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1.
Heliyon ; 10(10): e30307, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38774331

ABSTRACT

The common strain black carp (Cyprinus carpio var. baisenensis) is a culturally important carp strain that is raised and cultured in Guangxi Province, China. Its color reflects the interactions between the Burau people and their surrounding environment. The population of the common carp black strain was isolated and cultured in a rice-fish integration system. To explore the genetic diversity and protection of germplasm resources, we analyzed mitochondrial DNA (mtDNA) sequences, specifically the displacement loop (D-loop) and cytochrome b (Cytb), using single-nucleotide polymorphisms (SNP). We compared these sequences with those from four other local common carp populations. The study included a total of 136 adult common carps from five strain populations: the common black carp strain (HJ = 31), Jian (F = 30), Heilongjiang (H = 10), Songpu (S = 31), and Saijiang (SJ = 34). The results of the Cytb and D-loop analyses showed that the Heilongjiang carp (H) and Saijiang (SJ) populations had the highest levels of haplotype diversity (0.867 ± 0.034785) and nucleotide diversity (π = 0.0063 ± 0.000137 and 0.0093 ± 0.000411), respectively. On the other hand, the Common carp black strain population (HJ) exhibited the lowest haplotype diversity in both Cytb and D-loop, with haplotype 2 being the most commonly observed among the populations. Private haplotypes dominated the five common carp populations, which were significantly different at P<0.001. Furthermore, analyzing the coefficient of genetic differentiation (Fst), the highest genetic difference was observed between Saijiang (SJ) and Heilongjiang (H) (Fst = 0.963), whereas the lowest was observed between Songpu (S) and the Common carp black strain population (HJ) (Fst = 0.019) for the Cytb gene sequences. For the D-loop, the Common carp black strain population (HJ) and Songpu (S) (Fst = 0.7) had the highest values, and Heilongjiang (H) and Common black carp strain (HJ) had an Fst of 0.125. Additionally, the AMOVA analysis revealed a higher level of variance for the Cytb and D-loop genes, indicating lower genetic diversity within the local carp community. On the other hand, the phylogenetic tree analysis showed that the five carp populations were closely related and formed a distinct cluster. The distinct cluster of populations suggests a common ancestor or recent gene flow, possibly due to geographic proximity or migration history, and unique genetic characteristics, possibly due to adaptations or selective pressures. The results of this study provide valuable insights into the genetic diversity of the common strain black carp, which can have implications for conservation, breeding programs, evolutionary studies, and fisheries management.

2.
Cell Rep Med ; : 101547, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38703764

ABSTRACT

Non-clear cell renal cell carcinomas (non-ccRCCs) encompass diverse malignant and benign tumors. Refinement of differential diagnosis biomarkers, markers for early prognosis of aggressive disease, and therapeutic targets to complement immunotherapy are current clinical needs. Multi-omics analyses of 48 non-ccRCCs compared with 103 ccRCCs reveal proteogenomic, phosphorylation, glycosylation, and metabolic aberrations in RCC subtypes. RCCs with high genome instability display overexpression of IGF2BP3 and PYCR1. Integration of single-cell and bulk transcriptome data predicts diverse cell-of-origin and clarifies RCC subtype-specific proteogenomic signatures. Expression of biomarkers MAPRE3, ADGRF5, and GPNMB differentiates renal oncocytoma from chromophobe RCC, and PIGR and SOSTDC1 distinguish papillary RCC from MTSCC. This study expands our knowledge of proteogenomic signatures, biomarkers, and potential therapeutic targets in non-ccRCC.

