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21.
Liu Y Takahashi S Ogasawara H Seo HG Kawagoe M Hirasawa F Guo N Ueno Y Kameda T Sugiyama T 《Biomedical research (Tokyo, Japan)》2005,26(1):9-14
A novel substance, #675, found from an Streptomyces sp. SM675 culture medium, dose-dependently stimulates the proliferation of human functional liver cell 4 (FLC4). When FLC4 cells were incubated under conditions without fetal bovine serum (FBS), typical features of apoptotic cell death such as shrinkage and nuclear condensation appeared; high molecular weight (HMW) DNA fragments were found; and caspase-3 and poly (ADP-ribose) polymerase (PARP) proteins were cleaved. When FLC4 cells were incubated with #675 and without FBS, the cells grew healthy, no HMW DNA fragments were found, and caspase-3 and PARP cleavage weakened, suggesting that #675 protects FLC4 cells from apoptosis induced by FBS-deprivation. The quantitative reverse-transcribed polymerase chain reaction did not show differences in PARP or Bcl-2 mRNA expression in FLC4 cells incubated with or without #675, indicating other genes may be involved in this anti-apoptosis effect. These results show that #675 enhances FLC4 proliferation via an apoptosis-inhibition pathway, implying potential pharmacological and clinical applications. 相似文献
22.
Young-Sook Kim Graham D. Johnson Jungkyun Seo Alejandro Barrera Thomas N. Cowart William H. Majoros Alejandro Ochoa Andrew S. Allen Timothy E. Reddy 《Genome research》2021,31(5):877
High-throughput reporter assays such as self-transcribing active regulatory region sequencing (STARR-seq) have made it possible to measure regulatory element activity across the entire human genome at once. The resulting data, however, present substantial analytical challenges. Here, we identify technical biases that explain most of the variance in STARR-seq data. We then develop a statistical model to correct those biases and to improve detection of regulatory elements. This approach substantially improves precision and recall over current methods, improves detection of both activating and repressive regulatory elements, and controls for false discoveries despite strong local correlations in signal.Gene regulation is of foundational importance to nearly all biological processes, and variation in gene regulatory activity plays a major role in human disease risk (Lee and Young 2013; Parker et al. 2013; Finucane et al. 2015). A major step toward measuring regulatory activity across the human genome has been the development of high-throughput reporter assays such as STARR-seq (Arnold et al. 2013) that allow regulatory element activity to be quantified with high-throughput sequencing rather than with optical detection of a fluorescent or luminescent signal.High-throughput reporter assays create substantial analytical challenges that are distinct from other sequencing-based genomic assays. There is significant local variation in high-throughput reporter assay signal. We show here that, across data from several laboratories, most of that variation can be explained by features of the underlying genomic sequence and experimental procedures rather than by regulatory element activity. For example, nucleotide composition can alter PCR efficiency leading to under- and overrepresentation of some sequences. Meanwhile, highly repetitive sequences often do not align uniquely to the human reference genome, also biasing signal estimates. Additional analytical challenges include that STARR-seq signals can be both positive and negative, reflecting activation and repression, and the boundaries of regulatory elements are typically unknown and must therefore be estimated from the data. Those challenges together impact signal representations, hinder estimation of regulatory element activity, and cause false positives and false negatives when left unaddressed.Taken together, key requirements of statistical methods to analyze STARR-seq data are the ability to identify and estimate the effect of both activating and repressing regulatory elements while also correcting for underlying sequence biases in high-throughput reporter assays. A statistical model was recently introduced that corrects technical biases and detects regulatory elements in STARR-seq, but the model is limited to detecting only activating regulatory elements (Lee et al. 2020). Considering repression is a crucial gene regulation mechanism (Courey and Jia 2001), overlooking repressive elements may limit understanding of gene regulation with STARR-seq. To overcome that challenge, our correcting reads and analysis of differentially active elements (CRADLE) model takes a two-step approach. First, CRADLE uses a generalized linear regression model to estimate and correct major biases that we have identified in STARR-seq data. Next, CRADLE detects regions with statistically significant regulatory activity from the bias-corrected signals while rigorously controlling FDR. In doing so, CRADLE substantially improves the use of STARR-seq by providing a robust estimation of regulatory activity and improved visualization of raw signals. 相似文献
23.
