Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “VACATIONS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 757 records · Page 42Linked to original sources
PubMed1995

Structural studies of the roles of residues 82 and 85 at the interactive face of cytochrome c.

A combination of structural, functional, and mutagenic experiments has been used to study the roles of the invariant Phe82 and highly conserved Leu85 residues in cytochrome c, especially with respect to the complexation interface with electron transfer partners and maintenance of the hydrophobic heme pocket. Structural analyses show that the F82Y, L85A, and F82Y/L85A mutant proteins all retain the characteristic cytochrome c fold, but that conformational alterations are introduced in the direct vicinity of the mutation sites. In particular, the additional hydroxyl group of Tyr82 is in direct spatial conflict with the side chain of Leu85 in the F82Y mutant protein, leading to rotation of the side chain of Tyr82 out toward the protein surface. This strain is relieved in the F82Y/L85A mutant protein where the phenyl ring of Tyr82 is accommodated in a conformation comparable to that of the phenylalanine normally present at this location. In addition, the available space vacated by the replacement of Leu85 with an alanine allows for the inclusion of two new internal water molecules, one of which is bound to Tyr82 and the other to Arg13. In contrast, in the L85A mutant protein, no internal water molecules are observed in this exclusively hydrophobic pocket, which is partially filled by shifts in nearby side chains. Overall, the conformational changes observed result from the optimization of side chain packing to reflect the spatial requirements of new side chains, the minimization of both vacant internal space and the solvent exposure of hydrophobic groups, and the attainment of maximal hydrogen bonding between available polar groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1994

Mapping the lipoyl groups of the pyruvate dehydrogenase complex by use of gold cluster labels and scanning transmission electron microscopy.

This paper describes the organization of lipoyl moieties within the pyruvate dehydrogenase (PDH) complex from Escherichia coli as studied in the scanning transmission electron microscope (STEM). The PDH complex is a multienzyme complex consisting of E1, pyruvate dehydrogenase, E2, dihydrolipoyl transacetylase, and E3, dihydrolipoyl dehydrogenase. The core of the complex is the cubic 24-subunit E2 component, which contains the lipoyl moieties bonded to lipoyl-bearing domains. E1 and E3 are associated along the edges (E1) and on the faces (E3) of the core. The lipoyl moieties were reduced with NADH and alkylated with a p-maleimidobenzoyl undecagold cluster complex. The gold labels were found to be bound very nearly specifically by dihydrolipoyl transacetylase (E2). Undecagold clusters were imaged directly by the STEM and also digitally mapped by radial mass analysis. The mass of the E2E3 subcomplex is about half that of the PDH complex. The PDH complex and GC-PDH are both about 420 A in diameter, as determined by radial mass analysis, and the E2E3 subcomplex and GC-E2E3 are 320 and 350 A, respectively. The outer boundary of the E2E3 subcomplex was clearly shown in STEM micrographs by the undecagold labels in GC-E2E3. Data obtained from radial mass analysis of GC-E2E3 and the unlabeled E2E3 subcomplex also showed that the size of the subcomplex is extended by the lipoyl-bearing domains surrounding the central E2 core. The capabilities of lipoyl moieties to undergo translocation over long distances through structural mobility in the lipoyl-bearing domains was confirmed by the observation that many of the lipoyl groups in E2E3 subcomplexes relax outward into space vacated by the removal of E1 during the preparation of the subcomplex from PDH complex. Radial mass analysis of the PDH complex and GC-PDH indicates that lipoyl groups are distributed over a large region of the PDH complex, extending from the central core to 170-180 A from the center of the complex, with the highest density at about 75 A from the particle centers, near the interface between E2 and the associated components E1 and E3.

Escherichia coli↗
PubMed1987

Iron(III) clusters bound to horse spleen apoferritin: an X-ray absorption and Mössbauer spectroscopy study that shows that iron nuclei can form on the protein.

