Single-Cell Heterogeneity Analysis and CRISPR Screen Identify Key β-Cell-Specific Disease Genes

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Osteoactivin fragments produced by ectodomain shedding induce MMP-3 expression via ERK pathway in mouse NIH-3T3 fibroblasts

Intact osteoactivin, a novel type I membrane glycoprotein, were shed at a dibasic motif in the juxtamembrane region in C2C12 myoblasts. Extracellular fragments were secreted into the culture media by a putative metalloprotease. Extracellular fragments of osteoactivin, but not control protein, induced matrix metalloprotease-3 (MMP-3) expression in NIH-3T3 fibroblasts. Epidermal growth factor (ERK) kinase inhibitors inhibited the osteoactivin-mediated MMP-3 expression, whereas the extracellular fragment of osteoactivin activated ERK1/2 and p38 in the mitogen-activated protein kinase pathway. Our results suggest that the extracellular fragments of osteoactivin produced by shedding act as a growth factor to induce MMP-3 expression via the ERK pathway in fibroblasts.     

Regulation of HD-ZIP III Genes by MicroRNA 165

MicroRNAs (miRNAs) 165 and 166 are able to cleave their target mRNAs of HD-ZIP III genes, thus regulating the functions of these genes. Although it is generally accepted that both miR165 and miR166 perform the same functions in the regulation of HD-ZIP III genes in Arabidopsis, no experimental data are available to support this notion. Recent work has shown that overexpression of miR166 downregulates the expression of three HD-ZIP III genes, ATHB-9/PHV, ATHB-14/PHB and ATHB-15, which in turn recapitulates the phenotypes of simultaneous loss-of-function mutations of these genes. In the March issue of Plant & Cell Physiology, we have demonstrated that overexpression of miR165 leads to the down-regulation of all five HD-ZIP III genes, and concomitantly recapitulates the phenotypes of loss-of-function mutation of IFL1/REV and those of simultaneous loss-of-function mutations of IFL1/REV, ATHB-9/PHV and ATHB-14/PHB. These results indicate that miR165 and miR166 differentially regulate the functions of HD-ZIP III genes in Arabidopsis. In this addendum, we show that overexpression of the antisense form of the miR165a gene leads to formation of amphivasal vascular bundles, a phenotype reminiscent of that of the dominant mutation of IFL1/REV. This finding provides direct evidence for a role of miR165 in regulation of vascular patterning.Key Words: HD-ZIP III genes, miR165, miR166, organ polarity, vascular patterning     

Characterization of structural and optical properties of Mn2+-doped Zn2GeO4 nanorods as an efficient green phosphor for solid-state lighting

A series of Mn²⁺-doped zinc germinate ZGO:xMn²⁺ (x = 0–0.05) nanorods was synthesized successfully using a hydrothermal method. XRD revealed that crystal phases of the ZGO:xMn²⁺ were rhombohedral and in the R-3 space group. The Williamson–Hall equation was also used to explain the strain, nanocrystalline size, and stacking fault. Green LEDs were successfully fabricated by coating ZGO:Mn²⁺ nanorods onto UV-LED chips. For high color purity, CIE of the fabricated green LEDs were (0.2404, 0.5428), which made this material a promising candidate for fabrication of UV-based green LEDs.     

Isolation of Aspergillus caninus (Synonym: Phialosimplex caninus) from a Canine Iliac Lymph node

Mycopathologia - Aspergillus caninus (synonym: Phialosimplex caninus) is an anamorphic fungus species associated with systemic infections in dogs that has been transferred from the genus...     

Autophagy-competent mitochondrial translation elongation factor TUFM inhibits caspase-8-mediated apoptosis

Mitochondria support multiple cell functions, but an accumulation of dysfunctional or excessive mitochondria is detrimental to cells. We previously demonstrated that a defect in the autophagic removal of mitochondria, termed mitophagy, leads to the acceleration of apoptosis induced by herpesvirus productive infection. However, the exact molecular mechanisms underlying activation of mitophagy and regulation of apoptosis remain poorly understood despite the identification of various mitophagy-associated proteins. Here, we report that the mitochondrial translation elongation factor Tu, a mitophagy-associated protein encoded by the TUFM gene, locates in part on the outer membrane of mitochondria (OMM) where it acts as an inhibitor of altered mitochondria-induced apoptosis through its autophagic function. Inducible depletion of TUFM potentiated caspase-8-mediated apoptosis in virus-infected cells with accumulation of altered mitochondria. In addition, TUFM depletion promoted caspase-8 activation induced by treatment with TNF-related apoptosis-inducing ligand in cancer cells, potentially via dysregulation of mitochondrial dynamics and mitophagy. Importantly, we revealed the existence of and structural requirements for autophagy-competent TUFM on the OMM; the GxxxG motif within the N-terminal mitochondrial targeting sequences of TUFM was required for self-dimerization and mitophagy. Furthermore, we found that autophagy-competent TUFM was subject to ubiquitin-proteasome-mediated degradation but stabilized upon mitophagy or autophagy activation. Moreover, overexpression of autophagy-competent TUFM could inhibit caspase-8 activation. These studies extend our knowledge of mitophagy regulation of apoptosis and could provide a novel strategic basis for targeted therapy of cancer and viral diseases.Subject terms: Macroautophagy, Microbiology     

Genomic Organization and Mutation Analysis ofp73in Oligodendrogliomas with Chromosome 1 p-Arm Deletions

p73, a protein having substantial structural and functional similarity to p53, has recently been identified and demonstrated to be a potential tumor suppressor. Its location on human chromosome 1p36.33 implicates p73 as a candidate for neuroblastoma. Like neuroblastoma, oligodendrogliomas also show a high frequency of deletions in chromosome 1p36.3. To determine whetherp73is a potential tumor suppressor gene involved in the development of oligodendrogliomas, we performed mutation analysis ofp73in oligodendrogliomas with chromosome 1 p-arm deletions. We first determined the genomic organization and the intron–exon boundary sequences of thep73gene by long PCR, vectorette PCR, and Southern hybridization. This gene spans about 65 kb with a large first intron. Primer pairs for the amplification of each of the 13 p73 encoding exons were designed in corresponding introns. The amplicons were then analyzed using the denaturing high-performance liquid chromatography system for mutations in thep73gene. Twenty oligodendroglioma samples with 1p36.3 deletions were screened, but no mutations were detected except for several polymorphisms. It is thus clear thatp73is not a candidate gene for oligodendroglioma despite its location in the frequently deleted 1p36.3 region.