Miracle-dz/UniFAR-FTUs huggingface dataset:
Pulsed focused ultrasound lowers interstitial fluid pressure and increases nanoparticle delivery and penetration in head and neck squamous cell carcinoma xenograft tumors

Nanocarriers offer a promising approach to significantly improve therapeutic delivery to solid tumors as well as limit the side effects associated with anti-cancer agents. However, their relatively large size can negatively affect their ability to efficiently penetrate into more interior tumor regions, ultimately reducing therapeutic efficacy. Poor penetration of large agents such as nanocarriers is attributed to factors in the tumor microenvironment such as elevated interstitial fluid pressure (IFP) and fibrillar collagen in the extracellular matrix. Our previous studies reported that pretreatment of solid tumor xenografts with nondestructive pulsed focused ultrasound (pFUS) can improve the delivery and subsequent therapy of a variety of therapeutic formulations in different tumor models, where the results were associated with expanded extracellular spaces (ECS), an increase in hydraulic conductivity, and decrease in tissue stiffness. Here, we demonstrate the inverse relationship between IFP and the penetration of systemically administered nanoparticle (NP) probes, where IFP increased from the tumor periphery to their center. Furthermore, we show that pretreatment with pFUS can safely reduce IFP and improve NP delivery; especially into the center of the tumors. These results coincide with effects generated in the fibrillar collagen network microstructure in the ECS as determined by quantitative polarized light microscopy. Whole tumor and histomorphometric analysis, however, did not show significant differences in collagen area fraction or collagen feature solidity, as well as tumor cross-sectional area and aspect ratio, as a result of the treatments. We present a biophysical model connecting the experimental results, where pFUS-mediated cytoarchitectural changes are associated with improved redistribution of the interstitial fluid and lower IFP. The resulting improvement in NP delivery supports our previous therapeutic studies and may have implications for clinical applications to improve therapeutic outcomes in cancer therapy.
Effects of livestock breed and grazing intensity on biodiversity and production in grazing systems. 1. Nutritive value of herbage and livestock performance

Summary Reduction of grazing intensity and the use of traditional instead of commercial breeds has frequently been recommended to meet biodiversity and production goals in sustainable grazing systems in Europe. To test the impact of such practices across a range of contrasting grassland types, integrated measurements of foraging behaviour, agronomic production and botanical, structural and invertebrate biodiversity were made over three years on four sites in the UK, Germany, France and Italy. The sites in the UK and Germany were mesotrophic grassland with high productivity and low to moderate initial levels of plant diversity, and were grazed by cattle. The French site was a semi-natural, species-rich grassland grazed by cattle. The Italian site contained a wider range in plant diversity, from species-rich to mesotrophic grassland, and was grazed by sheep. The treatments were: MC, moderate grazing intensity with a commercial breed – this was designed to utilize herbage growth for optimum livestock production; LC, lenient grazing intensity with a commercial breed – this was designed to increase biodiversity by not fully utilizing herbage growth; and LT, lenient grazing intensity with a traditional breed – this was also designed to increase biodiversity. Neither fertilizers nor pesticides were applied. The nutritive value of the herbage and the performance of the livestock were measured. Mean stocking rates were proportionately 0·30–0·40 lower and mean sward heights and herbage mass on offer were 0·30–0·50 higher on the LC and LT treatments compared with the MC treatment. The proportion of live and dead material, and leaves and stems in the herbage, its chemical composition and nutritive value were little affected by the treatments. Individual livestock performance, measured as liveweight gain, showed no consistent response to treatment. In Germany, performance on the MC treatment was slightly lower than on the LC and LT treatments but no such difference was found on the sites in the other countries. Livestock breed did not have a strong effect on livestock performance. In the UK and France the traditional breeds had a lower performance but this was not the case in Germany or Italy. Livestock performance per ha of the LC and LT treatments was up to 0·40 lower than of the MC treatment. It is concluded that biodiversity-targeted extensive grazing systems have potential to be integrated into intensive livestock production systems because the individual livestock performance reaches a similar level compared to a moderate grazing intensity. Traditional breeds did not have a production advantage over commercial breeds on extensively managed pastures.
The genetic architecture of maternal effects across ontogeny in the red deer

