Endocytotic formation of vesicles and other membranous structures induced by Ca2+ and axolemmal injury

Vesicles and/or other membranous structures that form after axolemmal damage have recently been shown to repair (seal) the axolemma of various nerve axons. To determine the origin of such membranous structures, (1) we internally dialyzed isolated intact squid giant axons (GAs) and showed that elevation of intracellular Ca21 .100 uM produced membranous structures similar to those in axons transected in Ca21-containing physiological saline; (2) we exposed GA axoplasm to Ca21- containing salines and observed that membranous structures did not form after removing the axolemma and glial sheath but did form in severed GAs after .99% of their axoplasm was removed by internal perfusion; (3) we examined transected GAs and crayfish medial giant axons (MGAs) with time-lapse confocal fluorescence microscopy and showed that many injuryinduced vesicles formed by endocytosis of the axolemma; (4) we examined the cut ends of GAs and MGAs with electron microscopy and showed that most membranous structures were single-walled at short (5–15 min) post-transection times, whereas more were double- and multi-walled and of probable glial origin after longer (30–150 min) post-transection times; and (5) we examined differential interference contrast and confocal images and showed that large and small lesions evoked similar injury responses in which barriers to dye diffusion formed amid an accumulation of vesicles and other membranous structures. These and other data suggest that Ca21 inflow at large or small axolemmal lesions induces various membranous structures (including endocytotic vesicles) of glial or axonal origin to form, accumulate, and interact with each other, preformed vesicles, and/or the axolemma to repair the axolemmal damage.This work was supported by grants from National Institutes of Health (NIH; NS31256) and the State of Texas (Advanced Technology 3658-446).Neuroscienc

The poetry of Celtic places

This paper examines the radical shift in the place of Celts in the French imagination during the course of the nineteenth century, by focusing on two versions of a passage describing Wales by Michelet: the first written in his travel journal (1834), the second published by his widow (1893). Wales, by virtue of being a Celtic place, allows Michelet to deepen his understanding of France. Whereas juxtaposition of the two versions of his text reveals something of the French state’s attitude toward the ambiguously domestic and exotic Celtic “other.

Differential weight loss with intermittent fasting or daily calorie restriction in low‐ and high‐fitness phenotypes

Recent interest has focused on the benefits of time‐restricted feeding strategies, including intermittent fasting, for weight loss. It is not yet known whether intermittent fasting is more effective than daily caloric restriction at stimulating weight loss and how each is subject to individual differences. Here, rat models of leanness and obesity, artificially selected for intrinsically high (HCR) and low (LCR) aerobic capacity, were subjected to intermittent fasting and 50% calorie restrictive diets in two separate experiments using male rats. The lean, high‐fitness HCR and obesity‐prone, low‐fitness LCR rats underwent 50% caloric restriction while body weight and composition were monitored. The low‐fitness LCR rats were better able to retain lean mass than the high‐fitness HCR rats, without significantly different proportional loss of weight or fat. In a separate experiment using intermittent fasting in male HCR and LCR rats, alternate‐day fasting induced significantly greater loss of weight and fat mass in LCR compared with HCR rats, although the HCR rats had a more marked reduction in ad libitum daily food intake. Altogether, this suggests that intermittent fasting is an effective weight‐loss strategy for those with low intrinsic aerobic fitness; however, direct comparison of caloric restriction and intermittent fasting is warranted to determine any differential effects on energy expenditure in lean and obesity‐prone phenotypes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/168438/1/eph13033_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/168438/2/eph13033.pd

Differential weight loss with intermittent fasting or daily calorie restriction in low‐ and high‐fitness phenotypes

Recent interest has focused on the benefits of time‐restricted feeding strategies, including intermittent fasting, for weight loss. It is not yet known whether intermittent fasting is more effective than daily caloric restriction at stimulating weight loss and how each is subject to individual differences. Here, rat models of leanness and obesity, artificially selected for intrinsically high (HCR) and low (LCR) aerobic capacity, were subjected to intermittent fasting and 50% calorie restrictive diets in two separate experiments using male rats. The lean, high‐fitness HCR and obesity‐prone, low‐fitness LCR rats underwent 50% caloric restriction while body weight and composition were monitored. The low‐fitness LCR rats were better able to retain lean mass than the high‐fitness HCR rats, without significantly different proportional loss of weight or fat. In a separate experiment using intermittent fasting in male HCR and LCR rats, alternate‐day fasting induced significantly greater loss of weight and fat mass in LCR compared with HCR rats, although the HCR rats had a more marked reduction in ad libitum daily food intake. Altogether, this suggests that intermittent fasting is an effective weight‐loss strategy for those with low intrinsic aerobic fitness; however, direct comparison of caloric restriction and intermittent fasting is warranted to determine any differential effects on energy expenditure in lean and obesity‐prone phenotypes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/168438/1/eph13033_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/168438/2/eph13033.pd

