PROTEIN L-ISOASPARTYL METHYLTRANSFERASE protects enolase dysfunction by repairing isoaspartyl-induced damage and is positively implicated in agronomically important seed traits.

The protein-repairing enzyme (PRE) PROTEIN L-ISOASPARTYL METHYLTRANSFERASE (PIMT) influences seed vigor by repairing isoaspartyl-mediated protein damage in seeds. However, PIMTs function in other seed traits, and the mechanisms by which PIMT affects such seed traits are still poorly understood. Herein, through molecular, biochemical, and genetic studies using overexpression and RNAi lines in Oryza sativa and Arabidopsis thaliana, we demonstrate that PIMT not only affects seed vigor but also affects seed size and weight by modulating enolase (ENO) activity. We have identified ENO2, a glycolytic enzyme, as a PIMT interacting protein through Y2H cDNA library screening, and this interaction was further validated by BiFC and co-immunoprecipitation assay. We show that mutation or suppression of ENO2 expression results in reduced seed vigor, seed size, and weight. We also proved that ENO2 undergoes isoAsp modification that affects its activity in both in vivo and in vitro conditions. Further, using MS/MS analyses, amino acid residues that undergo isoAsp modification in ENO2 were identified. We also demonstrate that PIMT repairs such isoAsp modification in ENO2 protein, protecting its vital cellular functions during seed maturation and storage, and plays a vital role in regulating seed size, weight, and seed vigor. Taken together, our study identified ENO2 as a novel substrate of PIMT, and both ENO2 and PIMT in turn implicate in agronomically important seed traits.

Self-powered, wide spectral UV response out-of-plane photodetector based on ZnO/porous silicon heterostructure.

The photoresponse of the ZnO/porous silicon (p-Si) heterojunction is studied in an out-of-plane contact configuration. p-Si substrate is fabricated by anodic etching followed by the electrochemical deposition of ZnO NR film, forming ZnO/p-Si heterojunction. XRD study is done to understand the effect of the substrate on ZnO film growth in terms of strain and crystal size. UV-vis absorbance spectrum shows a broad absorption for wavelengths from 230 to 380 nm. The PL emission shows two narrow and prominent electron transition peaks at 263 and 383 nm and a peak of ∼550 nm corresponding to defects. The 263 nm wavelength responsivity of the photodetector from UV-vis and PL data suggests the presence of a defective SiOxas an intermediate layer between ZnO and p-Si. The photodetector is measured for its spectral selectivity and responsivity for both 266 and 370 nm. Under self-powered conditions, the device shows a low dark current of a few nA and enhancement of ∼100 nA and ∼1.37µA for both wavelengths. A responsivity of 527 mA W-1and 10.5µA W-1and detectivity of 2.5 × 1010and 2.9 × 107Jones at 1 V bias under 266 and 370 nm UV illumination are observed. The fast rise/decay time of 67/65 ms and 29/18 ms is observed for the self-powered condition of the device under both wavelengths respectively. The photoresponse of the modified ZnO/SiOx/p-Si heterojunction for both wavelengths is analyzed for the electron transfer mechanism using the heterojunction band bending model. The short circuit current and open circuit voltage of the photodetector is estimated to be 293 nA, 56.33 mV, and 13.63µA, 124.8 mV for 266 and 370 nm, respectively. It is concluded that the 266 nm responsivity comes from the defects in SiOxintermediate layer, and the photocurrent generated in the device is due to tunneling across the junction.

Validation and identification of promising gene specific markers governing foliar disease resistance in groundnut (Arachis hypogaea L.).

