Aging and the metrics of time

In contrast to clock time, which is extrinsic, universal and reversible, age is an intrinsic, directed measure of the state of a particular system. It is proposed that if the dynamical equations of a given system are cast into canonical form, a time scale intrinsic to that system can be derived. The metric which converts a given intrinsic time to clock time is derived in terms of the given system's constitutive parameters. Age becomes a question of similitude, two systems being in corresponding states (i.e. at the same age) at identical instants of intrinsic time (not clock time).It is further proposed that there is an intrinsic time associated with any dissipative process and that the coupling coefficients, L_ik, of irreversible thermodynamics are metrics which scale the passage of intrinsic time to clock time as measured by a standard harmonic oscillator. Thus in addition to the long standing conjecture that entropy production determines the direction of time's arrow there also is a sense in which it determines the rate of its flow.     

Integrated detection of intrinsic fluorophores in live microbial cells using an array of thin film amorphous silicon photodetectors

Two-dimensional fluorescence spectroscopy (2D FS) provides a non-invasive means to assess cell condition without the introduction of changes to the cell environment. The method relies on the measurement of the excitation-emission fluorescence intensity matrix of key intrinsic fluorophores, like aromatic amino acids, enzyme cofactors, and vitamins. Commonly used detection systems are complex, with multiple bandpass filters, and are hard to miniaturize. Here, an amorphous silicon photodetector array system integrated with amorphous silicon-carbon alloy filters designed to detect three key fluorophores - tryptophan (Trp), reduced nicotine adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) - is demonstrated. These intrinsic fluorophores were detected in pure solutions and also in suspended yeast cells. The array system was used to monitor changes in intrinsic fluorophore concentration when a yeast cell solution was subject to a thermal shock stress.     

外周神经再生机制的研究进展

在特定环境和神经元自身生长能力激活的条件下,受损的外周神经能自我再生,而中枢神经系统却无法实现。受损的外周神经元生长能力的激活受多种因素调节,包括内在因素(如胞浆环磷酸腺苷(cAMP)水平)和外在因素(如细胞外基质、神经营养因子和细胞因子等)。该文主要对现阶段外周神经再生的内在及外在因素的分子机制进行综述。     

Neural networks in intestinal immunoregulation

Key physiological functions of the intestine are governed by nerves and neurotransmitters. This complex control relies on two neuronal systems: an extrinsic innervation supplied by the two branches of the autonomic nervous system and an intrinsic innervation provided by the enteric nervous system. As a result of constant exposure to commensal and pathogenic microflora, the intestine developed a tightly regulated immune system. In this review, we cover the current knowledge on the interactions between the gut innervation and the intestinal immune system. The relations between extrinsic and intrinsic neuronal inputs are highlighted with regards to the intestinal immune response. Moreover, we discuss the latest findings on mechanisms underlying inflammatory neural reflexes and examine their relevance in the context of the intestinal inflammation. Finally, we discuss some of the recent data on the identification of the gut microbiota as an emerging player influencing the brain function.     

Visual deprivation suppresses L5 pyramidal neuron excitability by preventing the induction of intrinsic plasticity

In visual cortex monocular deprivation (MD) during a critical period (CP) reduces the ability of the deprived eye to activate cortex, but the underlying cellular plasticity mechanisms are incompletely understood. Here we show that MD reduces the intrinsic excitability of layer 5 (L5) pyramidal neurons and enhances long-term potentiation of intrinsic excitability (LTP-IE). Further, MD and LTP-IE induce reciprocal changes in K(v)2.1 current, and LTP-IE reverses the effects of MD on intrinsic excitability. Taken together these data suggest that MD reduces intrinsic excitability by preventing sensory-drive induced LTP-IE. The effects of MD on excitability were correlated with the classical visual system CP, and (like the functional effects of MD) could be rapidly reversed when vision was restored. These data establish LTP-IE as a candidate mechanism mediating loss of visual responsiveness within L5, and suggest that intrinsic plasticity plays an important role in experience-dependent refinement of visual cortical circuits.     

Olfactory coding: revealing intrinsic representations of odors.

Recent studies have applied optical imaging of intrinsic signals to the rodent olfactory system, providing a unique view of how odorous molecules are represented in the central nervous system.     

