Post-translational modification (PTM) is a critical and rapid mechanism to regulate all the major cellular processes through the modification of diverse protein substrates. Substrate-specific ...covalent attachment of ubiquitin and Small Ubiquitin-Like Modifier (SUMO) with the target proteins, known as ubiquitination and SUMOylation, respectively, are crucial PTMs that regulate almost every process in the cell by modulating the stability and fidelity of the proteins. Ubiquitination and SUMOylation play a very significant role to provide tolerance to the plants in adverse environmental conditions by activating/deactivating the pre-existing proteins to a great extent. We reviewed the importance of ubiquitination and SUMOylation in plants, implicating its prospects in various abiotic stress regulations. An exhaustive study of molecular mechanisms of ubiquitination and SUMOylation of plant proteins and their role will contribute to the understanding of physiology underlying mitigation of the abiotic stresses and survival in plants. It will be helpful to strategize the improvement of crops for abiotic stress tolerance.
ObjectivesTo estimate the potential impact of expanding services offered by the Joint Effort for Elimination of Tuberculosis (JEET), the largest private sector engagement initiative for tuberculosis ...(TB) in India.DesignWe developed a mathematical model of TB transmission dynamics, coupled with a cost model.SettingAhmedabad and New Delhi, two cities with contrasting levels of JEET coverage.ParticipantsEstimated patients with TB in Ahmedabad and New Delhi.InterventionsWe investigated the epidemiological impact of expanding three different public–private support agency (PPSA) services: provider recruitment, uptake of cartridge-based nucleic acid amplification tests and uptake of adherence support mechanisms (specifically government supplied fixed-dose combination drugs), all compared with a continuation of current TB services.ResultsOur results suggest that in Delhi, increasing the use of adherence support mechanisms among private providers should be prioritised, having the lowest incremental cost-per-case-averted between 2020 and 2035 of US$170 000 (US$110 000–US$310 000). Likewise in Ahmedabad, increasing provider recruitment should be prioritised, having the lowest incremental cost-per-case averted of US$18 000 (US$12 000–US$29 000).ConclusionResults illustrate how intervention priorities may vary in different settings across India, depending on local conditions, and the existing degree of uptake of PPSA services. Modelling can be a useful tool for identifying these priorities for any given setting.
G protein-coupled receptors (GPCRs) constitute the largest family of transmembrane proteins in metazoans that mediate the regulation of various physiological responses to discrete ligands through ...heterotrimeric G protein subunits. The existence of GPCRs in plant is contentious, but their comparable crucial role in various signaling pathways necessitates the identification of novel remote GPCR-like proteins that essentially interact with the plant G protein α subunit and facilitate the transduction of various stimuli. In this study, we identified three putative GPCR-like proteins (OsGPCRLPs) (LOC_Os06g09930.1, LOC_Os04g36630.1, and LOC_Os01g54784.1) in the rice proteome using a stringent bioinformatics workflow. The identified OsGPCRLPs exhibited a canonical GPCR 'type I' 7TM topology, patterns, and biologically significant sites for membrane anchorage and desensitization. Cluster-based interactome mapping revealed that the identified proteins interact with the G protein α subunit which is a characteristic feature of GPCRs. Computational results showing the interaction of identified GPCR-like proteins with G protein α subunit and its further validation by the membrane yeast-two-hybrid assay strongly suggest the presence of GPCR-like 7TM proteins in the rice proteome. The absence of a regulator of G protein signaling (RGS) box in the C- terminal domain, and the presence of signature motifs of canonical GPCR in the identified OsGPCRLPs strongly suggest that the rice proteome contains GPCR-like proteins that might be involved in signal transduction.G protein-coupled receptors (GPCRs) constitute the largest family of transmembrane proteins in metazoans that mediate the regulation of various physiological responses to discrete ligands through heterotrimeric G protein subunits. The existence of GPCRs in plant is contentious, but their comparable crucial role in various signaling pathways necessitates the identification of novel remote GPCR-like proteins that essentially interact with the plant G protein α subunit and facilitate the transduction of various stimuli. In this study, we identified three putative GPCR-like proteins (OsGPCRLPs) (LOC_Os06g09930.1, LOC_Os04g36630.1, and LOC_Os01g54784.1) in the rice proteome using a stringent bioinformatics workflow. The identified OsGPCRLPs exhibited a canonical GPCR 'type I' 7TM topology, patterns, and biologically significant sites for membrane anchorage and desensitization. Cluster-based interactome mapping revealed that the identified proteins interact with the G protein α subunit which is a characteristic feature of GPCRs. Computational results showing the interaction of identified GPCR-like proteins with G protein α subunit and its further validation by the membrane yeast-two-hybrid assay strongly suggest the presence of GPCR-like 7TM proteins in the rice proteome. The absence of a regulator of G protein signaling (RGS) box in the C- terminal domain, and the presence of signature motifs of canonical GPCR in the identified OsGPCRLPs strongly suggest that the rice proteome contains GPCR-like proteins that might be involved in signal transduction.
