bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intestinal mucus and gut-vascular barrier: FxR-modulated entry sites for pathological bacterial translocation in liver cirrhosis
Authors: Sorribas M. , Jakob M. O. , Yilmaz B. , Li H. , Stutz D. , Noser Y. , de Gottardi A. , Moghadamrad S. , Hassan M. , Albillos A. , Francés R. , Juanola O. , Spadoni I. , Rescigno M. , Wiest R. 
Published: July 2019

AbstractBackground and aimsPathological bacterial translocation (PBT) in liver cirrhosis (LC) is the hallmark for spontaneous bacterial infections increasing mortality several-fold. Factors known to contribute to PBT in LC are among others an increased intestinal permeability of which however, the mucus layer has not been addressed so far in detail. A clear route of translocation for luminal intestinal bacteria is yet to be defined but we hypothesize that the recently described gut vascular barrier (GVB) is impaired in experimental portal hypertension leading to increased accessibility of the vascular compartment for translocating bacteria.ResultsHealthy and pre-hepatic portal-hypertensive (PPVL) mice lack translocation of FITC-dextran and GFP-Escherichia colifrom the small intestine to the liver whereas bile-duct-ligated (BDL) and CCl4-induced cirrhotic mice demonstrate pathological translocation which is not altered by prior thoracic-duct ligation. Mucus layer is reduced in thickness with loss of goblet-cells and Muc2-staining and expression in cirrhotic but not PPVL-mice associated with bacterial overgrowth in inner mucus layer and pathological translocation of GFP-E.colithrough the ileal epithelium. GVB is profoundly altered in BDL and CCl4-mice with Ileal extravasation of large-sized 150 kDa-FITC-dextran but only minor in PPVL-mice. This pathological endothelial permeability and accessibility in cirrhotic mice associates with an augmented expression of PV1 in intestinal vessels. OCA but not fexaramine stabilizes the GVB whereas both FXR-agonists ameliorate gut-liver-translocation of GFP-E.coli.ConclusionsLiver cirrhosis but not portal hypertension per se grossly impairs the endothelial and muco-epithelial barriers promoting PBT to the portal-venous circulation. Both barriers appear FXR-modulated with –agonists reducing PBT via the portal-venous route.
Vaccine antigen, Factor H binding protein, is typically a non-lipidated precursor that localises to the meningococcal surface by Slam
Authors: da Silva RAG , Karlyshev AV , Oldfield NJ , Wooldridge KG , Bayliss CD , Ryan A , Griffin R 
Published: July 2019

AbstractMeningococcal surface lipoprotein, Factor H binding protein (FHbp), is the sole antigen of the Trumenba vaccine (Pfizer) and one of four antigens of the Bexsero vaccine (GSK) targetingNeisseria meningitidisserogroup B isolates. Lipidation of FHbp is assumed to occur for all isolates and its surface localisation is conducted by surface lipoprotein assembly modulator, Slam.We show in 91% of a collection of UK isolates (1742/1895) non-synonymous single nucleotide polymorphisms (SNPs) in the signal peptide of FHbp. A single SNP, common to all, alters a polar amino acid that abolishes processing, including lipidation and signal peptide cleavage. Rather than the toxic accumulation of the precursor in the periplasm as expected from disrupting the canonical processing pathway, remarkably the FHbp precursor is translocated to the outer membrane and surface-localised by Slam. Thus we show Slam is not lipoprotein-specific. In a panel of isolates expressing precursor FHbp at the surface, we investigated their binding to human factor H and their susceptibility to antibody-mediated killing. Our findings have implications for Trumenba and Bexsero and provide key insights for lipoprotein-based vaccines in development.
Reciprocity and behavioral heterogeneity govern the stability of social networks
Authors: Dakin Roslyn , Ryder T. Brandt 
Published: July 2019

