Central adaptation models of the vestibulo-ocular and optokinetic systems

A theoretical analysis of two models of the vestibulo-ocular and optokinetic systems was performed. Each model contains a filter element in the vestibular periphery to account for peripheral adaptation, and a filter element in the central vestibulooptokinetic circuit to account for central adaptation. Both models account for1 adaptation, i.e. a response decay to a constant angular acceleration input, in both peripheral vestibular afferent and vestibulo-ocular reflex (VOR) responses and2 the reversal phases of optokinetic after-nystagmus (OKAN) and the VOR and3 oscillatory behavior such as periodic alternating nystagmus. The two models differ regarding the order of their VOR transfer function. Also, they predict different OKAN patterns following a prolonged optokinetic stimulus. These models have behavioral implications and suggest future experiments.     

Immunological diagnosis of Mycoplasma pneumonias]

A complex of immunological cell tests with M. pneumoniae antigen (the lymphocyte blast-cell transformation test, the allergic neutrophil alteration test) was carried out in order to establish the correlation between the results of positive seroconversion and the sepcific immunological reactivity of lymphoid cells in pneumonia patients. Mycoplasmic cutireactive allergen, when used for the accelerated diagnosis of mycoplasmic pneumonia in humans, was shown to be specific and safe. Cuti-allergic tests with mycoplasmic allergen allowed to diagnose mycoplasmic pneumonia at early stages (beginning from days 5--7), which ensures the possibility of indicating etiotropic treatment to patients in due time.     

Variations in left and right ventricular oxygen balance produced by paired electrical stimulations

The possible differential effect of positive inotropic stimulation upon regional myocardial oxygen balance in the two ventricles was investigated during tachycardia and paired electrical stimulation. Isometric contractile force was measured by strain gauge arches; local coronary blood supply was measured by thermistor probes and intracellular NADH redox level was recorded using surface fluorometry. It was found that when contractility was increased by paired stimulation at a basic rate of 140 bpm, the inotropic response was more pronounced in the right ventricle (97.2 +/- 11.5%) than in the left (63.1 +/- 12.6%). Coronary blood supply to the left ventricle increased by 117.8 +/- 30.4% and the corresponding NADH redox level increased by 54.3 +/- 19.9%. When the contractile force was increased to the same extent (64.1 +/- 8.9%) by single stimulation at a rate of 210 bpm, the coronary flow to the left ventricle was increased by only 36.4 +/- 11.0% and the NADH state rose by 67.1 +/- 12.1%. It is concluded that paired stimulation reduced the mechanical limitation to flow during tachycardia, thus allowing coronary blood supply to increase in response to positive inotropic stimulation, thereby preserving a relatively improved oxygen state. It was also observed that the ratio contractile force/blood supply (contraction efficiency) was usually proportional to the NADH redox level (oxygen balance). Nevertheless, variations observed in the force/supply ratio for the left ventricle indicate that the NADH redox level cannot be predicted quantitatively by the force/supply ratio.     

Changes in Respiratory Metabolism during Aging in Seeds and Isolated Axes of Soybean

Cyanide-sensitive O₂ uptake was observed in the isolated embryonicaxis of soybean [Glycine max L. merr. cv. ‘Essex’]within 5 min after wetting and the O₂ uptake rate during thefirst h of imbibition was directly proportional to axis moisturecontent. Within 10 min after wetting, O₂ uptake was lower inaged low vigor (LV) axes than in high vigor (HV) axes imbibedeither in water (LV axes sustain imbibition injury) or in 30%w/v polyethylene glycol (LV axes do not sustain imbibition injury).Mitochondria isolated from LV axes after 4- and 24-h imbibitionwere characterized by lower O₂ uptake, ADP:O, and respiratorycontrol ratios relative to HV mitochondria. A plot of O₂ uptakevs temperature between 10 and 25?C revealed a break in the slopebetween 13 and 16?C for HV, but not LV, axes. Since LV axessustained water uptake injury at all temperatures tested, whereasHV axes sustained chilling injury only below 16?C, the dataindicate two temperature-O₂ uptake relationships: one for injuredtissues and one for non-injured tissues. We conclude that deteriorationper se involves impairment of respiratory metabolism in thesoybean embryonic axis. Chilling (10?C; HV and LV axes) andimbibitional (25?C; LV axes) injuries during the initial minof inbibition further disrupt respiratory metabolism and interferewith subsequent mitochondrial development and axis growth. ¹Scientific Articles No. A-3548, Contribution No. 6623 of theMaryland Agricultural Experiment Station. (Received May 25, 1983; Accepted September 28, 1983)     