Maternal effects, either environmental or genetic in origin, are an underappreciated source of phenotypic variance in natural populations. Maternal genetic effects have the potential to constrain or enhance the evolution of offspring traits depending on their magnitude and their genetic correlation with direct genetic effects. We estimated the maternal effect variance and its genetic component for 12 traits expressed over the life history in a pedigreed population of wild red deer (morphology, survival/longevity, breeding success). We only found support for maternal genetic effect variance in the two neonatal morphological traits: birth weight ( hMg2 = 0.31) and birth leg length ( hMg2 = 0.17). For these two traits, the genetic correlation between maternal and direct additive effects was not significantly different from zero, indicating no constraint to evolution from genetic architecture. In contrast, variance in maternal genetic effects enhanced the additive genetic variance available to respond to natural selection. Maternal effect variance was negligible for late‐life traits. We found no evidence for sex differences in either the direct or maternal genetic architecture of offspring traits. Our results suggest that maternal genetic effect variance declines over the lifetime, but also that this additional heritable genetic variation may facilitate evolutionary responses of early‐life traits.
Leaf Responses to Reduced Iron Availability in Two Tomato Genotypes: T3238FER (Iron Efficient) and T3238fer (Iron Inefficient)

Abstract The present work is aimed at evaluating some effects induced by different levels of iron availability in the growth medium for two different tomato (Lycopersicon esculentum Mill.) genotypes, the T3238fer (Tfer), unable to activate mechanisms for iron mobilization and uptake known as “strategy I,” and its correspondent wild‐type T3238FER (TFER). By using different iron concentration in the growth solution, the most suitable iron level to induce phenotypic differences between the two genotypes without being lethal for the mutant was found to be 40 µM Fe‐Na‐EDTA. The analyses were carried out also on plants grown with 80 µM Fe‐Na‐EDTA, an iron concentration at which the two genotypes showed no phenotypic differences. A significant decrease in total leaf iron and chlorophyll content was detected in both genotypes following reduction of iron concentration in the nutrient solution, and was particularly evident in Tfer40, which showed symptoms of chlorosis. The photo‐electron transport rate of the whole chain was significantly affected by growth conditions as well as by genotype, the lowest activity being detected in Tfer40 plants. Chlorophyll a fluorescence analysis revealed an increase in non‐photochemical quenching (q NP) of Tfer plants grown at both iron concentrations, indicating the activation of photoprotective mechanisms, which, however, were not sufficient to prevent photoinhibition when plants were grown at 40 µM iron, as indicated by significant reduction in PSII photochemistry (F v/F m) and photochemical quenching (q P). The actual quantum yield of PSII (ΦPSII) and the intrinsic PSII efficiency (ΦEXC) showed the same behavior of q P and F v/F m ratio. A significant effect of mutation and iron supply on all the pigments was detected, and was particularly evident in the mutant grown at 40 µM iron. A different behavior was shown by the three pigments involved in the xantophyll cycle, violaxanthin being less affected than chlorophylls and the other carotenoids, and zeaxanthin even increasing, due to the xanthophyll cycle activation. In conclusion, the interaction between iron deprivation and fer mutation induced functional alterations to the photosynthetic apparatus. Anyway, as far as concerns the photo‐electron transport activity, the influence of fer mutation seemed to occur independently from iron supply.
Changes in spectral properties of ageing and senescing maize and sunflower leaves

