ProSAP1 and membrane nanodomain-associated syndapin I promote postsynapse formation and function

Insights into mechanisms coordinating membrane remodeling, local actin nucleation, and postsynaptic scaffolding during postsynapse formation are important for understanding vertebrate brain function. Gene knockout and RNAi in individual neurons reveal that the F-BAR protein syndapin I is a crucial postsynaptic coordinator in formation of excitatory synapses. Syndapin I deficiency caused significant reductions of synapse and dendritic spine densities. These syndapin I functions reflected direct, SH3 domain–mediated associations and functional interactions with ProSAP1/Shank2. They furthermore required F-BAR domain-mediated membrane binding. Ultra-high-resolution imaging of specifically membrane-associated, endogenous syndapin I at membranes of freeze-fractured neurons revealed that membrane-bound syndapin I preferentially occurred in spines and formed clusters at distinct postsynaptic membrane subareas. Postsynaptic syndapin I deficiency led to reduced frequencies of miniature excitatory postsynaptic currents, i.e., to defects in synaptic transmission phenocopying ProSAP1/Shank2 knockout, and impairments in proper synaptic ProSAP1/Shank2 distribution. Syndapin I–enriched membrane nanodomains thus seem to be important spatial cues and organizing platforms, shaping dendritic membrane areas into synaptic compartments.     

Pathological and parasitological findings in a wild red titi monkey, <Emphasis Type="Italic">Callicebus cupreus</Emphasis> (Pitheciidae,Platyrrhini)

An adult female red titi monkey (Callicebus cupreus) was found in a moribund state below a sleeping site at the Estación Biológica Quebrada Blanco in Peruvian Amazonia. Before death, the animal showed frequent convulsions. Post-mortem examination revealed the presence of Prosthenorchis elegans (Acanthocephala) in the small intestine. Major pathological findings concerned the digestive tract and the liver. Adult P. elegans provoked multifocal subacute to chronic enteritis with formation of ulcers in the small and large intestine. The liver revealed a severe chronic-active granulomatous hepatitis. While the cause of death could not be unambiguously identified, the infestation with P. elegans is likely to have played a key role in the pathogenesis of the chronic ulcerative enteritis and subsequent hepatitis; it possibly had a severe and long-term impact on the host’s resource utilisation and defence against intruding pathogens and toxins of the digestive tract. The death of the animal is attributed to the chronic inflammatory processes in the digestive tract.     

Syndapin oligomers interconnect the machineries for endocytic vesicle formation and actin polymerization

Syndapins were proposed to interconnect the machineries for vesicle formation and actin polymerization, as they interact with dynamin and the Arp2/3 complex activator N-WASP (neural Wiskott-Aldrich syndrome protein). Syndapins, however, have only one Src homology 3 domain mediating both interactions. Here we show that syndapins self-associate via direct syndapin/syndapin interactions, providing a molecular mechanism for the coordinating role of syndapin. Cross-link studies with overexpressed and endogenous syndapins suggest that predominantly dimers form in vivo. Our analyses show that the N-terminal Fes/Cip4 homology domain but not the central coiled-coil domain is sufficient for oligomerization. Additionally, a second interface located further C-terminally mediated interactions with the N terminus. The Src homology 3 domain and the NPF region are not involved and thus available for further interactions interconnecting different syndapin binding partners. Our analyses showed that self-association is crucial for syndapin function. Both syndapin-mediated cytoskeletal rearrangements and endocytosis were disrupted by a self-association-deficient mutant. Consistent with a role of syndapins in linking actin polymerization bursts with endocytic vesicle formation, syndapin-containing complexes had a size of 300-500 kDa in gel filtration analysis and contained both dynamin and N-WASP. The existence of an interconnection of the GTPase dynamin with N-WASP via syndapin oligomers was demonstrated both by coimmunoprecipitations and by reconstitution at membranes in intact cells. The interconnection was disrupted by coexpression of syndapin mutants incapable of self-association. Syndapin oligomers may thus act as multivalent organizers spatially and temporally coordinating vesicle fission with local actin polymerization.     

The three‐component system EsrISR regulates a cell envelope stress response in Corynebacterium glutamicum

When the cell envelope integrity is compromised, bacteria trigger signaling cascades resulting in the production of proteins that counteract these extracytoplasmic stresses. Here, we show that the two‐component system EsrSR regulates a cell envelope stress response in the Actinobacterium Corynebacterium glutamicum. The sensor kinase EsrS possesses an amino‐terminal phage shock protein C (PspC) domain, a property that sets EsrSR apart from all other two‐component systems characterized so far. An integral membrane protein, EsrI, whose gene is divergently transcribed to the esrSR gene locus and which interestingly also possesses a PspC domain, acts as an inhibitor of EsrSR under non‐stress conditions. The resulting EsrISR three‐component system is activated among others by antibiotics inhibiting the lipid II cycle, such as bacitracin and vancomycin, and it orchestrates a broad regulon including the esrI‐esrSR gene locus itself, genes encoding heat shock proteins, ABC transporters, and several putative membrane‐associated or secreted proteins of unknown function. Among those, the ABC transporter encoded by cg3322‐3320 was shown to be directly involved in bacitracin resistance of C. glutamicum. Since similar esrI‐esrSR loci are present in a large number of actinobacterial genomes, EsrISR represents a novel type of stress‐responsive system whose components are highly conserved in the phylum Actinobacteria.     

