Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.528
Filtrar
1.
FASEB J ; 36 Suppl 12022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35554253

RESUMO

Alzheimer's disease (AD) is a progressively debilitating neurodegenerative disease that exacts a heavy toll on our social and health care systems. AD is presumably caused by pathogenic variants in a large number of genes working in concert with environmental factors and personal behaviors. However, despite years of worldwide efforts, only a few dozen AD-associated genes have been identified to date. Employing the gene-to-gene damaging variant rate (g2gDVR) analysis of published datasets containing 181,388 subjects we discovered 2114 potentially AD-associated genes, of which 711 were linked to the higher AD prevalence among African-Americans. The DVRs of these genes in AD population (55,460 subjects found in NIAGADS) were at least two-fold higher than those in the general population (125,748 subjects in gnomAD) with false discovery rate less than 1x10-12 . The advantage of the g2gDVR method for studies of disease is that it focuses on variants expected to impact gene function, in contrast to methods based on SNP analysis, such as GWAS, that are gene-agnostic. In combination with transcriptome profiling of 21 brain regions from 2728 human AD and control samples (collected from various GEO datasets) we identified three of the 711 genes (GNB5, SNAP91 and AKAP11) that were candidate causative genes based on their reduced expression in both hippocampus and entorhinal cortex regions of AD patient brains. In the context of the APP/PSEN1 mouse model of AD, we further confirmed that Gnb5 heterozygosity exacerbates the formation of both amyloid plaques and neurofibrillary tangles, the hallmarks of AD brain neuropathology. These results suggested that the g2gDVR analysis method is highly effective in identification of AD-associated genes and is expected to be broadly applicable to other polygenic diseases.

2.
FASEB J ; 36 Suppl 12022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35554303

RESUMO

Neuropathic pain is a chronic disorder resulting from damage to the afferent nerve fibers or central pain pathways and is often a complication in pathological conditions such as diabetes, shingles, multiple sclerosis, and stroke. The opioid epidemic has elucidated the need for more efficacious treatments for neuropathic pain. In 2019 alone, nearly 1.6 million people were diagnosed with an opioid use disorder and 48,000 people died from a synthetic opioid overdose. Despite the addictive properties, opioids are still the most frequently prescribed pain medication, even for chronic neuropathic pain. Heterotrimeric G-proteins consisting of the α, ß, and γ subunits convey extracellular signals sensed by G-protein coupled receptors (GPCRs) to intracellular effectors. The Gß5 subunit is a divergent member of the G-protein ß subunit family as it does not bind to traditional γ subunits. Instead, Gß5 complexes with the R7 subfamily of the regulators of G-protein signaling (R7-RGS) containing 4 members: RGS6, 7, 9 and 11. The Gß5/R7-RGS complex acts as a GTPase accelerating protein (GAP) for G-protein αi/o (Gαi/o) subunits. Previous studies have established the integral role of R7-RGS proteins in pain transmission via their interactions with Gαi/o-coupled receptors including opioid and metabotropic gamma-aminobutyric acid (GABA-B) receptors. Our lab has shown the lack of Gß5 in sensory ganglia diminishes mechanical, thermal, and chemical nociception. However, the conditional knockout of Gß5 in Rgs7 expressing neurons reduces only mechanical nociception. This Gß5/RGS7-dependent mechanical nociception relies on GABA-B receptor signaling as indicated by the rescue of mechanical nociception in Rgs7-Cre; Gnb5 fl/fl mice after treatment with 2-hydroxysaclofen, a GABA-B antagonist. We also established that Rgs9 expressing neurons regulate thermal nociception via a Gß5-dependent pathway as assayed by the hotplate test in Rgs9-Cre; Gnb5 fl/fl mice. The purpose of this project has been to understand the molecular role of each R7-RGS member in the regulation of pain transmission. First, we confirmed co-localization between the Gnb5 transcript and all four R7-RGS mRNA transcripts in murine dorsal root ganglia (DRG) using the RNAscope HiPlex assay, a novel in situ hybridization technique. We then established the co-localization patterns between each R7-RGS member and various pain related receptors including Mrgprd, Trpa1, and Trpv1. Our RNAscope results support the behavioral tests since Rgs7 transcripts highly co-express with Mrgprd, a mechanical nociceptor, while Rgs9 transcripts most frequently co-express with Trpv1, a thermosensitive receptor. These results suggest that each R7-RGS member might regulate unique types of nociception. We have also shown that Rgs11 transcripts co-localize with Trpv1 and Trpa1 receptor transcripts which indicates Rgs11 might regulate the chemical nociception as tested by capsaicin and mustard oil administration in the eye-wipe test. Next, we aim to study the possible roles of Rgs6 and Rgs11 in regulating chemical nociception using conditional Gß5 knockout mice mediated by Rgs6-cre and Rgs11-cre, respectively.

