Na+/K+-ATPase Inhibition Partially Mimics the Ethanol-Induced Increase of the Golgi Cell-Dependent Component of the Tonic GABAergic Current in Rat Cerebellar Granule Cells

Cerebellar granule cells (CGNs) are one of many neurons that express phasic and tonic GABAergic conductances. Although it is well established that Golgi cells (GoCs) mediate phasic GABAergic currents in CGNs, their role in mediating tonic currents in CGNs (CGN-I_tonic) is controversial. Earlier studies suggested that GoCs mediate a component of CGN-I_tonic that is present only in preparations from immature rodents. However, more recent studies have detected a GoC-dependent component of CGN-I_tonic in preparations of mature rodents. In addition, acute exposure to ethanol was shown to potentiate the GoC component of CGN-I_tonic and to induce a parallel increase in spontaneous inhibitory postsynaptic current frequency at CGNs. Here, we tested the hypothesis that these effects of ethanol on GABAergic transmission in CGNs are mediated by inhibition of the Na⁺/K⁺-ATPase. We used whole-cell patch-clamp electrophysiology techniques in cerebellar slices of male rats (postnatal day 23–30). Under these conditions, we reliably detected a GoC-dependent component of CGN-I_tonic that could be blocked with tetrodotoxin. Further analysis revealed a positive correlation between basal sIPSC frequency and the magnitude of the GoC-dependent component of CGN-I_tonic. Inhibition of the Na⁺/K⁺-ATPase with a submaximal concentration of ouabain partially mimicked the ethanol-induced potentiation of both phasic and tonic GABAergic currents in CGNs. Modeling studies suggest that selective inhibition of the Na⁺/K⁺-ATPase in GoCs can, in part, explain these effects of ethanol. These findings establish a novel mechanism of action of ethanol on GABAergic transmission in the central nervous system.     

Inhibitory effect of the flavonoid silymarin on the erythrocyte hemolysis induced by phenylhydrazine

The flavonoid silymarin, which is used as a therapeutical agent in the treatment of liver diseases, can inhibit the hemolysis and lipid peroxidation induced by phenylhydrazine on erythrocytes obtained from rats treated with the flavonoid. This effect is ascribed to the antioxidant properties as a free radical scavenger exhibited by the flavonoid. Silymarin failed to inhibit the glutathione depletion induced by phenylhydrazine on erythrocytes. It is proposed that the flavonoid acts at the membrane level of the cell avoiding the lipid peroxidative and fluidizing effect of phenylhydrazine.     

Snapshot prediction of carbon productivity,carbon and protein content in a Southern Ocean diatom using FTIR spectroscopy

Diatoms, an important group of phytoplankton, bloom annually in the Southern Ocean, covering thousands of square kilometers and dominating the region''s phytoplankton communities. In their role as the major food source to marine grazers, diatoms supply carbon, nutrients and energy to the Southern Ocean food web. Prevailing environmental conditions influence diatom phenotypic traits (for example, photophysiology, macromolecular composition and morphology), which in turn affect the transfer of energy, carbon and nutrients to grazers and higher trophic levels, as well as oceanic biogeochemical cycles. The paucity of phenotypic data on Southern Ocean phytoplankton limits our understanding of the ecosystem and how it may respond to future environmental change. Here we used a novel approach to create a ‘snapshot'' of cell phenotype. Using mass spectrometry, we measured nitrogen (a proxy for protein), total carbon and carbon-13 enrichment (carbon productivity), then used this data to build spectroscopy-based predictive models. The models were used to provide phenotypic data for samples from a third sample set. Importantly, this approach enabled the first ever rate determination of carbon productivity from a single time point, circumventing the need for time-series measurements. This study showed that Chaetoceros simplex was less productive and had lower protein and carbon content during short-term periods of high salinity. Applying this new phenomics approach to natural phytoplankton samples could provide valuable insight into understanding phytoplankton productivity and function in the marine system.     