AbstractThe dynamics of social networks can determine the transmission of information, the spread of diseases, and the evolution of behavior. Despite this broad importance, a general framework for predicting social network stability has not been proposed. Here, we present longitudinal data on the social dynamics of a cooperative bird species, the wire-tailed manakin, to evaluate the potential causes of temporal network stability. We find that when partners interact less frequently, and when the breadth of social connectedness within the network increases, the social network is subsequently less stable. Social connectivity was also negatively associated with the temporal persistence of coalition partnerships on an annual timescale. This negative association between connectivity and stability was surprising, especially given that individual manakins who were more connected also had more stable partnerships. This apparent paradox arises from a within-individual behavioral trade-off between partnership quantity and quality. Crucially, this trade-off is easily masked by behavioral variation among individuals. Using a simulation, we show that these results are explained by a simple model that combines among-individual behavioral heterogeneity and reciprocity within the network. As social networks become more connected, individuals face a trade-off between partnership quantity and maintenance. This model also demonstrates how among-individual behavioral heterogeneity, a ubiquitous feature of natural societies, can improve social stability. Together, these findings provide unifying principles that are expected to govern diverse social systems.Significance StatementIn animal societies, social partnerships form a dynamic network that can change over time. Why are some social network structures more stable than others? We addressed this question by studying a cooperative bird species in which social behavior is important for fitness, similar to humans. We found that stable social networks are characterized by more frequent interactions, but sparser connectivity throughout the network. Using a simulation, we show how both results can be explained by a simple model of reciprocity. These findings indicate that social stability is governed by a trade-off whereby individuals can either maintain a few high-quality partners, or increase partner number. This fundamental trade-off may govern the dynamics and stability of many societies, including in humans.
West Asian sources of the Eurasian component in Ethiopians: a reassessment
Authors: Molinaro Ludovica , Montinaro Francesco , Kivisild Toomas , Pagani Luca 
Published: July 2019

SummaryPrevious genome-scale studies of populations living today in Ethiopia have found evidence of recent gene flow from an Eurasian source, dating to the last 3,000 years1,2,3,4. Haplotype1 and genotype data based analyses of modern2,4 and ancient data (aDNA)3,5 have considered Sardinia-like proxy2, broadly Levantine1,4 or Neolithic Levantine3 populations as a range of possible sources for this gene flow. Given the ancient nature of this gene flow and the extent of population movements and replacements that affected West Asia in the last 3000 years, aDNA evidence would seem as the best proxy for determining the putative population source. We demonstrate, however, that the deeply divergent, autochthonous African component which accounts for ∼50% of most contemporary Ethiopian genomes, affects the overall allele frequency spectrum to an extent that makes it hard to control for it and, at once, to discern between subtly different, yet important, Eurasian sources (such as Anatolian or Levant Neolithic ones). Here we re-assess pattern of allele sharing between the Eurasian component of Ethiopians (here called “NAF” for Non African) and ancient and modern proxies area after having extracted NAF from Ethiopians through ancestry deconvolution, and unveil a genomic signature compatible with population movements that affected the Mediterranean area and the Levant after the fall of the Minoan civilization.
Antinociceptive and Antioxidant Activities of Methanolic Extract of Leaves of Azadirachta Indica (Neem)
Authors: Mali Akash S , Thorat Mahesh B , Ghadge Dhairyasheel M. , Nikam Kumodini A. , Sawant Shraddha , Shaikh Farida , Vhatkar Nayana , Shinde Swapnja , Gonghade Kavyashree , Tamboli Munaf A. 
Published: July 2019

