ABSTRACT
The G-protein-coupled bile acid receptor (GPBAR) conveys the cross-membrane signalling of a vast variety of bile acids and is a signalling hub in the liver-bile acid-microbiota-metabolism axis1-3. Here we report the cryo-electron microscopy structures of GPBAR-Gs complexes stabilized by either the high-affinity P3954 or the semisynthesized bile acid derivative INT-7771,3 at 3 Å resolution. These structures revealed a large oval pocket that contains several polar groups positioned to accommodate the amphipathic cholic core of bile acids, a fingerprint of key residues to recognize diverse bile acids in the orthosteric site, a putative second bile acid-binding site with allosteric properties and structural features that contribute to bias properties. Moreover, GPBAR undertakes an atypical mode of activation and G protein coupling that features a different set of key residues connecting the ligand-binding pocket to the Gs-coupling site, and a specific interaction motif that is localized in intracellular loop 3. Overall, our study not only reveals unique structural features of GPBAR that are involved in bile acid recognition and allosteric effects, but also suggests the presence of distinct connecting mechanisms between the ligand-binding pocket and the G-protein-binding site in the G-protein-coupled receptor superfamily.
Subject(s)
Bile Acids and Salts/metabolism , Cryoelectron Microscopy , Receptors, G-Protein-Coupled/metabolism , Receptors, G-Protein-Coupled/ultrastructure , Allosteric Regulation/drug effects , Bile Acids and Salts/chemistry , Binding Sites/drug effects , Cholic Acids/chemistry , Cholic Acids/pharmacology , GTP-Binding Protein alpha Subunits, Gs/chemistry , GTP-Binding Protein alpha Subunits, Gs/metabolism , GTP-Binding Protein alpha Subunits, Gs/ultrastructure , Humans , Ligands , Models, Molecular , Protein Binding , Receptors, G-Protein-Coupled/agonists , Receptors, G-Protein-Coupled/chemistry , Substrate SpecificityABSTRACT
BACKGROUND: Transforming growth factor ß (TGF-ß) superfamily genes can regulate various processes, especially in embryogenesis, adult development, and homeostasis. To understand the evolution and divergence patterns of the TGF-ß superfamily in scallops, genome-wide data from the Bay scallop (Argopecten irradians), the Zhikong scallop (Chlamys farreri) and the Yesso scallop (Mizuhopecten yessoensis) were systematically analysed using bioinformatics methods. RESULTS: Twelve members of the TGF-ß superfamily were identified for each scallop. The phylogenetic tree showed that these genes were grouped into 11 clusters, including BMPs, ADMP, NODAL, GDF, activin/inhibin and AMH. The number of exons and the conserved motif showed some differences between different clusters, while genes in the same cluster exhibited high similarity. Selective pressure analysis revealed that the TGF-ß superfamily in scallops was evolutionarily conserved. The spatiotemporal expression profiles suggested that different TGF-ß members have distinct functions. Several BMP-like and NODAL-like genes were highly expressed in early developmental stages, patterning the embryonic body plan. GDF8/11-like genes showed high expression in striated muscle and smooth muscle, suggesting that these genes may play a critical role in regulating muscle growth. Further analysis revealed a possible duplication of AMH, which played a key role in gonadal growth/maturation in scallops. In addition, this study found that several genes were involved in heat and hypoxia stress in scallops, providing new insights into the function of the TGF-ß superfamily. CONCLUSION: Characteristics of the TGF-ß superfamily in scallops were identified, including sequence structure, phylogenetic relationships, and selection pressure. The expression profiles of these genes in different tissues, at different developmental stages and under different stresses were investigated. Generally, the current study lays a foundation for further study of their pleiotropic biological functions in scallops.
