Habituation and adaptation of the vestibuloocular reflex: a model of differential control by the vestibulocerebellum

Summary We habituated the dominant time constant of the horizontal vestibuloocular reflex (VOR) of rhesus and cynomolgus monkeys by repeated testing with steps of velocity about a vertical axis and adapted the gain of the VOR by altering visual input with magnifying and reducing lenses. After baseline values were established, the nodulus and ventral uvula of the vestibulocerebellum were ablated in two monkeys, and the effects of nodulouvulectomy and flocculectomy on VOR gain adaptation and habituation were compared. The VOR time constant decreased with repeated testing, rapidly at first and more slowly thereafter. The gain of the VOR was unaffected. Massed trials were more effective than distributed trials in producing habituation. Regardless of the schedule of testing, the VOR time constant never fell below the time constant of the semicircular canals (5 s). This finding indicates that only the slow component of the vestibular response, the component produced by velocity storage, was habituated. In agreement with this, the time constant of optokinetic after-nystagmus (OKAN) was habituated concurrently with the VOR. Average values for VOR habituation were obtained on a per session basis for six animals. The VOR gain was adapted by natural head movements in partially habituated monkeys while they wore ×2.2 magnifying or ×0.5 reducing lenses. Adaptation occurred rapidly and reached about ±30%, similar to values obtained using forced rotation. VOR gain adaptation did not cause additional habituation of the time constant. When the VOR gain was reduced in animals with a long VOR time constant, there were overshoots in eye velocity that peaked at about 6–8 s after the onset or end of constant-velocity rotation. These overshoots occurred at times when the velocity storage integrator would have been maximally activated by semicircular canal input. Since the activity generated in the canals is not altered by visual adaptation, this finding indicates that the gain element that controls rapid changes in eye velocity in the VOR is separate from that which couples afferent input to velocity storage. Nodulouvulectomy caused a prompt and permanent loss of habituation, returning VOR time constants to initial values. VOR gain adaptation, which is lost after flocculectomy, was unaffected by nodulouvulectomy. Flocculectomy did not alter habituation of the VOR or of OKAN. Using a simplified model of the VOR, the decrease in the duration of vestibular nystagmus due to habituation was related to a decrement in the dominant time constant of the velocity storage integrator (1/h ₀). Nodulouvulectomy, which reversed habituation, would be effected by decreasing h ₀, thereby increasing the VOR time constant. Small values of h ₀ would cause velocity storage to approach an ideal integrative process, leading the system to become unstable. By controlling the VOR time constant through habituation, the nodulus and uvula can stabilize the slow component of the VOR. VOR gain adaptation was related to a modification of the direct vestibular path gain g ₁, without altering the coupling to velocity storage g ₀ or its time constant (1/h ₀). The mismatched direct- and indirect-pathway gains simulated the overshoots in the dynamic response to a step in velocity, that were observed experimentally. We conclude that independent distributed elements in the VOR modify its dynamic response, under control of separate parts of the vestibulocerebellum.     

Regional sequence homologies in starch-degrading enzymes

The enzymatic hydrolysis of starch, consisting of linear (amylose) and branched (amylopectin) glucose polymers, is catalyzed by -, - and glucoamylases (-amylases), cyclodextrinases, -glucosidases, and debranching enzymes. Saccharomyces cerevisiae cannot utilize starch. Our laboratory has previously co-expressed the Bacillus amyloliquefaciens -amylase (AMY) and the Saccharomyces diastaticus glucoamylase (STA2) genes in S. cerevisiae. A gene encoding a debranching enzyme (pullulanase) from Klebsiella pneumoniae ATCC15050 was cloned and its nucleotide sequence determined. This gene will be co-expressed with the - and -amylase to produce an amylolytic S. cerevisiae strain. Extensive data base comparisons of the K. pneumoniae pullulanase amino-acid sequence with the the amino-acid sequences of other debranching enzymes and -, - and -amylases (from bacteria, yeasts, higher fungi and higher eukaryotes), indicated that these debranching enzymes have amino-acid regions similar to those found in -amylases. The conserved regions in -amylases comprise key residues that are implicated in substrate binding, catalysis, and calcium binding and are as follows. Region 1: DVVINH; region 2: GFRLDAAKH and region 4: FVDNHD. When comparing conserved regions, no similarity could be detected between debranching enzymes and - and -amylases. Present address: M.P.I. für Biophysikalische Chemie, Postfach 2841, D-3400 Göttingen, Germany (until 31 Dec 1993)     

Fatigue and fitness modelled from the effects of training on performance

Summary The purpose of this study was to compare two ways of estimating both fatigue and fitness indicators from systems model of the effects of training on performance. The model was applied to data concerning the training of a hammer thrower. The variations in performance were mathematically related to the successive amounts of training. The model equation was composed of negative (NF) and positive (PF) functions. The NF and PF were associated with the fatigue and fitness estimated in previous studies. Using another method, fatigue and fitness indicators were estimated from a combination of NF and PF. The influence of training on performance was negatively associated with fatigue (NI), and positively to fitness (PI). The changes in performance were well described by the model in the present study (r = 0.96,N = 19,P<0.001). Significant correlations were observed between NF and NI (r = 0.93,P < 0.001) on the one hand and between PF and PI (r = 0.90,P < 0.001) on the other. The absolute values and the time variations of PI and NI were closer to the change in performance than NF and PF. The NF and PF were accounted for mainly by the accumulation of amounts of training. On the other hand, NI and PI were accounted for rather by the impact of these amounts of training on performance.     

