High Altitude Adaptation and Phylogenetic Analysis of Tibetan Horse Based on the Mitochondrial Genome

研究测定了西藏那曲(4,500 m)、云南中甸(3,300 m)、云南德钦(3,300 m)地区3匹藏马线粒体全基因组序列.3个地区的藏马线粒体基因组全长以及结构均与韩国济州岛的马类似,但比瑞典马线粒体基因组短.藏马基因组在DNA序列上的两两相似性达99.3%.通过对线粒体蛋白编码区的分析发现,NADH6基因的蛋白序列在三匹藏马中均表现快速进化的现象.这表明NADH6基因在藏马高原适应进化过程中扮演着重要角色.此外,利用7匹藏马的D-loop区域序列以及与其亲缘关系较近的马的序列首次构建的藏马的系统发育树显示,那曲藏马与中甸、德钦藏马属于不同的分支,且存在较大的遗传多样性,表明藏马可能为多地区起源.

Visuomotor feedback gains upregulate during the learning of novel dynamics.

At an early stage of learning novel dynamics, changes in muscle activity are mainly due to corrective feedback responses. These feedback contributions to the overall motor command are gradually reduced as feedforward control is learned. The temporary increased use of feedback could arise simply from the large errors in early learning with either unaltered gains or even slightly downregulated gains, or from an upregulation of the feedback gains when feedforward prediction is insufficient. We therefore investigated whether the sensorimotor control system alters feedback gains during adaptation to a novel force field generated by a robotic manipulandum. To probe the feedback gains throughout learning, we measured the magnitude of involuntary rapid visuomotor responses to rapid shifts in the visual location of the hand during reaching movements. We found large increases in the magnitude of the rapid visuomotor response whenever the dynamics changed: both when the force field was first presented, and when it was removed. We confirmed that these changes in feedback gain are not simply a byproduct of the change in background load, by demonstrating that this rapid visuomotor response is not load sensitive. Our results suggest that when the sensorimotor control system experiences errors, it increases the gain of the visuomotor feedback pathways to deal with the unexpected disturbances until the feedforward controller learns the appropriate dynamics. We suggest that these feedback gains are upregulated with increased uncertainty in the knowledge of the dynamics to counteract any errors or disturbances and ensure accurate and skillful movements.

Active dendrites: Adaptation to spike-based communication

Computational analyses of dendritic computations often assume stationary inputs to neurons, ignoring the pulsatile nature of spike-based communication between neurons and the moment-to-moment fluctuations caused by such spiking inputs. Conversely, circuit computations with spiking neurons are usually formalized without regard to the rich nonlinear nature of dendritic processing. Here we address the computational challenge faced by neurons that compute and represent analogue quantities but communicate with digital spikes, and show that reliable computation of even purely linear functions of inputs can require the interplay of strongly nonlinear subunits within the postsynaptic dendritic tree.Our theory predicts a matching of dendritic nonlinearities and synaptic weight distributions to the joint statistics of presynaptic inputs. This approach suggests normative roles for some puzzling forms of nonlinear dendritic dynamics and plasticity.

Improving LVCSR system combination using neural network language model cross adaptation

State-of-the-art large vocabulary continuous speech recognition (LVCSR) systems often combine outputs from multiple subsystems developed at different sites. Cross system adaptation can be used as an alternative to direct hypothesis level combination schemes such as ROVER. The standard approach involves only cross adapting acoustic models. To fully exploit the complimentary features among sub-systems, language model (LM) cross adaptation techniques can be used. Previous research on multi-level n-gram LM cross adaptation is extended to further include the cross adaptation of neural network LMs in this paper. Using this improved LM cross adaptation framework, significant error rate gains of 4.0%-7.1% relative were obtained over acoustic model only cross adaptation when combining a range of Chinese LVCSR sub-systems used in the 2010 and 2011 DARPA GALE evaluations. Copyright © 2011 ISCA.

Integrated online speaker clustering and adaptation

For many applications, it is necessary to produce speech transcriptions in a causal fashion. To produce high quality transcripts, speaker adaptation is often used. This requires online speaker clustering and incremental adaptation techniques to be developed. This paper presents an integrated approach to online speaker clustering and adaptation which allows efficient clustering of speakers using the same accumulated statistics that are normally used for adaptation. Using a consistent criterion for both clustering and adaptation should yield gains for both stages. The proposed approach is evaluated on a meetings transcription task using audio from multiple distant microphones. Consistent gains over standard clustering and adaptation were obtained. Copyright © 2011 ISCA.

Use of contexts in language model interpolation and adaptation

Language models (LMs) are often constructed by building multiple individual component models that are combined using context independent interpolation weights. By tuning these weights, using either perplexity or discriminative approaches, it is possible to adapt LMs to a particular task. This paper investigates the use of context dependent weighting in both interpolation and test-time adaptation of language models. Depending on the previous word contexts, a discrete history weighting function is used to adjust the contribution from each component model. As this dramatically increases the number of parameters to estimate, robust weight estimation schemes are required. Several approaches are described in this paper. The first approach is based on MAP estimation where interpolation weights of lower order contexts are used as smoothing priors. The second approach uses training data to ensure robust estimation of LM interpolation weights. This can also serve as a smoothing prior for MAP adaptation. A normalized perplexity metric is proposed to handle the bias of the standard perplexity criterion to corpus size. A range of schemes to combine weight information obtained from training data and test data hypotheses are also proposed to improve robustness during context dependent LM adaptation. In addition, a minimum Bayes' risk (MBR) based discriminative training scheme is also proposed. An efficient weighted finite state transducer (WFST) decoding algorithm for context dependent interpolation is also presented. The proposed technique was evaluated using a state-of-the-art Mandarin Chinese broadcast speech transcription task. Character error rate (CER) reductions up to 7.3 relative were obtained as well as consistent perplexity improvements. © 2012 Elsevier Ltd. All rights reserved.

