Turning it inside out: The organization of human septin heterooligomers.

Septin family proteins are quite similar to each other both within and between eukaryotic species. Typically, multiple discrete septins co-assemble into linear heterooligomers (usually hexameric or octameric rods) with a variety of cellular functions. We know little about how incorporation of different septins confers different properties to such complexes. This issue is especially acute in human cells where 13 separate septin gene products (often produced in multiple forms arising from alternative start codons and differential splicing) are expressed in a tissue-specific manner. Based on sequence alignments and phylogenetic criteria, human septins fall into four distinct groups predictive of their interactions, that is, members of the same group appear to occupy the same position within oligomeric septin protomers, which are "palindromic" (have twofold rotational symmetry about a central homodimeric pair). Many such protomers are capable of end-to-end polymerization, generating filaments. Over a decade ago, a study using X-ray crystallography and single-particle electron microscopy deduced the arrangement within recombinant heterohexamers comprising representatives of three human septin groups-SEPT2, SEPT6, and SEPT7. This model greatly influenced subsequent studies of human and other septin complexes, including how incorporating a septin from a fourth group forms heterooctamers, as first observed in budding yeast. Two recent studies, including one in this issue of Cytoskeleton, provide clear evidence that, in fact, the organization of subunits within human septin heterohexamers and heterooctamers is inverted relative to the original model. These findings are discussed here in a broader context, including possible causes for the initial confusion

Type 2 Innate Lymphoid Cells Protect against Colorectal Cancer Progression and Predict Improved Patient Survival.

Chronic inflammation of the gastrointestinal (GI) tract contributes to colorectal cancer (CRC) progression. While the role of adaptive T cells in CRC is now well established, the role of innate immune cells, specifically innate lymphoid cells (ILCs), is not well understood. To define the role of ILCs in CRC we employed complementary heterotopic and chemically-induced CRC mouse models. We discovered that ILCs were abundant in CRC tumours and contributed to anti-tumour immunity. We focused on ILC2 and showed that ILC2-deficient mice developed a higher tumour burden compared with littermate wild-type controls. We generated an ILC2 gene signature and using machine learning models revealed that CRC patients with a high intratumor ILC2 gene signature had a favourable clinical prognosis. Collectively, our results highlight a critical role for ILC2 in CRC, suggesting a potential new avenue to improve clinical outcomes through ILC2-agonist based therapeutic approaches

Initiating a state of the art system for real-time supply chain coordination

Intelligent Wireless Web (IWW) employs the capabilities of high speed wireless networks and exploits the parallel advancements in Internet-based technologies such as the Semantic Web, Web Services, Agent-based Technologies, and context awareness. Considering its great potentials to be applied in business systems, we have devised an innovative model, based on the IWW services, for a typical mobile real-time supply chain coordination system which has been developed and tested in a real operational environment. Our article investigates the proposed system in this way: at the start, the building blocks of the IWW are discussed in detail. Then, we fully explain the basic concepts of mobile real-time supply chain coordination and concentrate on the motivations to implement such a modern system. The vision of intelligent wireless web services, as discussed in this paper, centers on the need to provide mobile supply chain members highly specific data and services in real-time on an as-needed basis, with the flexibility of use for the user. In this regard, we investigate nine enabling technologies of the IWW for our system and discuss how, by exploiting the convergence and synergy between different technologies, it has become possible to deliver intelligent wireless web support to mobile real-time supply chain coordination. Afterwards, a practical framework is clearly established in four phases. This initiative system has been implemented in the laboratory and has passed the evaluation processes successfully. Further details will be announced in near future in another research article.Coordination mechanism Real-time system Supply chain management Business Applications Intelligent Wireless Web Semantic web Multi-agent system Context awareness Mobility Ubiquity

A transcriptional program for detecting TGFbeta-induced EMT in cancer

Most cancer deaths are due to metastasis, and <i>epithelial-to-mesenchymal transition</i> (EMT) plays a central role in driving cancer cell metastasis. EMT is induced by different stimuli, leading to different signaling patterns and therapeutic responses. <i>Transforming growth factor beta</i> (TGFbeta) is one of the best-studied drivers of EMT, and many drugs are available to target this signalling pathway. A comprehensive bioinformatics approach was employed to derive a signature for TGFbeta-induced EMT which can be used to score TGFbeta-driven EMT in cells and clinical specimens. Considering this signature in pan-cancer cell and tumour datasets, a number of cell lines (including Basal B breast cancer and cancers of the central nervous system) show evidence for TGFbeta-driven EMT and carry a low mutational burden across the TGFbeta signalling pathway. Further, significant variation is observed in the response of high scoring cell lines to some common cancer drugs. Finally, this signature was applied to pan-cancer data from The Cancer Genome Atlas to identify tumour types with evidence of TGFbeta-induced EMT. Tumour types with high scores showed significantly lower survival rates compared to those with low scores, and also carry a lower mutational burden in the TGFbeta pathway. The current transcriptomic signature demonstrates reproducible results across independent cell line and cancer datasets and identifies samples with strong mesenchymal phenotypes likely to be driven by TGFbeta. Implications: The TGFbeta-induced EMT signature may be useful to identify patients with mesenchymal-like tumours that could benefit from targeted therapeutics to inhibit pro-mesenchymal TGFbeta signalling and disrupt the metastatic cascade