Ferritin is a complex of a hollow, spherical protein and a hydrous, ferric oxide core of less than or equal to 4500 iron atoms inside the apoprotein coat; the apoprotein has multiple (ca. 12) binding sites for monoatomic metal ions, e.g., Fe(II), V(IV), Tb(III), that may be important in the initiation of iron core formation. In an earlier study we observed that the oxidation of Fe(II) vacated some, but not all, of the metal-binding sites, suggesting migration of some Fe during oxidation, possibly to form nucleation clusters; some Fe(III) remained bound to the protein. Preliminary extended X-ray absorbance fine structure (EXAFS) analysis of the same Fe(III)-apoferritin complex showed an environment distinct from ferritin cores, but the data did not allow a test of the Fe cluster hypothesis. In this paper, with improved EXAFS data and with Mössbauer data on the same complex formed with 57Fe, we clearly show that the Fe(III) in the distinctive environment is polynuclear (Fe atoms with Fe-Fe = 3.5 A and TB = 7 K). Moreover, the arrangement of atoms is such that Fe(III) atoms appear to have both carboxylate-like ligands, presumably from apoferritin, and oxo bridges to the other iron atoms. Thus the protein provides sites not only for initiation but also for nucleation of the iron core. Sites commodious enough and with sufficient conserved carboxylate ligands to accommodate such a nucleus occur inside the protein coat at the subunit dimer interfaces. Such Fe(III)-apoferritin nucleation complexes can be used to study the properties of the several members of the apoferritin family.

Animals↗
PubMed2001

Histidine 90 function in 4-chlorobenzoyl-coenzyme a dehalogenase catalysis.

4-chlorobenzoyl-coenzyme A (4-CBA-CoA) dehalogenase catalyzes the hydrolytic dehalogenation of 4-CBA-CoA by attack of Asp145 on the C4 of the substrate benzoyl ring to form a Meisenheimer intermediate (EMc), followed by expulsion of chloride ion to form an arylated enzyme intermediate (EAr) and, finally, ester hydrolysis in EAr to form 4-hydroxybenzoyl-CoA (4-HBA-CoA). This study examines the contribution of the active site His90 to catalysis of this reaction pathway. The His90 residue was replaced with glutamine by site-directed mutagenesis. X-ray crystallographic analysis of H90Q dehalogenase complexed with 4-HBA-CoA revealed that the positions of the catalytic groups are unchanged from those observed in the structure of the 4-HBA-CoA-wild-type dehalogenase complex. The one exception is the Gln90 side chain, which is rotated away from the position of the His90 side chain. The vacated His90 site is occupied by two water molecules. Kinetic techniques were used to evaluate ligand binding and catalytic turnover rates in the wild-type and H90Q mutant dehalogenases. The rate constants for 4-CBA-CoA (both 7 microM(-1) x s(-1)) and 4-HBA-CoA (33 and 11 microM(-1) x s(-1)) binding to the two dehalogenases are similar in value. For wild-type dehalogenase, the rate constant for a single turnover is 2.3 s(-1) while that for multiple turnovers is 0.7 s(-1). For H90Q dehalogenase, these rate constants are 1.6 x 10(-2) and 2 x 10(-4) s(-1). The rate constants for EMc formation in wild-type and mutant dehalogenase are approximately 200 s(-1) while the rate constants for EAr formation are 40 and 0.3 s(-1), respectively. The rate constant for hydrolysis of EAr in wild-type dehalogenase is 20 s(-1) and in the H90Q mutant, 0.13 s(-1). The 133-fold reduction in the rate of EAr formation in the mutant may be the result of active site hydration, while the 154-fold reduction in the rate EAr hydrolysis may be the result of lost general base catalysis. Substitution of the His90 with Gln also introduces a rate-limiting step which follows catalysis, and may involve renewing the catalytic site through a slow conformational change.

Binding Sites↗
PubMed1997

The entropic penalty of ordered water accounts for weaker binding of the antibiotic novobiocin to a resistant mutant of DNA gyrase: a thermodynamic and crystallographic study.