BACKGROUND: Groundnut is vulnerable to the major foliar fungal disease viz., late leaf spot (LLS) and rust in kharif season, which results in severe yield losses. Until now, LLS and rust resistance linked markers were developed based on GPBD 4 as a major donor source and were validated in its derivatives only, which restricted their use in marker assisted selection (MAS) involving other donors. METHODS AND RESULTS: The current study focused to validate LLS and rust resistance linked markers employing advanced breeding lines of F6 generation, derived from nine different crosses involving nine diverse parents, to identify potential markers for marker-assisted breeding of LLS and rust resistance in groundnut. Out of 28-trait linked markers used for validation, 8 were polymorphic (28.57%). Marker-trait association (MTA) and Single Marker Analysis (SMA) revealed that the SSR marker pPGPseq5D05 is significantly associated with both LLS (15.8% PVE) and rust (17.5% PVE) resistance, whereas, the marker IPAHM103 is tightly linked with rust resistance (26.8% PVE) alone. In silico analysis revealed that the marker gene for IPAHM103 is a zinc finger protein and the marker gene for pPGPseq5D05 is an ADP-ribosylation factor GTPase-activating protein. Both these protein products impart resistance or tolerance to biotic stress in crop plants. Two other markers namely, GMLQ975 and pPGPseq13A10 were also found to be associated with LLS resistance explaining MTA up to 60%. CONCLUSION: These gene specific markers will enable us to screen more number of germplasm lines or newly developed lines in MAS schemes for LLS and rust resistance using a wide range of resistant sources.

PyFaceWipe: a new defacing tool for almost any MRI contrast.

RATIONALE AND OBJECTIVES: Defacing research MRI brain scans is often a mandatory step. With current defacing software, there are issues with Windows compatibility and researcher doubt regarding the adequacy of preservation of brain voxels in non-T1w scans. To address this, we developed PyFaceWipe, a multiplatform software for multiple MRI contrasts, which was evaluated based on its anonymisation ability and effect on downstream processing. MATERIALS AND METHODS: Multiple MRI brain scan contrasts from the OASIS-3 dataset were defaced with PyFaceWipe and PyDeface and manually assessed for brain voxel preservation, remnant facial features and effect on automated face detection. Original and PyFaceWipe-defaced data from locally acquired T1w structural scans underwent volumetry with FastSurfer and brain atlas generation with ANTS. RESULTS: 214 MRI scans of several contrasts from OASIS-3 were successfully processed with both PyFaceWipe and PyDeface. PyFaceWipe maintained complete brain voxel preservation in all tested contrasts except ASL (45%) and DWI (90%), and PyDeface in all tested contrasts except ASL (95%), BOLD (25%), DWI (40%) and T2* (25%). Manual review of PyFaceWipe showed no failures of facial feature removal. Pinna removal was less successful (6% of T1 scans showed residual complete pinna). PyDeface achieved 5.1% failure rate. Automated detection found no faces in PyFaceWipe-defaced scans, 19 faces in PyDeface scans compared with 78 from the 224 original scans. Brain atlas generation showed no significant difference between atlases created from original and defaced data in both young adulthood and late elderly cohorts. Structural volumetry dice scores were ≥ 0.98 for all structures except for grey matter which had 0.93. PyFaceWipe output was identical across the tested operating systems. CONCLUSION: PyFaceWipe is a promising multiplatform defacing tool, demonstrating excellent brain voxel preservation and competitive defacing in multiple MRI contrasts, performing favourably against PyDeface. ASL, BOLD, DWI and T2* scans did not produce recognisable 3D renders and hence should not require defacing. Structural volumetry dice scores (≥ 0.98) were higher than previously published FreeSurfer results, except for grey matter which were comparable. The effect is measurable and care should be exercised during studies. ANTS atlas creation showed no significant effect from PyFaceWipe defacing.

Removal of emerging contaminants in conventional and advanced biological wastewater treatment plants in India-a comparison of treatment technologies.

Emerging contaminants (ECs) are a growing concern for the environment and human health. The study investigates 20 commonly reported ECs in 10 wastewater treatment plants (WWTPs) in urban to semi-urban settlements of north India over two years in the summer and winter. The selected plants were based on waste stabilization pond (WSP), up-flow anaerobic sludge blanket (UASB), activated sludge process (ASP), anoxic-aerobic process (AO), anaerobic-anoxic-oxic process, biodenipho process, sequencing batch reactor, and densadeg-biofor process. Of the 20 ECs, all 20 were identified in the influent and effluent, and 13 were identified in the final sludge on at least one occasion. The concentration in the influent, effluent, and sludge varied in the range from 2.5 ng/L to 77.4 µg/L, below limit of detection (LOD) to 1.984 µg/L, and < LOD to 1.41 µg/g, respectively. Acetaminophen and caffeine were predominately detected in the influent, whereas naproxen, ciprofloxacin, and carbamazepine were predominant in the effluent. The total removal in the plants was found in the range of 40.3-68.6%, mainly attributed to biodegradation/biotransformation. Removal of ECs by WWTPs, ranked by a relative removal criterion, followed the order: Biological nutrient removal based plants > WSP > UASB > densadeg-biofor > AO > ASP > combitreat-SBR. The risk assessment showed the risk to algae from antibiotics and triclosan, daphnia from triclosan, and fish from triclosan and hormones.

