Functional expression cloning reveals proapoptotic role for protein phosphatase 4

Functional expression cloning strategies are highly suitable for the analysis of the molecular control of apoptosis. This approach has two critical advantages. Firstly, it eliminates prior assumptions about the properties of the proteins involved, and, secondly, it selectively targets proteins that are causally involved in apoptosis control and which affect the crucial cellular decision between survival and death. The application of this strategy to the isolation of cDNAs conferring resistance to dexamethasone and gamma-irradiation resulted in the isolation of a partial cDNA for the catalytic subunit of protein phosphatase 4 (PP4). Cells transfected with this partial cDNA in an expression vector downregulated PP4 and were resistant to both dexamethasone and UV radiation, as demonstrated by both membrane integrity and colony-forming assays. These observations suggest that PP4 plays an important proapoptotic role in T lymphocytes.

A concise summary of the International System of Units, the SI

The Bureau International des Poids et Mesures, the BIPM, was established by Article 1 of the Convention du Mètre, on 20 May 1875, and is charged with providing the basis for a single, coherent system of measurements to be used throughout the world. The decimal metric system, dating from the time of the French Revolution, was based on the metre and the kilogram. Under the terms of the 1875 Convention, new international prototypes of the metre and kilogram were made and formally adopted by the first Conférence Générale des Poids et Mesures (CGPM) in 1889. Over time this system developed, so that it now includes seven base units. In 1960 it was decided at the 11th CGPM that it should be called the Système International d’Unités, the SI (in English: the International System of Units). The SI is not static but evolves to match the world’s increasingly demanding requirements for measurements at all levels of precision and in all areas of science, technology, and human endeavour. This document is a summary of the SI Brochure, a publication of the BIPM which is a statement of the current status of the SI. The seven base units of the SI, listed in Table 1, provide the reference used to define all the measurement units of the International System. As science advances, and methods of measurement are refined, their definitions have to be revised. The more accurate the measurements, the greater the care required in the realization of the units of measurement.

Reversing insect pollinator decline

Pollination by insects enables the reproduction of flowering plants and is critical to UK agriculture.1 Insect pollinators have declined globally, with implications for food security and wild habitats. This POSTnote summarises the causes for the recent trends, gaps in knowledge and possible strategies for reversing pollinator decline.

Protein phosphatase 2A and phosphoprotein SET regulate androgen production by P450c17

Cytochrome P450c17 catalyzes 17 alpha-hydroxylation needed for cortisol synthesis and 17,20 lyase activity needed to produce sex steroids. Serine phosphorylation of P450c17 specifically increases 17,20 lyase activity, but the physiological factors regulating this effect remain unknown. Treating human adrenal NCI-H295A cells with the phosphatase inhibitors okadaic acid, fostriecin, and cantharidin increased 17,20 lyase activity, suggesting involvement of protein phosphatase 2A (PP2A) or 4 (PP4). PP2A but not PP4 inhibited 17,20 lyase activity in microsomes from cultured cells, but neither affected 17 alpha-hydroxylation. Inhibition of 17,20 lyase activity by PP2A was concentration-dependent, could be inhibited by okadaic acid, and was restored by endogenous protein kinases. PP2A but not PP4 coimmunoprecipitated with P450c17, and suppression of PP2A by small interfering RNA increased 17,20 lyase activity. Phosphoprotein SET found in adrenals inhibited PP2A, but not PP4, and fostered 17,20 lyase activity. The identification of PP2A and SET as post-translational regulators of androgen biosynthesis suggests potential additional mechanisms contributing to adrenarche and hyperandrogenic disorders such as polycystic ovary syndrome.

Identification and analysis of novel mitotic inhibitors of the Caenorhabditis elegans Aurora B kinase