Novobiocin is an antibiotic which binds to a 24 kDa fragment from the B subunit of DNA gyrase. Naturally occurring resistance arises from mutation of Arg-136 which hydrogen bonds to the coumarin ring of novobiocin. We have applied calorimetry to characterize the binding of novobiocin to wild-type and R136H mutant 24 kDa fragments. Upon mutation, the Kd increases from 32 to 1200 nM at 300 K. The enthalpy of binding is more favorable for the mutant (DeltaH degrees shifts from -12.1 to -17.5 kcal/mol), and the entropy of binding is much less favorable (TDeltaS degrees changes from -1.8 to -9.4 kcal/mol). Both of these changes are in the direction opposite to that expected if the loss of the Arg residue reduces hydrogen bonding. The change in heat capacity at constant pressure upon binding (DeltaCp) shifts from -295 to -454 cal mol-1 K-1. We also report the crystal structure, at 2.3 A resolution, of a complex between the R136H 24 kDa fragment and novobiocin. Although the change in DeltaCp often would be interpreted as reflecting increased burial of hydrophobic surface on binding, this structure reveals a small decrease. Furthermore, an ordered water molecule is sequestered into the volume vacated by removal of the guanidinium group. There are large discrepancies when the measured thermodynamic parameters are compared to those estimated from the structural data using empirical relationships. These differences seem to arise from the effects of sequestering ordered water molecules upon complexation. The water-mediated hydrogen bonds linking novobiocin to the mutant protein make a favorable enthalpic contribution, whereas the immobilization of the water leads to an entropic cost and a reduction in the heat capacity of the system. Such a negative contribution to DeltaCp, DeltaH degrees , and TDeltaS degrees appears to be a general property of water molecules that are sequestered when ligands bind to proteins.

Binding Sites↗
PubMed1998

Active site modifications in a double mutant of liver alcohol dehydrogenase: structural studies of two enzyme-ligand complexes.

The oxidation of alcohol to aldehyde by horse liver alcohol dehydrogenase (LADH) requires the transfer of a hydride ion from the alcohol substrate to the cofactor nicotinamide adenine dinucleotide (NAD). A quantum mechanical tunneling contribution to this hydride transfer step has been demonstrated in a number of LADH mutants designed to enhance or diminish this effect [Bahnson, B. J., et al. (1997) Proc. Natl. Acad. Sci. U.S.A. 94, 12797-12802]. The active site double mutant Phe93 --> Trp/Val203 --> Ala shows a 75-fold reduction in catalytic efficiency relative to that of the native enzyme, and reduced tunneling relative to that of either single mutant. We present here two crystal structures of the double mutant: a 2.0 A complex with NAD and the substrate analogue trifluoroethanol and a 2.6 A complex with the isosteric NAD analogue CPAD and ethanol. Changes at the active site observed in both complexes are consistent with reduced activity and tunneling. The NAD-trifluoroethanol complex crystallizes in the closed conformation characteristic of the active enzyme. However, the NAD nicotinamide ring rotates away from the substrate, toward the space vacated by replacement of Val203 with the smaller alanine. Replacement of Phe93 with the larger tryptophan also produces unfavorable steric contacts with the nicotinamide carboxamide group, potentially destabilizing hydrogen bonds required to maintain the closed conformation. These contacts are relieved in the second complex by rotation of the CPAD pyridine ring into an unusual syn orientation. The resulting loss of the carboxamide hydrogen bonds produces an open conformation characteristic of the apoenzyme.

Alanine↗
PubMed2001

A distal histidine mutant (H52Q) of yeast cytochrome c peroxidase catalyzes the oxidation of H(2)O(2) instead of its reduction.

A H52Q variant of yeast cytochrome c peroxidase (CcP), in which the distal histidine is replaced by glutamine, catalyzes oxidation of H(2)O(2) instead of reduction. This redirection of catalytic action is detected by protein film voltammetry. In the presence of H(2)O(2), wild-type CcP, adsorbed on a graphite electrode, shows a strong catalytic reduction wave commencing at about 0.8V (pH 5.4); by contrast, H52Q does not exhibit this activity but instead shows a catalytic oxidation current at potentials in the region of 0.9 V. The oxidation current is partly suppressed in the presence of tetranitromethane (a superoxide scavenger) and is not observed for other mutants studied, including H52A. The only significant structural change in the H52Q variant is that the Q-52 side chain occupies the space vacated by the H-52 imidazole; specifically, the N-epsilon atom that is believed to transfer a proton and induce O--O cleavage is replaced, to within 0.75 A, by the carbamide-O. Thus, while the weakly basic amide functionality is unable to serve in the reorganization of bound H(2)O(2), it is able to facilitate its oxidation, most obviously by serving as a H-bond acceptor to assist formation of a labile superoxide intermediate.

Binding Sites↗
PubMed2005

Origin of the unusual kinetics of iron deposition in human H-chain ferritin.

