Tuberculosis is associated with expansion of a motile,permissive and immunomodulatory CD16+ monocyte population via the IL-10/STAT3 axis

The human CD14⁺ monocyte compartment is composed by two subsets based on CD16 expression. We previously reported that this compartment is perturbed in tuberculosis (TB) patients, as reflected by the expansion of CD16⁺ monocytes along with disease severity. Whether this unbalance is beneficial or detrimental to host defense remains to be elucidated. Here in the context of active TB, we demonstrate that human monocytes are predisposed to differentiate towards an anti-inflammatory (M2-like) macrophage activation program characterized by the CD16⁺CD163⁺MerTK⁺pSTAT3⁺ phenotype and functional properties such as enhanced protease-dependent motility, pathogen permissivity and immunomodulation. This process is dependent on STAT3 activation, and loss-of-function experiments point towards a detrimental role in host defense against TB. Importantly, we provide a critical correlation between the abundance of the CD16⁺CD163⁺MerTK⁺pSTAT3⁺ cells and the progression of the disease either at the local level in a non-human primate tuberculous granuloma context, or at the systemic level through the detection of the soluble form of CD163 in human sera. Collectively, this study argues for the pathogenic role of the CD16⁺CD163⁺MerTK⁺pSTAT3⁺ monocyte-to-macrophage differentiation program and its potential as a target for TB therapy, and promotes the detection of circulating CD163 as a potential biomarker for disease progression and monitoring of treatment efficacy.     

The oligomerization of a family of four genetically clustered human gastrointestinal mucins

Mucins are synthesized and secreted by many epithelia. They are complex glycoproteins that offer cytoprotection. In their functional configuration, mucins form oligomers by a biosynthetic process that is poorly understood. A family of four human gastrointestinal mucin genes (MUC2, MUC5AC, MUC5B, and MUC6) is clustered to chromosome 11p15.5. To study oligomerization of these related mucins, we performed metabolic labeling experiments with [35S]amino acids in LS174T cells, and isolated mucin precursors by specific immunoprecipitations that were analyzed on SDS-PAGE. Each of the precursors of MUC2, MUC5AC, MUC5B, and MUC6 formed a single species of disulfide-linked homo-oligomer within 1 h after pulse labeling. Based on apparent molecular masses, these oligomeric precursors were most likely dimers. Inhibition of vesicular RER-to-Golgi transport, with brefeldin A and CCCP, did not affect the dimerization of MUC2 precursors, localizing dimerization to the RER. O-Glycosylation of MUC2 followed dimerization. Inhibition of N- glycosylation by tunicamycin retarded, but did not inhibit, dimerization, indicating that N-glycans play a role in efficient dimerization of MUC2 precursors. Based on sequence homology, the ability of MUC2, MUC5AC, MUC5B and MUC6 to dimerize most likely resides in their C-terminal domains. Thus, the RER-localized dimerization of secretory mucins likely proceeds by similar mechanisms, which is an essential step in the formation of the human gastrointestinal mucus- gels.      

PHYTOALEXIN DEFICIENT 4 affects reactive oxygen species metabolism,cell wall and wood properties in hybrid aspen (Populus tremula L. × tremuloides)

The PHYTOALEXIN DEFICIENT 4 (PAD4) gene in Arabidopsis thaliana (AtPAD4) is involved in the regulation of plant – pathogen interactions. The role of PAD4 in woody plants is not known; therefore, we characterized its function in hybrid aspen and its role in reactive oxygen species (ROS)‐dependent signalling and wood development. Three independent transgenic lines with different suppression levels of poplar PAD expression were generated. All these lines displayed deregulated ROS metabolism, which was manifested by an increased H₂O₂ level in the leaves and shoots, and higher activities of manganese superoxide dismutase (MnSOD) and catalase (CAT) in the leaves in comparison to the wild‐type plants. However, no changes in non‐photochemical quenching (NPQ) between the transgenic lines and wild type were observed in the leaves. Moreover, changes in the ROS metabolism in the pad4 transgenic lines positively correlated with wood formation. A higher rate of cell division, decreased tracheid average size and numbers, and increased cell wall thickness were observed. The results presented here suggest that the Populus tremula × tremuloides PAD gene might be involved in the regulation of cellular ROS homeostasis and in the cell division – cell death balance that is associated with wood development.     

A new genus and species of scorpionfly (Mecoptera) from Baltic amber,with an unusually developed postnotal organ

A new genus and species of fossil scorpionflies (Mecoptera) Baltipanorpa damzeni gen. et sp.n. is described from two well‐preserved male specimens in Baltic amber (middle Eocene: Lutetian). The most characteristic feature of the new taxon is an unusually developed postnotal organ on abdominal tergum IV. This is the most extremely developed example of this organ among Mecoptera and the only observation of notal and postnotal organs among fossil scorpionflies. The following combination of characters are provided to distinguish the new genus from other Panorpidae: Sc, short; R₁ and R₂ two‐branched; A₁ joins posterior margin of wing only at same level as fork of vein Rs; unusual shape of abdomen, abdominal segments I–IV strongly reduced, abdominal segment V elongate and widened, segments VII and VIII strongly elongate; notal and postnotal organs present, strongly developed process (postnotal organ) on tergum IV, unknown in all described extant and fossil scorpionflies. Different types of notal organs of Mecoptera are compared and their function and morphology are discussed. Morphological analysis of notal and postnotal organs in extant species permits us to conclude that B. damzeni sp.n. is characterized by the most developed and complex notal organs in all Mecoptera.     

