We describe a new reverse-genetics system that allows one to efficiently generate inf luenza A viruses entirely from cloned cDNAs.

For nuclear export of proteins, the formation of a ternary export complex composed of the export substrate, a cellular export factor and Ran-GTP is crucial. CRM1 is a cellular export factor for proteins containing leucine-rich nuclear export signals (NESs). Although the NES sequence is crucial for nuclear export, its exact role in the formation of the ternary export complex is controversial. Here we demonstrate an interaction between human CRM1 (hCRM1) and influenza A virus NS2 protein, which contains an NES motif in its N-terminal region. Replacement of the hydrophobic amino acids in the NES motif did not abolish NS2's interaction with hCRM1. Using our recently established systems for the generation of influenza virus or virus-like particles from cloned cDNAs, we found that NS2 is essential for nuclear export of influenza virus ribonucleoprotein (RNP) complexes, and that alteration of the NS2-NES abrogated this event and influenza virus generation. These findings suggest that the NS2-NES is not crucial for the interaction of this protein with hCRM1, but is for the formation of the ternary export complex with Ran-GTP.

The pantropical genus Begonia is the sixth-largest genus of flowering plants, including 1870 species. The sections of Begonia are used frequently as analogues to genera in other families but, despite their taxonomic utility, few of the current sections have been examined in the light of molecular phylogenetic analyses. We present herein the largest, most representative phylogeny of Begonia published to date and a subsequent provisional sectional classification of the genus. We utilised three plastid markers for 574 species and 809 accessions of Begonia and used Hillebrandia as an outgroup to produce a dated phylogeny. The relationships between some species and sections are poorly resolved, but many sections and deeper nodes receive strong support. We recognise 70 sections of Begonia including 5 new sections: Astrothrix, Ephemera, Jackia, Kollmannia, and Stellandrae; 4 sections are reinstated from synonymy: Australes, Exalabegonia, Latistigma and Pereira; and 5 sections are newly synonymised. The new sectional classification is discussed with reference to identifying characters and previous classifications.

It is unclear whether the regulatory distinction between non-identifiable and identifiable information — information used to determine informed consent practices for the use of clinically derived samples for genetic research — is meaningful to patients. The objective of this study was to examine patients’ attitudes and preferences regarding use of anonymous and identifiable clinical samples for genetic research. Telephone interviews were conducted with 1,193 patients recruited from general medicine, thoracic surgery, or medical oncology clinics at five United States academic medical centers. Wanting to know about research being done was important to 72% of patients when samples would be anonymous and to 81% of patients when samples would be identifiable. Only 17% wanted to know about the identifiable scenario but not the anonymous scenario (i.e., following the regulatory distinction). Curiosity-based reasons were the most common (37%) among patients who wanted to know about anonymous samples. Of patients wanting to know about either scenario, approximately 57% would require researchers to seek permission, whereas 43% would be satisfied with notification only. Patients were more likely to support permission (versus notification) in the anonymous scenario if they had more education, were Black, less religious, in better health, more private, and less trusting of researchers. The sample, although not representative of the general population, does represent patients at academic medical centers whose clinical samples may be used for genetic research. Few patients expressed preferences consistent with the regulatory distinction between non-identifiable and identifiable information. Data from this study should cause policy-makers to question whether this distinction is useful in relation to research with previously collected clinically derived samples.

Palliative care has been one of the most rapidly growing fields of health care in the United States in the past decade. The benefits of palliative care have now been shown in multiple clinical trials, with increased patient and provider satisfaction, equal or better symptom control, more discernment of and honoring choices about place of death, fewer and less intensive hospital admissions in the last month of life, less anxiety and depression, less caregiver distress, and cost savings. The cost savings come from cost avoidance, or movement of a patient from a high cost setting to a lower cost setting. Barriers to expanded use include physician resistance, unrealistic expectations of patients and families, and lack of workforce. The future of palliative care includes more penetration into other fields such as nephrology, neurology, and surgery; further discernment of the most effective and cost-effective models; and establishment of more outpatient services.

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Aim The complex palaeogeography of the Malesian archipelago, characterized by the evolution of an ever-changing mosaic of terrestrial and marine areas throughout the Cenozoic, provides the geographic backdrop for the remarkable diversification of Malesian Begonia (> 450 species). This study aimed to investigate the origin of Malesian Begonia, the directionality of dispersal events within the Malesian archipelago and the impact of ancient water gaps on colonization patterns, and to identify drivers of diversification.Location Asia, Southeast Asia, Malesia.Methods Plastid DNA sequence data of representatives of all families of the Cucurbitales and Fagales (matK, rbcL, trnL intron, trnL-F spacer, 4076 aligned positions, 92 taxa) and a sample of all major Asian Begonia sections (ndhA intron, ndhF-rpl32 spacer, rpl32-trnL spacer, 4059 aligned positions, 112 taxa) were analysed under an uncorrelated-rates relaxed molecular clock model to estimate the age of the Begonia crown group divergence and divergence ages within Asian Begonia. Ancestral areas were reconstructed using a likelihood approach implementing a dispersal-extinction-cladogenesis model, and with a Bayesian approach to dispersal-vicariance analysis.

SummaryFewer than half of children with high-risk neuroblastoma survive. Many of these tumors harbor high-level amplification of MYCN, which correlates with poor disease outcome. Using data from our large drug screen we predicted, and subsequently demonstrated, that MYCN-amplified neuroblastomas are sensitive to the BCL-2 inhibitor ABT-199. This sensitivity occurs in part through low anti-apoptotic BCL-xL expression, high pro-apoptotic NOXA expression, and paradoxical, MYCN-driven upregulation of NOXA. Screening for enhancers of ABT-199 sensitivity in MYCN-amplified neuroblastomas, we demonstrate that the Aurora Kinase A inhibitor MLN8237 combines with ABT-199 to induce widespread apoptosis. In diverse models of MYCN-amplified neuroblastoma, including a patient-derived xenograft model, this combination uniformly induced tumor shrinkage, and in multiple instances led to complete tumor regression.