The Influence of Intrinsic Muscle Properties on Musculoskeletal System Stability: A Modelling Study

The objective of this study is to investigate how the intrinsic mechanical properties of muscles will affect the musculoskeletal system stability. A typical musculoskeletal joint driven by a pair of antagonist muscles confined only in the sigittal plane was constructed. The dynamic characteristics of the flexor and extensor muscles induced by neural inputs were represented by three dynamic processes: neural excitation, muscle activation and muscle contraction dynamics. The muscle contraction mechanics was described using a modified Hill's model with a Contractile Element (CE), a parallel elastic element and a serial elastic element. Additionally, the change of muscle Physiological Cross-Sectional Area (PCSA) and pennation angle during muscle contraction were also considered. A set of dynamic simulations were conducted by applying an external impulsive force at the distal part of the musculoskeletal system. Sensitivity analysis was conducted to investigate the effect of the CE's force-length relationship, the CE's force-velocity relationship, the force-length relationship of the serial elastic element, the parallel elastic element and the pennation angle on the system stability. The results show that the muscles with full intrinsic mechanical properties are sufficient to stabilize the system subject to an impulsive force perturbation without reflexive changes in activations. To guarantee a self-stabilizing ability, a proper CE's force-velocity relationship, the existence of a series elastic element and a sufficient muscle co-contraction level are necessary. This study would provide insight into the intrinsic design and function of the musculoskeletal system, and also give implications for the design of bionic actuators, biomimetic robotics and prosthetic devices.     

The generation and diversification of spinal motor neurons: signals and responses

Motor neurons are probably the best characterised neuronal class in the vertebrate central nervous system and have become a paradigm for understanding the mechanisms that control the development of vertebrate neurons. For many investigators working on this problem the chick embryo is the model system of choice and from these studies a picture of the steps involved in motor neuron generation has begun to emerge. These findings suggest that motor neuron generation is shaped by extracellular signals that regulate intrinsic, cell-autonomous determinants at sequential steps during development. The chick embryo has played a prominent role in identifying the sources of these signals, defining their molecular identities and determining the cell intrinsic programs they regulate.     

Candidate glutamatergic neurons in the visual system of Drosophila

The visual system of Drosophila contains approximately 60,000 neurons that are organized in parallel, retinotopically arranged columns. A large number of these neurons have been characterized in great anatomical detail. However, studies providing direct evidence for synaptic signaling and the neurotransmitter used by individual neurons are relatively sparse. Here we present a first layout of neurons in the Drosophila visual system that likely release glutamate as their major neurotransmitter. We identified 33 different types of neurons of the lamina, medulla, lobula and lobula plate. Based on the previous Golgi-staining analysis, the identified neurons are further classified into 16 major subgroups representing lamina monopolar (L), transmedullary (Tm), transmedullary Y (TmY), Y, medulla intrinsic (Mi, Mt, Pm, Dm, Mi Am), bushy T (T), translobula plate (Tlp), lobula intrinsic (Lcn, Lt, Li), lobula plate tangential (LPTCs) and lobula plate intrinsic (LPi) cell types. In addition, we found 11 cell types that were not described by the previous Golgi analysis. This classification of candidate glutamatergic neurons fosters the future neurogenetic dissection of information processing in circuits of the fly visual system.     

First principle study of cysteine molecule on intrinsic and Au-doped graphene surface as a chemosensor device

To search for a high sensitivity sensor for cysteine, we investigated the adsorption of cysteine on intrinsic and Au-doped graphene sheets using density functional theory calculations. Binding energy is primarily determined by the type of atom which is closer to the adsorbed sheet. Compared with intrinsic graphene, Au-doped graphene system has higher binding energy value and shorter connecting distance, in which strong Au-S, Au-N and Au-O chemical bond interaction play the key role for stability. Furthermore, the density of states results show orbital hybridization between cysteine and Au-doped graphene sheet, but slight hybridization between the cysteine molecule and intrinsic graphene sheet. Large charge transfers exist in Au-doped graphene-cysteine system. The results of DOS and charge transfer calculations suppose that the electronic properties of graphene can be tuned by the adsorption site of cysteine. Therefore, graphene and Au-doped graphene system both possess sensing ability, except that Au-doped graphene is a better sensor for cysteine than intrinsic graphene.     

