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Selegiline transdermal system is a recently approved monoamine oxidase inhibitor antidepressant. Medications that inhibit monoamine oxidase type A can augment the pressor effects of sympathomimetic amines, increasing the potential for hypertensive crisis. This study examined the potential for drug-drug interactions during treatment with selegiline transdermal system and pseudoephedrine or phenylpropanolamine. Two studies were conducted with 25 healthy volunteers to assess changes in blood pressure and heart rate during administration of pseudoephedrine or phenylpropanolamine alone or together with selegiline transdermal system. No significant differences in mean maximum changes in vital signs occurred with pseudoephedrine. No significant differences were found in mean maximum changes in systolic heart rate with phenylpropanolamine; however, 4 of 12 subjects each experienced 1 isolated protocol-defined minimal pressor response without concurrent adverse effects (1 with phenylpropanolamine alone; 3 with phenylpropanolamine + selegiline transdermal system). Pharmacokinetic parameters obtained following selegiline transdermal system and pseudoephedrine or phenylpropanolamine were unremarkable. The results suggest that selegiline transdermal system 6 mg/24 h does not significantly alter the pharmacodynamics or pharmacokinetics of either pseudoephedrine or phenylpropanolamine when administered to healthy volunteers; however, it is prudent to avoid coadministration of selegiline transdermal system and sympathomimetics. [ABSTRACT FROM AUTHOR]

Selegiline transdermal system (STS) is a recently approved monoamine oxidase inhibitor antidepressant. This article reports results from 3 studies examining the potential for cytochrome P450-dependent pharmacokinetic interactions between STS and 3 psychotropic medications that might be coadministered. Three open-label, randomized, Latin square, 3-sequence crossover design studies were conducted with healthy volunteers to determine the pharmacokinetic parameters of STS 6 mg/24 h and test drug (alprazolam, olanzapine, or risperidone) when administered alone and concomitantly. All pharmacokinetic parameters of interest were unaltered following selegiline or test drug monotherapy when compared to concomitant therapy. This was confirmed by least squares mean ratios and their 90% confidence intervals of log(e)-transformed C(max) and AUC(tau) values, using either standard bioequivalence criteria of 80% to 125% or study-defined 70% to 143% boundary criteria. These results demonstrate that STS 6 mg/24 h may provide an antidepressant option that is unlikely to result in CYP450-mediated pharmacokinetic drug-drug interactions. [ABSTRACT FROM AUTHOR]

The oral tyramine pressor test was administered to healthy males during treatment with a selegiline transdermal system (STS; 6 mg/24 h). The tyramine sensitivity factor (TSF) was calculated from the ratio of baseline and on-treatment tyramine pressor doses. The tyramine sensitivity factor value following 9 days of treatment with the selegiline transdermal system was 1.85 +/- 0.10. Extended treatment, 33 days, produced a small, clinically nonmeaningful increase in this value. The tyramine sensitivity factor for the selegiline transdermal system was similar to that following treatment with 10 mg/d of oral selegiline capsules but more than 20 times less than observed during tranylcypromine treatment. A larger increase in the tyramine sensitivity factor was observed following extended selegiline transdermal system treatment at a higher dose (12 mg/24 h), which was significantly decreased following coadministration of tyramine capsules with a meal. These results suggest a wide tyramine safety margin for the selegiline transdermal system and provide evidence that the 6-mg/24-h selegiline transdermal system can be administered safely without dietary tyramine restrictions. [ABSTRACT FROM AUTHOR]

A report from the International Union of Crystallography Commission on Magnetic Structures outlining the recommendations for communicating commensurate magnetic structures.