Subject(s)
Pectinidae , Animals , Phylogeny , Pectinidae/genetics , Pectinidae/metabolism , Genome , Transforming Growth Factor beta/genetics , Transforming Growth Factor beta/metabolismABSTRACT
BACKGROUND: Neuromyelitis Optica Spectrum Disorder (NMOSD) is an inflammatory autoimmune disease with high risk of recurrence and disability, the treatment goal is a recurrence free state. Area postrema (AP) is one of the most common involved area of NMOSD, which may have a particular significance in the pathogenesis of NMOSD and clinical heterogeneity. Our study is to investigate the clinical and recurrent characteristics AP onset NMOSD patients. METHODS: A retrospective study was done in a cohort of 166 AQP4-IgG seropositive NMOSD patients which were identified by the 2015 IPND criteria. The patients were divided into AP onset (APO-NMOSD) group and non-AP onset (NAPO-NMOSD) group based on the initial episode location. Clinical features and recurrence differences of two groups were compared. RESULTS: The APO-NMOSD group and NAPO-NMOSD group had a population ratio of 24:142. APO-NMOSD patients were younger (34.6y VS 42.3y, P = 0.013), had lower EDSS at first episode (0.7 VS 4.2, p = 0.028) and last follow up (1.9 VS 3.3, p = 0.001), more likely to have multi-core lesions at the first attack (33.3% VS 9.2%, P = 0.001). Also, they had a higher annual recurrence rate (0.4 ± 0.28 VS 0.19 ± 0.25, P = 0.012). In natural course NMOSD patients without immunotherapy, APO-NMSOD had a shorter time of first relapse (P < 0.001) and higher annual recurrence rate (0.31 ± 0.22 VS 0.16 ± 0.26, P = 0.038) than NAPO-NMOSD. APO-NMOSD group also have a higher risk of having the first relapsing compared to optic neuritis onset-NMOSD (HR 2.641, 95% CI 1.427-4.887, p = 0.002) and myelitis onset-NMOSD group (HR 3.593, 95% CI 1.736-7.438, p = 0.001). Compared to NAPO-NMOSD, APO-NMOSD has a higher likelihood of brainstem recurrence (28.6% vs. 4.7%, p<0.001) during the first recurrence, while NAPO-NMOSD is more susceptible to optic nerve involvement (10.7% vs. 41.1%, p = 0.01). CONCLUSION: AQP4-IgG seropositive NMOSD patients with AP onset are youngers and have higher risk of recurrence. Clinicians should pay attention to AP damage in NMOSD, as it indicates a potential risk of recurrence. TRIAL REGISTRATION: Retrospectively registered.
Subject(s)
Area Postrema , Neuromyelitis Optica , Recurrence , Humans , Neuromyelitis Optica/epidemiology , Neuromyelitis Optica/diagnosis , Female , Retrospective Studies , Adult , Male , Middle Aged , Area Postrema/pathology , Young Adult , Cohort Studies , Aquaporin 4/immunologyABSTRACT
KEY MESSAGE: The soybean gene GmSABP2-1 encodes methyl salicylate esterase and its overexpression led to significant reduction in development of pathogenic soybean cyst nematode. Soybean cyst nematode (SCN, Heterodera glycines) is one of the most devastating pests of soybean (Glycine max L. Merr.). In searching for SCN-defense genes, a soybean gene of the methylesterase (MES) family was found to be upregulated in an SCN-resistant soybean line and downregulated in an SCN-susceptible line upon SCN infection. This gene was designated as GmSABP2-1. Here, we report on biochemical and overexpression studies of GmSABP2-1 to examine its possible function in SCN resistance. The protein encoded by GmSABP2-1 is closely related to known methyl salicylate esterases. To determine the biochemical function of GmSABP2-1, a full-length cDNA of GmSABP2-1 was cloned into a protein expression vector and expressed in Escherichia coli. The resulting recombinant GmSABP2-1 was demonstrated to catalyze the demethylation of methyl salicylate. The biochemical properties of GmSABP2-1 were determined. Its apparent Km value was 46.2 ± 2.2 µM for methyl salicylate, comparable to those of the known methyl salicylate esterases. To explore the biological significance of GmSABP2-1 in soybean defense against SCN, we first overexpressed GmSABP2-1 in transgenic hairy roots of an SCN-susceptible soybean line. When infected with SCN, GmSABP2-1-overexpressing hairy roots showed 84.5% reduction in the development of SCN beyond J2 stage. To provide further genetic evidence for the role of GmSABP2-1 in SCN resistance, stable transgenic soybean plants overexpressing GmSABP2-1 were produced. Analysis of the GmSABP2-1-overexpressing lines showed a significant reduction in SCN development compared to non-transgenic plants. In conclusion, we demonstrated that GmSABP2-1 encodes methyl salicylate esterase and functions as a resistance-related gene against SCN.
