AT‐Specific DNA Binding of Binuclear Ruthenium Complexes at the Border of Threading Intercalation

The binuclear ruthenium complex [μ‐bidppz(phen)₄Ru₂]⁴⁺ has been extensively studied since the discovery of its unusual threading intercalation interaction with DNA, a binding mode with extremely slow binding and dissociation kinetics. The complex has been shown to be selective towards long stretches of alternating AT base pairs, which makes it interesting, for example, as a model compound for anti‐malaria drugs due to the high AT content of the genome of the malaria parasite P. falciparum. We have investigated the effect of bridging ligand structure on threading intercalation ability and found that length and rigidity as well as the size of the intercalated ring system are all factors that affect the rate and selectivity of the threading intercalation. In particular, we discovered a new DNA‐threading compound, [μ‐dppzip(phen)₄Ru₂]⁴⁺, which appears to be just at the border of being capable of threading intercalation and displays even greater selectivity for AT‐DNA than the parent compound, [μ‐bidppz(phen)₄Ru₂]⁴⁺.     

Dicaesium silver zinc thio­cyanate,Cs2[AgZn(SCN)5]

The title compound, dicaesium(I)‐μ‐thio­cyanato‐κ²N:S‐zinc(II)‐tetra‐μ‐thio­cyanato‐κ²S:N‐argentate(I), crystallizes in the orthorhombic space group Pmn2₁ and contains units of composition AgZn(SCN)₃ lying on a mirror plane and bonded together through Cs⁺ ions and thio­cyanate groups. The crystal studied contained equal numbers of inversion twins.     

Quantitative Proteomic Analysis of Optimal Cutting Temperature (OCT) Embedded Core-Needle Biopsy of Lung Cancer

With recent advances in understanding the genomic underpinnings and oncogenic drivers of pathogenesis in different subtypes, it is increasingly clear that proper pretreatment diagnostics are essential for the choice of appropriate treatment options for non-small cell lung cancer (NSCLC). Tumor tissue preservation in optimal cutting temperature (OCT) compound is commonly used in the surgical suite. However, proteins recovered from OCT-embedded specimens pose a challenge for LC-MS/MS experiments, due to the large amounts of polymers present in OCT. Here we present a simple workflow for whole proteome analysis of OCT-embedded NSCLC tissue samples, which involves a simple trichloroacetic acid precipitation step. Comparisons of protein recovery between frozen versus OCT-embedded tissue showed excellent consistency with more than 9200 proteins identified. Using an isobaric labeling strategy, we quantified more than 5400 proteins in tumor versus normal OCT-embedded core needle biopsy samples. Gene ontology analysis indicated that a number of proliferative as well as squamous cell carcinoma (SqCC) marker proteins were overexpressed in the tumor, consistent with the patient’s pathology based diagnosis of “poorly differentiated SqCC”. Among the most downregulated proteins in the tumor sample, we noted a number of proteins with potential immunomodulatory functions. Finally, interrogation of the aberrantly expressed proteins using a candidate approach and cross-referencing with publicly available databases led to the identification of potential druggable targets in DNA replication and DNA damage repair pathways. We conclude that our approach allows LC-MS/MS proteomic analyses on OCT-embedded lung cancer specimens, opening the way to bring powerful proteomics into the clinic.

Open image in new window

Graphical Abstract ?

     

Functionalized fullerenes in self-assembled monolayers

Anisotropy of intermolecular and molecule-substrate interactions holds the key to controlling the arrangement of fullerenes into 2D self-assembled monolayers (SAMs). The chemical reactivity of fullerenes allows functionalization of the carbon cages with sulfur-containing groups, thiols and thioethers, which facilitates the reliable adsorption of these molecules on gold substrates. A series of structurally related molecules, eight of which are new fullerene compounds, allows systematic investigation of the structural and functional parameters defining the geometry of fullerene SAMs. Scanning tunnelling microscopy (STM) measurements reveal that the chemical nature of the anchoring group appears to be crucial for the long-range order in fullerenes: the assembly of thiol-functionalized fullerenes is governed by strong molecule-surface interactions, which prohibit formation of ordered molecular arrays, while thioether-functionalized fullerenes, which have a weaker interaction with the surface than the thiols, form a variety of ordered 2D molecular arrays owing to noncovalent intermolecular interactions. A linear row of fullerene molecules is a recurring structural feature of the ordered SAMs, but the relative alignment and the spacing between the fullerene rows is strongly dependent on the size and shape of the spacer group linking the fullerene cage and the anchoring group. Careful control of the chemical functionality on the carbon cages enables positioning of fullerenes into at least four different packing arrangements, none of which have been observed before. Our new strategy for the controlled arrangement of fullerenes on surfaces at the molecular level will advance the development of practical applications for these nanomaterials.     

