Ecological Modeling from Time-Series Inference: Insight into Dynamics and Stability of Intestinal Microbiota

The intestinal microbiota is a microbial ecosystem of crucial importance to human health. Understanding how the microbiota confers resistance against enteric pathogens and how antibiotics disrupt that resistance is key to the prevention and cure of intestinal infections. We present a novel method to infer microbial community ecology directly from time-resolved metagenomics. This method extends generalized Lotka–Volterra dynamics to account for external perturbations. Data from recent experiments on antibiotic-mediated Clostridium difficile infection is analyzed to quantify microbial interactions, commensal-pathogen interactions, and the effect of the antibiotic on the community. Stability analysis reveals that the microbiota is intrinsically stable, explaining how antibiotic perturbations and C. difficile inoculation can produce catastrophic shifts that persist even after removal of the perturbations. Importantly, the analysis suggests a subnetwork of bacterial groups implicated in protection against C. difficile. Due to its generality, our method can be applied to any high-resolution ecological time-series data to infer community structure and response to external stimuli.     

Interferon-Inducible Mechanism of Dendritic Cell-Mediated HIV-1 Dissemination Is Dependent on Siglec-1/CD169

Human immunodeficiency virus type 1 (HIV-1) interactions with myeloid dendritic cells (DCs) can result in virus dissemination to CD4⁺ T cells via a trans infection pathway dependent on virion incorporation of the host cell derived glycosphingolipid (GSL), GM3. The mechanism of DC-mediated trans infection is extremely efficacious and can result in infection of multiple CD4⁺ T cells as these cells make exploratory contacts on the DC surface. While it has long been appreciated that activation of DCs with ligands that induce type I IFN signaling pathway dramatically enhances DC-mediated T cell trans infection, the mechanism by which this occurs has remained unclear until now. Here, we demonstrate that the type I IFN-inducible Siglec-1, CD169, is the DC receptor that captures HIV in a GM3-dependent manner. Selective downregulation of CD169 expression, neutralizing CD169 function, or depletion of GSLs from virions, abrogated DC-mediated HIV-1 capture and trans infection, while exogenous expression of CD169 in receptor-naïve cells rescued GSL-dependent capture and trans infection. HIV-1 particles co-localized with CD169 on DC surface immediately following capture and subsequently within non-lysosomal compartments that redistributed to the DC – T cell infectious synapses upon initiation of T cell contact. Together, these findings describe a novel mechanism of pathogen parasitization of host encoded cellular recognition machinery (GM3 – CD169 interaction) for DC-dependent HIV dissemination.     

Wild fledgling tits do not mob in response to conspecific or heterospecific mobbing calls

Mobbing, where birds harass a predator through a combination of vocalizations and stereotyped behaviours, is an effective anti-predator behaviour for many species. Mobbing may be particularly important for juveniles, as these individuals are often more vulnerable than adults. Although the component behaviours of mobbing are often considered to be un-learned, there are few confirmatory data, and the developmental trajectory of mobbing is unknown. In this study, we tested whether conspecific or heterospecific mobbing calls initiated mobbing behaviour in juvenile Blue Tits Cyanistes caeruleus. We located wild adult and recently fledged juvenile Blue Tits and presented them with playback recordings of adult conspecific (Blue Tit) and heterospecific (Great Tit Parus major) mobbing alarm calls. Although adult birds readily mob in response to these types of playbacks, juveniles did not exhibit characteristic mobbing behaviour. Some juveniles did, however, exhibit individual components of mobbing behaviour found in mobbing, despite not producing adult-like mobbing behaviour in response to either conspecific or heterospecific playback. These results suggest that, although birds might be capable of mobbing as juveniles, the associations between the non-vocal stereotyped mobbing behaviours and mobbing calls may be learned.     

Juvenile hormone-like substances can induce vitellogenesis in the tick Ornithodoros moubata (Acarina: Argasidae)

Topical application of different juvenile hormone analogs (JHA) or of a mixture of stereoisomers of insect juvenile hormone (JH) 1 and 3 to fed virgin female Ornithodoros moubata immediately after feeding induced vitellogenesis and egg-laying in up to 70% of treated females. In controls only 13.7% oviposited. The eggs were sterile, with abnormal shape, but their number versus the weight of engorged females was normal or sometimes greater than in mated females. However, preoviposition period was longer than in mated females.

It was more difficult to induce egg-laying by similar topical applications 100 days after feeding of virgin females. A maximum of 58% of ovipositing females was obtained with a very high dosage of JH mixture (500 fig). Injection of this mixture into the females was more potent; 15 to 50 fig induced oviposition in about 60% of the females. The preoviposition period was also longer than in control females.

Our results suggest the presence of a JH-like substance which is involved in the hormonal control of vitellogenesis. However, since natural isomers of JH were much less efficient than isomeric mixtures or JHA, we suppose that the natural tick hormone does not correspond to JH, but rather to a JH-like substance.     

