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508 result(s) for "Montgomery, Jonathan"
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Biochar and compost effects on soil microbial communities and nitrogen induced respiration in turfgrass soils
We examined the effect of a labile soil amendment, compost, and recalcitrant biochar on soil microbial community structure, diversity, and activity during turfgrass establishment. Two application rates of biochar (B1 at 12.5 t ha -1 and B2 at 25 t ha -1 ), a 5 centimeter (cm) green waste compost treatment (CM) in top soil, a treatment with 12.5 t ha -1 biochar and 5 cm compost (B1+CM), and an unamended control (CK) treatment were prepared and seeded with tall fescue. Overall, results of phospholipid fatty acid analysis (PLFA) profiling and Illumina high-throughput sequencing of 16S rRNA genes amplified from soil DNA revealed significant shifts in microbial community structures in the compost amended soils whereas in biochar amended soils communities were more similar to the control, unamended soil. Similarly, increases in enzymatic rates (6–56%) and nitrogen-induced respiration (94%) were all largest in compost amended soils, with biochar amended soils exhibiting similar patterns to the control soils. Both biochar and compost amendments impacted microbial community structures and functions, but compost amendment, whether applied alone or co-applied with biochar, exhibited the strongest shifts in the microbial community metrics examined. Our results suggest application of compost to soils in need of microbiome change (reclamation projects) or biochar when the microbiome is functioning and long-term goals such as carbon sequestration are more desirable.
Complexes of vertebrate TMC1/2 and CIB2/3 proteins form hair-cell mechanotransduction cation channels
Calcium and integrin-binding protein 2 (CIB2) and CIB3 bind to transmembrane channel-like 1 (TMC1) and TMC2, the pore-forming subunits of the inner-ear mechano-electrical transduction (MET) apparatus. These interactions have been proposed to be functionally relevant across mechanosensory organs and vertebrate species. Here, we show that both CIB2 and CIB3 can form heteromeric complexes with TMC1 and TMC2 and are integral for MET function in mouse cochlea and vestibular end organs as well as in zebrafish inner ear and lateral line. Our AlphaFold 2 models suggest that vertebrate CIB proteins can simultaneously interact with at least two cytoplasmic domains of TMC1 and TMC2 as validated using nuclear magnetic resonance spectroscopy of TMC1 fragments interacting with CIB2 and CIB3. Molecular dynamics simulations of TMC1/2 complexes with CIB2/3 predict that TMCs are structurally stabilized by CIB proteins to form cation channels. Overall, our work demonstrates that intact CIB2/3 and TMC1/2 complexes are integral to hair-cell MET function in vertebrate mechanosensory epithelia.
A Single Salt Bridge in VIM-20 Increases Protein Stability and Antibiotic Resistance under Low-Zinc Conditions
Antibiotic resistance is a growing clinical threat. One of the most serious areas of concern is the ability of some bacteria to degrade carbapenems, drugs that are often reserved as last-resort antibiotics. Resistance to carbapenems can be conferred by a large group of related enzymes called metallo-β-lactamases that rely on zinc ions for function and for overall stability. Here, we studied an extensive panel of 45 different metallo-β-lactamases from a subfamily called VIM to discover what changes are emerging as resistance evolves in clinical settings. Enhanced resistance to some antibiotics was observed. We also found that at least one VIM variant developed a new ability to remain more stable under conditions where zinc availability is limited, and we determined the origin of this stability in atomic detail. These results suggest that zinc scarcity helps drive the evolution of this resistance determinant. To understand the evolution of Verona integron-encoded metallo-β-lactamase (VIM) genes ( bla VIM ) and their clinical impact, microbiological, biochemical, and structural studies were conducted. Forty-five clinically derived VIM variants engineered in a uniform background and expressed in Escherichia coli afforded increased resistance toward all tested antibiotics; the variants belonging to the VIM-1-like and VIM-4-like families exhibited higher MICs toward five out of six antibiotics than did variants belonging to the widely distributed and clinically important VIM-2-like family. Generally, maximal MIC increases were observed when cephalothin and imipenem were tested. Additionally, MIC determinations under conditions with low zinc availability suggested that some VIM variants are also evolving to overcome zinc deprivation. The most profound increase in resistance was observed in VIM-2-like variants (e.g., VIM-20 H229R) at low zinc availability. Biochemical analyses reveal that VIM-2 and VIM-20 exhibited similar metal binding properties and steady-state kinetic parameters under the conditions tested. Crystal structures of VIM-20 in the reduced and oxidized forms at 1.25 Å and 1.37 Å resolution, respectively, show that Arg229 forms an additional salt bridge with Glu171. Differential scanning fluorimetry of purified proteins and immunoblots of periplasmic extracts revealed that this difference increases thermostability and resistance to proteolytic degradation when zinc availability is low. Therefore, zinc scarcity appears to be a selective pressure driving the evolution of multiple metallo-β-lactamase families, although compensating mutations use different mechanisms to enhance resistance. IMPORTANCE Antibiotic resistance is a growing clinical threat. One of the most serious areas of concern is the ability of some bacteria to degrade carbapenems, drugs that are often reserved as last-resort antibiotics. Resistance to carbapenems can be conferred by a large group of related enzymes called metallo-β-lactamases that rely on zinc ions for function and for overall stability. Here, we studied an extensive panel of 45 different metallo-β-lactamases from a subfamily called VIM to discover what changes are emerging as resistance evolves in clinical settings. Enhanced resistance to some antibiotics was observed. We also found that at least one VIM variant developed a new ability to remain more stable under conditions where zinc availability is limited, and we determined the origin of this stability in atomic detail. These results suggest that zinc scarcity helps drive the evolution of this resistance determinant.
