Improving the flame retardance of polyisocyanurate foams by dibenzo[d,f][1,3,2]dioxaphosphepine 6-oxide-containing additives

A series of new flame retardants (FR) based on dibenzo[d,f][1,3,2]dioxaphosphepine 6-oxide (BPPO) incorporating acrylates and benzoquinone were developed previously. In this study, we examine the fire behavior of the new flame retardants in polyisocyanurate (PIR) foams. The foam characteristics, thermal decomposition, and fire behavior are investigated. The fire properties of the foams containing BPPO-based derivatives were found to depend on the chemical structure of the substituents. We also compare our results to state-of-the-art non-halogenated FR such as triphenylphosphate and chemically similar phosphinate, i.e. 9,10-dihydro-9-oxa-10- phosphaphenanthrene-10-oxide (DOPO), based derivatives to discuss the role of the phosphorus oxidation state

Effective Halogen-Free Flame-Retardant Additives for Crosslinked Rigid Polyisocyanurate Foams: Comparison of Chemical Structures

The impact of phosphorus-containing flame retardants (FR) on rigid polyisocyanurate (PIR) foams is studied by systematic variation of the chemical structure of the FR, including non-NCO-reactive and NCO-reactive dibenzo[d,f][1,3,2]dioxaphosphepine 6-oxide (BPPO)- and 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO)-containing compounds, among them a number of compounds not reported so far. These PIR foams are compared with PIR foams without FR and with standard FRs with respect to foam properties, thermal decomposition, and fire behavior. Although BPPO and DOPO differ by just one oxygen atom, the impact on the FR properties is very significant: when the FR is a filler or a dangling (dead) end in the PIR polymer network, DOPO is more effective than BPPO. When the FR is a subunit of a diol and it is fully incorporated in the PIR network, BPPO delivers superior results

Attrition of X Chromosome Inactivation in Aged Hematopoietic Stem Cells

During X chromosome inactivation (XCI), the inactive X chromosome (Xi) is recruited to the nuclear lamina at the nuclear periphery. Beside X chromosome reactivation resulting in a highly penetrant aging-like hematopoietic malignancy, little is known about XCI in aged hematopoietic stem cells (HSCs). Here, we demonstrate that LaminA/C defines a distinct repressive nuclear compartment for XCI in young HSCs, and its reduction in aged HSCs correlates with an impairment in the overall control of XCI. Integrated omics analyses reveal higher variation in gene expression, global hypomethylation, and significantly increased chromatin accessibility on the X chromosome (Chr X) in aged HSCs. In summary, our data support the role of LaminA/C in the establishment of a special repressive compartment for XCI in HSCs, which is impaired upon aging

BRCA1 mislocalization leads to aberrant DNA damage response in heterozygous ABRAXAS1 mutation carrier cells

Peer reviewe

Haematopoietic stem cells in perisinusoidal niches are protected from ageing.

With ageing, intrinsic haematopoietic stem cell (HSC) activity decreases, resulting in impaired tissue homeostasis, reduced engraftment following transplantation and increased susceptibility to diseases. However, whether ageing also affects the HSC niche, and thereby impairs its capacity to support HSC function, is still widely debated. Here, by using in-vivo long-term label-retention assays we demonstrate that aged label-retaining HSCs, which are, in old mice, the most quiescent HSC subpopulation with the highest regenerative capacity and cellular polarity, reside predominantly in perisinusoidal niches. Furthermore, we demonstrate that sinusoidal niches are uniquely preserved in shape, morphology and number on ageing. Finally, we show that myeloablative chemotherapy can selectively disrupt aged sinusoidal niches in the long term, which is linked to the lack of recovery of endothelial Jag2 at sinusoids. Overall, our data characterize the functional alterations of the aged HSC niche and unveil that perisinusoidal niches are uniquely preserved and thereby protect HSCs from ageing

Effective Halogen-Free Flame-Retardant Additives for Crosslinked Rigid Polyisocyanurate Foams: Comparison of Chemical Structures

The impact of phosphorus-containing flame retardants (FR) on rigid polyisocyanurate (PIR) foams is studied by systematic variation of the chemical structure of the FR, including non-NCO-reactive and NCO-reactive dibenzo[d,f][1,3,2]dioxaphosphepine 6-oxide (BPPO)- and 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO)-containing compounds, among them a number of compounds not reported so far. These PIR foams are compared with PIR foams without FR and with standard FRs with respect to foam properties, thermal decomposition, and fire behavior. Although BPPO and DOPO differ by just one oxygen atom, the impact on the FR properties is very significant: when the FR is a filler or a dangling (dead) end in the PIR polymer network, DOPO is more effective than BPPO. When the FR is a subunit of a diol and it is fully incorporated in the PIR network, BPPO delivers superior results

