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Infectious diseases, including the coronavirus disease 2019 (COVID-19) pandemic that has brought the world to a standstill, are emerging at an unprecedented rate with a substantial impact on public health and global economies. For many life-threatening global infectious diseases, such as human immunodeficiency virus (HIV) infection, malaria and influenza, effective vaccinations are still lacking. There are numerous roadblocks to developing new vaccines, including a limited understanding of immune correlates of protection to these global infections. To induce a reproducible, strong immune response against difficult pathogens, sophisticated nanovaccine technologies are under investigation. In contrast to conventional vaccines, nanovaccines provide improved access to lymph nodes, optimal packing and presentation of antigens, and induction of a persistent immune response. This Review provides a perspective on the global trends in emerging nanoscale vaccines for infectious diseases and describes the biological, experimental and logistical problems associated with their development, and how immunoengineering can be leveraged to overcome these challenges. This Review provides an overview of the advantages and disadvantages of nanoscale vaccines against infectious diseases, focusing in particular on the immunological responses they can elicit, depending on their physicochemical properties and functionalization, and on the challenges their production face.

Severe SARS-CoV-2 infection 1 has been associated with highly inflammatory immune activation since the earliest days of the COVID-19 pandemic 2 – 5 . More recently, these responses have been associated with the emergence of self-reactive antibodies with pathologic potential 6 – 10 , although their origins and resolution have remained unclear 11 . Previously, we and others have identified extrafollicular B cell activation, a pathway associated with the formation of new autoreactive antibodies in chronic autoimmunity 12 , 13 , as a dominant feature of severe and critical COVID-19 (refs. 14 – 18 ). Here, using single-cell B cell repertoire analysis of patients with mild and severe disease, we identify the expansion of a naive-derived, low-mutation IgG1 population of antibody-secreting cells (ASCs) reflecting features of low selective pressure. These features correlate with progressive, broad, clinically relevant autoreactivity, particularly directed against nuclear antigens and carbamylated proteins, emerging 10–15 days after the onset of symptoms. Detailed analysis of the low-selection compartment shows a high frequency of clonotypes specific for both SARS-CoV-2 and autoantigens, including pathogenic autoantibodies against the glomerular basement membrane. We further identify the contraction of this pathway on recovery, re-establishment of tolerance standards and concomitant loss of acute-derived ASCs irrespective of antigen specificity. However, serological autoreactivity persists in a subset of patients with postacute sequelae, raising important questions as to the contribution of emerging autoreactivity to continuing symptomology on recovery. In summary, this study demonstrates the origins, breadth and resolution of autoreactivity in severe COVID-19, with implications for early intervention and the treatment of patients with post-COVID sequelae. Single-cell B cell repertoire analysis identifies the expansion of a naive-derived population of antibody-secreting cells contributing to de novo autoreactivity in patients with severe COVID-19 and those with post-COVID symptoms.

PurposeThis systematic review aims to assess and evaluate quantitative evidence on the association between informal caregiving and mental health in young people.MethodsThis review was registered in PROSPERO (CRD42021251666). We conducted our search in the following four databases: Medline (PubMed and OVID), EMBASE, PsycInfo and Web of Science. The last search was performed on the 17th of March of 2021. Quantitative studies that focused on carers aged 25 years or less and compared the mental health status of carers and non-carers were eligible for inclusion. Two reviewers independently assessed articles for eligibility and performed the quality assessment using the Risk of Bias tool in Non-Randomised Studies of Exposures (ROBINS-E).ResultsWe identified a total of ten eligible articles. Mental health outcomes included depression, anxiety and other mental or emotional problems. Nine out of the ten studies showed that being a young carer was consistently associated with poor mental health. However, the overall quality of evidence was low, and longitudinal data were limited to three articles. The primary sources of bias were confounding and outcome measurement.ConclusionYoung carers experience poorer mental health outcomes than their non-caring peers. However, we identified an overall lack of quantitative evidence of high methodological rigour. To establish if young caring leads to poor mental health, future research should focus on addressing the identified methodological limitations and understanding the mechanisms explaining these associations. Addressing these gaps can better inform the allocation of appropriate support and resources to optimise the mental health of young carers.

