From elusive thio- and selenosilanoic acids to copper(I) complexes with intermolecular Si=E -> Cu-O-Si coordination modes (E = S, Se)

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG geförderten) Allianz- bzw. Nationallizenz frei zugänglich.This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.The facile synthesis of the first stable selenosilanoic acid–base adduct LSi([double bond, length as m-dash]Se)OH(dmap) 3 (L = CH[C(Me)NAr]2, Ar = 2,6-iPr2C6H3, dmap = 4-dimethylaminopyridine), the heavier analogue of the thiosilanoic acid adduct LSi([double bond, length as m-dash]S)OH(dmap) 1, is reported. Both adducts 1 and 3 react readily with MesCu (Mes = 2,4,6-trimethylphenyl) to form the novel dimeric Cu(I) complexes [LSi([double bond, length as m-dash]E)OCu]2 (4: E = S; 5: E = Se) with unprecedented intermolecular Si[double bond, length as m-dash]E → Cu–O–Si coordination modes. The latter are efficient pre-catalysts for the Cu(I)-mediated aziridination of styrene with PhI[double bond, length as m-dash]N(Ts) (Ts = tosyl)

Block of death-receptor apoptosis protects mouse cytomegalovirus from macrophages and is a determinant of virulence in immunodeficient hosts.

The inhibition of death-receptor apoptosis is a conserved viral function. The murine cytomegalovirus (MCMV) gene M36 is a sequence and functional homologue of the human cytomegalovirus gene UL36, and it encodes an inhibitor of apoptosis that binds to caspase-8, blocks downstream signaling and thus contributes to viral fitness in macrophages and in vivo. Here we show a direct link between the inability of mutants lacking the M36 gene (ΔM36) to inhibit apoptosis, poor viral growth in macrophage cell cultures and viral in vivo fitness and virulence. ΔM36 grew poorly in RAG1 knockout mice and in RAG/IL-2-receptor common gamma chain double knockout mice (RAGγC(-/-)), but the depletion of macrophages in either mouse strain rescued the growth of ΔM36 to almost wild-type levels. This was consistent with the observation that activated macrophages were sufficient to impair ΔM36 growth in vitro. Namely, spiking fibroblast cell cultures with activated macrophages had a suppressive effect on ΔM36 growth, which could be reverted by z-VAD-fmk, a chemical apoptosis inhibitor. TNFα from activated macrophages synergized with IFNγ in target cells to inhibit ΔM36 growth. Hence, our data show that poor ΔM36 growth in macrophages does not reflect a defect in tropism, but rather a defect in the suppression of antiviral mediators secreted by macrophages. To the best of our knowledge, this shows for the first time an immune evasion mechanism that protects MCMV selectively from the antiviral activity of macrophages, and thus critically contributes to viral pathogenicity in the immunocompromised host devoid of the adaptive immune system

Kinesin family member 6 (kif6) is necessary for spine development in zebrafish

Author Posting. © The Author(s), 2014. This is the author's version of the work. It is posted here by permission of John Wiley & Sons for personal use, not for redistribution. The definitive version was published in Developmental Dynamics 243 (2014): 1646–1657, doi:10.1002/dvdy.24208.Idiopathic scoliosis is a form of spinal deformity that affects 2–3% of children and results in curvature of the spine without structural defects of the vertebral units. The pathogenesis of idiopathic scoliosis remains poorly understood, in part due to the lack of a relevant animal model. We performed a forward mutagenesis screen in zebrafish to identify new models for idiopathic scoliosis. We isolated a recessive zebrafish mutant, called skolios, which develops isolated spinal curvature that arises independent of vertebral malformations. Using meiotic mapping and whole genome sequencing, we identified a nonsense mutation in kinesin family member 6 (kif6gw326) unique to skolios mutants. Three additional kif6 frameshift alleles (gw327, gw328, gw329) were generated with transcription activator-like effector nucleases (TALENs). Zebrafish homozygous or compound heterozygous for kif6 frameshift mutations developed a scoliosis phenotype indistinguishable from skolios mutants, confirming that skolios is caused by the loss of kif6. Although kif6 may play a role in cilia, no evidence for cilia dysfunction was seen in kif6gw326 mutants. Overall, these findings demonstrate a novel role for kif6 in spinal development and identify a new candidate gene for human idiopathic scoliosis.2015-11-1

Effects of root dehydration on biomechanical properties of woody roots of <i>Ulex europaeus</i>

Aims: Effects of root water status on root tensile strength and Young’s modulus were studied in relation to root reinforcement of slopes. Methods: Biomechanical properties of woody roots, Ulex europaeus, were tested during progressive dehydration and after thirty-day moisture equilibration in soil with contrasting water contents. Root diameter, water content and water loss were recorded and root water potential versus water content relation was investigated. Tensile stresses induced by root contraction upon dehydration were measured. Results: Root tensile strength and Young’s modulus increased abruptly when root water content dropped below 0.5 g g −1. The strength increase was due to root radial and axial contraction induced by root water potential drop. Diameter decrease and strength gain were the largest for thin roots because of the relatively larger evaporative surface per volume of thin roots. Largely negative water potentials in dry soil induced root drying, affecting root biomechanical properties. Conclusion: Root water status is a factor that can cause (inappropriately) high strength values and the large variability reported in literature for thin roots. Therefore, all root diameter classes should have consistent moisture for fair comparison. Testing fully hydrated roots should be the routine protocol, given that slope instability occurs after heavy rainfall. </p