Microbial community diversity and composition varies with habitat characteristics and biofilm function in macrophyte‐rich streams

Biofilms in streams play an integral role in ecosystem processes and function yet few studies have investigated the broad diversity of these complex prokaryotic and eukaryotic microbial communities. Physical habitat characteristics can affect the composition and abundance of microorganisms in these biofilms by creating microhabitats. Here we describe the prokaryotic and eukaryotic microbial diversity of biofilms in sand and macrophyte habitats (i.e. epipsammon and epiphyton, respectively) in five macrophyte‐rich streams in Jutland, Denmark. The macrophyte species varied in growth morphology, C:N stoichiometry, and preferred stream habitat, providing a range in environmental conditions for the epiphyton. Among all habitats and streams, the prokaryotic communities were dominated by common phyla, including Alphaproteobacteria, Bacteriodetes, and Gammaproteobacteria, while the eukaryotic communities were dominated by Stramenopiles (i.e. diatoms). For both the prokaryotes and eukaryotes, the epipsammon were consistently the most diverse communities and the epiphytic communities were generally similar among the four macrophyte species. However, the communities on the least complex macrophyte, Sparganium emersum, had the lowest richness and evenness and fewest unique OTUs, whereas the macrophyte with the most morphological complexity, Callitriche spp., had the highest number of unique OTUs. In general, the microbial taxa were ubiquitously distributed across the relatively homogeneous Danish landscape as determined by measuring the similarity among communities (i.e. Sørensen similarity index). Furthermore, we found significant correlations between microbial diversity (i.e. Chao1 rarefied richness and Pielou's evenness) and biofilm structure and function (i.e. C:N ratio and ammonium uptake efficiency, respectively); communities with higher richness and evenness had higher C:N ratios and lower uptake efficiency. In addition to describing the prokaryotic and eukaryotic community composition in stream biofilms, our study indicates that 1) physical habitat characteristics influence microbial diversity and 2) the variation in microbial diversity may dictate the structural and functional characteristics of stream biofilm communities.     

Shifting paradigms in restoration of the world's coral reefs

Many ecosystems around the world are rapidly deteriorating due to both local and global pressures, and perhaps none so precipitously as coral reefs. Management of coral reefs through maintenance (e.g., marine‐protected areas, catchment management to improve water quality), restoration, as well as global and national governmental agreements to reduce greenhouse gas emissions (e.g., the 2015 Paris Agreement) is critical for the persistence of coral reefs. Despite these initiatives, the health and abundance of corals reefs are rapidly declining and other solutions will soon be required. We have recently discussed options for using assisted evolution (i.e., selective breeding, assisted gene flow, conditioning or epigenetic programming, and the manipulation of the coral microbiome) as a means to enhance environmental stress tolerance of corals and the success of coral reef restoration efforts. The 2014–2016 global coral bleaching event has sharpened the focus on such interventionist approaches. We highlight the necessity for consideration of alternative (e.g., hybrid) ecosystem states, discuss traits of resilient corals and coral reef ecosystems, and propose a decision tree for incorporating assisted evolution into restoration initiatives to enhance climate resilience of coral reefs.     

Cellular reprogramming for clinical cartilage repair

The repair of articular cartilage needs a sufficient number of chondrocytes to replace the defect tissue, and therefore, expansion of cells is generally required. Chondrocytes derived by cellular reprogramming may provide a solution to the limitations of current (stem) cell-based therapies. In this article, two distinct approaches—induced pluripotent stem cell (iPSC)-mediated reprogramming and direct lineage conversion—are analysed and compared according to criteria that encompass the qualification of the method and the derived chondrocytes for the purpose of clinical application. Progress in iPSC generation has provided insights into the replacement of reprogramming factors by small molecules and chemical compounds. As follows, multistage chondrogenic differentiation methods have shown to improve the chondrocyte yield and quality. Nevertheless, the iPSC ‘detour’ remains a time- and cost-consuming approach. Direct conversion of fibroblasts into chondrocytes provides a slight advantage over these aspects compared to the iPSC detour. However, the requirement of constitutive transgene expression to inhibit hypertrophic differentiation limits this approach of being translated to the clinic. It can be concluded that the quality of the derived chondrocytes highly depends on the characteristics of the reprogramming method and that this is important to keep in mind during the experimental set-up. Further research into both reprogramming approaches for clinical cartilage repair has to include proper control groups and epigenetic profiling to optimize the techniques and eventually derive functionally stable articular chondrocytes.