Perceptions and experience of employment regulation in UK small firms

The view that excessive regulation constrains small business growth has been a persistent theme within business and policy communities, although recent studies have demonstrated the actual effects of regulation to be relatively modest. A prior small-scale study proposed four reasons why employment legislation does 'not damage' small firms. We attempt to assess the robustness of these propositions in a large-scale survey of 16 779 small firms. Results provide empirical support for three propositions. Firstly, perceived dissatisfaction masks actual effects. Secondly, competitive conditions mediate regulatory effects; however, even resource-constrained firms reported few negative effects. Thirdly, informality eases regulatory impact. Results failed to confirm that older laws are 'routinised'. Length of time as a business owner was found to be more influential than age of regulation, with owners who have been in business for many years having a longer 'window of exposure' increasing their likelihood of experiencing negative and positive effects

Germplasm diversity of sunflower volatile terpenoid profiles across vegetative and reproductive organs

Received: September 4th, 2022 ; Accepted: December 4th, 2022 ; Published: December 24th, 2022 ; Corresponding author: [email protected] sunflower (Helianthus annuus) is the fourth most important oilseed crop globally and is known to have experienced multiple genetic bottlenecks during domestication and improvement. Homogenization of crop germplasm may limit breeding efforts to improve pest and pathogen resistance or optimize other biotic interactions like pollinator attraction. Such interactions are often strongly influenced by plant phytochemistry, especially volatile compounds like terpenoids. Here we use solid-phase microextraction gas chromatography mass spectrometry (SPME GC-MS) to evaluate volatile phytochemistry across leaves, involucral bracts, disc florets, and ray floret petals in a collection of twelve inbred lines selected to represent a cross-section of sunflower germplasm diversity. Results indicate considerable compositional diversity of volatiles among lines, though substantial reduction in total volatile abundance relative to wild H. annuus. From leaves and bracts to disc florets and petals, we observe a strong increase in the proportion of monoterpenoids relative to sesquiterpenoids accompanying the transition to reproductive structures, with consistently over 85% monoterpenoids in disc florets and petals. This pattern is driven by substantially higher production of monoterpenoids (especially alpha-pinene and sabinene) in reproductive structures. Sesquiterpenoid production is roughly similar across organs, and in leaves varies among lines from 21–55% of volatiles, dominated by cadinene-type sesquiterpenoids. This work suggests that the compositional diversity of volatile terpenoids within cultivated germplasm may be sufficient for many breeding applications, though for breeding increased volatile production the use of wild H. annuus and other wild Helianthus germplasm may be necessary

Functional interactions between bottom-up synthetic cells and living matter for biomedical applications

Bottom-up synthetic cells, where diverse non-living materials are combined in creative ways in order to construct increasingly life-like and adaptive systems, are fast approaching a level of function that will enable significant advances in solving specific biomedical challenges. Over the last 10 years, we have seen a wide variety of synthetic cell based approaches to challenges in regulating antimicrobial activity, delivering cargo to mammalian cells, and “growth support”. Despite this progress, there has not been a widespread uptake of synthetic cell technologies in biomedical engineering. In this Review, we highlight both the strengths and limitations of these existing synthetic cell applications, as well as give an overview of the state-of-the-art of synthetic cell technology that has yet been applied to cellular contexts. In doing so we aim to identify opportunities for the advancement of this unique intersection of research fields

Saccade dysmetria indicates attenuated visual exploration in autism spectrum disorder

