RESUMEN
BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD), one of the most common human monogenic diseases, is characterized by the presence of numerous fluid-filled renal cysts and is a leading cause of end-stage renal disease (ESRD). Urinary biomarkers may be useful for predicting the variable course of ADPKD progression from cyst growth to ESRD. METHODS: To identify candidate urinary biomarkers of ADPKD progression, we used CRISPR/Cas9 genome editing to generate porcine fibroblasts with mono- and biallelic ADPKD gene knockout (PKD2+/- and PKD2-/-, respectively). We then performed RNA-sequencing analysis on these cells. RESULTS: Levels of osteopontin (OPN), which is expressed by renal epithelial tubular cells and excreted into urine, were reduced in PKD2-/- cells but not in PKD2+/- cells. OPN levels were also reduced in the renal cyst cells of ADPKD patients. Next, we investigated whether OPN excretion was decreased in patients with ADPKD via enzyme-linked immunosorbent assay. OPN levels excreted into renal cyst cell culture media and urine from ADPKD patients were decreased. To investigate whether OPN can predict the rate of ADPKD progression, we compared urinary excretion of OPN in ADPKD patients with slow progression and those with rapid progression. Those with rapid progression had an estimated glomerular filtration rate of >60 mL/min/1.73 m2 . Urinary OPN excretion levels were lower in rapid progressors than in slow progressors. CONCLUSION: These findings suggest that OPN is a useful urinary biomarker for predicting ADPKD progression.
RESUMEN
Autosomal dominant polycystic kidney disease (ADPKD), one of the most common human monogenic diseases (frequency of 1/1000-1/400), is characterized by numerous fluid-filled renal cysts (RCs). Inactivation of the PKD1 or PKD2 gene by germline and somatic mutations is necessary for cyst formation in ADPKD. To mechanistically understand cyst formation and growth, we isolated RCs from Korean patients with ADPKD and immortalized them with human telomerase reverse transcriptase (hTERT). Three hTERT-immortalized RC cell lines were characterized as proximal epithelial cells with germline and somatic PKD1 mutations. Thus, we first established hTERT-immortalized proximal cyst cells with somatic PKD1 mutations. Through transcriptome sequencing and Gene Ontology (GO) analysis, we found that upregulated genes were related to cell division and that downregulated genes were related to cell differentiation. We wondered whether the upregulated gene for the chemokine CXCL12 is related to the mTOR signaling pathway in cyst growth in ADPKD. CXCL12 mRNA expression and secretion were increased in RC cell lines. We then examined CXCL12 levels in RC fluids from patients with ADPKD and found increased CXCL12 levels. The CXCL12 receptor CXC chemokine receptor 4 (CXCR4) was upregulated, and the mTOR signaling pathway, which is downstream of the CXCL12/CXCR4 axis, was activated in ADPKD kidney tissue. To confirm activation of the mTOR signaling pathway by CXCL12 via CXCR4, we treated the RC cell lines with recombinant CXCL12 and the CXCR4 antagonist AMD3100; CXCL12 induced the mTOR signaling pathway, but the CXCR4 antagonist AMD3100 blocked the mTOR signaling pathway. Taken together, these results suggest that enhanced CXCL12 in RC fluids activates the mTOR signaling pathway via CXCR4 in ADPKD cyst growth. [BMB Reports 2019; 52(7): 463-468].
Asunto(s)
Quimiocina CXCL12/metabolismo , Riñón Poliquístico Autosómico Dominante/metabolismo , Células Cultivadas , Quimiocina CXCL12/genética , Humanos , Mutación , Riñón Poliquístico Autosómico Dominante/patología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Telomerasa/genética , Telomerasa/metabolismo , Regulación hacia ArribaRESUMEN
In this study a Sipuncula species Phascolosoma sp. was collected from seagrass area from Chuuk lagoon Micronesia and its complete mitochondrial genome analyzed. This is the second complete mitochondrial genome record from the genus after Phascolosoma esculenta. The total length of mitochondrial genome of the species is 16,571 bp, which is longer than P. esculenta record. Also, locations of tRNA-Gly and putative control region are different between two records. Furthermore, phylogenetic relationship of Phascolosoma sp. are investigated due to protein-coding genes of mitochondrial genome. Due to the lack of recorded data, P. esculenta has been observed is the closest species to Phascolosoma sp. and they are belonging to the monophyletic group.