The objective of this study was to determine the differences between maize (Zea mays L.) and sunflower (Helianthus annuus L.) in the pattern of leaf chlorophyll content and spectral properties occurring with leaf ageing and senescence. Chlorophyll accumulation and leaf spectral properties were determined in growing and senescing leaves of field-grown maize and sunflower hybrids. Measurements were taken at intervals of 3–4 days during the rapid stem elongation phase on leaf 11 for maize and leaf 17 for sunflower. Reflectance (R) and transmittance (T) spectra of adaxial surfaces of attached leaves were measured using a LI-COR 1800 hand-held spectroradiometer with an external integrating sphere, over the wavelength range from 400 to 100 nm. Absorptance (A) was computed as: A = 100-(R + T). In the growing leaf, chlorophyll content increased until full leaf expansion, while no changes in A and T were recorded. After full leaf expansion was reached, chlorophyll dropped from 514.3 to 328.0 μmol m−2 in maize and from 527.2 to 164.1 μmol m−2 in sunflower. Absorptance in the PAR region declined about 5% in maize and about 11% in sunflower and T increased about 1% in maize and 7% in sunflower. Within the PAR region, variations in A and T were recorded only in the green band (520–600 nm) for maize and in the green and red (630–690 nm) bands for sunflower. There were differences between maize and sunflower in the relative timing of the decrease in chlorophyll content and A in senescing leaves: maize retained chlorophyll longer than sunflower and A declined more slowly in maize as a result of the different length of leaf maturity and senescing stages.
CRISPR Meets Zebrafish: Accelerating the Discovery of New Therapeutic Targets

Bringing a new drug to the market costs an average of US$2.6 billion and takes more than 10 years from discovery to regulatory approval. Despite the need to reduce cost and time to increase productivity, pharma companies tend to crowd their efforts in the same indications and drug targets. This results in the commercialization of drugs that share the same mechanism of action (MoA) and, in many cases, equivalent efficacies among them—an outcome that helps neither patients nor the balance sheet of the companies trying to bring therapeutics to the same patient population. Indeed, the discovery of new therapeutic targets, based on a deeper understanding of the disease biology, would likely provide more innovative MoAs and potentially greater drug efficacies. It would also bring better chances for identifying appropriate treatments according to the patient’s genetic stratification. Nowadays, we count with an enormous amount of unprocessed information on potential disease targets that could be extracted from omics data obtained from patient samples. In addition, hundreds of pharmacological and genetic screenings have been performed to identify innovative drug targets. Traditionally, rodents have been the animal models of choice to perform functional genomic studies. The high experimental cost, combined with the low throughput provided by those models, however, is a bottleneck for discovering and validating novel genetic disease associations. To overcome these limitations, we propose that zebrafish, in conjunction with the use of CRISPR/Cas9 genome-editing tools, could streamline functional genomic processes to bring biologically relevant knowledge on innovative disease targets in a shorter time frame.
SLEEP/WAKE CYCLE PARAMETERS AND SLEEP/FATIGUE COMPLAINTS IN FEMALE NIGHT WORKERS

Adaptation to shift-work is influenced by the way workers schedule their lives, including allocation of sleep episodes. Female workers (n = 29) engaged at an assembly line were studied as to individual differences in sleep parameters in order to verify whether those differences could be related to the manifestation of sleep and fatigue complaints. The sample was composed of women (20–40 y) working at night from Monday to Friday. Sleep data were based on daily sleep logs which were filled out by the workers for 10 consecutive weeks. In the analyses of sleep data both diurnal episodes between consecutive night shifts and noctural sleep episodes preceding working nights were taken into account. Worker's complaints were analyzed through questions extracted from an interview form encompassing questions on fatigue associated with the work schedule and on dissatisfaction with sleep on weekdays and weekends. The analysis of diurnal episodes showed no significant correlation between the total amount of sleep per d.
COVID-19 Immunity Passport to Ease Travel Restrictions?

Lin H. Chen, MD, David O. Freedman, MD, Leo G. Visser, MD, PhD Division of Infectious Diseases and Travel Medicine, Mount Auburn Hospital, Cambridge, and Harvard Medical School, Boston, Massachusetts, USA Division of Infectious Diseases, William C. Gorgas Center for Geographic Medicine, University of Alabama at Birmingham, Birmingham, AL Department of Infectious Diseases, Leiden University, Leiden, The Netherlands
The integrity of the intradimer interface of the Hepatitis B Virus capsid protein dimer regulates capsid self-assembly.

