A Genetic Locus Regulates the Expression of Tissue-Specific mRNAs from Multiple Transcription Units

129 GIX- mice, unlike animals of the congeneic partner strain GIX+, do not express significant amounts of the retroviral antigens gp70 and p30. Evidence is presented indicating that the GIX phenotype is specified by a distinct regulatory gene acting on multiple transcription units to control the levels of accumulation of specific mRNA species. The steady-state levels of retroviral-homologous mRNA from the tissues of GIX+ and GIX- mice were examined by blot hybridization using as probes DNA fragments from cloned murine leukemia viruses. RNA potentially encoding viral antigens was reduced or absent in GIX- mice, even though no differences in integrated viral genomes were detected between these congeneic strains by DNA blotting. Tissue-specific patterns of accumulation of these RNA species were detected in brain, epididymis, liver, spleen, and thymus, and several distinct RNA species were found to be coordinately regulated with the GIX phenotype. Measurements of RNA synthesis suggest a major role for transcriptional control in the regulation of some retroviral messages

Determination of biomembrane bending moduli in fully atomistic simulations.

The bilayer bending modulus (Kc) is one of the most important physical constants characterizing lipid membranes, but precisely measuring it is a challenge, both experimentally and computationally. Experimental measurements on chemically identical bilayers often differ depending upon the techniques employed, and robust simulation results have previously been limited to coarse-grained models (at varying levels of resolution). This Communication demonstrates the extraction of Kc from fully atomistic molecular dynamics simulations for three different single-component lipid bilayers (DPPC, DOPC, and DOPE). The results agree quantitatively with experiments that measure thermal shape fluctuations in giant unilamellar vesicles. Lipid tilt, twist, and compression moduli are also reported

Loss of AND-34/BCAR3 Expression in Mice Results in Rupture of the Adult Lens

PURPOSE. AND-34/BCAR3 (Breast Cancer Anti-Estrogen Resistance 3) associates with the focal adhesion adaptor protein, p130CAS/BCAR1. Expression of AND-34 regulates epithelial cell growth pattern, motility, and growth factor dependence. We sought to establish the effects of the loss of AND-34 expression in a mammalian organism. METHODS. AND-34−/− mice were generated by homologous recombination. Histopathology, in situ hybridization, and western blotting were performed on murine tissues. RESULTS. Western analyses confirmed total loss of expression in AND-34−/− splenic lymphocytes. Mice lacking AND-34 are fertile and have normal longevity. While AND-34 is widely expressed in wild type mice, histologic analysis of multiple organs in AND-34−/− mice is unremarkable and analyses of lymphocyte development show no overt changes. A small percentage of AND-34−/− mice show distinctive small white eye lesions resulting from the migration of ruptured cortical lens tissue into the anterior chamber. Following initial vacuolization and liquefaction of the lens cortex first observed at postnatal day three, posterior lens rupture occurs in all AND-34−/− mice, beginning as early as three weeks and seen in all mice at three months. Western blot analysis and in situ hybridization confirmed the presence of AND-34 RNA and protein in lens epithelial cells, particularly at the lens equator. Prior data link AND-34 expression to the activation of Akt signaling. While Akt Ser 473 phosphorylation was readily detectable in AND-34+/+ lens epithelial cells, it was markedly reduced in the AND-34−/− lens epithelium. Basal levels of p130Cas phosphorylation were higher in AND-34+/+ than in AND-34−/− lens epithelium. CONCLUSIONS. These results demonstrate the loss of AND-34 dysregulates focal adhesion complex signaling in lens epithelial cells and suggest that AND-34-mediated signaling is required for maintenance of the structural integrity of the adult ocular lens.National Institutes of Health (RO1 CA114094); Logica Foundatio

Shwartzman reaction after human renal homotransplantation.

