Ionic and molecular transport in aqueous solution through 2D and layered nanoporous membranes

Abstract Two-dimensional (2D) materials provide an intriguing means to not only study physical phenomena but also serve as disruptive membranes for ionic selectivity and sensing based applications. Atomic thinness of these materials affords a unique environment in an all-surface material to unlock challenges towards improving desalination, energy harvesting and DNA sensing. This review provides an overview on some common 2D materials used in membrane applications for solving these challenges along with opportunities where 2D materials could add value to existing solutions. Following this, different types of 2D materials and structures are discussed with their relative advantages and disadvantages highlighted. Fabrication and methods of creating pores within 2D membranes are then presented with a focus on altering surface characteristics. Selected works within the field are highlighted and placed into a wider context, comparing their merits and shortfalls. A discussion of state-of-the-art performance for ionic transport, molecular sensing and power generation is then presented. This review concludes with an outlook on emerging methods and discussing exciting future directions.</jats:p

Gene therapy restores vision in rd1 mice after removal of a confounding mutation in Gpr179

The rd1 mouse with a mutation in the Pde6b gene was the first strain of mice identified with a retinal degeneration. However, AAV-mediated gene supplementation of rd1 mice only results in structural preservation of photoreceptors, and restoration of the photoreceptor-mediated a-wave, but not in restoration of the bipolar cell-mediated b-wave. Here we show that a mutation in Gpr179 prevents the full restoration of vision in rd1 mice. Backcrossing rd1 with C57BL6 mice reveals the complete lack of b-wave in a subset of mice, consistent with an autosomal recessive Mendelian inheritance pattern. We identify a mutation in the Gpr179 gene, which encodes for a G-protein coupled receptor localized to the dendrites of ON-bipolar cells. Gene replacement in rd1 mice that are devoid of the mutation in Gpr179 successfully restores the function of both photoreceptors and bipolar cells, which is maintained for up to 13 months. Our discovery may explain the failure of previous gene therapy attempts in rd1 mice, and we propose that Grp179 mutation status should be taken into account in future studies involving rd1 mice

Phytochemical and comparative antidiabetic studies of leaf extracts of Viscum album from different plant hosts

Phytochemical screening and evaluation of antidiabetic activity of leaf extracts of Viscum album from four different plant hosts were carried out using standard procedures. The results of the phytochemical screening revealed that the different leaf extracts vary in their phytochemical constituents depending on the plant host. Moreso, all the leaf extracts of Viscum album demonstrated significant (p&lt;0.001) lowering of blood glucose level (BGL) in alloxan-induced diabetic rats. The leaf extract of V. album from Dennettia tripetala exhibited the highest antidiabetic activity than the other extracts followed by Citrus sinensis and Pisium guajava and their activities were more pronounced than that of standard drug, glibenclamide during acute study. On prolonged treatment, Viscum album leaf extracts from C. sinensis (VAC ) and P. guajava (VAP) had comparably higher antidiabetic effects than the other extracts and glibenclamide. These were followed by that from Dacroydes edulis (VAD) while Dennettia tripetala (VADT) had the lowest antidiabetic effect. Although V. album possesses antidiabetic property, its antidiabetic efficacy depends on its phytochemical constituents which in turn depends on the plant host.Keywords: Mistletoe, Hyperglycemia, Alloxan, Glibenclamid

Quantification of fluoroquinolone uptake through the outer membrane channel OmpF of Escherichia coli

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.Decreased drug accumulation is a common cause of antibiotic resistance in microorganisms. However, there are few reliable general techniques capable of quantifying drug uptake through bacterial membranes. We present a semiquantitative optofluidic assay for studying the uptake of autofluorescent drug molecules in single liposomes. We studied the effect of the Escherichia coli outer membrane channel OmpF on the accumulation of the fluoroquinolone antibiotic, norfloxacin, in proteoliposomes. Measurements were performed at pH 5 and pH 7, corresponding to two different charge states of norfloxacin that bacteria are likely to encounter in the human gastrointestinal tract. At both pH values, the porins significantly enhance drug permeation across the proteoliposome membranes. At pH 5, where norfloxacin permeability across pure phospholipid membranes is low, the porins increase drug permeability by 50-fold on average. We estimate a flux of about 10 norfloxacin molecules per second per OmpF trimer in the presence of a 1 mM concentration gradient of norfloxacin. We also performed single channel electrophysiology measurements and found that the application of transmembrane voltages causes an electric field driven uptake in addition to concentration driven diffusion. We use our results to propose a physical mechanism for the pH mediated change in bacterial susceptibility to fluoroquinolone antibiotics.This work was supported by a European Research Council (ERC) Grant (261101 Passmembrane) to UFK. JC acknowledges support from an Internal Graduate Studentship, Trinity College, Cambridge, and a Research Studentship from the Cambridge Philosophical Society. SP was supported by the Leverhulme Trust through an Early Career Fellowship. TM acknowledges support from the Konrad-Adenauer Foundation and the German National Merit Foundation. HB, YB and MW are part of the TRANSLOCATION consortium and have received support from the Innovative Medicines Joint Undertaking under grant agreement 115525, the European Union’s seventh framework program (FP7/2007-2013), and European Federation of Pharmaceutical Industries and Associates companies in-kind contribution