Chiral multiferroics offer remarkable capabilities for controlling quantum devices at multiple levels. However, these materials are rare due to the competing requirements of long-range orders and strict symmetry constraints. In this study, we present experimental evidence that the coexistence of ferroelectric, magnetic orders, and crystallographic chirality is achievable in hybrid organic-inorganic perovskites [(R/S)-β-methylphenethylamine] 2 CuCl 4 . By employing Landau symmetry mode analysis, we investigate the interplay between chirality and ferroic orders and propose a novel mechanism for chirality transfer in hybrid systems. This mechanism involves the coupling of non-chiral distortions, characterized by defining a pseudo-scalar quantity, ξ = p ⋅ r ( p represents the ferroelectric displacement vector and r denotes the ferro-rotational vector), which distinguishes between (R)- and (S)-chirality based on its sign. Moreover, the reversal of this descriptor's sign can be associated with coordinated transitions in ferroelectric distortions, Jahn-Teller antiferro-distortions, and Dzyaloshinskii-Moriya vectors, indicating the mediating role of crystallographic chirality in magnetoelectric correlations., (© 2024. The Author(s).)

Boron substitution represents a promising approach to stabilize carbon clathrate structures, but no thermodynamically stable substitution schemes have been identified for frameworks other than the type-VII (sodalite) structure type. To investigate the possibility for additional tetrahedral carbon-based clathrate networks, more than 5000 unique boron decoration schemes were investigated computationally for type-I and type-II carbon clathrates with a range of guest elements including Li, Na, K, Rb, Cs, Mg, Ca, Sr, and Ba. Density functional theory calculations were performed at 10 and 50 GPa, and the stability and impact of boron substitution were evaluated. The results indicate that the boron-substituted carbon clathrates are stabilized under high-pressure conditions. Full cage occupancies of intermediate-sized guest atoms (e.g., Na, Ca, and Sr) are the most favorable energetically. Clathrate stability is maximized when the boron atoms are substituted within the hexagonal rings of the large [5 12 6 2 ]/[5 12 6 4 ] cages. Several structures with favorable formation enthalpies <-200 meV/atom were predicted, and type-I Ca 8 B 16 C 30 is on the convex hull at 50 GPa. This structure represents the first thermodynamically stable type-I clathrate identified and suggests that boron-substituted carbon clathrates may represent a large family of diamond-like framework materials with a range of structure types and guest/framework substitutions.

Organic-inorganic metal hybrids with their tailorable lattice dimensionality and intrinsic spin-splitting properties are interesting material platforms for spintronic applications. While the spin decoherence process is extensively studied in lead- and tin-based hybrids, these systems generally show short spin decoherence lifetimes, and their correlation with the lattice framework is still not well-understood. Herein, we synthesized magnetic manganese hybrid single crystals of (4-fluorobenzylamine) 2 MnCl 4 , (( R )-3-fluoropyrrolidinium)MnCl 3 , and (pyrrolidinium) 2 MnCl 4 , which represent a change in lattice dimensionality from 2D and 1D to 0D, and studied their spin decoherence processes using continuous-wave electron spin resonance spectroscopy. All manganese hybrids exhibit nanosecond-scale spin decoherence time τ 2 dominated by the symmetry-directed spin exchange interaction strengths of Mn 2+ -Mn 2+ pairs, which is much longer than lead- and tin-based metal hybrids. In contrast to the similar temperature variation laws of τ 2 in 2D and 0D structures, which first increase and gradually drop afterward, the 1D structure presents a monotonous rise of τ 2 with the temperatures, indicating the strong correlation of spin decoherence with the lattice rigidity of the inorganic framework. This is also rationalized on the basis that the spin decoherence is governed by the competitive contributions from motional narrowing (prolonging the τ 2 ) and electron-phonon coupling interaction (shortening the τ 2 ), both of which are thermally activated, with the difference that the former is more pronounced in rigid crystalline lattices.

The close association between bacteria and insect hosts has played an indispensable role in insect diversity and ecology. Thus, continued characterization of such insect-associated-microbial communities is imperative, especially those of saprophagous scarab beetles. The bacterial community of the digestive tract of adults and larvae of the cetoniine scarab species Cotinis nitida is characterized according to life stage, gut structure, and sex via high-throughput 16S rRNA gene amplicon sequencing. Through permutational ANOVAs of the resulting sequences, bacterial communities of the digestive system are shown to differ significantly between adults and larvae in taxon richness, evenness and relatedness. Significant bacterial community-level differences are also observed between the midgut and hindgut in adult beetles, while no significant host-sex differences are observed. The partitioning between bacterial communities in the larval digestive system is shown through significant differences in two distinct hindgut regions, the ileum and the expanded paunch, but not between the midgut and ileum portion of the hindgut region. These data further corroborate the hypothesis of strong community partitioning in the gut of members of the Scarabaeoidea, suggest hypotheses of physiological-digestive association, and also demonstrate the presence of a seemingly unusual non-scarab-associated taxon. These findings contribute to a general portrait of scarabaeoid digestive tract bacterial communities while illuminating the microbiome of a common new world cetoniine of the Gymnetini-a tribe largely neglected in scarab and beetle microbiome and symbiosis literature., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kucuk, Campbell, Lyon, Shelby and Caterino.)

