Modelling stellar evolution in mass-transferring binaries and gravitational-wave progenitors with METISSE

Massive binaries are vital sources of various transient processes, including gravitational-wave mergers. However, large uncertainties in the evolution of massive stars, both physical and numerical, present a major challenge to the understanding of their binary evolution. In this paper, we upgrade our interpolation-based stellar evolution code METISSE to include the effects of mass changes, such as binary mass transfer or wind-driven mass loss, not already included within the input stellar tracks. METISSE's implementation of mass loss (applied to tracks without mass loss) shows excellent agreement with the SSE fitting formulae and with detailed MESA tracks, except in cases where the mass transfer is too rapid for the star to maintain equilibrium. We use this updated version of METISSE within the binary population synthesis code BSE to demonstrate the impact of varying stellar evolution parameters, particularly core overshooting, on the evolution of a massive (25M$_\odot$ and 15M$_\odot$) binary system with an orbital period of 1800 days. Depending on the input tracks, we find that the binary system can form a binary black hole or a black hole-neutron star system, with primary(secondary) remnant masses ranging between 4.47(1.36)M$_\odot$ and 12.30(10.89)M$_\odot$, and orbital periods ranging from 6 days to the binary becoming unbound. Extending this analysis to a population of isolated binaries uniformly distributed in mass and orbital period, we show that the input stellar models play an important role in determining which regions of the binary parameter space can produce compact binary mergers, paving the way for predictions for current and future gravitational-wave observatories.Comment: 19 pages, 14 figures, accepted for publication in MNRA

HAWAIIAN SKIRT, and F-box gene from Arabidopsis, is a new player in the microRNA pathway

F-box proteins belong to a multi-protein E3 ubiquitin ligase complex (SCF) that target proteins for degradation via the proteasome.We demonstrated that HAWAIIAN SKIRT(HWS), an Arabidopsis ubiquitin protein ligase (SCFHWS), regulates organ growth, flower development and timing of abscission. Mutants of this gene (hws-1) are pleiotropic and the most obvious phenotype is the fusion of its floral organs, a phenotype shared with the cuc1/cuc2 double mutants and over-expressing lines of MIR164B. To understand the molecular mechanisms of HWS during plant development, an ethylmethylsulphonate mutagenized population of hws-1 seeds was generated and screened for mutations suppressing the hws-1 sepal fusion. We isolated shs-1/hws-1, shs-2/hws-1, and shs-3/hws-1, (suppressor of hws-1) mutants. Mapping analyses shown that shs1 is mutated in the miRNA164 binding site of CUPSHAPED COTYLEDON1 (CUC1) mRNA; while shs-2 and shs-3 are novel alleles of the plant homolog of Exporting-5 HASTY (HST), known to be important in miRNA biogenesis, function and transport. Consequently, we renamed them cuc1-1D, hst23 and hst24, respectively. We demonstrated that transcript levels of CUC1 and CUPSHAPED COTYLEDON 2 (CUC2), and MIR164 change in cuc1-1D and in hws-1 mutants; analyses revealed a role for HWS in cell proliferation and control of floral organ number. Additional genetic crosses between hws-1 and mutant lines for genes in the miRNA pathway were performed and double mutants obtained shown restoration of the hws-1 sepal fusion phenotype. Our data propose HWS as a new regulator in miRNA pathway and reveal a role for HWS to control floral organ number and cell proliferation

HAWAIIAN SKIRT controls size and floral organ number by modulating CUC1 and CUC2 expression

The Arabidopsis thaliana F-box gene HAWAIIAN SKIRT (HWS) affects organ growth and the timing of floral organ abscission. The loss-of-function hws-1 mutant exhibits fused sepals and increased organ size. To understand the molecular mechanisms of HWS during plant development, we mutagenized hws-1 seeds with ethylmethylsulphonate (EMS) and screened for mutations suppressing hws-1 associated phenotypes. We isolated the shs1/hws-1 (suppressor of hws-1) mutant in which hws-1 sepal fusion phenotype was suppressed. The shs1/hws-1 mutant carries a G→A nucleotide substitution in the MIR164 binding site of CUP-SHAPED COTYLEDON 1 (CUC1) mRNA. CUC1 and CUP-SHAPED COTYLEDON 2 (CUC2) transcript levels were altered in shs1, renamed cuc1-1D, and in hws-1 mutant. Genetic interaction analyses using single, double and triple mutants of cuc1-1D, cuc2-1D (a CUC2 mutant similar to cuc1-1D), and hws-1, demonstrate that HWS, CUC1 and CUC2 act together to control floral organ number. Loss of function of HWS is associated with larger petal size due to alterations in cell proliferation and mitotic growth, a role shared with the CUC1 gene

Teaching Strategies: Teaching Beyond the Basics: Young Children Participate in a Cognitive Apprenticeship: Tunde Szecsi, Editor

Community members have a variety of funds of knowledge they could contribute as specialists in collaborative experiences with teachers. Yet, despite having such invaluable culture capital, speciali..