4.
J Exp Clin Cancer Res ; 41(1): 172, 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35546239

RESUMO

BACKGROUND: Lung cancer is the leading cause of cancer death, partially owing to its extensive heterogeneity. The analysis of intertumor heterogeneity has been limited by an inability to concurrently obtain tissue from synchronous metastases unaltered by multiple prior lines of therapy. METHODS: In order to study the relationship between genomic, epigenomic and T cell repertoire heterogeneity in a rare autopsy case from a 32-year-old female never-smoker with left lung primary late-stage lung adenocarcinoma (LUAD), we did whole-exome sequencing (WES), DNA methylation and T cell receptor (TCR) sequencing to characterize the immunogenomic landscape of one primary and 19 synchronous metastatic tumors. RESULTS: We observed heterogeneous mutation, methylation, and T cell patterns across distinct metastases. Only TP53 mutation was detected in all tumors suggesting an early event while other cancer gene mutations were later events which may have followed subclonal diversification. A set of prevalent T cell clonotypes were completely excluded from left-side thoracic tumors indicating distinct T cell repertoire profiles between left-side and non left-side thoracic tumors. Though a limited number of predicted neoantigens were shared, these were associated with homology of the T cell repertoire across metastases. Lastly, ratio of methylated neoantigen coding mutations was negatively associated with T-cell density, richness and clonality, suggesting neoantigen methylation may partially drive immunosuppression. CONCLUSIONS: Our study demonstrates heterogeneous genomic and T cell profiles across synchronous metastases and how restriction of unique T cell clonotypes within an individual may differentially shape the genomic and epigenomic landscapes of synchronous lung metastases.

5.
Blood ; 2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35512188

RESUMO

There is a growing body of evidence that therapy-related myeloid neoplasms (t-MNs) with driver gene mutations arise in the background of clonal hematopoiesis (CH) under the positive selective pressure of chemo- and radiation therapies (CRT). Uncovering the exposure relationships that provide selective advantage to specific CH mutations is critical to understanding the pathogenesis and etiololgy of t-MNs. In a systematic analysis of 416 patients with t-MN and detailed prior exposure history, we found that TP53 mutations were significantly associated with prior treatment with thalidomide analogs, specifically lenalidomide. We demonstrated experimentally that lenalidomide treatment provides a selective advantage to Trp53-mutant hematopoietic stem and progenitor cells (HSPCs) in vitro and in vivo, the effect of which was specific to Trp53-mutant HSPCs and was not observed in HSPCs with other CH mutations. Due to differences in CK1a degradation, pomalidomide treatment did not provide an equivalent level of selective advantage to Trp53-mutant HSPCs providing a biological rationale for its use in patients at high risk for t-MN. These findings highlight the role of lenalidomide treatment in promoting TP53-mutated t-MNs and offer a potential alternative strategy to mitigate the risk of t-MN development.

6.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 39(2): 359-369, 2022 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-35523558

RESUMO

In existing vascular interventional surgical robots, it is difficult to accurately detect the delivery force of the catheter/guidewire at the slave side. Aiming to solve this problem, a real-time force detection system was designed for vascular interventional surgical (VIS) robots based on catheter push force. Firstly, the transfer process of catheter operating forces in the slave end of the interventional robot was analyzed and modeled, and the design principle of the catheter operating force detection system was obtained. Secondly, based on the principle of stress and strain, a torque sensor was designed and integrated into the internal transmission shaft of the slave end of the interventional robot, and a data acquisition and processing system was established. Thirdly, an ATI high-precision torque sensor was used to build the experimental platform, and the designed sensor was tested and calibrated. Finally, sensor test experiments under ideal static/dynamic conditions and simulated catheter delivery tests based on actual human computed tomography (CT) data and vascular model were carried out. The results showed that the average relative detection error of the designed sensor system was 1.26% under ideal static conditions and 1.38% under ideal dynamic stability conditions. The system can detect on-line catheter operation force at high precision, which is of great significance towards improving patient safety in interventional robotic surgery.