Proper execution of mitosis requires the accurate segregation of replicated DNA into each daughter cell. The highly conserved mitotic kinase AIR-2/Aurora B is a dynamic protein that interacts with subsets of cofactors and substrates to coordinate chromosome segregation and cytokinesis in Caenorhabdiris elegans. To identify components of the AIR-2 regulatory pathway, a genome-wide RNAi-based screen for suppressors of air-2 temperature-sensitive mutant lethality was conducted. Here, I present evidence that two classes of suppressors identified in this screen are bona fide regulators of the AIR-2 kinase. The strongest suppressor cdc-48.3, encodes an Afg2/Spaf-related Cdc48-like AAA+ ATPase that regulates AIR-2 kinase activity and stability during C. elegans embryogenesis. Loss of CDC-48.3 suppresses the lethality of air-2 mutant embryos, marked by the restoration of the dynamic behavior of AIR-2 and rescue of chromosome segregation and cytokinesis defects. Loss of CDC-48.3 leads to mitotic delays and abnormal accumulation of AIR-2 during late telophase/mitotic exit. In addition, AIR-2 kinase activity is significantly upregulated from metaphase through mitotic exit in CDC-48.3 depleted embryos. Inhibition of the AIR-2 kinase is dependent on (1) a direct physical interaction between CDC-48.3 and AIR-2, and (2) CDC-48.3 ATPase activity. Importantly, the increase in AIR-2 kinase activity does not correlate with the stabilization of AIR-2 in late mitosis. Hence, CDC-48.3 is a bi-functional inhibitor of AIR-2 that is likely to act via distinct mechanisms. The second class of suppressors consists of psy-2/smk-1 and pph-4.1, which encode two components of the conserved PP4 phosphatase complex that is essential for spindle assembly, chromosome segregation, and overall mitotic progression. AIR-2 and its substrates are likely to be targets of this complex since mitotic AIR-2 kinase activity is significantly increased during mitosis when either PSY-2/SMK-1 or PPH-4.l is depleted. Altogether, this study demonstrates that during the C. elegans embryonic cell cycle, regulators including the CDC-48.3 ATPase and PP4 phosphatase complex interact with and control the kinase activity, targeting behavior and protein stability of the Aurora B kinase to ensure accurate and timely progression of mitosis. ^

Distribution of planktonic foraminifera in Pleistocene sediments of the New Jersey margin, NW Atlantic Ocean

Abundance records of planktonic foraminifera (>150 µm) from the upper 520 m of ODP Site 1073 (Hole 1073A, Leg 174A, 639 m water depth) have been integrated with SPECMAP-derived isotope stratigraphy, percentage of calcium carbonate, and coarse sediment fraction data in order to investigate the Pleistocene climatic history of the New Jersey margin. Six planktonic taxonomic groups dominate the foraminiferal assemblage at Site 1073: Neogloboquadrina pachyderma (d) (mean 33.8%), Turborotalita quinqueloba (18.5%), N. pachyderma (s) (18.4%), Globigerina bulloides group (11.4%), Globorotalia inflata group (9.4%), and Globigerinita glutinata (4.1%). Based on the distributions of these six foraminiferal groups, the Pleistocene section can be divided into three paleoclimatic intervals: Interval I (intermediate) corresponds to the Quaternary sediments from sequence boundary pp1 to the seafloor (79.5-0 mbsf; Emiliania huxleyi acme [85 ka] at 72 mbsf); Interval II (warm) occurs between sequence boundaries pp3 and pp1 (325-79.5 mbsf; last occurrence of Pseudoemiliania lacunosa [460 ka] at 330 mbsf); and Interval III (coldest) occurs between sequence boundaries pp4 and pp3 (520-325 mbsf; Calcareous nannofossils and dinocysts in proximity to pp4 indicate that the sedimentary record for 0.9-1.7 Ma is either missing altogether or highly condensed within the basal few meters of the section). Neogloboquadrina pachyderma (d) displays eight peaks of abundance which correlate, for the most part, with depleted delta18O values, increases in calcium carbonate percentages, low coarse fraction percentages, increased planktonic fragmentation (greater dissolution), and low N. pachyderma (s) abundances. These intervals are interpreted as representing warmer/interglacial conditions. Neogloboquadrina pachyderma (s) displays seven peaks of abundance which correlate, for the most part, with delta18O increases, decreases in calcium carbonate percentages, increases in coarse fraction percentages, and low N. pachyderma (d) abundances. These intervals are interpreted as representing cooler/glacial conditions. In Interval III, a faunal response to relative changes in sea-surface temperature is reflected by abundance peaks in Neogloboquadrina pachyderma (d), followed by Turborotalita quinqueloba and then N. pachyderma (s) (proceeding from warmest to coolest, respectively). This tripartite response is consistent with the oxygen isotope record and, although not as clear, also occurs in Intervals I and II. Six peaks/peak intervals of Globigerina bulloides abundance are closely matched by peaks in Globigerinita glutinata and occur within oxygen isotope stage (OIS) 2 (latter part) 3, 4, 5, 8, 9, 13(?), 14(?), and 15(?). We speculate that these intervals reflect increased upwelling and nutrient levels during both glacials and interglacials. Eight peak intervals of Globorotalia inflata show a general inverse correlation with G. bulloides and may reflect lowered nutrient and warmer surface waters.

Compendio Mathematico : en que se contienen todas las materias mas principales de las Ciencias que tratan de la Cantidad

Que comprehende: Trigonometria; secciones conicas; maquinaria

Flosculus de clericorum et sacerdotum excellentiis et aliis quae ad eorum vitam statum & honorem pertinent

Sign.: [hoja]4, A-Z4, Aa-Pp4, Qq2