Increased Serum LIGHT Levels Correlate with Disease Progression and Severity of Interstitial Pneumonia in Patients with Dermatomyositis: A Case Control Study

BackgroundActivated CD8+ T cells play an important role in the pathogenesis of dermatomyositis (DM) with interstitial pneumonia (IP). Serum CD8+ T-cell activator, LIGHT, and Th1/Th2/Th17 cytokines were measured in DM-IP patients and compared with clinical parameters to investigate their usefulness.MethodsThe correlations between the clinical findings and serum LIGHT and Th1/Th2/Th17 cytokine levels were investigated in 21 patients with DM-IP (14 with rapidly progressive IP [RPIP] and 7 with chronic IP [CIP], including 4 fatal cases of IP).ResultsThe median serum LIGHT level was 119 (16–335.4) pg/ml, which was higher than that in healthy control subjects and DM patients without IP. The median serum IL–6 level was 14.7 (2.4–154.5) pg/ml (n = 13). The other cytokines were detected in only a few patients. The median serum LIGHT level in DM-RPIP patients (156 [49.6–335.4] pg/ml) was significantly higher than that in DM-CIP patients (94.3 [16–164.2] pg/ml) (P = 0.02). The serum IL–6 level did not correlate with either progression or outcome of DM-IP. ROC curve analysis determined a serum LIGHT level of ≥120 pg/ml to be the cut-off value for the rapid progression of DM-IP. Serum LIGHT levels correlated significantly with %DLco (R = 0.55, P = 0.04) and total ground-glass opacity scores (R = 0.72, P = 0.0002). The serum LIGHT level significantly decreased to 100.5 (12.4–259.3) pg/ml 4 weeks after treatment initiation (P = 0.04).ConclusionsThe serum LIGHT level may be a promising marker of disease progression and severity in patients with DM-IP.     

Nucleotide sequence of a Sendai virus genome region covering the entire M gene and the 3'' proximal 1013 nucleotides of the F gene.

We determined the sequence of the 2,138 nucleotides in the Sendai virus genome just following the 3' proximal 3,686 nucleotides which we had previously reported (Nucleic Acids Res. 11, 7317-7330, 1983). This covers the entire third gene of 1,173 nucleotides and the 3' proximal 1,013 nucleotides of the fourth gene. Like the NP and P+C genes, both the third and fourth genes start from consensus sequence R1 (3'-UCCCAC(or UA)UUUC) at the 3' end and the third gene terminates with consensus sequence R2 (3'-AUUCUUUUU) at the 5' end. The third gene was identified as M, and the deduced 348 amino acids indicated that the M protein is rich in basic residues and has hydrophobic domains near the C-terminal. The fourth gene, although sequencing is not complete yet, was identified as F, since a large open reading frame found in the gene contains the characteristic sequence of 20 amino acids located at the N-terminal of the F1 protein. Analyses of the amino acid sequence suggested that the structure of the F gene product is NH2-signal peptide-F2-F1-COOH.     

Chondrosarcoma of the trachea. A case report and literature review

The cytologic presentation of a case of chondrosarcoma of the trachea in a 72-year-old man is described. A mass detected on routine chest roentgenogram and defined by CT scan was used to make a touch imprint smear during partial tumor resection. The cytologic findings included round or polygonal cells with occasional binucleation, round hyperchromatic nuclei and prominent nucleoli, present in an amorphous pink-violet or light-blue background containing fragments of chondroid tissue. The histopathology was interpreted as a low-grade chondrosarcoma. Cartilaginous tumors of the trachea should be considered in the differential diagnosis of upper airway obstruction.     