A large geometric distortion in the first photointermediate of rhodopsin, determined by double-quantum solid-state NMR

Double-quantum magic-angle-spinning NMR experiments were performed on 11,12-C-13(2)-retinylidene-rhodopsin under illumination at low temperature, in order to characterize torsional angle changes at the C11-C12 photoisomerization site. The sample was illuminated in the NMR rotor at low temperature (similar to 120 K) in order to trap the primary photointermediate, bathorhodopsin. The NMR data are consistent with a strong torsional twist of the HCCH moiety at the isomerization site. Although the HCCH torsional twist was determined to be at least 40A degrees, it was not possible to quantify it more closely. The presence of a strong twist is in agreement with previous Raman observations. The energetic implications of this geometric distortion are discussed

Is physician assessment of alcohol consumption useful in predicting risk of severe liver disease among people with HIV and HIV/HCV co-infection?

Background Alcohol consumption is a known risk factor for liver disease in HIV-infected populations. Therefore, knowledge of alcohol consumption behaviour and risk of disease progression associated with hazardous drinking are important in the overall management of HIV disease. We aimed at assessing the usefulness of routine data collected on alcohol consumption in predicting risk of severe liver disease (SLD) among people living with HIV (PLWHIV) with or without hepatitis C infection seen for routine clinical care in Italy. Methods We included PLWHIV from two observational cohorts in Italy (ICONA and HepaICONA). Alcohol consumption was assessed by physician interview and categorized according to the National Institute for Food and Nutrition Italian guidelines into four categories: abstainer; moderate; hazardous and unknown. SLD was defined as presence of FIB4 > 3.25 or a clinical diagnosis of liver disease or liver-related death. Cox regression analysis was used to evaluate the association between level of alcohol consumption at baseline and risk of SLD. Results Among 9542 included PLWHIV the distribution of alcohol consumption categories was: abstainers 3422 (36%), moderate drinkers 2279 (23%), hazardous drinkers 637 (7%) and unknown 3204 (34%). Compared to moderate drinkers, hazardous drinking was associated with higher risk of SLD (adjusted hazard ratio, aHR = 1.45; 95% CI: 1.03–2.03). After additionally controlling for mode of HIV transmission, HCV infection and smoking, the association was attenuated (aHR = 1.32; 95% CI: 0.94–1.85). There was no evidence that the association was stronger when restricting to the HIV/HCV co-infected population. Conclusions Using a brief physician interview, we found evidence for an association between hazardous alcohol consumption and subsequent risk of SLD among PLWHIV, but this was not independent of HIV mode of transmission, HCV-infection and smoking. More efforts should be made to improve quality and validity of data on alcohol consumption in cohorts of HIV/HCV-infected individuals

Scanned Probe Oxidation onp-GaAs(100) Surface with an Atomic Force Microscopy

Locally anodic oxidation has been performed to fabricate the nanoscale oxide structures onp-GaAs(100) surface, by using an atomic force microscopy (AFM) with the conventional and carbon nanotube (CNT)-attached probes. The results can be utilized to fabricate the oxide nanodots under ambient conditions in noncontact mode. To investigate the conversion of GaAs to oxides, micro-Auger analysis was employed to analyze the chemical compositions. The growth kinetics and the associated mechanism of the oxide nanodots were studied under DC voltages. With the CNT-attached probe the initial growth rate of oxide nanodots is in the order of ~300 nm/s, which is ~15 times larger than that obtained by using the conventional one. The oxide nanodots cease to grow practically as the electric field strength is reduced to the threshold value of ~2 × 107 V cm−1. In addition, results indicate that the height of oxide nanodots is significantly enhanced with an AC voltage for both types of probes. The influence of the AC voltages on controlling the dynamics of the AFM-induced nanooxidation is discussed

Early life inter-kingdom interactions shape the immunological environment of the airways

Background: There is increasing evidence that the airway microbiome plays a key role in the establishment of respiratory health by interacting with the developing immune system early in life. While it has become clear that bacteria are involved in this process, there is a knowledge gap concerning the role of fungi. Moreover, the inter-kingdom interactions that influence immune development remain unknown. In this prospective exploratory human study, we aimed to determine early post-natal microbial and immunological features of the upper airways in 121 healthy newborns. Results: We found that the oropharynx and nasal cavity represent distinct ecological niches for bacteria and fungi. Breastfeeding correlated with changes in microbiota composition of oropharyngeal samples with the greatest impact upon the relative abundance of Streptococcus species and Candida. Host transcriptome profiling revealed that genes with the highest expression variation were immunological in nature. Multi-omics factor analysis of host and microbial data revealed unique co-variation patterns. Conclusion: These data provide evidence of a diverse multi-kingdom microbiota linked with local immunological characteristics in the first week of life that could represent distinct trajectories for future respiratory health

Selection for Replicases in Protocells

PMCID: PMC3649988This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited