The impact of ionic liquids on amyloid fibrilization of AB16-22 : tuning the rate of fibrilization using a reverse Hofmeister strategy

We have shown that the amyloid fibrilization of A&szlig;16-22 follows a reverse hofmeister trend in pILs. Fast fibrilization rates of seconds can be achieved.<br /

Increased hydrolysis by Thermomyces lanuginosus lipase for omega-3 fatty acids in the presence of a protic ionic liquid

We report that the hydrolytic performance of Thermomyces lanuginosus lipase, TLL, and its selectivity towards concentrating clinically important omega 3 fatty acids was increased by the addition of a protic ionic liquid, pIL, Triethylammonium mesylate, TeaMs. We show that TeaMs has a structure altering effect on TLL, changing both the secondary and tertiary structure of TLL. The thermal activity of TLL was also significantly enhanced by the addition of TeaMs.<br /

Sustainability in the biopharmaceutical industry: seeking a holistic perspective

Biopharmaceuticals manufacturing is a critical component of the modern healthcare system, with emerging new treatments composed of increasingly complex biomolecules offering solutions to chronic and debilitating disorders. While this sector continues to grow, it strongly exhibits “boom-to-bust” performance which threatens its long-term viability. Future trends within the industry indicate a shift towards continuous production systems using single use technologies that raises sustainability issues, yet research in this area is sparse and lacks consideration of the complex interactions between environmental, social and economic concerns. The authors outline a sustainability-focused vision and propose opportunities for research to aid the development of a more integrated approach that would enhance the sustainability of the industry

Mechanistic studies on the uptake and intracellular trafficking of novel cyclodextrin transfection complexes by intestinal epithelial cells

Oral delivery of gene therapeutics would facilitate treatment of local intestinal disease, including colon cancer and inflammatory bowel disease, thus avoiding invasive surgery. The aims of this study were to investigate; if the orientation of the lipid tail on the cyclodextrin (CD) influenced the efficacy of a novel poly-6-cationic amphiphilic CD to transfect intestinal enterocytes; the endocytotic uptake pathway(s), and, the intracellular trafficking of the CD.DNA complexes. Inhibitors of clathrin- and caveolae- mediated endocytosis and macropinocytosis were used to determine the mechanism(s) of CD.DNA uptake by both undifferentiated and differentiated Caco-2 cells. Cell surface heparan sulphate proteoglycans were involved in the association of CD.DNA complexes with undifferentiated Caco-2 cells. Complexation of pDNA with CD facilitated significant levels of pDNA uptake and gene expression (comparable to PEI) in both undifferentiated and differentiated Caco-2 cells. Disruption of intracellular vesicular trafficking reduced transfection activity. CD was also capable of transfecting the more physiologically relevant differentiated Caco-2 model. Macropinocytosis was responsible for the uptake of CD.DNA transfection complexes by both undifferentiated and differentiated Caco-2 cells. The ability of this novel CD to transfect differentiated intestinal cells indicates the potential of this vector for oral gene delivery

pH-Dependent Silica Nanoparticle Dissolution and 1 Cargo Release

The dissolution of microporous silica nanoparticles (NP) in aqueous environments of different biologically relevant pH was studied in order to assess their potential as drug delivery vehicles. Silica NPs, loaded with fluorescein, were prepared using different organosilane precursors (tetraethoxysilane, ethyl triethoxysilane or a 1:1 molar ratio of both) and NP dissolution was evaluated in aqueous conditions at pH 4, pH 6 and pH 7.4. These conditions correspond to the acidity of the intracellular environment (late endosome, early endosome, cytosol respectively) and gastrointestinal tract (‘fed’ stomach, duodenum and jejunum respectively). All NPs degraded at pH 6 and pH 7.4, while no dissolution was observed at pH 4. NP dissolution could be clearly visualised as mesoporous hollows and surface defects using electron microscopy, and was supported by UV–vis, fluorimetry and DLS data. The dissolution profiles of the NPs are particularly suited to the requirements of oral drug delivery, whereby NPs must resist degradation in the harsh acidic conditions of the stomach (pH 4), but dissolve and release their cargo in the small intestine (pH 6–7.4). Particle cores made solely of ethyl triethoxysilane exhibited a ‘burst release’ of encapsulated fluorescein at pH 6 and pH 7.4, whereas NPs synthesised with tetraethoxysilane released fluorescein in a more sustained fashion. Thus, by varying the organosilane precursor used in NP formation, it is possible to modify particle dissolution rates and tune the release profile of encapsulated fluorescein. The flexible synthesis afforded by silica NPs to achieve pH-responsive dissolution therefore makes this class of nanomaterial an adaptable platform that may be well suited to oral delivery applications

