Aging-related changes in the sensitivity of the system of respiratory control and the intensity of free-radical processes in humans

Results of a comparative study of the sensitivity of the system of respiratory control to increases in the CO₂ concentration and the intensity of free-radical processes in young and elderly subjects are described. It is shown that normal (natural) aging is accompanied by a decrease in the sensitivity of the respiratory system to hypercapnic stimulation and a parallel significant decrease in the activity of catalase in the blood of examined subjects. Mechanisms responsible for the modifications of the sensitivity of the system of respiratory control to hypercapnia are discussed; these shifts can be at least partly related to changes in the intensity of production of free radicals observed in elderly subjects. Neirofiziologiya/Neurophysiology, Vol. 40, No. 1, pp. 53–57, January–February, 2008.     

Means for efficient electron beam generation in wide-aperture open-discharge light sources

The interaction of a plasma in the accelerating gap of an open discharge with a strong external electric field and with the cathode surface has been investigated theoretically and experimentally. In a pulsed nanosecond discharge, the ion inertia and plasma screening of the electric field cause a fast growth of the electric field E in the cathode region and a decrease in the length of the latter. Along with a reduction of the electron multiplication factor at high electric fields, this leads to a substantial decrease in the ion flux toward the cathode, which allows one to develop highly efficient open-discharge light sources with a long lifetime and low cathode sputtering. In this respect, continuous and quasi-continuous discharges are less advantageous because of the smaller increase in the electric field in the cathode region. The Townsend coefficients of charge multiplication and electron emission at high electric fields typical of open discharges have been measured for the first time. Fast ions and atoms extracted from the plasma of the accelerating gap significantly affect the cathode emission properties. In particular, photoemission is enhanced by more than one order of magnitude and becomes the main mechanism for electron generation. This also increases the efficiency and lifetime of open-discharge light sources.     

Oculomotor activities in monkeys with N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced syndrome of parkinsonism

In twoMacaca rhesus monkeys that received repeated N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) injections (single dose 0.2 mg/kg, i.m.; cumulative dose 11.2–13.3 mg), changes in characteristics of spontaneous saccadic eye movements and vestibulo-ocular reflex (VOR) were evaluated. With the development of severe behavioral disturbances, amplitude of spontaneous saccadic eye movements gradually decreased. Pronounced changes in duration of saccadic eye movements, frequency of spontaneous saccades, and their pattern were observed. No changes in parameters of VOR slow component were recorded, but high total MPTP doses suppressed fast phase of the reflex.Neirofiziologiya/Neurophysiology, Vol. 25, No. 3, pp. 184–190, May–June, 1993.     

Nonuniformity of calcium efflux from pancreatic acinar cells and its analysis by mathematical model of calcium diffusion and buffering in extracellular solution

We studied spatial and temporal patterns of Ca²⁺ extrusion from pancreatic acinar cells evoked by acetylcholine(ACh)-induced activation of plasma membrane calcium pumps. Using a modification of an earlier developed model, we estimated the time course of extracellular calcium concentration changes near the basal pole of a cell in the case, when calcium ions are released from the same site on the cell surface, and in the case when they are extruded from the apical pole and diffuse to the basal one. It is concluded that at the first stage of ACh-induced Ca²⁺ extrusion the appearance of Ca²⁺ elevation near the basal pole of the cells cannot be explained as a result of diffusion, but is mainly determined by Ca²⁺ efflux from this pole. The results also show that there are plasma membrane calcium pumps in both apical and basal parts of pancreatic acinar cells, but the activity of the pumps is substantially higher in the apical region.     

Raphe serotonin neuron‐specific oxytocin receptor knockout reduces aggression without affecting anxiety‐like behavior in male mice only

Serotonin and oxytocin influence aggressive and anxiety‐like behaviors, though it is unclear how the two may interact. That the oxytocin receptor is expressed in the serotonergic raphe nuclei suggests a mechanism by which the two neurotransmitters may cooperatively influence behavior. We hypothesized that oxytocin acts on raphe neurons to influence serotonergically mediated anxiety‐like, aggressive and parental care behaviors. We eliminated expression of the oxytocin receptor in raphe neurons by crossing mice expressing Cre recombinase under control of the serotonin transporter promoter (Slc6a4) with our conditional oxytocin receptor knockout line. The knockout mice generated by this cross are normal across a range of behavioral measures: there are no effects for either sex on locomotion in an open‐field, olfactory habituation/dishabituation or, surprisingly, anxiety‐like behaviors in the elevated O and plus mazes. There was a profound deficit in male aggression: only one of 11 raphe oxytocin receptor knockouts showed any aggressive behavior, compared to 8 of 11 wildtypes. In contrast, female knockouts displayed no deficits in maternal behavior or aggression. Our results show that oxytocin, via its effects on raphe neurons, is a key regulator of resident‐intruder aggression in males but not maternal aggression. Furthermore, this reduction in male aggression is quite different from the effects reported previously after forebrain or total elimination of oxytocin receptors. Finally, we conclude that when constitutively eliminated, oxytocin receptors expressed by serotonin cells do not contribute to baseline anxiety‐like behaviors or maternal care.     