From microorganisms to humans, ferritin plays a central role in the biological management of iron. The ferritins function as iron storage and detoxification proteins by oxidatively depositing iron as a hydrous ferric hydroxide mineral core within their shell-like structures. The mechanism by which the mineral core is formed has been the subject of intense investigation for many years. A diiron ferroxidase site located on the H-chain subunit of vertebrate ferritins catalyzes the oxidation of Fe(II) to Fe(III) by molecular oxygen. A previous stopped-flow kinetics study of a transient mu-peroxodiFe(III) intermediate formed at this site revealed very unusual kinetics curves, the shape of which depended markedly on the amount of iron presented to the protein. In the present work, a mathematical model for catalysis is developed that explains the observed kinetics. The model consists of two sequential mechanisms. In the first mechanism, turnover of iron at the ferroxidase site is rapid, resulting in steady-state production of the peroxo intermediate with continual formation of the mineral core until the available Fe(II) in solution is consumed. At this point, the second mechanism comes into play whereby the peroxo intermediate decays and the ferroxidase site is postulated to vacate its complement of iron. The kinetic data reveal for the first time that Fe(II) in excess of that required to saturate the ferroxidase site promotes rapid turnover of Fe(III) at this site and that the ferroxidase site plays a role in catalysis at all levels of iron loading of the protein (48-800 Fe/protein). The data also provide evidence for a second intermediate, a putative hydroperoxodiFe(III) complex, that is a decay product of the peroxo intermediate.

Ferric Compounds↗
PubMedDate not supplied

Morphological and molecular changes in the inner hair cell region of the rat cochlea after amikacin treatment.

This study investigates the morphological and molecular changes that occur in the inner hair cell area of the rat cochlea following aminoglycoside treatment. Rats were injected daily with 500 mg/kg of amikacin between postnatal day 9 (PND9) and PND16. Cochleae were examined at PND16 to PND120 using both scanning and transmission electron microscopy and molecular fluorescent labeling. The inner hair cells showed obvious signs of apoptosis in response to amikacin treatment and most of them were missing by one week after the end of the aminoglycoside exposure period. Concomitantly, the epithelium became scarred as the surrounding supporting cells expanded and filled the space vacated by the missing IHCs. The mid-basolateral region of these modified supporting cells was surrounded by many afferent and efferent terminals. However, these cells expressed neither calbindin nor SNAP25, proteins that are both expressed by IHCs in the normal, untreated organ of Corti in the rat. In addition, these supporting cells remained attached to the basal lamina by a thin cytoplasmic process. The supporting cells surrounding the inner hair cells therefore appear unable to convert directly into inner hair cells following aminoglycoside induced hair-cell loss but may be able to provide trophic support for the remaining afferent and efferent neurites.

Actins↗
PubMed2001

Reduced sun exposure and tanning in children after 2 years of a school-based intervention (Australia).

OBJECTIVE: This paper presents the results of the evaluation of measured suntan and parent-reported sun exposure in participating children after 2 years of the Kidskin study, a 5-year school-based sun protection intervention undertaken in Perth, Western Australia (1995-1999). METHODS: The study involves three groups: a control, a "moderate", and a "high" intervention group. Participants were 5 or 6 years of age at the beginning of the study. Control schools received the standard Health Education curriculum, while intervention schools received a multicomponent intervention including a specially designed curriculum. Children in the high intervention group also received program materials over the summer vacation and were offered sun-protective swimwear at low cost. At the end of the second summer, suntan was measured and parents completed a questionnaire about their child's sun-related behavior. RESULTS: Children in the intervention groups--especially the high group--were less tanned at the end of the summer; this effect was greater for the back than for the forearms. These children were also reported to have received less sun exposure and made greater use of sun protection measures. CONCLUSION: Intensive school-based interventions can reduce tanning and reported sun exposure in children.

Child↗
PubMed2002

Experimental evidence of an age-specific shift in chemical detection of predators in a lizard.

