-like molecule containing the gp120-binding domain of the receptor for human immunodeficiency virus blocks HIV-1 infection of T cells and monocytes. Its long plasma half-life, other antibody-like properties, and potential to block all HIV isolates, make it a good candidate for therapeutic use.