Background: Visual exploration in autism spectrum disorder (ASD) is characterized by attenuated social attention. The underlying oculomotor function during visual exploration is understudied, whereas oculomotor function during restricted viewing suggested saccade dysmetria in ASD by altered pontocerebellar motor modulation. Methods: Oculomotor function was recorded using remote eye tracking in 142 ASD participants and 142 matched neurotypical controls during free viewing of naturalistic videos with and without human content. The sample was heterogenous concerning age (6–30 years), cognitive ability (60–140 IQ), and male/female ratio (3:1). Oculomotor function was defined as saccade, fixation, and pupil‐dilation features that were compared between groups in linear mixed models. Oculomotor function was investigated as ASD classifier and features were correlated with clinical measures. Results: We observed decreased saccade duration (∆M = −0.50, CI [−0.21, −0.78]) and amplitude (∆M = −0.42, CI [−0.12, −0.72]), which was independent of human video content. We observed null findings concerning fixation and pupil‐dilation features (POWER = .81). Oculomotor function is a valid ASD classifier comparable to social attention concerning discriminative power. Within ASD, saccade features correlated with measures of restricted and repetitive behavior. Conclusions: We conclude saccade dysmetria as ASD oculomotor phenotype relevant to visual exploration. Decreased saccade amplitude and duration indicate spatially clustered fixations that attenuate visual exploration and emphasize endogenous over exogenous attention. We propose altered pontocerebellar motor modulation as underlying mechanism that contributes to atypical (oculo‐)motor coordination and attention function in ASD

Regulating Chemokine-Receptor Interactions through the Site-Specific Bioorthogonal Conjugation of Photoresponsive DNA Strands

Oligonucleotide conjugation has emerged as a versatile molecular tool for regulating protein activity. A state-of-the-art labeling strategy includes the site-specific conjugation of DNA, by employing bioorthogonal groups genetically incorporated in proteins through unnatural amino acids (UAAs). The incorporation of UAAs in chemokines has to date, however, remained underexplored, probably due to their sometimes poor stability following recombinant expression. In this work, we designed a fluorescent stromal-derived factor-1β (SDF-1β) chemokine fusion protein with a bioorthogonal functionality amenable for click reactions. Using amber stop codon suppression, p-azido-L-phenylalanine was site-specifically incorporated in the fluorescent N-terminal fusion partner, superfolder green fluorescent protein (sfGFP). Conjugation to single-stranded DNAs (ssDNA), modified with a photocleavable spacer and a reactive bicyclononyne moiety, was performed to create a DNA-caged species that blocked the receptor binding ability. This inhibition was completely reversible by means of photocleavage of the ssDNA strands. The results described herein provide a versatile new direction for spatiotemporally regulating chemokine-receptor interactions, which is promising for tissue engineering purposes.</p

Regulating Chemokine-Receptor Interactions through the Site-Specific Bioorthogonal Conjugation of Photoresponsive DNA Strands

Oligonucleotide conjugation has emerged as a versatile molecular tool for regulating protein activity. A state-of-the-art labeling strategy includes the site-specific conjugation of DNA, by employing bioorthogonal groups genetically incorporated in proteins through unnatural amino acids (UAAs). The incorporation of UAAs in chemokines has to date, however, remained underexplored, probably due to their sometimes poor stability following recombinant expression. In this work, we designed a fluorescent stromal-derived factor-1β (SDF-1β) chemokine fusion protein with a bioorthogonal functionality amenable for click reactions. Using amber stop codon suppression, p-azido-L-phenylalanine was site-specifically incorporated in the fluorescent N-terminal fusion partner, superfolder green fluorescent protein (sfGFP). Conjugation to single-stranded DNAs (ssDNA), modified with a photocleavable spacer and a reactive bicyclononyne moiety, was performed to create a DNA-caged species that blocked the receptor binding ability. This inhibition was completely reversible by means of photocleavage of the ssDNA strands. The results described herein provide a versatile new direction for spatiotemporally regulating chemokine-receptor interactions, which is promising for tissue engineering purposes.</p