Assuntos
Procedimentos Cirúrgicos Robóticos , Robótica , Cateteres , Desenho de Equipamento , Humanos , Fenômenos Mecânicos , Procedimentos Cirúrgicos Robóticos/métodos
7.
Plant Physiol ; 2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35512056

RESUMO

Grass embryos possess structures that do not occur in any other flowering plants. Due to the specific embryo structure and position, grass embryo surfaces may be exposed to surrounding air under partial caryopsis-soil contact conditions, but whether caryopses of the grass family (Poaceae) can sense soil air humidity to initiate successful germination under partial caryopsis-soil contact conditions remain unknown. Here, we found that grass embryos have the unique ability to absorb water from atmospheric water vapor under partial caryopsis-soil contact conditions. To absorb atmospheric moisture, grass embryos developed profuse and highly elongated hairs on the embryo surface. These hairs, classically known as coleorhiza hairs, developed only on the embryo surface exposed to humid air, and submergence of the embryo surface inhibited their development. In addition to humid air-dependent development, almost all other developmental features of coleorhiza hairs were substantially different from root hairs. However, coleorhiza hair development was regulated by ROOTHAIRLESS 1. Besides the genetic control of coleorhiza hair development, we also identified how caryopses manage to keep the hairs turgid in natural open environments as the hairs were highly sensitive to dry air exposure. Moreover, we video-documented the regulation of developmental processes. The unique humid air-dependent coleorhiza hair development and their ability to absorb water from water vapor present in microsites or soil air give grasses advantages in germination and seedling establishment. Ultimately, coleorhiza hairs may have contributed to the ecological success of the grass family.

8.
ACS Appl Mater Interfaces ; 14(18): 21159-21172, 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35502844

RESUMO

Aqueous zinc-ion batteries (ZIBs) have received great attention due to their environmental friendliness and high safety. However, cathode materials with slow diffusion dynamics and dissolution in aqueous electrolytes hindered their further application. To address these issues, in this work, a MnO2-2 cathode doped with 1.12 wt % Ag was prepared, and after 1000 cycles of charge/discharge at 1 A·g-1, the capacity remained at 114 mA·h·g-1 (only 57.7 mA·h·g-1 for pristine MnO2). Cyclic voltammetry (CV), the galvanostatic intermittent titration technique (GITT), the electrochemical quartz crystal microbalance (EQCM) method, and density functional theory (DFT) calculation on pristine δ-MnO2 and MnO2-2 also proved the superior performance of MnO2-2. More investigation disclosed that its superior performance is attributed to the improved diffusion kinetics of the cathode brought by the enriched oxygen vacancy defects due to the formation of Ag-O-Mn bonds. Meanwhile, the kinetic mechanism of the Zn/MnO2-2 cell can be described as a reversible process of the dissolution/precipitation of the ZHS phase and consequent insertion/extraction of Zn2+ and H3O+. Herein, the primary issues of ZIB cathode materials have been addressed and solved to a certain extent. More importantly, such a modification in the design of the advanced manganese-based aqueous ZIB cathode materials can provide further insight and facilitate the development and application of this large-scale energy storage system in the near future.

