catena-Poly[[bis­(dimethyl­ammonium) [cadmate(II)-bis­(μ-1,1′:4′,1′′-terphenyl-3,3′′-dicarboxyl­ato)]] dimethyl­formamide disolvate]

In the title compound, {(C2H8N)2[Cd(C20H12O4)2]·2C3H7NO}n, the CdII ion lies on a twofold rotation axis and is in a distorted octa­hedral CdO6 environment, defined by four O atoms of two μ2-coordinated 1,1′:4′,1′′-terphenyl-3,3′′-dicarboxyl­ate (DCT) ligands and two O atoms of two μ1-coordinated DCT ligands. Both types of DCT ligands act as bridging, forming a one-dimensional polymeric structure propagating parallel to [10]

The role of intrinsic disorder and dynamics in the assembly and function of the type II secretion system

International audienceMany Gram-negative commensal and pathogenic bacteria use a type II secretion system (T2SS) to transport proteins out of the cell. These exported proteins or substrates play a major role in toxin delivery, maintaining biofilms, replication in the host and subversion of host immune responses to infection. We review the current structural and functional work on this system and argue that intrinsically disordered regions and protein dynamics are central for assembly, exo-protein recognition, and secretion competence of the T2SS. The central role of intrinsic disorder-order transitions in these processes may be a particular feature of type secretion

Relaxing the Irrevocability Requirement for Online Graph Algorithms

Online graph problems are considered in models where the irrevocability requirement is relaxed. Motivated by practical examples where, for example, there is a cost associated with building a facility and no extra cost associated with doing it later, we consider the Late Accept model, where a request can be accepted at a later point, but any acceptance is irrevocable. Similarly, we also consider a Late Reject model, where an accepted request can later be rejected, but any rejection is irrevocable (this is sometimes called preemption). Finally, we consider the Late Accept/Reject model, where late accepts and rejects are both allowed, but any late reject is irrevocable. For Independent Set, the Late Accept/Reject model is necessary to obtain a constant competitive ratio, but for Vertex Cover the Late Accept model is sufficient and for Minimum Spanning Forest the Late Reject model is sufficient. The Matching problem has a competitive ratio of 2, but in the Late Accept/Reject model, its competitive ratio is 3/2

Circulating levels of DNA-histone complex and dsDNA are independent prognostic factors of disseminated intravascular coagulation

AbstractIntroductionNeutrophils can be induced to release DNA combined with histones. The resulting neutrophil extracellular trap (NET) provides a scaffold for growing hemostatic plug. Therefore, the NET formation may be inevitable in clinical conditions that are characterized by formation of vascular thrombi. Thus far, there have been no reports on the clinical significance of NET in disseminated intravascular coagulation (DIC). Therefore, we investigated circulating levels of NET in DIC and analyzed their potential values to assess coagulation severity and predict clinical outcome.MethodsThe plasma levels of DNA-histone complexes and double-stranded DNA (dsDNA), considered to be in vivo markers of NET, were measured in 199 patients suspected of having DIC and 20 healthy controls.ResultThe circulating levels of DNA-histone complexes and dsDNA were significantly elevated in overt-DIC. The increased levels of these two markers correlated with the severity of coagulopathy including DIC score and D-dimer. Multivariable Cox regression analysis, adjusted for the conventional DIC markers, revealed that elevated DNA-histone complexes and dsDNA are poor independent prognostic markers.ConclusionThe circulating levels of NET release reflect the coagulation activation and adverse clinical outcomes in patients with DIC, thereby providing potential clinical relevance for mortality prediction in DIC

Targeting BTK for the treatment of FLT3-ITD mutated acute myeloid leukemia

Approximately 20% of patients with acute myeloid leukaemia (AML) have a mutation in FMS-like-tyrosine-kinase-3 (FLT3). FLT3 is a trans-membrane receptor with a tyrosine kinase domain which, when activated, initiates a cascade of phosphorylated proteins including the SRC family of kinases. Recently our group and others have shown that pharmacologic inhibition and genetic knockdown of Bruton's tyrosine kinase (BTK) blocks AML blast proliferation, leukaemic cell adhesion to bone marrow stromal cells as well as migration of AML blasts. The anti-proliferative effects of BTK inhibition in human AML are mediated via inhibition of downstream NF-κB pro-survival signalling however the upstream drivers of BTK activation in human AML have yet to be fully characterised. Here we place the FLT3-ITD upstream of BTK in AML and show that the BTK inhibitor ibrutinib inhibits the survival and proliferation of FLT3-ITD primary AML blasts and AML cell lines. Furthermore ibrutinib inhibits the activation of downstream kinases including MAPK, AKT and STAT5. In addition we show that BTK RNAi inhibits proliferation of FLT3-ITD AML cells. Finally we report that ibrutinib reverses the cyto-protective role of BMSC on FLT3-ITD AML survival. These results argue for the evaluation of ibrutinib in patients with FLT3-ITD mutated AML

Ecology: a prerequisite for malaria elimination and eradication

* Existing front-line vector control measures, such as insecticide-treated nets and residual sprays, cannot break the transmission cycle of Plasmodium falciparum in the most intensely endemic parts of Africa and the Pacific * The goal of malaria eradication will require urgent strategic investment into understanding the ecology and evolution of the mosquito vectors that transmit malaria * Priority areas will include understanding aspects of the mosquito life cycle beyond the blood feeding processes which directly mediate malaria transmission * Global commitment to malaria eradication necessitates a corresponding long-term commitment to vector ecolog

In pulmonary arterial hypertension, reduced BMPR2 promotes rndothelial-to-mesenchymal transition via HMGA1 and its target slug