During the hepatitis B virus lifecycle, 120 copies of homodimeric capsid protein assemble around a copy of reverse transcriptase and viral RNA and go on to produce an infectious virion. Assembly needs to be tightly regulated by protein conformational change to ensure symmetry, fidelity and reproducibility. Here we show that structures at the intradimer interface regulate conformational changes at the distal interdimer interface and so regulate assembly. A pair of interacting charged residues, D78 from each monomer, conspicuously located at the top of a four-helix bundle that forms the intradimer interface, were mutated to serine to disrupt communication between the two monomers. The mutation slowed assembly and destabilized dimer to thermal and chemical denaturation. Mutant dimers showed evidence of transient partial unfolding based on appearance of new proteolytically-sensitive sites. Though mutant dimer was less stable, the resulting capsids were as stable as wildtype, based on assembly and thermal denaturation studies. Cryo-EM image reconstructions of capsid indicated that the subunits adopted an "open" state more usually associated with free dimer and that the spike tips were either disordered or highly flexible. Molecular dynamics simulations provide mechanistic explanations for these results, suggesting that D78 stabilizes helix 4a, which forms part of the intradimer interface, by capping its N-terminus and hydrogen-bonding to nearby residues, whereas the D78S mutation disrupts these interactions, leading to partial unwinding of helix 4a. This in turn weakens the connection from helix 4 and the intradimer interface to helix 5, which forms the interdimer interface.
Temporal Asynchrony of Adult Emergence Between Leucopis argenticollis and Leucopis piniperda (Diptera: Chamaemyiidae), Predators of the Hemlock Woolly Adelgid (Hemiptera: Adelgidae), with Implications for Biological Control

Abstract Two species of silver fly, Leucopis argenticollis (Zetterstedt) and Leucopis piniperda (Malloch) (Diptera: Chamaemyiidae), from the Pacific Northwest region of North America have been identified as potential biological control agents of hemlock woolly adelgid (Hemiptera: Adelgidae: Adelges tsugae Annand) in eastern North America.The two predators are collectively synchronized with A. tsugae development.To determine whether adult emergence of the two species of silver fly are also synchronized with one another, we collected adult Leucopis which emerged from A. tsugae-infested western hemlock [Pinaceae: Tsuga heterophylla (Raf.) Sarg. ] from four sites in the Pacific Northwest over a 29-d period. Specimens were collected twice daily in the laboratory and identified to species using DNA barcoding. The study found that more adult Leucopis were collected in the evening than the morning. Additionally, the daily emergences of adults over the 29-d sampling period exhibited sinusoidal-like fluctuations of peak abundance of each species, lending evidence to a pattern of temporal partitioning.This pattern could have logistical implications for their use as biological control agents in eastern North America, namely the need to release both species for maximum efficacy in decreasing A. tsugae populations.
Statin use does not decrease the incidence of post-endoscopic retrograde cholangiopancreatography pancreatitis

Three-Hydroxy-3-methyl-glutaryl-coenzyme A (HMG co-A) reductase inhibitors (statins) represent an effective therapeutic tool used worldwide in the treatment of dyslipidemia, and a growing body of evidence supports also their pleiotropic anti-inflammatory properties [1,2]. In spite of preliminary discording results, several recent studies demonstrated that the chronic use of statins may appear as a protective factor against acute pancreatitis (AP) [3–6]. Based on these premises, statin use was found to be associated with lower rates of iatrogenic pancreatitis after interventional endoscopic procedures, such as endoscopic ultrasound (EUS) tissue sampling [7] or endoscopic retrograde cholangio-pancreatography (ERCP) [8]. However, these promising findings have been recently debunked in larger studies which did not find a significant benefit with statin chronic use in decreasing post-ERCP pancreatitis (PEP) [9,10]. In order to shed further light on this controversial topic, we reviewed our series of patients treated with ERCP at our tertiary center from 2006 to 2019. Local ethic committee approved this retrospective series.
Serum alarmin S100A8/S100A9 levels and its potential role as biomarker in myocarditis