The Spindle Assembly Checkpoint Is Required for Hematopoietic Progenitor Cell Engraftment

Summary: The spindle assembly checkpoint plays a pivotal role in preventing aneuploidy and transformation. Many studies demonstrate impairment of this checkpoint in cancer cells. While leukemia is frequently driven by transformed hematopoietic stem and progenitor cells (HSPCs), the biology of the spindle assembly checkpoint in such primary cells is not very well understood. Here, we reveal that the checkpoint is fully functional in murine progenitor cells and, to a lesser extent, in hematopoietic stem cells. We show that HSPCs arrest at prometaphase and induce p53-dependent apoptosis upon prolonged treatment with anti-mitotic drugs. Moreover, the checkpoint can be chemically and genetically abrogated, leading to premature exit from mitosis, subsequent enforced G1 arrest, and enhanced levels of chromosomal damage. We finally demonstrate that, upon checkpoint abrogation in HSPCs, hematopoiesis is impaired, manifested by loss of differentiation potential and engraftment ability, indicating a critical role of this checkpoint in HSPCs and hematopoiesis. : In this report, Andreas Brown and colleagues demonstrate that cycling hematopoietic stem and progenitor cells activate the spindle assembly checkpoint as a response to anti-mitotic stress. The authors further reveal that inhibition of the checkpoint causes impairment of progenitor function, whereas it appears to be less crucial for hematopoietic stem cells. Keywords: mitotic checkpoint, spindle assembly checkpoint, hematopoietic stem cells, hematopoietic progenitor cells, genome stability, hematopoiesis, SAC, reversine, micronucle

Multifunctional methacrylate-based coatings for glass and metal surfaces

In order to prevent freshwater biofouling glass and metal surfaces were coated with novel transparent methacrylate-based copolymers. The multifunctionality of the copolymers, such as adhesion to the substrate, surface polarity, mechanical long-term stability in water, and ability to form metal complexes was inserted by the choice of suitable comonomers. The monomer 2-acetoacetoxy ethyl methacrylate (AAMA) was used as complexing unit to produce copper(II) complexes in the coating’s upper surface layer. The semifluorinated monomer 1H,1H,2H,2H-perfluorodecyl methacrylate was employed to adjust the surface polarity and wettability. Comprehensive surface characterization techniques, such as X-ray photoelectron spectroscopy (XPS) and contact angle measurements showed that surface compositions and properties can be easily adjusted by varying the concentrations of the comonomers. The formation of copper(II) complexes along the copolymer chains and their stability against washing out with plenty of water was proven by XPS. Copolymers containing semifluorinated comonomers significantly inhibited the growth of Achnanthidium species. Copolymers with copper-loaded AAMA-sequences were able to reduce both the growth of Achnanthidium spec. and Staphylococcus aureus

Partial Reduction in BRCA1 Gene Dose Modulates DNA Replication Stress Level and Thereby Contributes to Sensitivity or Resistance

BRCA1 is a well-known breast cancer risk gene, involved in DNA damage repair via homologous recombination (HR) and replication fork protection. Therapy resistance was linked to loss and amplification of the BRCA1 gene causing inferior survival of breast cancer patients. Most studies have focused on the analysis of complete loss or mutations in functional domains of BRCA1. How mutations in non-functional domains contribute to resistance mechanisms remains elusive and was the focus of this study. Therefore, clones of the breast cancer cell line MCF7 with indels in BRCA1 exon 9 and 14 were generated using CRISPR/Cas9. Clones with successful introduced BRCA1 mutations were evaluated regarding their capacity to perform HR, how they handle DNA replication stress (RS), and the consequences on the sensitivity to MMC, PARP1 inhibition, and ionizing radiation. Unexpectedly, BRCA1 mutations resulted in both increased sensitivity and resistance to exogenous DNA damage, despite a reduction of HR capacity in all clones. Resistance was associated with improved DNA double-strand break repair and reduction in replication stress (RS). Lower RS was accompanied by increased activation and interaction of proteins essential for the S phase-specific DNA damage response consisting of HR proteins, FANCD2, and CHK1