Regulation of L-periaxin by the Ubiquitin/Proteasome pathway

The morphological changes required for the ensheathment of peripheral nerve axons by Schwann cells are believed to be regulated by the cell cytoskeleton and its associated proteins. Control of the levels of these proteins is likely to be necessary for the assembly of compact myelin and the stability of the sheath.L-periaxin was initially identified as a putative cytoskeleton-associated protein expressed by myelin-forming Schwann cells based upon its insolubility in non-ionic detergent. The pattern of developmental expression of L-periaxin and its shift in localisation from the adaxonal to abaxonal membranes of myelinating Schwann cells following their association with axons, implied a role in the stabilisation of the myelin sheath. In this work, an F-box containing protein termed Fbxl6, was found to associate with the C-terminal acidic region of L-periaxin, in a search for binding partners of Lperiaxin using the yeast two-hybrid method. The observed interaction was verified by in vitro pull down assays using mouse sciatic nerve homogenate and L-periaxin generated by in vitro transcription/ translation.F-box proteins have been identified as components of a multi-enzyme complex termed SCF (Skp 1 / Cullin 1/F-box), which is responsible for the recruitment of substrates for ubiquitination and subsequent destruction. Fbxl6 belongs to the leucinerich repeat (LRR)-containing subfamily of F-box proteins. The C-terminal LRR region of the protein serves as the binding site for L-periaxin. whereas the F-box motif permits association with the core SCF complex. L-periaxin was detected as a ubiquitin conjugate in sciatic nerve explant cultures. Ubiquitination of the protein acts as a signal for degradation by the 26S proteasome, as revealed by stabilisation of L-periaxin upon inhibition of the proteasome by epoxomicin.The participation of L-periaxin in a recently identified dystroglycan- dystrophinrelated protein 2 (DRP2) complex, suggests an indirect role for Fbxl6 in the structural and signalling functions of the cortical cytoskeleton. Regulation of the levels of Lperiaxin by the ubiquitin/ proteasome pathway, mediated by Fbxl6, is likely to be important for the stabilisation of the Schwann cell-axon unit

Update on the human and mouse lipocalin (LCN) gene family, including evidence the mouse Mup cluster is result of an evolutionary bloom .

Lipocalins (LCNs) are members of a family of evolutionarily conserved genes present in all kingdoms of life. There are 19 LCN-like genes in the human genome, and 45 Lcn-like genes in the mouse genome, which include 22 major urinary protein (Mup) genes. The Mup genes, plus 29 of 30 Mup-ps pseudogenes, are all located together on chromosome (Chr) 4; evidence points to an evolutionary bloom that resulted in this Mup cluster in mouse, syntenic to the human Chr 9q32 locus at which a single MUPP pseudogene is located. LCNs play important roles in physiological processes by binding and transporting small hydrophobic molecules -such as steroid hormones, odorants, retinoids, and lipids-in plasma and other body fluids. LCNs are extensively used in clinical practice as biochemical markers. LCN-like proteins (18-40 kDa) have the characteristic eight β-strands creating a barrel structure that houses the binding-site; LCNs are synthesized in the liver as well as various secretory tissues. In rodents, MUPs are involved in communication of information in urine-derived scent marks, serving as signatures of individual identity, or as kairomones (to elicit fear behavior). MUPs also participate in regulation of glucose and lipid metabolism via a mechanism not well understood. Although much has been learned about LCNs and MUPs in recent years, more research is necessary to allow better understanding of their physiological functions, as well as their involvement in clinical disorders

Update of the keratin gene family: evolution, tissue-specific expression patterns, and relevance to clinical disorders.

Intermediate filament (IntFil) genes arose during early metazoan evolution, to provide mechanical support for plasma membranes contacting/interacting with other cells and the extracellular matrix. Keratin genes comprise the largest subset of IntFil genes. Whereas the first keratin gene appeared in sponge, and three genes in arthropods, more rapid increases in keratin genes occurred in lungfish and amphibian genomes, concomitant with land animal-sea animal divergence (~ 440 to 410 million years ago). Human, mouse and zebrafish genomes contain 18, 17 and 24 non-keratin IntFil genes, respectively. Human has 27 of 28 type I "acidic" keratin genes clustered at chromosome (Chr) 17q21.2, and all 26 type II "basic" keratin genes clustered at Chr 12q13.13. Mouse has 27 of 28 type I keratin genes clustered on Chr 11, and all 26 type II clustered on Chr 15. Zebrafish has 18 type I keratin genes scattered on five chromosomes, and 3 type II keratin genes on two chromosomes. Types I and II keratin clusters-reflecting evolutionary blooms of keratin genes along one chromosomal segment-are found in all land animal genomes examined, but not fishes; such rapid gene expansions likely reflect sudden requirements for many novel paralogous proteins having divergent functions to enhance species survival following sea-to-land transition. Using data from the Genotype-Tissue Expression (GTEx) project, tissue-specific keratin expression throughout the human body was reconstructed. Clustering of gene expression patterns revealed similarities in tissue-specific expression patterns for previously described "keratin pairs" (i.e., KRT1/KRT10, KRT8/KRT18, KRT5/KRT14, KRT6/KRT16 and KRT6/KRT17 proteins). The ClinVar database currently lists 26 human disease-causing variants within the various domains of keratin proteins