Isolation of specific and biologically active peptides that bind cells from patients with acute myeloid leukemia (AML)

<p>Abstract</p> <p>Purpose</p> <p>In a departure from conventional strategies to improve treatment outcome for myeloid malignancies, we report the isolation of leukemia-specific peptides using a phage display library screened with freshly obtained human myeloid leukemia cells.</p> <p>Results</p> <p>A phage display library was screened by 5 rounds of biopanning with freshly isolated human AML cells. Individual colonies were randomly picked and after purification, biologic activity (growth and differentiation) on fresh AML cells was profiled. Ten peptides were synthesized for further biological studies. Multiple peptides were found to selectively bind to acute myeloid leukemia (AML) cells. The peptides bound to leukemia cells, were internalized and could induce proliferation and/or differentiation in the target patient cells. Two of the peptides, HP-A2 and HP-G7, appeared to have a novel mechanism of inducing differentiation since they did not cause G1 arrest in cycling cells even as the expression of the differentiation marker CD11b increased.</p> <p>Conclusion</p> <p>Peptide induced differentiation of leukemia cells offers a novel treatment strategy for myeloid malignancies, whereas their ability to induce proliferation could be harnessed to make cells more sensitive to chemotherapy. Conceptually, these leukemia specific peptides can also be used to refine diagnosis, document minimal residual disease, and selectively deliver toxins to malignant cells.</p

A single residue substitution in the receptor-binding domain of H5N1 hemagglutinin is critical for packaging into pseudotyped lentiviral particles

© 2012 Tang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Serological studies for influenza infection and vaccine response often involve microneutralization and hemagglutination inhibition assays to evaluate neutralizing antibodies against human and avian influenza viruses, including H5N1. We have previously characterized lentiviral particles pseudotyped with H5-HA (H5pp) and validated an H5pp-based assay as a safe alternative for high-throughput serological studies in BSL-2 facilities. Here we show that H5-HAs from different clades do not always give rise to efficient production of H5pp and the underlying mechanisms are addressed. Methodology/Findings: We have carried out mutational analysis to delineate the molecular determinants responsible for efficient packaging of HA from A/Cambodia/40808/2005 (H5Cam) and A/Anhui/1/2005 (H5Anh) into H5pp. Our results demonstrate that a single A134V mutation in the 130-loop of the receptor binding domain is sufficient to render H5Anh the ability to generate H5Anh-pp efficiently, whereas the reverse V134A mutation greatly hampers production of H5Cam-pp. Although protein expression in total cell lysates is similar for H5Anh and H5Cam, cell surface expression of H5Cam is detected at a significantly higher level than that of H5Anh. We further demonstrate by several independent lines of evidence that the behaviour of H5Anh can be explained by a stronger binding to sialic acid receptors implicating residue 134. Conclusions: We have identified a single A134V mutation as the molecular determinant in H5-HA for efficient incorporation into H5pp envelope and delineated the underlying mechanism. The reduced binding to sialic acid receptors as a result of the A134V mutation not only exerts a critical influence in pseudotyping efficiency of H5-HA, but has also an impact at the whole virus level. Because A134V substitution has been reported as a naturally occurring mutation in human host, our results may have implications for the understanding of human host adaptation of avian influenza H5N1 virusesThis work was supported by grants from the Research Fund for the Control of Infectious Diseases of Hong Kong (RFCID#08070972), the Area of Excellence Scheme of the University Grants Committee (grant AoE/M-12/-06 of the Hong Kong Special Administrative Region, China), the French Ministry of Health, and the RESPARI project of the Institut Pasteur International Network

Ciliary Beating Recovery in Deficient Human Airway Epithelial Cells after Lentivirus Ex Vivo Gene Therapy

Primary Ciliary Dyskinesia is a heterogeneous genetic disease that is characterized by cilia dysfunction of the epithelial cells lining the respiratory tracts, resulting in recurrent respiratory tract infections. Despite lifelong physiological therapy and antibiotics, the lungs of affected patients are progressively destroyed, leading to respiratory insufficiency. Recessive mutations in Dynein Axonemal Intermediate chain type 1 (DNAI1) gene have been described in 10% of cases of Primary Ciliary Dyskinesia. Our goal was to restore normal ciliary beating in DNAI1–deficient human airway epithelial cells. A lentiviral vector based on Simian Immunodeficiency Virus pseudotyped with Vesicular Stomatitis Virus Glycoprotein was used to transduce cultured human airway epithelial cells with a cDNA of DNAI1 driven by the Elongation Factor 1 promoter. Transcription and translation of the transduced gene were tested by RT–PCR and western blot, respectively. Human airway epithelial cells that were DNAI1–deficient due to compound heterozygous mutations, and consequently had immotile cilia and no outer dynein arm, were transduced by the lentivirus. Cilia beating was recorded and electron microscopy of the cilia was performed. Transcription and translation of the transduced DNAI1 gene were detected in human cells treated with the lentivirus. In addition, immotile cilia recovered a normal beat and outer dynein arms reappeared. We demonstrated that it is possible to obtain a normalization of ciliary beat frequency of deficient human airway epithelial cells by using a lentivirus to transduce cells with the therapeutic gene. This preliminary step constitutes a conceptual proof that is indispensable in the perspective of Primary Ciliary Dyskinesia's in vivo gene therapy. This is the first time that recovery of cilia beating is demonstrated in this disease