The pro-neurotrophin receptor sortilin is a major neuronal apolipoprotein E receptor for catabolism of amyloid-β peptide in the brain

Apolipoprotein E (APOE) is the major risk factor for sporadic Alzheimer's disease. Among other functions, APOE is proposed to sequester neurotoxic amyloid-{beta} (A{beta}) peptides in the brain, delivering them to cellular catabolism via neuronal APOE receptors. Still, the receptors involved in this process remain controversial. Here, we identified the pro-neurotrophin receptor sortilin as major endocytic pathway for clearance of APOE/A{beata} complexes in neurons. Sortilin binds APOE with high affinity. Lack of receptor expression in mice results in accumulation of APOE and of A{beta} in the brain and in aggravated plaque burden. Also, primary neurons lacking sortilin exhibit significantly impaired uptake of APOE/A{beta} complexes despite proper expression of other APOE receptors. Despite higher than normal brain APOE levels, sortilin-deficient animals display anomalies in brain lipid metabolism (e.g., accumulation of sulfatides) seen in APOE-deficient mice, indicating functional deficiency in cellular APOE uptake pathways. Together, our findings identified sortilin as an essential neuronal pathway for APOE-containing lipoproteins in vivo and suggest an intriguing link between A{beta} catabolism and pro-neurotrophin signaling converging on this receptor

The Shaqadud Archaeological Project (Sudan): exploring prehistoric cultural adaptations in the Sahelian hinterlands

The authors present preliminary results from a new research project based in Jebel Shaqadud, Sudan. Their findings highlight the potential for this region's archaeological record to expand our understanding of the adaptation strategies used by human groups in arid north-east African environments away from rivers and lakes during the Holocene. Furthermore, they present exceptionally early radiocarbon dates that push postglacial human occupation in the eastern Sahel back to the twelfth millennium BP

Ectopic callose deposition into woody biomass modulates the nano-architecture of macrofibrils

Plant biomass plays an increasingly important role in the circular bioeconomy, replacing non-renewable fossil resources. Genetic engineering of this lignocellulosic biomass could benefit biorefinery transformation chains by lowering economic and technological barriers to industrial processing. However, previous efforts have mostly targeted the major constituents of woody biomass: cellulose, hemicellulose and lignin. Here we report the engineering of wood structure through the introduction of callose, a polysaccharide novel to most secondary cell walls. Our multiscale analysis of genetically engineered poplar trees shows that callose deposition modulates cell wall porosity, water and lignin contents and increases the lignin-cellulose distance, ultimately resulting in substantially decreased biomass recalcitrance. We provide a model of the wood cell wall nano-architecture engineered to accommodate the hydrated callose inclusions. Ectopic polymer introduction into biomass manifests in new physico-chemical properties and offers new avenues when considering lignocellulose engineering.Bourdon et al. demonstrate the possibility to ectopically synthesize callose, a polymer restricted to primary cell walls, into Arabidopsis and aspen secondary cell walls to manipulate their ultrastructure and ultimately reduce their recalcitrance

Comparison of Human Memory CD8 T Cell Responses to Adenoviral Early and Late Proteins in Peripheral Blood and Lymphoid Tissue

Treatment of invasive adenovirus (Ad) disease in hematopoietic stem cell transplant (SCT) recipients with capsid protein hexon-specific donor T cells is under investigation. We propose that cytotoxic T cells (CTLs) targeted to the late protein hexon may be inefficient in vivo because the early Ad protein E3-19K downregulates HLA class I antigens in infected cells. In this study, CD8+ T cells targeted to highly conserved HLA A2-restricted epitopes from the early regulatory protein DNA polymerase (P-977) and late protein hexon (H-892) were compared in peripheral blood (PB) and tonsils of naturally infected adults. In tonsils, epitope-specific pentamers detected a significantly higher frequency of P-977+CD8+ T cells compared to H-892+CD8+ T cells; this trend was reversed in PB. Tonsil epitope-specific CD8+ T cells expressed IFN-γ and IL-2 but not perforin or TNF-α, whereas PB T cells were positive for IFN-γ, TNF-α, and perforin. Tonsil epitope-specific T cells expressed lymphoid homing marker CCR7 and exhibited lower levels of the activation marker CD25 but higher proliferative potential than PB T cells. Finally, in parallel with the kinetics of mRNA expression, P-977-specific CTLs lysed targets as early as 8 hrs post infection. In contrast, H-892-specific CTLs did not kill unless infected fibroblasts were pretreated with IFN-γ to up regulate HLA class I antigens, and cytotoxicity was delayed until 16–24 hours. These data show that, in contrast to hexon CTLs, central memory type DNA polymerase CTLs dominate the lymphoid compartment and kill fibroblasts earlier after infection without requiring exogenous IFN-γ. Thus, use of CTLs targeted to both early and late Ad proteins may improve the efficacy of immunotherapy for life-threatening Ad disease in SCT recipients