• Gamma-tocotrienol stimulates the proliferation, differentiation, and mineralization in osteoblastic MC3T3-E1 cells

      Xu, Weili; He, Pan; He, Shenghua; Cui, Pengju; Mi, Yaqing; Yang, Yang; Li, Yang; Zhou, Shaobo; Harbin Institute of Technology; Harbin Medical University; et al. (Hindawi Publishing Corporation, 2018-01-15)
      Gamma-tocotrienol, a major component of tocotrienol-rich fraction of palm oil, has been suggested to exhibit bone protective effects in vivo. However, the effects of γ-tocotrienol on osteoblast cells are still unclear. In this study, the effects of γ-tocotrienol on the proliferation, differentiation, and mineralization in osteoblastic MC3T3-E1 cells were investigated. Our results showed that γ-tocotrienol (2–8 μmol/L) significantly improved the cell proliferation (), but it did not affect cell cycle progression. γ-Tocotrienol significantly increased alkaline phosphatase (ALP) activity (), secretion levels of osteocalcin (OC) and osteonectin (ON), and mRNA levels of collagen type I (Col I) of MC3T3-E1 cells. Meanwhile, we found that γ-tocotrienol is promoted in differentiation MC3T3-E1 cells by upregulation of the expression of Runx2 protein. Moreover, the number of bone nodules increased over 2.5-fold in cells treated with γ-tocotrienol (2–8 μmol/L) for 24 d compared to control group. These results indicated that γ-tocotrienol at low dose levels, especially 4 μmol/L, could markedly enhance the osteoblastic function by increasing the proliferation, differentiation, and mineralization of osteoblastic MC3T3-E1 cells. Moreover, our data also indicated that Runx2 protein may be involved in these effects. Further studies are needed to determine the potential of γ-tocotrienol as an antiosteoporotic agent.
    • Ganoderic acid A potentiates antioxidant effect and protection of mitochondrial membrane and reduction the apoptosis rate in primary hippocampal neurons treated with magnesium free medium

      Jiang, Zhi-Mei; Qiu, Hong-Bin; Wang, Shu-Qiu; Guo, J.; Yang, ZW; Zhou, Shaobo; Harbin Medical University; Jiamusi University; University of Bedfordshire (2018-02-01)
    • Gene family expansions and contractions are associated with host range in plant pathogens of the genus Colletotrichum

      Baroncelli, Riccardo; Amby, Daniel Buchvaldt; Zapparata, Antonio; Sarrocco, Sabrina; Vannacci, Giovanni; Le Floch, Gaétan; Harrison, Richard; Holub, Eric; Sukno, Serenella A.; Sreenivasaprasad, Surapareddy; et al. (BioMed Central, 2016-08-05)
      Many species belonging to the genus Colletotrichum cause anthracnose disease on a wide range of plant species. In addition to their economic impact, the genus Colletotrichum is a useful model for the study of the evolution of host specificity, speciation and reproductive behaviors. Genome projects of Colletotrichum species have already opened a new era for studying the evolution of pathogenesis in fungi. We sequenced and annotated the genomes of four strains in the Colletotrichum acutatum species complex (CAsc), a clade of broad host range pathogens within the genus. The four CAsc proteomes and secretomes along with those representing an additional 13 species (six Colletotrichum spp. and seven other Sordariomycetes) were classified into protein families using a variety of tools. Hierarchical clustering of gene family and functional domain assignments, and phylogenetic analyses revealed lineage specific losses of carbohydrate-active enzymes (CAZymes) and proteases encoding genes in Colletotrichum species that have narrow host range as well as duplications of these families in the CAsc. We also found a lineage specific expansion of necrosis and ethylene-inducing peptide 1 (Nep1)-like protein (NLPs) families within the CAsc. This study illustrates the plasticity of Colletotrichum genomes, and shows that major changes in host range are associated with relatively recent changes in gene content.
    • Genetic modifications of metallothionein enhance the tolerance and bioaccumulation of heavy metals in Escherichia coli