The alarmin S100A8/S100A9 (S100A8/A9) is released by activated monocytes/macrophages and neutrophils in the setting lymphocytic myocarditis (MC). We recently demonstrated its therapeutic potential in experimental acute MC. Now, we investigated the diagnostic relevance of S100A8/A9 serum levels in patients with suspected acute and chronic MC and in patients with heart failure without cardiac inflammation.
Microalgae proteins: production, separation, isolation, quantification, and application in food and feed

Abstract Many countries have been experienced an increase in protein consumption due to the population growth and adoption of protein-rich dietaries. Unfortunately, conventional-based protein agroindustry is associated with environmental impacts that might aggravate as the humankind increase. Thus, it is important to screen for novel protein sources that are environmentally friendly. Microalgae farming is a promising alternative to couple the anthropic emissions with the production of food and feed. Some microalgae show protein contents two times higher than conventional protein sources. The use of whole microalgae biomass as a protein source in food and feed is simple and well-established. Conversely, the production of microalgae protein supplements and isolates requires the development of feasible and robust processes able to fractionate the microalgae biomass in different value-added products. Since most of the proteins are inside the microalgae cells, several techniques of disruption have been proposed to increase the efficiency to extract them. After the disruption of the microalgae cells, the proteins can be extracted, concentrated, isolated or purified allowing the development of different products. This critical review addresses the current state of the production of microalgae proteins for multifarious applications, and possibilities to concatenate the production of proteins and advanced biofuels.
Urbanization and Carpobrotus edulis invasion alter the diversity and composition of soil bacterial communities in coastal areas.

Coastal dunes are ecosystems of high conservation value that are strongly impacted by human disturbances and biological invasions in many parts of the world. Here we assessed how urbanization and Carpobrotus edulis invasion affect soil bacterial communities on the north-western coast of Spain, by comparing the diversity, structure and composition of soil bacterial communities in invaded and uninvaded soils from urban and natural coastal dune areas. Our results suggest that coastal dune bacterial communities contain large numbers of rare taxa, mainly belonging to the phyla Actinobacteria and Proteobacteria. We found that the presence of the invasive C. edulis increased the diversity of soil bacteria andchanged community composition, while urbanization only influenced bacterial community composition. Furthermore, the effects of invasion on community composition were conditional on urbanization. These results were contrary to predictions, as both C. edulis invasion and urbanization have been shown to affect soil abiotic conditions of the studied coastal dunes in a similar manner, and therefore were expected to have similar effects on soil bacterial communities. Our results suggest that other factors (e.g. pollution) might be influencing the impact of urbanization on soil bacterial communities, preventing an increase in the diversity of soil bacteria in urban areas.
Site‐to‐site differences in pollinator visitation patterns in a Louisiana iris hybrid zone

We studied pollinator visitation rates and movement patterns in experimental arrays of irises at two sites within a Louisiana iris hybrid zone. Arrays contained single-flowered stems of red-flowered I. fulva, blue-flowered I. hexagona, and purple-flowered F1 hybrids. At one site, where I. hexagona was the only wild-growing iris, queen bumble bees were the most common pollinator, and the rank order of pollinator visit rates was I. hexagonaI. fulva. At a second site, where I. fulva predominated in the wild, hummingbirds were the most common pollinators, and this order was reversed: I. hexagona<F1<I. fulva. Thus, at both sites, the naturally occurring iris was visited most frequently and F1 flowers were visited more frequently than the non-native species. Pollinators used both long-distance and short-distance cues to discriminate among flowers, and differences in visit rates seemed to be based on differences in the ease of access to pollen and nectar rewards on flowers of different size. Analysis of movement patterns between flowers showed that pollinators were more likely to make parental-F1 transitions than heterospecific transitions. These data suggest that pollinator behavior acts as a partial barrier to initial hybridization, although this barrier largely breaks down after F1 formation. Our results help to explain the existence of many introgressed populations of Louisiana iris, despite the fact that F1s are extremely rare in the wild.