Subject(s)
Glycine max , Plant Diseases , Salicylates , Tylenchoidea , Animals , Carboxylic Ester Hydrolases/metabolism , Carboxylic Ester Hydrolases/genetics , Disease Resistance/genetics , Gene Expression Regulation, Plant , Glycine max/genetics , Glycine max/parasitology , Plant Diseases/parasitology , Plant Diseases/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Plants, Genetically Modified , Salicylates/metabolism , Tylenchoidea/physiology , Tylenchoidea/pathogenicityABSTRACT
BACKGROUND: The neural correlate of cognitive deficits in bipolar disorder (BD) is an issue that warrants further investigation. However, relatively few studies have examined the intrinsic functional connectivity (FC) underlying cognitive deficits involving sustained attention and executive function at both the region and network levels, as well as the different relationships between connectivity patterns and cognitive performance, in BD patients and healthy controls (HCs). METHODS: Patients with BD (n = 59) and HCs (n = 52) underwent structural and resting-state functional magnetic resonance imaging and completed the Wisconsin Card Sorting Test (WCST), the continuous performance test and a clinical assessment. A seed-based approach was used to evaluate the intrinsic FC alterations in three core neurocognitive networks (the default mode network [DMN], the central executive network [CEN] and the salience network [SN]). Finally, we examined the relationship between FC and cognitive performance by using linear regression analyses. RESULTS: Decreased FC was observed within the DMN, in the DMN-SN and DMN-CEN and increased FC was observed in the SN-CEN in BD. The alteration direction of regional FC was consistent with that of FC at the brain network level. Decreased FC between the left posterior cingulate cortex and right anterior cingulate cortex was associated with longer WCST completion time in BD patients (but not in HCs). CONCLUSIONS: These findings emphasize the dominant role of the DMN in the psychopathology of BD and provide evidence that cognitive deficits in BD may be associated with aberrant FC between the anterior and posterior DMN.
Subject(s)
Bipolar Disorder , Humans , Bipolar Disorder/complications , Bipolar Disorder/diagnostic imaging , Executive Function , Neural Pathways/diagnostic imaging , Magnetic Resonance Imaging/methods , Brain/diagnostic imaging , Brain Mapping/methods , CognitionABSTRACT
Water security is a critical concern due to intensifying anthropogenic activities and climate change. Delineating a water-related ecological security pattern can help to optimize spatial configuration, which in turn can inform sustainable water management. However, the methodology remains unclear. In this study, we developed a framework linking ecosystem service flow to water-related ecological security pattern; hence, we identified the sources, sinks, key corridors, and vulnerable nodes in Fujian Province, China. Our results revealed that the sources were located inland at high altitudes with a decreasing area trend in the south and an increasing area trend in the north, whereas the sinks were spread in coastal areas and exhibited a decreasing trend with relatively stable spatial distribution. The water-related ecological security has degraded as represented by a decreasing ecological supply-demand ratio over the last 30 years. Key corridors were identified in 17.12% of the rivers, and 22.5% of the vulnerable nodes were recognized as early warning nodes. Climate variability affected source distribution, while anthropogenic activities drove sink dynamics. These findings have important implications including landscape pattern planning and sustainable water management in the context of accelerated land use/cover and climate changes.
Subject(s)
Conservation of Natural Resources , Ecosystem , China , Rivers , Anthropogenic EffectsABSTRACT
One critical question for water security and sustainable development is how water quality responses to the changes in natural factors and human activities, especially in light of the expected exacerbation in water scarcity. Although machine learning models have shown noticeable advances in water quality attribution analysis, they have limited interpretability in explaining the feature importance with theoretical guarantees of consistency. To fill this gap, this study built a modelling framework that employed the inverse distance weighting method and the extreme gradient boosting model to simulate the water quality at grid scale, and adapted the Shapley additive explanation to interpret the contributions of the drivers to water quality over the Yangtze River basin. Different from previous studies, we calculated the contribution of features to water quality at each grid within river basin and aggregated the contribution from all the grids as the feature importance. Our analysis revealed dramatic changes in response magnitudes of water quality to drivers within river basin. Air temperature had high importance in the variability of key water quality indicators (i.e. ammonia-nitrogen, total phosphorus, and chemical oxygen demand), and dominated the changes of water quality in Yangtze River basin, especially in the upstream region. In the mid- and downstream regions, water quality was mainly affected by human activities. This study provided a modelling framework applicable to robustly identify the feature importance by explaining the contribution of features to water quality at each grid.