      Li, Xuefen; Ren, Zhumei; Crabbe, M. James C.; Wang, Lan; Ma, Wenli; Shanxi University; University of Oxford; University of Bedfordshire (Elsevier, 2021-07-13)
      Metallothioneins (MTs) are low molecular weight cysteine-rich proteins that bind to metals. Owing to their high cysteine (Cys) content, MTs are effective mediators of heavy metal detoxification. To enhance the heavy metal binding ability of MT from the freshwater crab Sinopotamon henanense (ShMT), sequence-based multiple sequence alignment (MSA) and structure-based molecular docking simulation (MDS) were conducted in order to identify amino acid residues that could be mutated to bolster such metal-binding activity. Site-directed mutagenesis was then used to modify the primary structure of ShMT, and the recombinant proteins were further enhanced using the SUMO fusion expression system to yield SUMO-ShMT1, SUMO-ShMT2, and SUMO-ShMT3 harboring one-, two-, and three- point mutations, respectively. The resultant modified proteins were primarily expressed in a soluble form and exhibited the ability to readily bind to heavy metals. Importantly, these modified proteins exhibited significantly enhanced heavy metal binding capacities, and they improved Cd2+, Cu2+ and Zn2+ tolerance and bioaccumulation in Escherichia coli (E. coli) in a manner dependent upon the number of introduced point mutations (SUMO-ShMT3 > SUMO-ShMT2 > SUMO-ShMT1 > SUMO-ShMT > control). Indeed, E. coli cells harboring the pET28a-SUMO-ShMT3 expression vector exhibited maximal Cd2+, Cu2+, and Zn2+ bioaccumulation that was increased by 1.86 ± 0.02-, 1.71 ± 0.03-, and 2.13 ± 0.02-fold relative to that in E. coli harboring the pET28a-SUMO-ShMT vector. The present study offers a basis for the preparation of genetically engineered bacteria that are better able to bioaccumulate and tolerate heavy metals, thus providing a foundation for biological heavy metal water pollution treatment.
    • The genome and transcriptome of Trichormus sp NMC-1: insights into adaptation to extreme environments on the Qinghai-Tibet Plateau

      Qiao, Qin; Huang, Yanyan; Qi, Ji.; Qu, Mingzhi; Jiang, Chen; Lin, Pengcheng; Li, Renhui; Song, Lirong; Yonezawa, Takahiro; Hasegawa, Masami; et al. (NATURE PUBLISHING GROUP, 2016-07-06)
      The Qinghai-Tibet Plateau (QTP) has the highest biodiversity for an extreme environment worldwide, and provides an ideal natural laboratory to study adaptive evolution. In this study, we generated a draft genome sequence of cyanobacteria Trichormus sp. NMC-1 in the QTP and performed whole transcriptome sequencing under low temperature to investigate the genetic mechanism by which T. sp. NMC-1 adapted to the specific environment. Its genome sequence was 5.9 Mb with a G+C content of 39.2% and encompassed a total of 5362 CDS. A phylogenomic tree indicated that this strain belongs to the Trichormus and Anabaena cluster. Genome comparison between T. sp. NMC-1 and six relatives showed that functionally unknown genes occupied a much higher proportion (28.12%) of the T. sp. NMC-1 genome. In addition, functions of specific, significant positively selected, expanded orthogroups, and differentially expressed genes involved in signal transduction, cell wall/membrane biogenesis, secondary metabolite biosynthesis, and energy production and conversion were analyzed to elucidate specific adaptation traits. Further analyses showed that the CheY-like genes, extracellular polysaccharide and mycosporine-like amino acids might play major roles in adaptation to harsh environments. Our findings indicate that sophisticated genetic mechanisms are involved in cyanobacterial adaptation to the extreme environment of the QTP.
    • Genome sequence of the biocontrol agent coniothyrium minitans conio (IMI 134523)

