A socially just recovery from the COVID-19 pandemic: a call for action on the social determinants of urban health inequalities

From bustling business districts to vibrant cultural life, many of the things that make life in cities advantageous can be attributed to their ability to bring people together. Diverse social networks, which promote productivity and innovation, can, however, act as a vector for disease transmission during a pandemic. The social distancing and lockdown measures implemented during the COVID-19 pandemic have brought fast-paced city life to a standstill, giving citizens pause to recognise the necessity of adequate living conditions, the value of access to healthcare and the privilege of digital technology. Many of these response efforts have left the most socioeconomically disadvantaged at greater risk of catching and dying from COVID-19. They have exacerbated existing health inequalities and given rise to new ones. Many are calling for a socially just recovery, including 5 million health professionals representing over 50 countries in their open letter to the United Nations calling for ethical global leadership.1 The need for action on health inequalities was evident before the pandemic but this crisis provides an unprecedented opportunity for change and cities can be a focal point for this. While each city will require a unique recovery strategy from the pandemic, this commentary calls for a health equity approach to be universally adopted. Grounded in the Social Determinants of Health framework,2 this commentary suggests three ways cities could change as a result of the COVID-19 pandemic in the housing, healthcare and technology sectors. Public and urban health professionals could engage multi-level stakeholders from civil society to governments at local and national levels to improve daily living conditions, promote access to healthcare and harness the power of digital technologies to address urban health inequalities

Tracking the Endosomal Escape: A Closer Look at Calcein and Related Reporters

Crossing the cellular membrane and delivering active pharmaceuticals or biologicals into the cytosol of cells is an essential step in the development of nanomedicines. One of the most important intracellular processes regarding the cellular uptake of biologicals is the endolysosomal pathway. Sophisticated nanocarriers are developed to overcome a major hurdle, the endosomal entrapment, and delivering their cargo to the required site of action. In parallel, in vitro assays are established analyzing the performance of these nanocarriers. Among them, the release of the membrane‐impermeable dye calcein has become a popular and straightforward method. It is accessible for most researchers worldwide, allows for rapid conclusions about the release potential, and enables the study of release mechanisms. This review is intended to provide an overview and guidance for scientists applying the calcein release assay. It comprises a survey of several applications in the study of endosomal escape, considerations of potential pitfalls, challenges, and limitations of the assay, and a brief summary of complementary methods. Based on this review, it is hoped to encourage further research groups to take advantage of the calcein release assay for their own purposes and help to create a database for more efficient cross‐correlations between nanocarriers

Sequential conformational transitions and α-helical supercoiling regulate a sensor histidine kinase

Sensor histidine kinases are central to sensing in bacteria and in plants. They usually contain sensor, linker, and kinase modules and the structure of many of these components is known. However, it is unclear how the kinase module is structurally regulated. Here, we use nano- to millisecond time- resolved X-ray scattering to visualize the solution structural changes that occur when the light-sensitive model histidine kinase YF1 is activated by blue light. We find that the coiled coil linker and the attached histidine kinase domains undergo a left handed rotation within microseconds. In a much slower second step, the kinase domains rearrange internally. This structural mechanism presents a template for signal transduction in sensor histidine kinases

Re-ordering connections: UK healthcare workers' experiences of emotion management during the COVID-19 pandemic

This paper examines the impact of disruptions to the organisation and delivery of healthcare services and efforts to re-order care through emotion management during the COVID-19 pandemic in the UK. Framing care as an affective practice, studying healthcare workers' (HCWs) experiences enables better understanding of how interactions between staff, patients and families changed as a result of the pandemic. Using a rapid qualitative research methodology, we conducted interviews with frontline HCWs in two London hospitals during the peak of the first wave of the pandemic and sourced public accounts of HCWs' experiences of the pandemic from social media (YouTube and Twitter). We conducted framework analysis to identify key factors disrupting caring interactions. Fear of infection and the barriers of physical distancing acted to separate staff from patients and families, requiring new affective practices to repair connections. Witnessing suffering was distressing for staff, and providing a 'good death' for patients and communicating care to families was harder. In addition to caring for patients and families, HCWs cared for each other. Infection control measures were important for limiting the spread of COVID-19 but disrupted connections that were integral to care, generating new work to re-order interactions

Missing the human connection: A rapid appraisal of healthcare workers' perceptions and experiences of providing palliative care during the COVID-19 pandemic.

