Do Alterations in the Rate of Gastric Emptying after Injection Sclerotherapy for Oesophageal Varices Play any Role in the Development of Portal Hypertensive Gastropathy?

Bleeding from portal hypertensive gastropathy (PHG) has been estimated to account for upto 30% of all upper gastrointestinal haemorrhage in patients with cirrhosis and portal hypertension. Although portal hypertension seems to be an essential prerequisite, the precise mechanisms responsible for the development of PHG are unknown. The aim of this study was to examine the role of injection sclerotherapy of oesophageal varices in the development of PHG. Gastric emptying was studied using a radionuclide test meal with the emptying characteristics of a slow liquid in 57 patients with cirrhosis and/or portal hypertension (median age 53 yrs), of whom 34 had received injection sclerotherapy for their oesophageal varices and 20 normal healthy volunteers (median age 42 yrs). As vagal damage is associated with more rapid emptying of liquids, despite hold up of solids, this technique might be expected to demonstrate such damage if gastric emptying was accelerated. The results indicated that there was no difference in the rate of gastric emptying between normal healthy volunteers and portal hypertensive patients. However, patients who had received injection sclerotherapy emptied their stomachs faster than those who had not (p<0.05). Furthermore, the speed of gastric emptying correlated directly with the number of injections (r=0.41; p=0.02) and the volume of sclerosant injected (r=0.39; p=0.03). These observations suggest that injection sclerotherapy for oesophageal varices results in disturbances of gastric emptying that may contribute to the pathogenesis of portal hypertensive gastropathy

Epithelial senescence in idiopathic pulmonary fibrosis is propagated by small extracellular vesicles

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease that affects 3 million people worldwide. Senescence and small extracellular vesicles (sEVs) have been implicated in the pathogenesis of IPF, although how sEVs promote disease remains unclear. Here, we profile sEVs from bronchial epithelial cells and determine small RNA (smRNA) content. METHODS: Conditioned media was collected and sEVs were isolated from normal human bronchial epithelial cells (NHBEs) and IPF-diseased human bronchial epithelial cells (DHBEs). RESULTS: Increased sEV release from DHBEs compared to NHBEs (n = 4; p < 0.05) was detected by nanoparticle tracking analysis. NHBEs co-cultured with DHBE-derived sEVs for 72 h expressed higher levels of SA-β-Gal and γH2AX protein, p16 and p21 RNA and increased secretion of IL6 and IL8 proteins (all n = 6-8; p < 0.05). sEVs were also co-cultured with healthy air-liquid interface (ALI) cultures and similar results were observed, with increases in p21 and p16 gene expression and IL6 and IL8 (basal and apical) secretion (n = 6; p < 0.05). Transepithelial electrical resistance (TEER) measurements, a reflection of epithelial barrier integrity, were decreased upon the addition of DHBE-derived sEVs (n = 6; p < 0.05). smRNA-sequencing identified nineteen significantly differentially expressed miRNA in DHBE-derived sEVs compared to NHBE-derived sEVs, with candidate miRNAs validated by qPCR (all n = 5; p < 0.05). Four of these miRNAs were upregulated in NHBEs co-cultured with DHBE-derived sEVs and three in healthy ALI cultures co-cultured with DHBE-derived sEVs (n = 3-4; p < 0.05). CONCLUSIONS: This data demonstrates that DHBE-derived sEVs transfer senescence to neighbouring healthy cells, promoting the disease state in IPF

A trait‐based approach to plant species selection to increase functionality of farmland vegetative strips

Farmland vegetative strips are a proven source of support for ecosystem services and are globally used to mitigate effects of agricultural intensification. However, increasing pressures on agricultural land require increases in their functionality, such as supporting multiple ecosystem services concurrently. The plant species sown in a vegetative strip seed mix determine the establishment, plant community, and ecosystem services that are supported. Currently, there is no clearly defined or structured method to select plant species for multifunctional vegetative strips. Plant traits determine how plants support ecosystem services. Also, the establishment and persistence of plant communities is influenced by key internal and external factors. We propose a novel, evidence‐informed method of multifunctional vegetative strip design based on these essential traits and factors. This study had three distinct stages. The first identified plant traits that support water quality protection, pollinators and/or crop pest natural enemies, using existing research evidence. We then identified key factors affecting plant community establishment and persistence. Finally, we applied these standardized methods to design a multifunctional vegetative strip for a specific case study (UK lowland farmland). Key plant traits identified, included floral display size, flower color, nectar content, leaf surface area, leaf trichome density, percentage fine roots, root length, rooting depth, and root density. Key internal and external establishment factors included life history, native status, distribution, established competitive strategy, associated floristic diversity, flowering time and duration, and preferred soil type and pH. In the United Kingdom case study, we used five different plant traits and all of the identified factors to design a seed mix for a multifunctional vegetative strip. We present a transferable method of vegetative strip design that can be adapted for other ecosystem services and climates. It provides landowners and advisors with an evidence‐informed approach to increase field margin functionality while supporting farmland biodiversity