Rapid induction of functional and morphological continuity between severed ends of mammalian or earthworm myelinated axons

The inability to rapidly restore the loss of function that results from severance (cutting or crushing) of PNS and CNS axons is a severe clinical problem. As a novel strategy to help alleviate this problem, we have developed in vitro procedures using Ca2+-free solutions of polyethylene glycol (PEG solutions), which within minutes induce functional and morphological continuity (PEG-induced fusion) between the cut or crushed ends of myelinated sciatic or spinal axons in rats. Using a PEG-based hydrogel that binds to connective tissue to provide mechanical strength at the lesion site and is nontoxic to nerve tissues in earthworms and mammals, we have also developed in vivo procedures that permanently maintain earthworm myelinated medial giant axons whose functional and morphological integrity has been restored by PEG-induced fusion after axonal severance. In all these in vitro or in vivo procedures, the success of PEG-induced fusion of sciatic or spinal axons and myelinated medial giant axons is measured by the restored conduction of action potentials through the lesion site, the presence of intact axonal profiles in electron micrographs taken at the lesion site, and/or the intra-axonal diffusion of fluorescent dyes across the lesion site. These and other data suggest that the application of polymeric fusiogens (such as our PEG solutions), possibly combined with a tissue adherent (such as our PEG hydrogels), could lead to in vivo treatments that rapidly and permanently repair cut or crushed axons in the PNS and CNS of adult mammals, including humans. [on SciFinder (R)

Rapid induction of functional and morphological continuity between severed ends of mammalian or earthworm myelinated axons

The inability to rapidly restore the loss of function that results from severance (cutting or crushing) of PNS and CNS axons is a severe clinical problem. As a novel strategy to help alleviate this problem, we have developed in vitro procedures using Ca21-free solutions of polyethylene glycol (PEG solutions), which within minutes induce functional and morphological continuity (PEG-induced fusion) between the cut or crushed ends of myelinated sciatic or spinal axons in rats. Using a PEG-based hydrogel that binds to connective tissue to provide mechanical strength at the lesion site and is nontoxic to nerve tissues in earthworms and mammals, we have also developed in vivo procedures that permanently maintain earthworm myelinated medial giant axons whose functional and morphological integrity has been restored by PEG-induced fusion after axonal severance. In all these in vitro or in vivo procedures, the success of PEG-induced fusion of sciatic or spinal axons and myelinated medial giant axons is measured by the restored conduction of action potentials through the lesion site, the presence of intact axonal profiles in electron micrographs taken at the lesion site, and/or the intra-axonal diffusion of fluorescent dyes across the lesion site. These and other data suggest that the application of polymeric fusiogens (such as our PEG solutions), possibly combined with a tissue adherent (such as our PEG hydrogels), could lead to in vivo treatments that rapidly and permanently repair cut or crushed axons in the PNS and CNS of adult mammals, including humans.These studies were funded by National Institutes of Health Grants NS31256 and HD31484, a Texas Advanced Technology grant to G.D.B., personal funds of G.D.B., and National Science Foundation Grant BES-9696020 to J.A.H.Neuroscienc

Rapid induction of functional and morphological continuity between severed ends of mammalian or earthworm myelinated axons

The inability to rapidly restore the loss of function that results from severance (cutting or crushing) of PNS and CNS axons is a severe clinical problem. As a novel strategy to help alleviate this problem, we have developed in vitro procedures using Ca21-free solutions of polyethylene glycol (PEG solutions), which within minutes induce functional and morphological continuity (PEG-induced fusion) between the cut or crushed ends of myelinated sciatic or spinal axons in rats. Using a PEG-based hydrogel that binds to connective tissue to provide mechanical strength at the lesion site and is nontoxic to nerve tissues in earthworms and mammals, we have also developed in vivo procedures that permanently maintain earthworm myelinated medial giant axons whose functional and morphological integrity has been restored by PEG-induced fusion after axonal severance. In all these in vitro or in vivo procedures, the success of PEG-induced fusion of sciatic or spinal axons and myelinated medial giant axons is measured by the restored conduction of action potentials through the lesion site, the presence of intact axonal profiles in electron micrographs taken at the lesion site, and/or the intra-axonal diffusion of fluorescent dyes across the lesion site. These and other data suggest that the application of polymeric fusiogens (such as our PEG solutions), possibly combined with a tissue adherent (such as our PEG hydrogels), could lead to in vivo treatments that rapidly and permanently repair cut or crushed axons in the PNS and CNS of adult mammals, including humans.These studies were funded by National Institutes of Health Grants NS31256 and HD31484, a Texas Advanced Technology grant to G.D.B., personal funds of G.D.B., and National Science Foundation Grant BES-9696020 to J.A.H.Neuroscienc