Cultivating the next generation of leaders : How postdocs, principal investigators and institutes can nurture and select for leadership competencies.

The transition from postdoc to PI is the most challenging career step. Peer groups, PIs and research institution can help postdocs to acquire the necessary skills and experience. [Image: see text]

Regional impact assessment of air quality improvement: The air quality lifecourse assessment tool (AQ-LAT) for the West Midlands combined authority (WMCA) area.

Poor air quality is the largest environmental health risk in England. In the West Midlands, UK, ∼2.9 million people are affected by air pollution with an average loss in life expectancy of up to 6 months.

Multiplexed Transactivation of Mammalian Cells Using dFnCas12a-VPR.

CRISPR activation provides an invaluable tool for experimental biologists to convert correlations into causation by directly observing phenotypic changes upon targeted changes in gene expression. With few exceptions, most diseases are caused by complex polygenic interactions, with multiple genes contributing to define the output of a gene network. As such researchers are increasingly interested in tools that can offer not only control but also the capacity to simultaneously upregulate multiple genes.

An optogenetic cell therapy to restore control of target muscles in an aggressive mouse model of amyotrophic lateral sclerosis.

Breakdown of neuromuscular junctions (NMJs) is an early pathological hallmark of amyotrophic lateral sclerosis (ALS) that blocks neuromuscular transmission, leading to muscle weakness, paralysis and, ultimately, premature death. Currently, no therapies exist that can prevent progressive motor neuron degeneration, muscle denervation, or paralysis in ALS. Here, we report important advances in the development of an optogenetic, neural replacement strategy that can effectively restore innervation of severely affected skeletal muscles in the aggressive SOD1 mouse model of ALS, thus providing an interface to selectively control the function of targeted muscles using optical stimulation.

Do We Collaborate With What We Design?

The use of terms like "collaboration" and "co-workers" to describe interactions between human beings and certain artificial intelligence (AI) systems has gained significant traction in recent years. Yet, it remains an open question whether such anthropomorphic metaphors provide either a fertile or even a purely innocuous lens through which to conceptualize designed commercial products. Rather, a respect for human dignity and the principle of transparency may require us to draw a sharp distinction between real and faux peers.

The cholesterol depleting agent, (2-Hydroxypropyl)-ß-cyclodextrin, does not affect disease progression in SOD1 mice.

Previously, we demonstrated that Amyloid Precursor Protein (APP) contributes to pathology in the SOD1 mouse model of ALS and that genetic ablation of APP in SOD1 mice significantly improved multiple disease parameters, including muscle innervation and motor neuron survival. We also observed elevated levels of potentially neurotoxic Aß peptides that have been implicated in Alzheimer's Disease (AD) pathogenesis, within motor neurons and astrocytes in SOD1 mice. More recently, it has been shown that blocking Aß production improves outcome measures in SOD1 mice.

The Winchcombe meteorite, a unique and pristine witness from the outer solar system.

Direct links between carbonaceous chondrites and their parent bodies in the solar system are rare. The Winchcombe meteorite is the most accurately recorded carbonaceous chondrite fall. Its pre-atmospheric orbit and cosmic-ray exposure age confirm that it arrived on Earth shortly after ejection from a primitive asteroid.

Multi-stakeholder Engagement for the Sustainable Development Goals: Introduction to the Special Issue.

The world is not on track to achieve Agenda 2030-the approach chosen in 2015 by all UN member states to engage multiple stakeholders for the common goal of sustainable development. The creation of the 17 Sustainable Development Goals (SDGs) arguably offered a new take on sustainable development by adopting hybrid and principle-based governance approaches, where public, private, not for profit and knowledge-institutions were invited to engage around achieving common medium-term targets. Cross-sector partnerships and multi-stakeholder engagement for sustainability have consequently taken shape.

Multiplexed activation in mammalian cells using a split-intein CRISPR/Cas12a based synthetic transcription factor.

The adoption of CRISPR systems for the generation of synthetic transcription factors has greatly simplified the process for upregulating endogenous gene expression, with a plethora of applications in cell biology, bioproduction and cell reprogramming. The recently discovered CRISPR/Cas12a (Cas12a) systems offer extended potential, as Cas12a is capable of processing its own crRNA array, to provide multiple individual crRNAs for subsequent targeting from a single transcript. Here we show the application of dFnCas12a-VPR in mammalian cells, with the Francisella novicida Cas12a (FnCas12a) possessing a shorter PAM sequence than Acidaminococcus sp.

Paleomagnetic evidence for a disk substructure in the early solar system.

Astronomical observations and isotopic measurements of meteorites suggest that substructures are common in protoplanetary disks and may even have existed in the solar nebula. Here, we conduct paleomagnetic measurements of chondrules in CO carbonaceous chondrites to investigate the existence and nature of these disk substructures. We show that the paleomagnetism of chondrules in CO carbonaceous chondrites indicates the presence of a 101 ± 48 μT field in the solar nebula in the outer solar system (~3 to 7 AU from the Sun).

Association Between Baseline Anti-cyclic Citrullinated Peptide Antibodies and 6-Month Clinical Response Following Abatacept or TNF Inhibitor Treatment: A Real-World Analysis of Biologic-Experienced Patients with RA.

Introduction: Anti-cyclic citrullinated peptide (anti-CCP) antibodies are associated with poor prognosis in patients with rheumatoid arthritis (RA). Previous data from randomized controlled trials and clinical practice have shown anti-CCP-positive (+) patients had a better response to treatment with abatacept or tumor necrosis factor inhibitor (TNFi) treatment than those who were anti-CCP negative. This study assessed the association between baseline anti-CCP2 [a surrogate for anti-citrullinated protein antibody (ACPA)] concentration and 6-month treatment responses to abatacept or TNFi in patients with RA.