Identification of Rhodococcus equi using the polymerase chain reaction

K.S. BELL, J.C. PHILP, N. CHRISTOFI AND D.W.J. AW. 1996. Two regions in the gene coding for 16S rRNA in Rhodococcus equi were selected as species-specific primer sequences for the polymerase chain reaction (PCR). PCR using these primers was tested against 10 strains of R. equi (including the type strain) and gave positive results for all but was negative for all other tested species of Rhodococcus ; representatives of the most closely related genera and a number of other bacterial species. This method could therefore be used to identify this species which can infect the lungs or other organs of horses, pigs, humans and other animals.     

The Hsp56 component of steroid receptor complexes binds to immobilized FK506 and shows homology to FKBP-12 and FKBP-13.

Extracts from human Jurkat cells or from calf thymus contain a 60-kDa protein that is bound to immobilized FK506. As expected, the NH2-terminal sequences of the 60-kDa protein from these two species were found to be nearly the same. We were surprised to discover, however, that the sequence of the human protein was identical to that of Hsp56, a heat shock protein of unknown function that has been shown to be a component of several steroid receptor complexes. Further analysis of the calf thymus protein revealed a peptide with homology to a region near the COOH terminus of both FKBP-12 and FKBP-13. It would appear, therefore, that this 60-kDa protein, or as we refer to it provisionally, "Hsp56," could have the capacity to bind FK506 directly. These observations lead us to speculate that "Hsp56" may mediate immunosuppression and inhibition of T-cell proliferation by FK506 and may do so via a cytosolic signal transduction pathway separate, but not necessarily exclusive, from that of FKBP-12 and FKBP-13.     

Isolation of Escherichia coli K-12 Mutants with Altered Levels of β-N-Acetylglucosaminidase

Eight mutants with less than 25% of the wild-type level of beta-N-acetylglucosaminidase activity have been isolated from Escherichia coli K-12. Studies on these mutants suggest that less than 1% of the wild-type level of this enzyme may be adequate for the normal growth and division of E. coli cells.     

Extended lifespan traded for diapause in Daphnia

1. Most freshwater crustaceans of the genus Daphnia are cyclically parthenogenetic organisms that are well adapted to unstable habitats due to their short life cycle, wide phenotypic plasticity, and the ability to produce protective diapausing eggs in anticipation of environmental deterioration. Short lifespan and heterogonic reproduction are typical features of Daphnia in a broad spectrum of freshwater habitats, from small temporary pools to large permanent lakes. However, in some locations, departures may be observed from this typical life history pattern to obligate asexuality or extended lifespan. 2. A 3‐year field study in a deep ultraoligotrophic fish‐free alpine‐type lake (Czarny Staw in the Tatra mountains in southern Poland) revealed the coexistence of two closely related asexual lineages of Daphnia of the pulex complex, which differ in body colour (transparent versus orange) and in their strategies for surviving long winters. 3. The ‘transparent’ clone of European origin exhibits an ephemeral lifestyle. It completes its life cycle within a single season, forming two generations of active specimens during the short summer and producing diapausing eggs late in the season. Transparent individuals live no longer than 5–6 months in this cold lake and survive winter exclusively in the form of diapausing eggs. 4. Individuals of the ‘orange’ lineage, which are closely related to eastern Nearctic Daphnia pulicaria, exhibit a biennial lifestyle unique to this genus. They do not form diapausing eggs or produce them only occasionally. Instead, they are active throughout the year and live for up to 13–14 months. Reproduction is postponed until the second year of life when food conditions have improved. Rich lipid reserves accumulated in the first season fuel them during the long winter and permit early reproduction the following spring. 5. Possible reasons for the evolution of obligatory parthenogenesis and long lifespan in Daphnia are discussed.     

Early Cretaceous record of microboring organisms in skeletons of growing corals

Ko?odziej, B., Golubic, S., Bucur, I.I., Radtke, G. & Tribollet, A. 2011: Early Cretaceous record of microboring organisms in skeletons of growing corals. Lethaia, Vol. 45, pp. 34–45. A spectacularly preserved assemblage of microbial euendoliths, penetrating into skeletons of growing scleractinian corals, has been recognized in Early Aptian (Early Cretaceous) reef limestone of the Rar?u Mountains (East Carpathians, NE Romania). Microboring euendolithic filaments were found in five coral colonies of the suborder Microsolenina. They remained in part well‐preserved, often impregnated with iron oxides, which made them visible even in strongly recrystallized parts of coral skeletons. Filaments of a wide range of sizes (2–40 μm in diameter) were concentrated within medium parts of coral septa, oriented along the septa in the direction of the coral growth. The larger filaments were tubular, occurring in bundles and branched into finer, often tapering branches. Their behaviour and organization were quite similar to the modern euendolithic siphonalean chlorophyte Ostreobium. Filament diameters exceeded those reported for the modern species, but covered a similarly wide size range. Narrower frequently branching filaments, 4–8 μm in diameter, resemble distal branching patterns of modern Ostreobium quekettii. Some very thin filaments (ca. 1–2 μm) observed within skeleton or inside the large tubular filaments, sometimes associated with globular swellings, may represent euendolithic fungi. The recrystallization of coral skeleton had limited effect on preservation of euendoliths due to their impregnation with iron oxides; microbial euendoliths were subjected to different taphonomic changes. □Chlorophytes, Early Cretaceous, fungi, microbial euendoliths, Romania, scleractinian corals.