On the Mechanism of Action of SJ-172550 in Inhibiting the Interaction of MDM4 and p53

SJ-172550 (1) was previously discovered in a biochemical high throughput screen for inhibitors of the interaction of MDMX and p53 and characterized as a reversible inhibitor (J. Biol. Chem. 2010; 285∶10786). Further study of the biochemical mode of action of 1 has shown that it acts through a complicated mechanism in which the compound forms a covalent but reversible complex with MDMX and locks MDMX into a conformation that is unable to bind p53. The relative stability of this complex is influenced by many factors including the reducing potential of the media, the presence of aggregates, and other factors that influence the conformational stability of the protein. This complex mechanism of action hinders the further development of compound 1 as a selective MDMX inhibitor

CropPol: a dynamic, open and global database on crop pollination

This is the final version. Available from Wiley via the DOI in this record The original dataset (v1.1.0) of the CropPol database can be accessed from the ECOLOGY repository. Main upgrades of these datasets will be versioned and deposited in Zenodo (DOI: 10.5281/zenodo.5546600)Data availability. V.C. Computer programs and data-processing algorithms: The algorithms used in deriving, processing, or transforming data can be accessed in the DataS1.zip file and the Zenodo repository (DOI: 10.5281/zenodo.5546600). V.D. Archiving: The data is archived for long-term storage and access in Zenodo (DOI: 10.5281/zenodo.5546600)Seventy five percent of the world's food crops benefit from insect pollination. Hence, there has been increased interest in how global change drivers impact this critical ecosystem service. Because standardized data on crop pollination are rarely available, we are limited in our capacity to understand the variation in pollination benefits to crop yield, as well as to anticipate changes in this service, develop predictions, and inform management actions. Here, we present CropPol, a dynamic, open and global database on crop pollination. It contains measurements recorded from 202 crop studies, covering 3,394 field observations, 2,552 yield measurements (i.e. berry weight, number of fruits and kg per hectare, among others), and 47,752 insect records from 48 commercial crops distributed around the globe. CropPol comprises 32 of the 87 leading global crops and commodities that are pollinator dependent. Malus domestica is the most represented crop (32 studies), followed by Brassica napus (22 studies), Vaccinium corymbosum (13 studies), and Citrullus lanatus (12 studies). The most abundant pollinator guilds recorded are honey bees (34.22% counts), bumblebees (19.19%), flies other than Syrphidae and Bombyliidae (13.18%), other wild bees (13.13%), beetles (10.97%), Syrphidae (4.87%), and Bombyliidae (0.05%). Locations comprise 34 countries distributed among Europe (76 studies), Northern America (60), Latin America and the Caribbean (29), Asia (20), Oceania (10), and Africa (7). Sampling spans three decades and is concentrated on 2001-05 (21 studies), 2006-10 (40), 2011-15 (88), and 2016-20 (50). This is the most comprehensive open global data set on measurements of crop flower visitors, crop pollinators and pollination to date, and we encourage researchers to add more datasets to this database in the future. This data set is released for non-commercial use only. Credits should be given to this paper (i.e., proper citation), and the products generated with this database should be shared under the same license terms (CC BY-NC-SA). This article is protected by copyright. All rights reserved.OBServ Projec

Incorporating endoscope in middle ear surgery

We conducted a study to evaluate the use of a pediatric rigid otoendoscope for determining the extent of middle ear disease and for assessing ossicular integrity and mobility during tympanoplasty. Our study population was made up of 132 patients who were undergoing surgery for the treatment of chronic suppurative otitis media; of this group, 41 patients underwent otoendoscopy and 91 underwent scutum lowering for purposes of visualization. In the otoendoscopy group, the ossicles were successfully visualized and their mobility assessed in 34 patients; the remaining 7 patients subsequently underwent scutum lowering. A 30° endoscope allowed for complete visualization of the middle ear in almost all of the 34 cases. The mean duration of surgery for the 34 patients in the otoendoscopy group was 62.85 minutes (±15.57), which was significantly shorter than the duration of surgery (71.23 ± 15.65 min) for the 98 patients who underwent scutum lowering (p \u3c 0.005). A total of 50 patients required less than 60 minutes of surgical time-26 of 34 (76.5%) in the endoscopy group and 24 of 98 (24.5%) in the scutum-lowering group. Statistical analysis revealed that the possibility of completing a procedure in less than 60 minutes was 73.65% (±12.56%) when endoscopy was used and 58.62% (±12.60%) when scutum lowering was used-again, a statistically significant difference (p \u3c 0.005). We conclude that incorporation of an angled otoendoscope into middle ear surgery is a worthwhile alternative to scutum lowering

Chemico-mineralogical changes of ultramafic topsoil during stockpiling: implications for post-mining restoration

International audienceLateritic topsoils, which are usually removed and stored apart before mining operations take place, play an essential role in the success of post-mining restoration. They contain elements to recover chemical (organic matter, nutrients) and biological (seed and bud banks, microorganisms) fertility of the soil. Conserving topsoil fertility during storage time is essential for a successful use of topsoil during restoration. In this study, different chemico-mineralogical properties of a lateritic topsoil from the Goro nickel mine (New Caledonia) were monitored from its original in situ emplacement on the soil profile, immediately after its stockpiling and after 24 months of storage. Our analyses show that topsoil experienced noticeable changes immediately after storage, mostly produced by mixing of different soil profiles. Cation Exchange Capacities and concentrations of most elements did not vary even after 24 months of storage. However, a slight reduction of Ni, Cr, K, Na and of the C:N ratio, and an increase of Ca have been observed. Stockpiling has not affected negatively the chemical fertility of the topsoil, although biological parameters should be considered to have a complete view of stockpiling sustainability

Insurance coverage and the heterogeneity of health and drug spending in the United States

The rise in health expenditure in the U.S. has generated interest in the determinants of health expenditure at the micro-level; however, individuals may exhibit differential behaviour across different types of health care. In addition, public and private insurance may have an heterogeneous effect on expenditure. In this paper, we examine the determinants of health expenditure with a multivariate regression model along with controls for insurance choice and unobserved health care utilization. We find age-related effects and evidence of moral hazard related to private insurance, while the primary effect of income on expenditure appears to be through the purchase of insurance. The implications of the study are that: (i) policymakers should be less concerned about the effect of ageing on health expenditure; (ii) drug spending may not be related to the expansion of public insurance coverage; and (iii) income may have a negative impact on most elements of health spending