Subject(s)
Environmental Monitoring , Water Quality , Humans , Anthropogenic Effects , Rivers , Biological Oxygen Demand AnalysisABSTRACT
Pheromone receptors (PRs) recognize specific pheromone compounds to guide the behavioral outputs of insects, which are the most diverse group of animals on earth. The activation of PRs is known to couple to the calcium permeability of their coreceptor (Orco) or putatively with G proteins; however, the underlying mechanisms of this process are not yet fully understood. Moreover, whether this transverse seven transmembrane domain (7TM)-containing receptor is able to couple to arrestin, a common effector for many conventional 7TM receptors, is unknown. Herein, using the PR BmOR3 from the silk moth Bombyx mori and its coreceptor BmOrco as a template, we revealed that an agonist-induced conformational change of BmOR3 was transmitted to BmOrco through transmembrane segment 7 from both receptors, resulting in the activation of BmOrco. Key interactions, including an ionic lock and a hydrophobic zipper, are essential in mediating the functional coupling between BmOR3 and BmOrco. BmOR3 also selectively coupled with Gi proteins, which was dispensable for BmOrco coupling. Moreover, we demonstrated that trans-7TM BmOR3 recruited arrestin in an agonist-dependent manner, which indicates an important role for BmOR3-BmOrco complex formation in ionotropic functions. Collectively, our study identified the coupling of G protein and arrestin to a prototype trans-7TM PR, BmOR3, and provided important mechanistic insights into the coupling of active PRs to their downstream effectors, including coreceptors, G proteins, and arrestin.
Subject(s)
Bombyx , Insect Proteins , Receptors, Odorant , Animals , Bombyx/chemistry , Bombyx/genetics , Bombyx/metabolism , HEK293 Cells , Humans , Hydrophobic and Hydrophilic Interactions , Insect Proteins/chemistry , Insect Proteins/genetics , Insect Proteins/metabolism , Protein Domains , Receptors, Odorant/chemistry , Receptors, Odorant/genetics , Receptors, Odorant/metabolismABSTRACT
The stress sensitization model indicates that early adversity (e.g., childhood stress) sensitizes individuals to subsequent proximal stress (e.g., stressful life events in adult life), thereby increasing their vulnerability to psychiatric disorders. However, the effect of stress sensitization on suicidality in patients with major depressive disorder (MDD) has not been previously investigated. Data for the present study were derived from the Objective Diagnostic Markers and Personalized Intervention in MDD Patients (ODMPIM) study. The psychiatric diagnosis and suicidal ideation were evaluated by the Mini-International Neuropsychiatric Interview (M.I.N.I.). We used a multiple logistic analysis to examine the association among childhood adversity (CA), adulthood adversity (AA) and suicidal ideation. Among 1084 MDD patients, 48.6% had suicidal ideation and 65.6% experienced life adversity during their childhood or adulthood. Patients who reported suicidal ideation were more likely to report CA (46.7% vs. 38.7%, P = 0.008) or AA (49.5% vs. 40.9%, P = 0.004) than patients without suicidal ideation. Patients who experienced two waves of adversity (both CA and AA) were associated with higher rates of suicidal ideation (odds ratio = 1.68, 95% CI = 1.19-2.37, P = 0.003); however, neither CA nor AA alone was associated with suicidal ideation. This study first verifies the hypothesis of stress sensitization on suicidal ideation in patients with MDD. Focusing on stress sensitization may enhance the early identification of MDD patients at suicidal risk and the ability to provide timely and appropriate intervention. Clinicaltrials.gov identifier: NCT02023567.
