Deciphering the Mechanism of On-Surface Dehydrogenative C-C Coupling Reactions.

On-surface synthesis has proven to be a powerful approach for fabricating various low-dimensional covalent nanostructures with atomic precision that could be challenging for conventional solution chemistry. Dehydrogenative Caryl-Caryl coupling is one of the most popular on-surface reactions, of which the mechanisms, however, have not been well understood due to the lack of microscopic insights into the intermediates that are fleetingly existing under harsh reaction conditions. Here, we bypass the most energy-demanding initiation step to generate and capture some of the intermediates at room temperature (RT) via the cyclodehydrobromination of 1-bromo-8-phenylnaphthalene on a Cu(111) surface. Bond-level scanning probe imaging and manipulation in combination with DFT calculations allow for the identification of chemisorbed radicals, cyclized intermediates, and dehydrogenated products. These intermediates correspond to three main reaction steps, namely, debromination, cyclization (radical addition), and H elimination. H elimination is the rate-determining step as evidenced by the predominant cyclized intermediates. Furthermore, we reveal a long-overlooked pathway of dehydrogenation, namely, atomic hydrogen-catalyzed H shift and elimination, based on the observation of intermediates for H shift and superhydrogenation and the proof of a self-amplifying effect of the reaction. This pathway is further corroborated by comprehensive theoretical analysis on the reaction thermodynamics and kinetics.

Photoinduced Amyloid Fibril Degradation for Controlled Cell Patterning.

Amyloid-like fibrils are a special class of self-assembling peptides that emerge as a promising nanomaterial with rich bioactivity for applications such as cell adhesion and growth. Unlike the extracellular matrix, the intrinsically stable amyloid-like fibrils do not respond nor adapt to stimuli of their natural environment. Here, a self-assembling motif (CKFKFQF), in which a photosensitive o-nitrobenzyl linker (PCL) is inserted, is designed. This peptide (CKFK-PCL-FQF) assembles into amyloid-like fibrils comparable to the unsubstituted CKFKFQF and reveals a strong response to UV-light. After UV irradiation, the secondary structure of the fibrils, fibril morphology, and bioactivity are lost. Thus, coating surfaces with the pre-formed fibrils and exposing them to UV-light through a photomask generate well-defined areas with patterns of intact and destroyed fibrillar morphology. The unexposed, fibril-coated surface areas retain their ability to support cell adhesion in culture, in contrast to the light-exposed regions, where the cell-supportive fibril morphology is destroyed. Consequently, the photoresponsive peptide nanofibrils provide a facile and efficient way of cell patterning, exemplarily demonstrated for A549, Chinese Hamster Ovary, and Raw Dual type cells. This study introduces photoresponsive amyloid-like fibrils as adaptive functional materials to precisely arrange cells on surfaces.

Targeted therapy of cognitive deficits in fragile X syndrome.

Breaking an impasse in finding mechanism-based therapies of neuropsychiatric disorders requires a strategic shift towards alleviating individual symptoms. Here we present a symptom and circuit-specific approach to rescue deficits of reward learning in Fmr1 knockout mice, a model of Fragile X syndrome (FXS), the most common monogenetic cause of inherited mental disability and autism. We use high-throughput, ecologically-relevant automated tests of cognition and social behavior to assess effectiveness of the circuit-targeted injections of designer nanoparticles, loaded with TIMP metalloproteinase inhibitor 1 protein (TIMP-1). Further, to investigate the impact of our therapeutic strategy on neuronal plasticity we perform long-term potentiation recordings and high-resolution electron microscopy. We show that central amygdala-targeted delivery of TIMP-1 designer nanoparticles reverses impaired cognition in Fmr1 knockouts, while having no impact on deficits of social behavior, hence corroborating symptom-specificity of the proposed approach. Moreover, we elucidate the neural correlates of the highly specific behavioral rescue by showing that the applied therapeutic intervention restores functional synaptic plasticity and ultrastructure of neurons in the central amygdala. Thus, we present a targeted, symptom-specific and mechanism-based strategy to remedy cognitive deficits in Fragile X syndrome.

Adsorption of gas-phase elemental mercury by sulphonitrided steel sheet. Effect of hydrogen treatment.

Coal combustion, which is one of the most important energy sources of electricity generation, produces airborne pollutants: NOx, CO2, SO2, particulates and Hg°. A range of technologies is being developed to reduce the environmental impact of coal-fired power stations. No optimal technology that can be broadly applied exists as yet, but sorption of mercury is considered a promising approach. We report a novel adsorbent, which shows an extraordinary mechanical resistance and high adsorption capacity of mercury vapour. These adsorbent samples were synthesized in the gas sulphonitriding process using steel sheets. The chemisorption capacity of the sorbent materials, the process of the thermal desorption of mercury and the effect of the hydrogen activation treatment have been investigated in the work. It has been established that the capacity of mercury chemisorption increased more than twice after the heating treatment of the adsorbent in H2 atmosphere at 500 °C in comparison with the non-activated one. The mechanism of activation has been elucidated in the paper. For the purpose of comparison, activated carbon was also investigated.

A clarification for the subgenera of Paramacrobiotus Guidetti, Schill, Bertolani, Dandekar and Wolf, 2009, with respect to the International Code of Zoological Nomenclature.

The recent re-description of Paramacrobiotus Guidetti, Schill, Bertolani, Dandekar and Wolf, 2009 has inadvertently led to the description of an objective synonym within its subgenera nominal taxa. To resolve this issue, we have re-described both subgenera, and proposed a new substitute name for one subgenus, in line with the International Code of Zoological Nomenclature. Additionally we have confirmed the placement of two recently published Paramacrobiotus species, not included in the last revision, within the respective subgenera established herein.