RESUMEN
Sipuncula (peanut worms) is a traditional phylum which consists of unsegmented bilateral symmetric marine worms. Although it is accepted as a phylum, the phylogenetic position of Sipuncula has been questionable. There is lack of molecular record on Sipuncula species while morphological data is not enough to distinguish the closer relationships between Annelida and Sipuncula. In order to add more data to genomic library of sipunculan species, Phascolosoma pacificum (Keferstein, 1866) was collected from seagrass area of Chuuk lagoon/Micronesia and its complete mitochondrial genome sequenced. Furthermore, phylogenetic relationship of the phylum Sipuncula and the other Trochozoan phyla investigate due to mitochondrial protein coding genes. Although there is lack of recorded data, our results support the idea that Sipuncula are nested within Annelida according to phylogenetic analyses of mitochondrial protein coding genes.
RESUMEN
The sacoglossans are small sea slugs in the Heterobranchia. In this study, mitochondrial genome of a sacoglossan sea slug, Elysia ornata (Swainson, 1840) is analyzed and phylogenetic tree of the species in the Heterobranchia is reconstructed based on amino acid sequences of mitochondrial protein coding genes. The phylogenetic relationship analysis shows that E. ornata belongs to the monophyletic Sacoglossa in the Heterobranchia and the Sacoglossa shows sister group relationship with a lineage including Anaspidea and Siphonarioidea. This is the fourth record for the mitochondrial genome of sacoglossan sea slugs.
RESUMEN
A complete mitochondrial genome was sequenced from a grapsid crab, Grapsus tenuicrustatus (Herbst 1783), which was collected from a rocky intertidal zone of Chuuk lagoon. The size of mitochondrial genome is 15,858 bp with 31.9% A, 22.8% C, 12.2% G and 33.1% T distribution. Furthermore phylogenetic relationships of the Grapsoidea evaluated due to mitochondrial protein-coding genes. As per the obtained results, the families Grapsidae and Varunidae have sister group relationship in the superfamily Grapsoidea.
RESUMEN
Complete mitochondrial genome of the knobbed rock shell sea snail Menathais tuberosa (Röding, 1798) has been sequenced and phylogenetic relationships evaluated due to mitochondrial protein coding genes. The size of mitochondrial genome for M. tuberosa is 15,294 bp and the nucleotide composition of the mitochondrial genome is 28.4% A, 16.5% C, 17.6% G and 37.5% T. Reconstructed phylogenetic tree of the Neogastropoda showed that M. tuberosa is in the monophyletic Muricidae. This is the first record of complete mitochondrial genome from the genus.
RESUMEN
The complete mitochondrial genome sequenced from a xanthid crab, Leptodius sanguineus which was collected from a rocky intertidal area in Chuuk lagoon. The mitochondrial genome size of L. sanguineus evaluated as 15,480 bp with 33.6% A, 24% C, 11.2% G and 31.2% T and mitochondrial gene order of L. sanguineus is typical to brachyuran species. Phylogenetic analysis shows that the family Xanthidae has sister group relationship with a lineage including the families Portunidae and Menippidae in the subsection Heterotremata. This is the first report for the complete mitochondrial genome from the xanthid crabs.
RESUMEN
Complete mitochondrial genome of smooth-handed ghost crab Ocypode cordimanus (Latreille, 1818) has been sequenced and phylogenetic relationships evaluated due to mitochondrial protein coding genes. This is the second record of complete mitochondrial genome from the genus. The size of mitochondrial genome for O. cordimanus is 15,604 bp and the nucleotide distribution of the mitochondrial genome is 31.8% A, 21.8% C, 11.9% G and 34.5% T.
