ABSTRACT
OBJECTIVE: The study aimed to determine the efficacy of foot muscle exercises in children with DS having pes planus. METHODS: Forty-seven subjects randomly assigned to foot muscle exercises (study group) or an arch support insole with one-leg balance exercises (control group), thrice weekly intervention for 12-weeks followed by a home program with residual effect assessed after 24-weeks from baseline. RESULTS: The motor functions were significantly improved in both groups (p = 0.00). A positive residual effect was found in the study group for both parameters. Whilst in the control group it failed to give a positive residual effect for GMFM-88, while PBS yielded positive outcomes. The study group showed significantly better results than the control group in comparison. CONCLUSION: The novel finding suggests that the foot muscle exercise has the potential to improve motor functions in children with Down syndrome and it can be used as an alternative therapeutic approach to the conventional method.
Subject(s)
Down Syndrome , Exercise Therapy , Flatfoot , Foot , Muscle, Skeletal , Humans , Down Syndrome/rehabilitation , Down Syndrome/physiopathology , Male , Child , Female , Flatfoot/rehabilitation , Flatfoot/physiopathology , Flatfoot/therapy , Exercise Therapy/methods , Foot/physiopathology , Muscle, Skeletal/physiopathology , Treatment Outcome , AdolescentABSTRACT
Cold stress significantly limits the yield and quality of tomato. Deciphering the key genes related to cold tolerance is important for selecting and breeding superior cold-tolerant varieties. γ-aminobutyric acid (GABA) responds to various types of stress by rapidly accumulating in plant. In this study, glutamic acid decarboxylase (GAD2) was a positive regulator to enhance cold stress tolerance of tomato. Overexpression of SlGAD2 decreased the extent of cytoplasmic membrane damage and increased the endogenous GABA content, antioxidant enzyme activities, and reactive oxygen species (ROS) scavenging capacity in response to cold stress, whereas Slgad2 mutant plants showed the opposite trend. In addition, SlGAD2 induced anthocyanin biosynthesis in response to cold stress by increasing the content of endogenous GABA. Further study revealed that SlGAD2 expression was negatively regulated by the transcription factor SlTHM27. However, the transcript levels of SlTHM27 were repressed under cold stress. Antioxidant enzyme activities, SlGAD2 transcript levels, GABA and anthocyanin contents were significantly increased in Slthm27 mutant plants. Further, our study demonstrated that SlTHM27 decreases SlGAD2-promoted cold resistance in tomato by repressing SlGAD2 transcription. Overall, our results showed that the SlTHM27-SlGAD2 model regulates the cold tolerance in tomato by regulating GABA and anthocyanin.
ABSTRACT
Saline-alkali is an important abiotic stressor influencing tomato production. Exogenous methyl jasmonate (MeJA) is well known to increase tomato resistance to a variety of stresses, although its exact mechanism is yet unknown. In this study we confirmed that 22.5 µmol/l MeJA could significantly improve the saline-alkali stress resistance of tomato. Saline-alkali (300 mM) stress increased the endogenous MeJA and jasmonic acid (JA) contents of tomato by 18.8 and 13.4%, respectively. Exogenous application of 22.5 µmol/l MeJA increased the endogenous MeJA and JA contents in tomato by 15.2 and 15.9%, respectively. Furthermore, we found an important transcription factor, SlWRKY80, which responded to MeJA, and constructed its overexpressing and knockout lines through genetic transformation. It was found that SlWRKY80 actively regulated tomato resistance to saline-alkali stress, and the spraying of exogenous MeJA (22.5 µmol/l) reduced the sensitivity of SlWRKY80 knockout lines to saline-alkali stress. The SlWRKY80 protein directly combines with the promoter of SlSPDS2 and SlNHX4 to positively regulate the transcription of SlSPDS2 and SlNHX4, thereby promoting the synthesis of spermidine and Na+/K+ homeostasis, actively regulating saline-alkali stress. The augmentation of JA content led to a notable reduction of 70.6% in the expression of SlJAZ1, and the release of the SlWRKY80 protein interacting with SlJAZ1. In conclusion, we revealed the mechanism of exogenous MeJA in tomato stress resistance through multiple metabolic pathways, elucidated that exogenous MeJA further promotes spermidine synthesis and Na+/K+ homeostasis by activating the expression of SlWRKY80, which provides a new theoretical basis for the study of the JA stress resistance mechanism and the production of tomato.
