Regenerative Behavior Research Articles

Investigation of a 2R All-Optical Regenerator Based on Four-Wave Mixing in a Semiconductor Optical Amplifier

The properties of an all-optical 2R regenerator based on four-wave mixing (FWM) in a semiconductor optical amplifier (SOA) are investigated. The regeneration is based on the nonlinear FWM transfer function and a study of the system's static behavior reveals the operating conditions, under which the transfer function approaches most the ideal, step-like discrimination characteristic function. A fiber Bragg grating (FBG) is employed in order to overcome the SOAs speed limitations due to limited carrier dynamics. The simulations with dynamic input data by means of extinction ratio (ER) and Q-factor calculations, showed satisfactory regenerative behavior up to 40 Gb/s.

Preferential loss of EC coupling gradation at positive membrane potentials in rat ventricular myocytes.

Rat ventricular myocytes switched from a solution containing 1 mM extracellular Ca to one containing 5 mM extracellular Ca exhibited larger Ca currents that inactivated more rapidly. Their Ca transients exhibited a slower decay. In some cells the amplitude of the Ca transients increased markedly, but not in others. Strikingly, in about half the cells examined, the graded nature of the Ca transients over the range of positive membrane potentials was lost, as were Ca transients elicited upon repolarization. These changes were manifest without equivalent loss of gradation over the range of negative membrane potentials (-35 to 0 mV). Such preferential loss of gradation at positive membrane potentials also occurred in solutions devoid of extracellular and/or intracellular Na, and was abolished by nifedipine. The results suggest that Ca-induced Ca release from the SR at positive potentials can saturate or become regenerative if the Ca entry trigger is increased. The lack of a similar effect at negative potentials indicates that large numbers of activated L-type channels are critical for induction of regenerative behavior.

Modeling plasma membrane and endoplasmic reticulum excitability in pituitary cells

The response of gonadotrophs to secretagogues involves dose-dependent, complex dynamic patterns of electrical activity and inositol 1,4,5-trisphosphate (InsP 3)-induced Ca 2+ mobilization, including pulsatility and oscillations on multiple time scales from milliseconds to minutes. Detailed in vitro experiments have enabled the identification of key mechanisms that underlie the plasma membrane (PM) electrical excitability and endoplasmic reticulum (ER) calcium excitability. We summarize these findings and review computer simulations of a biophysical model that resynthesizes and couples these components and that reproduces quantitatively the observed time courses and dose-response characteristics, as well as effects of various pharamacological manipulations. The theory suggests that cytosolic calcium is the primary messenger in coordinating the PM and ER regenerative behaviors during ER depletion and refilling.

Ca2+ excitability of the ER membrane: an explanation for IP3-induced Ca2+ oscillations.

Recent research dealing with experiments and theoretical models of Ca2+ excitability of the endoplasmic reticulum (ER) membrane induced by inositol 1,4,5-trisphosphate (IP3) is reviewed. Ca2+ excitability refers to the ability of a small increment of cytoplasmic Ca2+ concentration ([Ca2+]i) to trigger a large [Ca2+]i pulse or oscillations. Such nonlinear regenerative behavior is conferred by the existence of IP3 channels and Ca(2+)-ATPase transporters on the ER membrane, which extends throughout the cytoplasm. Ca2+ excitability resembles the plasma membrane electrical excitability of neurons and other cells: it is driven by the ionic concentration gradient across the ER membrane (higher Ca2+ concentration inside the ER); each [Ca2+]i spike partially consumes the prestored energy that is reestablished through ATP-dependent active transport; and [Ca2+]i, the excitation variable, controls the nonlinear dynamic release rate of ER Ca2+. This review focuses on the kinetic models based on these features and on experiments dealing with the kinetic properties of [Ca2+]i-dependent gating of the IP3 receptor channel. We summarize evidence in favor of two roles for [Ca2+]i in gating the channel's opening: activation at a rapid time scale and inactivation on a slower time scale. Exploiting an analogy to the well-known Hodgkin-Huxley model for neuronal electrical excitability, we show how Ca2+ excitability of the ER membrane can be explained by these gating properties combined with the ER Ca2+ pump activity. The theory's ability to predict is illustrated by comparing calculated with experimental [Ca2+]i responses for pituitary gonadotrophs under various stimulus conditions.

