Synaptic effects induced in efferent neurons of the parietal associative cortex of the cat by stimulation of the cerebellar nuclei

Properties of EPSP, evoked in efferent neurons of the parietal associative cortex by stimulation of the cerebellar nuclei, were studied in acute experiments on anesthetized and immobilized cats; intracellular recording was used. The neurons were identified by their antidromic activation after stimulation of the motor cortex, pontinen.n. proprii, or red nucleus. The effects of stimulation of the cerebellar nuclei were of oligo- and polysynaptic nature. The latencies of cerebellofugal EPSP correlated with the latencies of antidromic activation, and correlations were significant both in the cases when the effects of stimulation of separate efferent projections (cortico-cortical, cortico-pontine, or cortico-rubral) and the effects of stimulation of separate cerebellar nuclei were analyzed. The functional role of the efferent systems of the parietal associative cortex and significance of functional parameters of the neurons constituting these systems are discussed.Neirofiziologiya/Neurophysiology, Vol. 27, No. 3, pp. 190–198, May–June, 1995.     

A multiplatform strategy for the discovery of conventional monoclonal antibodies that inhibit the voltage-gated potassium channel Kv1.3

Identifying monoclonal antibodies that block human voltage-gated ion channels (VGICs) is a challenging endeavor exacerbated by difficulties in producing recombinant ion channel proteins in amounts that support drug discovery programs. We have developed a general strategy to address this challenge by combining high-level expression of recombinant VGICs in Tetrahymena thermophila with immunization of phylogenetically diverse species and unique screening tools that allow deep-mining for antibodies that could potentially bind functionally important regions of the protein. Using this approach, we targeted human Kv1.3, a voltage-gated potassium channel widely recognized as a therapeutic target for the treatment of a variety of T-cell mediated autoimmune diseases. Recombinant Kv1.3 was used to generate and recover 69 full-length anti-Kv1.3 mAbs from immunized chickens and llamas, of which 10 were able to inhibit Kv1.3 current. Select antibodies were shown to be potent (IC₅₀<10 nM) and specific for Kv1.3 over related Kv1 family members, hERG and hNav1.5.     

Influence of Low-Intensity Electromagnetic Field on Some Biological Parameters of Freshwater Crustaceans <Emphasis Type="Italic">Daphnia magna</Emphasis> Straus

We have studied the effects of a low-intensity electromagnetic field (EMF) with a frequency of 30 MHz in continuous-wave and amplitude-modulation modes on Daphnia magna in a laboratory culture. The exposure range is from 10 to 10000 s. We examine the parental generation (irradiated) and three subsequent (F₁–F₃) generations (nonirradiated). It is found that irradiation does not affect the total fertility of any specimen in four generations (P–F₃), except for continuous EMF exposure for 10000 s, which increases the total fertility in generations F₂ and F₃ by 23 and 43%, respectively. Electromagnetic radiation has a significant impact on offspring quality and causes fetal abnormalities in the offspring of all generations.     

Plant Cd2+ and Zn2+ status effects on root and shoot heavy metal accumulation in Thlaspi caerulescens

* In this study we address the impact of changes in plant heavy metal, (i.e. zinc (Zn) and cadmium (Cd)) status on metal accumulation in the Zn/Cd hyperaccumulator, Thlaspi caerulescens. * Thlaspi caerulescens plants were grown hydroponically on both high and low Zn and Cd regimes and whole-shoot and -root metal accumulation, and root (109)Cd(2+) influx were determined. * High-Zn-grown (500 microm Zn) plants were found to be more Cd-tolerant than plants grown in standard Zn conditions (1 microm Zn). Furthermore, shoot Cd accumulation was significantly greater in the high-Zn-grown plants. A positive correlation was also found between shoot Zn accumulation and increased plant Cd status. Radiotracer (109)Cd root flux experiments demonstrated that high-Zn-grown plants maintained significantly higher root Cd(2+) influx than plants grown on 1 microm Zn. It was also found that both nickel (Ni) and copper (Cu) shoot accumulation were stimulated by high plant Zn status, while manganese (Mn) accumulation was not affected. * A speculative model is presented to explain these findings, suggesting that xylem loading may be one of the key sites responsible for the hyperaccumulation of Zn and Cd accumulation in Thlaspi caerulescens.     

