Tumor metastasis is the major cause of death among cancer patients, with >90% of cancer-related death attributable to the spreading of metastatic cells to secondary organs. Store-operated Ca(2+) ...entry (SOCE) is the predominant Ca(2+) entry mechanism in most cancer cells, and stromal interaction molecule 1 (STIM1) is the endoplasmic reticulum (ER) Ca(2+) sensor for store-operated channels. Here we reported that the STIM1 was overexpressed in colorectal cancer (CRC) patients. STIM1 overexpression in CRC was significantly associated with tumor size, depth of invasion, lymph node metastasis status and serum levels of carcinoembryonic antigen. Furthermore, ectopic expression of STIM1 promoted CRC cell motility, while depletion of STIM1 with short hairpin RNA inhibited CRC cell migration. Our data further suggested that STIM1 promoted CRC cell migration through increasing the expression of cyclooxygenase-2 (COX-2) and production of prostaglandin E2 (PGE2). Importantly, ectopically expressed COX-2 or exogenous PGE2 were able to rescue migration defect in STIM1 knockdown CRC cells, and inhibition of COX-2 with ibuprofen and indomethacin abrogated STIM1-mediated CRC cell motility. In short, our data provided clinicopathological significance for STIM1 and SOCE in CRC progression, and implicated a role for COX-2 in STIM1-mediated CRC metastasis. Our studies also suggested a new approach to inhibit STIM1-mediated metastasis with COX-2 inhibitors.
Metastasis is the predominant cause of death in breast cancer patients. Several lines of evidence have shown that microRNAs (miRs) can have an important role in cancer metastasis. Using isogenic ...pairs of low and high metastatic lines derived from a human breast cancer line, we have identified miR-149 to be a suppressor of breast cancer cell invasion and metastasis. We also identified GIT1 (G-protein-coupled receptor kinase-interacting protein 1) as a direct target of miR-149. Knockdown of GIT1 reduced migration/invasion and metastasis of highly invasive cells. Re-expression of GIT1 significantly rescued miR-149-mediated inhibition of cell migration/invasion and metastasis. Expression of miR-149 impaired fibronectin-induced focal adhesion formation and reduced phosphorylation of focal adhesion kinase and paxillin, which could be restored by re-expression of GIT1. Inhibition of GIT1 led to enhanced protein degradation of paxillin and α5β1 integrin via proteasome and lysosome pathways, respectively. Moreover, we found that GIT1 depletion in metastatic breast cancer cells greatly reduced α5β1-integrin-mediated cell adhesion to fibronectin and collagen. Low level of miR-149 and high level of GIT1 was significantly associated with advanced stages of breast cancer, as well as with lymph node metastasis. We conclude that miR-149 suppresses breast cancer cell migration/invasion and metastasis by targeting GIT1, suggesting potential applications of the miR-149-GIT1 pathway in clinical diagnosis and therapeutics.
Studying tissue composition and function in non-human primates (NHPs) is crucial to understand the nature of our own species. Here we present a large-scale cell transcriptomic atlas that encompasses ...over 1 million cells from 45 tissues of the adult NHP Macaca fascicularis. This dataset provides a vast annotated resource to study a species phylogenetically close to humans. To demonstrate the utility of the atlas, we have reconstructed the cell-cell interaction networks that drive Wnt signalling across the body, mapped the distribution of receptors and co-receptors for viruses causing human infectious diseases, and intersected our data with human genetic disease orthologues to establish potential clinical associations. Our M. fascicularis cell atlas constitutes an essential reference for future studies in humans and NHPs.
