Genetic tagging: contemporary molecular ecology

Population genetic analyses have been highly successful in deciphering inter- and intra-specific evolutionary relationships, levels of gene flow, genetic divergence and effective population sizes. Parameters estimated by traditional population genetic analyses are evolutionary averages and thus not necessarily relevant for contemporary ecological or conservation issues. Molecular data can, however, also provide insight into contemporary patterns of divergence, population size and gene flow when a sufficient number of variable loci are analysed to focus subsequent data analyses on individuals rather than populations. Genetic tagging of individuals is an example of such individual-based approaches and recent studies have shown it to be a viable alternative to traditional tagging methods. Owing to the ubiquitous presence of hyper-variable DNA sequences in eukaryote genomes it is in principle possible to tag any eukaryote species and the required DNA can be obtained indirectly from substrates such as faeces, sloughed skin and hair. The purpose of this paper is to present the concept of genetic tagging and to further advocate the extension of individual-based genetic analyses beyond the identification of individuals to other kinds of relationships, such as parent-offspring relations, which more fully exploit the genetic nature of the data.     

Multimodal regulation of myosin VI ensemble transport by cargo adaptor protein GIPC

A range of cargo adaptor proteins are known to recruit cytoskeletal motors to distinct subcellular compartments. However, the structural impact of cargo recruitment on motor function is poorly understood. Here, we dissect the multimodal regulation of myosin VI activity through the cargo adaptor GAIP-interacting protein, C terminus (GIPC), whose overexpression with this motor in cancer enhances cell migration. Using a range of biophysical techniques, including motility assays, FRET-based conformational sensors, optical trapping, and DNA origami–based cargo scaffolds to probe the individual and ensemble properties of GIPC–myosin VI motility, we report that the GIPC myosin-interacting region (MIR) releases an autoinhibitory interaction within myosin VI. We show that the resulting conformational changes in the myosin lever arm, including the proximal tail domain, increase the flexibility of the adaptor–motor linkage, and that increased flexibility correlates with faster actomyosin association and dissociation rates. Taken together, the GIPC MIR–myosin VI interaction stimulates a twofold to threefold increase in ensemble cargo speed. Furthermore, the GIPC MIR–myosin VI ensembles yield similar cargo run lengths as forced processive myosin VI dimers. We conclude that the emergent behavior from these individual aspects of myosin regulation is the fast, processive, and smooth cargo transport on cellular actin networks. Our study delineates the multimodal regulation of myosin VI by the cargo adaptor GIPC, while highlighting linkage flexibility as a novel biophysical mechanism for modulating cellular cargo motility.     

Fatigue In Teenagers on the interNET - The FITNET Trial. A randomized clinical trial of web-based cognitive behavioural therapy for adolescents with chronic fatigue syndrome: study protocol. [ISRCTN59878666]

Background  

Chronic Fatigue Syndrome (CFS) is increasingly recognized as a cause of disability and inactivity in adolescents in the Netherlands. CFS is characterized by unexplained fatigue lasting more than 6 months. Cognitive Behavioural Therapy (CBT) has proven to be effective. However, CBT availability for adolescents with CFS is limited and requires special therapeutic skills not always readily available. An alternative to the face-to-face CBT is FITNET, a web-based therapeutic program designed specifically for adolescents diagnosed with CFS, and their parents. This new CBT approach appeals to the modern youth, who grow up with internet as their main source of information. A web-based program offers the opportunity to lower thresholds for the acceptance and realization of healthcare. This treatment can be activated at any chosen time. The communication between patient and therapist can elapse asynchronously. If effective, this web-based program would greatly increase the therapeutic accessibility.     

Transport genes and chemotaxis in Laribacter hongkongensis: a genome-wide analysis

Background

Laribacter hongkongensis is a Gram-negative, sea gull-shaped rod associated with community-acquired gastroenteritis. The bacterium has been found in diverse freshwater environments including fish, frogs and drinking water reservoirs. Using the complete genome sequence data of L. hongkongensis, we performed a comprehensive analysis of putative transport-related genes and genes related to chemotaxis, motility and quorum sensing, which may help the bacterium adapt to the changing environments and combat harmful substances.

Results

A genome-wide analysis using Transport Classification Database TCDB, similarity and keyword searches revealed the presence of a large diversity of transporters (n = 457) and genes related to chemotaxis (n = 52) and flagellar biosynthesis (n = 40) in the L. hongkongensis genome. The transporters included those from all seven major transporter categories, which may allow the uptake of essential nutrients or ions, and extrusion of metabolic end products and hazardous substances. L. hongkongensis is unique among closely related members of Neisseriaceae family in possessing higher number of proteins related to transport of ammonium, urea and dicarboxylate, which may reflect the importance of nitrogen and dicarboxylate metabolism in this assacharolytic bacterium. Structural modeling of two C⁴-dicarboxylate transporters showed that they possessed similar structures to the determined structures of other DctP-TRAP transporters, with one having an unusual disulfide bond. Diverse mechanisms for iron transport, including hemin transporters for iron acquisition from host proteins, were also identified. In addition to the chemotaxis and flagella-related genes, the L. hongkongensis genome also contained two copies of qseB/qseC homologues of the AI-3 quorum sensing system.

Conclusions

The large number of diverse transporters and genes involved in chemotaxis, motility and quorum sensing suggested that the bacterium may utilize a complex system to adapt to different environments. Structural modeling will provide useful insights on the transporters in L. hongkongensis.