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.     

Effects of guanidinium cations on structural,optoelectronic and photovoltaic properties of perovskites

Guanidinium (GA) cations are intentionally introduced in MAPbl3 perovskite by considering its potential capability of stabilizing the material through plenty of...     

Ca[Ag2(SCN)4]·2H2O

Calcium tetra­thio­cyanato­diargentate(I) dihydrate, Ca[Ag₂(SCN)₄]·2H₂O, contains eight‐membered Ag₄S₄ rings bonded together through shared atoms to form layers parallel to (100). The thio­cyanate groups link the layers to Ca–O chains running parallel to the c axis. The Ca atom is located on a twofold rotation axis parallel to b and is surrounded by four water molecules of crystallization and four thio­cyanate N atoms in a distorted square antiprism.     

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.     

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⁺.     

Techniques of differential scanning calorimetry for quantification of low contents of amorphous phases

Differential scanning calorimetry (DSC) is one of the most frequently used techniques for analyzing small concentrations of amorphous phases in a crystalline matrix. In recent years novel enhanced DSC approaches have been intensively looked for to improve parameters such as sensitivity, accuracy, and detection limit of the technique. Low levels of amorphous phases can be quantitatively determined in DSC by measuring the heat capacity change associated with the glass transition. In this short review the potentials provided by the HyperDSC and StepScan DSC techniques are discussed. Examples illustrate the advantages and disadvantages of the techniques and compare their abilities to detect small glass transitions and determine low contents of amorphous phases in samples which are mostly crystalline.     

A One‐Pot Synthesis of N‐Aryl‐2‐Oxazolidinones and Cyclic Urethanes by the Lewis Base Catalyzed Fixation of Carbon Dioxide into Anilines and Bromoalkanes

The multicomponent assembly of pharmaceutically relevant N‐aryl‐oxazolidinones through the direct insertion of carbon dioxide into readily available anilines and dibromoalkanes is described. The addition of catalytic amounts of an organosuperbase such as Barton's base enables this transformation to proceed with high yields and exquisite substrate functional‐group tolerance under ambient CO₂ pressure and mild temperature. This report also provides the first proof‐of‐principle for the single‐operation synthesis of elusive seven‐membered ring cyclic urethanes.     

整体柱在线净化-液相色谱-高分辨质谱法快速测定牛奶中15种糖皮质激素

将自制的在线固相萃取柱与液相色谱串联四极杆静电轨道离子阱质谱技术相结合,建立了快速测定牛奶中15种糖皮质激素类药物的新方法.样品采用乙腈均质提取2 min,经自制在线固相萃取小柱富集净化,在Waters CORTECS T3(150 mm ×2.1 mm,5μm)分析柱上实现良好分离,外标法定量.15种目标物质量浓度在...     

714名0—6岁儿童头发中微量元素水平的研究

报道了深圳市南山区７１４名０￣６岁儿童头发中６种必需微量和宏量元素的水平，分析了不同年龄、性别儿童６种元素的异常状况，研究结果表明，儿童头发中锌、铜、铁、钙和锰元素缺乏状况相当严重总缺乏率占８９．９％。     

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.