Several pathogenic bacteria strains were isolated from dead larvae of the weevil, Rhynchophorus ferrugineus Oliver, collected on palm trees in Taiwan, China. Strains of pure cultures were temporarily ...named TW‐1, TW‐2, TW‐3, TW‐4, TW‐5, TW‐6, TW‐7, TW‐8, TW‐9, TW‐10, TW‐11, TW‐12, TW‐13 and TW‐14. These strains were identified by synthetically using colony morphological characters, physiological and biochemical tests and molecular biological analysis. Our results showed that these 14 isolated strains belonged to four genera and five species. The expected approximate 1400‐bp bands were obtained through 16S rDNA universal primer amplification. The sequencing results obtained from a commercial sequencing company were initially compared with a corresponding database from NCBI using BLAST, and a phylogenetic tree was constructed using mega 5.1 software. The phylogenetic results indicated that these isolated strains had more than 99% homology with type strains. To further confirm these strains, numerous physiological and biochemical indexes were confirmed. TW‐1, TW‐2, TW‐3, TW‐9, TW‐12, TW‐13 and TW‐14 were identified as Serratia marcescens; TW‐4, TW‐5, TW‐8 and TW‐10 as Staphylococcus sciuri; TW‐6 as Klebsiella pneumonia subsp. pneumonia; TW‐7 as Proteus vulgaris and TW‐11 as Proteus mirabilis. The preliminary single‐dose bioassay on fourth instar larvae showed that S. marcescens had a higher virulence at a density of 1.89 OD600 (56.37% mortality) than the other strains. The corrected mortalities of the other strains were all less than 50%. The lowest toxicities were found for P. vulgaris and P. mirabilis where the corrected mortalities were only 28.18% and 25.57%, respectively. LC50 of S. marcescens was 1.2 × 107 CFU/ml inoculums. Our results indicated that S. marcescens from facultative cultivable bacterial flora isolated from R. ferrugineus could potentially be used as a microbial control agent for this widespread pest.
The ocnus (ocn) gene encodes a protein abundant in the testes, implying its role in testis development. When Drosophila melanogaster is infected with the endosymbiont wMel Wolbachia, which affects ...the spermatogenesis of its hosts, ocn is downregulated in the third‐instar larval testes, suggesting a role of ocn in spermatogenesis. In this study, we knocked down ocn in the testes and found that the hatch rates of embryos derived from ocn‐knockdown males were significantly decreased, and 84.38% of the testes were much smaller in comparison to controls. Analysis of the smaller testes showed no germ cells but they had an extended hub. Using RNA‐sequencing (RNA‐Seq), we identified 69 genes with at least a twofold change (q‐value < 5%) in their expression after ocn knockdown; of these, eight testes‐specific and three reproduction‐related genes were verified to be significantly downregulated using quantitative reverse transcription‐PCR. Three genes (orientation disruptor, p24‐2 and CG13541) were also significantly downregulated in the presence of Wolbachia. Furthermore, 98 genes were not expressed when ocn was knocked down in testes. These results suggest that ocn plays a crucial role in male germ cell development in Drosophila, possibly by regulating the expression of multiple spermatogenesis‐related genes. Our data provide important information to help understand the molecular regulatory mechanisms underlying spermatogenesis.
Highlights • The expression of PHB1 was downregulated following SCI in rats. • Ad-PHB1 administration promoted functional recovery in rats with SCI. • Ad-PHB1 administration following SCI reduced ...apoptosis. • Ad-PHB1 administration following SCI suppressed ER stress. • Ad-PHB1 administration following SCI restored mitochondrial function.
Some gamma-ray bursts (GRBs) have a tera-electron volt (TeV) afterglow, but the early onset of this has not been observed. We report observations with the Large High Altitude Air Shower Observatory ...(LHAASO) of the bright GRB 221009A, which serendipitously occurred within the instrument's field of view. More than 64,000 photons >0.2 TeV were detected within the first 3000 seconds. The TeV flux began several minutes after the GRB trigger and then rose to a peak ~10 seconds later. This was followed by a decay phase, which became more rapid ~650 seconds after the peak. We interpret the emission using a model of a relativistic jet with half-opening angle of ~0.8°. This is consistent with the core of a structured jet and could explain the high isotropic energy of this GRB.