Subject(s)
Adverse Childhood Experiences , Depressive Disorder, Major , Adult , China/epidemiology , Depressive Disorder, Major/epidemiology , Depressive Disorder, Major/psychology , Humans , Psychiatric Status Rating Scales , Risk Factors , Suicidal IdeationABSTRACT
OBJECTIVES: Genome-wide analyses of antidepressant response have suggested that genes initially associated with risk for schizophrenia may also serve as promising candidates for selective serotonin reuptake inhibitor (SSRI) efficacy. Protein tyrosine phosphatase, receptor-type, zeta-1 (PTPRZ1) has previously been shown to be associated with schizophrenia, but it has not been investigated as a predictor of antidepressant efficacy. The main objective of the study was to assess whether SSRI-mediated depressive and anxiety symptom remission in Chinese patients with major depressive disorder (MDD) are associated with specific PTPRZ1 variants. METHODS: Two independent cohorts were investigated, the first sample (N = 344) received an SSRI (i.e. fluoxetine, sertraline, citalopram, escitalopram, fluvoxamine, or paroxetine) for 8 weeks. The second sample (N = 160) only received escitalopram for 8 weeks. Hamilton Depression and Hamilton Anxiety Rating Scale scores at 8-weeks post-baseline in both cohorts were used to determine remission status. Five PTPRZ1 variants (rs12154537, rs6466810, rs6466808, rs6955395, and rs1918031) were genotyped in both cohorts. RESULTS: Anxiety symptom remission was robustly associated with PTPRZ1 rs12154537 (P = 0.004) and the G-G-G-G haplotype (rs12154537-rs6466810-rs6466808-rs6955395; P = 0.005) in cohort 2 but not cohort 1 (mixed SSRI use). Associations with depressive symptom remission did not survive correction for multiple testing. CONCLUSIONS: These findings suggest that PTPRZ1 variants may serve as a marker of escitalopram-mediated anxiety symptom remission in MDD.
Subject(s)
Depressive Disorder, Major , Anxiety/drug therapy , Anxiety/genetics , Citalopram/adverse effects , Depressive Disorder, Major/drug therapy , Depressive Disorder, Major/genetics , Escitalopram , Genetic Variation , Genome-Wide Association Study , Humans , Receptor-Like Protein Tyrosine Phosphatases, Class 5 , Selective Serotonin Reuptake Inhibitors/adverse effects , Treatment OutcomeABSTRACT
A new photoelectrochemical enzyme biosensor based on an extended-gate field-effect transistor (EGFET) was constructed for the highly sensitive detection of glyphosate based on the inhibition of acetylcholinesterase (AChE) activity by glyphosate. First, a two-step hydrothermal method was used to introduce ZnO and CdS onto an activated indium tin oxide (ITO) electrode to prepare a CdS/ZnO/ITO electrode. Then, AChE was immobilized on CdS/ZnO/ITO with chitosan to obtain an AChE/CdS/ZnO EGFET sensor. Under optimal experimental conditions, the logarithmic value of glyphosate in the range of 1.0 × 10-15-1.0 × 10-11 mol L-1 exhibited a good linear relationship with the photo-drain current response. The detection limit was 3.8 × 10-16 mol L-1 (signal-to-noise ratio = 3). The results show that the AChE/CdS/ZnO EGFET sensor has extremely high sensitivity and good selectivity. Moreover, the sensor was used for the determination of glyphosate in vegetables, demonstrating its application for the real-time detection of samples.
Subject(s)
Biosensing Techniques , Zinc Oxide , Acetylcholinesterase , Electrodes , Glycine/analogs & derivatives , Limit of Detection , GlyphosateABSTRACT
BACKGROUND: It remains unclear which size of particles has the strongest effects on heart rate variability (HRV). OBJECTIVE: To explore the association between HRV parameters and daily variations of size-fractionated particle number concentrations (PNCs). METHODS: We conducted a longitudinal repeated-measure study among 78 participants with a 24-h continuous ambulatory Holter electrocardiographic recorder in Shanghai, China, from January 2015 to June 2019. Linear mixed-effects models were employed to evaluate the changes of HRV parameters associated with PNCs of 7 size ranges from 0.01 to 10 µm after controlling for environmental and individual confounders. RESULTS: On the concurrent day, decreased HRV parameters were associated with increased PNCs of 0.01-0.3 µm, and smaller particles showed greater effects. For an interquartile range increase in ultrafine particles (UFP, those < 0.1 µm, 2453 particles/cm3), the declines in very-low-frequency power, low-frequency power, high-frequency power, standard deviation of normal R-R intervals, root mean square of the successive diï¬erences between R-R intervals and percentage of adjacent normal R-R intervals with a difference ≥ 50 ms were 5.06% [95% confidence interval (CI): 2.09%, 7.94%], 7.65% (95%CI: 2.73%, 12.32%), 9.49% (95%CI: 4.64%, 14.09%), 5.10% (95%CI: 2.21%, 7.91%), 8.09% (95%CI: 4.39%, 11.65%) and 24.98% (95%CI: 14.70%, 34.02%), respectively. These results were robust to the adjustment of criteria air pollutants, temperature at different lags, and the status of heart medication. CONCLUSIONS: Particles less than 0.3 µm (especially UFP) may dominate the acute effects of particulate air pollution on cardiac autonomic dysfunction.