Probiotics may have the potential to protect against breast cancer, partly through systemic immunomodulatory action and active impact upon intestinal microbiota. Given a few clinical studies on their curative role, we conducted a systematic review of the potential effects of probiotics in breast cancer patients and survivors of breast cancer, aiming to support further clinical studies. A literature search was performed using PubMed, Embase, and the CENTRAL databases from inception through to March 2022. A total of eight randomized clinical trials were identified from thirteen articles published between 2004 and 2022. We evaluated quality-of-life measures, observed bacterial species and diversity indices, probiotic-related metabolites, inflammatory biomarkers, and other responses in breast cancer patients and survivors. Results were synthesized qualitatively and quantitatively using random-effects meta-analysis. Different probiotics supplements utilized included Lactobacillus species alone (Lacto), with or without estriol; probiotic combinations of Lactobacillus with Bifidobacterium (ProLB), with or without prebiotic fructooligosaccharides (FOS); ProLB plus Streptococcus and FOS (ProLBS + FOS); and ProLB plus Enterococcus (ProLBE). We found that use of ProLBS with FOS in breast cancer patients and use of ProLBE in survivors of breast cancer show potential benefits in countering obesity and dyslipidemia. ProLBS with FOS use decreases pro-inflammatory TNF-α in breast cancer survivors and improves quality of life in those with breast-cancer-associated lymphedema. Supplementing probiotics capsules (10 9 CFU) with a prebiotic and using an intake duration of 10 weeks could provide a better approach than probiotics alone., Competing Interests: The authors declare no conflict of interest.

Interleukin-10 (IL-10) is an anti-inflammatory cytokine that has a major protective role against intestinal inflammation. We recently revealed that intestinal epithelial cells in vitro regulate NFκB-driven transcriptional responses to TNF via an autocrine mechanism dependent on IL-10 secretion. Here in this study, we investigated the impact of IL-10 deficiency on the NFκB pathway and its downstream targets in the small intestinal mucosa in vivo. We observed dysregulation of TNF, IκBα, and A20 gene and protein expression in the small intestine of steady-state or TNF-injected Il10 -/- mice, compared to wild-type C57BL6/J counterparts. Upon TNF injection, tissue from the small intestine showed upregulation of NFκB p65[RelA] activity, which was totally diminished in Il10 -/- mice and correlated with reduced levels of TNF, IκBα, and A20 expression. In serum, whilst IgA levels were noted to be markedly downregulated in IL-10-deficient - mice, normal levels of mucosal IgA were seen in intestine mucosa. Importantly, dysregulated cytokine/chemokine levels were observed in both serum and intestinal tissue lysates from naïve, as well as TNF-injected Il10 -/- mice. These data further support the importance of the IL-10-canonical NFκB signaling pathway axis in regulating intestinal mucosa homeostasis and response to inflammatory triggers in vivo.