Prediction of MYCN Gene Amplification in Pediatric Neuroblastomas: Development of a Deep Learning-Based Tool for Automatic Tumor Segmentation and Comparative Analysis of Computed Tomography-Based Radiomics Features Harmonization.

OBJECTIVE: MYCN oncogene amplification is closely linked to high-grade neuroblastoma with poor prognosis. Accurate quantification is essential for risk assessment, which guides clinical decision making and disease management. This study proposes an end-to-end deep-learning framework for automatic tumor segmentation of pediatric neuroblastomas and radiomics features-based classification of MYCN gene amplification. METHODS: Data from pretreatment contrast-enhanced computed tomography scans and MYCN status from 47 cases of pediatric neuroblastomas treated at a tertiary children's hospital from 2009 to 2020 were reviewed. Automated tumor segmentation and grading pipeline includes (1) a modified U-Net for tumor segmentation; (2) extraction of radiomic textural features; (3) feature-based ComBat harmonization for removal of variabilities across scanners; (4) feature selection using 2 approaches, namely, ( a ) an ensemble approach and ( b ) stepwise forward-and-backward selection method using logistic regression classifier; and (5) radiomics features-based classification of MYCN gene amplification using machine learning classifiers. RESULTS: Median train/test Dice score for modified U-Net was 0.728/0.680. The top 3 features from the ensemble approach were neighborhood gray-tone difference matrix (NGTDM) busyness, NGTDM strength, and gray-level run-length matrix (GLRLM) low gray-level run emphasis, whereas those from the stepwise approach were GLRLM low gray-level run emphasis, GLRLM high gray-level run emphasis, and NGTDM coarseness. The top-performing tumor classification algorithm achieved a weighted F1 score of 97%, an area under the receiver operating characteristic curve of 96.9%, an accuracy of 96.97%, and a negative predictive value of 100%. Harmonization-based tumor classification improved the accuracy by 2% to 3% for all classifiers. CONCLUSION: The proposed end-to-end framework achieved high accuracy for MYCN gene amplification status classification.

The Interaction Between Brain-Derived Neurotrophic Factor Levels and Alcohol Consumption, Sleep Disturbance and Sex-Hormones in Alcohol Use Disorders.

AIMS: Brain-derived neurotrophic factor (BDNF) levels may be associated with alcohol use disorders (AUD) and alcohol consumption, correlate with sleep disturbance and be influenced by sex differences and sex hormones. These associations have not been examined in a single sample accounting for all these factors. METHODS: Data from 190 participants (29.4% female) with AUD were utilized. Sleep quality, craving intensity, depression, anxiety and alcohol consumption were assessed using the Pittsburgh Sleep Quality Index (PSQI), Penn Alcohol Craving Scale (PACS), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7) and Timeline Follow Back for 90 days(TLFB 90). Inventory of Drug Taking Situations (IDTS) assessed the tendency to drink in positive/negative emotional states. Serum BDNF (sBDNF) and plasma sex hormones (estrogen, progesterone, testosterone, FSH and SHBG) were measured. Pearson correlation analyses were used to examine the association between sBDNF and these measures in the entire sample and in men and women separately. Higher order interaction effects between these factors were evaluated for their association with sBDNF using a backward selection model. RESULTS: No significant correlations between sBDNF levels and sex hormones, PSQI, PHQ-9, PACS, IDTS scores and alcohol consumption were found (all P-values > 0.05). sBDNF levels were negatively correlated with GAD-7 scores in men (r = -0.1841; P = 0.03). When considering all quadratic and two-way interactions among PSQI, PHQ-9, GAD-7, mean and max drinks/day, number of drinking days, heavy drinking days, and sex no higher order moderating effects of sBDNF levels were found. CONCLUSION: Our study revealed no significant associations between sBDNF and alcohol measures, sleep, depression and sex hormones suggesting limited utility as a biomarker.