Language model cross adaptation for LVCSR system combination

State-of-the-art large vocabulary continuous speech recognition (LVCSR) systems often combine outputs from multiple sub-systems that may even be developed at different sites. Cross system adaptation, in which model adaptation is performed using the outputs from another sub-system, can be used as an alternative to hypothesis level combination schemes such as ROVER. Normally cross adaptation is only performed on the acoustic models. However, there are many other levels in LVCSR systems' modelling hierarchy where complimentary features may be exploited, for example, the sub-word and the word level, to further improve cross adaptation based system combination. It is thus interesting to also cross adapt language models (LMs) to capture these additional useful features. In this paper cross adaptation is applied to three forms of language models, a multi-level LM that models both syllable and word sequences, a word level neural network LM, and the linear combination of the two. Significant error rate reductions of 4.0-7.1% relative were obtained over ROVER and acoustic model only cross adaptation when combining a range of Chinese LVCSR sub-systems used in the 2010 and 2011 DARPA GALE evaluations. © 2012 Elsevier Ltd. All rights reserved.

Transducer and base compliance alter the in situ 6 dof force measured from muscle during an isometric contraction in a multi-joint limb.

Although musculoskeletal models are commonly used, validating the muscle actions predicted by such models is often difficult. In situ isometric measurements are a possible solution. The base of the skeleton is immobilized and the endpoint of the limb is rigidly attached to a 6-axis force transducer. Individual muscles are stimulated and the resulting forces and moments recorded. Such analyses generally assume idealized conditions. In this study we have developed an analysis taking into account the compliances due to imperfect fixation of the skeleton, imperfect attachment of the force transducer, and extra degrees of freedom (dof) in the joints that sometimes become necessary in fixed end contractions. We use simulations of the rat hindlimb to illustrate the consequences of such compliances. We show that when the limb is overconstrained, i.e., when there are fewer dof within the limb than are restrained by the skeletal fixation, the compliances of the skeletal fixation and of the transducer attachment can significantly affect measured forces and moments. When the limb dofs and restrained dofs are matched, however, the measured forces and moments are independent of these compliances. We also show that this framework can be used to model limb dofs, so that rather than simply omitting dofs in which a limb does not move (e.g., abduction at the knee), the limited motion of the limb in these dofs can be more realistically modeled as a very low compliance. Finally, we discuss the practical implications of these results to experimental measurements of muscle actions.

Is titin a 'winding filament'? A new twist on muscle contraction.

Recent studies have demonstrated a role for the elastic protein titin in active muscle, but the mechanisms by which titin plays this role remain to be elucidated. In active muscle, Ca(2+)-binding has been shown to increase titin stiffness, but the observed increase is too small to explain the increased stiffness of parallel elastic elements upon muscle activation. We propose a 'winding filament' mechanism for titin's role in active muscle. First, we hypothesize that Ca(2+)-dependent binding of titin's N2A region to thin filaments increases titin stiffness by preventing low-force straightening of proximal immunoglobulin domains that occurs during passive stretch. This mechanism explains the difference in length dependence of force between skeletal myofibrils and cardiac myocytes. Second, we hypothesize that cross-bridges serve not only as motors that pull thin filaments towards the M-line, but also as rotors that wind titin on the thin filaments, storing elastic potential energy in PEVK during force development and active stretch. Energy stored during force development can be recovered during active shortening. The winding filament hypothesis accounts for force enhancement during stretch and force depression during shortening, and provides testable predictions that will encourage new directions for research on mechanisms of muscle contraction.

Cooperation of Mtmr8 with PI3K Regulates Actin Filament Modeling and Muscle Development in Zebrafish

Background: It has been shown that mutations in at least four myotubularin family genes (MTM1, MTMR1, 2 and 13) are causative for human neuromuscular disorders. However, the pathway and regulative mechanism remain unknown. Methodology/Principal Findings: Here, we reported a new role for Mtmr8 in neuromuscular development of zebrafish. Firstly, we cloned and characterized zebrafish Mtmr8, and revealed the expression pattern predominantly in the eye field and somites during early somitogenesis. Using morpholino knockdown, then, we observed that loss-of-function of Mtmr8 led to defects in somitogenesis. Subsequently, the possible underlying mechanism and signal pathway were examined. We first checked the Akt phosphorylation, and observed an increase of Akt phosphorylation in the morphant embryos. Furthermore, we studied the PH/G domain function within Mtmr8. Although the PH/G domain deletion by itself did not result in embryonic defect, addition of PI3K inhibitor LY294002 did give a defective phenotype in the PH/G deletion morphants, indicating that the PH/G domain was essential for Mtmr8's function. Moreover, we investigated the cooperation of Mtmr8 with PI3K in actin filament modeling and muscle development, and found that both Mtmr8-MO1 and Mtmr8-MO2+LY294002 led to the disorganization of the actin cytoskeleton. In addition, we revealed a possible participation of Mtmr8 in the Hedgehog pathway, and cell transplantation experiments showed that Mtmr8 worked in a non-cell autonomous manner in actin modeling. Conclusion/Significance: The above data indicate that a conserved functional cooperation of Mtmr8 with PI3K regulates actin filament modeling and muscle development in zebrafish, and reveal a possible participation of Mtmr8 in the Hedgehog pathway. Therefore, this work provides a new clue to study the physiological function of MTM family members.