Phase imaging quality improvement by modification of AFM probes' cantilever.

Imaging of the surface of materials by atomic force microscopy under tapping and phase imaging mode, with use of modified probes is addressed. In this study, the circularly shaped holes located in varying distance from the probe base, were cut out by focused ion beam. Such modification was a consequence of the results of the previous experiments (probe tip sharpening and cantilever thinning) where significant improvement of image quality in tapping and phase imaging mode has been revealed. The solution proposed herein gives similar results, but is much simpler from the technological point of view. Shorter exposition time of the tip onto gallium ions during FIB processing allows to reduce material degradation. The aim of this modification was to change harmonic oscillators' properties in the simplest and fastest way, to obtain stronger signal for higher resonant frequencies, which can be advantageous for improving the quality of imaging in PI mode. Probes shaped in that way were used for AFM investigations with Bruker AFM nanoscope 8. As a testing material, titanium roughness standard sample, supplied by Bruker, was used. The results have shown that the modifications performed within these studies influence the oscillation of the probes, which in some cases may result in deterioration of the imaging quality under tapping mode for one or both self-resonant frequencies. However, phase imaging results obtained using modified probes are of higher quality. The numerical simulations performed by application of finite element method were used to explain the results obtained experimentally. Phenomenon described within this study allows to apply developed modelling methodology for prediction of effects of various modifications on the probes' tip, and as a result, to predict how proposed modifications will affect AFM imaging quality.

Do urban and rural residents living in Poland differ in their ways of coping with chronic diseases?

OBJECTIVE: Chronic disease is a critical life event which demands significant psychological adjustment. Coping strategies and resources such as sense of coherence, self-efficacy, etc. remain factors affecting stress response. PATIENTS AND METHODS: The examined group included patients with ischemic heart disease (n = 134), type 1 diabetes mellitus (n = 109) or rheumatoid arthritis (n = 92). 159 patients came from urban area whereas 176 came from rural setting. All patients filled up inventories of life satisfaction, severity of depression, coping strategies, self-efficacy, social support and sense of coherence. RESULTS: The analysis showed that patients from rural areas had higher levels of well-being, i.e., were characterized by lower severity of depression. The predictors of satisfaction with life included two types of resources i.e. self-efficacy, social support and two coping strategies i.e. turning to religion and self-distraction (R2 = 0.39; F = 26.87**). Life satisfaction was determined by social support, sense of coherence and positive reappraisal (R2 = 0.36; F = 29.11**). CONCLUSIONS: Rural/urban differences in the use of coping strategies may be associated with environmental or lifestyle differences. Patients with IHD, T1D or RA in Polish rural areas are high risk for depression so they may need help in finding systematic contact with specialists of healthcare.

Not all water mazes are created equal: cyclin D2 knockout mice with constitutively suppressed adult hippocampal neurogenesis do show specific spatial learning deficits.

Studies using the Morris water maze to assess hippocampal function in animals, in which adult hippocampal neurogenesis had been suppressed, have yielded seemingly contradictory results. Cyclin D2 knockout (Ccnd2(-/-)) mice, for example, have constitutively suppressed adult hippocampal neurogenesis but had no overt phenotype in the water maze. In other paradigms, however, ablation of adult neurogenesis was associated with specific deficits in the water maze. Therefore, we hypothesized that the neurogenesis-related phenotype might also become detectable in Ccnd2(-/-) mice, if we used the exact setup and protocol that in our previous study had revealed deficits in mice with suppressed adult neurogenesis. Ccnd2(-/-) mice indeed learned the task and developed a normal preference for the goal quadrant, but were significantly less precise for the exact goal position and were slower in acquiring efficient and spatially more precise search strategies. Upon goal reversal (when the hidden platform was moved to a new position) Ccnd2(-/-) mice showed increased perseverance at the former platform location, implying that they were less flexible in updating the previously learned information. Both with respect to adult neurogenesis and behavioral performance, Ccnd2(+/-) mice ranged between wild types and knockouts. Importantly, hippocampus-dependent learning was not generally impaired by the mutation, but specifically functional aspects relying on precise and flexible encoding were affected. Whether ablation of adult neurogenesis causes a specific behavioral phenotype thus also depends on the actual task demands. The test parameters appear to be important variables influencing whether a task can pick up a contribution of adult neurogenesis to test performance.

1H, 13C and 15N NMR data for indolo[2,3-b]quinolines, a novel potent anticancer drug family.

The complete NMR signal assignment of title compounds were carried out by extensive use of 1D and 2D NMR techniques (1H, 13C, COSY, HSQC and HMBC).

Refined preparation of 1alpha,3-dipyrrolidino-androsta-3,5-diene-17-one, a key intermediate in the exemestane synthesis.

A significant improvement of the patent route for exemestane synthesis has been achieved. The key intermediate 1alpha,3-dipyrrolidino-androsta-3,5-diene-17-one (7) was obtained in a good yield and effectively used without further isolation in the next reaction step. The original analytical method for the identification and quantification of the substrate androsta-1,4-diene-3,17-dione (ADD, 6), intermediate 7 and 1-pyrrolidinoandrosta-1,3,5-triene-17-one (9) impurity in the reaction mixture was applied. Due to the newly developed process, the economical synthesis of the final pharmaceutical product in a large scale was possible. In addition, the complete NMR characteristics of 7 was described for the first time. The experiments were also analyzed with the theoretical quantum mechanical density functional B3LYP calculations for the energy outputs in model reactions. Based on these studies hypothetical routes of key intermediate (7) formation have been suggested. These predictions were consistent with the solutions of kinetic equations fitted to the experimental curves for time-dependence of three components of the reaction mixture.