Fate of emerging contaminants in a sequencing batch reactor and potential of biological activated carbon as tertiary treatment for the removal of persisting contaminants.

The study aims to understand the occurrence and removal of 20 emerging contaminants (ECs) in each unit process of a sequencing batch reactor-based wastewater treatment plant (WWTP) and explore the potential of biological activated carbon (BAC) for the treatment of residual ECs and organic matter in the secondary effluent. Analgesic-acetaminophen, anti-inflammatory drug-ibuprofen, and stimulant-caffeine were detected at high concentrations in the influent. Most of the removal was observed in the biological treatment stage in the SBR basins. The mass load of the ECs was 2.93 g/d in the secondary effluent and 0.4 g/d in the final sludge, while the total removal of the mass load of ECs till the secondary treatment stage was 93.22%. 12 of the 20 ECs were removed by more than 50%, while carbamazepine (negative removal), sulfamethoxazole, and trimethoprim were removed by less than 20%. As a polishing step and to remove residual ECs, two BAC units were studied for 11,000 bed volumes (324 days). Packed column studies on granular activated carbon were conducted, and GAC development to BAC was monitored. SEM and FTIR were used to confirm and characterize the BAC. The BAC appeared to be more hydrophobic than the GAC. The BAC removed 78.4% and 40% of the dissolved ECs and organic carbon at an optimum EBCT of 25 min. Carbamazepine, sulfamethoxazole, and trimethoprim were removed by 61.5, 84, and 52.2%, respectively. Parallel column tests revealed adsorption as an important mechanism for the removal of positively charged compounds. The results indicate that the BAC is an effective tertiary/polishing technique for removing organic and micropollutants in the secondary wastewater effluent.

Structural Insights into Dihydroxylation of Terephthalate, a Product of Polyethylene Terephthalate Degradation.

Biodegradation of terephthalate (TPA) is a highly desired catabolic process for the bacterial utilization of this polyethylene terephthalate (PET) depolymerization product, but to date, the structure of terephthalate dioxygenase (TPDO), a Rieske oxygenase (RO) that catalyzes the dihydroxylation of TPA to a cis-diol, is unavailable. In this study, we characterized the steady-state kinetics and first crystal structure of TPDO from Comamonas testosteroni KF1 (TPDOKF1). TPDOKF1 exhibited substrate specificity for TPA (kcat/Km = 57 ± 9 mM-1 s-1). The TPDOKF1 structure harbors characteristic RO features as well as a unique catalytic domain that rationalizes the enzyme's function. The docking and mutagenesis studies reveal that its substrate specificity for TPA is mediated by the Arg309 and Arg390 residues, positioned on opposite faces of the active site. Additionally, residue Gln300 is also proven to be crucial for the activity, as its mutation to alanine decreases the activity (kcat) by 80%. This study delineates the structural features that dictate the substrate recognition and specificity of TPDO. IMPORTANCE Global plastic pollution has become the most pressing environmental issue. Recent studies on enzymes depolymerizing polyethylene terephthalate plastic into terephthalate (TPA) show some potential for tackling this. Microbial utilization of this released product, TPA, is an emerging and promising strategy for waste-to-value creation. Research in the last decade has identified terephthalate dioxygenase (TPDO) as being responsible for initiating the enzymatic degradation of TPA in a few Gram-negative and Gram-positive bacteria. Here, we determined the crystal structure of TPDO from Comamonas testosteroni KF1 and revealed that it possesses a unique catalytic domain featuring two basic residues in the active site to recognize TPA. Biochemical and mutagenesis studies demonstrated the crucial residues responsible for the substrate specificity of this enzyme.

CAFT: a deep learning-based comprehensive abdominal fat analysis tool for large cohort studies.

