Chalones and the Control of Normal, Regenerative, and Neoplastic Growth of the Skin

SYNOPSIS Chalones,inhibitors of cell dmsion have been isolatedand studied from a number of mammalian tissues, most notably,the epidermis The epidermal rhalone is a glycoprotein It exhibitsconsiderable, but not complete specificity The epidermal chalone decreases mitotic activity by inhibitingcells in the G 2 phase of the cell cycle from entering mitosis,and probably also by inhibiting ceils in the G 1 phase of thecell cycle from entering mitosis To inhibit cells in G 2 fromentering mitosis the chilone requnes adrenalin, and for maximalactivity hydrocortisone It is not known if idrenalin and hydrocortisoneare required for chalone inhibition of cells in G 1 In addition to inhibiting cell division in normal epidermalcells the epidermal chalone can inhibit cell division in regeneratingepidermal cells induced to proliferate by chemical damage Thephase of the cell cycle in which the chalone inhibits legeneratingepidermal cells from entering mitosis is not known Epidermal tumors contain a decreased amount of chalone Mitosisin epidermal tumors is inhibited by treatment with epidermalchalone Tumor cells are inhibitedfrom entering mitosis fromeither the G 1 or G 2 phases of the cell cycle Chalones are said to inhibit mitosis by a negative feedbackmechanism However, experiments which presumably result in adecrease in chalone concentration do not result in an increasein mitotic activity It is suggested that if chalones are physiological controllers of cell division they do not act by a simplenegative feedback mechanism but require the action of a substanceto decrease their concentration     

The Electrical Control of Growth in Plant Tissue 7

Goldsworthy, A. and Rathore, K. S. 1985. The electrical controlof growth in plant tissue cultures: The polar transport of auxin.—J.exp. Bot. 36: 1134–1141. The reasons for a many-fold stimulation of shoot formation anda 60–70% stimulation of growth in tobacco callus causedby passing a very weak electric current (1 or 2 µA) betweenthe callus and the culture medium have been investigated. Thestimulation of callus growth occurred only when the callus wasmade negative to the medium and then only when IAA was added.It was abolished, even in the presence of IAA, by the additionof TIBA which is an inhibitor of polar auxin transport, andalso when the IAA was substituted by either IAN or the syntheticauxin 2,4-D, neither of which show significant polar transport.This suggests that the electrical treatment may have alignedthe physiological polarities of the callus cells so as to promotethe polar transport of IAA into the tissue when the callus wasnegative to the medium. If so, the enhanced shoot formationmay have been due to the parallel orientation of the growthaxes of individual cells so as to make the production of organformingmeristems more likely. The mechanism of the effect and its relationshipto the natural forces controlling differentiation is discussed. Key words: —Auxin, electrophysiology, polarity, tissue-culture, tobacco, transport     

Immediate-Early Gene Expression during Regenerative and Mitogen-Induced Liver Growth in the Rat

The nongenotoxic carcinogens phenobarbitone (PB) and methyl clofenapate (MCP) and the hepatomitogen pregnenolone 16α carbonitrile (PCN) are direct inducers of hepatic S -phase in rats, whereas the S -phase seen after partial hepatectomy is regenerative. We have investigated S -phase and immediate-early gene expression (c-myc and c-jun) in rat liver following these treatments to study the differences in gene expression associated with direct vs. regenerative responses. Both partial hepatectomy (one- and two-thirds) and mitogen treatment caused an increase in hepatic S -phase that peaked around 36 hours. Two-thirds partial hepatectomy caused the greatest increase in S -phase followed by one-third partial hepatectomy, then the mitogens PCN, MCP, and PB in that order. This order of response was also seen with c-jun and to a lesser degree with c-myc expression, suggesting that immediate-early gene expression might be linked not only to regenerative S -phase but also to direct mitogen-induced responses. © 1997 John Wiley & Sons, Inc. J Biochem Toxicol 12: 79–82, 1998     

Regenerative biology and medicine

The replacement of damaged tissues and organs with tissue and organ transplants or bionic implants has serious drawbacks. There is now emerging a new approach to tissue and organ replacement, regenerative biology and medicine. Regenerative biology seeks to understand the cellular and molecular differences between regenerating and non-regenerating tissues. Regenerative medicine seeks to apply this understanding to restore tissue structure and function in damaged, non-regenerating tissues. Regeneration is accomplished by three mechanisms, each of which uses or produces a different kind of regeneration-competent cell. Compensatory hyperplasia is regeneration by the proliferation of cells which maintain all or most of their differentiated functions (e.g., liver). The urodele amphibians regenerate a variety of tissues by the dedifferentiation of mature cells to produce progenitor cells capable of division. Many tissues contain reserve stem or progenitor cells that are activated by injury to restore the tissue while simultaneously renewing themselves. All regeneration-competent cells have two features in common. First, they are not terminally differentiated and can re-enter the cell cycle in response to signals in the injury environment. Second, their activation is invariably accompanied by the dissolution of the extracellular matrix (ECM) surrounding the cells, suggesting that the ECM is an important regulator of their state of differentiation. Regenerative medicine uses three approaches. First is the transplantation of cells into the damaged area. Second is the construction of bioartificial tissues by seeding cells into a biodegradable scaffold where they produce a normal matrix. Third is the use of a biomaterial scaffold or drug delivery system to stimulate regeneration in vivo from regeneration-competent cells. There is substantial evidence that non-regenerating mammalian tissues harbor regeneration-competent cells that are forced into a pathway of scar tissue formation. Regeneration can be induced if the factors leading to scar formation are inhibited and the appropriate signaling environment is supplied. An overview of regenerative mechanisms, approaches of regenerative medicine, research directions, and research issues will be given.     