AbstractGraphical abstractBackgroundAzadirachta indica (Neem) is a communal plant of Meliaceae family called Neem Or Kadunimb in Maharashtra, India Neem stated anti-inflammatory through regulation of proinflammatory enzyme activities with COX and LOX enzyme. Previous studies show that Azadirachta Indica (neem) and its chief constituents play essential role in anticancer management via the modulation of different molecular pathways including NF-κB, p53, PI3K/Akt, Bcl-2, pTEN and VEGF. Many parts of the plant are traditionally used in the treatment of various pharmacological action, the analgesic activity of Neem Seed Oil has already reported but Neem Leaves.MethodsThe antinociceptive activity of Azadirachta Indica Leaves (AZIL) was examined using heat-induced-mechanical (hot-plate and tail-immersion test) and chemical-induced (acetic acid, formalin, glutamic acid, cinnamaldehyde) nociception models in mice at 50,100, and 200 mg/kg doses. ATP-sensitive K+ channel pathway, cyclic guanosine monophosphate (cGMP) pathway and involvement of opioid system was also tested using glibenclamide, methylene blue and naloxone/morphine respectively. The methanolic extract of leaves of A.Indica was assessed by using different in vitro antioxidant models of screening like scavenging of 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical, nitric oxide radical, superoxide anion radical, and hydroxyl radical.ResultsAZIL showed antinociceptive activity and antioxidant activity. In both hot plate and tail immersion tests AZIL significantly increases the latency to the thermal stimuli. In acetic acid-induced writhing test the extract repressed the number of abdominal writhing. Similarly, AZIL produced substantial dose-dependent inhibition of paw licking in both neurogenic and inflammatory pain induced by intraplanar injection of formalin. As well, AZIL also expressively withdrawn cinnamaldehyde-induced pain and the glutamate-induced pain in mice. It was also proved that pretreatment with naloxone significantly reversed the antinociception produced by AZIL in mechanical tests signifying the involvement of opioid system in its effect. Furthermore, administration of methylene blue, enhanced AZIL induced antinociception while glibenclamide, an ATP-sensitive K+ channel antagonist, could not converse antinociceptive activity induced by AZIL.ConclusionBased on the results of the present study it can be said that AZIL keeps significant antinociceptive activity which acts in both central and peripheral mechanisms.Ethnopharmacological relevanceAzadiracta Indica having family Melliases is one of the common medicinal plant in United states and south Asia including India, Pakistan, Bangladesh. Various parts of the plants used in treatment of many inflammatory conditions, skin diseases, tooth protection, antidiabetic in the form of oil and herbal porridge.
An engineered serum albumin-binding AAV9 capsid achieves improved liver transduction after intravenous delivery in mice
Authors: Jin Quan , Qiao Chunping , Li Jianbin , Li Juan , Xiao Xiao 
Published: July 2019

ABSTRACTRecombinant adeno-associated viral (AAV) vectors are frequently used to deliver nucleic acids for in vivo applications and are currently the leading platform for therapeutic gene delivery in gene therapy clinical trials. Presently, there is a need for improved AAV vectors with optimized transduction efficiency in target tissues. In these studies, an engineered albumin-binding consensus domain (ABDCon) was incorporated into the AAV9 capsid via fusion to the N-terminus of the AAV9 VP2 capsid protein to generate a variant AAV9 capsid with albumin-binding properties. The variant capsid, called AAV9-ABDCon, formed viable genome-containing vector particles and exhibited binding to human serum albumin. The AAV9 capsid, on the other hand, was not found to bind to human serum albumin by the methods used in this study. Following intravenous administration, the modified AAV9-ABDCon vector was found to achieve higher levels of transduction in liver tissue compared to AAV9. These findings suggest that serum albumin-binding may be a potential method to augment AAV-mediated liver-directed gene delivery.
Comparative genomics in plant fungal pathogens (Mycosphaerellaceae): variation in mitochondrial composition due to at least five independent intron invasions
Authors: Arcila Juliana E. , Arango Rafael E. , Torres Javier M. , Arias Tatiana 
Published: July 2019