In three human recipients, five renal homografts were destroyed within a few minutes to hours after their revascularization in the new host. The kidneys, removed one to 54 days later, had cortical necrosis. The major vessels were patent, but the arterioles and glomeruli were the site of fibrin deposition. There was little or no fixation of host immunoglobulins in the homografts. The findings were characteristic of a generalized Shwartzman reaction. Although the cause (or causes) of the Shwartzman reaction in our patients is not known, they may have been conditioned by the bacterial contamination and hemolysis that often attend hemodialysis, by immunosuppression and by the transplantation itself. Some of the patients have preformed lymphocytotoxic antibodies. Thus, certain patients may be predisposed. High-risk patients should be recognized and treated prophylactically with anticoagulants

Complementary Patents and Market Structure

Many high technology goods are based on standards that require several essential patents owned by different IP holders. This gives rise to a complements and a double mark-up problem. We compare the welfare effects of two different business strategies dealing with these problems. Vertical integration of an IP holder and a downstream producer solves the double mark-up problem between these firms. Nevertheless, it may raise royalty rates and reduce output as compared to non-integration. Horizontal integration of IP holders solves the complements problem but not the double mark-up problem. Vertical integration discourages entry and reduces innovation incentives, while horizontal integration always benefits from entry and innovatio

The Pump Song

Turquoise and Orange cartoon of adults on water pump and photograph of Oreste and his Queensland Orchestrahttps://scholarsjunction.msstate.edu/cht-sheet-music/13501/thumbnail.jp

A Human-Derived Monoclonal Antibody Targeting Extracellular Connexin Domain Selectively Modulates Hemichannel Function

Connexin hemichannels, which are plasma membrane hexameric channels (connexons) composed of connexin protein protomers, have been implicated in a host of physiological processes and pathological conditions. A number of single point pathological mutations impart a "leaky" character to the affected hemichannels, i.e., make them more active or hyperactive, suggesting that normal physiological condition could be recovered using selective hemichannel inhibitors. Recently, a human-derived monoclonal antibody named abEC1.1 has been shown to inhibit both wild type and hyperactive hemichannels composed of human (h) connexin 26 (hCx26) subunits. The aims of this work were (1) to characterize further the ability of abEC1.1 to selectively modulate connexin hemichannel function and (2) to assess its in vitro stability in view of future translational applications. In silico analysis of abEC1.1 interaction with the hCx26 hemichannel identified critically important extracellular domain amino acids that are conserved in connexin 30 (hCx30) and connexin 32 (hCx32). Patch clamp experiments performed in HeLa DH cells confirmed the inhibition efficiency of abEC1.1 was comparable for hCx26, hCx30 and hCx32 hemichannels. Of note, even a single amino acid difference in the putative binding region reduced drastically the inhibitory effects of the antibody on all the other tested hemichannels, namely hCx30.2/31.3, hCx30.3, hCx31, hCx31.1, hCx37, hCx43 and hCx45. Plasma membrane channels composed of pannexin 1 were not affected by abEC1.1. Finally, size exclusion chromatography assays showed the antibody does not aggregate appreciably in vitro. Altogether, these results indicate abEC1.1 is a promising tool for further translational studies

Testing Prospects for Reliable Diatom Nanotechnology in Microgravity

The worldwide effort to grow nanotechnology, rather than use lithography, focuses on diatoms, single cell eukaryotic algae with ornate silica shells, which can be replaced by oxides and ceramics, or reduced to elemental silicon, to create complex nanostructures with compositions of industrial and electronics importance. Diatoms produce an enormous variety of structures, some of which are microtubule dependent and perhaps sensitive to microgravity. The NASA Single Loop for Cell Culture (SLCC) for culturing and observing microorganisms permits inexpensive, low labor in-space experiments. We propose to send up to the International Space Station diatom cultures of the three diatom species whose genomes are being sequenced, plus the giant diatoms of Antarctica (up to 2 mm diameter for a single cell) and the unique colonial diatom, Bacillaria paradoxa. Bacillaria cells move against each other in partial synchrony, like a sliding deck of cards, by a microfluidics mechanism. Will normal diatoms have aberrant pattern and shape or motility compared to ground controls? The generation time is typically one day, so that many generations may be examined from one flight. Rapid, directed evolution may be possible running the SLCC as a compustat. The shell shapes and patterns are preserved in hard silica, so that the progress of normal and aberrant morphogenesis may be followed by drying samples on a moving filter paper "diatom tape recorder". With a biodiversity of 100,000 distinct species, diatom nanotechnology may offer a compact and portable nanotechnology toolkit for exploration anywhere