Intravitreal Transplantation of a Segment of Peripheral Nerve Enhances Axonal Regeneration of Retinal Ganglion Cells Following Distal Axotomy

Neurons of the central nervous system are able to regenerate their axons into a peripheral nerve (PN) graft when they are axotomized close to the cell bodies. Very few, if any, damaged axons can regrow into the PN graft when the axonal injury is made distant to the cell bodies. We show here that a segment of viable PN transplanted intravitreally enhances the regenerative response of distally axotomized retinal ganglion cells. We hypothesize that trophic substances released from the intravitreal PN segment may enable retinal ganglion cells to regenerate their damaged axons into the PN graft even after a distal axotomy. This suggests that the regenerative behavior of an axotomized neuron is influenced by both the local environment at the damaged tip of the axon and the local environment surrounding the cell body. This finding provides evidence that the PN grafting technique may be useful for repairing long tract pathways in the central nervous system even when the damage is inflicted far away from the cell bodies.

Proliferative Response of Hepatocytes Transplanted into Spleen or Solid Support

Understanding the regenerative behavior of transplanted hepatocytes is of great importance for developing and improving such novel therapeutic strategies as hepatocellular transplantation and ex vivo gene therapy. In this study the proliferative responsiveness of transplanted syngeneic rat hepatocytes was examined in relation to the timing of the administration of a mitogenic stimulus. For this purpose nuclear bromodeoxyuridine incorporation after partial hepatectomy was investigated during the early post-transplant phase. The response of intrasplenically transplanted hepatocytes was compared to that of liver cells engrafted in polytetrafluoroethylene solid supports that had been implanted intraperitoneally 4 weeks prior to transplantation. Nonstimulated, engrafted hepatocytes exhibited a labeling index of ∼0-1% independent of the transplantation technique used. This "spontaneous" labeling index did not change with time. Partial hepatectomy, executed simultaneously with hepatocyte transplantation through either technique, did not result in significant alteration of this proliferation index. Delayed kinetics were found not to be responsible for this lack of responsiveness. When the mitogenic stimulus was given between 2 and 6 weeks post-transplantation, a significant increase in labeling index was observed in comparison to sham-treated control animals. Maximal labeling indices of ∼3-4% were found if the stimulus took place at 4 weeks post-transplantation. Both the pattern and the extent of the proliferative response seen in liver cells engrafted in solid supports were similar to the ones found in intrasplenic hepatocytes, indicating adequate vascularization of the supports. This data provides the first description of proliferative response in hepatocytes transplanted by the solid support technique, which may offer an attractive alternative to the intrasplenic route. It further suggests that, in analogy with the in vitro situation, a lag time exists between hepatocyte isolation/transplantation and their maximal responsiveness to physiological stimuli. It is concluded that timing of the administration of a proliferative stimulus is important for obtaining a maximal response of transplanted hepatocytes during the early post-transplantation phase.

Spinal cord transection in adult rats: effects of local infusion of nerve growth factor on the corticospinal tract axons.