AbstractFungi provide new opportunities to study highly differentiated mitochondrial DNA. Mycosphaerellaceae is a highly diverse fungal family containing a variety of pathogens affecting many economically important crops.Mitochondria plays a major role in fungal metabolism and fungicide resistance but up until now only two annotated mitochondrial genomes have been published in this family. We sequenced and annotated mitochondrial genomes of selected Mycosphaerellaceae species that diverged ∼66 MYA. During this time frame, mitochondrial genomes expanded significantly due to at least five independent invasions of introns into different electron transport chain genes. Comparative analysis revealed high variability in size and gene order among mitochondrial genomes even of closely related organisms, truncated extra gene copies and, accessory genes in some species. Gene order variability was common probably due to rearrangements caused by mobile intron invasion. Three threecox1copies and bicistronic transcription ofnad2-nad3andatp6-atp8inPseudocercospora fijiensiswere confirmed experimentally. Even though we found variation in mitochondrial genome composition, there was no evidence of hybridization when comparing nuclear and mitochondrial dataset sets for fungal plant pathogens analyzed here. Disentangling the causes of variation in mitochondrial genome composition in plant pathogenic fungal move us closer to understanding the molecular mechanisms responsible for vital functions in fungi ultimately aiding in controlling these diseases.
Non-sedating benzodiazepines cause contractile paralysis and tissue damage in the parasitic blood flukeSchistosoma mansoni
Authors: McCusker Paul , Mian Yeunus , Li Guanguan , Olp Michael D. , Tiruveedhula V. V. N. Phani Babu , Rashid Farjana , Golani Lalit Kumar , Smith Brian C. , Cook James M. , Chan John D. 
Published: July 2019

AbstractParasitic flatworm infections (e.g. tapeworms and fluke worms) are treated by a limited number of drugs. In most cases, control is reliant upon praziquantel (PZQ) monotherapy. However, PZQ is ineffective against sexually immature parasites, and there have also been several concerning reports of cestode and trematode infections with poor PZQ cure-rates, emphasizing the need for alternative therapies to treat these infections. We have revisited a series of benzodiazepines, given the known anti-schistosomal activity of meclonazepam (MCLZ). MCLZ was discovered in the 1970’s but was not brought to market due to dose-limiting sedative side effects. However, in the decades since there have been advances in our understanding of the benzodiazepine GABAAreceptor sub-types that drive sedation and the development of sub-type selective, non-sedating ligands. Additionally, the sequencing of flatworm genomes reveals that parasitic trematodes and cestodes have lost GABAAR-like ligand gated anion channels, indicating that MCLZ’s anti-parasitic target is likely distinct from the human receptors that drive sedation. Therefore, we screened a library of classical and non-sedating 1,4-benzodiazepines againstSchistosoma mansoniand identified a series of imidazobenzodiazepines that immobilize wormsin vitro. One of these hits, Xhe-II-048 also disrupted the parasite tegument, causing extensive vacuole formation beneath the apical membrane. The imidazobenzodiazepine compound series identified has a dramatically lower (∼1 log) affinity for human central benzodiazepine binding site and is a promising starting point for the development of novel anti-schistosomal benzodiazepines with minimal host side-effects.Author SummaryOver 200 million people are infected with schistosomiasis, yet there are limited therapeutic options available to treat this disease. The benzodiazepine meclonazepam is known to cure both intestinal and urinary schistosomiasis in animal and human studies, but dose-limiting sedation has been a barrier to its development. Little is known about the structure-activity relationship of meclonazepam and other benzodiazepines on schistosomes, or the identity of the parasite receptor for these compounds. However, schistosomes lack obvious homologs to the human GABAARs that cause sedation. This indicates that the parasite target of this drug is distinct from the host receptors that underpin dose-limiting side effects of meclonazepam, and raises the possibility that benzodiazepines with poor GABAAR affinity may still retain anti-parasitic effects. Here, we report anin vitroscreen of various benzodiazepines against schistosomes, and the identification of hit compounds that are active against worms yet possess reduced affinity for the human GABAARs that cause sedation.
Image-based Phenotyping and Genetic Analysis of Potato Skin Set and Color
Authors: Caraza-Harter Maria V. , Endelman Jeffrey B. 
Published: July 2019