Control of CydB and GltA1 expression by the SenX3 RegX3 two component regulatory system of Mycobacterium tuberculosis

Two component regulatory systems are used widely by bacteria to coordinate changes in global gene expression profiles in response to environmental signals. The SenX3-RegX3 two component system of Mycobacterium tuberculosis has previously been shown to play a role in virulence and phosphate-responsive control of gene expression. We demonstrate that expression of SenX3-RegX3 is controlled in response to growth conditions, although the absolute changes are small. Global gene expression profiling of a RegX3 deletion strain and wild-type strain in different culture conditions (static, microaerobic, anaerobic), as well as in an over-expressing strain identified a number of genes with changed expression patterns. Among those were genes previously identified as differentially regulated in aerobic culture, including ald (encoding alanine dehydrogenase) cyd,encoding a subunit of the cytochrome D ubiquinol oxidase, and gltA1, encoding a citrate synthase. Promoter activity in the upstream regions of both cydB and gltA1 was altered in the RegX3 deletion strain. DNA-binding assays confirmed that RegX3 binds to the promoter regions of ald, cydB and gltA1 in a phosphorylation-dependent manner. Taken together these data suggest a direct role for the SenX-RegX3 system in modulating expression of aerobic respiration, in addition to its role during phosphate limitation.     

Enamel thickness,microstructure and development in Afropithecus turkanensis

Afropithecus turkanensis, a 17-17.5 million year old large-bodied hominoid from Kenya, has previously been reported to be the oldest known thick-enamelled Miocene ape. Most investigations of enamel thickness in Miocene apes have been limited to opportunistic or destructive studies of small samples. Recently, more comprehensive studies of enamel thickness and microstructure in Proconsul, Lufengpithecus, and Dryopithecus, as well as extant apes and fossil humans, have provided information on rates and patterns of dental development, including crown formation time, and have begun to provide a comparative context for interpretation of the evolution of these characters throughout the past 20 million years of hominoid evolution. In this study, enamel thickness and aspects of the enamel microstructure in two A. turkanensis second molars were quantified and provide insight into rates of enamel apposition, numbers of cells actively secreting enamel, and the time required to form regions of the crown. The average value for relative enamel thickness in the two molars is 21.4, which is a lower value than a previous analysis of this species, but which is still relatively thick compared to extant apes. This value is similar to those of several Miocene hominoids, a fossil hominid, and modern humans. Certain aspects of the enamel microstructure are similar to Proconsul nyanzae, Dryopithecus laietanus, Lufengpithecus lufengensis, Graecopithecus freybergi and Pongo pygmaeus, while other features differ from extant and fossil hominoids. Crown formation times for the two teeth are 2.4-2.6 years and 2.9-3.1 years respectively. These times are similar to a number of extant and fossil hominoids, some of which appear to show additional developmental similarities, including thick enamel. Although thick enamel may be formed through several developmental pathways, most Miocene hominoids and fossil hominids with relatively thick enamel are characterized by a relatively long period of cuspal enamel formation and a rapid rate of enamel secretion throughout the whole cusp, but a shorter total crown formation time than thinner-enamelled extant apes.     

The "practical mathematics" of recording three-dimensional eye position using scleral coils.