4.
Ann Geriatr Med Res ; 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38651272

ABSTRACT

Background: Advances in blood biomarker discovery have enabled the improved diagnosis and prognosis of Alzheimer's disease (AD). Most branched-chain amino acids, except isoleucine (Ile), are correlated with both mild cognitive impairment (MCI) and AD. Therefore, this study investigated the association between serum Ile levels and MCI/AD. Methods: This study stratified 700 participants from the Alzheimer's Disease Neuroimaging Initiative database into four diagnostic groups: cognitively normal, stable MCI, progressive MCI, and AD. Analysis of covariance and chi-square analyses were used to test the demographic data. Receiver operating curve analyses were used to calculate the diagnostic accuracy of different biomarkers and were compared using MedCalc 20. Additionally, Cox proportional hazards models were used to measure the ability of serum Ile levels to predict disease conversion. Finally, a linear mixed-effects model was used to evaluate the associations between serum Ile levels and cognition, brain structure, and metabolism. Results: Serum Ile concentration was decreased in AD and demonstrated significant diagnostic efficacy. The combination of serum Ile and cerebrospinal fluid (CSF) phosphorylated tau (P-tau) levels improved the diagnostic accuracy in AD compared to T-tau alone. Serum Ile levels significantly predicted the conversion from MCI to AD (cutoff value = 78.3 µM). Finally, the results of this study also revealed a correlation between serum Ile levels and the Alzheimer's Disease Assessment Scale cognitive subscale Q4. Conclusions: Serum Ile level may be a potential biomarker of AD. Ile had independent diagnostic efficacy and significantly improved the diagnostic accuracy of CSF P-tau in AD. Patients with MCI with a lower serum Ile level had a higher risk of progression to AD and a worse cognition assessment.

5.
Cancer Cell ; 41(1): 139-163.e17, 2023 01 09.
Article in English | MEDLINE | ID: mdl-36563681

ABSTRACT

Clear cell renal cell carcinomas (ccRCCs) represent ∼75% of RCC cases and account for most RCC-associated deaths. Inter- and intratumoral heterogeneity (ITH) results in varying prognosis and treatment outcomes. To obtain the most comprehensive profile of ccRCC, we perform integrative histopathologic, proteogenomic, and metabolomic analyses on 305 ccRCC tumor segments and 166 paired adjacent normal tissues from 213 cases. Combining histologic and molecular profiles reveals ITH in 90% of ccRCCs, with 50% demonstrating immune signature heterogeneity. High tumor grade, along with BAP1 mutation, genome instability, increased hypermethylation, and a specific protein glycosylation signature define a high-risk disease subset, where UCHL1 expression displays prognostic value. Single-nuclei RNA sequencing of the adverse sarcomatoid and rhabdoid phenotypes uncover gene signatures and potential insights into tumor evolution. In vitro cell line studies confirm the potential of inhibiting identified phosphoproteome targets. This study molecularly stratifies aggressive histopathologic subtypes that may inform more effective treatment strategies.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Proteogenomics , Humans , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , Treatment Outcome , Prognosis , Biomarkers, Tumor/genetics
6.
Sci Prog ; 105(3): 368504221124047, 2022.
Article in English | MEDLINE | ID: mdl-36113148

ABSTRACT

This study was conducted to investigate the effect of methomyl (MET) on water quality, growth and antioxidant system of genetically improved farmed tilapia (GIFT, Oreochromis niloticus) in the presence of peppermint as a floating bed. The concentration of NH3-N, NO2--N, NO3--N and TP in T3 (with 200 g wet peppermint) was significantly lower (P < 0.05) than that in T2 (100 g), T1 (50 g) and control, and the nutrient removal rates were 61.90%, 31.59%, 59.86% and 45.92% in 20 days, respectively. Juveniles GIFT (5.1 ± 0.2 g) were exposed to sub-lethal concentrations of 0.2, 2.0, 20 and 200 µg/L of MET for 45 days. After 6 weeks of a feeding trial, percentage weight gain (PWG), specific growth rate (SGR) and feed conversion ratio (FCR) were significantly decreased in 0.2, 2.0, 20 µg/L MET groups respectively and increased in the 200 µg/L MET group. Compared with the control, no significant changes in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) were detected in the 0.2 µg/L group. The significant increase in activities of SOD, CAT and GPx was accompanied by a diminution in reduced glutathione (GSH) levels resulting with tilapia exposed to 2.0, 20, or 200 µg/L for 45 days. The highest rates observed in SOD, CAT, GPx were 157.63%, 164.05% and 167.46% of the control respectively, and the lowest inhibition rate in GSH was 66.42% of the control. Peppermint as a floating bed can alleviate the adverse effects of MET, such as growth retardation and oxidative stress.