ABSTRACTImage-based phenotyping offers new opportunities for fast, objective, and reliable measurement for breeding and genetics research. In the current study, image analysis was used to quantify potato skin color and skin set, which are critical for the marketability of new varieties. A set of 15 red potato varieties and advanced breeding lines was evaluated over two years at a single location, with two harvest times in the second year. After mechanical harvest and grading, 7-8 representative tubers per plot were photographed, and the photos were analyzed with ImageJ to measure skinning (as % surface area) and skin color using the Hue, Chroma and Lightness (HCL) representation. The plot-based heritability was consistently high (> 0.77) across traits and environments; the genetic correlation between environments was also high, ranging from 0.81 to 0.98. Significant increases in Lightness and Chroma, as well as a decrease in skinning, were observed at the late compared to early harvest, while the opposite trends for color were observed after six weeks of storage. The three color traits were unexpectedly collinear in this study, with the first principal component explaining 86% of the variation. This result may reflect the physiology of red color in potato, but the highly selected nature of the 15 genotypes may also be a factor. Image-based phenotyping offers new opportunities to advance genetic gain and understanding for tuber appearance traits that have been difficult to precisely measure in the past.
Social inhibition maintains adaptivity and consensus of foraging honeybee swarms in dynamic environments
Authors: Bidari Subekshya , Peleg Orit , Kilpatrick Zachary P 
Published: July 2019

AbstractTo effectively forage in natural environments, organisms must adapt to changes in the quality and yield of food sources across multiple timescales. Individuals foraging in groups act based on both their private observations and the opinions of their neighbors. How do these information sources interact in changing environments? We address this problem in the context of honeybee swarms, showing inhibitory social interactions help maintain adaptivity and consensus needed for effective foraging. Individual and social interactions of a mathematical swarm model shape the nutrition yield of a group foraging from feeders with temporally switching food quality. Social interactions improve foraging from a single feeder if temporal switching is fast or feeder quality is low. When the swarm chooses from multiple feeders, the most effective form of social interaction is direct switching, whereby bees flip the opinion of nestmates foraging at lower yielding feeders. Model linearization shows that effective social interactions increase the fraction of the swarm at the correct feeder (consensus) and the rate at which bees reach that feeder (adaptivity). Our mathematical framework allows us to compare a suite of social inhibition mechanisms, suggesting experimental protocols for revealing effective swarm foraging strategies in dynamic environments.
Associated habitat and suitability modeling of goldenseal (Hydrastis canadensisL.) in Pennsylvania: explaining and predicting species distribution in a northern edge of range state
Authors: Zuiderveen Grady H. , Chen Xin , Burkhart Eric P. , Miller Douglas A. 
Published: July 2019

AbstractGoldenseal (Hydrastis canadensisL.) is a well-known perennial herb indigenous to forested areas in eastern North America. Owing to conservation concerns including wild harvesting for medicinal markets, habitat loss and degradation, and an overall patchy and often inexplicable absence in many regions, there is a need to better understand habitat factors that help determine the presence and distribution of goldenseal populations. In this study, flora and edaphic factors associated with goldenseal populations throughout Pennsylvania—a state near the northern edge of its range—were documented and analyzed to identify habitat indicators and provide possible in situ stewardship and farming (especially forest-based farming) guidance. Additionally, maximum entropy (Maxent) modeling was applied to better predict where suitable habitat might be encountered more broadly and explain species absence from regions of the state (and the northeastern states). Habitat study results identified rich, mesic, woodland sites as being suitable for goldenseal. The most prevalent overstory tree associates on such sites were tulip-poplar (Liriodendron tulipiferaL.) and sugar maple (Acer saccharumMarshall), and the most common understory associates were spicebush (Lindera benzoinL.), Virginia creeper (Parthenocissus quinquefolia(L.) Planch.), Jack-in-the-pulpit (Arisaema triphyllum(L.) Schott), mayapple (Podophyllum peltatumL.), wood fern (Drypoteris marginalis(L.) A. Gray), and rattlesnake fern (Botrypus virginianus(L.) Michx.). Loam soils were the most common textural class (average sand, silt, and clay ratio of 50:30:20) with an average pH of 6.2 and high variation in macronutrients. While such sites are widespread in the state, Maxent modeling suggested the present distribution in Pennsylvania is largely restricted by winter temperatures and bedrock type. The latter of these, in turn, is correlated in part with land use legacy (e.g., clearing for farming or livestock grazing), especially in southeast portions of the state.