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We evaluated how the gender composition of top-cited authors within different subfields of research has evolved over time. We considered 9,071,122 authors with at least 5 full papers in Scopus as of September 1, 2022. Using a previously validated composite citation indicator, we identified the 2% top-cited authors for each of 174 science subfields (Science-Metrix classification) in 4 separate publication age cohorts (first publication pre-1992, 1992-2001, 2002-2011, post-2011). Using NamSor we assigned 3,784,507 authors as men, and 2,011,616 as women (for 36.1% gender assignment uncertain). Men outnumbered women 1.88-fold among all authors, decreasing from 3.93-fold to 1.36-fold over time. Men outnumbered women 3.21-fold among top-cited authors, decreasing from 6.41-fold to 2.28-fold over time. In the youngest (post-2011) cohort, 32/174 (18%) subfields had >=50% women, 97/174 (56%) subfields had >=30% women, and 3 subfields had =

Adeno-associated virus (AAV)-based gene therapy could be facilitated by the development of molecular switches to control the magnitude and timing of expression of therapeutic transgenes. RNA interference (RNAi)-based approaches hold unique potential as a clinically proven modality to pharmacologically regulate AAV gene dosage in a sequence-specific manner. We present a generalizable RNAi-based rheostat wherein hepatocyte-directed AAV transgene expression is silenced using the clinically validated modality of chemically modified small interfering RNA (siRNA) conjugates or vectorized co-expression of short hairpin RNA (shRNA). For transgene induction, we employ REVERSIR technology, a synthetic high-affinity oligonucleotide complementary to the siRNA or shRNA guide strand to reverse RNAi activity and rapidly recover transgene expression. For potential clinical development, we report potent and specific siRNA sequences that may allow selective regulation of transgenes while minimizing unintended off-target effects. Our results establish a conceptual framework for RNAi-based regulatory switches with potential for infrequent dosing in clinical settings to dynamically modulate expression of virally-delivered gene therapies.

Lipids contribute to hematopoiesis and membrane properties and dynamics, however, little is known about the role of lipids in megakaryopoiesis. Here, a lipidomic analysis of megakaryocyte progenitors, megakaryocytes, and platelets revealed a unique lipidome progressively enriched in polyunsaturated fatty acid (PUFA)-containing phospholipids. In vitro, inhibition of both exogenous fatty acid functionalization and uptake and de novo lipogenesis impaired megakaryocyte differentiation and proplatelet production. In vivo, mice on a high saturated fatty acid diet had significantly lower platelet counts, which was prevented by eating a PUFA-enriched diet. Fatty acid uptake was largely dependent on CD36, and its deletion in mice resulted in thrombocytopenia. Moreover, patients with a CD36 loss-of-function mutation exhibited thrombocytopenia and increased bleeding. Our results suggest that fatty acid uptake and regulation is essential for megakaryocyte maturation and platelet production, and that changes in dietary fatty acids may be a novel and viable target to modulate platelet counts.

The cellular lipidome is comprised of thousands of unique lipid species. This complexity underpins the many roles of lipids in cellular biology. How lipidome composition varies between cell types and how such differences contribute to cell-specific functionality is poorly understood. Here, using mass spectrometry-based targeted lipidomics, we have characterised the cellular lipid landscape of the human and mouse immune systems (www.cellularlipidatlas.com). We find that myeloid and lymphoid cell lineages have unique lipid compositions, notably in the usage of ester and ether bonds within glycerophospholipids (PLs) and PL acyl chain composition. To determine if immune cell-specific lipid phenotypes promote cell-specific functional properties we focused on differences in poly-unsaturated fatty acid (PUFA)-containing PL, the levels of which are markedly higher in lymphoid cells relative to myeloid cells. We firstly show that differences in PUFA-PL content provides a mechanistic basis for previously described differences in immune cell susceptibility to ferroptosis, a form of cell death driven by iron-dependent lipid peroxidation, and secondly, that the low PUFA-PL content of neutrophils restrains NADPH oxidase-driven ferroptosis. In summary, we show that the lipid landscape is a defining feature of immune cell identity and that cell-specific lipid phenotypes underpin aspects of immune cell physiology.

An “omics”-style approach was used to evaluate the complex relationship between whisky aroma and dilution with water, typically suggested as a way to better appreciate whisky. A set of 25 samples, including Bourbons, ryes, single-malt and blended Scotches, and Irish whiskies were chemically profiled at six dilution levels (100, 90, 80, 70, 60, and 50% whisky/water), while a subset of six whiskies (three Bourbons, three Scotches) at four dilution levels (100, 80, 60, and 40% whisky/water) were chemically profiled and subjected to sensory analysis by a trained panel (n = 20). Untargeted volatile analysis was performed using headspace solid-phase microextraction gas chromatography coupled with mass spectrometry (HS-SPME-GC-MS) and sensory analysis was performed using descriptive analysis (DA). Results were evaluated using multivariate statistical techniques, including multifactor analysis (MFA) and partial least squares discriminant analysis (PLS-DA). Dilution decreased headspace concentration of hydrophilic aroma compounds and increased concentration of more hydrophobic compounds, which agreed with DA results. Dilution above 80% whisky/20% water reduced differences within whisky styles, though differences between American (Bourbon, rye) and Scotch styles (single malt, blended) continued to increase with further dilution. This provides important insight into how dilution of whisky during consumption changes consumer perception, as well as the usefulness of HS-SPME-GC-MS as a proxy for human olfaction.