BACKGROUND: There is increasing appreciation of the association of obesity beyond co-morbidities, such as cancers, Type 2 diabetes, hypertension, and stroke to also impact upon the muscle to give rise to sarcopenic obesity. Phenotypic knowledge of obesity is crucial for profiling and management of obesity, as different fat-subcutaneous adipose tissue depots (SAT) and visceral adipose tissue depots (VAT) have various degrees of influence on metabolic syndrome and morbidities. Manual segmentation is time consuming and laborious. Study focuses on the development of a deep learning-based, complete data processing pipeline for MRI-based fat analysis, for large cohort studies which include (1) data augmentation and preprocessing (2) model zoo (3) visualization dashboard, and (4) correction tool, for automated quantification of fat compartments SAT and VAT. METHODS: Our sample comprised 190 healthy community-dwelling older adults from the Geri-LABS study with mean age of 67.85 ± 7.90 years, BMI 23.75 ± 3.65 kg/m2, 132 (69.5%) female, and mainly Chinese ethnicity. 3D-modified Dixon T1-weighted gradient-echo MR images were acquired. Residual global aggregation-based 3D U-Net (RGA-U-Net) and standard 3D U-Net were trained to segment SAT, VAT, superficial and deep subcutaneous adipose tissue depots (SSAT and DSAT). Manual segmentation from 26 subjects was used as ground truth during training. Data augmentations, random bias, noise and ghosting were carried out to increase the number of training datasets to 130. Segmentation accuracy was evaluated using Dice and Hausdorff metrics. RESULTS: The accuracy of segmentation was SSAT:0.92, DSAT:0.88 and VAT:0.9. Average Hausdorff distance was less than 5 mm. Automated segmentation significantly correlated R2 > 0.99 (p < 0.001) with ground truth for all 3-fat compartments. Predicted volumes were within ± 1.96SD from Bland-Altman analysis. CONCLUSIONS: DL-based, comprehensive SSAT, DSAT, and VAT analysis tool showed high accuracy and reproducibility and provided a comprehensive fat compartment composition analysis and visualization in less than 10 s.

CT-based morphologic and radiomics features for the classification of MYCN gene amplification status in pediatric neuroblastoma.

PURPOSE: MYCN onco-gene amplification in neuroblastoma confers patients to the high-risk disease category for which prognosis is poor and more aggressive multimodal treatment is indicated. This retrospective study leverages machine learning techniques to develop a computed tomography (CT)-based model incorporating semantic and non-semantic features for non-invasive prediction of MYCN amplification status in pediatric neuroblastoma. METHODS: From 2009 to 2020, 54 pediatric patients treated for neuroblastoma at a specialized children's hospital with pre-treatment contrast-enhanced CT and MYCN status were identified (training cohort, n = 44; testing cohort, n = 10). Six morphologic features and 107 quantitative gray-level texture radiomics features extracted from manually drawn volume-of-interest were analyzed. Following feature selection and class balancing, the final predictive model was developed with eXtreme Gradient Boosting (XGBoost) algorithm. Accumulated local effects (ALE) plots were used to explore main effects of the predictive features. Tumor texture maps were also generated for visualization of radiomics features. RESULTS: One morphologic and 2 radiomics features were selected for model building. The XGBoost model from the training cohort yielded an area under the receiver operating characteristics curve (AUC-ROC) of 0.930 (95% CI, 0.85-1.00), optimized F1-score of 0.878, and Matthews correlation coefficient (MCC) of 0.773. Evaluation on the testing cohort returned AUC-ROC of 0.880 (95% CI, 0.64-1.00), optimized F1-score of 0.933, and MCC of 0.764. ALE plots and texture maps showed higher "GreyLevelNonUniformity" values, lower "Strength" values, and higher number of image-defined risk factors contribute to higher predicted probability of MYCN amplification. CONCLUSION: The machine learning model reliably classified MYCN amplification in pediatric neuroblastoma and shows potential as a surrogate imaging biomarker.

Presence of enlarged perivascular spaces is associated with reduced processing speed in asymptomatic, working-aged adults.

BACKGROUND: Enlarged perivascular spaces (ePVS) and white matter hyperintensities (WMHs) are recognised neuroimaging lesions for symptomatic and/or occult cerebral small vessel disease (CSVD) that are linked with the predisposition to cardiocerebrovascular risk and neurocognitive impairment. This study aimed to determine the interrelation between the WMHs and ePVS, neurocognition, and cardiocerebrovascular risk profiles in asymptomatic working-aged adults at a single-center population-based cohort. METHODS: Fifty-four asymptomatic subjects (mean age: 39.6 ± 11.6 years) with low-to-moderate cardiocerebrovascular risk measured by QRISK3 prediction score were recruited and underwent neurocognitive evaluation and 3T MRI brain scan. Contour plot with multiple logistic and linear regression were utilized to study the interrelation between the variables. RESULTS: The presence of WMHs and ePVS was associated with hypertension, systolic blood pressure, QRISK3 score, and age, whereby asymptomatic older subjects had higher prevalence for WHMs and ePVS (mean age: WMHs [46.6 ± 12.2 years]; ePVS [43.12 ± 12.2 years]). Higher ePVS load and reduced hippocampal volume among ePVS subjects was associated with reduced processing speed (odd ratio, 1.06; 95% confidence interval: 1.00 to 1.13) and reduced working memory performance (standardized ß coefficients, -0.46 [95% CI: 0.46 to 12.1], p < 0.05), respectively. CONCLUSIONS: Albeit from a single center in the suburban east coast peninsular Malaysia, this study is to first from the region to highlight the subtle impacts of occult CSVD manifestations (WMHs and ePVS) on some aspects of neurocognition in an otherwise asymptomatic, relatively young working-aged adults with low-to-moderate cardiocerebrovascular risk scores.

Arabidopsis protein l-ISOASPARTYL METHYLTRANSFERASE repairs isoaspartyl damage to antioxidant enzymes and increases heat and oxidative stress tolerance.

Stressful environments accelerate the formation of isoaspartyl (isoAsp) residues in proteins, which detrimentally affect protein structure and function. The enzyme PROTEIN l-ISOASPARTYL METHYLTRANSFERASE (PIMT) repairs other proteins by reverting deleterious isoAsp residues to functional aspartyl residues. PIMT function previously has been elucidated in seeds, but its role in plant survival under stress conditions remains undefined. Herein, we used molecular, biochemical, and genetic approaches, including protein overexpression and knockdown experiments, in Arabidopsis to investigate the role of PIMTs in plant growth and survival during heat and oxidative stresses. We demonstrate that these stresses increase isoAsp accumulation in plant proteins, that PIMT activity is essential for restricting isoAsp accumulation, and that both PIMT1 and PIMT2 play an important role in this restriction and Arabidopsis growth and survival. Moreover, we show that PIMT improves stress tolerance by facilitating efficient reactive oxygen species (ROS) scavenging by protecting the functionality of antioxidant enzymes from isoAsp-mediated damage during stress. Specifically, biochemical and MS/MS analyses revealed that antioxidant enzymes acquire deleterious isoAsp residues during stress, which adversely affect their catalytic activities, and that PIMT repairs the isoAsp residues and thereby restores antioxidant enzyme function. Collectively, our results suggest that the PIMT-mediated protein repair system is an integral part of the stress-tolerance mechanism in plants, in which PIMTs protect antioxidant enzymes that maintain proper ROS homeostasis against isoAsp-mediated damage in stressful environments.

Early postnatal irradiation-induced age-dependent changes in adult mouse brain: MRI based characterization.

BACKGROUND: Brain radiation exposure, in particular, radiotherapy, can induce cognitive impairment in patients, with significant effects persisting for the rest of their life. However, the main mechanisms leading to this adverse event remain largely unknown. A study of radiation-induced injury to multiple brain regions, focused on the hippocampus, may shed light on neuroanatomic bases of neurocognitive impairments in patients. Hence, we irradiated BALB/c mice (male and female) at postnatal day 3 (P3), day 10 (P10), and day 21 (P21) and investigated the long-term radiation effect on brain MRI changes and hippocampal neurogenesis. RESULTS: We found characteristic brain volume reductions in the hippocampus, olfactory bulbs, the cerebellar hemisphere, cerebellar white matter (WM) and cerebellar vermis WM, cingulate, occipital and frontal cortices, cerebellar flocculonodular WM, parietal region, endopiriform claustrum, and entorhinal cortex after irradiation with 5 Gy at P3. Irradiation at P10 induced significant volume reduction in the cerebellum, parietal region, cingulate region, and olfactory bulbs, whereas the reduction of the volume in the entorhinal, parietal, insular, and frontal cortices was demonstrated after irradiation at P21. Immunohistochemical study with cell division marker Ki67 and immature marker doublecortin (DCX) indicated the reduced cell division and genesis of new neurons in the subgranular zone of the dentate gyrus in the hippocampus after irradiation at all three postnatal days, but the reduction of total granule cells in the stratum granulosun was found after irradiation at P3 and P10. CONCLUSIONS: The early life radiation exposure during different developmental stages induces varied brain pathophysiological changes which may be related to the development of neurological and neuropsychological disorders later in life.