Ecdysteroids in females and eggs of the Ixodid tick Amblyomma hebraeum

Summary

A mated Amblyomma hebraeum female will engorge on a host for about 8 days before detaching and beginning the maturation of its single egg batch which is laid during a period of about 30 days. The feeding period is characterized by an important synthesis of endocuticular material occurring before the rapid feeding phase. This latter phase, correlated with an enormous weight uptake, shows an increase of ecdysteroid levels measured in the whole animal by RIA. However, the hemolymphatic levels of ecdysteroids remain very low (12 pg 20-hydroxyecdysone equivalent (20-OH-E eq.) per μ1. Within 4 days after detachment, the salivary glands degenerate. Ecdysteroid levels in the whole animal continue to increase, reaching high values (about 500 ng 20-OH-E eq./tick) at the moment of oviposition which begins 10–14 days after dropping. During the same period, hemolymphatic ecdysteroid levels increase, rising to a peak (600 pg 20-OH-E eq./μ1) 1 day prior to the beginning of oviposition. Then, the levels decrease and stabilize around 250 pg 20-OH-E eq./μl during egg-laying. Freshly laid eggs contain large amounts of ecdysteroids (2744 pg 20-OH-E eq./mg).

20-Hydroxyecdysone and ecdysone have been found to be the major free ecdysteroids in hemolymph, ovaries and eggs (verified by the HPLC-RIA technique and GC-MF of silylated HPLC fractions). Helix juice (or esterase) labile ecdysteroid conjugates do not seem to be present to any noticeable extent in hemolymph, ovaries and eggs.     

Assimilation without groups?

In “Origins and Destinations”, Luthra, Soehl and Waldinger aim at “extending the canon” in research on immigrant integration. They do so by studying group and individual level characteristics across a large number of origin groups, thereby replacing group labels with theoretically relevant variables at the group level. In this review, three challenges in this endeavour are discussed: First of all, the analyses do not allow to disentangle the impact of group and individual level characteristics for all variables alike. Secondly, a primary data collection more tailored to the specifics of their conceptual framework is needed. This would many conclusions about how contexts of emigration and immigration truly matter above and beyond individual characteristic on a more solid ground. And third, the authors’ aim to abandon the use of origin group categories in empirical research on immigrant integration may come at a price.     

The Four Canonical TPR Subunits of Human APC/C Form Related Homo-Dimeric Structures and Stack in Parallel to Form a TPR Suprahelix

The anaphase-promoting complex or cyclosome (APC/C) is a large E3 RING-cullin ubiquitin ligase composed of between 14 and 15 individual proteins. A striking feature of the APC/C is that only four proteins are involved in directly recognizing target proteins and catalyzing the assembly of a polyubiquitin chain. All other subunits, which account for > 80% of the mass of the APC/C, provide scaffolding functions. A major proportion of these scaffolding subunits are structurally related. In metazoans, there are four canonical tetratricopeptide repeat (TPR) proteins that form homo-dimers (Apc3/Cdc27, Apc6/Cdc16, Apc7 and Apc8/Cdc23). Here, we describe the crystal structure of the N-terminal homo-dimerization domain of Schizosaccharomyces pombe Cdc23 (Cdc23^Nterm). Cdc23^Nterm is composed of seven contiguous TPR motifs that self-associate through a related mechanism to those of Cdc16 and Cdc27. Using the Cdc23^Nterm structure, we generated a model of full-length Cdc23. The resultant “V”-shaped molecule docks into the Cdc23-assigned density of the human APC/C structure determined using negative stain electron microscopy (EM). Based on sequence conservation, we propose that Apc7 forms a homo-dimeric structure equivalent to those of Cdc16, Cdc23 and Cdc27. The model is consistent with the Apc7-assigned density of the human APC/C EM structure. The four canonical homo-dimeric TPR proteins of human APC/C stack in parallel on one side of the complex. Remarkably, the uniform relative packing of neighboring TPR proteins generates a novel left-handed suprahelical TPR assembly. This finding has implications for understanding the assembly of other TPR-containing multimeric complexes.     

Structural and biochemical characterization of Rv2140c,a phosphatidylethanolamine-binding protein from Mycobacterium tuberculosis

Rv2140c is one of many conserved Mycobacterium tuberculosis proteins for which no molecular function has been identified. We have determined a high-resolution crystal structure of the Rv2140c gene product, which reveals a dimeric complex that shares strong structural homology with the phosphatidylethanolamine-binding family of proteins. Rv2140c forms low-millimolar interactions with a selection of soluble phosphatidylethanolamine analogs, indicating that it has a role in lipid metabolism. Furthermore, the small molecule locostatin binds to the Rv2140c ligand-binding site and also inhibits the growth of the model organism Mycobacterium smegmatis.