Optimal risk stratification with machine learning (ML) from myocardial perfusion imaging (MPI) includes both clinical and imaging data. While most imaging variables can be derived automatically, ...clinical variables require manual collection, which is time-consuming and prone to error. We determined the fewest manually input and imaging variables required to maintain the prognostic accuracy for major adverse cardiac events (MACE) in patients undergoing a single-photon emission computed tomography (SPECT) MPI.
This study included 20 414 patients from the multicentre REFINE SPECT registry and 2984 from the University of Calgary for training and external testing of the ML models, respectively. ML models were trained using all variables (ML-All) and all image-derived variables (including age and sex, ML-Image). Next, ML models were sequentially trained by incrementally adding manually input and imaging variables to baseline ML models based on their importance ranking. The fewest variables were determined as the ML models (ML-Reduced, ML-Minimum, and ML-Image-Reduced) that achieved comparable prognostic performance to ML-All and ML-Image. Prognostic accuracy of the ML models was compared with visual diagnosis, stress total perfusion deficit (TPD), and traditional multivariable models using area under the receiver-operating characteristic curve (AUC). ML-Minimum (AUC 0.798) obtained comparable prognostic accuracy to ML-All (AUC 0.799, P = 0.19) by including 12 of 40 manually input variables and 11 of 58 imaging variables. ML-Reduced achieved comparable accuracy (AUC 0.796) with a reduced set of manually input variables and all imaging variables. In external validation, the ML models also obtained comparable or higher prognostic accuracy than traditional multivariable models.
Reduced ML models, including a minimum set of manually collected or imaging variables, achieved slightly lower accuracy compared to a full ML model but outperformed standard interpretation methods and risk models. ML models with fewer collected variables may be more practical for clinical implementation.
Network biology approaches have emerged as a promising tool to study disease mechanisms and explain comorbidities. Network biology approaches can be applied to integrate the complex neural networks ...that can help in understanding the molecular mechanisms of neurodevelopmental disorders and hence provide an insight into the diagnosis and treatment of these disorders.
To identify priority genes involved in ADHD through multiple system biology approach and its subsequent treatment through molecular interaction studies.
In the present study, genes related to the neurodevelopmental disorders associated with ADHD were identified. STRING plugin on cytoscape was used to construct network and identify the hub genes. Further, expression, mutational, and regulatory analysis of the identified priority genes was done to evaluate its expression in brain. Computational drug designing approaches were further applied to identify the natural drug that can target the identified priority gene for the treatment of neurodevelopmental disorders.
The present study is an attempt to identify the priority genes and thereby explain the molecular mechanism of neurodevelopmental disorders using computational network biology approaches in integration with other in-silico tools.
Our study concludes that GRIN2B can be a potential target in the mechanism of different neurodevelopmental disorders. The docking of GRIN2B receptor with neuroprotectant phytochemicals revealed that Asiatic acid, a naturally occurring pentacyclic triterpenoid, extracted from Centella asiatica can be used as a potential phytocompound for the treatment of Neurodevelopmental Disorders.
