The COVID-19 pandemic: local to global implications as perceived by urban ecologists.

The global COVID-19 pandemic is affecting everyone, but in many different ways, stimulating contrasting reactions and responses: opportunities for some, difficulties for many. A simple survey of how individual workers in urban ecology have been coping with COVID-19 constraints found divergent responses to COVID-19 on people's activities, both within countries and between continents. Many academics felt frustrated at being unable to do fieldwork, but several saw opportunities to change ways of working and review their engagement with the natural world. Some engaging with social groups found new ways of sharing ideas and developing aspirations without face-to-face contact. Practitioners creating and managing urban greenspaces had to devise ways to work and travel while maintaining social distancing. Many feared severe funding impacts from changed local government priorities. Around the world, the COVID-19 pandemic has amplified issues, such as environmental injustice, disaster preparation and food security, that have been endemic in most countries across the global south in modern times. However, developing and sustaining the strong community spirit shown in many places will speed economic recovery and make cities more resilient against future geophysical and people-made disasters. Significantly, top-down responses and one-size-fits-all solutions, however good the modelling on which they are based, are unlikely to succeed without the insights that local knowledge and community understanding can bring. We all will have to look at disaster preparation in a more comprehensive, caring and consistent way in future.

Development of GoSlo-SR-5-69, a potent activator of large conductance Ca2+-activated K+ (BK) channels.

We have designed, synthesised and characterised the effects of a number of novel anthraquinone derivatives and assessed their effects on large conductance, Ca(2+) activated K(+) (BK) channels recorded from rabbit bladder smooth muscle cells using the excised, inside/out configuration of the patch clamp technique. These compounds are members of the GoSlo-SR family of compounds, which potently open BK channels and shift the voltage required for half maximal activation (V1/2) negatively. The efficacy of the anilinoanthraquinone derivatives was enhanced when the size of ring D was increased, since the cyclopentane and cyclohexane derivatives shifted the V1/2, by -24 ± 6 mV and -54 ± 8 mV, respectively, whereas the cycloheptane and cyclooctane derivatives shifted the V1/2 by -61 ± 6 mV and -106 ± 6 mV. To examine if a combination of hydrophobicity and steric bulking of this region further enhanced their ability to open BK channels, we synthesised a number of naphthalene and tetrahydro-naphthalene derivatives. The tetrahydro-2-naphthalene derivative GoSlo-SR-5-69 was the most potent and efficacious of the series since it was able to shift the activation V1/2 by greater than -100 mV when applied at a concentration of 1 µM and had an EC50 of 251 nM, making it one of the most potent and efficacious BK channel openers synthesised to date.

Structure-activity relationships of a novel group of large-conductance Ca(2+)-activated K(+) (BK) channel modulators: the GoSlo-SR family.

Opening up ion channels: We synthesised a series of anthraquinone analogues, called the GoSlo-SR family. Their effects on bladder smooth muscle BK channels were examined and, as shown, shifted voltage dependent activation >-100 mV (at 10 µM). They were more efficacious than NS11021 and could provide a new scaffold for the design of efficacious BK openers.

Whole-animal senescent cytotoxic T cell removal using antibodies linked to magnetic nanoparticles.

A major type of unwanted cells that accumulate in aging are anergic cytotoxic T cells. These cells often have virus-specific T cell receptors, as well as other surface markers that distinguish them from their youthful counterparts, and they are thought to play a major role in the decline of the immune system with age. Here we consider two surface markers thought to define these cells in mice, CD8 and Killer cell lectin-like receptor G1 (KLRG1), and a means we developed to remove these cells from the blood of aged C57BL/6 mice. Using antibodies with magnetic nanoparticles linked to their Fc domains, we first developed a method to use magnets to filter out the unwanted cells from the blood and later constructed a device that does this automatically. We demonstrated that this device could reduce the KLRG1-positive CD8 cell count in aged mouse blood by a factor of 7.3 relative to the total CD8 cell compartment, reaching a level typically seen only in very young animals.

Medical bioremediation: a concept moving toward reality.

Abstract A major driver of aging is catabolic insufficiency, the inability of our bodies to break down certain substances that accumulate slowly throughout the life span. Even though substance buildup is harmless while we are young, by old age the accumulations can reach a toxic threshold and cause disease. This includes some of the most prevalent diseases in old age-atherosclerosis and macular degeneration. Atherosclerosis is associated with the buildup of cholesterol and its oxidized derivatives (particularly 7-ketocholesterol) in the artery wall. Age-related macular degeneration is associated with carotenoid lipofuscin, primarily the pyridinium bisretinoid A2E. Medical bioremediation is the concept of reversing the substance accumulations by using enzymes from foreign species to break down the substances into forms that relieve the disease-related effect. We report on an enzyme discovery project to survey the availability of microorganisms and enzymes with these abilities. We found that such microorganisms and enzymes exist. We identified numerous bacteria having the ability to transform cholesterol and 7-ketocholesterol. Most of these species initiate the breakdown by same reaction mechanism as cholesterol oxidase, and we have used this enzyme directly to reduce the toxicity of 7-ketocholesterol, the major toxic oxysterol, to cultured human cells. We also discovered that soil fungi, plants, and some bacteria possess peroxidase and carotenoid cleavage oxygenase enzymes that effectively destroy with varied degrees of efficiency and selectivity the carotenoid lipofuscin found in macular degeneration.