Ultra-high-resolution observations of persistent null-point reconnection in the solar corona

MMagnetic reconnection is a key mechanism involved in solar eruptions and is also a prime possibility to heat the low corona to millions of degrees. Here, we present ultra-high-resolution extreme ultraviolet observations of persistent null-point reconnection in the corona at a scale of about 390 km over one hour observations of the Extreme-Ultraviolet Imager on board Solar Orbiter spacecraft. The observations show formation of a null-point configuration above a minor positive polarity embedded within a region of dominant negative polarity near a sunspot. The gentle phase of the persistent null-point reconnection is evidenced by sustained point-like high-temperature plasma (about 10 MK) near the null-point and constant outflow blobs not only along the outer spine but also along the fan surface. The blobs appear at a higher frequency than previously observed with an average velocity of about 80 km s−1 and life-times of about 40 s. The null-point reconnection also occurs explosively but only for 4 minutes, its coupling with a mini-filament eruption generates a spiral jet. These results suggest that magnetic reconnection, at previously unresolved scales, proceeds continually in a gentle and/or explosive way to persistently transfer mass and energy to the overlying coron

A review of the systematic biology of fossil and living bony-tongue fishes, Osteoglossomorpha (Actinopterygii: Teleostei)

The bony-tongue fishes, Osteoglossomorpha, have been the focus of a great deal of morphological, systematic, and evolutionary study, due in part to their basal position among extant teleostean fishes. This group includes the mooneyes (Hiodontidae), knifefishes (Notopteridae), the abu (Gymnarchidae), elephantfishes (Mormyridae), arawanas and pirarucu (Osteoglossidae), and the African butterfly fish (Pantodontidae). This morphologically heterogeneous group also has a long and diverse fossil record, including taxa from all continents and both freshwater and marine deposits. The phylogenetic relationships among most extant osteoglossomorph families are widely agreed upon. However, there is still much to discover about the systematic biology of these fishes, particularly with regard to the phylogenetic affinities of several fossil taxa, within Mormyridae, and the position of Pantodon. In this paper we review the state of knowledge for osteoglossomorph fishes. We first provide an overview of the diversity of Osteoglossomorpha, and then discuss studies of the phylogeny of Osteoglossomorpha from both morphological and molecular perspectives, as well as biogeographic analyses of the group. Finally, we offer our perspectives on future needs for research on the systematic biology of Osteoglossomorpha

5-aminosalicylic acid inhibits stem cell function in human adenoma derived cells: Implications for chemoprophylaxis in colorectal tumorigenesis

Background: Most colorectal cancers (CRC) arise sporadically from precursor lesions: colonic polyps. Polyp resection prevents progression to CRC. Risk of future polyps is proportional to the number and size of polyps detected at screening, allowing identification of high-risk individuals who may benefit from effective chemoprophylaxis. We aimed to investigate the potential of 5-aminosalicylic acid (5-ASA), a medication used in the treatment of ulcerative colitis, as a possible preventative agent for sporadic CRC. Methods: Human colorectal adenoma (PC/AA/C1, S/AN/C1 and S/RG/C2), transformed adenoma PC/AA/C1/SB10 and carcinoma cell lines (LS174T and SW620) were treated with 5-ASA. The effect on growth in two- and three-dimensional (3D) culture, β-catenin transcriptional activity and on cancer stemness properties of the cells were investigated. Results: 5-ASA was shown, in vitro, to inhibit the growth of adenoma cells and suppress β-catenin transcriptional activity. Downregulation of β-catenin was found to repress expression of stem cell marker LGR5 (leucine-rich G protein-coupled receptor-5) and functionally suppress stemness in human adenoma and carcinoma cells using 3D models of tumorigenesis. Conclusions: 5-ASA can suppress the cancer stem phenotype in adenoma-derived cells. Affordable and well-tolerated, 5-ASA is an outstanding candidate as a chemoprophylactic medication to reduce the risk of colorectal polyps and CRC in those at high risk

The crystal structure of the Leishmania infantum Silent Information Regulator 2 related protein 1: implications to protein function and drug design.