The spinal cord of adult female rats was completely transected at the T8 level. Nerve growth factor (NGF) was administered at the lesion site via indwelling, implanted, osmotic minipumps. Purified NGF was supplied at doses of 100, 200, and 500 micrograms during a 30-day period. Control rats were treated with saline. At the end of the treatment, the proximal stump of corticospinal tract axons in the spinal cord was labeled with anterograde transported horseradish peroxidase (HRP) injected into the sensorimotor cortex. In control rats, the corticospinal tract axons ended abruptly, proximal to the zone of maximal damage. Sterile swellings developed at the axon tips, and no labeled axonal sprouts were apparent. On the contrary, in NGF-treated animals, the leading front of the corticospinal tract axons showed a trend of approaching the zone of maximal damage following abnormal paths through the dorsal-injured white matter. Axonal sprouts were seen more proximally, traveling toward the transection site in aberrantly located dorsal paths, completely outside the normal position of the corticospinal tract. NGF seems to partly restore the pattern of the regenerative behavior of the severed corticospinal tract axons after spinal cord transection in newborn rats, i.e., the induction of axonal sprouting in aberrantly located dorsal paths. An automated image analysis of the HRP reaction field close to the transection site demonstrated that the density of HRP-labeled axons in the corticospinal tract was significantly higher in the NGF-treated rats than in the control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of instabilities observed in electrical characteristics of silicon-on-insulator MOSFETs, both above and below threshold voltage

A simple model is presented to analyse the consequences of the body potential on electrical instabilities in SOI MOSFETs. The analysis accounts for both the regenerative and nonregenerative behaviour that is typically observed in these devices and relates them to the bias condition and critical device parameters.

Ontogenetic changes in the regenerative ability of chick retinal ganglion cells as revealed by organ explants

Whereas mature neurons in the central nervous system (CNS) of birds lack the capability of regenerating axons after injury, embryonic nerve cells are able to do so. The time course of this decline of regenerative ability was investigated in ganglion cells from embryonic chick retinae. Retinal strips from 7- to 19-day-old embryos (E7-E19) were explanted and cultured in vitro. The numbers of retinal ganglion cell (RGC) neurites that had extended during the first 22-23 h incubation, their elongation rates, and morphometric parameters of the growth cones were measured to characterize the regenerative behavior. We observed two periods of decline in neuritic growth: the first from E7 to E9, and another from E14 to E19. The first decrease may reflect a gradually disappearing portion of neurons which produced their axons de novo. The second decline coincides with the major period of synaptogenesis by ganglion cell axons in ovo. The time required for initiation of axonal outgrowth increased, accordingly, from less than 3 h in explants from younger retinae (E7-E16) to 10-12 h for E17 and E19 explants. Axonal elongation rates ranged between 36 micron/h and 56 micron/h (mean values) for E7-E13 explants, but were significantly lower for cells from E14-E19 retinae (13-21 microns/h). Morphologically, neurites and growth cones for RGC explanted before E17 were characterized by their high variability. They possessed more filopodia than mature neurons (E17, E19), fasciculated to a higher degree and branched more frequently. In addition, older neurites appeared "stiffer" and were morphologically simpler.(ABSTRACT TRUNCATED AT 250 WORDS)

A note on the classification of Q-processes when Q is not regular

We shall provide a classification of states for processes other than the Feller minimal process. In particular, we shall study the regularity, recurrence, transience, etc. of these processes. Our results are based on the observation that certain honest Q-processes exhibit regenerative behaviour. We shall also comment on the problem of determining stationary distributions directly from the transition rates.

A note on the classification of Q-processes when Q is not regular

We shall provide a classification of states for processes other than the Feller minimal process. In particular, we shall study the regularity, recurrence, transience, etc. of these processes. Our results are based on the observation that certain honest Q-processes exhibit regenerative behaviour. We shall also comment on the problem of determining stationary distributions directly from the transition rates.

Maximum Power Spectroscopy of n‐Type a‐Si:H, c‐Si, CdSe , and InP in Nonaqueous Photoelectrochemical Cells

Amorphous silicon photoanodes in a nonaqueous photoelectrochemical cell show wavelength dependence of their power outputs. This behavior has been studied by maximum power spectroscopy (MPS) and compared to similar experiments with conventional short‐circuit spectroscopy. The derivative maximum power output under constant chopped input power (MPS) shows dependence on the wavelength distribution in superimposed fixed beams, whereas the conventional short‐circuit measurements do not. Single‐crystal substrates of n‐Si, , and do not show any differences between the spectroscopies. Rotating ring‐disk electrode studies confirm the regenerative behavior of the and electrodes with the couple in solution.

