A Versatile Electrochemical Batch Reactor for Synthetic Organic and Inorganic Transformations and Analytical Electrochemistry

A standardized and versatile electrochemical batch reactor that has wide applicability in both organic and inorganic synthesis and analytical electrochemistry has been developed. A variety of synthetic electrochemical transformations have been performed to showcase the versatility and demonstrate the reactor, including the synthesis of five Cu(I)–NHC complexes, two Au(I)–NHC complexes, and one Fe(II)–NHC complex as well as an Fe(III)–salen complex. The reactor is based on a commercially available vial with an adapted lid, making it inexpensive and highly flexible. It features a fixed interelectrode distance, which is crucial for reproducibility, along with the ability to accommodate a variety of interchangeable electrode materials. The reactor has also been used in conjunction with a parallel plate, allowing rapid screening and optimization of an organic electrochemical transformation. Cyclic voltammetry has been performed within the reactor on a range of imidazolium salt analytes with the use of an external potentiostat. The ability to use this reactor for both analytical and synthetic organic and inorganic chemistry is enabled by a flexible and characterizable design

Prevalence and causes of vision loss in sub-Saharan Africa in 2015: magnitude, temporal trends and projections

Background This study aimed to assess the prevalence and causes of vision loss in sub-Saharan Africa (SSA) in 2015, compared with prior years, and to estimate expected values for 2020. Methods A systematic review and meta-analysis assessed the prevalence of blindness (presenting distance visual acuity <3/60 in the better eye), moderate and severe vision impairment (MSVI; presenting distance visual acuity <6/18 but ≥3/60) and mild vision impairment (MVI; presenting distance visual acuity <6/12 and ≥6/18), and also near vision impairment (<N6 or N8 in the presence of ≥6/12 best-corrected distance visual acuity) in SSA for 1990, 2010, 2015 and 2020. In SSA, age-standardised prevalence of blindness, MSVI and MVI in 2015 were 1.03% (80% uncertainty interval (UI) 0.39–1.81), 3.64% (80% UI 1.71–5.94) and 2.94% (80% UI 1.05–5.34), respectively, for male and 1.08% (80% UI 0.40–1.93), 3.84% (80% UI 1.72–6.37) and 3.06% (80% UI 1.07–5.61) for females, constituting a significant decrease since 2010 for both genders. There were an estimated 4.28 million blind individuals and 17.36 million individuals with MSVI; 101.08 million individuals were estimated to have near vision loss due to presbyopia. Cataract was the most common cause of blindness (40.1%), whereas undercorrected refractive error (URE) (48.5%) was the most common cause of MSVI. Sub-Saharan West Africa had the highest proportion of blindness compared with the other SSA subregions. Conclusions Cataract and URE, two of the major causes of blindness and vision impairment, are reversible with treatment and thus promising targets to alleviate vision impairment in SSA

Molecular Modeling Study for Interaction between Bacillus subtilis Obg and Nucleotides

The bacterial Obg proteins (Spo0B-associated GTP-binding protein) belong to the subfamily of P-loop GTPase proteins that contain two equally and highly conserved domains, a C-terminal GTP binding domain and an N-terminal glycine-rich domain which is referred as the “Obg fold” and now it is considered as one of the new targets for antibacterial drug. When the Obg protein is associated with GTP, it becomes activated, because conformation of Obg fold changes due to the structural changes of GTPase switch elements in GTP binding site. In order to investigate the effects and structural changes in GTP bound to Obg and GTPase switch elements for activation, four different molecular dynamics (MD) simulations were performed with/without the three different nucleotides (GTP, GDP, and GDP + Pi) using the Bacillus subtilis Obg (BsObg) structure. The protein structures generated from the four different systems were compared using their representative structures. The pattern of Cα-Cα distance plot and angle between the two Obg fold domains of simulated apo form and each system (GTP, GDP, and GDP+Pi) were significantly different in the GTP-bound system from the others. The switch 2 element was significantly changed in GTP-bound system. Also root-mean-square fluctuation (RMSF) analysis revealed that the flexibility of the switch 2 element region was much higher than the others. This was caused by the characteristic binding mode of the nucleotides. When GTP was bound to Obg, its γ-phosphate oxygen was found to interact with the key residue (D212) of the switch 2 element, on the contrary there was no such interaction found in other systems. Based on the results, we were able to predict the possible binding conformation of the activated form of Obg with L13, which is essential for the assembly with ribosome

The Goldbeter-Koshland switch in the first-order region and its response to dynamic disorder

In their classical work (Proc. Natl. Acad. Sci. USA, 1981, 78:6840-6844), Goldbeter and Koshland mathematically analyzed a reversible covalent modification system which is highly sensitive to the concentration of effectors. Its signal-response curve appears sigmoidal, constituting a biochemical switch. However, the switch behavior only emerges in the "zero-order region", i.e. when the signal molecule concentration is much lower than that of the substrate it modifies. In this work we showed that the switching behavior can also occur under comparable concentrations of signals and substrates, provided that the signal molecules catalyze the modification reaction in cooperation. We also studied the effect of dynamic disorders on the proposed biochemical switch, in which the enzymatic reaction rates, instead of constant, appear as stochastic functions of time. We showed that the system is robust to dynamic disorder at bulk concentration. But if the dynamic disorder is quasi-static, large fluctuations of the switch response behavior may be observed at low concentrations. Such fluctuation is relevant to many biological functions. It can be reduced by either increasing the conformation interconversion rate of the protein, or correlating the enzymatic reaction rates in the network.Comment: 23 pages, 4 figures, accepted by PLOS ON

SILAC-based proteomic quantification of chemoattractant-induced cytoskeleton dynamics on a second to minute timescale