RESUMEN
In this study, a complete mitochondrial genome of a nudibranch species, Sakuraeolis japonica was sequenced and analyzed. The mitochondrial genome size is 15,059 bp with 28.1% A, 14.9% C, 19.3% G, and 37.7% T nucleotide distributions. This is the eighth record for complete mitochondrial genome of the Nudibranchia and first record for the genus. Furthermore, phylogenetic relationship of S. Japonica in the Nudibranchia was investigated by using protein-coding genes of complete mitochondrial genome. The present study suggests that S. japonica belongs to the family Facelinidae and it is placed in monophyletic Nudibranchia. The closest species to S. japonica are Chromodoris magnifica and Chromodoris quadricolor that belong to the family Chromodorididae.
RESUMEN
In this study, complete nucleotide sequences of the mitochondrial genome of a nudibranch species, Hypselodoris festiva (A. Adams, 1861) were determined and characterized. The mitogenome size is 14 880 bp. This is the longest among the known nudibranch mitochondrial genomes. Furthermore, phylogenetic relationship of H. festiva in the Nudibranchia reconstructed due to amino acid sequences of mitochondrial protein coding genes. This is the sixth record for complete mitochondrial genome of the Nudibranchia.
RESUMEN
This study aims to improve the efficiency of disassembly planning in remanufacturing environment. Even though disassembly processes are considered as the reverse of the corresponding assembly processes, under some technological and management constraints the feasible and efficient disassembly planning can be achieved by only well-designed algorithms. In this paper, we propose a heuristic for disassembly planning with the existence of disassembled part/subassembly demands. A mathematical model is formulated for solving this problem to determine the sequence and quantity of disassembly operations to minimize the disassembly costs under sequence-dependent setup and capacity constraints. The disassembly costs consist of the setup cost, part inventory holding cost, disassembly processing cost, and purchasing cost that resulted from unsatisfied demand. A simple but efficient heuristic algorithm is proposed to improve the quality of solution and computational efficiency. The main idea of heuristic is to divide the planning horizon into the smaller planning windows and improve the computational efficiency without much loss of solution quality. Performances of the heuristic are investigated through the computational experiments.
RESUMEN
Traveling sales man problem with precedence constraints is one of the most notorious problems in terms of the efficiency of its solution approach, even though it has very wide range of industrial applications. We propose a new evolutionary algorithm to efficiently obtain good solutions by improving the search process. Our genetic operators guarantee the feasibility of solutions over the generations of population, which significantly improves the computational efficiency even when it is combined with our flexible adaptive searching strategy. The efficiency of the algorithm is investigated by computational experiments.
Asunto(s)
Algoritmos , Modelos Teóricos , Solución de ProblemasRESUMEN
Hepatocellular carcinoma (HCC) is one of the most prevalent gastrointestinal malignant tumors in Southeast Asia. Thirty-one cirrhotic HCC, 14 noncirrhotic HCC, and 13 metastastic HCC in the Korean population were investigated on microdissected tissues for chromosomal aberrations by degenerate oligonucleotide-primed polymerase chain reaction (PCR) comparative genomic hybridization. A number of prominent sites of genomic imbalances were observed. The gains of 1q, 6p, 7, 8q, 12q, 13q3-q32, 16p, 17q, and 20q and the losses of 1p, 4q, 6q, 8p, 9p, and 13q regions were observed with a similar high frequency in all types. Various chromosomal aberrations were observed preferentially to specific types. Gains of 4p15-pter, 10q24-qter, 18p11-pter, and 19p10-pter and a loss of 11q14-q22 were observed in the cirrhotic HCC, whereas losses of 14q21-q23 and 10q22-q23 were observed in noncirrhotic HCC. In metastatic HCC, gains of 3q25-qter and Xp21-pter and losses of 21q11-qter and Y were observed. The recurrent gains and losses of chromosomal regions identified in this study are consistent with several previous observations and provide possible candidate regions for the involvement of tumorigenesis and progressions of HCC.