Regenerative medicine

Regenerative medicine can be defined as the possibility to replace aged/damaged cells by genetically similar young and functional cells. This could be reached by using human embryonic stem cells, eventually from cloned human embryos, or pluripotent adult stem cells. The range of the possible differentiation fates of these latter cells has recently been shown to be strikingly large. Although considerable works remains necessary to develop this new type of medicine, to assure its efficacy and safety, it nevertheless represents one of the major medical breakthroughs expected for the future.     

Electrical Stimulation Improves Microbial Salinity Resistance and Organofluorine Removal in Bioelectrochemical Systems

Fed batch bioelectrochemical systems (BESs) based on electrical stimulation were used to treat p-fluoronitrobenzene (p-FNB) wastewater at high salinities. At a NaCl concentration of 40 g/liter, p-FNB was removed 100% in 96 h in the BES, whereas in the biotic control (BC) (absence of current), p-FNB removal was only 10%. By increasing NaCl concentrations from 0 g/liter to 40 g/liter, defluorination efficiency decreased around 40% in the BES, and in the BC it was completely ceased. p-FNB was mineralized by 30% in the BES and hardly in the BC. Microorganisms were able to store 3.8 and 0.7 times more K⁺ and Na⁺ intracellularly in the BES than in the BC. Following the same trend, the ratio of protein to soluble polysaccharide increased from 3.1 to 7.8 as the NaCl increased from 0 to 40 g/liter. Both trends raise speculation that an electrical stimulation drives microbial preference toward K⁺ and protein accumulation to tolerate salinity. These findings are in accordance with an enrichment of halophilic organisms in the BES. Halobacterium dominated in the BES by 56.8% at a NaCl concentration of 40 g/liter, while its abundance was found as low as 17.5% in the BC. These findings propose a new method of electrical stimulation to improve microbial salinity resistance.     

Systems Biology of Growth Factor-Induced Receptor Endocytosis

Clathrin-mediated endocytosis sorts for degradation of more than 50 different growth factor receptors capable of relaying growth and differentiation signals by means of their cytoplasm-facing, intrinsic tyrosine kinase activity. The kinetics and alternative routings of receptor endocytosis critically regulate growth factor signaling, which underscores the importance of understanding mechanisms underlying fail-safe operation (robustness) and fidelity of the pathway. Like other robust systems, a layered hub-centric network controls receptor endocytosis. Characteristically, the modular hubs (e.g., AP2–Eps15 and Hrs) contain a membrane-anchoring lipid-binding domain, an ubiquitin-binding module, which recruits ubiquitinylated cargo, and a machinery enabling homo-assembly. Scheduled hub transitions, as well as cascades of Rab family guanosine triphosphatases and membrane bending machineries, define points of commitment to vesicle budding, thereby securing unidirectional trafficking. System's bistability permits stimulation by a growth factor, which oscillates a series of switches based on posttranslational protein modifications (i.e., phosphorylation, ubiquitinylation and neddylation), as well as transient low-affinity/high-avidity protein assemblies. Cbl family ubiquitin ligases, along with a set of phosphotyrosine-binding adaptors (e.g., Grb2), integrate receptor endocytosis into the densely wired networks of signal transduction pathways, which are involved in health and disease.     

再生研究与再生医学

再生是大自然的普遍现象。再生过程干细胞的激活与成熟细胞的去分化,再生与肿瘤的关系等都使得这一领域越来越成为各个国家研究与投资的热点。对自然再生过程的研究将有助于发展人类的细胞疗法。随着对再生研究的深入,将有可能揭示如何选择性的再次激活指导哺乳动物早期发育的基因和蛋白质,以此来诱导受伤或生病的人类组织的再生,再生医学方兴末艾。     

Supervisory Control of Functionally-Expandable Manufacturing Systems

Supervisory controllers have traditionally coordinated the various resources of manufacturing systems, such as flexible manufacturing workcells, for the production of a priori set families of part types. This paper expands on this capability by allowing the control of the production of new part types side by side with previously defined and planned for nominal part types. The proposed basic workcell supervisory-control approach advocates the use of a pair of non-communicating independent supervisors, synthesized individually but working in concert, to achieve the production of existing and new part types: nominal and complementary supervisors, respectively. The nominal supervisor is responsible for controlling the behavior of the nominal system, producing the set of a priori planned-for part types, whereas the complementary supervisor controls the flow of the a priori unplanned-for new part types.     

线性广义系统的无源控制

研究线性广义系统在有界能量外部输入作用下的无源控制问题,给出广义系统容许且具有严格无源性的充分条件,并且在一定条件下设计一个状态反馈控制器使得闭环系统容许,同时具有严格无源性．