9.
FASEB J ; 36 Suppl 12022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35560642

RESUMO

The prevalence and devastating effects of Alzheimer's Disease (AD) and lack of effective treatments underscore the need to determine genes and molecular pathways with pathophysiologic relevance to develop targeted therapies. Prior unpublished bioinformatic analysis by our laboratory of genomic and brain transcript expression data from subjects with and without AD has identified hundreds of potential AD causative genes, one being GNB5, which encodes the protein Gß5. Gß5 is a divergent member of the G-protein ß subunit family and is primarily expressed in neuronal tissues. It is known to stabilize members of the R7-Regulator of G-protein Signaling (RGS) subfamily that exert GTPase Accelerating Protein (GAP) activities on Gαi/o proteins during G-protein coupled receptor (GPCR) signaling. Homozygous lack of Gß5 causes significant neuronal and behavioral impairments in both mice and humans; however, the impact of GNB5 heterozygosity requires further examination. For this project, we demonstrated through fear conditioning behavioral tasks involving hippocampus and amygdala function that learning and memory deficits existed in mice heterozygous for Gnb5. In addition, the potential relevance of GNB5 in AD pathogenesis was confirmed in an APP/PSEN1 double transgenic AD mouse model in which missing even one copy of the Gnb5 gene enhanced amyloid plaque and neurofibrillary tangle formations in multiple brain regions of mice including, the entorhinal cortex, hippocampus, and frontal cortex. These results were confirmed by traditional immunohistochemistry methods as well as immunostaining of transparent mouse brains cleared using the clear, unobstructed brain/body imaging cocktails and computational analysis (CUBIC) method. We further demonstrated that the exacerbated AD pathology may be caused, at least in part, by the increased vulnerability of heterozygous GNB5 mouse neurons to the toxicity of Aß42 peptide oligomers which have been linked to beta-amyloid plaque formation. Our data suggest the involvement of GNB5 regulated GPCR signaling in the progression of AD pathology and illustrates a potential new therapeutic target for attenuation of cellular pathology associated with AD.

10.
Bull Entomol Res ; 112(3): 327-334, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35543297

RESUMO

The majority of plant viral disease is transmitted and spread by insect vectors in the field. The small brown planthopper, Laodelphax striatellus (Fallén), is the only efficient vector for rice black-streaked dwarf virus (RBSDV), a devastating plant virus that infects multiple grain crops, including rice, maize, and wheat. Adenosine triphosphate (ATP)-binding cassette (ABC) transporters participate in various biological processes. However, little is known about whether ABC transporters affect virus infection in insects. In this study, RBSDV accumulation was significantly reduced in L. striatellus after treatment with verapamil, an effective inhibitor of ABC transporters. Thirty-four ABC transporter genes were identified in L. striatellus and expression analysis showed that LsABCF2 and LsABCG9 were significantly upregulated and downregulated, respectively, after RBSDV infection. LsABCF2 and LsABCG9 were expressed during all developmental stages, and LsABCG9 was highly expressed in the midgut of L. striatellus. Knockdown of LsABCF2 promoted RBSDV accumulation, while knockdown of LsABCG9 suppressed RBSDV accumulation in L. striatellus. Our data showed that L. striatellus might upregulate the expression of LsABCF2 and downregulate LsABCG9 expression to suppress RBSDV infection. These results will contribute to understanding the effects of ABC transporters on virus transmission and provide theoretical basis for virus management in the field.


Assuntos
Hemípteros , Oryza , Vírus de Plantas , Viroses , Transportadores de Cassetes de Ligação de ATP/genética , Trifosfato de Adenosina , Animais , Hemípteros/genética , Insetos Vetores , Doenças das Plantas , Vírus de Plantas/genética
11.
mSystems ; : e0003322, 2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35477306

RESUMO

Mexican Americans have a high prevalence of diabetes and burden of diabetes-related complications, highlighting the need for novel preventive strategies and noninvasive predictors of diabetes risk tailored to this population. Changes in the gut microbiome have the potential to predict diabetes. Here, we aimed to identify alterations in the gut microbiome associated with diabetes in the high-risk population of Mexican Americans in South Texas. Stool samples were collected from 216 subjects from the population-based Cameron County Hispanic Cohort. Among them, 75 had type 2 diabetes. Taxonomic and functional profiling of the stool samples were assessed by 16S and shotgun metagenomic sequencing, and the influence of genetic factors was explored. The gut microbiome of subjects with diabetes was enriched with proinflammatory Proteobacteria members (Enterobacteriaceae, Escherichia-Shigella) and depleted of butyrate-producing Clostridiales members (Faecalibacterium prausnitzii, Peptostreptococcaceae, and Clostridium sensu stricto 1). The accompanying metagenomic changes in subjects with diabetes suggested dysregulated amino acid metabolism, reduced galacturonate and glucuronate catabolism (correlating with Faecalibacterium prausnitzii abundance), and enriched heme biosynthesis (correlating with Enterobacteriaceae abundance). Polymorphism rs7129790 near MMP27 was strongly associated with high Proteobacteria abundance and was more frequent in this cohort and in individuals of Mexican ancestry than in Europeans. In conclusion, Mexican Americans in South Texas with diabetes display distinct gut microbiome and metagenomic signatures. These signatures may have utility in risk modeling and disease prevention in this high-risk population. IMPORTANCE The gut microbiome composition varies across ethnicities and geographical locations, yet studies on diabetes-associated microbiome changes specific to high-risk Mexican Americans are lacking. Here, we aimed to identify specific alterations associated with diabetes in this population, as well as host genetic factors that may explain increased disease susceptibility in this ethnic group. Using samples from a population-based cohort of Mexican Americans with a high prevalence of obesity and diabetes, we confirmed findings from studies on other ethnicities that suggested promotion of a chronic proinflammatory environment, loss of butyrate production, and compromised intestinal barrier integrity. High abundance of proinflammatory Proteobacteria was associated with a polymorphism that was more frequent in this cohort and in individuals of Mexican ancestry than in Europeans. Validation of microbiome-based risk models for diabetes should be evaluated in prospective cohort studies.