The risk posed by predation is one of the most fundamental aspects of an animal's environment. Avoidance of predators implies an ability to obtain reliable information about the risk of predation, and for many species, chemosensory cues are likely to be an important source of such information. Chemosensory cues reliably reveal the presence of predators or their presence in the recent past. We used retreat site selection experiments to test whether the Australian scincid lizard Eulamprus heatwolei uses chemical cues for predator detection and avoidance. Both adult and juvenile lizards were given the choice of retreat sites treated with scents from invertebrate predators, as well as sympatric and allopatric snake predators. Some of the snake predators were known to eat E. heatwolei, while others did not pose a predation threat. All invertebrate predators posed a risk to juveniles, but not adults because of their size. We found that juvenile E. heatwolei avoided predator odors more strongly than adults. Juveniles avoided both invertebrate predators and snakes, and the strongest response was toward the funnel web spider, the only ambush predator used in this experiment. This result may demonstrate the importance of predator ecology in the evolution of predator detection mechanisms, with chemical cues being more useful in detecting sedentary predators than active predators. Adult lizards showed no avoidance behavior toward predator odors. This result suggests an age specific shift in predator avoidance behavior as lizards get older and become too large for many predators. However, adults showed no response to the odor from the red-bellied black snake, a known predator of adult E. heatwolei. This finding further demonstrates the importance of predator ecology when examining communication between predators and prey. Chemical cues, which are persistent long after predators have vacated the area, may not be useful in detecting the red-bellied black snake, a wide-ranging active forager.

Age Factors↗
PubMed1998

Administrative update: utilization of services. III. Factors affecting emergency service utilization at a rural community mental health center.

Various factors may contribute to cyclical fluctuations in mental health emergency service utilization. Information regarding service utilization patterns would assist the planning and administration of such programs. Five years of data on emergency service contacts at a rural community mental health center were analyzed retrospectively in order to clarify which of an array of potential factors actually affect the utilization of emergency services. One way analyses of variance (ANOVA) or analogous nonparametric tests were performed. Furthermore analyses of significant group differences were performed by means of multiple comparison tests and confidence intervals. Significant associations with number of emergency contacts were found for season, day of week, holidays, school vacations and weather conditions. This study helps to elucidate those factors affecting psychiatric emergency service utilization at a rural community mental health center. Such factors may differ from those affecting other indicators of psychopathology.

Adult↗
PubMed2000

A mathematical programming approach for scheduling physicians in the emergency room.

Preparing a schedule for physicians in the emergency room is a complex task, which requires taking into account a large number of (often conflicting) rules, related to various aspects: limits on the number of consecutive shifts or weekly hours, special rules for night shifts and weekends, seniority rules, vacation periods, individual preferences,... In this paper, we present a mathematical programming approach to facilitate this task. The approach models the situation in a major hospital of the Montreal region (approximately 20 physicians are members of the working staff). We show that the approach can significantly reduce the time and the effort required to construct a six-month schedule. A human expert, member of the working staff, typically requires a whole dedicated week to perform this task, with the help of a spreadsheet. With our approach, a schedule can be completed in less than one day. Our approach also generates better schedules than those produced by the expert, because it can take into account simultaneously more rules than any human expert can do.

Emergency Service, Hospital↗
PubMed2003

Familias Unidas: the efficacy of an intervention to promote parental investment in Hispanic immigrant families.

This paper reports a test of the efficacy of Familias Unidas, a Hispanic-specific, ecologically focused, parent-centered preventive intervention, in promoting protection against and reducing risk for adolescent behavior problems. Specifically, the intervention was designed to foster parental investment, reduce adolescent behavior problems, and promote adolescent school bonding/academic achievement, all protective factors against drug abuse and delinquency. One-hundred sixty seven Hispanic families of 6th and 7th grade students from three South Florida public schools were stratified by grade within school and randomly assigned to intervention and no-intervention control conditions. Results indicated that Familias Unidas was efficacious in increasing parental investment and decreasing adolescent behavior problems, but that it did not significantly impact adolescent school bonding/academic achievement. Summer-vacation rates of adolescent behavior problems were six times higher in the control condition than in the intervention condition. Furthermore, change in parental investment during the intervention was predictive of subsequent levels of adolescent behavior problems. The findings suggest that Familias Unidas is efficacious in promoting protection and reducing risk for adolescent problem behaviors in poor immigrant Hispanic families.

Adolescent↗
PubMed1997

Experimental task and speaker effects on parent-child interactions of aggressive and depressed/anxious children.