      Patel, Denise; Shittu, Taiwo Adewale; Baroncelli, Riccardo; Muthumeenakshi, Sreenivasaprasad; Osborne, Thomas H.; Janganan, Thamarai K.; Sreenivasaprasad, Surapareddy; University of Bedfordshire (American Phytopathological Society, 2021-02-16)
      Coniothyrium minitans (synonym, Paraphaeosphaeria minitans) is a highly specific mycoparasite of the wide host range crop pathogen Sclerotinia sclerotiorum. The capability of C. minitans to destroy the sclerotia of S. sclerotiorum has been well recognized and it is available as a widely used biocontrol product Contans WG. We present the draft genome sequence of C. minitans Conio (IMI 134523), which has previously been used in extensive studies that formed part of a registration package of the commercial product. This work provides a distinctive resource for further research into the molecular basis of mycoparasitism to harness the biocontrol potential of C. minitans.
    • Genome size diversity and its impact on the evolution of land plants

      Pellicer, Jaume; Hidalgo, Oriane; Dodsworth, Steven; Leitch, Ilia J.; Royal Botanic Gardens, Kew (MDPI AG, 2018-02-14)
      Genome size is a biodiversity trait that shows staggering diversity across eukaryotes, varying over 64,000-fold. Of all major taxonomic groups, land plants stand out due to their staggering genome size diversity, ranging ca. 2400-fold. As our understanding of the implications and significance of this remarkable genome size diversity in land plants grows, it is becoming increasingly evident that this trait plays not only an important role in shaping the evolution of plant genomes, but also in influencing plant community assemblages at the ecosystem level. Recent advances and improvements in novel sequencing technologies, as well as analytical tools, make it possible to gain critical insights into the genomic and epigenetic mechanisms underpinning genome size changes. In this review we provide an overview of our current understanding of genome size diversity across the different land plant groups, its implications on the biology of the genome and what future directions need to be addressed to fill key knowledge gaps.
    • Genome size diversity in angiosperms and its influence on gene space

      Dodsworth, Steven; Leitch, Andrew R.; Leitch, Ilia J.; Queen Mary University of London; Royal Botanic Gardens, Kew (Elsevier Ltd, 2015-11-21)
      Genome size varies c. 2400-fold in angiosperms (flowering plants), although the range of genome size is skewed towards small genomes, with a mean genome size of 1C = 5.7 Gb. One of the most crucial factors governing genome size in angiosperms is the relative amount and activity of repetitive elements. Recently, there have been new insights into how these repeats, previously discarded as ‘junk’ DNA, can have a significant impact on gene space (i.e. the part of the genome comprising all the genes and gene-related DNA). Here we review these new findings and explore in what ways genome size itself plays a role in influencing how repeats impact genome dynamics and gene space, including gene expression.
    • Genome skimming for next-generation biodiversity analysis

      Dodsworth, Steven; Queen Mary University of London; Royal Botanic Gardens, Kew (Elsevier Ltd, 2015-07-20)
    • Genome-wide repeat dynamics reflect phylogenetic distance in closely related allotetraploid Nicotiana (Solanaceae)