Subject(s)
Cichlids , Mentha , Animals , Antioxidants/pharmacology , Catalase/pharmacology , Cichlids/physiology , Glutathione/pharmacology , Glutathione Peroxidase/pharmacology , Liver , Mentha piperita , Methomyl/pharmacology , Nitrogen Dioxide/pharmacology , Superoxide Dismutase/pharmacology , Water Quality
7.
Int J Anal Chem ; 2022: 7434426, 2022.
Article in English | MEDLINE | ID: mdl-35992556

ABSTRACT

This study was conducted to investigate the effect of methomyl (MET) on the growth and antioxidant system of GIFT (5.28 ± 0.12, n = 180) in the presence of water spinach (Ipomoea aquatica) aas a floating bed. Four treatment groups have been established, named control (0), 2, 20, and 200 µg/L MET. Results showed that at moderate temperatures such as 25°C to 30°C, tilapia's feed consumption increased and body weight improved. SOD, CAT, and GSH in the liver of GIFT indicated the significant increase under MET exposure. MET reduced the growth rate of GIFT, and water spinach reduced part of the water quality indexes in the MET (<200 µg/L) groups. Water spinach altered GIFT's hepatic oxidation system to some extent and effectively absorbed MET in water and transferred it to itself, and the degradation time was lower than the dietary standard time which termed as 15-20 days. Growing water spinach in farmed waters partially decomposes MET and prevents it from causing damage to GIFT's liver.

8.
Aging Clin Exp Res ; 34(8): 1807-1817, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35362856

ABSTRACT

BACKGROUND: The introduction of metabolomics makes it possible to study the characteristic changes of peripheral metabolism in Alzheimer's disease (AD). Recent studies have found that the levels of valine are related to mild cognitive impairment (MCI) and AD. AIMS: This study aimed to further clarify the characteristics of valine levels in MCI and AD. METHODS: A total of 786 participants from the Alzheimer's Disease Neuroimaging Initiative-1 (ADNI-1) cohort were selected to evaluate the relationships between serum valine and cerebrospinal fluid (CSF) biomarkers, brain structure (magnetic resonance imaging, MRI), cerebral glucose metabolism (18F-fluorodeoxyglucose-positron emission tomography, FDG-PET), and cognitive declines, through different cognitive subgroups. RESULTS: Serum valine was decreased in patients with AD compared with cognitive normal (CN) and stable MCI (sMCI), and in progressive MCI (pMCI) compared with CN. Serum valine was negatively correlated with CSF total tau (t-tau) and phosphorylated tau (p-tau) in pMCI. Serum valine significantly predicted conversion from MCI to AD. In addition, serum valine was related to the rate of change of cerebral glucose metabolism during the follow-up period in pMCI. CONCLUSIONS: Serum valine may be a peripheral biomarker of pMCI and AD, and its level predicts the progression of MCI to AD. Our study may help to reveal the metabolic changes during AD disease trajectory and its relationship to clinical phenotype.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Alzheimer Disease/cerebrospinal fluid , Amyloid beta-Peptides/metabolism , Biomarkers/metabolism , Brain/diagnostic imaging , Brain/metabolism , Cognitive Dysfunction/cerebrospinal fluid , Cognitive Dysfunction/diagnostic imaging , Disease Progression , Glucose , Humans , Positron-Emission Tomography , Valine , tau Proteins
9.
Sensors (Basel) ; 22(7)2022 Mar 29.
Article in English | MEDLINE | ID: mdl-35408233