Asiatic acid can be used as a therapeutic agent against GRIN2B receptor for treatment of ADHD.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This research study aimed to evaluate and compare the capability of four various bite registration materials to reproduce precise interocclusal relationships in the vertical dimension.
Ideal ...maxillary and mandibular casts were mounted on the semi-adjustable articulator in maximum intercuspation after mock tooth preparation on 46, 47, and 48. Models were scanned by the Medit T500 Dental Lab Scanner, and initial reading was noted at the predetermined points. Ten interocclusal bite registrations were made using four materials (CADbite, Jet Bite, Ramitec, and Aluwax). The mandibular model was demounted and again remounted using the interocclusal records, and the final reading was noted after scanning.
Ramitec showed superior results when compared to polyvinyl bite registration material and Aluwax, but the differences between Ramitec, CADbite, and Jet Bite were nonsignificant.
Although all four materials are suitable for clinical use, elastomeric materials showed superior results. In that, polyether was found to be the best.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Standard clinical interpretation of myocardial perfusion imaging (MPI) has proven prognostic value for predicting major adverse cardiovascular events (MACE). However, personalizing predictions to a ...specific event type and time interval is more challenging. We demonstrate an explainable deep learning model that predicts the time-specific risk separately for all-cause death, acute coronary syndrome (ACS), and revascularization directly from MPI and 15 clinical features. We train and test the model internally using 10-fold hold-out cross-validation (n = 20,418) and externally validate it in three separate sites (n = 13,988) with MACE follow-ups for a median of 3.1 years (interquartile range IQR: 1.6, 3.6). We evaluate the model using the cumulative dynamic area under receiver operating curve (cAUC). The best model performance in the external cohort is observed for short-term prediction - in the first six months after the scan, mean cAUC for ACS and all-cause death reaches 0.76 (95% confidence interval CI: 0.75, 0.77) and 0.78 (95% CI: 0.78, 0.79), respectively. The model outperforms conventional perfusion abnormality measures at all time points for the prediction of death in both internal and external validations, with improvement increasing gradually over time. Individualized patient explanations are visualized using waterfall plots, which highlight the contribution degree and direction for each feature. This approach allows the derivation of individual event probability as a function of time as well as patient- and event-specific risk explanations that may help draw attention to modifiable risk factors. Such a method could help present post-scan risk assessments to the patient and foster shared decision-making.
Bone defects show a slow rate of osteoconduction and imperfect reconstruction, and the current treatment strategies to treat bone defects suffer from limitations like immunogenicity, lack of cell ...adhesion, and the absence of osteogenic activity. In this context, bioactive supramolecular peptides and peptide gels offer unique opportunities to develop biomaterials that can play a dominant role in the biomineralization of bone tissues and promote bone formation. In this article, we have demonstrated the potential of six tetrapeptides for specific binding to hydroxyapatite (HAp), a major inorganic component of the bone, and their effect on the growth and osteogenic differentiation of mesenchymal stem cells (MSCs). We adopted a simplistic approach of rationally designing amphiphilic peptides by incorporating amino acids, Ser, pSer, Pro, Hyp, Asp, and Glu, which are present in either collagenous or noncollagenous proteins and render properties like antioxidant, calcification, and mineralization. A total of six tetrapeptides, Trp–Trp–His–Ser (WWHS), Trp–Trp–His–pSer (WWHJ), Trp–Trp–His–Pro (WWHP), Trp–Trp–His–Hyp (WWHO), Trp–Trp–His–Asp (WWHD), and Trp–Trp–His–Glu (WWHE), were synthesized. Four peptides were found to self-assemble into nanofibrillar gels resembling the extracellular matrix (ECM), and the remaining two peptides (WWHJ, WWHP) self-assembled into nanorods. The peptides showed excellent cell adhesion, encapsulation, proliferation, and migration and induced the differentiation of mesenchymal stem cells (MSCs), as evident from the enhanced mineralization, resulting from the upregulation of osteogenic markers, RUNX 2, COL I, OPN, and OCN, alkaline phosphatase (ALP) production, and calcium deposition. The peptides also induced the downregulation of inflammatory markers, TNF-α and iNOS, and the upregulation of the anti-inflammatory marker, IL-10, resulting in M2 macrophage polarization. RANKL and TRAP genes were downregulated in a coculture system of MC3T3-E1 and RAW 264.7 cells, implying that peptides promote osteogenesis and inhibit osteoclastogenesis. The peptide-based biomaterials developed in this work can enhance bone regeneration capacity and show strong potential as scaffolds for bone tissue engineering.