      Dodsworth, Steven; Jang, Tae-Soo; Struebig, Monika; Chase, Mark W.; Weiss-Schneeweiss, Hanna; Leitch, Andrew R.; Queen Mary University of London; Royal Botanic Gardens, Kew; University of Vienna; University of Western Australia (Springer-Verlag Wien, 2016-11-01)
      Nicotiana sect. Repandae is a group of four allotetraploid species originating from a single allopolyploidisation event approximately 5 million years ago. Previous phylogenetic analyses support the hypothesis of N. nudicaulis as sister to the other three species. This is concordant with changes in genome size, separating those with genome downsizing (N. nudicaulis) from those with genome upsizing (N. repanda, N. nesophila, N. stocktonii). However, a recent analysis reflecting genome dynamics of different transposable element families reconstructed greater similarity between N. nudicaulis and the Revillagigedo Island taxa (N. nesophila and N. stocktonii), thereby placing N. repanda as sister to the rest of the group. This could reflect a different phylogenetic hypothesis or the unique evolutionary history of these particular elements. Here we re-examine relationships in this group and investigate genome-wide patterns in repetitive DNA, utilising high-throughput sequencing and a genome skimming approach. Repetitive DNA clusters provide support for N. nudicaulis as sister to the rest of the section, with N. repanda sister to the two Revillagigedo Island species. Clade-specific patterns in the occurrence and abundance of particular repeats confirm the original (N. nudicaulis (N. repanda (N. nesophila ? N. stocktonii))) hypothesis. Furthermore, overall repeat dynamics in the island species N. nesophila and N. stocktonii confirm their similarity to N. repanda and the distinctive patterns between these three species and N. nudicaulis. Together these results suggest that broad-scale repeat dynamics do in fact reflect evolutionary history and could be predicted based on phylogenetic distance.
    • Genomic analysis of field pennycress (Thlaspi arvense) provides insights into mechanisms of adaptation to high elevation

      Geng, Yu-peng; Guan, Yabin; Qiong, La; Lu, Shugang; An, Miao; Crabbe, M. James C.; Qi, Ji.; Zhao, Fangqing; Qiao, Qin; Zhang, Ti-Cao; et al. (Springer Nature, 2021-07-22)
      Background: Understanding how organisms evolve and adapt to extreme habitats is of crucial importance in evolutionary ecology. Altitude gradients are an important determinant of the distribution pattern and range of organisms due to distinct climate conditions at different altitudes. High-altitude regions often provide extreme environments including low temperature and oxygen concentration, poor soil, and strong levels of ultraviolet radiation, leading to very few plant species being able to populate elevation ranges greater than 4000 m. Field pennycress (Thlaspi arvense) is a valuable oilseed crop and emerging model plant distributed across an elevation range of nearly 4500 m. Here, we generate an improved genome assembly to understand how this species adapts to such different environments. Results: We sequenced and assembled de novo the chromosome-level pennycress genome of 527.3 Mb encoding 31,596 genes. Phylogenomic analyses based on 2495 single-copy genes revealed that pennycress is closely related to Eutrema salsugineum (estimated divergence 14.32–18.58 Mya), and both species form a sister clade to Schrenkiella parvula and genus Brassica. Field pennycress contains the highest percentage (70.19%) of transposable elements in all reported genomes of Brassicaceae, with the retrotransposon proliferation in the Middle Pleistocene being likely responsible for the expansion of genome size. Moreover, our analysis of 40 field pennycress samples in two highand two low-elevation populations detected 1,256,971 high-quality single nucleotide polymorphisms. Using three complementary selection tests, we detected 130 candidate naturally selected genes in the Qinghai-Tibet Plateau (QTP) populations, some of which are involved in DNA repair and the ubiquitin system and potential candidates involved in high-altitude adaptation. Notably, we detected a single base mutation causing loss-of-function of the FLOWERING LOCUS C protein, responsible for the transition to early flowering in high-elevation populations. Conclusions: Our results provide a genome-wide perspective of how plants adapt to distinct environmental conditions across extreme elevation differences and the potential for further follow-up research with extensive data from additional populations and species.
    • Genomic repeat abundances contain phylogenetic signal