Cytoskeletal dynamics during cell behaviours ranging from endocytosis and exocytosis to cell division and movement is controlled by a complex network of signalling pathways, the full details of which are as yet unresolved. Here we show that SILAC-based proteomic methods can be used to characterize the rapid chemoattractant-induced dynamic changes in the actin–myosin cytoskeleton and regulatory elements on a proteome-wide scale with a second to minute timescale resolution. This approach provides novel insights in the ensemble kinetics of key cytoskeletal constituents and association of known and novel identified binding proteins. We validate the proteomic data by detailed microscopy-based analysis of in vivo translocation dynamics for key signalling factors. This rapid large-scale proteomic approach may be applied to other situations where highly dynamic changes in complex cellular compartments are expected to play a key role

Systematic review and stratified meta-analysis of the efficacy of RhoA and Rho kinase inhibitors in animal models of ischaemic stroke

There is currently only one clinically approved drug, tissue plasminogen activator (tPA), for the treatment of acute ischaemic stroke. The RhoA pathway, including RhoA and its downstream effector Rho kinase (ROCK), has been identified as a possible therapeutic target. Our aim was to assess the impact of study design characteristics and study quality on reported measures of efficacy and to assess for the presence and impact of publication bias. We conducted a systematic review and meta-analysis on publications describing the efficacy of RhoA and ROCK inhibitors in animal models of focal cerebral ischaemia where outcome was assessed as a change in lesion size or neurobehavioural score, or both. We identified 25 published papers which met our inclusion criteria. RhoA and ROCK inhibitors reduced lesion size by 37.3% in models of focal cerebral ischaemia (95% CI, 28.6% to 46.0%, 41 comparisons), and reduced neurobehavioural data by 40.5% (33.4% to 47.7%, 30 comparisons). Overall study quality was low (median=4, interquartile range 3-5) and measures to reduce bias were seldom reported. Publication bias was prevalent and associated with a substantial overstatement of efficacy for lesion size. RhoA and ROCK inhibitors appear to be effective in animal models of stroke. However the low quality score, publication bias and limited number of studies are areas which need attention prior to conducting clinical trials

Prevalence and causes of blindness and vision impairment: magnitude, temporal trends and projections in South and Central Asia

BACKGROUND: To assess prevalence and causes of vision loss in Central and South Asia. METHODS: A systematic review of medical literature assessed the prevalence of blindness (presenting visual acuity<3/60 in the better eye), moderate and severe vision impairment (MSVI; presenting visual acuity <6/18 but ≥3/60) and mild vision impairment (MVI; presenting visual acuity <6/12 and ≥6/18) in Central and South Asia for 1990, 2010, 2015 and 2020. RESULTS: In Central and South Asia combined, age-standardised prevalences of blindness, MSVI and MVI in 2015 were for men and women aged 50+years, 3.72% (80% uncertainty interval (UI): 1.39-6.75) and 4.00% (80% UI: 1.41-7.39), 16.33% (80% UI: 8.55-25.47) and 17.65% (80% UI: 9.00-27.62), 11.70% (80% UI: 4.70-20.32) and 12.25% (80% UI:4.86-21.30), respectively, with a significant decrease in the study period for both gender. In South Asia in 2015, 11.76 million individuals (32.65% of the global blindness figure) were blind and 61.19 million individuals (28.3% of the global total) had MSVI. From 1990 to 2015, cataract (accounting for 36.58% of all cases with blindness in 2015) was the most common cause of blindness, followed by undercorrected refractive error (36.43%), glaucoma (5.81%), age-related macular degeneration (2.44%), corneal diseases (2.43%), diabetic retinopathy (0.16%) and trachoma (0.04%). For MSVI in South Asia 2015, most common causes were undercorrected refractive error (accounting for 66.39% of all cases with MSVI), followed by cataract (23.62%), age-related macular degeneration (1.31%) and glaucoma (1.09%). CONCLUSIONS: One-third of the global blind resided in South Asia in 2015, although the age-standardised prevalence of blindness and MSVI decreased significantly between 1990 and 2015

Prevalence and causes of vision loss in East Asia in 2015: magnitude, temporal trends and projections

BACKGROUND: To determine the prevalence and causes of blindness and vision impairment (VI) in East Asia in 2015 and to forecast the trend to 2020. METHODS: Through a systematic literature review and meta-analysis, we estimated prevalence of blindness (presenting visual acuity <3/60 in the better eye), moderate-to-severe vision impairment (MSVI; 3/60≤presenting visual acuity <6/18), mild vision impairment (mild VI: 6/18≤presenting visual acuity <6/12) and uncorrected presbyopia for 1990, 2010, 2015 and 2020. A total of 44 population-based studies were included. RESULTS: In 2015, age-standardised prevalence of blindness, MSVI, mild VI and uncorrected presbyopia was 0.37% (80% uncertainty interval (UI) 0.12%-0.68%), 3.06% (80% UI 1.35%-5.16%) and 2.65% (80% UI 0.92%-4.91%), 32.91% (80% UI 18.72%-48.47%), respectively, in East Asia. Cataract was the leading cause of blindness (43.6%), followed by uncorrected refractive error (12.9%), glaucoma, age-related macular degeneration, corneal diseases, trachoma and diabetic retinopathy (DR). The leading cause for MSVI was uncorrected refractive error, followed by cataract, age-related macular degeneration, glaucoma, corneal disease, trachoma and DR. The burden of VI due to uncorrected refractive error, cataracts, glaucoma and DR has continued to rise over the decades reported. CONCLUSIONS: Addressing the public healthcare barriers for cataract and uncorrected refractive error can help eliminate almost 57% of all blindness cases in this region. Therefore, public healthcare efforts should be focused on effective screening and effective patient education, with access to high-quality healthcare