Constructive effects of fluctuations in genetic and biochemical regulatory systems

Biochemical and genetic regulatory systems that involve low concentrations of molecules are inherently noisy. This intrinsic stochasticity has received considerable interest recently, leading to new insights about the sources and consequences of noise in complex systems of genetic regulation. However, most prior work was devoted to the reduction of fluctuation and the robustness of cellular function with respect to intrinsic noise. Here, we focus on several scenarios in which the inherent molecular fluctuations are not merely a nuisance, but act constructively and bring about qualitative changes in the dynamics of the system. It will be demonstrated that in many typical situations biochemical and genetic regulatory systems may utilize intrinsic noise to their advantage.     

Intrinsic and environmental response pathways that regulate root system architecture

Root system development is an important agronomic trait. The right architecture in a given environment allows plants to survive periods of water of nutrient deficit, and compete effectively for resources. Root systems also provide an optimal system for studying developmental plasticity, a characteristic feature of plant growth. This review proposes a framework for describing the pathways regulating the development of complex structures such as root systems: intrinsic pathways determine the characteristic architecture of the root system in a given plant species, and define the limits for plasticity in that species. Response pathways co-ordinate environmental cues with development by modulating intrinsic pathways. The current literature describing the regulation of root system development is summarized here within this framework. Regulatory pathways are also organized based on their specific developmental effect in the root system. All the pathways affect lateral root formation, but some specifically target initiation of the lateral root, while others target the development and activation of the lateral root primordium, or the elongation of the lateral root. Finally, we discuss emerging approaches for understanding the regulation of root system architecture.     

Protein aggregation as a paradigm of aging

The process of physiological decline leading to death of the individual is driven by the deteriorating capacity to withstand extrinsic and intrinsic hazards, resulting in damage accumulation with age. The dynamic changes with time of the network governing the outcome of misfolded proteins, exemplifying as intrinsic hazards, is considered here as a paradigm of aging. The main features of the network, namely, the non-linear increase of damage and the presence of amplifying feedback loops within the system are presented through a survey of the different components of the network and related cellular processes in aging and disease.     

激光二极管微振动传感器在肌肉震颤检测中的应用

为了实现肌肉震颤的光学探测，本文设计并研制了一套基于光反馈效应的直接频率调制激光二极管微振动传感器。微弱机械振动信号的探测结果表明，该系统能实现无接触测量。在此基础上，对人体前臂内侧屈肌群紧张收缩时的肌肉震颤进行了非接触测量，研究了肌肉震颤的特性，研究结果提示：最大自发收缩量是肌肉收缩的固有能力，而肌肉震颤的峰值频率是肌肉的固有属性，这两者是从相互独立的不同的侧面反映肌肉的特征；肌肉震颤的幅度是肌肉在和情况下的一种反应，在一定的限度内这种反应与肌肉的能力之间没有明显关系。     

Investigating a network model of word generation with positron emission tomography.

By using positron emission tomography (PET) we examined the biological validity of a network model describing changes in cerebral activity associated with intrinsic and extrinsic word generation. The production of words not specified by an extrinsic stimulus constitutes willed or intrinsic generation. Perceiving a heard word is an example of extrinsic generation. The model incorporates three neuronal systems: a pool that stores word representations in a distributed fashion, an afferent system conveying sensory input to the pool and a modulating system that alters the responsivity of neurons in the pool. Simulations based on the model suggested that intrinsic generation would be associated with low activity in the pool, consequent on reduced modulation, and extrinsic generation with high activity. We measured cerebral activity with PET during intrinsic (verbal fluency) and extrinsic (responding to heard words) word generation and found this pattern of changes in the left superior temporal region. We were able to designate this region the site of the distributed word store and implicate the left dorsolateral prefrontal cortex (DLPFC) as the source of modulation. The relation between the superior temporal gyrus and DLPFC was shown by examining the correlation between the two regions in terms of cerebral activity. We conclude that the left DLPFC is responsible for modulating the responsivity of a neural system in the superior temporal gyrus and is the probable mediator of changes in attentional and intentional states that underlies the intrinsic generation of words.     

The development of intrinsic excitability in mouse retinal ganglion cells

Activity-dependent refinement of synaptic connections occurs throughout the developing nervous system, including the visual system. Retinal ganglion cells (RGCs) overproduce synapses then refine them in an activity-dependent manner that segregates RGC connections into multicellular patterns, such as eye-specific regions and retinotopic maps. Ferrets additionally segregate ON and OFF retinogeniculate pathways in an activity-dependent manner. It was unknown whether differences in ON versus OFF intrinsic and spontaneous activity occur in postnatal mouse. The work reported here measured the intrinsic properties and spontaneous activity of morphologically identified postnatal mouse RGCs, and tested the hypothesis that mouse ON and OFF RGCs develop differences in spontaneous activity. We found developmental changes in resting potential, action potential threshold, depolarization to threshold, action potential width, action potential patterns, and maximal firing rates. These results are consistent with the maturation of the intrinsic properties of RGCs extending through the first three postnatal weeks. However, there were no differences among mouse ON, OFF, and multistratified RGCs in intrinsic excitability, spontaneous synaptic drive or spontaneous action potential patterns. The absence of differences between ON and OFF activity patterns is unlike the differences that arise in ferrets. In contrast to the ferret, the ON and OFF target neurons in the mouse are organized in a random pattern, not layers. This supports the hypothesis that the absence of systematic differences in activity results in the nonlayered distribution of retinogeniculate connections.     

Chaotic dynamics may determine the effect of inter-patch migration on metapopulation survival

A simple, strategic model of a system of habitat fragments connected by conservation corridors is presented. The intrinsic dynamics of the population on each fragment are stochastic. In addition, at each generation there is a probability of a catastrophic event occurring which affects all the habitat fragments by greatly reducing the size of the population on each. Global extinction is considered to occur when all the populations simultaneously fall below a threshold value. If the intrinsic dynamics on each fragment are simple cycles or a stable equilibrium, then the addition of conservation corridors does not reduce the frequency of global extinction. This is because migration between fragments induces their populations to have values which are similar to each other. However, if the intrinsic population dynamics are chaotic then the probability of global extinction is greatly reduced by the introduction of conservation corridors. Although local extinction is likely, the chaos acts to oppose the synchronising effect of migration. Often a subset of the populations survive a catastrophe and can recolonize the other patches.     

Patterns and mechanisms of changes in the dermal cover of agnathans and fishes

According to the leading Russian evolutionary morphologists, A.N. Severtsov, A.V. Rumyantsev, and I.I. Schmalhausen, the skin and its derivatives in vertebrates are an autonomous system, with specific self-organization and intrinsic mechanisms and principles of development, which only slightly depend on abiotic and biotic factors. Evolution of tissues in dermal cover proceeded in parallel and following a mosaic pattern and was not tightly connected with phylogeny. The classification of histogenetic stages proposed by Rumyantsev, i.e., from ancestral dentin-like to cosmoid, ganoid, and bony tissues is accepted. Changes in histogenesis of the dermal cover are considered to depend primarily on intrinsic causes (such as gene expression, tissue interaction, connection with sensory system, and hormonal effects). Modern paleontological and embryological data provide evidence that ancestral mechanisms of histogenesis are stable and transferred from lower to higher levels of structural organization.     

Mouse embryonic retina delivers information controlling cortical neurogenesis

The relative contribution of extrinsic and intrinsic mechanisms to cortical development is an intensely debated issue and an outstanding question in neurobiology. Currently, the emerging view is that interplay between intrinsic genetic mechanisms and extrinsic information shape different stages of cortical development. Yet, whereas the intrinsic program of early neocortical developmental events has been at least in part decoded, the exact nature and impact of extrinsic signaling are still elusive and controversial. We found that in the mouse developing visual system, acute pharmacological inhibition of spontaneous retinal activity (retinal waves-RWs) during embryonic stages increase the rate of corticogenesis (cell cycle withdrawal). Furthermore, early perturbation of retinal spontaneous activity leads to changes of cortical layer structure at a later time point. These data suggest that mouse embryonic retina delivers long-distance information capable of modulating cell genesis in the developing visual cortex and that spontaneous activity is the candidate long-distance acting extrinsic cue mediating this process. In addition, these data may support spontaneous activity to be a general signal coordinating neurogenesis in other developing sensory pathways or areas of the central nervous system.