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus. The outbreak of CHIKV infection has been seen in many tropical and subtropical regions of the biosphere. Current reports evidenced that after outbreaks in 2005–06, the fitness of this virus propagating in Aedes albopictus enhanced due to the epistatic mutational changes in its envelope protein. In our study, we evaluated the prevalence of intrinsically disordered proteins (IDPs) and IDP regions (IDPRs) in CHIKV proteome. IDPs/IDPRs are known as members of a ‘Dark Proteome’ that defined as a set of polypeptide segments or whole protein without unique three-dimensional structure within the cellular milieu but with significant biological functions, such as cell cycle regulation, control of signaling pathways, and maintenance of viral proteomes. However, the intrinsically disordered aspects of CHIKV proteome and roles of IDPs/IDPRs in the pathogenic mechanism of this important virus have not been evaluated as of yet. There are no existing reports on the analysis of intrinsic disorder status of CHIKV. To fulfil this goal, we have analyzed the abundance and functionality of IDPs/IDPRs in CHIKV proteins, involved in the replication and maturation. It is likely that these IDPs/IDPRs can serve as novel targets for disorder based drug design.

Key messageExtensive crosstalk exists among ABA and different phytohormones that modulate plant tolerance against different abiotic stress.Being sessile, plants are exposed to a wide range of abiotic stress (drought, heat, cold, salinity and metal toxicity) that exert unwarranted threat to plant life and drastically affect growth, development, metabolism, and yield of crops. To cope with such harsh conditions, plants have developed a wide range of protective phytohormones of which abscisic acid plays a pivotal role. It controls various physiological processes of plants such as leaf senescence, seed dormancy, stomatal closure, fruit ripening, and other stress-related functions. Under challenging situations, physiological responses of ABA manifested in the form of morphological, cytological, and anatomical alterations arise as a result of synergistic or antagonistic interaction with multiple phytohormones. This review provides new insight into ABA homeostasis and its perception and signaling crosstalk with other phytohormones at both molecular and physiological level under critical conditions including drought, salinity, heavy metal toxicity, and extreme temperature. The review also reveals the role of ABA in the regulation of various physiological processes via its positive or negative crosstalk with phytohormones, viz., gibberellin, melatonin, cytokinin, auxin, salicylic acid, jasmonic acid, ethylene, brassinosteroids, and strigolactone in response to alteration of environmental conditions. This review forms a basis for designing of plants that will have an enhanced tolerance capability against different abiotic stress.

Informal care can exert adverse effects on the mental health of young people. Bullying victimisation is an important determinant of mental disorders. Young carers are at elevated risk of bullying. We quantify the mental health effects of informal care among Australian adolescents and the extent to which these effects are transmitted through school bullying. We used data from the Longitudinal Study of Australian Children. Participants were classified as non-carers, light carers (caring for < 10 h/week) and moderate-to-heavy carers (caring for 10 + h/week). Mental health was measured using the Kessler Psychological Distress Scale (K10). Using a counterfactual approach to mediation analysis, total effects (TE) of informal care on mental health were decomposed into natural direct effects (NDE—mental health effects not transmitted through school bullying) and natural indirect effects (NIE—mental health effects transmitted through school bullying). The TE of informal caring was 0.71 (95%CI − 0.03, 1.49) for light carers and 1.72 (95%CI 0.45, 3.02) for moderate-to-heavy carers. While school bullying explained 27% of the TE among moderate-to-heavy carers (NIE: 0.46; 95%CI 0.12, 0.91) there was weak evidence of mediation for light carers. Our findings indicate that the mental health effects of moderate-to-heavy caregiving can be reduced by school bullying interventions.

Optical trapping and patterning cells or microscopic particles is fascinating. We developed a light sheet-based optical tweezer to trap dielectric particles and live HeLa cells. The technique requires the generation of a tightly focussed diffraction-limited light-sheet realized by a combination of cylindrical lens and high NA objective lens. The resultant field is a focussed line (along x -axis) perpendicular to the beam propagation direction ( z -axis). This is unlike traditional optical tweezers that are fundamentally point-traps and can trap one particle at a time. Several spherical beads undergoing Brownian motion in the solution are trapped by the lightsheet gradient potential, and the time (to reach trap-centre) is estimated from the video captured at 230 frames/s. High-speed imaging of beads with increasing laser power shows a steady increase in trap stiffness with a maximum of 0.00118 pN/nm at 52.5 mW. This is order less than the traditional point-traps, and hence may be suitable for applications requiring delicate optical forces. On the brighter side, light sheet tweezer (LOT) can simultaneously trap multiple objects with the distinct ability to manipulate them in the transverse ( xy ) plane via translation and rotation. However, the trapped beads displayed free movement along the light-sheet axis ( x -axis), exhibiting a single degree of freedom. Furthermore, the tweezer is used to trap and pattern live HeLa cells in various shapes and structures. Subsequently, the cells were cultured for a prolonged period of time (> 18 h), and cell viability was ascertained. We anticipate that LOT can be used to study constrained dynamics of microscopic particles and help understand the patterned cell growth that has implications in optical imaging, microscopy, and cell biology.