Background—We previously reported high-throughput RNA sequencing analyses that identified heightened expression of the chromatin architectural factor High Mobility Group AT-hook 1 (HMGA1) in pulmonary arterial endothelial cells (PAECs) from patients who had idiopathic pulmonary arterial hypertension (PAH) in comparison with controls. Because HMGA1 promotes epithelial-to-mesenchymal transition in cancer, we hypothesized that increased HMGA1 could induce transition of PAECs to a smooth muscle (SM)–like mesenchymal phenotype (endothelial-to-mesenchymal transition), explaining both dysregulation of PAEC function and possible cellular contribution to the occlusive remodeling that characterizes advanced idiopathic PAH. Methods and Results—We documented increased HMGA1 in PAECs cultured from idiopathic PAH versus donor control lungs. Confocal microscopy of lung explants localized the increase in HMGA1 consistently to pulmonary arterial endothelium, and identified many cells double-positive for HMGA1 and SM22α in occlusive and plexogenic lesions. Because decreased expression and function of bone morphogenetic protein receptor 2 (BMPR2) is observed in PAH, we reduced BMPR2 by small interfering RNA in control PAECs and documented an increase in HMGA1 protein. Consistent with transition of PAECs by HMGA1, we detected reduced platelet endothelial cell adhesion molecule 1 (CD31) and increased endothelial-to-mesenchymal transition markers, αSM actin, SM22α, calponin, phospho-vimentin, and Slug. The transition was associated with spindle SM-like morphology, and the increase in αSM actin was largely reversed by joint knockdown of BMPR2 and HMGA1 or Slug. Pulmonary endothelial cells from mice with endothelial cell–specific loss of Bmpr2 showed similar gene and protein changes. Conclusions—Increased HMGA1 in PAECs resulting from dysfunctional BMPR2 signaling can transition endothelium to SM-like cells associated with PAH

Freshwater and Terrestrial Algae from Ny-Ålesund and Blomstrandhalvøya Island (Svalbard)

A field survey of algae and cyanobacteria from terrestrial and freshwater habitats in the vicinity of Ny-Ålesund and on Blomstrandhalvøya Island (Svalbard) was performed in June 2009, and results were compared with data from our fieldwork in June 2006. In total, we identified 30 taxa belonging to 23 genera from the specimens collected near Ny-Ålesund (26 taxa) and on Blomstrandhalvøya Island (24 taxa). Five species previously unrecorded from this locality are depicted, including astaxanthin-containing Haematococcus sp. collected from Blomstrandhalvøya Island. This is the first report on a Haematococcus species from the High Arctic.Une étude sur le terrain portant sur les algues et les cyanobactéries d’habitats terrestres et dulçaquicoles dans les environs de Ny-Ålesund et de l’île Blomstrandhalvøya (Svalbard) a été réalisée en juin 2009, et les résultats ont été comparés aux données de notre travail sur le terrain effectué en juin 2006. En tout, nous avons identifié 30 taxons appartenant à 23 genres à partir de spécimens prélevés près de Ny-Ålesund (26 taxons) et de Blomstrandhalvøya (24 taxons). Cinq espèces qui n’avaient jamais été répertoriées dans cette localité sont illustrées, dont l’Haematococcus sp. contenant de l’astaxanthine recueillie à l’île Blomstrandhalvøya. Il s’agit de la première fois que l’espèce Haematococcus a été signalée dans l’Extrême-Arctique

Gyroid Optical Metamaterials: Calculating the Effective Permittivity of Multidomain Samples

Gold gyroid optical metamaterials are known to possess a reduced plasma frequency and linear dichroism imparted by their intricate subwavelength single gyroid morphology. The anisotropic optical properties are, however, only evident when a large individual gyroid domain is investigated. Multidomain gyroid metamaterials, fabricated using a polyisoprene-$b$-polystyrene-$b$-poly(ethylene oxide) triblock terpolymer and consisting of multiple small gyroid domains with random orientation and handedness, instead exhibit isotropic optical properties. Comparing three effective medium models, we here show that the specular reflectance spectra of such multidomain gyroid optical metamaterials can be accurately modeled over a broad range of incident angles by a Bruggeman effective medium consisting of a random wire array. This model accurately reproduces previously published results tracking the variation in normal incidence reflectance spectra of gold gyroid optical metamaterials as a function of host refractive index and volume fill fraction of gold. The effective permittivity derived from this theory confirms the change in sign of the real part of the permittivity in the visible spectral region (so, that gold gyroid metamaterials exhibit both dielectric and metallic behavior at optical wavelengths). That a Bruggeman effective medium can accurately model the experimental reflectance spectra implies that small multidomain gold gyroid optical metamaterials behave both qualitatively and quantitatively as an amorphous composite of gold and air (i.e., nanoporous gold) and that coherent electromagnetic contributions arising from the subwavelength gyroid symmetry are not dominant.This research was supported through the Swiss National Science Foundation through the National Center of Competence in Research Bio-Inspired Materials and grant numbers 200021_163220 (to U.S.) and PZ00P2_168223 (to B.D.W.), the Adolphe Merkle Foundation, the Engineering and Physical Sciences Research Council (EPSRC) through the Cambridge NanoDTC EP/G037221/1, EP/L027151/1, and EP/ G060649/1, and ERC LINASS 320503 and from the European Union’s Horizon 2020 Research and Innovation Programme under the Marie Sklodowska-Curie grant agreement no. 706329 (to I.G.). Y.G. and U.W. thank the National Science Foundation (DMR-1409105) for financial support

Selection for Replicases in Protocells

PMCID: PMC3649988This 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