The research leading to these results received funding from the European Community’s Seventh Framework Programme under grant agreement No.602773 (Project KINDRED).The de novo crystal structure of the Leishmania infantum Silent Information Regulator 2 related protein 1 (LiSir2rp1) has been solved at 1.99Å in complex with an acetyl-lysine peptide substrate. The structure is broadly commensurate with Hst2/SIRT2 proteins of yeast and human origin, reproducing many of the structural features common to these sirtuin deacetylases, including the characteristic small zinc-binding domain, and the larger Rossmann-fold domain involved in NAD+-binding interactions. The two domains are linked via a cofactor binding loop ordered in open conformation. The peptide substrate binds to the LiSir2rp1 protein via a cleft formed between the small and large domains, with the acetyl-lysine side chain inserting further into the resultant hydrophobic tunnel. Crystals were obtained only with recombinant LiSir2rp1 possessing an extensive internal deletion of a proteolytically-sensitive region unique to the sirtuins of kinetoplastid origin. Deletion of 51 internal amino acids (P253-E303) from LiSir2rp1 did not appear to alter peptide substrate interactions in deacetylation assays, but was indispensable to obtain crystals. Removal of this potentially flexible region, that otherwise extends from the classical structural elements of the Rossmann-fold, specifically the β8-β9 connector, appears to result in lower accumulation of the protein when expressed from episomal vectors in L. infantum SIR2rp1 single knockout promastigotes. The biological function of the large serine-rich insertion in kinetoplastid/trypanosomatid sirtuins, highlighted as a disordered region with strong potential for post-translational modification, remains unknown but may confer additional cellular functions that are distinct from their human counterparts. These unique molecular features, along with the resolution of the first kinetoplastid sirtuin deacetylase structure, present novel opportunities for drug design against a protein target previously established as essential to parasite survival and proliferation.Publisher PDFPeer reviewe

Critical science plan for the Daniel K. Inouye solar telescope (DKIST)

The National Science Foundation’s Daniel K. Inouye Solar Telescope (DKIST) will revolutionize our ability to measure, understand, and model the basic physical processes that control the structure and dynamics of the Sun and its atmosphere. The first-light DKIST images, released publicly on 29 January 2020, only hint at the extraordinary capabilities that will accompany full commissioning of the five facility instruments. With this Critical Science Plan (CSP) we attempt to anticipate some of what those capabilities will enable, providing a snapshot of some of the scientific pursuits that the DKIST hopes to engage as start-of-operations nears. The work builds on the combined contributions of the DKIST Science Working Group (SWG) and CSP Community members, who generously shared their experiences, plans, knowledge, and dreams. Discussion is primarily focused on those issues to which DKIST will uniquely contribute

Diagnosis and management of Cornelia de Lange syndrome:first international consensus statement

Cornelia de Lange syndrome (CdLS) is an archetypical genetic syndrome that is characterized by intellectual disability, well-defined facial features, upper limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in any one of seven genes, all of which have a structural or regulatory function in the cohesin complex. Although recent advances in next-generation sequencing have improved molecular diagnostics, marked heterogeneity exists in clinical and molecular diagnostic approaches and care practices worldwide. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria, both for classic CdLS and non-classic CdLS phenotypes, molecular investigations, long-term management and care planning

Docking and database screening reveal new classes of Plasmodium falciparum dihydrofolate reductase inhibitors

Plasmodium falciparum dihydrofolate reductase (PfDHFR) is an important target for antimalarial chemotherapy. Unfortunately, the emergence of resistant parasites has significantly reduced the efficiency of classical antifolate drugs such as cycloguanil and pyrimethamine. In this study, an approach toward molecular docking of the structures contained in the Available Chemicals Directory (ACD) database to search for novel inhibitors of PfDHFR is described. Instead of docking the whole ACD database, specific 3D pharmacophores were used to reduce the number of molecules in the database by excluding a priori molecules lacking essential requisites for the interaction with the enzyme and potentially unable to bind to resistant mutant PfDHFRs. The molecules in the resulting focused database were then evaluated with regard to their fit into the PfDHFR active site. Twelve new compounds whose structures are completely unrelated to known antifolates were identified and found to inhibit, at the micromolar level, the wild-type and resistant mutant PfDHFRs harboring A16V, S108T, A16V + S108T, C59R + S108N + I164L, and N51I + C59R + S108N + 1164L mutations. Depending on the functional groups interacting with key active site residues of the enzyme, these inhibitors were classified as N-hydroxyamidine, hydrazine, urea, and thiourea derivatives. The structures of the complexes of the most active inhibitors, as refined by molecular mechanics and molecular dynamics, provided insight into how these inhibitors bind to the enzyme and suggested prospects for these novel derivatives as potential leads for antimalarial development