Coarse-grained simulation reveals key features of HIV-1 capsid self-assembly

The maturation of HIV-1 viral particles is essential for viral infectivity. During maturation, many copies of the capsid protein (CA) self-assemble into a capsid shell to enclose the viral RNA. The mechanistic details of the initiation and early stages of capsid assembly remain to be delineated. We present coarse-grained simulations of capsid assembly under various conditions, considering not only capsid lattice self-assembly but also the potential disassembly of capsid upon delivery to the cytoplasm of a target cell. The effects of CA concentration, molecular crowding, and the conformational variability of CA are described, with results indicating that capsid nucleation and growth is a multi-stage process requiring well-defined metastable intermediates. Generation of the mature capsid lattice is sensitive to local conditions, with relatively subtle changes in CA concentration and molecular crowding influencing self-assembly and the ensemble of structural morphologies

Species trait shifts in vegetation and soil seed bank during fen degradation

Fens in Central Europe are characterised by waterlogged organic substrate and low productivity. Human-induced changes due to drainage and mowing lead to changes in plant species composition from natural fen communities to fen meadows and later to over-drained, degraded meadows. Moderate drainage leads to increased vegetation productivity, and severe drainage results in frequent soil disturbances and less plant growth. In the present article, we analyse changes in plant trait combinations in the vegetation and the soil seed bank as well as changes in the seed bank types along gradient of drainage intensity. We hypothesize that an increase in productivity enhances traits related to persistence and that frequent disturbance selects for regeneration traits. We use multivariate statistics to analyse data from three disturbance levels: undisturbed fen, slightly drained fen meadow and severely drained degraded meadow. We found that the abundance of plants regenerating from seeds and accumulating persistent seed banks was increasing with degradation level, while plants reproducing vegetatively were gradually eliminated along the same trajectory. Plants with strong resprouting abilities increased during degradation. We also found that shifts in trait combinations were similar in the aboveground vegetation and in soil seed banks. We found that the density of short-term persistent seeds in the soil is highest in fen meadows and the density of long-term persistent seeds is highest in degraded meadows. The increase in abundance of species with strong regeneration traits at the cost of species with persistence-related traits has negative consequences for the restoration prospects of severely degraded sites

Frequent burning promotes invasions of alien plants into a mesic African savanna

Fire is both inevitable and necessary for maintaining the structure and functioning of mesic savannas. Without disturbances such as fire and herbivory, tree cover can increase at the expense of grass cover and over time dominate mesic savannas. Consequently, repeated burning is widely used to suppress tree recruitment and control bush encroachment. However, the effect of regular burning on invasion by alien plant species is little understood. Here, vegetation data from a long-term fire experiment, which began in 1953 in a mesic Zimbabwean savanna, were used to test whether the frequency of burning promoted alien plant invasion. The fire treatments consisted of late season fires, lit at 1-, 2-, 3-, and 4-year intervals, and these regularly burnt plots were compared with unburnt plots. Results show that over half a century of frequent burning promoted the invasion by alien plants relative to areas where fire was excluded. More alien plant species became established in plots that had a higher frequency of burning. The proportion of alien species in the species assemblage was highest in the annually burnt plots followed by plots burnt biennially. Alien plant invasion was lowest in plots protected from fire but did not differ significantly between plots burnt triennially and quadrennially. Further, the abundance of five alien forbs increased significantly as the interval (in years) between fires became shorter. On average, the density of these alien forbs in annually burnt plots was at least ten times as high as the density of unburnt plots. Plant diversity was also altered by long-term burning. Total plant species richness was significantly lower in the unburnt plots compared to regularly burnt plots. These findings suggest that frequent burning of mesic savannas enhances invasion by alien plants, with short intervals between fires favouring alien forbs. Therefore, reducing the frequency of burning may be a key to minimising the risk of alien plant spread into mesic savannas, which is important because invasive plants pose a threat to native biodiversity and may alter savanna functioning

Cirsium species show disparity in patterns of genetic variation at their range-edge, despite similar patterns of reproduction and isolation

Genetic variation was assessed across the UK geographical range of Cirsium acaule and Cirsium heterophyllum. A decline in genetic diversity and increase in population divergence approaching the range edge of these species was predicted based on parallel declines in population density and seed production reported seperately. Patterns were compared with UK populations of the widespread Cirsium arvense.Populations were sampled along a latitudinal transect in the UK and genetic variation assessed using microsatellite markers. Cirsium acaule shows strong isolation by distance, a significant decline in diversity and an increase in divergence among range-edge populations. Geographical structure is also evident in C. arvense, whereas no such patterns are seen in C.heterophyllum. There is a major disparity between patterns of genetic variation in C. acaule and C. heterophyllum despite very similar patterns in seed production and population isolation in these species. This suggests it may be misleading to make assumptions about the geographical structure of genetic variation within species based solely on the present-day reproduction and distribution of populations