Increased Patient Safety-Related Incidents Following the Transition into Daylight Savings Time.

BACKGROUND: "Spring forward," the start of daylight savings time (DST), reduces sleep opportunity by an hour. Insufficient sleep in healthcare workers resulting from the spring forward time change could potentially result in an increase in medical errors. OBJECTIVE: We examined the change in reported patient safety-related incidents (SRIs), in the week following the transition into and out of DST over a period of 8 years. DESIGN: Observational study SETTING: A US-based large healthcare organization with sites across multiple states MEASUREMENTS: Voluntarily reported SRIs that occurred 7 days prior to and following the spring and fall time changes for years 2010-2017 were ascertained. SRIs likely resulting from human error were identified separately. The changes in the number of SRIs (either all SRIs or SRIs restricted to those likely resulting from human error) from the week before and after the time change (either spring or fall) were modeled using a negative binomial mixed model with a random effect to correct for non-independent observations in consecutive weeks. RESULTS: Over the 8-year period, we observed 4.2% (95% CI: - 1.1 to 9.7%; p = 0.12) and 8.8% (95% CI: - 2.5 to 21.5%; p = 0.13) increases in overall SRIs in the 7 days following DST when compared with 7 days prior for spring and fall, respectively. By restricting to SRIs likely resulting from human errors, we observed 18.7% (95% CI: 5.6 to 33.6%; p = 0.004) and 4.9% (95% CI: - 1.3 to 11.5%; p = 0.12) increases for spring and fall, respectively. CONCLUSION: Policy makers and healthcare organizations should evaluate delayed start of shifts or other contingency measures to mitigate the increased risk of SRIs during transition to DST in spring.

Narciclasine attenuates diet-induced obesity by promoting oxidative metabolism in skeletal muscle.

Obesity develops when caloric intake exceeds metabolic needs. Promoting energy expenditure represents an attractive approach in the prevention of this fast-spreading epidemic. Here, we report a novel pharmacological strategy in which a natural compound, narciclasine (ncls), attenuates diet-induced obesity (DIO) in mice by promoting energy expenditure. Moreover, ncls promotes fat clearance from peripheral metabolic tissues, improves blood metabolic parameters in DIO mice, and protects these mice from the loss of voluntary physical activity. Further investigation suggested that ncls achieves these beneficial effects by promoting a shift from glycolytic to oxidative muscle fibers in the DIO mice thereby enhancing mitochondrial respiration and fatty acid oxidation (FAO) in the skeletal muscle. Moreover, ncls strongly activates AMPK signaling specifically in the skeletal muscle. The beneficial effects of ncls treatment in fat clearance and AMPK activation were faithfully reproduced in vitro in cultured murine and human primary myotubes. Mechanistically, ncls increases cellular cAMP concentration and ADP/ATP ratio, which further lead to the activation of AMPK signaling. Blocking AMPK signaling through a specific inhibitor significantly reduces FAO in myotubes. Finally, ncls also enhances mitochondrial membrane potential and reduces the formation of reactive oxygen species in cultured myotubes.

Correction to: Identification of emerging contaminants and their transformation products in a moving bed biofilm reactor (MBBR)-based drinking water treatment plant around River Yamuna in India.

The original version of this article unfortunately contains mistakes introduced during the production phase. Figures 7, 8, and 10 were incorrectly captured.

Identification of emerging contaminants and their transformation products in a moving bed biofilm reactor (MBBR)-based drinking water treatment plant around River Yamuna in India.

