206 research outputs found
Venomics Study of <em>Protobothrops flavoviridis</em> Snake: How Venom Proteins Have Evolved and Diversified?
Venomics projects have been conducted to disclose the divergent profiles and evolution of various venomous animals. Here, we describe the venomics project including genome and transcriptome of habu snake, leading to drug discovery. Venomics project including the decoding of their whole genomes revealed partly a producing mechanism of various venom proteins including accelerated evolution and alternative splicing and how the toxic organisms have evolved from the nontoxic ones. In addition, the venomics analysis of transcriptomes and proteomes beyond species reveals the relationship between the geographical distribution and evolution of toxic organisms. The abundance of different gene products within a gene family caused by accelerated evolution and alternative splicing may contribute to expand the repertoire of effective weapons to prey capture accompanied with neofunctionalization
Structures and Functions of C-type Lectins in Marine Invertebrates
Lectins distributing in all animal phyla form a diverse group of protein families that have in common the ability to recognize and bind certain carbohydrates. Although at least 13 animal lectin families are known to exist, many of marine invertebrate lectins are categorized in C-type lectin family, which was named from the Ca^-dependency for their carbohydrate binding activities. In contrast to a growing list of C-type lectins in marine invertebrates, their physiological roles are not fully understood. This review summarizes the structures and functions of marine invertebrate C-type lectins with our new findings
Improved Formalism for Precision Higgs Coupling Fits
Future e+e- colliders give the promise of model-independent determinations of
the couplings of the Higgs boson. In this paper, we present an improved
formalism for extracting Higgs boson couplings from e+e- data, based on the
Effective Field Theory description of corrections to the Standard Model. We
apply this formalism to give projections of Higgs coupling accuracies for
stages of the International Linear Collider and for other proposed e+e-
colliders.Comment: 34 pages, 4 figures; v4: clarifications and new references added; v5,
additional references adde
A novel technique for the measurement of the avalanche fluctuation of gaseous detectors
We have developed a novel technique for the measurement of the avalanche
fluctuation of gaseous detectors using a UV laser. The technique is simple and
requires a short data-taking time of about ten minutes. Furthermore, it is
applicable for relatively low gas gains. Our experimental setup as well as the
measurement principle, and the results obtained with a stack of Gas Electron
Multipliers (GEMs) operated in several gas mixtures are presented.Comment: 7 pages, 7 figures. For the proceedings of VCI2016, to be published
in Nucl. Instrum. Methods Phys. Res.
Urinary Fetuin-A Is a Novel Marker for Diabetic Nephropathy in Type 2 Diabetes Identified by Lectin Microarray
We analyzed the urine samples of patients with type 2 diabetes at various stages of diabetic nephropathy by lectin microarray to identify a biomarker to predict the progression of diabetic nephropathy. Japanese patients with type 2 diabetes at various stages of nephropathy were enrolled and we performed lectin microarray analyses (n = 17) and measured urinary excretion of fetuin-A (n = 85). The increased signals of urine samples were observed in Sia alpha 2-6Gal/GalNAc-binding lectins (SNA, SSA, TJA-I) during the progression of diabetic nephropathy. We next isolated sialylated glycoproteins by using SSA-lectin affinity chromatography and identified fetuin-A by liquid chromatography-tandem mass spectrometer. Urinary excretion of fetuin-A significantly increased during the progression of albuminuria (A1, 0.40 +/- 0.43; A2, 0.60 +/- 0.53; A3 1.57 +/- 1.13 ng/gCr; p = 7.29x10(-8)) and of GFR stages (G1, 0.39 +/- 0.39; G2, 0.49 +/- 0.45; G3, 1.25 +/- 1.18; G4, 1.34 +/- 0.80 ng/gCr; p = 3.89x10(-4)). Multivariate logistic regression analysis was employed to assess fetuin-A as a risk for diabetic nephropathy with microalbuminuria or GFR<60 mL/min. Fetuin-A is demonstrated as a risk factor for both microalbuminuria and reduction of GFR in diabetic nephropathy with the odds ratio of 4.721 (1.881-11.844) and 3.739 (1.785-7.841), respectively. Collectively, the glycan profiling analysis is useful method to identify the urine biomarkers and fetuin-A is a candidate to predict the progression of diabetic nephropathy
CHAC1 overexpression in human gastric parietal cells with Helicobacter pylori infection in the secretory canaliculi
Background
Cation transport regulator 1 (CHAC1), a newly discovered enzyme that degrades glutathione, is induced in Helicobacter pylori (H. pylori)‐infected gastric epithelial cells in culture. The CHAC1‐induced decrease in glutathione leads to an accumulation of reactive oxygen species and somatic mutations in TP53. We evaluated the possible correlation between H. pylori infection and CHAC1 expression in human gastric mucosa.