BACKGROUND: During infectious epidemics, healthcare workers are required to deliver traditional care while facing new pressures. Time and resource restrictions, a focus on saving lives and new safety measures can lead to traditional aspects of care delivery being neglected. AIM: Identify barriers to delivering end-of-life care, describe attempts to deliver care during the COVID-19 pandemic, and understand the impact this had on staff. DESIGN: A rapid appraisal was conducted incorporating a rapid review of policies from the United Kingdom, semi-structured telephone interviews with healthcare workers, and a review of mass print media news stories and social media posts describing healthcare worker's experiences of delivering care during the pandemic. Data were coded and analysed using framework analysis. SETTING/PARTICIPANTS: From a larger ongoing study, 22 interviews which mentioned death or caring for patients at end-of-life, eight government and National Health Service policies affecting end-of-life care delivery, eight international news media stories and 3440 publicly available social media posts were identified. The social media analysis centred around 274 original tweets with the highest reach, engagement and relevance. Incorporating multiple workstreams provided a broad perspective of end-of-life care during the COVID-19 pandemic in the United Kingdom. RESULTS: Three themes were developed: (1) restrictions to traditional care, (2) striving for new forms of care and (3) establishing identity and resilience. CONCLUSIONS: The COVID-19 pandemic prohibited the delivery of traditional care as practical barriers restricted human connections. Staff prioritised communication and comfort orientated tasks to re-establish compassion at end-of-life and displayed resilience by adjusting their goals

Structural photoactivation of a full-length bacterial phytochrome

Phytochromes are light sensor proteins found in plants, bacteria, and fungi. They function by converting a photon absorption event into a conformational signal that propagates from the chromophore through the entire protein. However, the structure of the photoactivated state and the conformational changes that lead to it are not known. We report time-resolved x-ray scattering of the full-length phytochrome from Deinococcus radiodurans on micro- and millisecond time scales. We identify a twist of the histidine kinase output domains with respect to the chromophore-binding domains as the dominant change between the photoactivated and resting states. The time-resolved data further show that the structural changes up to the microsecond time scales are small and localized in the chromophore-binding domains. The global structural change occurs within a few milliseconds, coinciding with the formation of the spectroscopic meta-Rc state. Our findings establish key elements of the signaling mechanism of full-length bacterial phytochromes

EHD2 is a mechanotransducer connecting caveolae dynamics with gene transcription

Caveolae are small invaginated pits that function as dynamic mechanosensors to buffer tension variations at the plasma membrane. Here we show that under mechanical stress, the EHD2 ATPase is rapidly released from caveolae, SUMOylated, and translocated to the nucleus, where it regulates the transcription of several genes including those coding for caveolae constituents. We also found that EHD2 is required to maintain the caveolae reservoir at the plasma membrane during the variations of membrane tension induced by mechanical stress. Metal-replica electron microscopy of breast cancer cells lacking EHD2 revealed a complete absence of caveolae and a lack of gene regulation under mechanical stress. Expressing EHD2 was sufficient to restore both functions in these cells. Our findings therefore define EHD2 as a central player in mechanotransduction connecting the disassembly of the caveolae reservoir with the regulation of gene transcription under mechanical stress

Interaction between a cationic surfactant-like peptide and lipid vesicles and its relationship to antimicrobial activity

We investigate the properties of an antimicrobial surfactant-like peptide (Ala)6(Arg), A6R, containing a cationic headgroup. The interaction of this peptide with zwitterionic (DPPC) lipid vesicles is investigated using a range of microscopic, X-ray scattering, spectroscopic, and calorimetric methods. The β-sheet structure adopted by A6R is disrupted in the presence of DPPC. A strong effect on the small-angle X-ray scattering profile is observed: the Bragg peaks from the DPPC bilayers in the vesicle walls are eliminated in the presence of A6R and only bilayer form factor peaks are observed. All of these observations point to the interaction of A6R with DPPC bilayers. These studies provide insight into interactions between a model cationic peptide and vesicles, relevant to understanding the action of antimicrobial peptides on lipid membranes. Notably, peptide A6R exhibits antimicrobial activity without membrane lysis

Applications of isothermal titration calorimetry - the research and technical developments from 2011 to 2015

Isothermal titration calorimetry is a widely used biophysical technique for studying the formation or dissociation of molecular complexes. Over the last 5years, much work has been published on the interpretation of isothermal titration calorimetry (ITC) data for single binding and multiple binding sites. As over 80% of ITC papers are on macromolecules of biological origin, this interpretation is challenging. Some researchers have attempted to link the thermodynamics constants to events at the molecular level. This review highlights work carried out using binding sites characterized using x-ray crystallography techniques that allow speculation about individual bond formation and the displacement of individual water molecules during ligand binding and link these events to the thermodynamic constants for binding. The review also considers research conducted with synthetic binding partners where specific binding events like anion-π and π-π interactions were studied. The revival of assays that enable both thermodynamic and kinetic information to be collected from ITC data is highlighted. Lastly, published criticism of ITC research from a physical chemistry perspective is appraised and practical advice provided for researchers unfamiliar with thermodynamics and its interpretation