Rhizobiome confer stress tolerance to ruderal plants, yet their ability to alleviate stress in crops is widely debated, and the associated mechanisms are poorly understood. We monitored the drought tolerance of maize (Zea mays) as influenced by the cross-inoculation of rhizobiota from a congeneric ruderal grass Andropogon virginicus (andropogon-inoculum), and rhizobiota from organic farm maintained under mesic condition (organic-inoculum). Across drought treatments (40% field capacity), maize that received andropogon-inoculum produced two-fold greater biomass. This drought tolerance translated to a similar leaf metabolomic composition as that of the well-watered control (80% field capacity) and reduced oxidative damage, despite a lower activity of antioxidant enzymes. At a morphological-level, drought tolerance was associated with an increase in specific root length and surface area facilitated by the homeostasis of phytohormones promoting root branching. At a proteome-level, the drought tolerance was associated with upregulation of proteins related to glutathione metabolism and endoplasmic reticulum-associated degradation process. Fungal taxa belonging to Ascomycota, Mortierellomycota, Archaeorhizomycetes, Dothideomycetes, and Agaricomycetes in andropogon-inoculum were identified as potential indicators of drought tolerance. Our study provides a mechanistic understanding of the rhizobiome-facilitated drought tolerance and demonstrates a better path to utilize plant-rhizobiome associations to enhance drought tolerance in crops., (© 2022 The Authors. The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.)

A magnetic superspace group (MSSG) simultaneously constrains both the magnetic and non-magnetic (e.g. displacive, occupational, rotation and strain) degrees of freedom of an incommensurately modulated magnetic crystal. We present the first enumeration and tabulation of all non-equivalent (3+d)-dimensional magnetic superspace groups for d = 1, 2 and 3 independent incommensurate modulations, along with a number, symbol and reference setting for each group. We explain the process for generating an exhaustive set of inequivalent magnetic superspace groups, describe several examples, and show how the tables can be accessed via the ISO(3+d)D interface within the ISOTROPY Software Suite. We recommend that published incommensurate magnetic structures indicate a magnetic superspace-group number and symbol from these tables, as well as the transformation matrix from the published group setting to the reference setting used in these tables.

The symbiosis of arbuscular mycorrhizal fungi (AMF) with plants, the most ancient and widespread association, exhibits phenotypes that range from mutualism to parasitism. However, we still lack an understanding of the cellular-level mechanisms that differentiate and regulate these phenotypes. We assessed the modulation in growth parameters and root metabolome of two sorghum accessions inoculated with two AMF species (Rhizophagus irregularis, Gigaspora gigantea), alone and in a mixture under phosphorus (P) limiting conditions. Rhizophagus irregularis exhibited a mutualistic phenotype with increased P uptake and plant growth. This positive outcome was associated with a facilitatory metabolic response including higher abundance of organic acids and specialized metabolites critical to maintaining a functional symbiosis. However, G. gigantea exhibited a parasitic phenotype that led to plant growth depression and resulted in inhibitory plant metabolic responses including the higher abundance of p-hydroxyphenylacetaldoxime with antifungal properties. These findings suggest that the differential outcome of plant-AMF symbiosis could be regulated by or reflected in changes in the root metabolome that arises from the interaction of the plant species with the specific AMF species. A mutualistic symbiotic association prevailed when the host plants were exposed to a mixture of AMF. Our results provide a metabolome-level landscape of plant-AMF symbiosis and highlight the importance of the identity of both AMF and crop genotypes in facilitating a mutualistic AMF symbiosis., (© 2022 The Authors. New Phytologist © 2022 New Phytologist Foundation.)

The NFκB transcription factors are major regulators of innate immune responses, and NFκB signal pathway dysregulation is linked to inflammatory disease. Here, we utilised bone marrow-derived macrophages from the p65-DsRedxp/IκBα-eGFP transgenic strain to study the functional implication of xenogeneic (human) RelA(p65) protein introduced into the mouse genome. Confocal imaging showed that human RelA is expressed in the cells and can translocate to the nucleus following activation of Toll-like receptor 4. RNA sequencing of lipid A-stimulated macrophages, revealed that human RelA impacts on murine gene transcription, affecting both non-NFκB and NFκB target genes, including immediate-early and late response genes, e.g., Fos and Cxcl10 . Validation experiments on NFκB targets revealed markedly reduced mRNA levels, but similar kinetic profiles in transgenic cells compared to wild-type. Enrichment pathway analysis of differentially expressed genes revealed interferon and cytokine signaling were affected. These immune response pathways were also affected in macrophages treated with tumor necrosis factor. Data suggests that the presence of xenogeneic RelA protein likely has inhibitory activity, altering specific transcriptional profiles of key molecules involved in immune responses. It is therefore essential that this information be taken into consideration when designing and interpreting future experiments using this transgenic strain.