ABSTRACT

The coexistence of radar and communication systems is necessary to facilitate new wireless systems and services due to the shortage of the useful radio spectrum. Moreover, changes in spectrum regulation will be introduced in which the spectrum is allocated in larger chunks and different radio systems need to share the spectrum. For example, 5G NR, LTE and Wi-Fi systems have to share the spectrum with S-band radars. Managing interference is a key task in coexistence scenarios. Cognitive radio and radar technologies facilitate using the spectrum in a flexible manner and sharing channel awareness between the two subsystems. In this paper, we propose a nullspace-based joint precoder-decoder design for coexisting multicarrier radar and multiuser multicarrier communication systems. The maximizing signal interference noise ratio (max-SINR) criterion and interference alignment (IA) constraints are employed in finding the precoder and decoder. By taking advantage of IA theory, a maximum degree of freedom upper bound for the K+1-radar-communication-user interference channel can be achieved. Our simulation studies demonstrate that interference can be practically fully canceled in both communication and radar systems. This leads to improved detection performance in radar and a higher rate in communication subsystems. A significant performance gain over a nullspace-based precoder-only design is also obtained.

10.
Sensors (Basel) ; 21(17)2021 Sep 03.
Article in English | MEDLINE | ID: mdl-34502812

ABSTRACT

Wireless sensing can be used for human identification by mining and quantifying individual behavior effects on wireless signal propagation. This work proposes a novel device-free biometric (DFB) system, WirelessID, that explores the joint human fine-grained behavior and body physical signatures embedded in channel state information (CSI) by extracting spatiotemporal features. In addition, the signal fluctuations corresponding to different parts of the body contribute differently to the identification performance. Inspired by the success of the attention mechanism in computer vision (CV), thus, to extract more robust features, we introduce the spatiotemporal attention function into our system. To evaluate the performance, commercial WiFi devices are used for prototyping WirelessID in a real laboratory environment with an average accuracy of 93.14% and a best accuracy of 97.72% for five individuals.


Subject(s)
Forensic Anthropology , Wireless Technology , Humans
11.
Front Microbiol ; 12: 659602, 2021.
Article in English | MEDLINE | ID: mdl-34127924

ABSTRACT

In a previous study, we found that the growth performance of the new strain of Huanghe carp is related to gene expression and bacterial community in the gut. In order to better understand the relationship between the gene expression level and bacterial abundance in the gut, we studied the growth performance, gut bacterial structure, and transcriptome profile in the 4th generation of the new carp strain (selection group) at harvesting time, and compared them with the control line (traditional Huanghe carp). Body weight, depth, width, and length increased 14.58, 7.14, 5.04, and 5.07%, respectively. The gut microbiome of the selection group also exhibited significantly higher species diversity parameters (Shannon, Simpson, and chao1). Both PCA and phylogenetic analyses divided all gut samples into two parts: control and selection group. Aeromonas was the dominant taxon in the control group, followed by Firmicutes and Roseomonas; in the selection group, Roseomonas was the dominant taxon, followed by Firmicutes and then Aeromonas. Among the 249 significantly differentially expressed genes, 194 were downregulated and 55 were upregulated. Functional GO annotation produced 13 terms in the biological process, 8 in the cellular component, and 7 in the molecular function categories. KEGG annotation indicated that most of these genes were associated with the immune-related pathways. A total of 2,892 pairs of genes (245) and baceterial genera (256) were analyzed using Pearson's correlation analysis. Most of the identified associations were mapped to the immune system, bacterial community, and cell differentiation categories. The top-10 bacterial genera identified by these analyses were Methylocystis, Ohtaekwangia, Roseomonas, Shewanella, Lutispora, GpVI, Desulfovibrio, Candidatus_Berkiella, Bordetella, and Azorhizobium. Genes paired with bacteria flora were divided into four functional categories: immune, growth, adipocyte differentiation, and nerve regulation. These genes may be related to the comparatively fast growth and high muscle polyunsaturated fatty acid content of the Huanghe carp new strain. Meanwhile, nerve regulation-related genes may be a reflection of the microbiota-gut-brain axis. These results illustrate that gut bacterial community structure is associated with the growth performance and gene expression in the Huanghe carp new strain.