12.
Entropy (Basel) ; 24(4)2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35455162

RESUMO

The molecular weight distribution is an important factor that affects the properties of polymers. A control algorithm based on the moment-generating function was proposed to regulate the molecular weight distribution for polymerization processes in this work. The B-spline model was used to approximate the molecular weight distribution, and the weight state space equation of the system was identified by the subspace state space system identification method based on the paired date of B-spline weights and control inputs. Then, a new performance criterion mainly consisting of the moment-generating function was constructed to obtain the optimal control input. The effectiveness of the proposed control method was tested in a styrene polymerization process. The molecular weight distribution of the styrene polymers can be approximated by the B-spline model effectively, and it can also be regulated towards the desired one under the proposed control method.

13.
Entropy (Basel) ; 24(4)2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35455176

RESUMO

The Organic Rankine Cycle (ORC) is one kind of appropriate energy recovery techniques for low grade heat sources. Since the mass flow rate and the inlet temperature of heat sources usually experience non-Gaussian fluctuations, a conventional linear quadratic performance criterion cannot characterize the system uncertainties adequately. This paper proposes a new model free control strategy which applies the (h,φ)-entropy criterion to decrease the randomness of controlled ORC systems. In order to calculate the (h,φ)-entropy, the kernel density estimation (KDE) algorithm is used to estimate the probability density function (PDF) of the tracking error. By minimizing the performance criterion mainly consisting of (h,φ)-entropy, a new control algorithm for ORC systems is obtained. The stability of the proposed control system is analyzed. The simulation results show that the ORC system under the proposed control method has smaller standard deviation (STD) and mean squared error (MSE), and reveals less randomness than those of the traditional PID control algorithm.

14.
NPJ Precis Oncol ; 6(1): 21, 2022 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-35379887

RESUMO

Desmoplastic small round cell tumor (DSRCT) is a highly aggressive soft tissue sarcoma that is characterized by the EWSR1-WT1 fusion protein. Patients present with hundreds of tumor implants in their abdominal cavity at various sites. To determine the genetic relatedness among these sites, exome and RNA sequencing were performed on 22 DSRCT specimens from 14 patients, four of whom had specimens from various tissue sites. Multi-site tumors from individual DSRCT patients had a shared origin and were highly related. Other than the EWSR1-WT1 fusion, very few secondary cancer gene mutations were shared among the sites. Among these, ARID1A, was recurrently mutated, which corroborates findings by others in DSRCT patients. Knocking out ARID1A in JN-DSRCT cells using CRISPR/CAS9 resulted in significantly lower cell proliferation and increased drug sensitivity. The transcriptome data were integrated using network analysis and drug target database information to identify potential therapeutic opportunities in EWSR1-WT1-associated pathways, such as PI3K and mTOR pathways. Treatment of JN-DSRCT cells with the PI3K inhibitor alpelisib and mTOR inhibitor temsirolimus reduced cell proliferation. In addition, the low mutation burden was associated with an immune-cold state in DSRCT. Together, these data reveal multiple genomic and immune features of DSRCT and suggest therapeutic opportunities in patients.

