今天收到了科学网博客的审查通过确认邮件，想着写点东西，但是无奈纽约是凌晨2点，似乎脑子更接近于真正的休息空载状态，想了一下把在 blogspot 上的两个贴了过来。前些日子记下的一点东西，是偶尔得闲的纪录。一个是推荐给刚接触这个静息态脑研究领域的文献： The First Set of R-fMRI Papers for Newcomers Back to 2006, when I came to picking up my first postdoc training in Beijing Normal University, I read four papers about resting state fMRI (R-fMRI), which I strongly recommend to the new people coming to this field. Until now, they are still holding the dominant impacts on this field. They are: B. Biswal, F. Yetkin, V. Haughton and J. Hyde, Functional connectivity in the motor cortex of resting human brain using echo-planar MRI, Magn. Reson. Med. 34 (4) (1995), pp. 537541. M.E. Raichle, A.M. MacLeod, A.Z. Snyder, W.J. Powers, D.A. Gusnard, G.L. Shulman, A default mode of brain function, Proc. Natl. Acad. Sci. U. S. A. 98 (2001), pp. 676682. M.D. Greicius, B. Krasnow, A.L. Reiss and V. Menon, Functional connectivity in the resting brain: a network analysis of the default mode hypothesis, Proc. Natl. Acad. Sci. U. S. A. 100 (2003), pp. 253258. M.D. Fox, A.Z. Snyder, J.L. Vincent, M. Corbetta, D.C. Van Essen and M.E. Raichle, The human brain is intrinsically organized into dynamic, anticorrelated functional networks, Proc. Natl. Acad. Sci. U. S. A. 102 (2005), pp. 96739678. 另外一个是读了最近一个计算神经科学综述后记下的文字： A time to unify computational models on human brain coming: computational neuroscience Today is the first day of 2010. I closed reading an excellent review paper Computational and dynamic models in neuroimaging which was in press in NeuroImage. In this review, from a perspective of mathematical modeling, Dr. Friston summarized those efforts on modeling brain's function and biophysics, which have extensively enriched the neuroimaging data exploration. Of particular importance, computational neuroscience now is tending to unify the resting-state and stimulus-invoked brain, which is an extremely important transition of neuroimaging research to go beyond understanding the human brain whatever rest or task involved. We can predict, in the future (e.g., see 2010 :), that the mining schemes from computational neuroscience, machine leaning and game theory will become pretty strong for both brain mechanism and prediction. In practice, two things might attract researchers: to develop a unify measure on brain dynamic, which means that the relevant measures should intrinsically reflect the dynamical process in the brain. (e.g., using the parameters from DCM or neuro-massive models, which hopefully can be solved out as in an inverse problem frame); to apply these schemes in various applications including theory of mind, cognitive components and their interactions, clinical diagnosis, etc. 都是些匆匆的文字，如不幸读到，希望有点用。
2008年创刊的Chemosensory Perception《化学感受感知》，ISSN: 1936-5802，美国（SPRINGER, 233 SPRING ST, NEW YORK, USA, NY, 10013）出版，2009年入选 Web of Science的Science Citation Index Expanded，目前在SCI数据库可以检索到该期刊2008年的第1卷1-4期到2009年的第2卷1-3期共50篇论文。 50 篇文章包括学术论文38篇、会议论文9篇、评论2篇、社论1篇。 50 篇文章的主要国家分布：美国20篇，英国9篇，法国7篇，德国6篇，瑞典5篇，荷兰4篇，澳大利亚、意大利、丹麦各3篇等。 50篇文章共被引用31次，其中2008年被引用2次，2009年被引用29次，平均引用0.62次， H指数为3（有3篇文章每篇最少被引用3次）。 该刊的主题： Identification of chemicals producing sensory response Identification of sensory response associated with chemicals Human in vivo response to chemical stimuli Human in vitro response to chemical stimuli Neuroimaging of chemosensory function Neurological processing of chemoreception Chemoreception mechanisms Psychophysics of chemoperception Trigeminal function Multisensory perception Contextual effect on chemo-perception Behavioral response to chemical stimuli Physiological factors effecting and contributing to chemo-perception Flavor and hedonics Memory and chemo-perception 网址： http://www.springerlink.com/content/120904/ 作者指南： http://www.springer.com/life+sci/food+science/journal/12078?detailsPage=contentItemPageCIPageCounter=489909 编委会： http://www.springer.com/life+sci/food+science/journal/12078?detailsPage=editorialBoard 在线投稿： http://www.editorialmanager.com/chpe/
衰老解密解出神经科学奥秘 前一篇博客说道咬定青山一个月，苦写衰老解密后续篇，是为何物？值得那么大惊小怪吗？不看不知道，一看 也不能全知道。因为该文章在博客中目前只能为洋片，只能给出洋文的片段： 所谓 可供专家钻研， 亦为大家开眼。 若要尽知详情， 耐心等待半年。 不过为了满足某些看客的好奇心，先贴上文章的引言，并附上与老外的争辩（择时而发），让网上冲浪的好手，一道领略科学风口浪尖的头晕目眩。 Aging Resolution Implying Resolution of Neurobiochemistry －－ Revealing the Missing Codes of Life Science Dazhong Yin Abstract While the enigma of aging is understood as a result of molecular dysfunction caused by increasing entropy due to the fail of maintenance systems, a brief history of the interpretation of aging mechanisms and the exact biochemistry connecting the entropy and biological aging is addressed. Lipofuscin formation mechanisms revealing irreparable accumulative changes represent the most important aging related alterations of entropy increase in biological kingdom, which is very different from the aging process of inorganic materials. A fifth level of aging mechanism studies that highlights the importance of functional groups of biochemistry, the missing codes of life science, is put forward in this review. Significance and validities of such life codes in biology beyond genomic and proteomic concepts has also been clarified. An open-minded pondering with functional groups of biomolecules, such as carbonyl stress, may explain fatigue and sleep biochemistry in neurobiochemistry and biomedicine in broad sense. When the 19 th World Congress of Gerontology and Geriatrics confirmed and