Towards new molecular photocatalysts for CO2 reduction: photo-induced electron transfer versus CO dissociation within [Os(NN)(CO)2Cl2] Complexes

Optical excitation in the visible region of trans-(Cl)-[Os(bpy)(CO)(2)Cl(2)] (bpy=2,2'-bipyridine; C1) and trans-(Cl)-[Os(dmbpy)(CO)(2)Cl(2)] (dmbpy=4,4'-dimethyl 2,2'-bipyridine; C2) is known to induce the common CO dissociation reaction. However, the quantum yield of the reactions is less than 0.15, although C1 and C2 display pronounced photoluminescence in the visible region at room temperature with a lifetime of few tens of nanoseconds. Taking into account the characteristics of their emitting state, we have investigated the capability of C1 and C2 to act as a photosensitiser in redox reactions in different solvents (MeCN, PrCN and DMF). The efficient oxidation and reduction of both complexes under continuous irradiation in the presence of a sacrificial electron acceptor or donor is reported here. The photo-induced transformations and the nature of the resulting compounds were analysed by UV/Vis and IR spectroscopies and cyclic voltammetry. Photo-induced oxidation of C1 and C2 leads to the corresponding monocarbonyl oxidised species, whereas photo-induced reduction under argon leads mainly to the formation of the corresponding Os-bonded molecular wires P1 and P2 after exchange of two electrons associated with the loss of two chloro ligands. The chemical yield of the latter reaction (around 65%) becomes quantitative by adding [Ru(bpy)(3)](2+) as an external redox photosensitiser. This behaviour has been used to photocatalyse the two electron, two proton conversion of CO(2) to CO. Turnover numbers (TON) of 11.5 and 19.5 have been obtained respectively for C1 and C2 after 4.5 h of irradiation under CO(2) in DMF with triethanolamine as the electron donor. TON can be slightly increased by adding [Ru(bpy)(3)](2+) to the solution.     

态射的Γ-Drazin逆和柱心-幂零分解

讨论态射的Γ-Drazin逆.给出了态射的Γ-Drazin逆的一些性质和柱心-幂零分解.     

关于F-正则性的注记

引进－环的Ｆ－正则根，具体讨论ｆ－正则性，得到了ｆ－正则－环的几个特征刻划以及结构定理，推广了Ｆ－正则－环的相应结果．举出ｖｏｎＮｅｕｍａｎｎ（弱、Ｆ－、ｆ－）正则的－环，而不是结合环的实例，并阐明上述几种正则性的区别．     

Regioselective acylation of aminoresorcinarenes

The acid catalyzed hydrolytic cleavage of the oxazine rings in the readily available tetraoxazine derivatives of resorcinarenes results in tetraaminoresorcinarenes. A similar process applied to C₂-symmetrical bisoxazine resorcinarene tetratosylates affords C_2v-symmetrical resorcinarenediamines. The mild acylation of these resorcinareneamines with BOC-anhydride or para-nitrophenyl ester proceeds selectively at the nitrogen atoms without affecting the hydroxyl groups. Most of the resulting resorcinareneamides are thus obtained in preparative yields and can be easily purified by simple crystallizations. In the crystalline state the compounds obtained are found to bind chloride anions through hydrogen bonds and electrostatic interactions and to display a chiral arrangement of hydrogen bonded functional groups at the wide rim of the macrocycle.     

Atypical perceptual narrowing in prematurely born infants is associated with compromised language acquisition at 2 years of age

Background

Protein aggregation plays important roles in several neurodegenerative disorders. For instance, insoluble aggregates of phosphorylated tau and of Aβ peptides are cornerstones in the pathology of Alzheimer's disease. Soluble protein aggregates are therefore potential diagnostic and prognostic biomarkers for their cognate disorders. Detection of the aggregated species requires sensitive tools that efficiently discriminate them from monomers of the same proteins. Here we have established a proximity ligation assay (PLA) for specific and sensitive detection of Aβ protofibrils via simultaneous recognition of three identical determinants present in the aggregates. PLA is a versatile technology in which the requirement for multiple target recognitions is combined with the ability to translate signals from detected target molecules to amplifiable DNA strands, providing very high specificity and sensitivity.

Results

For specific detection of Aβ protofibrils we have used a monoclonal antibody, mAb158, selective for Aβ protofibrils in a modified PLA, where the same monoclonal antibody was used for the three classes of affinity reagents required in the assay. These reagents were used for detection of soluble Aβ aggregates in solid-phase reactions, allowing detection of just 0.1 pg/ml Aβ protofibrils, and with a dynamic range greater than six orders of magnitude. Compared to a sandwich ELISA setup of the same antibody the PLA increases the sensitivity of the Aβ protofibril detection by up to 25-fold. The assay was used to measure soluble Aβ aggregates in brain homogenates from mice transgenic for a human allele predisposing to Aβ aggregation.

Conclusions

The proximity ligation assay is a versatile analytical technology for proteins, which can provide highly sensitive and specific detection of Aβ aggregates - and by implication other protein aggregates of relevance in Alzheimer's disease and other neurodegenerative disorders.     

Development of Counting Skills: Role of Spontaneous Focusing on Numerosity and Subitizing-Based Enumeration

Children differ in how much they spontaneously pay attention to quantitative aspects of their natural environment. We studied how this spontaneous tendency to focus on numerosity (SFON) is related to subitizing-based enumeration and verbal and object counting skills. In this exploratory study, children were tested individually at the age of 4–5 years on these skills. Results showed 2 primary relationships in children's number skills development. Performance in a number sequence production task, which is closely related to ordinal number sequence without reference to cardinality, is directly associated with SFON. Second, the association of SFON and object counting skills, which require relating cardinal and ordinal aspects of number, is mediated by subitizing-based enumeration. This suggests that there are multiple pathways to enumeration skills during development.