      Dodsworth, Steven; Chase, Mark W.; Kelly, Laura J.; Leitch, Ilia J.; Macas, Jiří; Novak, Petr; Piednoel, Mathieu; Weiss-Schneeweiss, Hanna; Leitch, Andrew R. (Oxford University Press, 2014-09-25)
      A large proportion of genomic information, particularly repetitive elements, is usually ignored when researchers are using next-generation sequencing. Here we demonstrate the usefulness of this repetitive fraction in phylogenetic analyses, utilizing comparative graph-based clustering of next-generation sequence reads, which results in abundance estimates of different classes of genomic repeats. Phylogenetic trees are then inferred based on the genome-wide abundance of different repeat types treated as continuously varying characters; such repeats are scattered across chromosomes and in angiosperms can constitute a majority of nuclear genomic DNA. In six diverse examples, five angiosperms and one insect, this method provides generally well-supported relationships at interspecific and intergeneric levels that agree with results from more standard phylogenetic analyses of commonly used markers. We propose that this methodology may prove especially useful in groups where there is little genetic differentiation in standard phylogenetic markers. At the same time as providing data for phylogenetic inference, this method additionally yields a wealth of data for comparative studies of genome evolution.
    • Genomics evolutionary history and diagnostics of the Alternaria alternata species group including apple and Asian pear pathotypes

      Armitage, Andrew D.; Cockerton, Helen M.; Sreenivasaprasad, Surapareddy; Woodhall, James; Lane, Charles R.; Harrison, Richard; Clarkson, John P. (Frontiers, 2020-01-23)
      The Alternaria section alternaria (Alternaria alternata species group) represents a diverse group of saprotroph, human allergens, and plant pathogens. Alternaria taxonomy has benefited from recent phylogenetic revision but the basis of differentiation between major phylogenetic clades within the group is not yet understood. Furthermore, genomic resources have been limited for the study of host-specific pathotypes. We report near complete genomes of the apple and Asian pear pathotypes as well as draft assemblies for a further 10 isolates representing Alternaria tenuissima and Alternaria arborescens lineages. These assemblies provide the first insights into differentiation of these taxa as well as allowing the description of effector and non-effector profiles of apple and pear conditionally dispensable chromosomes (CDCs). We define the phylogenetic relationship between the isolates sequenced in this study and a further 23 Alternaria spp. based on available genomes. We determine which of these genomes represent MAT1-1-1 or MAT1-2-1 idiomorphs and designate host-specific pathotypes. We show for the first time that the apple pathotype is polyphyletic, present in both the A. arborescens and A. tenuissima lineages. Furthermore, we profile a wider set of 89 isolates for both mating type idiomorphs and toxin gene markers. Mating-type distribution indicated that gene flow has occurred since the formation of A. tenuissima and A. arborescens lineages. We also developed primers designed to AMT14, a gene from the apple pathotype toxin gene cluster with homologs in all tested pathotypes. These primers allow identification and differentiation of apple, pear, and strawberry pathotypes, providing new tools for pathogen diagnostics.
    • The Gli3 transcription factor expressed in the thymus stroma controls thymocyte negative selection via Hedgehog-dependent and -independent mechanisms

      Hager-Theodorides, Ariadne L.; Furmanski, Anna L.; Ross, Susan; Outram, Susan V.; Rowbotham, Nicola J.; Crompton, Tessa (American Association of Immunologists, 2009-08-20)
      The Hedgehog (Hh) responsive transcription factor Gli3 is required for efficient thymocyte development in the fetus. In this study we show that Gli3, not detected in adult thymocytes, is expressed in the murine fetal and adult thymus stroma. PCR array analysis revealed Cxcl9, Rbp1, and Nos2 as novel target genes of Gli3. We show that Gli3 positively regulates the expression of these genes, most likely by suppressing an intermediate repressor. Deletion of autoreactive thymocytes depends on their interactions with the thymus stroma. Repression of the proapoptotic gene Nos2 in Gli3 mutants coincides with reduced apoptosis of double positive thymocytes undergoing negative selection in vitro and in vivo, and the production of autoreactive thymocytes. Taken together these data indicate that Gli3 controls thymocyte apoptosis and negative selection possibly via the regulation of Nos2. Defective Gli3 expression in the thymus stroma also resulted in decreased CD5 expression on mature thymocytes and inappropriate production of MHC class I-selected CD4+ cells, both consistent with reduced TCR signal strength. Overall our data indicate that Gli3 expressed in the thymus stroma regulates negative selection and TCR signal strength via Hh-dependent and -independent mechanisms, with implications for autoimmunity.
    • Goat and buffalo milk fat globule membranes exhibit better effects at inducing apoptosis and reduction the viability of HT-29 cells