Heat Treatment and Austenitization Temperature Effect on Microstructure and Impact Toughness of an Ultra-High Strength Steel
Heat treatment parameters were varied to determine the effect of normalizing and austenitizing temperature on the properties of an ultra-high strength wrought steel. Normalizing temperature did not have a significant effect on strength and ductility. Higher normalizing temperatures led to an increase in final prior austenite grain size and a slight loss in toughness. Austenitizing temperature of 825 °C was insufficient to produce a fully austenitic structure prior to quenching and led to sub-par impact behavior. The best properties were obtained after austenitizing at 915 °C followed by water quenching; the resulting quasi static properties were shown to be a yield strength of 1380 MPa with an ultimate tensile strength of 1670 MPa and 12.5% total ductility. Charpy V-notch impact properties as high as 52 J at −40 °C and 75 J at 25 °C and the behavior were achieved using higher austenitizing temperatures as well.
Research led by participants: a new social contract for a new kind of research
In recent years, there have been prominent calls for a new social contract that accords a more central role to citizens in health research. Typically, this has been understood as citizens and patients having a greater voice and role within the standard research enterprise. Beyond this, however, it is important that the renegotiated contract specifically addresses the oversight of a new, path-breaking approach to health research: participant-led research. In light of the momentum behind participant-led research and its potential to advance health knowledge by challenging and complementing traditional research, it is vital for all stakeholders to work together in securing the conditions that will enable it to flourish.
A new social contract for medical innovation
Despite burgeoning knowledge about the origins of disease founded on scientific advances, there are increasing public concerns that medical innovation is not helping patients in need fast enough. In the UK, Lord Saatchi's proposal for a Medical Innovation Bill is one manifestation of this concern, while the Minister for Life Sciences' current Innovative Medicines and Medical Technologies Review is another
Effects of Biochar and Compost on Turfgrass Establishment Rates
Organic soil amendments are a sustainable option for modifying soil structure and improving plant performance in the face of abiotic stressors such as drought and soil salinity. Of these amendments, biochar and compost have the added benefits of carbon sequestration and waste recycling. Establishment studies were conducted on tall fescue (Festuca arundinacea Schreb.) (syn., Schedonorus arundinaceus (Schreb.) Dumort and Lolium arundinaceum (Scop.) Holub) to assess the potential inhibition of establishment by compost and biochar products. Both green waste and biosolid compost impaired establishment rates, while biochar did not. In the field study, the green waste treatments were slower to reach 50% coverage than the untreated control or when biochar was added to the soil, but all treatments reached 75% and final coverage at a similar rate. Field application of compost had a positive effect on final root length and volume but a negative effect on tall fescue roots in the greenhouse. The negative effect of higher salts and volatiles in the biosolids compost was reduced when biosolids and biochar were incorporated into the soil simultaneously. This work represents one of the only large-scale field studies on turfgrass establishment comparing the impact of biochar and compost products on turfgrass establishment.
Montgomery on informed consent: an inexpert decision?
Montgomery v Lanarkshire HB is a deeply troubling decision when read closely. Paradoxically, its ruling supporting the principle of autonomy could be justified only by disregarding the individual patient's actual choices and characteristics in favour of a stereotype. The decision demonstrates a lack of expertise in dealing with specific clinical issues and misrepresents professional guidance. More fundamentally, it fails to appreciate the nature of professional expertise. This calls into question the competence of the courts to adjudicate on matters of clinical judgement and makes an attractive formulation of the test for disclosure obligations inherently unpredictable.