15.
Neurosci Lett ; : 136638, 2022 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-35447224

RESUMO

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder that is featured by the elevated loss of substantia nigra pars compacta dopaminergic neurons and the disruption of motor functions. Aberrant expression of circular RNAs (circRNAs) is correlated with neurodegenerative diseases. This study aimed to explore the role of circTLK1 in PD pathology. METHODS: MPTP-stimulated in vivo PD mouse model and MPP+ and rotenone-induced in vitro PD model were established to investigate the function of circTLK1/miR-26a-5p/DAPK1 axis during dopaminergic neuron injury. The motor function of mice was evaluated by using the Rotarod test. Brain tissue damage was checked by hematoxylin and eosin, TdT-mediated dUTP-biotin nick end labeling. Cell viability, apoptosis, and cytotoxicity were evaluated by cell counting kit 8 (CCK-8), flow cytometry, and LDH activity. The interaction between circTLK1 and miR-26a-5p as well as miR-26a-5p and DAPK1 was detected by luciferase reporter assay. RESULTS: The expression of circTLK1 was notably elevated in in vitro and in vivo PD models. Knockdown of circTLK1 significantly improved cell viability, suppressed apoptosis and cytotoxicity, whereas inhibition of miR-16a-5p and overexpression of DAPK1 abolished these effects. MiR-26a-5p acts as a sponge of DAPK1 to mediate circTLK1 functions. Luciferase reporter gene assay confirmed the interaction between circTLK1 and miR-26a-5p as well as miR-26a-5p and DAPK1. CONCLUSION: Depletion of circTLK1 mitigates dopaminergic neuron injury in vitro and in vivo, via releasing miR-26a-5p to target DAPK1 expression. Targeting circTLK1 may contribute to improving PD therapy.

16.
J Hazard Mater ; 433: 128795, 2022 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-35405588

RESUMO

Epidemiology studies have indicated that environmental cadmium exposure, even at low levels, will result in chronic cadmium accumulation in the kidney with profound adverse consequences and that the diabetic population is more susceptible. However, the underlying mechanisms are yet not fully understood. In the present study, we applied an animal model to study chronic cadmium exposure-induced renal injury and performed whole transcriptome profiling studies. Repetitive CdCl2 exposure resulted in cadmium accumulation and remarkable renal injuries in the animals. The diabetic ob/ob mice manifested increased severity of renal injury compared with the wild type C57BL/6 J littermate controls. RNA-Seq data showed that cadmium treatment induced dramatic gene expression changes in a dose-dependent manner. Among the differentially expressed genes include the apoptosis hallmark genes which significantly demarcated the treatment effects. Pathway enrichment and network analyses revealed biological oxidation (mainly glucuronidation) as one of the major stress responses induced by cadmium treatment. We next implemented a deep learning algorithm in conjunction with cloud computing and discovered a gene signature that can predict the degree of renal injury induced by cadmium treatment. The present study provided, for the first time, a comprehensive mechanistic understanding of chronic cadmium-induced nephrotoxicity in normal and diabetic populations at the whole genome level.


Assuntos
Cádmio , Aprendizado Profundo , Animais , Cádmio/metabolismo , Cloreto de Cádmio/toxicidade , Rim/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo
17.
Int J Mol Sci ; 23(7)2022 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-35408887

RESUMO

Grain size is an important component of quality and harvest traits in the field of rice breeding. Although numerous quantitative trait loci (QTLs) of grain size in rice have been reported, the molecular mechanisms of these QTLs remain poorly understood, and further research on QTL observation and candidate gene identification is warranted. In our research, we developed a suite of F2 intercross populations from a cross of 9311 and CG. These primary populations were used to map QTLs conferring grain size, evaluated across three environments, and then subjected to bulked-segregant analysis-seq (BSA-seq). In total, 4, 11, 12 and 14 QTLs for grain length (GL), grain width (GW), 1000-grain weight (TGW), and length/width ratio (LWR), respectively, were detected on the basis of a single-environment analysis. In particular, over 200 splicing-related sites were identified by whole-genome sequencing, including one splicing-site mutation with G>A at the beginning of intron 4 on Os03g0841800 (qGL3.3), producing a smaller open reading frame, without the third and fourth exons. A previous study revealed that the loss-of-function allele caused by this splicing site can negatively regulate rice grain length. Furthermore, qTGW2.1 and qGW2.3 were new QTLs for grain width. We used the near-isogenic lines (NILs) of these GW QTLs to study their genetic effects on individuals and pyramiding, and found that they have additive effects on GW. In summary, these discoveries provide a valuable genetic resource, which will facilitate further study of the genetic polymorphism of new rice varieties in rice breeding.