Predicting the effects of climate change on population connectivity and genetic diversity of an imperiled freshwater mussel,Cumberlandia monodonta (Bivalvia: Margaritiferidae), in riverine systems

In the face of global climate change, organisms may respond to temperature increases by shifting their ranges poleward or to higher altitudes. However, the direction of range shifts in riverine systems is less clear. Because rivers are dendritic networks, there is only one dispersal route from any given location to another. Thus, range shifts are only possible if branches are connected by suitable habitat, and stream‐dwelling organisms can disperse through these branches. We used Cumberlandia monodonta (Bivalvia: Unionoida: Margaritiferidae) as a model species to investigate the effects of climate change on population connectivity because a majority of contemporary populations are panmictic. We combined ecological niche models (ENMs) with population genetic simulations to investigate the effects of climate change on population connectivity and genetic diversity of C. monodonta. The ENMs were constructed using bioclimatic and landscape data to project shifts in suitable habitat under future climate scenarios. We then used forward‐time simulations to project potential changes in genetic diversity and population connectivity based on these range shifts. ENM results under current conditions indicated long stretches of highly suitable habitat in rivers where C. monodonta persists; populations in the upper Mississippi River remain connected by suitable habitat that does not impede gene flow. Future climate scenarios projected northward and headwater‐ward range contraction and drastic declines in habitat suitability for most extant populations throughout the Mississippi River Basin. Simulations indicated that climate change would greatly reduce genetic diversity and connectivity across populations. Results suggest that a single, large population of C. monodonta will become further fragmented into smaller populations, each of which will be isolated and begin to differentiate genetically. Because C. monodonta is a widely distributed species and purely aquatic, our results suggest that persistence and connectivity of stream‐dwelling organisms will be significantly altered in response to future climate change.     

Impaired NO-mediated vasodilation with increased superoxide but robust EDHF function in right ventricular arterial microvessels of pulmonary hypertensive rats

Pulmonary hypertension (PH) causes right ventricular (RV) hypertrophy and, according to the extent of pressure overload, eventual heart failure. We tested the hypothesis that the mechanical stress in PH-RV impairs the vasoreactivity of the RV coronary microvessels of different sizes with increased superoxide levels. Five-week-old male Sprague-Dawley rats were injected with monocrotaline (n=126) to induce PH or with saline as controls (n=114). After 3 wk, coronary arterioles (diameter = 30-100 microm) and small arteries (diameter = 100-200 microm) in the RV were visualized using intravital videomicroscopy. We evaluated ACh-induced vasodilation alone, in the presence of N(omega)-nitro-L-arginine methyl ester (L-NAME), in the presence of tetraethylammonium (TEA) or catalase with or without L-NAME, and in the presence of SOD. The degree of suppression in vasodilation by L-NAME and TEA was used as indexes of the contributions of endothelial nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF), respectively. In PH rats, ACh-induced vasodilation was significantly attenuated in both arterioles and small arteries, especially in arterioles. This decreased vasodilation was largely attributable to reduced NO-mediated vasoreactivity, whereas the EDHF-mediated vasodilation was relatively robust. The suppressive effect on arteriolar vasodilation by catalase was similar to TEA in both groups. Superoxide, as measured by lucigenin chemiluminescence, was significantly elevated in the RV tissues in PH. SOD significantly ameliorated the impairment of ACh-induced vasodilation in PH. Robust EDHF function will play a protective role in preserving coronary microvascular homeostasis in the event of NO dysfunction with increased superoxide levels.     

Transforming activity of purinergic receptor P2Y, G-protein coupled, 2 revealed by retroviral expression screening

Colorectal cancer (CRC) is one of the leading causes of cancer death in humans. In order to identify novel cancer-promoting genes in CRC, we here constructed a retroviral cDNA expression library from a CRC cell line RKO, and used it for a focus formation assay with mouse 3T3 fibroblasts, leading to the identification of 42 independent cDNAs. One of such cDNAs turned out to encode purinergic receptor P2Y, G-protein coupled, 2 (P2RY2). The oncogenic potential of P2RY2 was confirmed in vitro with the focus formation assay as well as soft agar-growth assay, and also in vivo with a tumorigenicity assay in nude mice. While our P2RY2 cDNA encodes a protein with two amino-acid substitutions compared to the reported one, we have confirmed that the wild-type P2RY2 has a strong transforming potential as well. These results indicate an unexpected role of P2RY2 in the carcinogenesis of human cancers.     