With an increasing human population and expansion of urban settlements, wild animals are often exposed to humans. As humans may be a threat, a neutral presence or a source of food, animals will benefit from continuously assessing the potential risk they pose in order to respond appropriately. Herring gulls, Larus argentatus, are increasingly breeding and foraging in urban areas, and thus have many opportunities to interact with humans. We recently found that herring gulls take longer to approach food when being watched by a human. However, it is not known whether aversion to human gaze arises from experience with humans, and whether individual differences in responsiveness are a result of differential exposure. Here, we tested whether herring gulls' responses to human gaze differ according to their age class and urbanization of their habitat. We measured the gulls' flight initiation distance when an experimenter approached with either a direct or an averted gaze. Neither gull age class nor urbanization significantly influenced the effect of human gaze on flight initiation distance. However, as recently fledged juveniles responded strongly to the experimenter's gaze, aversion to human gaze may not require extensive exposure to humans to develop. Gulls in urban areas could be approached more closely than those in rural areas, consistent with findings in other species. These results indicate that gaze aversion is present early in development and that exposure to humans may influence gulls' responses to perceived risk from humans. Investigating the processes generating individual differences in responses to humans will provide further insights into human–wildlife interactions and the effects of urbanization.

The effect of whole cluster at 50% (50% WC) and 100% additions (100% WC), as well as that of Dried stems (DS) on Pinot noir wines from the Edna Valley AVA of California (USA) were investigated over two consecutive vintages at commercial scale. Additions of 100% WC led to significant increases in pH and volatile acidity. Anthocyanins, polymeric pigments, and color were more influenced by vintage than by the winemaking treatments, but in the case of 100% WC wines, they were either unaffected or negatively affected. Conversely, the tannin content of the wines increased more or less proportional to the percentage of whole clusters and stems added, that is, 68% (50% WC), 100% (100% WC) and 90% (DS) in 2016 and 61% (50% WC), 123% (100% WC) and 137% (DS) in 2017, relative to Control (C) wines. GC-MS data showed higher relative levels of ethyl cinnamate and benzaldehyde in 100% WC wines and relative abundance of esters in DS wines. Descriptive sensory analysis showed that 100% WC additions led to vegetal, cooked fruit flavors and spicy (clove) notes, whereas DS additions produced wines that were more herbal, fruity and astringent, with lifted fruity notes related to esters, and astringency sensations related to enhanced tannin extraction from the stems. Both whole clusters and dried stem additions led to variable increases in perceived astringency, suggesting that they can be used to add mouthfeel and improve texture in Pinot noir wines.

Wildfires produce smoke that can carry organic compounds to a vineyard, which are then absorbed by the grape berry and result in wines with elevated levels of smoke-related phenols. These phenols have been found to have a large impact on the flavor of wines, being the cause of a smokey flavor with a lasting ashy aftertaste. When evaluating the sensory profile of these wines, there is an observed problem due to the lasting nature of these undesirable attributes and potential flavor carryover between samples. Through the use of standard and temporal attribute check-all-that-apply, this research desires to better understand the impact of smoke on the sensorial profiles of wines with various levels of smoke phenols (high, moderate, and low). Additionally, through the employment of different interstimulus protocols, the effectiveness of rinses on diminishing the smoke flavor in wines and optimal time separation were investigated. It was determined that a 1 g/L pectin rinse in between samples with a 120 s separation is optimal to ensure the removal of smoke attribute perception. This work also indicated the need to look deeper at the effects of the in-mouth hydrolysis of glyconjugate phenols that impact overall smoke flavor.

A wide range of factors including biotic and abiotic stresses influence anthocyanin accumulation in plants. In this study, experiments were designed to measure the effects of nutrient depletion on ...

Two studies were performed in Mount Vernon, WA, to identify bulb fennel (Foeniculum ×vulgare) cultivars and seeding practices best suited for the region. The first study evaluated 13 cultivars (Bronze, Finale, Florence, Genesi, Idillio, Orazio, Orion, Perfection, Preludio, Solaris, Tauro, Tenace, and Zefa Fino) over the course of 2 years; during the second year, the additional main factor of the seeding date was included. The second study evaluated three bulb fennel cultivars (Finale, Tauro, and Zefa Fino), four seeding dates (17 May, 31 May, 14 June, and 28 June 2018), and two planting methods (direct and transplant). Results of the two studies demonstrated that ‘Finale’, ‘Orazio’, ‘Preludio’, ‘Solaris’, and ‘Tenace’ had the greatest bulb production rate and yield and good bulb quality that met marketability standards. ‘Genesi’, ‘Orion’, and ‘Perfection’ had good bulb production during only 1 of the 2 years, whereas ‘Bronze’, ‘Florence’, ‘Idillio’, and ‘Zefa Fino’ had very low bulb productivity both years due to bolting. ‘Perfection’ and ‘Tauro’ exhibited internal cracking both years (incidence rates of 9.5% and 12.8%, respectively). The first harvest was 94 to 112 days after seeding during the first study. Direct seeded bulb fennel required 32 fewer days to harvest than transplanted bulb fennel during the second study. The average bulb circumference was 28.1 cm, with little variation between studies. Bulb tenderness for both studies was 617 g-force, on average, and the soluble solids concentration of bulbs in both studies was 4.9%. Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry based on 38 tentatively identified compounds demonstrated no difference in the phenolic content of bulb fennel due to the cultivar. In conclusion, bulb fennel cultivars well-suited for production in northwest Washington were identified and direct seeding was demonstrated to be a better planting method than transplanting.