      Ji, Xiaoxi; Xu, Weili; Cui, Jie; Ma, Ying; Zhou, Shaobo (Nature Publishing Group, 2019-02-22)
      Bovine milk fat globule membrane (MFGM) has shown many health benefits, however, there has not been much study on non-cattle MFGMs. The purpose of this study was to compare the anti-proliferation effects and investigate the mechanisms of MFGMs from bovine, goat, buffalo, yak and camel milk in HT-29 cells. Results showed that protein content in MFGM of yak milk is the highest among five MFGM. All MFGMs inhibited cellular proliferation which was in agreement with cell morphology and apoptosis. However, the number of cells in S-phase from 24 h to 72 h was increased significantly by treatment with goat, buffalo and bovine MFGMs (100 μg/mL), but not yak and camel. All MFGMs treatment significantly reduced the mitochondrial membrane potential (with an order of goat>buffalo>bovine>camel>yak) and Bcl-2 expression, but increased the expression of both Bax and Caspase-3. Taken together, the results indicate that all MFGMs, especially goat and buffalo MFGMs, showed better effects at inducing apoptosis and inhibition of the proliferation of HT-29 cells. The mechanism might be arresting the cell cycle at S phase, depolarization of mitochondrial membrane potential, down-regulation of Bcl-2 expression and increase of Bax and Caspase-3 expression.
    • Gut hormone regulation and secretion via FFA1 and FFA4

      Gribble, Fiona M.; Diakogiannaki, Eleftheria; Reimann, Frank (Springer New York LLC, 2016-11-22)
      The digestion, absorption and utilisation of dietary triglycerides are controlled by gut hormones, released from enteroendocrine cells along the length of the gastrointestinal tract. Major players in the detection of ingested lipids are the free fatty acid receptors FFA1 and FFA4, which are highly expressed on enteroendocrine cells. These receptors are activated when free fatty acids (FFA) are absorbed across the intestinal epithelium, and provide a dynamic hormonal signal indicating that lipids are arriving in the bloodstream from the gut. This review addresses our current knowledge of how ingested triglycerides modulate gut hormone release via FFA1 and FFA4.
    • A Gβ protein and the TupA co-regulator bind to protein kinase a Tpk2 to act as antagonistic molecular switches of fungal morphological changes

      Janganan, Thamarai K.; Chen, Gongyou; Chen, Daliang; Menino, Joao F.; Rodrigues, Fernando; Borges-Walmsley, Maria Ines; Walmsley, Adrian R.; University of Durham; University of Minho (PLOS, 2015-09-03)
      The human pathogenic fungus Paracoccidioides brasiliensis (Pb) undergoes a morphological transition from a saprobic mycelium to pathogenic yeast that is controlled by the cAMP-signaling pathway. There is a change in the expression of the Gβ-protein PbGpb1, which interacts with adenylate cyclase, during this morphological transition. We exploited the fact that the cAMP-signaling pathway of Saccharomyces cerevisiae does not include a Gβ-protein to probe the functional role of PbGpb1. We present data that indicates that PbGpb1 and the transcriptional regulator PbTupA both bind to the PKA protein PbTpk2. PbTPK2 was able to complement a TPK2Δ strain of S. cerevisiae, XPY5a/α, which was defective in pseudohyphal growth. Whilst PbGPB1 had no effect on the parent S. cerevisiae strain, MLY61a/α, it repressed the filamentous growth of XPY5a/α transformed with PbTPK2, behaviour that correlated with a reduced expression of the floculin FLO11. In vitro, PbGpb1 reduced the kinase activity of PbTpk2, suggesting that inhibition of PbTpk2 by PbGpb1 reduces the level of expression of Flo11, antagonizing the filamentous growth of the cells. In contrast, expressing the co-regulator PbTUPA in XPY5a/α cells transformed with PbTPK2, but not untransformed cells, induced hyperfilamentous growth, which could be antagonized by co-transforming the cells with PbGPB1. PbTUPA was unable to induce the hyperfilamentous growth of a FLO8Δ strain, suggesting that PbTupA functions in conjunction with the transcription factor Flo8 to control Flo11 expression. Our data indicates that P. brasiliensis PbGpb1 and PbTupA, both of which have WD/β-propeller structures, bind to PbTpk2 to act as antagonistic molecular switches of cell morphology, with PbTupA and PbGpb1 inducing and repressing filamentous growth, respectively. Our findings define a potential mechanism for controlling the morphological switch that underpins the virulence of dimorphic fungi.
    • Haptoglobin genotype-dependent anti-inflammatory signaling in CD163(+) macrophages