First documentation of detailed behaviors of endangered adult Sakhalin taimen <Emphasis Type="Italic">Parahucho perryi</Emphasis> in the Bekanbeushi River system,eastern Hokkaido,Japan, using bio-logging and acoustic telemetry concurrently

Behavior of adult Parahucho perryi was examined using bio-logging and acoustic telemetry concurrently in the Bekanbeushi River system, eastern Hokkaido, Japan, in 2009 and 2010. Based on 46.1–87.9 h data from five P. perryi (69.0–80.0 cm fork length) caught from Lake Akkeshi, they used upstream (n = 2), midstream (n = 3), and downstream (n = 4) habitats. Large variability in diel activity and depth occupation existed in each stream habitat; however, fish in the downstream habitat tended to be more active than those in the upper habitats and mainly occupied shallower depths than mean bottom depth in this habitat.     

Regulation of glial development by cystatin C

Cystatin C (CysC) is an endogenous cysteine proteases inhibitor produced by mature astrocytes in the adult brain. Previously we isolated CysC as a factor activating the glial fibrillary acidic protein (GFAP) promoter, and showed that CysC is expressed in astrocyte progenitors during development. Here we show that protease inhibitor activity increased daily in conditioned medium, and that this activity was mainly a result of CysC released from primary cultured cells. Human CysC added to the culture medium of primary brain cells increased the number of GFAP-positive and nestin-positive cells. Human CysC also increased the number of neurospheres formed from embryonic brain, and thus it increases the number of neural stem/precursor cells in a manner similar to glycosylated rat CysC. The addition of a neutralizing antibody, on the other hand, greatly decreased the number of GFAP and glutamate aspartate transporter (GLAST)-positive astrocytes. This decrease was reversed by the addition of CysC but not by another cysteine protease inhibitor. Thus, the promotion of astrocyte development by CysC appears to be independent of its protease inhibitor activity. The antibody increased the number of oligodendrocytes and their precursors. Therefore, CysC modifies glial development in addition to its activity against neural stem/precursor cells.     

Cyanobacterial Cell Lineage Analysis of the Spatiotemporal hetR Expression Profile during Heterocyst Pattern Formation in Anabaena sp. PCC 7120

Diazotrophic heterocyst formation in the filamentous cyanobacterium, Anabaena sp. PCC 7120, is one of the simplest pattern formations known to occur in cell differentiation. Most previous studies on heterocyst patterning were based on statistical analysis using cells collected or observed at different times from a liquid culture, which would mask stochastic fluctuations affecting the process of pattern formation dynamics in a single bacterial filament. In order to analyze the spatiotemporal dynamics of heterocyst formation at the single filament level, here we developed a culture system to monitor simultaneously bacterial development, gene expression, and phycobilisome fluorescence. We also developed micro-liquid chamber arrays to analyze multiple Anabaena filaments at the same time. Cell lineage analyses demonstrated that the initial distributions of hetR::gfp and phycobilisome fluorescence signals at nitrogen step-down were not correlated with the resulting distribution of developed heterocysts. Time-lapse observations also revealed a dynamic hetR expression profile at the single-filament level, including transient upregulation accompanying cell division, which did not always lead to heterocyst development. In addition, some cells differentiated into heterocysts without cell division after nitrogen step-down, suggesting that cell division in the mother cells is not an essential requirement for heterocyst differentiation.     

KATAMARI1/MURUS3 Is a novel golgi membrane protein that is required for endomembrane organization in Arabidopsis

In plant cells, unlike animal and yeast cells, endomembrane dynamics appear to depend more on actin filaments than on microtubules. However, the molecular mechanisms of endomembrane-actin filament interactions are unknown. In this study, we isolated and characterized an Arabidopsis thaliana mutant, katamari1 (kam1), which has a defect in the organization of endomembranes and actin filaments. The kam1 plants form abnormally large aggregates that consist of endoplasmic reticulum with actin filaments in the perinuclear region within the cells and are defective in normal cell elongation. Map-based cloning revealed that the KAM1 gene is allelic to the MUR3 gene. We demonstrate that the KAM1/MUR3 protein is a type II membrane protein composed of a short cytosolic N-terminal domain and a transmembrane domain followed by a large lumenal domain and is localized specifically on Golgi membranes. We further show that actin filaments interact with Golgi stacks via KAM1/MUR3 to maintain the proper organization of endomembranes. Our results provide functional evidence that KAM1/MUR3 is a novel component of the Golgi-mediated organization of actin functioning in proper endomembrane organization and cell elongation.