Temporary Urbanisms as Policy Alternatives to Enhance Health and Well-Being in the Post-Pandemic City.

Purpose Of Review: While there has been extensive discussion on the various forms of temporary uses in urban settings, little is known on the ways in which temporary and health urbanisms connect. Now, a turning point has been reached regarding the interactions between health and the built environment and the contributions made by urban planning and other built environment disciplines. In the context of the post-pandemic city, there is a need to develop a health-led temporary urbanism agenda than can be implemented in various settings both in the Global South and North.

Seasonality, climate change, and food security during pregnancy among Indigenous and non-Indigenous women in rural Uganda: Implications for maternal-infant health.

Background: Climate change is expected to decrease food security globally. Many Indigenous communities have heightened sensitivity to climate change and food insecurity for multifactorial reasons including close relationships with the local environment and socioeconomic inequities which increase exposures and challenge adaptation to climate change. Pregnant women have additional sensitivity to food insecurity, as antenatal undernutrition is linked with poor maternal-infant health.

Polarization under rising inequality and economic decline.

Social and political polarization is an important source of conflict in many societies. Understanding its causes has become a priority of scholars across disciplines. We demonstrate that shifts in socialization strategies analogous to political polarization can arise as a locally beneficial response to both rising wealth inequality and economic decline.

COVID-19 and Alternative Conceptualisations of Value and Risk in GPN Research.

The COVID-19 pandemic represents a major disturbance that has rippled across the world's population, states, economy, and central nervous system or global production networks transforming the traditional roles of states, firms, individuals/consumers, and geographies of production. This paper offers a critical and context-based approach to understanding globalization and localization by challenging the conceptualization of 'value' and 'risk' within the current global production networks framework as well as identifying key operational strategies in risk management and national security. An analysis of the adaptation strategies of the GPNs of 91 companies identifies the role played by four different forms of value in configuring production networks.

COVID-19, Virtual Church Services and a New Temporary Geography of Home.

The COVID-19 pandemic and subsequent lockdown measures implemented by the United Kingdom government from 23 March 2020 led to unprecedented adaptations from individuals and communities including places of worship, their clergy and congregations. This paper through a multi-disciplinary dialogue between human geography and theology explores the interrelations between place, space and the spiritual. It identifies the bricolage mechanisms that were developed rapidly by churches to shift towards providing virtual church services.

Meteorite evidence for partial differentiation and protracted accretion of planetesimals.

Modern meteorite classification schemes assume that no single planetary body could be source of both unmelted (chondritic) and melted (achondritic) meteorites. This dichotomy is a natural outcome of formation models assuming that planetesimal accretion occurred nearly instantaneously. However, it has recently been proposed that the accretion of many planetesimals lasted over ≳1 million years (Ma).

Confronting vaccine hesitancy: What nurses need to know.

This article reviews the origins of vaccine hesitancy, explores common misconceptions about vaccines, and discusses strategies for overcoming vaccine hesitancy.

Neglected Tropical Diseases in the Context of Climate Change in East Africa: A Systematic Scoping Review.

East Africa is highly affected by neglected tropical diseases (NTDs), which are projected to be exacerbated by climate change. Consequently, understanding what research has been conducted and what knowledge gaps remain regarding NTDs and climate change is crucial to informing public health interventions and climate change adaptation. We conducted a systematic scoping review to describe the extent, range, and nature of publications examining relationships between NTDs and climatic factors in East Africa.

Expanding and understanding the CRISPR toolbox for Bacillus subtilis with MAD7 and dMAD7.

The CRISPR-Cas9 system has become increasingly popular for genome engineering across all fields of biological research, including in the Gram-positive model organism Bacillus subtilis. A major drawback for the commercial use of Cas9 is the IP landscape requiring a license for its use, as well as reach-through royalties on the final product. Recently an alternative CRISPR nuclease, free to use for industrial R&D, MAD7 was released by Inscripta (CO).

The top-down solidification of iron asteroids driving dynamo evolution.

The cores of some small planetesimals, such as asteroid (16) Psyche, are thought to have been exposed through collisions during the early solar system that removed their mantles. These small bodies likely solidified from the top down representing a fundamentally different solidification regime to that of Earth's core. Here we derive simplified models of the downwards solidification of the metallic crust, and consider thermal convection and the potential for viscous delamination of the weak, warm base of the crust to provide a buoyancy flux sufficient to drive a dynamo.

What are the health outcomes of trans and gender diverse young people in Australia? Study protocol for the Trans20 longitudinal cohort study.

Introduction: Being transgender is frequently accompanied by gender dysphoria, which often coexists with mental health concerns. Increased referrals of transgender and gender diverse (TGD) youth to gender clinics have been observed in many countries. Nevertheless, there are limited empirical data on the presentation and outcomes of these patients, and there is an urgent need for more evidence to ensure optimal medical and psychosocial interventions.

A comprehensive toxicological safety assessment of an extract of Ageratum conyzoides.

A battery of toxicological studies was conducted to aid in the safety assessment of an ethanolic extract of Ageratum conyzoides for use as an ingredient in food. In accordance with internationally accepted standards, a bacterial reverse mutation test, an in vitro mammalian chromosomal aberration test, an in vivo mammalian micronucleus test, and a 90-day repeated-dose oral toxicity study in rats were performed. In the first three applied test systems, no evidence of mutagenicity, clastogenicity or genotoxicity was revealed.