Enzymatic Regulation of Protein-Protein Interactions in Artificial Cells

Membraneless organelles are important for spatial organization of proteins and regulation of intracellular processes. Proteins can be recruited to these condensates by specific protein–protein or protein–nucleic acid interactions, which are often regulated by post-translational modifications. However, the mechanisms behind these dynamic, affinity-based protein recruitment events are not well understood. Here, a coacervate system that incorporates the 14-3-3 scaffold protein to study enzymatically regulated recruitment of 14-3-3-binding proteins is presented, which mostly bind in a phosphorylation-dependent manner. Synthetic coacervates are efficiently loaded with 14-3-3, and phosphorylated binding partners, such as the c-Raf pS233/pS259 peptide (c-Raf), show 14-3-3-dependent sequestration with up to 161-fold increase in local concentration. The c-Raf domain is fused to green fluorescent protein (GFP-c-Raf) to demonstrate recruitment of proteins. In situ phosphorylation of GFP-c-Raf by a kinase leads to enzymatically regulated uptake. The introduction of a phosphatase into coacervates preloaded with the phosphorylated 14-3-3-GFP-c-Raf complex results in a significant cargo efflux mediated by dephosphorylation. Finally, the general applicability of this platform to study protein–protein interactions is demonstrated by the phosphorylation-dependent and 14-3-3-mediated active reconstitution of a split-luciferase inside artificial cells. This work presents an approach to study dynamically regulated protein recruitment in condensates, using native interaction domains.</p

Genomic DNA transposition induced by human PGBD5

Transposons are mobile genetic elements that are found in nearly all organisms, including humans. Mobilization of DNA transposons by transposase enzymes can cause genomic rearrangements, but our knowledge of human genes derived from transposases is limited. In this study, we find that the protein encoded by human PGBD5, the most evolutionarily conserved transposable element-derived gene in vertebrates, can induce stereotypical cut-and-paste DNA transposition in human cells. Genomic integration activity of PGBD5 requires distinct aspartic acid residues in its transposase domain, and specific DNA sequences containing inverted terminal repeats with similarity to piggyBac transposons. DNA transposition catalyzed by PGBD5 in human cells occurs genome-wide, with precise transposon excision and preference for insertion at TTAA sites. The apparent conservation of DNA transposition activity by PGBD5 suggests that genomic remodeling contributes to its biological function

A machine-learning data set prepared from the NASA solar dynamics observatory mission

In this paper, we present a curated data set from the NASA Solar Dynamics Observatory (SDO) mission in a format suitable for machine-learning research. Beginning from level 1 scientific products we have processed various instrumental corrections, down-sampled to manageable spatial and temporal resolutions, and synchronized observations spatially and temporally. We illustrate the use of this data set with two example applications: forecasting future extreme ultraviolet (EUV) Variability Experiment (EVE) irradiance from present EVE irradiance and translating Helioseismic and Magnetic Imager observations into Atmospheric Imaging Assembly observations. For each application, we provide metrics and baselines for future model comparison. We anticipate this curated data set will facilitate machine-learning research in heliophysics and the physical sciences generally, increasing the scientific return of the SDO mission. This work is a direct result of the 2018 NASA Frontier Development Laboratory Program. Please see the Appendix for access to the data set, totaling 6.5TBs

The effect of biomass ashes and potassium salts on MEA degradation for BECCS

This study investigates the comparative impact of inherently different biomass and coal ashes on the laboratory and pilot scale degradation of 30 wt% aqueous monoethanolamine (MEA), relevant to post-combustion CO2 capture. Thermal and oxidative degradation experiments were carried out at 135 °C and 40 °C respectively with CO2 loading (0.5 molCO2/molMEA), with and without the presence of ash. Nuclear magnetic resonance (NMR) data is provided for the major MEA degradation compounds such as N-(2-hydroxyethyl)formamide (HEF) and N-(2-hydroxyethyl)imidazole (HEI) along with the characterisation of a new MEA oxidative degradation product, N-(2-hydroxyethyl)imidazole-N-oxide (HEINO) which had been previously misassigned. Degradation products were quantified using 1H NMR and gas chromatography mass spectrometry (GC–MS) to assess the impact of potassium and various ashes from combustion (olive, white wood and two types of coal ash) on the rates of amine degradation. Woody biomass fly ashes were found to reduce the presence of the oxidative degradation products. Both types of coal fly ash and the olive biomass ash were found to enhance the formation the newly identified degradation product, HEINO. Solvent samples taken from a pilot scale facility support these laboratory findings