The progressive myoclonus epilepsy of the Lafora type (LD; MIM 254780) is a rare autosomal recessive disorder characterized by epilepsy, myoclonus, progressive neurological deterioration, and the presence of periodic acid-Schiff-positive polyglucosan inclusions (Lafora bodies). Mutations in the EPM2A gene have recently been found to cause LD and about 30 or more mutations have been reported thus far. LD is relatively common in countries of the Mediterranean Basin, the Middle East, India, and Pakistan. Although a few sporadic cases with the typical LD phenotype have also been reported in the Far East including Korea and Japan, a recent effort to find mutations in Japanese LD families was not successful. In the present study, we report two novel mutations in a Korean girl with LD; a 1-bp insertion mutation (c.223insC; G75fsX107) in exon 1 and a missense mutation (c.559A>G; T187A) in exon 3 of the EPM2A gene. To our knowledge, this is the first report of a genetically confirmed case of LD in Koreans and also in the Far East. 相似文献
24.
Image reconstruction of anisotropic conductivity tensor distribution in MREIT: computer simulation study 总被引:2,自引:0,他引:2
We describe a novel method of reconstructing images of an anisotropic conductivity tensor distribution inside an electrically conducting subject in magnetic resonance electrical impedance tomography (MREIT). MREIT is a recent medical imaging technique combining electrical impedance tomography (EIT) and magnetic resonance imaging (MRI) to produce conductivity images with improved spatial resolution and accuracy. In MREIT, we inject electrical current into the subject through surface electrodes and measure the z-component Bz of the induced magnetic flux density using an MRI scanner. Here, we assume that z is the direction of the main magnetic field of the MRI scanner. Considering the fact that most biological tissues are known to have anisotropic conductivity values, the primary goal of MREIT should be the imaging of an anisotropic conductivity tensor distribution. However, up to now, all MREIT techniques have assumed an isotropic conductivity distribution in the image reconstruction problem to simplify the underlying mathematical theory. In this paper, we firstly formulate a new image reconstruction method of an anisotropic conductivity tensor distribution. We use the relationship between multiple injection currents and the corresponding induced Bz data. Simulation results show that the algorithm can successfully reconstruct images of anisotropic conductivity tensor distributions. While the results show the feasibility of the method, they also suggest a more careful design of data collection methods and data processing techniques compared with isotropic conductivity imaging. 相似文献
25.
Kentaro Fujiwara Takanori Ochi Hiroyuki Koga Go Miyano Shogo Seo Tadaharu Okazaki Masahiko Urao Geoffrey J. Lane Risto J. Rintala Atsuyuki Yamataka 《Journal of pediatric surgery》2021,56(7):1136-1140
PurposeTo report the sequelae of and preventive strategies for selected lower urinary tract (LUT) complications, i.e., posterior urethral diverticulum (PUD), intraoperative LUT injuries, postoperative dysuria, and fistula recurrence in male imperforate anus (IA) with rectourethral/rectovesical (RU/RV) fistula after laparoscopy-assisted anorectoplasty (LAARP) or posterior sagittal anorectoplasty (PSARP).Methods153 boys with IA and RU/RV fistula treated 1986–2019 by LAARP (n = 56) or PSARP (n = 97) at two unrelated institutes were studied retrospectively.ResultsAfter mean follow-up of 17.0 years (range: 36.5 days-32.0 years), the overall incidences of LUT complications were: LAARP (6/56; 10.7%); PSARP (7/97; 7.2%); p = 0.55, comprising PUD: LAARP (n = 5), PSARP (n = 0); p = 0.006; injuries: LAARP (n = 0), PSARP (n = 5); p = 0.16; dysuria: LAARP (n = 1), PSARP (n = 1); p>0.999; and recurrence: LAARP (n = 0), PSARP (n = 1); p>0.999. Mean onset of PUD was 5.1 years (range: 1.0–15.1 years). Treatment: PUD: surgery (n = 2/5), conservative (n = 3/5); injuries: intraoperative repair (n = 5/5); dysuria: conservative (n = 2/2), and recurrence: redo PSARP (n = 1/1).ConclusionsStrategies devised to improve dissection accuracy resolved the specific technical issues causing LUT complications (remnant RU fistula dissection in LAARP and blind posterior access in PSARP). Currently, the incidence of new cases of PUD and LUT injuries is zero.Level of Evidence: Level III 相似文献
26.
