What regulates secretion of non-stored proteins by eukaryotic cells?

Protein secretion is conventionally viewed as taking place by either of two cellular routes, a regulated pathway, involving external stimuli and secretory granules, and a presumptive ‘constitutive’ pathway, which does not involve hormonal or neuronal stimuli or the production of secretory granules. The evidence reviewed here strongly suggests that there are post-synthesis rate-limiting steps for many proteins released by the ‘constitutive’ pathway and, hence, that regulation in some sense is involved here too. The nature of these rate-limiting determinants and events is discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/50183/1/950040507_ftp.pd

Feasibility study of silicon nitride protection of plastic encapsulated semiconductors

The application of low temperature silicon nitride protective layers on wire bonded integrated circuits mounted on lead frame assemblies is reported. An evaluation of the mechanical and electrical compatibility of both plasma nitride and photochemical silicon nitride (photonitride) passivations (parallel evaluations) of integrated circuits which were then encapsulated in plastic is described. Photonitride passivation is compatible with all wire bonded lead frame assemblies, with or without initial chip passivation. Plasma nitride passivation of lead frame assemblies is possible only if the chip is passivated before lead frame assembly. The survival rate after the environmental test sequence of devices with a coating of plasma nitride on the chip and a coating of either plasma nitride or photonitride over the assembled device is significantly greater than that of devices assembled with no nitride protective coating over either chip or lead frame

Use of an in vitro system to study the effects of lead on astrocyte-endothelial cell interactions: A model for studying toxic injury to the blood-brain barrier

We investigated the effect of inorganic lead on the interaction of immature rat astrocytes and bovine adrenal endothelial cells. The two cell types were cultured alone and in coculture in the presence or absence of lead acetate for up to 1 week. A battery of cell specific markers was used for cell identification. Newborn Sprague-Dawley rat brain astrocytes were more sensitive than bovine adrenal endothelial cells to the cytotoxic effects of 10-50 [mu] lead acetate, as demonstrated by a decrease in cell number and by the presence of intracellular vacuoles and detached cells. The number of astrocytes decreased to 50% of control after 4 days in culture at a concentration of 10 [mu] lead. In contrast, a mitogenic effect of lead was observed on the endothelial cells at this concentration, with an increase in cell number to 110% of control. In coculture, the two cell types demonstrated a distinctive cellular organization and the astrocytes were less sensitive to the cytotoxic effects of lead than when they were cultured alone. A lead-enhanced induction of a neural capillary enzyme activity, [gamma]-GTP, was detected histochemically in the coculture system. These results are consistent with a maturing of differentiating effect of the endothelial cells on the astrocytes, making them less susceptible to lead and mature enough to induce [gamma]-GTP activity in the endothelial cells.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27260/1/0000269.pd

Carbon tetrachloride depresses hepatic phospholipid synthesis in rats

40 h after an acute dose of CCl4 (11.3 mmol/kg), the incorporation of [1-3H]ethanolamine into rat hepatic microsomal phospholipids was inhibited to 70% of control. Incorporation into phospholipids of the inner and outer mitochondrial membranes was 30-35% of control. Rates of incorporation were equal to or above normal rates in all membranes 65 h after dosage. The activity of methyltransferase in microsomal fractions isolated from rats 10 to 66 h after dosage was depressed. These data suggest that the alteration of mitochondrial phospholipids that parallels mitochondrial dysfunction after acute CCl4 dosage could be attributed to a CCl4-induced inhibition of the microsomal phospholipid biosynthetic pathways.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25820/1/0000383.pd

Russell Lecture: Dark Star Formation and Cooling Instability

Optically thin cooling gas at most temperatures above 30K will make condensations by pressure pushing material into cool dense regions. This works without gravity. Cooling condensations will flatten and become planar/similarity solutions. Most star formation may start from cooling condensations - with gravity only important in the later stages. The idea that some of the dark matter could be pristine white dwarfs that condensed slowly on to planetary sized seeds without firing nuclear reactions is found lacking. However, recent observations indicate fifty times more halo white dwarfs than have been previously acknowledged; enough to make the halo fraction observed as MACHOS. A cosmological census shows that only 1% of the mass of the Universe is of known constitution.Comment: 32 Pages, Latex (uses aastex & natbib), 5 eps figures, submitted to ApJ April 200

Methane Flux in Cropland and Adjacent Riparian Buff ers with Different Vegetation Covers

While water quality functions of conservation buffers established adjacent to cropped fields have been widely documented, the relative contribution of these re-established perennial plant systems to greenhouse gases has not been completely documented. In the case of methane (CH(4)), these systems have the potential to serve as sinks of CH(4) or may provide favorable conditions for CH(4) production. This study quantifies CH(4) flux from soils of riparian buffer systems comprised of three vegetation types and compares these fluxes with those of adjacent crop fields. We measured soil properties and diel and seasonal variations of CH(4) flux in 7 to 17 yr-old re-established riparian forest buffers, warm-season and cool-season grass filters, and an adjacent crop field located in the Bear Creek watershed in central Iowa. Forest buffer and grass filter soils had significantly lower bulk density (P \u3c 0.01); and higher pH (P \u3c 0.01), total carbon (TC) (P \u3c 0.01), and total nitrogen (TN) (P \u3c 0.01) than crop field soils. There was no significant relationship between CH(4) flux and soil moisture or soil temperature among sites within the range of conditions observed. Cumulative CH(4) flux was -0.80 kg CH(4)-C ha(-1) yr(-1) in the cropped field, -0.46 kg CH(4)-C ha(-1) yr(-1) within the forest buffers, and 0.04 kg CH(4)-C ha(-1) yr(-1) within grass filters, but difference among vegetation covers was not significant. Results suggest that CH(4) flux was not changed after establishment of perennial vegetation on cropped soils, despite significant changes in soil properties

HER2 testing in breast cancer: Opportunities and challenges

Human epidermal growth factor receptor 2 (HER2) is overexpressed in 15-25% of breast cancers, usually as a result of HER2 gene amplification. Positive HER2 status is considered to be an adverse prognostic factor. Recognition of the role of HER2 in breast cancer growth has led to the development of anti-HER2 directed therapy, with the humanized monoclonal antibody trastuzumab (Herceptin (R)) having been approved for the therapy of HER2-positive metastatic breast cancer. Clinical studies have further suggested that HER2 status can provide important information regarding success or failure of certain hormonal therapies or chemotherapies. As a result of these developments, there has been increasing demand to perform HER2 testing on current and archived breast cancer specimens. This article reviews the molecular background of HER2 function, activation and inhibition as well as current opinions concerning its role in chemosensitivity and interaction with estrogen receptor biology. The different tissue-based assays used to detect HER2 amplification and overexpression are discussed with respect to their advantages and disadvantages, when to test (at initial diagnosis or pre-treatment), where to test (locally or centralized) and the need for quality assurance to ensure accurate and valid testing results

Association Between Body Mass Index and Clinical and Endoscopic Features of Eosinophilic Esophagitis

Because eosinophilic esophagitis (EoE) causes dysphagia, esophageal narrowing, and strictures, it could result in low body mass index (BMI), but there are few data assessing this