The Combination of Selenium and Vitamin E Inhibits Type I Collagen Formation in Cultured Hepatic Stellate Cells

This study investigated the effects of sodium selenite (Se) and of vitamin E (d-α-tochopherol) on the deposition of type I collagen by human LX-2 stellate cells. The cultured cells were treated with or without Se or vitamin E and with or without transforming growth factor β1 (TGFβ1). The combination of Se and vitamin E, but not either alone, protected against hepatic fibrosis by decreasing TGFβ1-mediated collagen secretion and accumulation by the stellate cells. This protective effect is due to a combination of decreased formation, decreased stability and increased degradation of the collagen. Effects of Se and vitamin E in decreasing α₁(I) collagen mRNA and increasing apoptosis of stellate cells indicate decreased formation of collagen, while decreases in transglutaminase 2, which catalyze cross-linking of collagen, lead to decreased stability of the secreted collagen. Effects of Se and vitamin E on reducing tissue inhibitor metalloproteinase 1 (TIMP-1) are associated with increased degradation. The combination of Se and vitamin E decreased lipid peroxidation, while Se alone increased the activity of the antioxidant enzyme thioredoxin reductase. In conclusion, the combination of Se and vitamin E protected against TGFβ1-mediated hepatic fibrosis by decreasing TGFβ1-mediated type I collagen accumulation by stellate cells. This effect is due to a combination of decreased formation, decreased stability and increased degradation of the collagen.     

Manifold aspects of specificity in a nematode–bacterium mutualism

Coevolution in mutualistic symbiosis can yield, because the interacting partners share common interests, to coadaptation: hosts perform better when associated with symbionts of their own locality than with others coming from more distant places. However, as the two partners of a symbiosis might also experience conflicts over part of their life cycle, coadaptation might not occur for all life‐history traits. We investigated this issue in symbiotic systems where nematodes (Steinernema) and bacteria (Xenorhabdus) reproduce in insects they have both contributed to kill. Newborn infective juveniles (IJs) that carry bacteria in their intestine then disperse from the insect cadaver in search of a new host to infect. We ran experiments where nematodes coinfect insects with bacteria that differ from their native symbiont. In both Steinernema carpocapsae/Xenorhabdus nematophila and Steinernema feltiae/Xenorhabdus bovienii symbioses, we detected an overall specificity which favours the hypothesis of a fine‐tuned co‐adaptation process. However, we also found that the life‐history traits involved in specificity strongly differ between the two model systems: when associated with strains that differ too much from their native symbionts, S. carpocapsae has low parasitic success, whereas S. feltiae has low survival in dispersal stage.     

Spectrum of Ocular Manifestations in?CLN2-Associated Batten (Jansky-Bielschowsky)?Disease Correlate with Advancing Age and Deteriorating Neurological Function

Background

Late infantile neuronal ceroid lipofuscinosis (LINCL), one form of Batten’s disease is a progressive neurodegenerative disorder resulting from a CLN2 gene mutation. The spectrum of ophthalmic manifestations of LINCL and the relationship with neurological function has not been previously described.

Methods

Patients underwent ophthalmic evaluations, including anterior segment and dilated exams, optical coherence tomography, fluorescein and indocyanine green angiography. Patients were also assessed with the LINCL Neurological Severity Scale. Ophthalmic findings were categorized into one of five severity scores, and the association of the extent of ocular disease with neurological function was assessed.

Results

Fifty eyes of 25 patients were included. The mean age at the time of exam was 4.9 years (range 2.5 to 8.1). The mean ophthalmic severity score was 2.6 (range 1 to 5). The mean neurological severity score was 6.1 (range 2 to 11). Significantly more severe ophthalmic manifestations were observed among older patients (p<0.005) and patients with more severe neurological findings (p<0.03). A direct correlation was found between the Ophthalmic Severity Scale and the Weill Cornell Neurological Scale (p<0.002). A direct association was also found between age and the ophthalmic manifestations (p<0.0002), with older children having more severe ophthalmic manifestations.

Conclusions

Ophthalmic manifestations of LINCL correlate closely with the degree of neurological function and the age of the patient. The newly established LINCL Ophthalmic Scale may serve as an objective marker of LINCL severity and disease progression, and may be valuable in the evaluation of novel therapeutic strategies for LINCL, including gene therapy.