Many workers have reported that ureteral peristaltic movement is controlled by the "so-called Pacemaker". But, in our recent studies, it was revealed that the existence of pacemaker is not always necessary for the peristaltic movement. In this study, we made isolated and non-isolated prototype models, using 18 mongrel dogs, to explore the influential factors on ureteral peristaltic discharge. Bilateral kidney and ureter were exposed transperitoneally. Unilateral upper urinary tract was prepared to preserve the pacemaker without renal blood supply, and contralateral one was prepared not to preserve the pacemaker by cutting at the proximal portion of the ureter. Vesico-ureteral reflux (VUR) was caused on these two models. A luminal pressure and ureteral electromyogram was recorded. In the result, there is spontaneous peristaltic discharges of the ureter which had the tendency to increase peristaltic frequency according to the increase of the luminal pressure. It was suggested that adequate expanding stimulation is the factor of peristaltic discharge to increase, and the peristaltic discharge under this condition propagates from upper to lower portion of the ureter. 相似文献
27.
True histiocytic lymphoma of the esophagus in an HIV-positive patient: an ultrastructural study 总被引:1,自引:0,他引:1
A 56-year-old white woman, seropositive for human immunodeficiency virus for 18 months without signs of acquired immunodeficiency syndrome, presented with retrosternal pain and progressive dysphagia secondary to an exophytic esophageal mass. Biopsies of the tumor showed a malignant neoplasm composed of pleomorphic, noncohesive cells growing in a diffuse, sheet-like fashion. Immunohistochemically, tumor cells were nonreactive with epithelial, lymphoid, neural, and monocyte/macrophage markers. Despite the noncontributory immunohistochemical findings, ultrastructural study of the tumor cells revealed convincing histiocytic features. Individual cells possessed long, slender filopodial projections, prominent Golgi apparatus, residual bodies, rare lysosomes, and prelysosomes. Immunoglobulin heavy chain and T-cell receptor gamma gene rearrangement studies detected no evidence of a clonal gene rearrangement. The patient responded poorly to chemotherapy and died 5 months after her initial symptom of dysphagia. 相似文献
28.
We present a patient with pancreatoblastoma along with a discussion of various cross-sectional imaging features. The tumor was a large multilocular cystic mass with solid components in the left retroperitoneal space. There were fine internal echoes on ultrasonography, and the signal intensity was high on both T1- and T2-weighted MR images in most of the locules, suggesting the presence of hemorrhagic debris. Among the various retroperitoneal organs displaced by the tumor, only the pancreatic tail was inseparable from the mass, suggesting that the pancreatic tail was the origin of the tumor. Pancreatoblastoma should be included in the differential diagnosis when a large left upper quadrant mass with these imaging features is seen in infants and young children. 相似文献
29.