Crater population and resurfacing of the Martian north polar layered deposits

Present-day accumulation in the north polar layered deposits (NPLD) is thought to occur via deposition on the north polar residual cap. Understanding current mass balance in relation to current climate would provide insight into the climatic record of the NPLD. To constrain processes and rates of NPLD resurfacing, a search for craters was conducted using images from the Mars Reconnaissance Orbiter Context Camera. One hundred thirty craters have been identified on the NPLD, 95 of which are located within a region defined to represent recent accumulation. High Resolution Imaging Science Experiment images of craters in this region reveal a morphological sequence of crater degradation that provides a qualitative understanding of processes involved in crater removal. A classification system for these craters was developed based on the amount of apparent degradation and infilling and where possible depth/diameter ratios were determined. The temporal and spatial distribution of crater degradation is interpreted to be close to uniform. Through comparison of the size-frequency distribution of these craters with the expected production function, the craters are interpreted to be an equilibrium population with a crater of diameter D meters having a lifetime of ~30.75D^(1.14) years. Accumulation rates within these craters are estimated at 7.2D^(−0.14) mm/yr, which corresponds to values of ~3–4 mm/yr and are much higher than rates thought to apply to the surrounding flat terrain. The current crater population is estimated to have accumulated in the last ~20 kyr or less

The formation of gullies on Mars today

A decade of high-resolution monitoring has revealed extensive activity in fresh Martian gullies. Flows within the gullies are diverse: they can be relatively light, neutral or dark, colourful or bland, and range from superficial deposits to 10 m-scale topographic changes. We observed erosion and transport of material within gullies, new terraces, freshly eroded channel segments, migrating sinuous curves, channel abandonment, and lobate deposits. We also observed early stages of gully initiation, demonstrating that these processes are not merely modifying pre-existing land-forms. The timing of activity closely correlates with the presence of seasonal CO2 frost, so the current changes must be part of ongoing gully formation that is driven largely by its presence. We suggest that the cumulative effect of many flows erodes alcoves and channels, and builds lobate aprons, with no involvement of liquid water. Instead, flows may be fluidized by sublimation of entrained CO2 ice or other mechanisms. The frequent activity is likely to have erased any features dating from high-obliquity periods, so fresh gully geomorphology at middle and high latitudes is not evidence for past liquid water. CO2 ice-driven processes may have been important throughout Martian geological history and their deposits could exist in the rock record, perhaps resembling debris-flow sediments.Mars Data Analysis Program [NNH13AV85I]; Mars Reconnaissance Orbiter HiRISE project12 month embargo; published 27 November 2017This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Plane of nutrition before and after 6 months of age in Holstein-Friesian bulls: II. Effects on metabolic and reproductive endocrinology and identification of physiological markers of puberty and sexual maturation

peer-reviewedThe aim of this study was (1) to examine the effect of plane of nutrition during the first and second 6 mo of life on systemic concentrations of reproductive hormones and metabolites in Holstein-Friesian dairy bulls, and (2) to establish relationships with age at puberty and postpubertal semen production potential. Holstein-Friesian bull calves (n = 83) with a mean (standard deviation) age and body weight of 17 (4.4) d and 52 (6.2) kg, respectively, were assigned to a high or low plane of nutrition for the first 6 mo of life. At 24 wk of age, bulls were reassigned, within treatment, either to remain on the same diet or to switch to the opposite diet until puberty, resulting in 4 treatment groups: high-high, high-low, low-low, and low-high. Monthly blood samples were analyzed for metabolites (albumin, urea, total protein, β-hydroxybutyrate, glucose, nonesterified fatty acid, triglycerides and creatinine), insulin, insulin-like growth factor-1, leptin, adiponectin, FSH, and testosterone. A GnRH challenge was carried out at 16 and 32 wk of age (n = 9 bulls per treatment). Blood was collected at 15-min intervals for 165 min, with GnRH administered (0.05 mg/kg of body weight, i.v.) immediately after the third blood sample. Blood samples were subsequently analyzed for LH, FSH, and testosterone. Stepwise regression was used to detect growth and blood measurements to identify putative predictors of age at puberty and subsequent semen quality traits. Metabolic hormones and metabolites, in general, reflected metabolic status of bulls. Although FSH was unaffected by diet, it decreased with age both in monthly samples and following GnRH administration. Testosterone was greater in bulls on the high diet before and after 6 mo of age. Testosterone concentrations increased dramatically after 6 mo of age. Luteinizing hormone was unaffected by diet following GnRH administration but basal serum LH was greater in bulls on a high diet before 6 mo of age. In conclusion, the plane of nutrition offered before 6 mo of age influenced metabolic profiles, which are important for promoting GnRH pulsatility, in young bull