12.
Genomics ; 113(4): 2547-2560, 2021 07.
Article in English | MEDLINE | ID: mdl-34029696

ABSTRACT

Water quality parameter dynamics, gut, sediment and water bacteria communities were studied to understand the environmental influence on the gut microbial community of a new strain of Huanghe common carp. A total of 3,384,078 raw tags and 5105 OTUs were obtained for the gut, water and sediment bacteria. The water quality had a stronger influence on the water bacteria community than gut and sediment bacteria communities. The ambient water quality parameters also significantly influenced the water and sediment bacteria communities. Comparing the gut, sediment, and water microbial communities, a relationship was found among them. However, gut bacteria were more closely related to sediment bacterial communities than to water bacteria communities. The results showed that the top three bacterial taxa were identical in gut and sediment samples in the early days of rearing. Interestingly, bacterial communities in the carp gut, water, and sediment had different adaptabilities to variations in environmental factors.


Subject(s)
Carps , Microbiota , Agriculture , Animals , Bacteria/genetics , Ponds , RNA, Ribosomal, 16S/genetics
13.
Sensors (Basel) ; 20(17)2020 Sep 03.
Article in English | MEDLINE | ID: mdl-32899348

ABSTRACT

Radio frequency interference, which makes it difficult to produce high-quality radar spectrograms, is a major issue for micro-Doppler-based human activity recognition (HAR). In this paper, we propose a deep-learning-based method to detect and cut out the interference in spectrograms. Then, we restore the spectrograms in the cut-out region. First, a fully convolutional neural network (FCN) is employed to detect and remove the interference. Then, a coarse-to-fine generative adversarial network (GAN) is proposed to restore the part of the spectrogram that is affected by the interferences. The simulated motion capture (MOCAP) spectrograms and the measured radar spectrograms with interference are used to verify the proposed method. Experimental results from both qualitative and quantitative perspectives show that the proposed method can mitigate the interference and restore high-quality radar spectrograms. Furthermore, the comparison experiments also demonstrate the efficiency of the proposed approach.

14.
Sensors (Basel) ; 20(6)2020 Mar 11.
Article in English | MEDLINE | ID: mdl-32168756

ABSTRACT

On the basis of realizing regional navigation, the Quasi-Zenith Satellite System (QZSS) has advanced navigation function, which leads to the broadcasting of more signals in a single frequency of QZSS signals. Current signal transmission technology cannot solve this problem, so it is necessary to design a signal multiplexing method. The current QZSS satellite interface document does not disclose the multiplexing modulation method of the signal transmission, which has a certain impact on the acquisition of high-precision observation data and further data processing. The iGMAS (International GNSS Monitoring & Assessment System) Monitoring and Evaluation Center of the 54th Research Institute of China Electronics Technology Group Corporation has used the low-distortion data acquisition and processing platform and refined signal software receiving processing algorithm of the iGMAS to complete the signal acquisition and analysis of QZSS satellites. Analysis of the multiplexing and modulation method and signal characteristics for the QZSS has been carried out, which can provide a reference for the design and data processing of high-precision receivers.