celebrated the explanation of biological aging in Paris in June 2009, most biological scientists still have been suffering the confusion of the aging mystery in related fields . Most gerontologic and geriatric scientists yet not really understand what exactly is the real value of the resolution of aging. While professor Hayflick stated aging phenotype is resulted from dysfunctional molecules caused by increasing entropy , the most headache question to many biomedical scientists becomes what is the exact biochemistry bridging the entropy and aging. More challengingly, questions were raised such as: since the enigma of aging is solved, namely maintenance systems are the determinants of longevity, thus how damage plays into the pathogenesis of degenerative diseases and how may the detailed understanding be needed to make practical use? The objective of this review is: 1) to review the history of aging interpretation and clarify further the exact biochemistry connecting the entropy and aging; 2) to address a fifth level of aging mechanism studies and highlight the missing code of life science; and 3) to predict significance and validities of such codes into a broad field of neurobiology and life sciences. 1. The Evolution of the Entropy-Related Aging Interpretation Before going into the detailed biochemical interpretation of entropy increase during senescence, a quick overview of the aging studies is fundamental. While over 300 aging theories being developed in biological history, about 30 of them are continuously regarded of importance . On one hand, these theories may be best divided in two categories, the genetic and stochastic parties. The genome relevance to aging mechanisms, after over 200 genes were discovered and identified, the pathophysiological maintenance network (system) is realized to mostly work together in determining the animals longevity (instead of being the driving force to accelerate aging) . On the other hand, the aging associated phenotypes and theories have been studied and classified mainly into four classes. Such classes are biologically ranked as at: 1) the whole animal level; 2) the organ level; 3) the cellular level; and finally 4) the molecular level . Whereas the enormous amount of data from all biological fields, particularly from various biomedical branches, have been so confusion in the literature, in some situation, aging investigation was dismissed as just too complicated for serious scientific study . It is sometimes suspected in the society of life sciences that Western biomedical research is getting lost in the forest of overloaded massive data, such as from genomics, proteomics, metabolomics and systems biology, a quickly growing field that will certainly add more complexity to the chaotic life science of gerontology and geriatrics. Should life science become more and more complicated or if there will be some simple access, or code, that could solve the mass? Not devoted to look for such code, however, we happened to view some biochemistry of life science in common under lipofuscin investigation . No matter how complicated and confusion the biological impairments start and/or develope, two major energy metabolism induced biological stresses representing most important biological side-reactions are understood as the key aging causes . These two are known as free radical oxidative stress and nonenzymatic glycosylation stress (being simplified as glycation stress later) . While the oxidative stress may finally form advanced lipid peroxidation end-products (ALEs), the glycation stress can result in advanced glycation end-products (AGEs) . By realizing with surprise that these two biochemical stress carry a similar middle step －－ carbonyl-amino reaction －－ the reaction was primarily pinpointed by the author as a common reaction during lipofuscin formation and it was proposed later as carbonyl toxification theory of aging in 1995 . Because the crosslinkages resulting from biological reactions are mostly irreparable , the carbonyl stress, and other biochemical cross-linking culprits had already been stressed in a crosslinkage theory of aging by Bjorksten already in 1968 . After a half-century, the carbonyl stress appears to remain as the key process of the crosslinkage-related inevitable aging alterations both intracellularly and extracellularly . Since a large number of experiments showed clear defects of the free radical theory of aging , Sohal and others, while verifying the free radical theory of aging (Orr and Sohal, 1994), has tried also to build up a new flagship to interpret aging mechanisms, the so called oxidative stress hypothesis of aging . The reformed theory is thoughtful, but it is unsatisfactory to consider oxidative stress and related impairments to be the genuine aging mechanism since most of such damages are repairable by maintenance system. When the oxidative stress theory was found not to correlate with the maximum lifespan (MLS), the understanding of aging mechanisms became much more confused than ever before . For clarifying the complex of concepts in the field, we propose to illustrate the problem with a quite simple formula as given below (Formula 1): Damages ( aging causes ) Repairing ( maintenance ) = Aging alterations ( aging process ) Formula 1. Aging mechanisms (and process) in a general view. From the formula, one may recognize simply that carbonyl stress-related age pigment formation is more significant than oxygen free radicals during real aging process simply because it contributes almost directly to the crucial accumulation-based aging process, the right side of the formula given above. Although a complete picture of biological aging mechanisms cannot be obtained only through the accumulation biochemistry of biological alterations (garbage accumulation , in the case of lipofuscin formation), a general picture of aging starts to emerge. Because no matter how complex the detailed aging mechanisms (causes and consequences etc.) may be, their main clues and the final results are available, especially the net result of impairments and restorations, which are highlighted by the accumulation biology of age pigments, the well known hallmark of aging as articulated primarily by Sohal et al. (Sohal, 1981; Porta, 1990; Yin, 1996; Szweda, et al. 2003). More open-mindedly, considering the nature of aging of all kind of materials, impairments and damages are encountered to either organic or inorganic materials. The difference is that inorganic materials can not repair the damages, but organisms may fix impairments and damages by direct or indirect means (such as protein restoration or cell proliferation) to renew life . Various physicochemical damages may be the direct causes of aging for inorganic materials. In the biological world, however, such damages are not the aging alterations/process per se . Most alterations of biological aging are accumulative instead of degradative, such as collagen crosslinking and lipofuscin formation. Referring to entropy, although Schrodinger predicted that the entropy increase must be inevitable in biological system , organisms with enough diet, however, have no problem to gain energy (to reduce entropy) to avoid simple energy dispersal (simply to eat more). The actual problem is how the system may maintain its designed functioning pattern. The entropy increase related biological change has never been understood (only remaining as imaginative physics and as empty talk in biochemistry) until systematic understanding of formation biochemistry of lipofuscin and age pigments . The age pigment associated changes implying the exact polymerization-associated molecular alterations in relation to entropy have been formally clarified only recently . Biochemically, the crosslinking reaction of unsaturated carbonyls with amino compounds seems to be a more important reaction inducing physiological aging-related alterations. This is simply due to the fact that unsaturated carbonyls have a molecular structure of second bite (namely, it contains a pair of conjugated carbonyls or similar structure like hydroxy-ene structure) so that a further reaction is possible if a detoxification process fails to follow the first bite. As a result, steady crosslinking of low energy potential due to cyclization and/or conjugation (with increased entropy!) and thus irreversible by-products can be produced. Organisms, if they have no enzyme to break down such side-reaction induced by-products (e.g. AGEs and ALEs) with their limited (gene programmed) types of enzymes, so they have to put up with and pile them up with age . In other words, whereas the instant damages of the free radical/Maillard reaction belongs to pathological causes, which are mostly repairable or reversible (e.g. in the case of early glycation), the carbonyl stress induces mainly the irreversible accumulative physiological alterations with aging. . To sum up, the crucial problem that the entropy theory of aging is requested to answer is what is the exact biochemistry behind the entropy increase during aging. Scientists have been missing an adequate resolution until recently . Biological side-reactions, which have been discussed comprehensively in the foregoing sections, occur spontaneously in life activities, mainly including free radical oxidation, non-enzymatic glycation, carbonyl stress and protein crosslinking, etc. provide the best answer . The irreparable impairments are the molecular explanation of entropy increase. For example, protein cyclic conjugation is an exergonic process that increases the entropy of living systems. Stochastic by-products of crosslinking accumulate gradually because they cannot be degraded by normal proteinases, such as the crosslinked connective tissues in blood vessel, in wrinkled skin and in other protein complex, like lipofuscin, fibrosis, amyloids, tangles, senile plaques or lens cataract in vivo , which may form due to either physiological or pathological reasons (Korenchevsky, 1961; Selye, 1970; Bailey, 2001; Diazani, 2003; Binder et al., 2005). 2. A New Level of Aging Mechanism Study Revealing Life Code Ten years after our carbonyl aging hypothesis proposed, the carbonyl stress aging is developed to have a broader coverage as the essential mechanisms of aging in 2005 . Whereas irreparable damage accumulation of biological side reaction is summarized as the general interpretation of aging, the age pigment biochemistry and the entropy law were integrated to support strongly the general aging theory. The general aging theory was first appreciated in China as an Excellent Contribution and awarded by Chinese Gerontologic Society in 2006 and 2007 . (不好意思， 本文只能就此打住。有兴趣者，请暂时虚怀，若对群山，所谓：对面能说话，相逢得半年。 不过实在熬不过那么久的，可以琢磨请我前往交流，轻微腐败即可，哈 )。
标签: 神经科学