The two commonly used systems of magnetic space-group (MSG) symbols, with accompanying numbers and settings, are those of Belov-Neronova-Smirnova (BNS) and Opechowski-Guccione (OG). The symbols from both systems have been used for several decades now. Both have advantages and disadvantages. Both present challenges of interpretation to novice and expert users alike, which can inhibit understanding and lead to errors in published magnetic structures. To address each of these challenges going forward, a new unified (UNI) MSG symbol is introduced, which combines a modified BNS symbol with essential information from the OG symbol.

Clostridioides difficile infection (CDI) is a leading cause of antibiotic-associated diarrhoea. Adhesion of this Gram-positive pathogen to the intestinal epithelium is a crucial step in CDI, with recurrence and relapse of disease dependent on epithelial interaction of its endospores. Close proximity, or adhesion of, hypervirulent strains to the intestinal mucosa are also likely to be necessary for the release of C. difficile toxins, which when internalized, result in intestinal epithelial cell rounding, damage, inflammation, loss of barrier function and diarrhoea. Interrupting these C. difficile -epithelium interactions could therefore represent a promising therapeutic strategy to prevent and treat CDI. Intake of dietary fibre is widely recognised as being beneficial for intestinal health, and we have previously shown that soluble non-starch polysaccharides (NSP) from plantain banana ( Musa spp.), can block epithelial adhesion and invasion of a number of gut pathogens, such as E. coli and Salmonellae. Here, we assessed the action of plantain NSP, and a range of alternative soluble plant fibres, for inhibitory action on epithelial interactions of C. difficile clinical isolates, purified endospore preparations and toxins. We found that plantain NSP possessed ability to disrupt epithelial adhesion of C. difficile vegetative cells and spores, with inhibitory activity against C. difficile found within the acidic (pectin-rich) polysaccharide component, through interaction with the intestinal epithelium. Similar activity was found with NSP purified from broccoli and leek, although seen to be less potent than NSP from plantain. Whilst plantain NSP could not block the interaction and intracellular action of purified C. difficile toxins, it significantly diminished the epithelial impact of C. difficile , reducing both bacteria and toxin induced inflammation, activation of caspase 3/7 and cytotoxicity in human intestinal cell-line and murine intestinal organoid cultures. Dietary supplementation with soluble NSP from plantain may therefore confer a protective effect in CDI patients by preventing adhesion of C. difficile to the mucosa, i.e. a "contrabiotic" effect, and diminishing its epithelial impact. This suggests that plantain soluble dietary fibre may be a therapeutically effective nutritional product for use in the prevention or treatment of CDI and antibiotic-associated diarrhoea., Competing Interests: NO’K is a present, and CR a past, employee of Provexis Plc. BC, HS and JR received additional funding support from the biotech partner Provexis Plc as part of the BBSRC Industrial CASE studentship (BB/I016783/1). JR is listed as inventor on patents held by Provexis Plc, in a licence agreement with the University of Liverpool, for use of complex oligosaccharides in the prevention or treatment of inflammatory bowel disease (US8945639B2), and for use of soluble fibres in antibiotic-associated diarrhoea (US20120165289A1). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Simpson, Roberts, Thompson, Leiper, Gittens, Trotter, Duckworth, Papoutsopoulou, Miyajima, Roberts, O’Kennedy, Rhodes and Campbell.)

A user-friendly web-based software tool called ' ISOTILT ' is introduced for detecting cooperative rigid-unit modes (RUMs) in networks of interconnected rigid units ( e.g. molecules, clusters or polyhedral units). This tool implements a recently described algorithm in which symmetry-mode patterns of pivot-atom rotation and displacement vectors are used to construct a linear system of equations whose null space consists entirely of RUMs. The symmetry modes are first separated into independent symmetry-mode blocks and the set of equations for each block is solved separately by singular value decomposition. ISOTILT is the newest member of the ISOTROPY Software Suite . Here, it is shown how to prepare structural and symmetry-mode information for use in ISOTILT , how to use each of ISOTILT 's input fields and options, and how to use and interpret ISOTILT output., (© Branton J. Campbell et al. 2021.)