The prevalence of emerging contaminants of concern in water regimes is very common these days. High anthropogenic intervention is leading to occurrence of various types of microcontaminants of concern in drinking water systems. Their removal using conventional form of treatment systems employed in water treatment plants is not widely researched upon. Their fate in the conventional as well as advanced water treatment system needs to be focused upon for efficient and safe water disposal. Some compounds may leave the system unchanged or some might transform into much more toxic byproduct. Moreover, understanding level of occurrence of these emerging contaminants in source water bodies is also quintessential for assessing their fate in treatment plant itself as well as in the final treated water. Here in this study, the occurrence and removal of various classes of emerging contaminants were investigated in a moving bed biofilm reactor (MBBR)-based advanced drinking water treatment plant (ADWTP) alongside one conventional drinking water treatment plant, both of which use River Yamuna as the source of water. Non-target analysis utilizing high-performance liquid chromatography combined with time of flight (HPLC-QToF) identified more than 300 compounds. Pharmaceuticals accounted for a major fraction (58%) of the identified compounds, followed by plasticizers and insecticides. Nine parent compound and their transformation products were additionally identified using solid-phase extraction followed by analysis using gas chromatography mass spectrometry and HPLC-QToF. The degradation pathway of the parent compounds in MBBR-based ADWTP was also analyzed in depth. The efficiency of each unit process of MBBR-based drinking water treatment plant was studied in terms of removal of few emerging contaminants. Pharmaceutical compound like diclofenac supposedly was persistent, even, toward the end of the treatment train. Semi-quantitative analysis revealed ineffective removal of pyridine, hydrochlorothiazide, and diethyl phthalate in the outlet of ADWTP. ADWTP was able to remove a few emerging contaminants, but a few were recalcitrant. Likewise, it was established that although some parent compounds were degraded, much more toxic transformation products were formed and were prevalent at the end of the treatment.

A simple and sensitive SYBR Gold-based assay to quantify DNA-protein interactions.

A simple, accessible, and inexpensive assay to quantify the strength of DNA-protein interactions was developed. The assay relies on capturing DNA-protein complexes using an affinity resin that binds tagged, recombinant proteins. Sequential washes with filtration spin cups and centrifugation remove non-specific interactions in a gentle, uniform manner and a final elution isolates specific DNA-protein complexes. SYBR Gold nucleic acid stain is added to the eluted product and the fluorescence intensity accurately quantifies the amount of captured DNA, ultimately illustrating the relative strength of the DNA-protein interaction. The major utility of the assay resides in the versatility and quantitative nature of the SYBR Gold:nucleic acid interaction, eliminating the need for customized or labeled oligos and permitting relatively inexpensive quantification of binding capacity. The assay also employs DNA-protein complex capture by the very common purification tag, 6xHis, but other tags could likely be utilized. Further, SYBR Gold fluorescence is compatible with a wide variety of instruments, including UV transilluminators, a staple to any molecular biology laboratory. This assay was used to compare the binding capacities of different auxin response factor (ARF) transcription factors to various dsDNA targets, including the classical AuxRE motif and several divergent sequences. Results from dose-response assays suggest that different ARF proteins might show distinct comparative affinities for AuxRE variants, emphasizing that specific ARF-AuxRE binding strengths likely contribute to the complex and fine-tuned cellular auxin response.

Methadone-Related Delirium: Prevalence, Causes, and Outcomes.

Goals consist of determining 5-year prevalence and recurrence of methadone-related delirium (MRD), along with causes, treatments, and outcomes. Sample comprised 81 patients in methadone maintenance treatment. Criteria for MRD encompassed delirium with high methadone serum levels plus alleviation of delirium upon lowering methadone serum levels. MRD occurred in 14 cases who had 25 episodes. MRD precipitants included physician prescribing (i.e., excessive methadone or medications slowing methadone metabolism), drug misuse, and renal-fluid alterations. Social affiliation (housing with family, intimate partner) reduced MRD; employment increased MRD. Recovery occurred in 23/25 episodes of MRD; two episodes progressed to dementia. Obtaining serum methadone levels fostered prompt recognition.