Subject(s)
Air Pollutants/analysis , Air Pollution/statistics & numerical data , Environmental Exposure/statistics & numerical data , Particulate Matter/analysis , Air Pollution/analysis , China , Female , Heart Diseases , Heart Rate/drug effects , Humans , Male , Middle Aged , Particle Size , TemperatureABSTRACT
Sustained hyperglycaemia and hyperlipidaemia incur endoplasmic reticulum stress (ER stress) and reactive oxygen species (ROS) overproduction in pancreatic ß-cells. ER stress or ROS causes c-Jun N-terminal kinase (JNK) activation, and the activated JNK triggers apoptosis in different cells. Nuclear receptor subfamily 4 group A member 1 (NR4A1) is an inducible multi-stress response factor. The aim of this study was to explore the role of NR4A1 in counteracting JNK activation induced by ER stress or ROS and the related mechanism. qPCR, Western blotting, dual-luciferase reporter and ChIP assays were applied to detect gene expression or regulation by NR4A1. Immunofluorescence was used to detect a specific protein expression in ß-cells. Our data showed that NR4A1 reduced the phosphorylated JNK (p-JNK) in MIN6 cells encountering ER stress or ROS and reduced MKK4 protein in a proteasome-dependent manner. We found that NR4A1 increased the expression of cbl-b (an E3 ligase); knocking down cbl-b expression increased MKK4 and p-JNK levels under ER stress or ROS conditions. We elucidated that NR4A1 enhanced the transactivation of cbl-b promoter by physical association. We further confirmed that cbl-b expression in ß-cells was reduced in NR4A1-knockout mice compared with WT mice. NR4A1 down-regulates JNK activation by ER stress or ROS in ß-cells via enhancing cbl-b expression.
Subject(s)
Endoplasmic Reticulum Stress , Insulin-Secreting Cells/metabolism , JNK Mitogen-Activated Protein Kinases/metabolism , Nuclear Receptor Subfamily 4, Group A, Member 1/metabolism , Reactive Oxygen Species/metabolism , Animals , Cell Line , Gene Expression Regulation , Hydrogen Peroxide/metabolism , MAP Kinase Kinase 4/metabolism , Mice , Mice, Knockout , Models, Biological , Nuclear Receptor Subfamily 4, Group A, Member 1/genetics , Phosphorylation , Promoter Regions, Genetic , Protein Binding , UbiquitinationABSTRACT
BACKGROUND: En bloc transurethral resection (ERBT) is a major topic of discussion as an alternative to conventional transurethral resection (cTURBT) for the treatment of non-muscle-invasive bladder cancer (NMIBC) addressing the limitations of cTURBT. METHODS: We searched through electronic databases including Embase, Cochrane Library, MEDLINE, Web of Science, PubMed, and Google Scholar for articles published up to April 1, 2019; RevMan 5.3 was used to conduct this meta-analysis. Results were expressed as 95% confidence intervals (CI) and risk differences (RD). RESULTS: Nine trials met the inclusion criteria (n = 1,020 patients): 1 study was a randomized controlled trial including a total of 142 participants, 4 studies had a prospective paired design including 605 patients, and 4 studies were retrospective (n = 273 patients). Duration of continuous postoperative bladder irrigation (RD -0.16; 95% CI -3.47 to 0.28; I2 = 97%; p = 0.10) and operation time (RD 0.05; 95% CI -0.23 to 0.32; I2 = 79%; p = 0.74) were not significantly different between ERBT and cTURBT. However, hospitalization time (I2 = 96%; χ2 = 203.16; p = 0.01) and catheterization time (I2 = 95%; χ2 = 163.24; p = 0.02), as well as 24-month recurrence rate (I2 = 0%; χ2 = 0.98; p = 0.008) were significantly better using the ERBT scheme. The incidence of urethral stricture between both schemes (95% CI -0.03 to 0.02; p = 0.50) was not different, but complications such as obturator nerve reflex (95% CI 0.01 to 0.12; p < 0.00001) and bladder perforation (95% CI 0.05 to 0.59; p = 0.50) were less frequent in the ERBT group. CONCLUSION: ERBT is an effective treatment approach with some advantages for NMIBC. Our meta-analysis revealed that hospitalization time, catheterization time, and 24-month recurrence rate is superior in patients treated with ERBT than cTURBT, and ERBT patients also have a lower complication rate. Furthermore, ERBT improves the quality of tumor specimens and decreases the frequency of repeat transurethral bladder cancer resection. Further randomized controlled trials are needed to confirm our results.