Understanding the genetic basis of complex traits is a fundamental goal of evolutionary genetics. Yet, the genetics controlling complex traits in many important species such as hemp (Cannabis sativa) remain poorly investigated. Because hemp's change in legal status with the 2014 and 2018 U.S. Federal Farm Bills, interest in the genetics controlling its numerous agriculturally important traits has steadily increased. To better understand the genetics of agriculturally important traits in hemp, we developed an F2 population by crossing two phenotypically distinct hemp cultivars (Carmagnola and USO31). Using whole-genome sequencing, we mapped quantitative trait loci (QTL) associated with variation in numerous agronomic and biochemical traits. A total of 69 loci associated with agronomic (34) and biochemical (35) trait variation were identified. We found that most QTL co-localized, suggesting that the phenotypic distinctions between Carmagnola and USO31 are largely controlled by a small number of loci. We identified TINY and olivetol synthase as candidate genes underlying co-localized QTL clusters for agronomic and biochemical traits, respectively. We functionally validated the olivetol synthase candidate by expressing the alleles in yeast. Gas chromatography-mass spectrometry assays of extracts from these yeast colonies suggest that the USO31 olivetol synthase is functionally less active and potentially explains why USO31 produces lower cannabinoids compared to Carmagnola. Overall, our results help modernize the genomic understanding of complex traits in hemp., (© The Author(s) 2021. Published by Oxford University Press on behalf of Genetics Society of America.)

The objective of this experiment was to evaluate the impact of protein supplementation and pasture contamination with gastrointestinal nematodes on the mitigation of parasitic infection in grazing lambs. We hypothesized that there would be no difference between protein supplementation and newly sown pasture in evaluating lamb growth and health parameters associated with parasitism. Furthermore, we questioned if there would be an interaction between protein supplementation and pasture type. A total of 192, 60-d-old lambs (28.3 ± 5.1 kg) were randomly assigned to one of four treatments: 1) new pasture without supplementation (NN); 2) new pasture with supplementation (NS); 3) established pasture without supplementation (EN); and 4) established pasture with supplementation (ES) and grazed for 112 d. Lambs were supplemented at a rate of 1% body weight/d. Supplemented lambs had greater body weight (BW) and average daily gain (ADG) when compared with non-supplemented lambs ( P < 0.04). Additionally, lambs on newly sown pasture demonstrated greater BW and ADG when compared with lambs grazing on established pasture ( P < 0.05). For lamb health, lambs in the EN treatment group had the greatest FAMACHA eye scores and lowest packed cell volume (PCV) over the course of the 112-d grazing period ( P < 0.05). Moreover, NS and ES treatment lambs demonstrated similar FAMACHA eye scores when compared with NN treatment lambs; however, NN treatment lambs showed lower PCV when compared with NS and ES treatment lambs ( P < 0.05). In evaluating fecal egg counts (FEC), lambs on new pasture or given supplement demonstrated lesser FEC when compared with those lambs on established pasture or not given supplement ( P < 0.05). Sixty-four lambs were harvested to evaluate total abomasum nematode counts which demonstrated that Haemonchus contortus represented approximately 80% of total nematodes. Furthermore, based upon gross margin analysis, lambs given a protein rich supplement on pasture had a 9.3 kg increase in lamb BW whereas newly sown pasture had a 1.3 kg increase in lamb BW. A protein rich supplement given to lambs grazing pastures contaminated primarily with H. contortus or placing lambs on newly sown pasture increases lamb BW and improves parasite resiliency. Selection of parasite management strategies may be influenced by cost of production and market opportunities., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society of Animal Science.)