On the varying degrees of cancerogenicity of modified gastroentero-anastomoses

In our serial investigations we checked the incidence of carcinomas in different cases of anastomoses and resections on the rat stomach. Moreover we supervised the regenerative behaviour of the gastric mucosa by means of in vivo autoradiography using 3H-thymidine. The experimental animals were divided into 5 treatment groups. We carried out gastroenterostomy on 9 animals (group I), Billroth's second operation on 7 animals (group II), a duodenal ligature, pyloroplasty and gastro-enterostomy with Braun's anastomosis on 10 animals (group III), a pylorectomy as well as Roux's gastro-enterostomy on 10 animals (group IV) and a laparotomy on 11 control animals (group V). The greatest tumour onset rates with 4 adenocarcinomas each were observed in the groups I and III, and with 5 carcinomas in group II 7 months after the operations. The labelling indices obtained autoradiographically are such that glandular hyperplasias with indices of over 13.3 p.c. and carcinomas with values of about 24.7 p.c. enable an unambiguous distinction from the values of the sound glandular gastric mucosa. Entero-gastric reflux is discussed in this paper as the most important cause of carcinogenesis.

Peripheral injury enhances central regeneration of primary sensory neurones.

The success of peripheral and fetal neural tissue in promoting outgrowth of axons from the adult mammalian central nervous system has tended to focus attention on local interactions between extending axons and their environment. The contribution to axon regeneration of biochemical and morphological changes in injured neurones is more difficult to evaluate. We report here that long spinal axons of primary sensory neurones are 100 times more likely to regenerate into peripheral nerve grafts if their peripheral axons are also cut. Regenerative behaviour at the axon tip seems to be strongly influenced by inducible events in the nerve cell.

The decay of sound in rooms with amplification systems

The regenerative behavior of sound reinforcement systems affects the sound level and interacts with the reverberative decay of souns in enclosures in which they operate, in ways not previously described. For a system of loop gain A(s)B(s), the sound levels will be −20 log[1 − A(s)B(s)](dB) above those predicted by classical feedforward methods. After the source of sound to be amplified is shut off, the regenerative loop will continue producing sound, and will take P/ − 57.6 log[A(s)B(s)](s) to decay 60 dB, where P is the regenerative path length (m). Methods for calculating and measuring the decaying loop, by itself and in combination with the room's reverberation time, are given.

Properties of cerebello-precerebellar reverberating circuits

Intracellular recordings were made from neurons of the red nucleus (RN) in cats where the cerebellar cortical effects were removed by chronic ablation of the intermediate part of the anterior lobe of the cerebellum. A prolonged depolarization could be elicited by stimulating the nucleus interpositus (IP) of the cerebellum, nucleus reticularis tegmenti pontis (NRTP) and the nucleus reticularis paramedianus (PMRN). This prolonged depolarization was abolished after cooling the inferior and middle cerebellar peduncles and persisted after ablation of the cerebral sensorimotor cortex. The prolonged depolarization was also recorded intracellularly from IP neurons. It was concluded that the prolonged depolarization set up in RN neurons is due to the repetitive discharges of IP neurons which produces tonic bombardment onto RN cells. The mechanisms of the repetitive discharges of IP neurons are considered to be due to impulse reverberation via the IP. The dynamic properties of the reverberating circuits were characterized by regenerative behavior. Above and below threshold, there were two states, the excited state where many constituent neurons were active, and the resting state where all neurons were inactive. It was found that cats with chronically stimulated cerebral peduncle (CP), and tested in an acute experiment, showed sometimes effective for inducing the prolonged depolarization and repetitive discharges of RN neurons by stimulation of IP. The prolonged depolarization thus produced could be reversibly abolished by cooling the middle and inferior cerebellar peduncles. The possible constituent neurons of the reverberating circuits were investigated in light of previous physiological investigations of stimulating the NRTP, PMRN, nucleus reticularis lateralis (LRN), nucleus olivaris inferior (IO) and recording EPSPs in RN cells. The RN cells receive axon reflex activation from NRTP and PMRN, and disynaptic excitation from NRTP, PMRN, LRN and IO. Based on these and other available data, the components of the cerebello-precerebellar reverberating circuits are discussed.