The present study was designed to evaluate whether functional impairment and/or protein expression of constitutive nitric oxide synthase (cNOS; endothelial NOS [eNOS] and neuronal NOS[nNOS]) was involved in impairment of endothelium-dependent relaxation of cavernous smooth muscle in hypercholesterolemic rabbits. New Zealand White rabbits were randomly divided into control and experimental groups. The control group (n=20) received a regular diet, while the two experimental groups (n=20 for each) were fed a 2% cholesterol diet for 4 and 8 weeks, respectively. We conducted isometric tension studies with endothelium-dependent and endothelium-independent vasodilators with or without preincubation with L-arginine and nonadrenergic, noncholinergic (NANC)-selective electrical field stimulation on isolated strips of corpus cavernosum. Expression of cNOS (eNOS and nNOS) protein was assessed by Western blot analysis. cNOS activities in both cytosolic and particulate fractions were measured by determining the conversion of L-[U-14C] arginine to L-[U-14C] citrulline. Blood levels of cholesterol were significantly higher (P < 0.01) in the experimental groups than in the control group. The relaxation responses to endothelium-dependent agents (acetylcholine and adenosine 5'-diphosphate [ADP]) were significantly reduced (P < 0.05) in both experimental groups, regardless of their incubation with L-arginine, compared with the control group. However, no differences were found among the three groups in the relaxation response to endothelium-independent agents (papaverine and nitroprusside) and to NANC-selective electrical field stimulation. There was no difference in immunoreactive nNOS from cytosolic and particulate fractions between the cavernous tissues of the control and experimental groups. nNOS protein levels in the particulate fractions were markedly lower than in the cytosolic fractions. The particulate cNOS activity was significantly decreased (P < 0.05) in the experimental groups compared with the control group, while the cytosolic cNOS activity in the experimental groups was not different from that found in the control group. Therefore, it is concluded that functional impairment of eNOS, rather than of nNOS, may lead to impairment of cavernous smooth muscle relaxation in response to endothelium-mediated stimuli in hypercholesterolemic rabbits. 相似文献
30.
Fucosidosis: four new mutations and a new polymorphism 总被引:2,自引:0,他引:2
Seo Hee-Chan; Willems Patrick J.; Kretz Keith A.; Martin Brian M.; O'Brien John S. 《Human molecular genetics》1993,2(4):423-429
Fucosidosis is a rare lysosomal storage disease due to a nearlycomplete deficiency of -L-fucosidase (EC 3.2.1.51
[EC]
). In thisstudy, all 8 exons of the -L-fucosidase structural gene (FUCA-1)were amplified by PCR methods, and the amplified products weresubcloned and sequenced. Five patient groups with fucosidosiswere selected according to their ethnic backgrounds and haplotypesfor RFLPs in FUCA-1. Four presumptive disease causing mutationswere detected: 1) A major deletion of DNA containing the lasttwo exons of FUCA-1 in two Algerian siblings. 2) A G to T mutationin exon 6 resulting in an in-frame termination codon (E375X)in eight Hispanic patients from Colorado and New Mexico. 3)A G to A mutation (G60D) in exon 1 in four Italian patientsand in three related French-American (Cajun) patients. ThisG60D mutation creates a unique site for Afl III. 4) A frameshiftmutation resulted from a two-base deletion in exon 2 (K151fs)in an Italian patient. This deletion obliterates a unique BstXIsite and creates a new BpmI site, and was found in only thispatient and in only one allele. The rationale for proposingthese defects as disease causing mutations includes pedigreeanalysis and the predicted consequences of each defect uponthe activity and the concentration of the enzyme. An A to Gtransition (Q281R) in exon 5 was found to be present in homozygousform in affected patients and also in normal subjects; it appearsto be a newly identified polymorphism. It causes a charge changeand may be responsible for the electrophoretic variant phenotypeof fucosidosis. This polymorphism is inherited concordant withthe RFLP PvuIIBglI haplotype 2 2, 2 2.The 4 new mutations identified here comprise 70% of allelesof the 25 fucosidosis patients in our study. 相似文献