A Copper(II) Tris-imidazolylphosphine Complex as a Structural and Functional Model of Flavonol 2,4-Dioxygenase

Reaction of tetrakis(acetonitrile)copper(I) perchlorate ([Cu(NCCH3)4][ClO4]), tris-1-ethyl-4-methylimidazolylphosphine (T1Et4MeIP) (1) and 3-hydroxyflavone (flavH) under ambient conditions produces an in-situ generated flavonol bound copper(II) complex, which converts to a stable green complex that formulates to [Cu(T1Et4MeIP)(flav)][ClO4] (2). The crystal structure of 2 was determined by X-ray diffraction and crystallizes in a triclinic system (P1¯ role= presentation style= box-sizing: border-box; margin: 0px; padding: 0px; display: inline-block; line-height: normal; font-size: 14.4px; word-spacing: normal; overflow-wrap: normal; text-wrap: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; border: 0px; position: relative; \u3e1¯) with unit cell dimensions of a = 14.537(15) Å, b = 15.794(14) Å, c = 17.044(17) Å, α = 65.58(3)˚, β = 86.80(5)˚, γ = 73.34(4)˚, V = 3376(6) Å3 and Z = 2. While the five-coordinate copper(II) complex is stable under ambient conditions in the solid state, it undergoes oxidative scission of the flavonol pyrone ring under photolytic (300 nm) and/or thermal (120 °C) conditions in the presence of molecular oxygen. The degradative process produces the corresponding methylated products: methylbenzoate, methyl salicylate and N,N-dimethylbenzamide. In addition, the previously undisclosed single crystal X-ray structure of tris-1-ethyl-4-methylimidazolylphosphine (1), T1Et4MeIP, is also reported

Bending the curve of global freshwater biodiversity loss: an emergency recovery plan

Despite their limited spatial extent, freshwater ecosystems host remarkable biodiversity, including one-third of all vertebrate species. This biodiversity is declining dramatically: Globally, wetlands are vanishing three times faster than forests, and freshwater vertebrate populations have fallen more than twice as steeply as terrestrial or marine populations. Threats to freshwater biodiversity are well documented but coordinated action to reverse the decline is lacking. We present an Emergency Recovery Plan to bend the curve of freshwater biodiversity loss. Priority actions include accelerating implementation of environmental flows; improving water quality; protecting and restoring critical habitats; managing the exploitation of freshwater ecosystem resources, especially species and riverine aggregates; preventing and controlling nonnative species invasions; and safeguarding and restoring river connectivity. We recommend adjustments to targets and indicators for the Convention on Biological Diversity and the Sustainable Development Goals and roles for national and international state and nonstate actors

Pollination and Predation Limit Fruit Set in a Shrub, Bourreria succulents (Boraginaceae), after Hurricanes on San Salvador Island, Bahamas 1

Hurricanes have been assumed to reduce the reproduction of plants, either directly by leaf stripping and stress or indirectly by reducing pollinators. I examined the pollination and fruit set of a common shrub, Bourreria succulenta , after hurricanes on San Salvador island, Bahamas. Contrary to the assumption of resource limitation, B. succulenta showed unusually prolific flowering after Hurricane Lili stripped leaves from most of the plants in October 1996. I predicted that the abundant flowering would saturate pollinators and that fruit set would be pollination-limited. Fruit set was strongly pollination-limited by 71 percent. Butterflies are probably the major pollinators and were present at the site, but they rarely visited B. succulenta flowers even though flowers were brimming with nectar. Nectarivorous birds (Bananaquits and Bahama Wbodstars) visit B. succulenta flowers, but their populations were decimated by Hurricane Lili and they rarely visited flowers during this time. Fruit set was also severely predation-limited; a moth caterpillar (Gelechiidae) was extremely abundant and ate buds, flowers, and fruits, causing a further 68 percent reduction in fruit set. Together, pollination limitation and predation limitation reduced fruit set to only 7 percent or less. Predation was also intense in 1999 after Hurricane Floyd and resulted in 11 percent fruit set or less. Whether or not hurricanes were the cause of limited pollinators or abundant predators, the resulting low fruit set could have population effects because hurricanes can provide opportunities for the recruitment of new plants. These results emphasize that understanding plant–animal interactions may be necessary for predicting the effects of hurricanes on plant reproductive success, which may affect subsequent recruitment. Species on small islands like San Salvador (150 km 2 ) with relatively few species may be especially vulnerable to environmental disturbances such as hurricanes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75721/1/j.1744-7429.2001.tb00184.x.pd

Patient-specific cancer genes contribute to recurrently perturbed pathways and establish therapeutic vulnerabilities in esophageal adenocarcinoma

Abstract: The identification of cancer-promoting genetic alterations is challenging particularly in highly unstable and heterogeneous cancers, such as esophageal adenocarcinoma (EAC). Here we describe a machine learning algorithm to identify cancer genes in individual patients considering all types of damaging alterations simultaneously. Analysing 261 EACs from the OCCAMS Consortium, we discover helper genes that, alongside well-known drivers, promote cancer. We confirm the robustness of our approach in 107 additional EACs. Unlike recurrent alterations of known drivers, these cancer helper genes are rare or patient-specific. However, they converge towards perturbations of well-known cancer processes. Recurrence of the same process perturbations, rather than individual genes, divides EACs into six clusters differing in their molecular and clinical features. Experimentally mimicking the alterations of predicted helper genes in cancer and pre-cancer cells validates their contribution to disease progression, while reverting their alterations reveals EAC acquired dependencies that can be exploited in therapy

Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine

Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Juxtaposing BTE and ATE – on the role of the European insurance industry in funding civil litigation

One of the ways in which legal services are financed, and indeed shaped, is through private insurance arrangement. Two contrasting types of legal expenses insurance contracts (LEI) seem to dominate in Europe: before the event (BTE) and after the event (ATE) legal expenses insurance. Notwithstanding institutional differences between different legal systems, BTE and ATE insurance arrangements may be instrumental if government policy is geared towards strengthening a market-oriented system of financing access to justice for individuals and business. At the same time, emphasizing the role of a private industry as a keeper of the gates to justice raises issues of accountability and transparency, not readily reconcilable with demands of competition. Moreover, multiple actors (clients, lawyers, courts, insurers) are involved, causing behavioural dynamics which are not easily predicted or influenced. Against this background, this paper looks into BTE and ATE arrangements by analysing the particularities of BTE and ATE arrangements currently available in some European jurisdictions and by painting a picture of their respective markets and legal contexts. This allows for some reflection on the performance of BTE and ATE providers as both financiers and keepers. Two issues emerge from the analysis that are worthy of some further reflection. Firstly, there is the problematic long-term sustainability of some ATE products. Secondly, the challenges faced by policymakers that would like to nudge consumers into voluntarily taking out BTE LEI