An 8‐week feeding trial was conducted to determine the dietary leucine requirement for juvenile swimming crabs reared in cement pools. Six isonitrogenous and isolipidic practical diets (430 g/kg ...crude protein and 70 g/kg crude lipid) were formulated to contain graded leucine levels which ranged from 16.7 to 26.7 g/kg (dry weight). Each diet was randomly assigned to triplicate groups of 60 juvenile swimming crabs (initial average weight 3.75 ± 0.12 g) that were stocked in rectangle plastic baskets. The results of the present study indicated that dietary leucine levels significantly influenced weight gain (WG) and specific growth ratio (SGR) (p < .05), crab fed the diet containing 22.7 g/kg leucine had significantly higher WG and SGR than those fed the other diets. Feed efficiency and protein efficiency ratio were not significantly affected by the dietary leucine levels (p > .05). Total protein, cholesterol, triglyceride and glucose in serum were significantly affected by the dietary leucine levels. Aspartate aminotransferase (AST) and alanine aminotransferase activities in hemolymph, AST and superoxide dismutase activities in hepatopancreas were significantly affected by dietary leucine levels; moreover, crab fed the 16.7 g/kg leucine diet had higher malondialdehyde in hemolymph and hepatopancreas than those fed the other diets. Crab fed the diet containing 24.9 g/kg leucine had higher phenoloxidase activity in hemolymph than those fed the other diets. Based on two‐slope broken‐line model of SGR against dietary leucine levels, the optimal dietary leucine requirement for growth was estimated to be 22.1 g/kg of the dry diet (corresponding to 51.4 g/kg of dietary protein on a dry weight basis). In summary, findings of this study indicated that dietary leucine could improve growth performance and antioxidant status.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background and Aims
We report the chemometric classification of commercial Chinese Cabernet Sauvignon dry red wines according to the winegrowing region based on the coupling of synchronous ...fluorescence (SF) and ultraviolet (UV)–visible (VIS) spectroscopies.
Methods and Results
Total SF spectra at a wavelength difference (Δλ) of 10–150 nm with 10‐nm intervals, UV spectra in the 240 to 380 nm range and VIS spectra in the 380‐ to 700‐nm range were recorded. A simple classification model was constructed by principal component analysis and linear discriminant analysis and was evaluated by external validation. The combined use of SF and UV–VIS spectroscopies offered clearer classification than the individual techniques. The Δλ in SF spectroscopy was revealed to play an important role in the classification. The combination of SF spectroscopy at Δλ 30, 60, 90 and 120 nm and UV–VIS spectroscopy achieved the highest prediction rate (79.2%).
Conclusions
The fusion of data from UV–VIS and SF spectroscopies at multiple Δλ with certain pitched intervals, which has retained more complementary and useful information, can mostly improve the classification of wines.
Significance of the Study
The joint use of the two complementary spectroscopies provides an alternative to discriminate wines from different geographical origins.
The diffuse Galactic γ-ray emission, mainly produced via interactions between cosmic rays and the interstellar medium and/or radiation field, is a very important probe of the distribution, ...propagation, and interaction of cosmic rays in the Milky Way. In this Letter, we report the measurements of diffuse γ rays from the Galactic plane between 10 TeV and 1 PeV energies, with the square kilometer array of the Large High Altitude Air Shower Observatory (LHAASO). Diffuse emissions from the inner (15°<l<125°, |b|<5°) and outer (125°<l<235°, |b|<5°) Galactic plane are detected with 29.1σ and 12.7σ significance, respectively. The outer Galactic plane diffuse emission is detected for the first time in the very- to ultra-high-energy domain (E>10 TeV). The energy spectrum in the inner Galaxy regions can be described by a power-law function with an index of -2.99±0.04, which is different from the curved spectrum as expected from hadronic interactions between locally measured cosmic rays and the line-of-sight integrated gas content. Furthermore, the measured flux is higher by a factor of ∼3 than the prediction. A similar spectrum with an index of -2.99±0.07 is found in the outer Galaxy region, and the absolute flux for 10≲E≲60 TeV is again higher than the prediction for hadronic cosmic ray interactions. The latitude distributions of the diffuse emission are consistent with the gas distribution, while the longitude distributions show clear deviation from the gas distribution. The LHAASO measurements imply that either additional emission sources exist or cosmic ray intensities have spatial variations.
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