Polymorphonuclear neutrophil-derived ectosomes interfere with the maturation of monocyte-derived dendritic cells

Polymorphonuclear neutrophils (PMNs) are a key component of the innate immune system. Their activation leads to the release of potent antimicrobial agents through degranulation. Simultaneously, PMNs release cell surface-derived microvesicles, so-called ectosomes (PMN-Ect). PMN-Ect are rightside-out vesicles with a diameter of 50-200 nm. They expose phosphatidylserine in the outer leaflet of their membrane and down-modulate monocyte/macrophage-activation in vitro. In this study, we analyzed the effects of PMN-Ect on maturation of human monocyte-derived dendritic cells (MoDCs). Intriguingly, exposing immature MoDCs to PMN-Ect modified their morphology, reduced their phagocytic activity, and increased the release of TGF-beta1. When immature MoDCs were incubated with PMN-Ect and stimulated with the TLR4 ligand LPS, the maturation process was partially inhibited as evidenced by reduced expression of cell surface markers (CD40, CD80, CD83, CD86, and HLA-DP DQ DR), inhibition of cytokine-release (IL-8, IL-10, IL-12, and TNF-alpha), and a reduced capacity to induce T cell proliferation. Together these data provide evidence that PMN-Ect have the ability to modify MoDC maturation and function. PMN-Ect may thus represent an as yet unidentified host-factor influencing MoDC maturation at the site of injury, thereby possibly impacting on downstream MoDC-dependent immunity.     

Identification of developmentally expressed proteins that functionally interact with Nedd4 ubiquitin ligase.

Nedd4 is a HECT domain-containing ubiquitin ligase that mediates ubiquitylation and proteasome degradation of target proteins. The molecular basis for the interaction of Nedd4 with substrates lies in its WW domains, which can bind proline-rich (PY) domains in target proteins. Nedd4 is a developmentally expressed protein and may have a fundamental role to play in embryonic processes. However, whether Nedd4 has such a function is currently unknown, in part because few developmentally regulated ubiquitylation substrates have been identified or characterized. We have carried out a yeast two-hybrid screen and identified four proteins expressed in the mid-gestation embryo that are able to interact with Nedd4. Characterization of their functional interaction with Nedd4 in vitro and in vivo demonstrated that three of the four are bona fide Nedd4 binding partners, and two have the capacity to be ubiquitylation substrates. One of these is the first identified nonviral substrate for Nedd4-mediated monoubiquitylation. Interestingly, neither of these two ubiquitylated proteins interacts with Nedd4 through PY-mediated mechanisms. For one of the three Nedd4 binding partners, there was no discernable evidence of ubiquitylation. However, this protein clearly associates with Nedd4 through its PY domains and can alter the location of Nedd4 in cells, suggesting a role other than as a ubiquitylation substrate.     

Middle Eocene–Early Pliocene Subantarctic planktic foraminiferal biostratigraphy of Site 1090, Agulhas Ridge

The analysis of planktic foraminiferal assemblages from Site 1090 (ODP Leg 177), located in the central part of the Subantarctic Zone south of South Africa, provided a geochronology of a 330-m-thick sequence spanning the Middle Eocene to Early Pliocene. A sequence of discrete bioevents enables the calibration of the Antarctic Paleogene (AP) Zonation with lower latitude biozonal schemes for the Middle–Late Eocene interval. In spite of the poor recovery of planktic foraminiferal assemblages, a correlation with the lower latitude standard planktic foraminiferal zonations has been attempted for the whole surveyed interval. Identified bioevents have been tentatively calibrated to the geomagnetic polarity time scale following the biochronology of Berggren et al. (1995). Besides planktic foraminiferal bioevents, the disappearance of the benthic foraminifera Nuttallides truempyi has been used to approximate the Middle/Late Eocene boundary. A hiatus of at least 11.7 Myr occurs between 78 and 71 m composite depth extending from the Early Miocene to the latest Miocene–Early Pliocene. Middle Eocene assemblages exhibit a temperate affinity, while the loss of several planktic foraminiferal species by late Middle to early Late Eocene time reflects cooling. During the Late Eocene–Oligocene intense dissolution caused impoverishment of planktic foraminiferal assemblages possibly following the emplacement of cold, corrosive bottom waters. Two warming peaks are, however, observed: the late Middle Eocene is marked by the invasion of the warmer water Acarinina spinuloinflata and Hantkenina alabamensis at 40.5 Ma, while the middle Late Eocene experienced the immigration of some globigerinathekids including Globigerinatheka luterbacheri and Globigerinatheka cf. semiinvoluta at 34.3 Ma. A more continuous record is observed for the Early Miocene and the Late Miocene–Early Pliocene where planktic foraminiferal assemblages show a distinct affinity with southern mid- to high-latitude faunas.     