Assuntos
Oryza , Mapeamento Cromossômico , Grão Comestível/genética , Humanos , Oryza/genética , Melhoramento Vegetal , Locos de Características Quantitativas
18.
Front Genet ; 13: 869859, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35480314

RESUMO

Background and Aims: Sudden cardiac death (SCD) was defined as an unexpected death from cardiac causes during a very short duration. It has been reported that Niemann-Pick type C1 (NPC1) gene mutations might be related to cardiovascular diseases. The purpose of the study is to investigate whether common genetic variants of NPC1 is involved in SCD susceptibility. Methods: Based on a candidate-gene-based approach and systematic screening strategy, this study analyzed an 8-bp insertion/deletion polymorphism (rs150703258) within downstream of NPC1 for the association with SCD risk in Chinese populations using 158 SCD cases and 524 controls. The association of rs150703258 and SCD susceptibility was analyzed using logistic regression. Genotype-phenotype correlation analysis was performed using public database including 1000G, expression quantitative trait loci (eQTL), and further validated by human heart tissues using PCR. Dual-luciferase assay was used to explore the potential regulatory role of rs150703258. Gene expression profiling interactive analysis and transcription factors prediction were performed. Results: Logistic regression analysis exhibited that the deletion allele of rs150703258 significantly increased the risk of SCD [odds ratio (OR) = 1.329; 95% confidence interval (95%CI):1.03-1.72; p = 0.0289]. Genotype-phenotype correlation analysis showed that the risk allele was significantly associated with higher expression of NPC1 at mRNA and protein expressions level in human heart tissues. eQTL analysis showed NPC1 and C18orf8 (an adjacent gene to NPC1) are both related to rs150703258 and have higher expression level in the samples with deletion allele. Dual-luciferase activity assays indicate a significant regulatory role for rs150703258. Gene expression profiling interactive analysis revealed that NPC1 and C18orf8 seemed to be co-regulated in human blood, arteries and heart tissues. In silico analysis showed that the rs150703258 deletion variant may create transcription factor binding sites. In addition, a rare 12-bp allele (4-bp longer than the insertion allele) of rs150703258 was discovered in the current cohort. Conclusion: In summary, our study revealed that rs150703258 might contribute to SCD susceptibility by regulating NPC1 and C18orf8 expression. This indel may be a potential marker for risk stratification and molecular diagnosis of SCD. Validations in different ethnic groups with larger sample size and mechanism explorations are warranted to confirm our findings.

19.
Chem Asian J ; 17(10): e202200088, 2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35319154

RESUMO

An efficient method for silver-catalyzed radical cascade arylthiodifluoromethylation/cyclization of isonitriles is disclosed. The transformation comprised addition of an arylthiodifluoromethyl radical generated in situ by the oxidative decarboxylation of arylthiodifluoroacetic salts to the isonitrile functionality to construct an ArSCF2 -C bond, followed by intramolecular cyclization to eventually afford 6-phenanthridinyldifluoromethyl aryl thioethers. The protocol provided a variety of 6-phenanthridinyldifluoromethyl aryl thioethers in medium to excellent yields with a good functional group tolerance under mild reaction conditions.

20.
Membranes (Basel) ; 12(3)2022 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-35323822

RESUMO

Polyvinyl alcohol (PVA) is one of the few biodegradable synthetic resins from petroleum-based sources that can alleviate white pollution in the environment. PVA film materials have excellent properties, such as high barrier, high transparency, high toughness, biocompatibility, and adjustable water solubility. However, due to the presence of hydrophilic hydroxyl groups in the side chain of PVA resin, when PVA film is placed in a humid or water environment, swelling or even dissolution will occur, which greatly limits its application. Therefore, it is necessary to modify PVA resin to improve water resistance without reducing other properties and can also impart various functionalities to it, thereby widening the application range. This paper reviews the water-resistant modification methods of polyvinyl alcohol and the application of water-resistant films and provides an outlook on the development trend of PVA water-resistant films.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...