Further experiments with ferns in culture: regeneration

Ferns in culture provide versatile and easily manipulated material for a wide variety of experiments and observations. This article supplements earlier reports of the vast experimental potential of these cryptogams and outlines laboratory exercises which reveal the regenerative behaviour of fern tissue

The structure of 180° supernumerary limbs and a hypothesis of their formation

The results of a detailed analysis of 100 supernumerary limbs generated by 180° ipsilateral rotation (on the same limb stump) of regeneration blastemas is presented. The limbs were analyzed in terms of their position of origin, frequency, cartilage structure by Victoria blue staining, and muscle structure by serial sections. Single, double, or triple supernumeraries can be produced at no unique position of origin, although the posterodorsal quadrant was preferred. Four classes of supernumerary limbs were generated by such operations—normal; double dorsal or double ventral; part normal/part mirror imaged; part normal/part inverted in approximately equal frequencies. After amputation of these supernumeraries the same muscle patterns are faithfully regenerated. A hypothesis to explain the production of these abnormal limbs is proposed based on the observed phenomenon of fusion of supernumerary blastemata, but their regenerative behaviour presents problems for current models of pattern formation. Similar results have been obtained with developing limb buds and the relation between development and regeneration is discussed.

The Chemical Behavior of Multibridged [2n] Cyclophanes

AbstractMultibridged [2n] cyclophanes comprise a novel class of aromatic compounds, in which two benzene rings are connected by three up to a maximum of six ethano bridges. Compared to classical nonannelated arenes, their most distinct chemical property is the ease with which, particularly the higher‐bridged homologs, take part in addition reactions (Diels‐Alder additions, hydrogenations, and ionic additions). On the other hand, the typical regenerative behavior of aromatic molecules is not fully suppressed in the [2n]cyclophanes as evidenced by such typical electrophilic aromatic substitution reactions as bromination, Friedel‐Crafts acylation, and nitration. Besides these reactions in which the benzene rings are either destroyed or retained, reactions at and with the ethano bridges, e.g. their cleavage, isomerization, and functionalization can also occur.

Ischemia and post-ischemic regeneration of the small intestinal mucosa: An enzyme-histochemical investigation

After ligation of the vascular arcades of the upper jejunum in rats, the ischemic damage to the intestinal mucosa and its regenerative behavior after ischemia lasting 120 minutes were investigated with histological and enzyme-histochemical methods. During the ischemic injury of the jejunal mucosa, there is rejection of hydropically swollen epithelial cells into the intestinal lumen advancing from the tip to the base of the villi without a previously detectable loss of activity of the enzymes investigated. At the end of ischemia lasting 120 minutes, there is complete destruction of the villi as well as the upper portions of the crypts. After rapid re-epithelialization of the mucosal surface by a flat epithelium, reformation of villi begins already after a 24 h period of regeneration. On the third day of regeneration, the intestinal mucosa has plump villi again. Their epithelia already show the morphological characteristics of mature enterocytes. On the other hand, enzymatic maturation of the enterocytes is only concluded between the first and second week of regeneration. An altered proliferation kinetics of the crypt epithelia due to the repair process is discussed as cause of this delayed enzymatic maturation of the enterocytes relative to the morphological differentiation. Although the intestinal mucosa has a regular villous structure again after regeneration lasting 8 days, enzyme histochemical finding in the lamina propria indicate that the process of repair is only complete here in the sixth week of regeneration.