      Landis, R. Clive; Philippidis, Pandelis; Domin, Jan; Boyle, Joseph J.; Haskard, Dorian O.; University of the West Indies; Imperial College London; University of Bedfordshire (Hindawi, 2013-12-31)
      Intraplaque hemorrhage causes adaptive remodelling of macrophages towards a protective phenotype specialized towards handling iron and lipid overload, denoted Mhem. The Mhem phenotype expresses elevated levels of hemoglobin (Hb) scavenger receptor, CD163, capable of endocytosing pro-oxidant free Hb complexed to acute phase protein haptoglobin (Hp). It is notable that individuals homozygous for the Hp 2 allele (a poorer antioxidant) are at increased risk of cardiovascular disease compared to the Hp 1 allele. In this study, we examined whether scavenging of polymorphic Hp:Hb complexes differentially generated downstream anti-inflammatory signals in cultured human macrophages culminating in interleukin (IL)-10 secretion. We describe an anti-inflammatory signalling pathway involving phosphatidylinositol-3-kinase activation upstream of Akt phosphorylation (pSer473Akt) and IL-10 secretion. The pathway is mediated specifically through CD163 and is blocked by anti-CD163 antibody or phagocytosis inhibitor. However, levels of pSer473Akt and IL-10 were significantly diminished when scavenging polymorphic Hp2-2:Hb complexes compared to Hp1-1:Hb complexes (P < 0.05). Impaired anti-inflammatory macrophage signaling through a CD163/pAkt/IL-10 axis may thus represent a possible Hp2-2 disease mechanism in atherosclerosis.
    • Hedgehog signalling promotes Th2-differentiation in naive human CD4 T-cells

      Yánez, Diana C.; Lau, Ching-In; Chawda, Mira Manilal; Ross, Susan; Furmanski, Anna L.; Crompton, Tessa; University College London; University of Bedfordshire; Universidad San Francisco de Quito (Journal of Allergy and Clinical Immunology, 2019-07-24)
      Original journal article Abstract: Here we show that differentiation of human naïve CD4 T-cells to Th2 is promoted by Hedgehog signaling and attenuated by SMO-inhibition. As Hedgehog proteins are produced by epithelial tissues this finding is important to understanding atopic disease.
    • How can we enable prisoners to want a better life?

      Crabbe, M. James C. (2019-04-26)
      60% of those convicted of offences re‐offend within two years at a cost to the taxpayer of c. £9.5 - £13 billion per year. In May 2018 the UK Government produced an Education and Employment Strategy for offenders that needed to ‘start with offenders themselves’. Based on a Friday Conversation presentation in Rawthmells coffeehouse in March 2019, James Crabbe FRSA asks ‘How can we enable prisoners to want a better life?’