15.
J Clin Invest ; 130(5): 2712-2726, 2020 05 01.
Article in English | MEDLINE | ID: mdl-32027624

ABSTRACT

Whether mutations in cancer driver genes directly affect cancer immune phenotype and T cell immunity remains a standing question. ARID1A is a core member of the polymorphic BRG/BRM-associated factor chromatin remodeling complex. ARID1A mutations occur in human cancers and drive cancer development. Here, we studied the molecular, cellular, and clinical impact of ARID1A aberrations on cancer immunity. We demonstrated that ARID1A aberrations resulted in limited chromatin accessibility to IFN-responsive genes, impaired IFN gene expression, anemic T cell tumor infiltration, poor tumor immunity, and shortened host survival in many human cancer histologies and in murine cancer models. Impaired IFN signaling was associated with poor immunotherapy response. Mechanistically, ARID1A interacted with EZH2 via its carboxyl terminal and antagonized EZH2-mediated IFN responsiveness. Thus, the interaction between ARID1A and EZH2 defines cancer IFN responsiveness and immune evasion. Our work indicates that cancer epigenetic driver mutations can shape cancer immune phenotype and immunotherapy.


Subject(s)
DNA-Binding Proteins/genetics , DNA-Binding Proteins/immunology , Mutation , Neoplasms/genetics , Neoplasms/immunology , Transcription Factors/genetics , Transcription Factors/immunology , Animals , Cell Line, Tumor , Chromatin Assembly and Disassembly/genetics , Chromatin Assembly and Disassembly/immunology , DNA-Binding Proteins/chemistry , Enhancer of Zeste Homolog 2 Protein/chemistry , Enhancer of Zeste Homolog 2 Protein/immunology , Epigenesis, Genetic , Female , Humans , Immunophenotyping , Immunotherapy , Interferons/genetics , Interferons/immunology , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/pathology , Melanoma/genetics , Melanoma/immunology , Melanoma/pathology , Mice , Neoplasms/pathology , Ovarian Neoplasms/genetics , Ovarian Neoplasms/immunology , Ovarian Neoplasms/pathology , Signal Transduction/genetics , Signal Transduction/immunology , Transcription Factors/chemistry , Tumor Escape/genetics , Tumor Escape/immunology
16.
Sensors (Basel) ; 19(24)2019 Dec 05.
Article in English | MEDLINE | ID: mdl-31817363

ABSTRACT

Compared with the previous GPS satellites, the first GPS III satellite adds a new civil signal L1C to the signal components of the L1 frequency in addition to the improvement of positioning accuracy, anti-interference ability, and service life. The selection and combination of signal modulation and multiplexing methods will affect the power ratio and phase relationship in the process of signal transmission. In the distribution of constellation of different modulation modes, the signal amplitudes of different signal constellation points will be affected by the nonlinear amplifiers of satellites. The analysis can assess its impact on navigation performance. The iGMAS monitoring and evaluation center of the 54th Research Institute of China Electronics Technology Group Corporation uses the low-distortion data acquisition and processing platform and refined signal software receiving processing algorithm of the iGMAS monitoring and evaluation center to complete the signal acquisition of the first satellite of GPS III over China, and processes accordingly for its signal modulation mode. Compared with the previous generation GPS of old system signals, it is found that the GPS signal of the new system not only adds the L1C frequency, but also the constant envelope multiplexing mode of the L1 frequency signal, and the power ratio of the internal signal components are also adjusted.

17.
Neoplasia ; 21(3): 322-330, 2019 03.
Article in English | MEDLINE | ID: mdl-30797188

ABSTRACT

Studies on the efficacy of small molecule inhibitors in Merkel cell carcinoma (MCC) have been limited and largely inconclusive. In this study, we investigated the therapeutic potential of a potent BET degrader, BETd-246, in the treatment of MCC. We found that MCC cell lines were significantly more sensitive to BETd-246 than to BET inhibitor treatment. Therapeutic targeting of BET proteins resulted in a loss of "MCC signature" genes but not MYC expression as previously described irrespective of Merkel cell polyomavirus (MCPyV) status. In MCPyV+ MCC cells, BETd-246 alone suppressed downstream targets in the MCPyV-LT Ag axis. We also found enrichment of HOX and cell cycle genes in MCPyV- MCC cell lines that were intrinsically resistant to BETd-246. Our findings uncover a requirement for BET proteins in maintaining MCC lineage identity and point to the potential utility of BET degraders for treating MCC.