The "gold standard" for recording the three-dimensional rotation of the eye involves placing two coils of wire, embedded in a soft plastic ring, on the sclera of the eye, then placing the subject inside a set of orthogonal oscillating magnetic fields, and using the currents induced in the eye coils to deduce the position of the coil, and hence of the eye, in space. Eye movements are actually eye rotations, which can be described mathematically by a special class of matrices, rotation matrices, or, alternatively, by a rotation vector related to the axis of the rotation. This article deals with the mathematical tools needed to implement the signal processing from such a multifield, dual-coil system and compute the precise rotational movement of the eye. One reason for making such careful measurements is to study an interesting constraint on eye movements, called Listing's law, which expresses ocular torsion, or rotation of the eye about its line of sight, in terms of the direction of gaze. Techniques for experimentally quantitating these constraints are also presented. Following a treatment of the "ideal" case, with coils and eye in perfect alignment, the additional techniques for dealing with various departures from ideality that are almost always encountered experimentally are examined. A final section deals with developing a validation protocol for eye movement analysis techniques using mechanical and computer simulations of eye movements.     

Repeated high doses of avermectins cause prolonged sterilisation, but do not kill, Onchocerca ochengi adult worms in African cattle

Background

Ivermectin (Mectizan?, Merck and CO. Inc.) is being widely used in the control of human onchocerciasis (Onchoverca volvulus) because of its potent effect on microfilariae. Human studies have suggested that, at the standard dose of 150 μg/kg an annual treatment schedule of ivermectin reversibly interferes with female worm fertility but is not macrofilaricidal. Because of the importance of determining whether ivermectin could be macrofilaricidal, the efficacy of high and prolonged doses of ivermectin and a related avermectin, doramectin, were investigated in cattle infected with O. ochengi.

Methods

Drugs with potential macrofilaricidal activity, were screened for the treatment of human onchocerciasis, using natural infections of O. ochengi in African cattle. Three groups of 3 cows were either treated at monthly intervals (7 treatments) with ivermectin (Ivomec^®, Merck and Co. Inc.) at 500 μg/kg or doramectin (Dectamax^®, Pfizer) at 500 μg/kg or not treated as controls. Intradermal nodules were removed at 6 monthly intervals and adult worms were examined for signs of drug activity.

Results

There was no significant decline in nodule diameter, the motility of male and female worms, nor in male and female viability as determined by the ability to reduce tetrazolium, compared with controls, at any time up to 24 months from the start of treatments (mpt). Embryogenesis, however, was abrogated by treatment, which was seen as an accumulation of dead and dying intra-uterine microfilariae (mf) persisting for up to 18 mpt. Skin mf densities in treated animals had fallen to zero by <3 mpt, but by 18 mpt small numbers of mf were found in the skin of some treated animals and a few female worms were starting to produce multi-cellular embryonic stages. Follow-up of the doramectin treated group at 36 mpt showed that mf densities had still only regained a small proportion of their pre-treatment levels.

Conclusion

These results have important implications for onchocerciasis control in the field. They suggest that ivermectin given at repeated high does may sterilise O. volvulus female worms for prolonged periods but is unlikely to kill them. This supports the view that control programmes may need to continue treatments with ivermectin for a period of decades and highlights the need to urgently identify new marcofiliaricidal compounds.     

Intrinsic regulation of spatiotemporal organization within the suprachiasmatic nucleus

The mammalian pacemaker in the suprachiasmatic nucleus (SCN) contains a population of neural oscillators capable of sustaining cell-autonomous rhythms in gene expression and electrical firing. A critical question for understanding pacemaker function is how SCN oscillators are organized into a coherent tissue capable of coordinating circadian rhythms in behavior and physiology. Here we undertake a comprehensive analysis of oscillatory function across the SCN of the adult PER2::LUC mouse by developing a novel approach involving multi-position bioluminescence imaging and unbiased computational analyses. We demonstrate that there is phase heterogeneity across all three dimensions of the SCN that is intrinsically regulated and extrinsically modulated by light in a region-specific manner. By investigating the mechanistic bases of SCN phase heterogeneity, we show for the first time that phase differences are not systematically related to regional differences in period, waveform, amplitude, or brightness. Furthermore, phase differences are not related to regional differences in the expression of arginine vasopressin and vasoactive intestinal polypeptide, two key neuropeptides characterizing functionally distinct subdivisions of the SCN. The consistency of SCN spatiotemporal organization across individuals and across planes of section suggests that the precise phasing of oscillators is a robust feature of the pacemaker important for its function.