Domain structure and function of matrix metalloprotease 23 (MMP23): role in potassium channel trafficking

MMP23 is a member of the matrix metalloprotease family of zinc- and calcium-dependent endopeptidases, which are involved in a wide variety of cellular functions. Its catalytic domain displays a high degree of structural homology with those of other metalloproteases, but its atypical domain architecture suggests that it may possess unique functional properties. The N-terminal MMP23 pro-domain contains a type-II transmembrane domain that anchors the protein to the plasma membrane and lacks the cysteine-switch motif that is required to maintain other MMPs in a latent state during passage to the cell surface. Instead of the C-terminal hemopexin domain common to other MMPs, MMP23 contains a small toxin-like domain (TxD) and an immunoglobulin-like cell adhesion molecule (IgCAM) domain. The MMP23 pro-domain can trap Kv1.3 but not closely-related Kv1.2 channels in the endoplasmic reticulum, preventing their passage to the cell surface, while the TxD can bind to the channel pore and block the passage of potassium ions. The MMP23 C-terminal IgCAM domain displays some similarity to Ig-like C2-type domains found in IgCAMs of the immunoglobulin superfamily, which are known to mediate protein–protein and protein–lipid interactions. MMP23 and Kv1.3 are co-expressed in a variety of tissues and together are implicated in diseases including cancer and inflammatory disorders. Further studies are required to elucidate the mechanism of action of this unique member of the MMP family.     

TPX2: of spindle assembly,DNA damage response,and cancer

For more than 15 years, TPX2 has been studied as a factor critical for mitosis and spindle assembly. These functions of TPX2 are attributed to its Ran-regulated microtubule-associated protein properties and to its control of the Aurora A kinase. Overexpressed in cancers, TPX2 is being established as marker for the diagnosis and prognosis of malignancies. During interphase, TPX2 resides preferentially in the nucleus where its function had remained elusive until recently. The latest finding that TPX2 plays a role in amplification of the DNA damage response, combined with the characterization of TPX2 knockout mice, open new perspectives to understand the biology of this protein. This review provides an historic overview of the discovery of TPX2 and summarizes its cytoskeletal and signaling roles with relevance to cancer therapies. Finally, the review aims to reconcile discrepancies between the experimental and pathological effects of TPX2 overexpression and advances new roles for compartmentalized TPX2.     

麻栗坡半蒴苣苔:越南苦苣苔科植物国家级分布新记录

麻栗坡半蒴苣苔Hemiboea malipoensis Y.H. Tan是最近才得以被描述的、原产自中国云南麻栗坡县的苦苣苔科新种,最近在越南北部河江省(Ha Giang Province)的全坝区(Quan Ba District)也发现了该种。该新记录种的凭证标本保存在越南生态与生物资源研究所标本馆(HN)和俄罗斯科马罗夫植物研究所(LE)。本文亦同时提供了本种的详细形态描述、彩色图片、物候、生态学、保育现状等信息和目前越南已知的半蒴苣苔属植物的检索表。     

On the Edge of Web-Based Multiple Sequence Alignment Services

There are many web-based multiple sequence alignment services accessible around the world. However, many researchers working on biological sequence analysis still struggle with inefficient, unfriendly user interface, and limited capability multiple sequence alignment software. In this study, we provide a comprehensive survey of regional and continental facilities that provide web-based alignment services. We also analyze and identify much needed services that are not available through these existing service providers. We then implement a web-based model to address these needs. From that perspective, our web-based multiple sequence alignment server, SeqAna, provides a unique set of services that none of these studied facilities have. For example, SeqAna provides a multiple sequence alignment scoring and ranking service. This service, the only of its kind, allows SeqAna’s users to perform multiple sequence alignment with several alignment tools and rank the results of these alignments in the order of quality. With this service, SeqAna’s users will be able to identify which alignment tools are more appropriate for their specific set of sequences. In addition, SeqAna’s users can customize a small alignment sample as a reference for SeqAna to automatically identify the best tool to align their large set of sequences.     