Subject(s)
Cystectomy/methods , Urinary Bladder Neoplasms/surgery , Humans , Neoplasm Invasiveness , Urethra , Urinary Bladder Neoplasms/pathologyABSTRACT
Genome-wide association study results have linked ADCK1 genetic variation with paliperidone efficacy in a European cohort. However, the generalizability of this locus to non-European populations is unknown. Han Chinese schizophrenia patients (n = 159) were treated with paliperidone palmitate and symptom severity was assessed over 3 months. Examination of 13 ADCK1 genetic variants revealed two single nucleotide polymorphisms (rs12590199, rs11159291) and one haplotype (rs2364747-rs12590199) associated with paliperidone palmitate response. Future work into ADCK1's function and its potential interaction with paliperidone is warranted.
Subject(s)
Antipsychotic Agents/pharmacology , Paliperidone Palmitate/pharmacology , Pharmacogenomic Testing , Pharmacogenomic Variants , Protein Kinases/genetics , Schizophrenia/drug therapy , Treatment Outcome , Adult , Antipsychotic Agents/administration & dosage , China , Female , Follow-Up Studies , Humans , Male , Paliperidone Palmitate/administration & dosage , Polymorphism, Single Nucleotide , Schizophrenia/genetics , Young AdultABSTRACT
Analysis of transcriptome sequence data from eggs and second-stage juveniles (J2s) of sugar beet cyst nematode (SBCN, Heterodera schachtii) identified the full-length genome of a positive-sense single-stranded RNA virus, provisionally named sugar beet cyst nematode virus 1 (SBCNV1). The SBCNV1 sequence was detected in both eggs and J2s, indicating its possible vertical transmission. The 9503-nucleotide genome sequence contains a single long open reading frame, which was predicted to encode a polyprotein with conserved domains for picornaviral structural proteins proximal to its amino terminus and RNA helicase, cysteine proteinase and RNA-dependent RNA polymerase (RdRp) conserved domains proximal to its carboxyl terminus, hallmarks of viruses belonging to the order Picornavirales. Phylogenetic analysis of the predicted SBCNV1 RdRp amino acid sequence indicated that the SBCNV1 sequence is most closely related to members of the family Secoviridae, which includes genera of nematode-transmitted plant-infecting viruses. SBCNV1 represents the first fully sequenced viral genome from SBCN.
Subject(s)
Beta vulgaris/parasitology , Picornaviridae/classification , Picornaviridae/isolation & purification , Transcriptome , Tylenchoidea/virology , Animals , Genome, Viral , Molecular Sequence Annotation , Open Reading Frames , Phylogeny , Picornaviridae/genetics , RNA-Dependent RNA Polymerase/genetics , Sequence Analysis, DNA , Sequence Analysis, RNA , Sequence Homology, Amino Acid , Tylenchoidea/genetics , Tylenchoidea/growth & development , Viral Proteins/geneticsABSTRACT
Plant terpene synthase genes (TPSs) have roles in diverse biological processes. Here, we report the functional characterization of one member of the soybean TPS gene family, which was designated GmAFS. Recombinant GmAFS produced in Escherichia coli catalysed the formation of a sesquiterpene (E,E)-α-farnesene. GmAFS is closely related to (E,E)-α-farnesene synthase gene from apple, both phylogenetically and structurally. GmAFS was further investigated for its biological role in defence against nematodes and insects. Soybean cyst nematode (SCN) is the most important pathogen of soybean. The expression of GmAFS in a SCN-resistant soybean was significantly induced by SCN infection compared with the control, whereas its expression in a SCN-susceptible soybean was not changed by SCN infection. Transgenic hairy roots overexpressing GmAFS under the control of the CaMV 35S promoter were generated in an SCN-susceptible soybean line. The transgenic lines showed significantly higher resistance to SCN, which indicates that GmAFS contributes to the resistance of soybean to SCN. In soybean leaves, the expression of GmAFS was found to be induced by Tetranychus urticae (two-spotted spider mites). Exogenous application of methyl jasmonate to soybean plants also induced the expression of GmAFS in leaves. Using headspace collection combined with gas chromatography-mass spectrometry analysis, soybean plants that were infested with T. urticae were shown to emit a mixture of volatiles with (E,E)-α-farnesene as one of the most abundant constituents. In summary, this study showed that GmAFS has defence roles in both below-ground and above-ground organs of soybean against nematodes and insects, respectively.
