Development of earth-abundant metal catalysts for carbon-boron and carbon-carbon bond forming reactions

We have developed a Markovnikov-selective cobalt-catalysed hydroboration of alkenes with pinacolborane at ambient temperature, using a bench-stable bipyridyl-oxazoline catalyst tBuBPOCoCl2 and NaOtBu as the in situ activator. This strategy has been applied to a variety of electronically and sterically differentiated styrene derivatives, bearing a range of functional groups, to give the secondary boronic esters in both high yield and regioselectivity. We have developed a manganese-catalysed homo-coupling of aryl-, alkenyl- and heterocyclic boronic acids across a range of electronically and sterically differentiated coupling partners. This mild and operationally simple coupling reaction uses commercially available and inexpensive manganese(III) acetylacetonate, ethanol as the solvent, and air as the terminal oxidant. This represents the first-stage in developing a new manganese-catalysed cross-coupling reaction for the synthesis biaryl compounds

Open structure and gating of the Arabidopsis mechanosensitive ion channel MSL10

Plants are challenged by drastically different osmotic environments during growth and development. Adaptation to these environments often involves mechanosensitive ion channels that can detect and respond to mechanical force. In the model plant Arabidopsis thaliana, the mechanosensitive channel MSL10 plays a crucial role in hypo-osmotic shock adaptation and programmed cell death induction, but the molecular basis of channel function remains poorly understood. Here, we report a structural and electrophysiological analysis of MSL10. The cryo-electron microscopy structures reveal a distinct heptameric channel assembly. Structures of the wild-type channel in detergent and lipid environments, and in the absence of membrane tension, capture an open conformation. Furthermore, structural analysis of a non-conductive mutant channel demonstrates that reorientation of phenylalanine side chains alone, without main chain rearrangements, may generate the hydrophobic gate. Together, these results reveal a distinct gating mechanism and advance our understanding of mechanotransduction

Predicting Aesthetic Score Distribution through Cumulative Jensen-Shannon Divergence

Aesthetic quality prediction is a challenging task in the computer vision community because of the complex interplay with semantic contents and photographic technologies. Recent studies on the powerful deep learning based aesthetic quality assessment usually use a binary high-low label or a numerical score to represent the aesthetic quality. However the scalar representation cannot describe well the underlying varieties of the human perception of aesthetics. In this work, we propose to predict the aesthetic score distribution (i.e., a score distribution vector of the ordinal basic human ratings) using Deep Convolutional Neural Network (DCNN). Conventional DCNNs which aim to minimize the difference between the predicted scalar numbers or vectors and the ground truth cannot be directly used for the ordinal basic rating distribution. Thus, a novel CNN based on the Cumulative distribution with Jensen-Shannon divergence (CJS-CNN) is presented to predict the aesthetic score distribution of human ratings, with a new reliability-sensitive learning method based on the kurtosis of the score distribution, which eliminates the requirement of the original full data of human ratings (without normalization). Experimental results on large scale aesthetic dataset demonstrate the effectiveness of our introduced CJS-CNN in this task.Comment: AAAI Conference on Artificial Intelligence (AAAI), New Orleans, Louisiana, USA. 2-7 Feb. 201

Cobalt-catalysed Markovnikov selective hydroboration of vinylarenes

A bipyridiyl-oxazoline cobalt catalyst tBuBPOCoCl2 has been developed for the Markovnikov selective hydroboration of alkenes using pinacolborane and NaOtBu as the in situ activator with up to >98 : 2 branched : linear selectivity (24 examples, 45-92% isolated yield)

Inhibition of epidermal growth factor receptor attenuates atherosclerosis via decreasing inflammation and oxidative stress

Atherosclerosis is a progressive disease leading to loss of vascular homeostasis and entails fibrosis, macrophage foam cell formation, and smooth muscle cell proliferation. Recent studies have reported that epidermal growth factor receptor (EGFR) is involved vascular pathophysiology and in the regulation of oxidative stress in macrophages. Although, oxidative stress and inflammation play a critical role in the development of atherosclerosis, the underlying mechanisms are complex and not completely understood. In the present study, we have elucidated the role of EGFR in high-fat diet-induced atherosclerosis in apolipoprotein E null mice. We show increased EGFR phosphorylation and activity in atherosclerotic lesion development. EGFR inhibition prevented oxidative stress, macrophage infiltration, induction of pro-inflammatory cytokines, and SMC proliferation within the lesions. We further show that EGFR is activated through toll-like receptor 4. Disruption of toll-like receptor 4 or the EGFR pathway led to reduced inflammatory activity and foam cell formation. These studies provide evidence that EGFR plays a key role on the pathogenesis of atherosclerosis, and suggests that EGFR may be a potential therapeutic target in the prevention of atherosclerosis development

Structural mechanism for gating of a eukaryotic mechanosensitive channel of small conductance

Mechanosensitive ion channels transduce physical force into electrochemical signaling that underlies an array of fundamental physiological processes, including hearing, touch, proprioception, osmoregulation, and morphogenesis. The mechanosensitive channels of small conductance (MscS) constitute a remarkably diverse superfamily of channels critical for management of osmotic pressure. Here, we present cryo-electron microscopy structures of a MscS homolog from Arabidopsis thaliana, MSL1, presumably in both the closed and open states. The heptameric MSL1 channel contains an unusual bowl-shaped transmembrane region, which is reminiscent of the evolutionarily and architecturally unrelated mechanosensitive Piezo channels. Upon channel opening, the curved transmembrane domain of MSL1 flattens and expands. Our structures, in combination with functional analyses, delineate a structural mechanism by which mechanosensitive channels open under increased membrane tension. Further, the shared structural feature between unrelated channels suggests the possibility of a unified mechanical gating mechanism stemming from membrane deformation induced by a non-planar transmembrane domain

Ligand and G-protein selectivity in the κ-opioid receptor

The κ-opioid receptor (KOR) represents a highly desirable therapeutic target for treating not only pain but also addiction and affective disorder