Reducing HIV Risk among Transgender Women in Thailand: A Quasi-Experimental Evaluation of the Sisters Program

Transgender women are particularly at risk of HIV infection, but little evidence exists on effective HIV prevention strategies with this population. We evaluated whether Sisters, a peer-led program for transgender women, could reduce HIV risks in Pattaya, Thailand. The study used time-location sampling to recruit 308 transgender women in Pattaya into a behavioral survey in 2011. Coarsened exact matching was used to create statistically equivalent groups of program participants and non-participants, based on factors influencing likelihood of program participation. Using multivariable logistic regression, we estimated effects of any program participation and participation by delivery channel on: condom use at last sex; consistent condom and condom/water-based lubricant use in the past 3 months with commercial, casual, and regular partners; and receipt of HIV testing in the past 6 months. Program coverage reached 75% of the population. In a matched sub-sample (n = 238), participation in outreach was associated with consistent condom/water-based lubricant use with commercial partners (AOR 3.22, 95% CI 1.64–6.31). Attendance at the Sisters drop-in center was associated with receiving an HIV test (AOR 2.58, 95% CI 1.47–4.52). Dedicated transgender-friendly programs are effective at reducing HIV risks and require expansion to better serve this key population and improve HIV prevention strategies.     

P22 repressor mutants deficient in co-operative binding and DNA loop formation.

We show here, both in vivo and in vitro, that P22 repressor binds co-operatively to operator sites separated by an integral number of turns of the DNA helix. We measure this co-operativity in vivo using an assay in which repression of a promoter requires co-operative binding of P22 repressors to two separated (non-adjacent) operator sites. We report the isolation of mutant repressors that have high affinity for single operator sites, but are defective in co-operative binding. Six different mutants, all bearing single amino acid changes in the carboxyl domain, have been isolated. We purified the two mutants most deficient in co-operative binding, and found that they bind non-co-operatively in vitro to adjacent as well as to non-adjacent pairs of operator sites.     

Selective interactions among Rh,ABO, and sex ratio of newborns

Summary The hypothesis that the Rh and ABO blood systems behave like the HLA system in relation to mother-conception tolerance-rejection mechanisms was tested in 25,501 mother-infant pairs. According to this hypothesis, heterozygotes carrying a paternal gene that is not present in their mother should be better tolerated than homozygotes. Significantly more BO infants born to AO mothers. AO infants born to BO mothers, Rh(+) heterozygotes born to Rh(-) mothers, and less significantly AO infants born to OO mothers confirm the hypothesis. Fewer homozygotes occurred in Rh(-) infants born to Rh(+) mothers and in O infants born to non-O mothers. Deviations from the Hardy-Weinberg equilibrium found in the ABO system were modified by the Rh and sex of the infant. These data strongly support the hypothesis that at least two feto-maternal systems influence the denstiny of pregnancies: the classical known incompatibility system which operates late in pregnancy and a new one which is based on the induction of maternal tolerance early in pregnancy: maternal tolerance seems to be better elicited by heterozygous eggs or embryos carrying a gene not present in the mother. The data also support the hypothesis that the sex ratio is influenced by feto-maternal tolerance-rejection mechanisms associated with the ABO and Rh systems.     

Ribosomal subunit antiassociation activity in rabbit reticulocyte lysates. Evidence for a low molecular weight ribosomal subunit antiassociation protein factor (Mr = 25,000)

A ribosomal subunit antiassociation activity has been purified from both the postribosomal supernatant and ribosomal salt-wash protein fractions of rabbit reticulocyte lysates. A majority (greater than 90%) of the activity is associated with a low molecular weight protein of Mr of approximately 25,000. A small but significant level of antiassociation activity (less than 10%) was found to be associated with higher molecular weight protein fractions. The purified 25,000-dalton antiassociation factor interacts with 60 S ribosomal subunits to prevent them from reassociating with 40 S ribosomal subunits. The factor does not seem to interact directly with 40 S subunits nor does it dissociate 80 S monosomes. The properties of this factor are thus similar to the eukaryotic initiation factor 6 isolated from both wheat germ and calf liver extracts.     

Chromosomal mapping and nucleotide sequence of a human DNA autonomously replicating sequence

A 1.1-kb human DNA fragment (ARSH1) capable of functioning as a putative origin of replication in yeast cells has been characterized both by in situ hybridization to human metaphase chromosomes and by DNA sequencing. Our hybridization studies show a preferential localization of ARSH1 in chromosome regions 1p34-36 and 2q34-37. DNA sequence analysis indicates that in addition to the consensus sequence required for ARS function in yeast cells, nuclear matrix-associated DNA motifs are also present in the 1.1-kb fragment. These results suggest that ARSH1 sequences may serve as points of anchorage to the nuclear matrix for chromosomes 1 and 2.