Parent-child interactions of aggressive and depressed/anxious clinic-referred children were observed during two different tasks: planning a vacation and discussing a conflict. Marked group differences were found as a function of the type of task, who was speaking (parent vs. child), and type of child psychopathology. Negative behaviors (e.g., Belittling and Blaming) were especially pronounced in the conflict task, whereas positive behaviors (e.g., Nurturing and Protecting) were more common in the planning task. Parents displayed other-directed behavior (e.g., Watching and Controlling), whereas children showed more self-directed behavior (e.g., Walling Off and Distancing), and patterns of child psychopathology interacted with task and speaker in theoretically important ways; for example, parents of aggressive children showed more Belittling and Blaming than their children in the conflict task, but not in the planning task. The findings highlight key factors that may need to be incorporated into models of parent-child interaction and child psychopathology.

Adolescent↗
PubMed2004

Otodectes cynotis (Acari: Psoroptidae): examination of survival off-the-host under natural and laboratory conditions.

The biological and environmental factors affecting survival off-the-host of Otodectes cynotis (Acari: Psoroptidae) ear mites were investigated under natural and laboratory conditions. From November 2000 to November 2002 mites were collected monthly from cats and divided into four groups according to sex and stage. In laboratory conditions, the mites were placed in an incubator with a steady 95% relative humidity (r.h.), a 10 degrees C. All the plates were examined by stereomicroscopy every 24 h until all the mites had died. The data were analysed statistically by multiple linear regression and survival analysis. At 10 degrees C, the maximum survival time of mites was between 15 and 17 days, while at 34 degrees C, it was between 5 and 6 days. The maximum survival time of adult females was significantly longer than that of other stages. No differences were observed in maximum survival times of mites that had been offered food and those that had not, or in the time (in days) to reach 50% mortality (LT50). When exposed to environmental conditions, the maximum survival time (12 days) was observed at temperatures ranging from 12.3 to 14.2 degrees C and r.h.s between 57.6 and 82.9%. Multiple regression analysis showed that temperature alone influenced the maximum survival time and LT50 of mites, and that the rate of survival declined linearly with increasing mean temperature. This basic understanding of off-host survival suggests that, places which have been inhabited by infected animals may need to be disinfected or remain vacated for at least 12 days before occupancy by clean cats or dogs.

Animals↗
PubMed2004

Estimating the compensating differential for employer-provided health insurance.

The theory of wage differentials argues that workers must pay for employer-provided group health insurance coverage through lower wages or reductions in other fringe benefits. This paper uses data from the 1988-90 Consumer Expenditure Survey (CEX) to estimate the wage-health insurance trade-off for male workers between the ages of 25 and 55. A fixed-effects model, which takes advantage of the rotating panel design of the CEX, is used to control for unobservable worker characteristics that are positively related with all forms of compensation, including wage earnings and health insurance coverage. I find a compensating differential for health insurance equal to roughly 10 to 11 percent of wages. Some caution is advised here due to the fact that I was unable to control for other fringe benefits, the most important being paid vacation and sick leave.

Adult↗
PubMedDate not supplied

The relationship of neuromuscular synapse elimination to synaptic degeneration and pathology: insights from WldS and other mutant mice.

Neuromuscular synapse elimination, Wallerian degeneration and peripheral neuropathies are not normally considered as related phenomena. However, recent studies of mutant and transgenic mice, particularly the Wld(S) mutant-in which orthograde degeneration is delayed following axotomy-suggest that re-evaluation of possible links between natural, traumatic and pathogenic regression of synapses may be warranted. During developmental synapse elimination from polyneuronally innervated junctions, some motor nerve terminals progressively and asynchronously vacate motor endplates. A form of asynchronous synapse withdrawal, strongly resembling synapse elimination, also occurs from mononeuronally-innervated motor endplates following axotomy in young adult Wld(S) mutant mice. A similar pattern is observed in skeletal muscles of several neuropathic mutants, including mouse models of dying-back neuropathies, motor neuron disease and-remarkably-models of neurodegenerative diseases such as Huntington's and Alzheimer's diseases. Taken together with recent analysis of synaptic remodelling at neuromuscular junctions in Drosophila, a strong candidate for a common regulatory mechanism in these diverse conditions is one based on protein ubiquitination/deubiquitination. Axotomised neuromuscular junctions in Wld(S) mutant mice offer favourable experimental opportunities for examining developmental mechanisms of synaptic regression, that may also benefit our understanding of how degeneration in the synaptic compartment of a neuron is initiated, and its role in progressive, whole-cell neuronal degeneration.

Animals↗