Improved insights into the transcriptomes of the human hookworm Necator americanus--fundamental and biotechnological implications

Hookworms of humans are blood-feeding parasitic nematodes of major socio-economic significance in a wide range of countries. They cause a neglected tropical disease (NTD) called "hookworm disease" (=necatoriasis and/or ancylostomiasis). Necator americanus is the most widely distributed hookworm of humans and is a leading cause of iron deficiency anaemia, which can cause physical and mental retardation and deaths in children as well as adverse maternal-foetal outcomes. Currently, there is a significant focus on the development of new approaches for the prevention and control of hookworms in humans. Technological advances are underpinning the discovery of drug and vaccine targets through insights into the molecular biology and genomics of these parasites and their relationship with the human host. In spite of the widespread socio-economic impacts of human necatoriasis, molecular datasets for N. americanus are scant, limiting progress in molecular research. The present article explores all currently available EST datasets for adult and larval stages of N. americanus using a semi-automated bioinformatic pipeline. In the current repertoire of molecules now available, some have been or are being considered as candidate vaccines against N. americanus. Among others, the most abundant sets of molecules relate to the pathogenesis-related protein (PRP) superfamily, comprising various members, such as the Ancylostoma-secreted or activation-associated proteins (ASPs) and the kunitz-type proteins, both of which are inferred to play key roles in the interplay between N. americanus and the human host. Understanding the molecular biology of these and other novel molecules discovered could have important implications for finding new ways of disrupting the pathways that they are involved in, and should facilitate the identification of new drug and vaccine targets. Also, the bioinformatic prediction of the essentiality of genes and gene products as well as molecular network connectivity of nematode-specific genes, together with sequencing by 454 technology, are likely to assist in the genomic discovery efforts in the very near future, to also underpin fundamental, molecular research of hookworms.     

Yeast systems biotechnology for the production of heterologous proteins

Systems biotechnology has been established as a highly potent tool for bioprocess development in recent years. The applicability to complex metabolic processes such as protein synthesis and secretion, however, is still in its infancy. While yeasts are frequently applied for heterologous protein production, more progress in this field has been achieved for bacterial and mammalian cell culture systems than for yeasts. A critical comparison between different protein production systems, as provided in this review, can aid in assessing the potentials and pitfalls of applying systems biotechnology concepts to heterologous protein producing yeasts. Apart from modelling, the methodological basis of systems biology strongly relies on postgenomic methods. However, this methodology is rapidly moving so that more global data with much higher sensitivity will be achieved in near future. The development of next generation sequencing technology enables an unexpected revival of genomic approaches, providing new potential for evolutionary engineering and inverse metabolic engineering.     

“El Niño” events recorded in dry-forest species of the lowlands of northwest Peru

The northwest coast of Peru (5°S, 80°W) is very sensitive to and impacted by the climate phenomenon El Niño-Southern Oscillation (ENSO). Though mainly desert, this warm, dry region contains an equatorial dry forest. We report the first dendrochronological studies from this region and identify several species that have dendrochronological potential. Short ring-width chronologies of Palo Santo (Bursera graveolens) show a well-developed response to the ENSO signal over the last 50 years and good inter-site correlations. Preliminary isotopic studies in Algarrobo (Prosopis sp.) also show evidence of the 1997–98 El Niño event. ENSO events have a strong effect on the variability in the growth of several species and thereby on the economy of rural communities where the wood is used for housing, cooking, furniture, tools, fodder and medicinal uses. The extensive use of wood in archeological sites also offers the possibility of ultimately developing longer records for some of these species.