Pathology of inverted Takotsubo cardiomyopathy

Myocardial dysfunction without coronary involvement may occur in acute cerebral diseases. The inverted Takotsubo pattern has been recently recognized as a novel heart neurologic stress-related syndrome. We report on the case of a 40-year-old woman presenting with massive subarachnoid hemorrhage and brain death. Echocardiography revealed an extensive left ventricular circumferential akinesis except at the apex. Histologic analysis of the heart confirmed the absence of myocardial infarction and revealed only sparse foci of myocyte necrosis with contraction bands in the akinetic areas.     

The biochemical characterization of E2, a T cell surface molecule involved in rosettes

We have previously identified a molecule on the T cell surface, which, in addition to CD2 is involved in the rosette phenomenon. This is a 32-kDa single polypeptide chain which we have termed E2. The studies reported here show striking patterns on the glycosylation status of E2. It is a heavily sialylated and glycosylated molecule, the sugar moieties accounting for almost half of its relative molecular mass (Mr). It carries no N-linked sugar residues, only O-linked oligosaccharides. Despite heavy glycosylation, the molecule appears to behave homogeneously on gel electrophoresis, both in terms of Mr and pI. Neuraminidase treatment of E2 lowered its Mr to 28 kDa; this was further decreased to 18 kDa after removal of O-linked sugar residues by treatment with O-glycanase. An identical reduction in size was observed after treatment with trifluoromethane sulfonic acid, showing that the molecule carries no detectable N-linked sugar residues. Moreover, endoglycosidase F and endoglycosidase H treatment of either the immunoprecipitates from 125I surface-labeled thymocytes, or of a purified preparation of E2, did not reduce the Mr of E2, nor did tunicamycin treatment of T cells. Two-dimensional gel electrophoresis revealed two discrete spots of acidic pI (4.4 and 4.6) that were still seen after neuraminidase treatment, though they had moderately shifted. Pulse-chase experiments revealed a single 28-kDa precursor form that could have been the unsialylated molecule. Finally, sequencing 14 amino acid residues of the N-terminal side revealed no homology with known proteins. Since the sugar moieties of adhesion protein could play an important role, the results obtained in this study will prove valuable to our understanding of the role exerted by the E2 molecule.     

Synthesis and polymerization of fluorinated acrylic monomers substituted in α-position, 2. Synthesis and polymerization of 2-perfluorohexylethyl α-acetoxyacrylate

The synthesis of 2-perfluorohexylethyl α-acetoxyacrylate (^b) H₂C?C(OAc)CO₂C₂H₄C₆F₁₃ ( 1 ) was performed in two steps starting from pyruvic acid and 2-perfluorohexylethanol (3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluoro-1-octanol) with an overall yield of about 50%. Esterification of pyruvic acid with the adequate fluorinated alcohol was followed by enol acetylation to give monomer 1 . Homopolymerization and copolymerization of 1 are easily carried out. From the kinetic study of the homopolymerization and copolymerization of 1 with styrene, the numerical values of the ratio square of the rate constant of propagation over the rate constant of termination k/k_t and of the copolymerization reactivity ratios r₁ and r₂ of the two monomers were determined.     

Prevalence, geographical distribution and genealogical investigations of mutation 188 of lipoprotein lipase gene in the French Canadian population of Québec

Familial lipoprotein lipase deficiency (FLD) is of particular interest to the French Canadian population of Québec since the largest concentration of homozygotes and carriers of this genetic disease in the world resides in this area. We have previously described a missense mutation (M-188) in the lipoprotein lipase (LPL) gene which was present in FLD patients belonging to different ancestries, including a number of French Canadians (Monsalve MV et al. J Clin Invest 1990: 86: 728-734). In the present report, we show that this mutation, although found in largest absolute numbers among French Canadians as compared to other groups in the world, accounts for only a small proportion (24%) of all the LPL mutant alleles in this population. The M-188 occurs either in the homozygote state or as a compound heterozygote with another LPL mutation. Analysis of geographic distribution indicates that the M-188 is more prevalent in western Québec, with the highest carrier rate in the Mauricie region. Genealogical reconstruction leads to the recognition of four founders for M-188, all emigrants from France to Québec in the 17th century.