Dosage compensation of the active X chromosome in mammals

Monosomy of the X chromosome owing to divergence between the sex chromosomes leads to dosage compensation mechanisms to restore balanced expression between the X and the autosomes. In Drosophila melanogaster, upregulation of the male X leads to dosage compensation. It has been hypothesized that mammals likewise upregulate their active X chromosome. Together with X inactivation, this mechanism would maintain balanced expression between the X chromosome and autosomes and between the sexes. Here, we show that doubling of the global expression level of the X chromosome leads to dosage compensation in somatic tissues from several mammalian species. X-linked genes are highly expressed in brain tissues, consistent with a role in cognitive functions. Furthermore, the X chromosome is expressed but not upregulated in spermatids and secondary oocytes, preserving balanced expression of the genome in these haploid cells. Upon fertilization, upregulation of the active X must occur to achieve the observed dosage compensation in early embryos.     

A second species of the genus Vietnamorpha Golovatch, 1984 (Polydesmida: Paradoxosomatidae) and notes on the generic relationship

A second Vietnamorpha species is described from Pu Mat National Park, north-central Vietnam. The new species is distinguished by the gonopod femorite being erect and cylindrically elongate; and the solenomere being completely sheathed by the solenophore, and being only exposed at the tip. The relationship between Vietnamorpha and several sulciferinine genera was analysed using a combination of a mitochondrial gene (16S rRNA) and two nuclear genes (18S and 28S rRNA). The genus Vietnamorpha is more closely related to the genus Anoplodesmus than to other sulciferinine genera.

www.zobank.org/urn:lsid:zoobank.org:pub:C8A19CFD-1329-427A-B380-08542BB25718     

Natural history of mesenchymal stem cells,from vessel walls to culture vessels

Mesenchymal stem/stromal cells (MSCs) can regenerate tissues by direct differentiation or indirectly by stimulating angiogenesis, limiting inflammation, and recruiting tissue-specific progenitor cells. MSCs emerge and multiply in long-term cultures of total cells from the bone marrow or multiple other organs. Such a derivation in vitro is simple and convenient, hence popular, but has long precluded understanding of the native identity, tissue distribution, frequency, and natural role of MSCs, which have been defined and validated exclusively in terms of surface marker expression and developmental potential in culture into bone, cartilage, and fat. Such simple, widely accepted criteria uniformly typify MSCs, even though some differences in potential exist, depending on tissue sources. Combined immunohistochemistry, flow cytometry, and cell culture have allowed tracking the artifactual cultured mesenchymal stem/stromal cells back to perivascular anatomical regions. Presently, both pericytes enveloping microvessels and adventitial cells surrounding larger arteries and veins have been described as possible MSC forerunners. While such a vascular association would explain why MSCs have been isolated from virtually all tissues tested, the origin of the MSCs grown from umbilical cord blood remains unknown. In fact, most aspects of the biology of perivascular MSCs are still obscure, from the emergence of these cells in the embryo to the molecular control of their activity in adult tissues. Such dark areas have not compromised intents to use these cells in clinical settings though, in which purified perivascular cells already exhibit decisive advantages over conventional MSCs, including purity, thorough characterization and, principally, total independence from in vitro culture. A growing body of experimental data is currently paving the way to the medical usage of autologous sorted perivascular cells for indications in which MSCs have been previously contemplated or actually used, such as bone regeneration and cardiovascular tissue repair.     

Genome-wide association study identifies susceptibility loci for dengue shock syndrome at MICB and PLCE1

Hypovolemic shock (dengue shock syndrome (DSS)) is the most common life-threatening complication of dengue. We conducted a genome-wide association study of 2,008 pediatric cases treated for DSS and 2,018 controls from Vietnam. Replication of the most significantly associated markers was carried out in an independent Vietnamese sample of 1,737 cases and 2,934 controls. SNPs at two loci showed genome-wide significant association with DSS. We identified a susceptibility locus at MICB (major histocompatibility complex (MHC) class I polypeptide-related sequence B), which was within the broad MHC region on chromosome 6 but outside the class I and class II HLA loci (rs3132468, P(meta) = 4.41 × 10(-11), per-allele odds ratio (OR) = 1.34 (95% confidence interval: 1.23-1.46)). We identified associated variants within PLCE1 (phospholipase C, epsilon 1) on chromosome 10 (rs3765524, P(meta) = 3.08 × 10(-10), per-allele OR = 0.80 (95% confidence interval: 0.75-0.86)). We identify two loci associated with susceptibility to DSS in people with dengue, suggesting possible mechanisms for this severe complication of dengue.