Characterization of Vertebrate Cohesin Complexes and Their Regulation in Prophase

In eukaryotes, sister chromatids remain connected from the time of their synthesis until they are separated in anaphase. This cohesion depends on a complex of proteins called cohesins. In budding yeast, the anaphase-promoting complex (APC) pathway initiates anaphase by removing cohesins from chromosomes. In vertebrates, cohesins dissociate from chromosomes already in prophase. To study their mitotic regulation we have purified two 14S cohesin complexes from human cells. Both complexes contain SMC1, SMC3, SCC1, and either one of the yeast Scc3p orthologs SA1 and SA2. SA1 is also a subunit of 14S cohesin in Xenopus. These complexes interact with PDS5, a protein whose fungal orthologs have been implicated in chromosome cohesion, condensation, and recombination. The bulk of SA1- and SA2-containing complexes and PDS5 are chromatin-associated until they become soluble from prophase to telophase. Reconstitution of this process in mitotic Xenopus extracts shows that cohesin dissociation does neither depend on cyclin B proteolysis nor on the presence of the APC. Cohesins can also dissociate from chromatin in the absence of cyclin-dependent kinase 1 activity. These results suggest that vertebrate cohesins are regulated by a novel prophase pathway which is distinct from the APC pathway that controls cohesins in yeast

ECONOMICS OF SEQUESTERING CARBON IN THE U.S. AGRICULTURAL SECTOR

Atmospheric concentrations of greenhouse gases can be reduced by withdrawing carbon from the atmosphere and sequestering it in soils and biomass. This report analyzes the performance of alternative incentive designs and payment levels if farmers were paid to adopt land uses and management practices that raise soil carbon levels. At payment levels below $10 per metric ton for permanently sequestered carbon, analysis suggests landowners would find it more cost effective to adopt changes in rotations and tillage practices. At higher payment levels, afforestation dominates sequestration activities, mostly through conversion of pastureland. Across payment levels, the economic potential to sequester carbon is much lower than the technical potential reported in soil science studies. The most cost-effective payment design adjusts payment levels to account both for the length of time farmers are willing to commit to sequestration activities and for net sequestration. A 50-percent cost-share for cropland conversion to forestry or grasslands would increase sequestration at low carbon payment levels but not at high payment levels.Carbon sequestration, greenhouse gas mitigation, afforestation, conservation tillage, no-till, incentive design, leakage, carbon stock, permanence, Environmental Economics and Policy,

Particle Sensor Using Solidly Mounted Resonators

This paper describes the development of a novel particle sensing system employing zinc oxide based solidly mounted resonator (SMR) devices for the detection of airborne fine particles (i.e., PM2.5 and PM10). The system operates in a dual configuration in which two SMR devices are driven by Colpitts-type oscillators in a differential mode. Particles are detected by the frequency shift caused by the mass of particles present on one resonator with while the other acts as a reference channel. Experimental validation of the system was performed inside an environmental chamber using a dust generator with the particles of known size and concentration. A sensor sensitivity of 4.6 Hz per μg/m3 was demonstrated for the SMRs resonating at a frequency of 970 MHz. Our results demonstrate that the SMR-based system has the potential to be implemented in CMOS technology as a low-cost, miniature smart particle detector for the real-time monitoring of airborne particles

Reproducibility of lymphovascular space invasion (LVSI) assessment in endometrial cancer

Aims Lymphovascular space invasion (LVSI) in endometrial cancer (EC) is an important prognostic variable impacting on a patient's individual recurrence risk and adjuvant treatment recommendations. Recent work has shown that grading the extent of LVSI further improves its prognostic strength in patients with stage I endometrioid EC. Despite this, there is little information on the reproducibility of LVSI assessment in EC. Therefore, we designed a study to evaluate interobserver agreement in discriminating true LVSI from LVSI mimics (Phase I) and reproducibility of grading extent of LVSI (Phase II). Methods and results Scanned haematoxylin and eosin (H&E) slides of endometrioid EC (EEC) with a predefined possible LVSI focus were hosted on a website and assessed by a panel of six European gynaecological pathologists. In Phase I, 48 H&E slides were included for LVSI assessment and in Phase II, 42 H&E slides for LVSI grading. Each observer was instructed to apply the criteria for LVSI used in daily practice. The degree of agreement was measured using the two-way absolute agreement average-measures intraclass correlation coefficient (ICC). Reproducibility of LVSI assessment (ICC = 0.64, P < 0.001) and LVSI grading (ICC = 0.62, P < 0.001) in EEC was substantial among the observers. Conclusions Given the good reproducibility of LVSI, this study further supports the important role of LVSI in decision algorithms for adjuvant treatment

Site of Blood Vessel Damage and Relevance of CD18 in a Murine Model of Immune Complex-Mediated Vasculitis

How neutrophils (polymorphonuclear neutrophils, PMNs) damage vessels in leukocytoclastic vasculitis (LcV) mediated by immune complexes (ICs) is unclear. If degradative enzymes and oxygen radicals are released from PMNs while adhering to the inner side of the vessel wall, they could be washed away by the blood stream or neutralized by serum protease inhibitors. We investigated if in LcV PMNs could damage vessels from the tissue side after transmigration. We used CD18-deficient (CD18−/−) mice because the absence of CD18 excludes transmigration of PMNs. When eliciting the Arthus reaction in ears of CD18−/− mice, deposition of ICs was not sufficient to recruit PMNs or to induce IC-mediated LcV. Injection of PMNs intradermally in CD18−/− mice allowed us to investigate if bypassing diapedesis and placing PMNs exclusively on the abluminal side leads to vascular destruction. We found that injected PMNs gathered around perivascular ICs, but did not cause vessel damage. Only intravenous injection of wild-type PMNs could re-establish the Arthus reaction in CD18−/− mice. Thus, PMNs cause vessel damage during diapedesis from the luminal side, but not from the perivascular space. We suggest that in order to shield the cytotoxic products from the blood stream, ICs induce particularly tight interactions between them, PMNs and endothelial cells