Loss of ACTN3 gene function alters mouse muscle metabolism and shows evidence of positive selection in humans

More than a billion humans worldwide are predicted to be completely deficient in the fast skeletal muscle fiber protein alpha-actinin-3 owing to homozygosity for a premature stop codon polymorphism, R577X, in the ACTN3 gene. The R577X polymorphism is associated with elite athlete status and human muscle performance, suggesting that alpha-actinin-3 deficiency influences the function of fast muscle fibers. Here we show that loss of alpha-actinin-3 expression in a knockout mouse model results in a shift in muscle metabolism toward the more efficient aerobic pathway and an increase in intrinsic endurance performance. In addition, we demonstrate that the genomic region surrounding the 577X null allele shows low levels of genetic variation and recombination in individuals of European and East Asian descent, consistent with strong, recent positive selection. We propose that the 577X allele has been positively selected in some human populations owing to its effect on skeletal muscle metabolism.     

A recurrent mutation in MED12 leading to R961W causes Opitz-Kaveggia syndrome

Opitz-Kaveggia syndrome (also known as FG syndrome) is an X-linked disorder characterized by mental retardation, relative macrocephaly, hypotonia and constipation. We report here that the original family for whom the condition is named and five other families have a recurrent mutation (2881C>T, leading to R961W) in MED12 (also called TRAP230 or HOPA), a gene located at Xq13 that functions as a thyroid receptor-associated protein in the Mediator complex.     

Early changes of cyclic nucleotide levels in a mitogenic reaction in the rat mesentery.

By measuring simultaneously cAMP and cGMP we found a biphasic time course with regard to cGMP and the cGMP/cAMP ratio very early in a mitogenic reaction in vivo. This is a new finding.     

Information processing along the course of a visual interneuron.

Locust ocellar retinal cells are innervated by giant second order cells, 2 mm long, which show discrete zones of integration along their course, including a major zone in the axonal length of the neuron. The complex synaptic arrangements which exist between higher-order afferent and efferent cells and these second order cells along their course suggests that transmission takes place by the electrotonic spread of slow potentials. The size and accessibility of these visual interneurons offers a unique preparation for examining mechanisms of graded synaptic transmission.     

Effect of ethanol on toxicity and metabolism of amphetamine in the mouse.

Ethanol, 3 g/kg i.p., did not significantly alter the acute toxicity of amphetamine in the mouse. However, the urinary metabolite pattern was changed, suggesting that ethanol suppressed metabolism of the stimulant during the initial 6 h period. After 24 h, the mouse metabolized the same fraction of a given dose of amphetamine, whether it was given as amphetamine alone or amphetamine mixed with 2,3 or 4 g/kg ethanol.     

A Transport Protocol and Its Formal Description for Local Networks

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Performance analysis of optimal channel estimation and multiuser detection in a randomly-spread CDMA channel

<正> This paper analyzes performance of optimal channel estimation and multiuser detection(MUD) in a block-fading code-division multiple-access (CDMA) channel on the assumptions of randomspreading and large-system limit,by using the replica method developed in statistical mechanics.The authors find that the asymptotic spectral efficiency of the linear minimum mean-squared error(LMMSE) MUD which was proposed and analyzed by Evans and Tse in 2000 is indistinguishable fromthat of the optimal MUD for small system loads.Our results imply that performance of MUD scarcelyimproves even if one spends more computational cost than that of the LMMSE MUD,i.e.,at most thecube of the number of users,on the above-described conditions.     

Building Organizational Identity: an Insider Action Research from a Founder’s Viewpoint

This paper features the implementation of an extensive insider action research, exhaustively following the framework of Coghlan and Brannick (2010, 2014). It consisted of two action research projects - the thesis action research and the core action research - which were done in a parallel manner, both following the iterative cycles of constructing, planning, taking, and evaluating action. The thesis action research was aimed at developing a theory on building organizational identity from the viewpoint of an organizational founder. On the other hand, the core action research was focused on promoting the specific identity of the Institute for Integrality, Inc. Quality and rigor were observed in the implementation of the action research cycles. In the fieldwork, there were three main cycles undertaken – understanding organizational identity, fine-tuning the practice of this identity, and designing the integration of this identity in organizational culture. Thereafter, significant learnings were derived from meta-learning in the form of content, process, and premise reflections. Finally, through the critical reflection of the project in the light of the experience and theory, A-Founder’s Integrative Theory of Organizational Identity Building was derived.     

Programmable and autonomous computing machine made of biomolecules.

Devices that convert information from one form into another according to a definite procedure are known as automata. One such hypothetical device is the universal Turing machine, which stimulated work leading to the development of modern computers. The Turing machine and its special cases, including finite automata, operate by scanning a data tape, whose striking analogy to information-encoding biopolymers inspired several designs for molecular DNA computers. Laboratory-scale computing using DNA and human-assisted protocols has been demonstrated, but the realization of computing devices operating autonomously on the molecular scale remains rare. Here we describe a programmable finite automaton comprising DNA and DNA-manipulating enzymes that solves computational problems autonomously. The automaton's hardware consists of a restriction nuclease and ligase, the software and input are encoded by double-stranded DNA, and programming amounts to choosing appropriate software molecules. Upon mixing solutions containing these components, the automaton processes the input molecule via a cascade of restriction, hybridization and ligation cycles, producing a detectable output molecule that encodes the automaton's final state, and thus the computational result. In our implementation 1012 automata sharing the same software run independently and in parallel on inputs (which could, in principle, be distinct) in 120 microl solution at room temperature at a combined rate of 109 transitions per second with a transition fidelity greater than 99.8%, consuming less than 10-10 W.