Doctors form an essential part of an effective response to the COVID-19 pandemic. We argue they have a duty to participate in pandemic response due to their special skills, but these skills vary ...between different doctors, and their duties are constrained by other competing rights. We conclude that while doctors should be encouraged to meet the demand for medical aid in the pandemic, those who make the sacrifices and increased efforts are owed reciprocal obligations in return. When reciprocal obligations are not met, doctors are further justified in opting out of specific tasks, as long as this is proportionate to the unmet obligation.
Interrogating biological systems is often limited by access to biological probes. The emergence of “click chemistry” has revolutionized bioconjugate chemistry by providing facile reaction conditions ...amenable to both biologic molecules and small molecule probes such as fluorophores, toxins, or therapeutics. One particularly popular version is the copper-catalyzed azide–alkyne cycloaddition (AAC) reaction, which has spawned new alternatives such as the strain-promoted azide–alkyne cycloaddition reaction, among others. This focused review highlights practical approaches to AAC reactions for the synthesis of peptide or protein bioconjugates and contrasts current challenges and limitations in light of recent advances in the field. The conical success of antibody drug conjugates has expanded the toolbox of linkers and payloads to facilitate practical applications of bioconjugation to create novel therapeutics and biologic probes. The AAC reaction in particular is poised to enable a large set of functionalized molecules as a combinatorial approach to high-throughput bioconjugate generation, screening, and honing of lead compounds.
While it is often suggested that individuals' pro-environmental behaviors may be linked with their subjective wellbeing, the strength and direction (e.g. positive or negative) of this relation is ...unclear. Because pro-environmental behaviors impact peoples' everyday lives, understanding this relation is critical for promoting long-term environmental solutions. Using a series of meta-analyses, we systematically reviewed the literature on the association between individuals' pro-environmental behaviors and their subjective wellbeing. We hypothesized that the relation between pro-environmental behavior and subjective wellbeing would be positive and strongest among types of behaviors (e.g. sustainable purchase decisions) and indicators of subjective wellbeing which more clearly reflect personal meaning (e.g. warm glow). We sourced studies via PsychINFO, PsychARTICLES, GreenFile, SocINDEX, Web of Science, and Scopus, as well as professional email lists, direct contact with authors who publish in this domain, data from the authorship team, and the European Social Survey (2016). We included studies with quantitative data on the relation between individuals' pro-environmental behavior and their subjective wellbeing, ultimately identifying 78 studies (73 published, 5 unpublished) for synthesis. Across multiple indicators of pro-environmental behaviors and subjective wellbeing, we found a significant, positive relation (overall r = .243), and this relation did not meaningfully differ across study characteristics (e.g. sample, design). As predicted, the relation was particularly strong for indicators of pro-environmental behavior and subjective wellbeing which clearly reflect meaning, such as sustainable purchase decisions (r = .291) and for warm glow (r = .408). We found a robust, positive relation between people's pro-environmental behaviors and subjective wellbeing, and initial evidence that this relation may be stronger the more clearly behaviors and indicators of subjective wellbeing reflect meaning. Our results indicate that program and policy-makers can seek opportunities to design 'win-win' sustainability programs which could positively impact both people and the environment.
There is evidence to suggest that host genomic factors may account for disease response variability in COVID-19 infection. In this paper, we consider if and how host genomics should influence ...decisions about vaccine allocation. Three potential host genetic factors are explored: vulnerability to infection, resistance to infection, and increased infectivity. We argue for the prioritisation of the genetically vulnerable in vaccination schemes, and evaluate the potential for ethical de-prioritisation of individuals with genetic markers for resistance. Lastly, we discuss ethical prioritisation of individuals with genetic markers for increased infectivity (those more likely to spread COVID-19).
Chromatin remodeling motors play essential roles in all DNA-based processes. These motors catalyze diverse outcomes ranging from sliding the smallest units of chromatin, known as nucleosomes, to ...completely disassembling chromatin. The broad range of actions carried out by these motors on the complex template presented by chromatin raises many stimulating mechanistic questions. Other well-studied nucleic acid motors provide examples of the depth of mechanistic understanding that is achievable from detailed biophysical studies. We use these studies as a guiding framework to discuss the current state of knowledge of chromatin remodeling mechanisms and highlight exciting open questions that would continue to benefit from biophysical analyses.
In the coming weeks and months SARS-CoV-2 may ravage countries with weak health systems and populations disproportionately affected by HIV, tuberculosis (TB), and other infectious diseases. Without ...safeguards and proper attention to global health equity and justice, the effects of this pandemic are likely to exacerbate existing health and socio-economic inequalities. This paper argues that achieving global health equity in the context of COVID-19 will require that notions of reciprocity and relational equity are introduced to the response.
Abiotic stresses which include drought and heat are amongst the main limiting factors for plant growth and crop productivity. In the field, these stress types are rarely presented individually and ...plants are often subjected to a combination of stress types. Sorghum bicolor is a cereal crop which is grown in arid and semi-arid regions and is particularly well adapted to the hot and dry conditions in which it originates and is now grown as a crop. In order to better understand the mechanisms underlying combined stress tolerance in this important crop, we have used microarrays to investigate the transcriptional response of Sorghum subjected to heat and drought stresses imposed both individually and in combination.
Microarrays consisting of 28585 gene probes identified gene expression changes equating to ~4% and 18% of genes on the chip following drought and heat stresses respectively. In response to combined stress ~20% of probes were differentially expressed. Whilst many of these transcript changes were in common with those changed in response to heat or drought alone, the levels of 2043 specific transcripts (representing 7% of all gene probes) were found to only be changed following the combined stress treatment. Ontological analysis of these 'unique' transcripts identified a potential role for specific transcription factors including MYB78 and ATAF1, chaperones including unique heat shock proteins (HSPs) and metabolic pathways including polyamine biosynthesis in the Sorghum combined stress response.
These results show evidence for both cross-talk and specificity in the Sorghum response to combined heat and drought stress. It is clear that some aspects of the combined stress response are unique compared to those of individual stresses. A functional characterization of the genes and pathways identified here could lead to new targets for the enhancement of plant stress tolerance, which will be particularly important in the face of climate change and the increasing prevalence of these abiotic stress types.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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•Chromatin remodelers remain poorly understood compared to motors like kinesins.•We show here the role of ATP in the coordination of a dimeric remodeler’s motors.•Constitutive ...dimerization increases the processivity of this dimeric enzyme.•Thus these enzymes use ATP and oligomeric state for regulation of their activity.
ATP-dependent chromatin remodelers are essential enzymes that restructure eukaryotic genomes to enable all DNA-based processes. The diversity and complexity of these processes arethe complexity of the enzymes that carry them out, making remodelers a challenging class of molecular motors to study by conventional methods. Here we use a single molecule biophysical assay to overcome some of these challenges, enabling a detailed mechanistic dissection of a paradigmatic remodeler reaction, that of sliding a nucleosome towards the longer DNA linker. We focus on how two motors of a dimeric remodeler coordinate to accomplish such directional sliding. We find that ATP hydrolysis by both motors promotes coordination, suggesting a role for ATP in resolving the competition for directional commitment. Furthermore, we show an artificially constitutive dimer is no more or less coordinated, but is more processive, suggesting a cell could modulate a remodeler’s oligomeric state to modulate local chromatin dynamics.
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