Materials and Methods
Both fresh‐frozen and formalin‐fixed paraffin‐embedded tissue samples of gastric mucosa with or without H. pylori infection were obtained from 41 esophageal cancer patients that underwent esophago‐gastrectomy. Fresh samples were used for real‐time polymerase chain reaction for H. pylori DNA and CHAC1 mRNA, and formalin‐fixed samples were used for immunohistochemistry with anti‐CHAC1 and anti‐H. pylori monoclonal antibodies. Double‐enzyme or fluorescence immunohistochemistry and immuno‐electron microscopy were used for further analysis.
Results
Significant CHAC1 overexpression was detected in H. pylori‐infected parietal cells that expressed the human proton pump/H,K‐ATPase α subunit, whereas a constitutively low level of CHAC1 mRNA expression was observed in the other samples regardless of the H. pylori infection status, reflecting the weak CHAC1 expression detected by immunohistochemistry in the fundic‐gland areas. Immuno‐electron microscopy revealed intact H. pylori cells in the secretory canaliculi of infected parietal cells. Some parietal cells exhibited positive nuclear signals for Ki67 in the neck zone of the gastric fundic‐gland mucosa with H. pylori infection.
Conclusion
Cation transport regulator 1 overexpression in H. pylori‐infected parietal cells may cause the H. pylori‐induced somatic mutations that contribute to the development of gastric cancer.This work was supported by the Japan Society
for the Promotion of Science KAKENHI (16K19077), and by the
Practical Research for Innovative Cancer Control from Japan Agency
for Medical Research and development, AMED
Alternative mRNA Splicing in Three Venom Families Underlying a Possible Production of Divergent Venom Proteins of the Habu Snake, Protobothrops flavoviridis
Snake venoms are complex mixtures of toxic proteins encoded by various gene families that function synergistically to incapacitate prey. A huge repertoire of snake venom genes and proteins have been reported, and alternative splicing is suggested to be involved in the production of divergent gene transcripts. However, a genome-wide survey of the transcript repertoire and the extent of alternative splicing still remains to be determined. In this study, the comprehensive analysis of transcriptomes in the venom gland was achieved by using PacBio sequencing. Extensive alternative splicing was observed in three venom protein gene families, metalloproteinase (MP), serine protease (SP), and vascular endothelial growth factors (VEGF). Eleven MP and SP genes and a VEGF gene are expressed as a total of 81, 61, and 8 transcript variants, respectively. In the MP gene family, individual genes are transcribed into different classes of MPs by alternative splicing. We also observed trans-splicing among the clustered SP genes. No other venom genes as well as non-venom counterpart genes exhibited alternative splicing. Our results thus indicate a potential contribution of mRNA alternative and trans-splicing in the production of highly variable transcripts of venom genes in the habu snake
The habu genome reveals accelerated evolution of venom protein genes
Evolution of novel traits is a challenging subject in biological research. Several snake lineages developed elaborate venom systems to deliver complex protein mixtures for prey capture. To understand mechanisms involved in snake venom evolution, we decoded here the ~1.4-Gb genome of a habu, Protobothrops flavoviridis. We identified 60 snake venom protein genes (SV) and 224 non-venom paralogs (NV), belonging to 18 gene families. Molecular phylogeny reveals early divergence of SV and NV genes, suggesting that one of the four copies generated through two rounds of whole-genome duplication was modified for use as a toxin. Among them, both SV and NV genes in four major components were extensively duplicated after their diversification, but accelerated evolution is evident exclusively in the SV genes. Both venom-related SV and NV genes are significantly enriched in microchromosomes. The present study thus provides a genetic background for evolution of snake venom composition
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