The EZH2 histone methyltransferase is required for B cells to form germinal centers (GC). Here we show that EZH2 mediates GC formation through repression of cyclin-dependent kinase inhibitor CDKN1A (p21 Cip1 ). Deletion of Cdkn1a rescues the GC reaction in Ezh2 −/− mice. Using a 3D B cell follicular organoid system that mimics the GC reaction, we show that depletion of EZH2 suppresses G1 to S phase transition of GC B cells in a Cdkn1a -dependent manner. GC B cells of Cdkn1a −/− Ezh2 −/− mice have high levels of phospho-Rb, indicating that loss of Cdkn1a enables progression of cell cycle. Moreover, the transcription factor E2F1 induces EZH2 during the GC reaction. E2f1 −/− mice manifest impaired GC responses, which is rescued by restoring EZH2 expression, thus defining a positive feedback loop in which EZH2 controls GC B cell proliferation by suppressing CDKN1A , enabling cell cycle progression with a concomitant phosphorylation of Rb and release of E2F1. The histone methyltransferase EZH2 silences genes by generating H3K27me3 marks. Here the authors use a 3D GC organoid and show EZH2 mediates germinal centre (GC) formation through epigenetic silencing of CDKN1A and release of cell cycle checkpoints.

PurposeUnaffordable housing has a negative impact on mental health; however, little is known about the causal pathways through which it transmits this effect. We examine the role of financial hardship and social support as mediators of this relationship.MethodsWe identified households where housing costs changed from affordable to unaffordable across two waves of the Household, Income and Labour Dynamics in Australia (HILDA) Survey (2014–2015). The sequential causal mediation analysis was used to decompose the total effect of unaffordable housing on mental health into the portion attributable to financial hardship and social support [natural indirect effect (NIE)] and the portion not occurring through measured pathways [natural direct effect (NDE)]. Mental health was measured using the Mental Health Inventory (MHI) and Kessler psychological distress (KPD) scale. Baseline covariates included age, sex, household income, financial hardship, social support, marital status and employment status. Bootstrapping with 1000 replications was used to calculate 95% confidence intervals (CIs). Multiple imputations using chained equations were applied to account for missing data.ResultsUnaffordable housing led to a change in mean mental health score on the MHI scale (− 1.3, 95% CI: − 2.1, − 0.6) and KPDS scale (0.9, 95% CI: 0.4, 1.4). Financial hardship accounted for 54% of the total effect on MHI scale and 53% on KPD scale. Collectively, financial hardship and social support explained 68% of the total effect on MHI scale and 67% on KPD scale, respectively.ConclusionsIn conclusion, the negative mental health effect of unaffordable housing is largely mediated through increased financial hardship.

Objective To identify the most commonly reviewed behaviour change techniques (BCTs) and their effectiveness based on consistency across reviews for lifestyle interventions of non-communicable diseases. Design Umbrella review of systematic reviews. Data sources PubMed, Embase, PsycINFO, Cochrane CENTRAL, Global Health. Data extraction and synthesis A narrative synthesis of extracted findings was conducted. The Behaviour Change Technique v1 Taxonomy was used to identify and code behaviour change techniques (e.g., goal setting) in a standardised manner, which were independently assessed by two reviewers. Study quality was independently assessed by two reviewers using the assessment of multiple systematic review tools. Results 26 reviews were included with a total of 72 BCT labels evaluated across the different lifestyle interventions and non-communicable diseases. A total of 13 BCT clusters were identified to be reported as effective. The most commonly reviewed BCTs and their effectiveness/ineffectiveness were as follows: ‘Goals and Planning’ (12 effective/1 ineffective), ‘Feedback and monitoring’ (9 effective/3 ineffective), ‘Social support’ (9 effective/1 ineffective), ‘Shaping knowledge’ (11 effective/1 ineffective), and ‘Natural consequences’ (6 effectiveness/ 2 ineffective). The vast majority of the studies were conducted in high-income and a few in upper middle-income countries, with hardly any studies from lower middle-income and lower income studies. Conclusion The most common BCTs were ‘Goals and Planning’, ‘Feedback and Monitoring’, ‘Shaping Knowledge’, ‘Social Support’, and ‘Natural Consequence’. Based on consistency across reviews, several BCTs such as ‘Goals and Planning’, Feedback and Monitoring’, ‘Shaping Knowledge’, and ‘Social Support’ have demonstrated effectiveness (Recommendation Grade A) in improving health behaviours across a limited range of NCDs. The evidence is less clear for other BCT techniques. It is also likely that not all BCTs will be transferable across different settings. There is a need for more research in this area, especially in low-middle-income countries. Protocol registration Registered on the International Prospective Register of Systematic Reviews; PROSPERO (CRD42020222832).