Dependence of the Activity of L-Amino Acid Oxidase in the Fungus Aspergillus nigerR-3 on the Source of Nitrogen in the Growth Medium

Various populations of peroxisomes in cells of Aspergillus nigerR-3 were formed under growth in media containing 0.5% glucose and various sources of nitrogen (1/4 of the optimal concentrations of (NH₄)₂SO₄, L-alanine, and L-methionine). Different levels of L-amino acid oxidase activity were found in these populations of peroxisomes.     

Identification of Thlaspi caerulescens genes that may be involved in heavy metal hyperaccumulation and tolerance. Characterization of a novel heavy metal transporting ATPase

Thlaspi caerulescens is a heavy metal hyperaccumulator plant species that is able to accumulate extremely high levels of zinc (Zn) and cadmium (Cd) in its shoots (30,000 microg g(-1) Zn and 10,000 microg g(-1) Cd), and has been the subject of intense research as a model plant to gain a better understanding of the mechanisms of heavy metal hyperaccumulation and tolerance and as a source of genes for developing plant species better suited for the phytoremediation of metal-contaminated soils. In this study, we report on the results of a yeast (Saccharomyces cerevisae) complementation screen aimed at identifying candidate heavy metal tolerance genes in T. caerulescens. A number of Thlaspi genes that conferred Cd tolerance to yeast were identified, including possible metal-binding ligands from the metallothionein gene family, and a P-type ATPase that is a member of the P1B subfamily of purported heavy metal-translocating ATPases. A detailed characterization of the Thlaspi heavy metal ATPase, TcHMA4, demonstrated that it mediates yeast metal tolerance via active efflux of a number of different heavy metals (Cd, Zn, lead [Pb], and copper [Cu]) out of the cell. However, in T. caerulescens, based on differences in tissue-specific and metal-responsive expression of this transporter compared with its homolog in Arabidopsis (Arabidopsis thaliana), we suggest that it may not be involved in metal tolerance. Instead, we hypothesize that it may play a role in xylem loading of metals and thus could be a key player in the hyperaccumulation phenotype expressed in T. caerulescens. Additionally, evidence is presented showing that the C terminus of the TcHMA4 protein, which contains numerous possible heavy metal-binding His and Cys repeats residues, participates in heavy metal binding. When partial peptides from this C-terminal domain were expressed in yeast, they conferred an extremely high level of Cd tolerance and Cd hyperaccumulation. The possibilities for enhancing the metal tolerance and phytoremediation potential of higher plants via expression of these metal-binding peptides are also discussed.     

Hidden population size estimation and diagnostics using two respondent-driven samples with applications in Armenia

Estimating the size of hidden populations is essential to understand the magnitude of social and healthcare needs, risk behaviors, and disease burden. However, due to the hidden nature of these populations, they are difficult to survey, and there are no gold standard size estimation methods. Many different methods and variations exist, and diagnostic tools are needed to help researchers assess method-specific assumptions as well as compare between methods. Further, because many necessary mathematical assumptions are unrealistic for real survey implementation, assessment of how robust methods are to deviations from the stated assumptions is essential. We describe diagnostics and assess the performance of a new population size estimation method, capture–recapture with successive sampling population size estimation (CR-SS-PSE), which we apply to data from 3 years of studies from three cities and three hidden populations in Armenia. CR-SS-PSE relies on data from two sequential respondent-driven sampling surveys and extends the successive sampling population size estimation (SS-PSE) framework by using the number of individuals in the overlap between the two surveys and a model for the successive sampling process to estimate population size. We demonstrate that CR-SS-PSE is more robust to violations of successive sampling assumptions than SS-PSE. Further, we compare the CR-SS-PSE estimates to population size estimations using other common methods, including unique object and service multipliers, wisdom of the crowd, and two-source capture–recapture to illustrate volatility across estimation methods.