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IJS, KILJ, NUK, PNG, UL, UM
The aim of this study was to evaluate and compare the shear bond strength of porcelain to the alloys of nickel-chromium (Ni-Cr), cobalt-chromium (Co-Cr), and titanium.
A total of 40 samples (25 mm × ...3 mm × 0.5 mm) were fabricated using smooth casting wax and cast using Ni-Cr, Co-Cr, and titanium alloys followed by porcelain buildup. The samples were divided into four groups with each group containing 10 samples (Group A1-10: sandblasted Ni-Cr alloy, Group B1-10: sandblasted Co-Cr alloy, Group C1-10: nonsandblasted titanium alloy, and Group D1-10: sandblasted titanium alloy). Shear bond strength was measured using a Universal Testing Machine.
ANOVA test and Tukey's honestly significance difference
test for multiple comparisons.
The mean shear bond strength values for these groups were 22.8960, 27.4400, 13.2560, and 25.3440 MPa, respectively, with sandblasted Co-Cr alloy having the highest and nonsandblasted titanium alloy having the lowest value.
It could be concluded that newer nickel and beryllium free Co-Cr alloys and titanium alloys with improved strength to weight ratio could prove to be good alternatives to the conventional nickel-based alloys when biocompatibility was a concern.
Coronavirus disease (COVID-19) spread across the globe through the human transmission. The World Health Organization suggested social distancing to curb the community spread. After national social ...lockdown started in India, air quality improved drastically. This further hypothesized to influence the environment and human health, and this study is positively the first to weigh it using multiple indices. The calculated environmental indices are photochemical ozone creation potential (POCP), acidification potential (AP), and eutrophication potential (EP). The cancer risk, chronic health index (CHI), and acute health index (AHI) were considered to calculate the health risk. The spatial trend change in the air pollution reflecting on these indices are calculated for four Indian megacities Delhi, Bangalore, Hyderabad, and Kolkata. Temporal variation was accounted for monthly (2019 vs 2020), one-week and two-weeks period during the social lockdown. The results showed a significant decrease in environmental and health risk during the lockdown due to a corresponding decrement in air pollution. The decrease in the particulate matter was found to play a vital role in altering the air pollution mediated risks of interest. Delhi showed a maximum difference in POCP and Acute HI by recording a dip of 70.79% and 43.53% respectively in 2020 during lockdown. The maximum reduction in health risk indices was 41%, 31%, 17%, 19% for Delhi, Bangalore, Hyderabad, and Kolkata. Bangalore recorded the maximum decline in EP, Cancer risk, Chronic HI by 66.66%, 58.62%, and 58.76% in 2020 compared to 2019. A maximum fall in AP was seen in Kolkata by 57.23% in 2020 among all cities. The connection between these drop-in indices and the cause of air pollutants were well discussed. This present paper gives more in-depth insights into air pollution's effect on environmental and health parameters by connecting and converging various air pollution aspects into a single scale. This study also enlightens the importance of controlling air pollution to have a better environment and healthy life to attain sustainable development.
Conceptual illustration of impact of COVID-19 enabled social lockdown on environmental and health risk indices in India. Display omitted
•Detailed study on COVID-19 lockdown vs environmental and health indices in India.•Included three time periods & four megacities Delhi, Mumbai, Bangalore & Kolkata.•Noticeable reduction in particulate matter and indices during lockdown.•Maximum health risk reduction in Delhi (41%) and Bangalore (31%).•Bangalore recorded maximum reduction in EP, Cancer risk, Chronic HI.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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