Subject(s)
Carcinoma, Merkel Cell/metabolism , Proteins/antagonists & inhibitors , Proteins/metabolism , Skin Neoplasms/metabolism , Acetanilides/pharmacology , Antigens, Viral, Tumor/genetics , Antigens, Viral, Tumor/metabolism , Carcinoma, Merkel Cell/drug therapy , Carcinoma, Merkel Cell/etiology , Carcinoma, Merkel Cell/pathology , Cell Cycle/genetics , Cell Line, Tumor , Dose-Response Relationship, Drug , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Genes, Homeobox , Heterocyclic Compounds, 3-Ring/pharmacology , Humans , Merkel cell polyomavirus/physiology , Polyomavirus Infections/complications , Polyomavirus Infections/virology , Proteolysis , Skin Neoplasms/drug therapy , Skin Neoplasms/etiology , Skin Neoplasms/pathology , Transcriptome
18.
Front Genet ; 9: 592, 2018.
Article in English | MEDLINE | ID: mdl-30581452

ABSTRACT

Common carp is one of the oldest and most popular cultured freshwater fish species both globally and in China. In a previous study, we used a carp strain with a long breeding tradition in China, named Huanghe, to create a new fast-growing strain by selection for fast growth for 6 years. The growth performance at 8 months of age has been improved by 20.84%. To achieve this, we combined the best linear unbiased prediction with marker-assisted selection techniques. Recent progress in genome-wide association studies and genomic selection in livestock breeding inspired common carp breeders to consider genome-based breeding approaches. In this study, we developed a 2b-RAD sequence assay as a means of investigating the quantitative trait loci in common carp. A total of 4,953,017,786 clean reads were generated for 250 specimens (average reads/specimen = 19,812,071) with BsaXI Restriction Enzyme. From these, 56,663 SNPs were identified, covering 50 chromosomes and 3,377 scaffolds. Principal component analysis indicated that selection and control groups are relatively clearly distinct. Top 1% of Fst values was selected as the threshold signature of artificial selection. Among the 244 identified loci, genes associated with sex-related factors and nutritional metabolism (especially fat metabolism) were annotated. Eighteen QTL were associated with growth parameters. Body length at 3 months of age and body weight (both at 3 and 8 months) were controlled by polygenic effects, but body size (length, depth, width) at 8 months of age was controlled mainly by several loci with major effects. Importantly, a single shared QTL (IGF2 gene) partially controlled the body length, depth, and width. By merging the above results, we concluded that mainly the genes related to neural pathways, sex and fatty acid metabolism contributed to the improved growth performance of the new Huanghe carp strain. These findings are one of the first investigations into the potential use of genomic selection in the breeding of common carp. Moreover, our results show that combining the Fst, QTL mapping and CRISPR-Cas9 methods can be an effective way to identify important novel candidate molecular markers in economic breeding programs.