Interleukin 10 (IL-10) is a pleiotropic, anti-inflammatory cytokine that has a major protective role in the intestine. Although its production by cells of the innate and adaptive immune system has been extensively studied, its intrinsic role in intestinal epithelial cells is poorly understood. In this study, we utilised both ATAC sequencing and RNA sequencing to define the transcriptional response of murine enteroids to tumour necrosis factor (TNF). We identified that the key early phase drivers of the transcriptional response to TNF within intestinal epithelium were NF κ B transcription factor dependent. Using wild-type and Il10 -/- enteroid cultures, we showed an intrinsic, intestinal epithelium specific effect of IL-10 deficiency on TNF-induced gene transcription, with significant downregulation of identified NF κ B target genes Tnf , Ccl20 , and Cxcl10 , and delayed overexpression of NF κ B inhibitor encoding genes, Nfkbia and Tnfaip3 . IL-10 deficiency, or immunoblockade of IL-10 receptor, impacted on TNF-induced endogenous NF κ B activity and downstream NF κ B target gene transcription. Intestinal epithelium-derived IL-10 appears to play a crucial role as a positive regulator of the canonical NF κ B pathway, contributing to maintenance of intestinal homeostasis. This is particularly important in the context of an inflammatory environment and highlights the potential for future tissue-targeted IL-10 therapeutic intervention., Competing Interests: VMDS is a director and shareholder of LifeGlimmer GmbH. FB has received salary from LifeGlimmer GmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Papoutsopoulou, Pollock, Walker, Tench, Samad, Bergey, Lenzi, Sheibani-Tezerji, Rosenstiel, Alam, Martins Dos Santos, Müller and Campbell.)

Microbial sulfur metabolism contributes to biogeochemical cycling on global scales. Sulfur metabolizing microbes are infected by phages that can encode auxiliary metabolic genes (AMGs) to alter sulfur metabolism within host cells but remain poorly characterized. Here we identified 191 phages derived from twelve environments that encoded 227 AMGs for oxidation of sulfur and thiosulfate (dsrA, dsrC/tusE, soxC, soxD and soxYZ). Evidence for retention of AMGs during niche-differentiation of diverse phage populations provided evidence that auxiliary metabolism imparts measurable fitness benefits to phages with ramifications for ecosystem biogeochemistry. Gene abundance and expression profiles of AMGs suggested significant contributions by phages to sulfur and thiosulfate oxidation in freshwater lakes and oceans, and a sensitive response to changing sulfur concentrations in hydrothermal environments. Overall, our study provides fundamental insights on the distribution, diversity, and ecology of phage auxiliary metabolism associated with sulfur and reinforces the necessity of incorporating viral contributions into biogeochemical configurations.

Here, we present 36 metagenomes, 59 metatranscriptomes, and 373 metagenome-assembled genomes (MAGs) from Chesapeake and Delaware Bay water samples. This data set will be useful for studying microbial biogeochemical cycling in estuaries.

The L-fucose-specific lectin from Aspergillus niger (ANL), isolated from the corneal smears of a keratitis patient was reported earlier. Here, we examined the interaction of ANL with human hepatocellular and colon cancer cells, evaluated its anti-cancer activity and diagnostic potential to detect aberrantly glycosylated tumour-associated serum glycoproteins such as alpha-fetoprotein (AFP). We observed that ANL strongly bound to both HepG2 and HT-29 cell-lines and this interaction was effectively blocked with L-fucose and mucin in a dose and time-dependent manner with an IC 50 of 1.25 and 5 μg/mL for HepG2 and HT-29 cells respectively at 48 hours. ANL treatment increased hypodiploidy and decreased the number of HepG2 cell in G 0 -G 1 phase at both 24 and 48 hours. Furthermore, ANL increased the level of apoptosis in both HepG2 and HT-29 cells in a time-dependent manner via enhanced production of reactive oxygen species and altered mitochondrial membrane potential, indicative of intrinsic apoptotis pathway activation. Immunoblot analysis confirmed the time-dependent elevation of levels of cytochrome c, initiator caspase-9 and activation of caspase-3. ANL immunohistochemistry on colon cancer tissue and quantification of AFP in HCC patient serum samples by developing an ANL-anti-AFP antibody sandwich enzyme-linked immunosorbent assay confirmed the diagnostic potential of ANL. Here, interaction of ANL with AFP could be effectively blocked in the presence of competing fucose-bearing glycans. We found ANL to be more sensitive than Lens culinaris lectin, a well-known fucose-specific lectin and currently used diagnostic agent. ANL can be further explored as a diagnostic and anti-cancer agent., (© 2021 John Wiley & Sons Ltd.)