Strain differences in the lethal factor exerted by submandibular glands transplanted from male mice

Zusammenfassung Der Lethalfaktor von Submandibulardrüsen-Transplantaten wurde bei Mäusen verschiedener Mutanten, C3H, CBA, BALB/c und C57BL, beobachtet. Die Intensität des Lethalfaktors war am stärksten in Transplantaten von BALB/c Mäusen und am geringsten in denen von C3H Mäusen. Die C57BL-Variante war am anfälligsten für den Lethalfaktor.     

Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses

The innate immune system senses viral infection by recognizing a variety of viral components (including double-stranded (ds)RNA) and triggers antiviral responses. The cytoplasmic helicase proteins RIG-I (retinoic-acid-inducible protein I, also known as Ddx58) and MDA5 (melanoma-differentiation-associated gene 5, also known as Ifih1 or Helicard) have been implicated in viral dsRNA recognition. In vitro studies suggest that both RIG-I and MDA5 detect RNA viruses and polyinosine-polycytidylic acid (poly(I:C)), a synthetic dsRNA analogue. Although a critical role for RIG-I in the recognition of several RNA viruses has been clarified, the functional role of MDA5 and the relationship between these dsRNA detectors in vivo are yet to be determined. Here we use mice deficient in MDA5 (MDA5-/-) to show that MDA5 and RIG-I recognize different types of dsRNAs: MDA5 recognizes poly(I:C), and RIG-I detects in vitro transcribed dsRNAs. RNA viruses are also differentially recognized by RIG-I and MDA5. We find that RIG-I is essential for the production of interferons in response to RNA viruses including paramyxoviruses, influenza virus and Japanese encephalitis virus, whereas MDA5 is critical for picornavirus detection. Furthermore, RIG-I-/- and MDA5-/- mice are highly susceptible to infection with these respective RNA viruses compared to control mice. Together, our data show that RIG-I and MDA5 distinguish different RNA viruses and are critical for host antiviral responses.     

A new superfamily,family, genus and species of marine amphipod,Protodulichia scandens,from Japan (Crustacea: Amphipoda: Senticaudata: Corophiida)

ABSTRACT

In this study, the new amphipod superfamily Protodulichioidea and family Protodulichiidae are established. Both belong to the infraorder Corophiida but is different from all known superfamilies and families. Amphipods included in the new superfamily and family are characterised by having a triangular head with large eyes, extremely long pereopod 7, and uropod 3 with a short peduncle and slender rami bearing a few robust setae. Protodulichia scandens gen. et sp. nov. is fully described here and its mast-building behaviour is also recorded.

urn:lsid:zoobank.org:pub:F6613B27-D954-4E4C-86CB-9FC5E9624334     

Temporal and seasonal variations in parasites of Metynnis lippincottianus (Characiformes: Characidae), a host from the eastern Amazon (Brazil)

ABSTRACT

This study investigated the influence of temporal and seasonal variation (rainy/dry cycle) on the component community structure and infracommunities of parasites in Metynnis lippincottianus from the eastern Amazon (Brazil). A total of 8,774 parasites representing 9 species and 22,765 parasites representing 12 species was collected in 2011 and 2016 respectively, but only 42.8% of the species were common to both study years. In both years, there was a dominance of Ichthyophthirius multifiliis and the component community was 51% dissimilar. The species richness of parasites and the Berger–Parker dominance were higher in 2016, while the evenness and Brillouin diversity were higher in 2011. The prevalence and abundance of I. multifiliis and P. pillulare, as well as the prevalence of Contracaecum sp. were higher in the rainy season. The abundance of Anacanthorus strongylophalus, Urocleidoides sp., Dadayus pacupeva and Dadaytrema oxycephala was higher in the dry season. Infection with Procamallanus (Spirocamallanus) inopinatus was not influenced by the season, while by Trichodina sp. occurred only in the dry season and Ergasilus xinguensis only in the rainy season. The species richness of parasites, Brillouin diversity index and evenness were higher in the dry season, while the Berger–Parker index was higher in the rainy season. Temporal variation of communities and infracommunities of parasites was influenced by the body size of host populations and increase in anthropogenic impacts. Effect of seasons on environmental quality, host size and availability of infective stages of parasites were the determining factors in structuring the component communities and infracommunities of parasites.     

Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation

While bile acids (BAs) have long been known to be essential in dietary lipid absorption and cholesterol catabolism, in recent years an important role for BAs as signalling molecules has emerged. BAs activate mitogen-activated protein kinase pathways, are ligands for the G-protein-coupled receptor (GPCR) TGR5 and activate nuclear hormone receptors such as farnesoid X receptor alpha (FXR-alpha; NR1H4). FXR-alpha regulates the enterohepatic recycling and biosynthesis of BAs by controlling the expression of genes such as the short heterodimer partner (SHP; NR0B2) that inhibits the activity of other nuclear receptors. The FXR-alpha-mediated SHP induction also underlies the downregulation of the hepatic fatty acid and triglyceride biosynthesis and very-low-density lipoprotein production mediated by sterol-regulatory-element-binding protein 1c. This indicates that BAs might be able to function beyond the control of BA homeostasis as general metabolic integrators. Here we show that the administration of BAs to mice increases energy expenditure in brown adipose tissue, preventing obesity and resistance to insulin. This novel metabolic effect of BAs is critically dependent on induction of the cyclic-AMP-dependent thyroid hormone activating enzyme type 2 iodothyronine deiodinase (D2) because it is lost in D2-/- mice. Treatment of brown adipocytes and human skeletal myocytes with BA increases D2 activity and oxygen consumption. These effects are independent of FXR-alpha, and instead are mediated by increased cAMP production that stems from the binding of BAs with the G-protein-coupled receptor TGR5. In both rodents and humans, the most thermogenically important tissues are specifically targeted by this mechanism because they coexpress D2 and TGR5. The BA-TGR5-cAMP-D2 signalling pathway is therefore a crucial mechanism for fine-tuning energy homeostasis that can be targeted to improve metabolic control.     

IkappaB kinase-alpha is critical for interferon-alpha production induced by Toll-like receptors 7 and 9

The Toll-like receptor (TLR) family has important roles in microbial recognition and dendritic cell activation. TLRs 7 and 9 can recognize nucleic acids and trigger signalling cascades that activate plasmacytoid dendritic cells to produce interferon-alpha (IFN-alpha) (refs 7, 8). TLR7/9-mediated dendritic cell activation is critical for antiviral immunity but also contributes to the pathogenesis of systemic lupus erythematosus, a disease in which serum IFN-alpha levels are elevated owing to plasmacytoid dendritic cell activation. TLR7/9-induced IFN-alpha induction depends on a molecular complex that contains a TLR adaptor, MyD88, and IFN regulatory factor 7 (IRF-7) (refs 10-14), but the underlying molecular mechanisms are as yet unknown. Here we show that IkappaB kinase-alpha (IKK-alpha) is critically involved in TLR7/9-induced IFN-alpha production. TLR7/9-induced IFN-alpha production was severely impaired in IKK-alpha-deficient plasmacytoid dendritic cells, whereas inflammatory cytokine induction was decreased but still occurred. Kinase-deficient IKK-alpha inhibited the ability of MyD88 to activate the Ifna promoter in synergy with IRF-7. Furthermore, IKK-alpha associated with and phosphorylated IRF-7. Our results identify a role for IKK-alpha in TLR7/9 signalling, and highlight IKK-alpha as a potential target for manipulating TLR-induced IFN-alpha production.     

Whole-genome sequencing of liver cancers identifies etiological influences on mutation patterns and recurrent mutations in chromatin regulators

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. We sequenced and analyzed the whole genomes of 27 HCCs, 25 of which were associated with hepatitis B or C virus infections, including two sets of multicentric tumors. Although no common somatic mutations were identified in the multicentric tumor pairs, their whole-genome substitution patterns were similar, suggesting that these tumors developed from independent mutations, although their shared etiological backgrounds may have strongly influenced their somatic mutation patterns. Statistical and functional analyses yielded a list of recurrently mutated genes. Multiple chromatin regulators, including ARID1A, ARID1B, ARID2, MLL and MLL3, were mutated in ～50% of the tumors. Hepatitis B virus genome integration in the TERT locus was frequently observed in a high clonal proportion. Our whole-genome sequencing analysis of HCCs identified the influence of etiological background on somatic mutation patterns and subsequent carcinogenesis, as well as recurrent mutations in chromatin regulators in HCCs.     

A Toll-like receptor recognizes bacterial DNA

DNA from bacteria has stimulatory effects on mammalian immune cells, which depend on the presence of unmethylated CpG dinucleotides in the bacterial DNA. In contrast, mammalian DNA has a low frequency of CpG dinucleotides, and these are mostly methylated; therefore, mammalian DNA does not have immuno-stimulatory activity. CpG DNA induces a strong T-helper-1-like inflammatory response. Accumulating evidence has revealed the therapeutic potential of CpG DNA as adjuvants for vaccination strategies for cancer, allergy and infectious diseases. Despite its promising clinical use, the molecular mechanism by which CpG DNA activates immune cells remains unclear. Here we show that cellular response to CpG DNA is mediated by a Toll-like receptor, TLR9. TLR9-deficient (TLR9-/-) mice did not show any response to CpG DNA, including proliferation of splenocytes, inflammatory cytokine production from macrophages and maturation of dendritic cells. TLR9-/- mice showed resistance to the lethal effect of CpG DNA without any elevation of serum pro-inflammatory cytokine levels. The in vivo CpG-DNA-mediated T-helper type-1 response was also abolished in TLR9-/- mice. Thus, vertebrate immune systems appear to have evolved a specific Toll-like receptor that distinguishes bacterial DNA from self-DNA.     

Formation of lipoperoxide in brain edema induced by cold injury

Zusammenfassung Biochemische Untersuchung zur Frage der Membranschädigung bei experimentellem Hirnödem: Lipoperoxid tritt 12 h nach der Traumatisierung in der höchsten Konzentration auf, was pathogenetisch bedeutungsvoll sein könnte.