A Mystery Unraveled: Non-tumorigenic pluripotent stem cells in human adult tissues

Embryonic stem cells and induced pluripotent stem cells have emerged as the gold standard of pluripotent stem cells and the class of 10 stem cell with the highest potential for contribution to regenerative and therapeutic application; however, their translational use is often impeded by teratoma formation, commonly associated with pluripotency. We discuss a population of nontumorigenic pluripotent stem cells, termed Multilineage Differentiating Stress Enduring (Muse) cells, which offer an innovative and 15 exciting avenue of exploration for the potential treatment of various human diseases. Areas covered: This review discusses the origin of Muse cells, describes in detail their various unique characteristics, and considers future avenues of their application and investigation with respect to what is currently known 20 of adult pluripotent stem cells in scientific literature. We begin by defining cell potency, then discussing both mesenchymal and various reported populations of pluripotent stem cells, and finally, delving into Muse cells and what sets them apart from their contemporaries. Expert opinion: Muse cells derived from adipose tissue (Muse-AT) are 25 efficiently, routinely and painlessly isolated from human lipoaspirate material, exhibit tripoblastic differentiation both spontaneously and under media-specific induction, and do not form teratomas. We describe qualities specific to Muse-ATcells and their potential impact on the field of regenerative medicine and cell therapy.Fil: Simerman, Ariel A.. University of California; Estados UnidosFil: Perone, Marcelo Javier. University of California; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires; ArgentinaFil: Gimeno, Maria Laura. University of California; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires; ArgentinaFil: Dumesic, Daniel A.. University of California; Estados UnidosFil: Chazenblak, Gregorio D.. University of California; Estados Unido

Bottom-up visions for future of food growing in cities

We report on community food growing as an instance of practice-based sustainability research focused on the design of interactive systems for food growing in future cities. We present a case study with a series of workshops using speculative and participatory design approaches focused on creatively exploring futures of urban food growing with a local neighbourhood community. Working with local grassroots communities is often perceived as more egalitarian for promoting viable long-term and embedded change in cities, yet little work has studied this approach for urban food growing. To explore how we might better articulate and conceptualize collaborative food growing futures, we discuss the creation of bottom-up visions as contestations to hegemonic narratives of power and control in cities. These are affected by, limitations of present resources and infrastructures, inability to work at scale due to lack of buy-in of stakeholders, and erroneous promises of future technologies. Through these reflections on grassroots futures as complex assemblages of social and material realities, we provoke researchers and practitioners to look at envisioning future possibilities with participants, as a web of practices and stakeholders. We further suggest that researchers and practitioners explore these interconnections through assemblages of socio-material realities and visions of high- and low-tech futures. This work is important because it provides a new approach to looking at the design of future technologies for cities and addressing systemic issues of hegemonic food systems through bottom-up actionable futures

Variation of leaf litter decomposition among rivers, lagoons and sea: an experiment from Corfu island (Greece)

In aquatic ecosystems, the decomposition of organic detritus represents one of the most important ecosystem functions, which support complex detritus-based food webs that determine the critical balance between carbon mineralization and sequestration. The performance of the decomposition process is usually expressed as rate of decomposition, being a synthetic measure that take into account both abiotic and biotic factors. Decomposition rates have been also applied to evaluate the ecological status in terms of ecological functionality. However, despite a growing number of studies have tested the rate of decomposition between leaves of different riparian tree species in different aquatic ecosystems including rivers, transitional waters and sea, no comparative study among ecosystems typology is available up to date. Here, we compare decomposition rates from rivers, lagoons and sea of Corfu island (Greece). Five sampling sites were fixed in each of the three of the most important rivers and lagoons; other five sampling sites were fixed in the sea around the island. Twelve leaf packs containing 3±0.005 g of oven-dried Phragmites australis leaves were submerged in April 2014 and retrieved in May 2014 (after 30 days). Abiotic parameters were recorded in both sampling times. The retrieved leaf packs were cleaned and the macroinvertebrates retained were removed, counted, identified at lower taxonomic level and weighted. Leaf pack decomposition rates were calculated, and their variability was compared within each aquatic ecosystem, within each ecosystem typology (river, lagoon, sea) and among ecosystem typology. The results are going to be presented on the poster