19.
Cancer Res ; 78(20): 5731-5740, 2018 10 15.
Article in English | MEDLINE | ID: mdl-30135193

ABSTRACT

Advanced prostate cancer initially responds to androgen deprivation therapy (ADT), but the disease inevitably recurs as castration-resistant prostate cancer (CRPC). Although CRPC initially responds to abiraterone and enzalutamide, the disease invariably becomes nonresponsive to these agents. Novel approaches are required to circumvent resistance pathways and to extend survival, but the mechanisms underlying resistance remain poorly defined. Our group previously showed the histone lysine-N-methyltransferase EZH2 to be overexpressed in prostate cancer and quantitatively associated with progression and poor prognosis. In this study, we screened a library of epigenetic inhibitors for their ability to render CRPC cells sensitive to enzalutamide and found that EZH2 inhibitors specifically potentiated enzalutamide-mediated inhibition of proliferation. Moreover, we identified antisense oligonucleotides (ASO) as a novel drug strategy to ablate EZH2 and androgen receptor (AR) expression, which may have advantageous properties in certain settings. RNA-seq, chromatin immunoprecipitation sequencing, and assay for transposase-accessible chromatin using sequencing demonstrated that EZH2 inhibition altered the AR cistrome to significantly upregulate AR signaling, suggesting an enhanced dependence of CRPC cells on this pathway following inhibition of EZH2. Combination treatment with ASO targeting EZH2 and AR transcripts inhibited prostate cancer cell growth in vitro and in vivo better than single agents. In sum, this study identifies EZH2 as a critical epigenetic regulator of ADT resistance and defines ASO-based cotargeting of EZH2 and AR as a promising strategy for the treatment of CRPC.Significance: Simultaneous targeting of lysine methyltransferase EZH2 and the AR with ASO proves a novel and effective therapeutic strategy in patients with CRPC. Cancer Res; 78(20); 5731-40. ©2018 AACR.


Subject(s)
Androgen Receptor Antagonists/pharmacology , Epigenesis, Genetic , Oligonucleotides, Antisense/genetics , Prostatic Neoplasms, Castration-Resistant/drug therapy , Prostatic Neoplasms, Castration-Resistant/genetics , Androgen Antagonists/pharmacology , Androstenes/pharmacology , Animals , Benzamides , Cell Line, Tumor , Cell Proliferation , Disease Progression , Drug Resistance, Neoplasm/drug effects , Enhancer of Zeste Homolog 2 Protein/metabolism , Humans , Male , Mice , Mice, SCID , Neoplasm Recurrence, Local/drug therapy , Neoplasm Transplantation , Nitriles , Phenylthiohydantoin/analogs & derivatives , Phenylthiohydantoin/pharmacology , Prognosis , Receptors, Androgen/metabolism , Signal Transduction
20.
Mol Cancer Res ; 16(7): 1125-1137, 2018 07.
Article in English | MEDLINE | ID: mdl-29025958

ABSTRACT

In aggressive prostate cancers, the oncoprotein STMN1 (also known as stathmin 1 and oncoprotein 18) is often overexpressed. STMN1 is involved in various cellular processes, including cell proliferation, motility, and tumor metastasis. Here, it was found that the expression of STMN1 RNA and protein is elevated in metastatic prostate cancers. Knockdown of STMN1 resulted in reduced proliferation and invasion of cells and tumor growth and metastasis in vivo Furthermore, miR-34a downregulated STMN1 by directly binding to its 3'-UTR. Overexpression of miR-34a in prostate cancer cells reduced proliferation and colony formation, suggesting that it is a tumor suppressor. The transcriptional corepressor C-terminal binding protein 1 (CtBP1) negatively regulated expression of miR-34a. Furthermore, gene expression profiling of STMN1-modulated prostate cancer cells revealed molecular alterations, including elevated expression of growth differentiation factor 15 (GDF15), which is involved in cancer progression and potentially in STMN1-mediated oncogenesis. Thus, in prostate cancer, CtBP1-regulated miR-34a modulates STMN1 expression and is involved in cancer progression through the CtBP1\miR-34a\STMN1\GDF15 axis.Implications: The CtBP1\miR-34a\STMN1\GDF15 axis is a potential therapeutic target for treatment of aggressive prostate cancer. Mol Cancer Res; 16(7); 1125-37. ©2017 AACR.


Subject(s)
Alcohol Oxidoreductases/genetics , DNA-Binding Proteins/genetics , Growth Differentiation Factor 15/genetics , MicroRNAs/genetics , Prostatic Neoplasms/genetics , Stathmin/genetics , Animals , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Disease Progression , Gene Expression Regulation, Neoplastic/genetics , Humans , Male , Mice , Prostate/metabolism , Prostate/pathology , Prostatic Neoplasms/pathology , Xenograft Model Antitumor Assays
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