Subject(s)
Glycine max/enzymology , Glycine max/parasitology , Insecta/physiology , Plant Proteins/metabolism , Plants, Genetically Modified/enzymology , Plants, Genetically Modified/parasitology , Pyrophosphatases/metabolism , Animals , Gene Expression Regulation, Plant , Nematoda/pathogenicity , Plant Proteins/genetics , Plants, Genetically Modified/genetics , Pyrophosphatases/genetics , Glycine max/geneticsABSTRACT
Soybean (Glycine max (L.) Merr.) salicylic acid methyl transferase (GmSAMT1) catalyses the conversion of salicylic acid to methyl salicylate. Prior results showed that when GmSAMT1 was overexpressed in transgenic soybean hairy roots, resistance is conferred against soybean cyst nematode (SCN), Heterodera glycines Ichinohe. In this study, we produced transgenic soybean overexpressing GmSAMT1 and characterized their response to various SCN races. Transgenic plants conferred a significant reduction in the development of SCN HG type 1.2.5.7 (race 2), HG type 0 (race 3) and HG type 2.5.7 (race 5). Among transgenic lines, GmSAMT1 expression in roots was positively associated with SCN resistance. In some transgenic lines, there was a significant decrease in salicylic acid titer relative to control plants. No significant seed yield differences were observed between transgenics and control soybean plants grown in one greenhouse with 22 °C day/night temperature, whereas transgenic soybean had higher yield than controls grown a warmer greenhouse (27 °C day/23 °C night) temperature. In a 1-year field experiment in Knoxville, TN, there was no significant difference in seed yield between the transgenic and nontransgenic soybean under conditions with negligible SCN infection. We hypothesize that GmSAMT1 expression affects salicylic acid biosynthesis, which, in turn, attenuates SCN development, without negative consequences to soybean yield or other morphological traits. Thus, we conclude that GmSAMT1 overexpression confers broad resistance to multiple SCN races, which would be potentially applicable to commercial production.
Subject(s)
Glycine max/genetics , Glycine max/parasitology , Plant Proteins/metabolism , Plants, Genetically Modified/genetics , Plants, Genetically Modified/parasitology , Tylenchoidea/physiology , Animals , Disease Resistance/genetics , Plant Diseases/genetics , Plant Diseases/parasitology , Plant Proteins/genetics , Plants, Genetically Modified/metabolism , Quantitative Trait Loci , Salicylic Acid/metabolism , Glycine max/metabolismABSTRACT
Multi-frequency time-of-flight (ToF) cameras have been used to recover the transient time profiles of optical responses such that multipath interference can be separated. The resolution of the recovered time profiles is limited by the highest modulation frequency. Here, we demonstrate a method based on log-sum sparsity regularization to recover transient time profiles of specular reflections. We show that it improves the ability of separating pulses better than the state-of-the-art regularization methods. As an application, we demonstrate the encoding and decoding of hidden images using mirror reflections.
ABSTRACT
A positive myocardial inotropic effect achieved using HNO/NO(-) , compared with NOâ , triggered attempts to explore novel nitroxyl donors for use in clinical applications in vascular and myocardial pharmacology. To develop M-NO complexes for nitroxyl chemistry and biology, modulation of direct nitroxyl-transfer reactivity of dinitrosyl iron complexes (DNICs) is investigated in this study using a Fe(III) -porphyrin complex and proteins as a specific probe. Stable dinuclear {Fe(NO)2 }(9) DNIC [Fe(µ-(Me) Pyr)(NO)2 ]2 was discovered as a potent nitroxyl donor for nitroxylation of Fe(III) -heme centers through an associative mechanism. Beyond the efficient nitroxyl transfer, transformation of DNICs into a chemical biology probe for nitroxyl and for pharmaceutical applications demands further efforts using in vitro/in vivo studies.