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BACKGROUND: Professional driving requires long hours of work, uncomfortable seats, negotiating rough terrain and highways, and possibly minor repairs and other auxiliary transportation duties. Heavy vehicle drivers driving vehicles such as trucks, bulldozers, etc. due to such working structures are more prone to various musculoskeletal disorders (MSDs) and pain, which is of great concern. OBJECTIVES: In the present study, it is planned to investigate possible ergonomic risk factors such as age, weight, driving exposure, seat suspension systems, lifting heavy weights causing MSDs in drivers of various heavy vehicles. The results of the study are expected to help drivers reduce the risk of MSDs. METHODS: For the present study, the Nordic questionnaire on musculoskeletal disorders was modified and standardized and was administered to the 48 heavy vehicle drivers randomly selected to collect the data. RESULTS: The analysis divulged that over the past 12 months, lower back pain (LBP) emerged as the most dominant pain experienced by 56% of drivers, followed by knee pain (KP) (43%) and neck pain (NP) (39%) respectively. The prevalence of shoulder pain (SP) was observed to be much lower than in previous literature. The logistic regression model further revealed that increasing age, poor suspension system and poor body posture were significantly associated with lower back pain. Additionally, a poor suspension system and lifting heavy weights had significant effect on the drivers' knee pain. CONCLUSION: The results demonstrated the evident necessity for ergonomic consideration in vehicle designing and ergonomic training for heavy vehicle drivers.
ABSTRACT
Different grasping gestures result in the change of muscular activity of the forearm muscles. Similarly, the muscular activity changes with a change in grip force while grasping the object. This change in muscular activity, measured by a technique called Electromyography (EMG) is used in the upper limb bionic devices to select the grasping gesture. Previous research studies have shown gesture classification using pattern recognition control schemes. However, the use of EMG signals for force manipulation is less focused, especially during precision grasping. In this study, an early predictive control scheme is designed for the efficient determination of grip force using EMG signals from forearm muscles and digit force signals. The optimal pattern recognition (PR) control schemes are investigated using three different inputs of two signals: EMG signals, digit force signals and a combination of EMG and digit force signals. The features extracted from EMG signals included Slope Sign Change, Willison Amplitude, Auto Regressive Coefficient and Waveform Length. The classifiers used to predict force levels are Random Forest, Gradient Boosting, Linear Discriminant Analysis, Support Vector Machines, k-nearest Neighbors and Decision Tree. The two-fold objectives of early prediction and high classification accuracy of grip force level were obtained using EMG signals and digit force signals as inputs and Random Forest as a classifier. The earliest prediction was possible at 1000 ms from the onset of the gripping of the object with a mean classification accuracy of 90 % for different grasping gestures. Using this approach to study, an early prediction will result in the determination of force level before the object is lifted from the surface. This approach will also result in better biomimetic regulation of the grip force during precision grasp, especially for a population facing vision deficiency.
ABSTRACT
The chemokine receptor CXCR4 is implicated in multiple diseases including inflammatory disorders, cancer growth and metastasis, and HIV/AIDS. CXCR4 targeting has been evaluated in treating cancer metastasis and therapy resistance. Cyclam derivatives, most notably AMD3100 (Plerixafor™), are a common motif in small molecule CXCR4 antagonists. However, AMD3100 has not been shown to be effective in cancer treatment as an individual agent. Configurational restriction and transition metal complex formation increases receptor binding affinity and residence time. In the present study, we have synthesized novel trans-IV locked cyclam-based CXCR4 inhibitors, a previously unexploited configuration, and demonstrated their higher affinity for CXCR4 binding and CXCL12-mediated signaling inhibition compared to AMD3100. These results pave the way for even more potent CXCR4 inhibitors that may provide significant efficacy in cancer therapy.
Subject(s)
Coordination Complexes , Cyclams , Heterocyclic Compounds , Benzylamines , Coordination Complexes/pharmacology , Heterocyclic Compounds/pharmacology , Heterocyclic Compounds/chemistry , Receptors, CXCR4/antagonists & inhibitorsABSTRACT
OBJECTIVE: To identify the patient-reported outcome measures (PROMs) after intracorporal anastomosis (ICA) during laparoscopic right hemicolectomy. STUDY DESIGN: An observational study. Place and Duration of the Study: Department of General Surgery, Griffith Base Hospital, New South Wales, Australia, from August 2022 till February 2023. METHODOLOGY: Participants who underwent laparoscopic intracorporeal right hemicolectomy were included in this study. Patients requiring emergency procedures or with a history of psychiatric illness were excluded. The Short Form-36 (SF-36); a quality of life (QoL) questionnaire employed focusing on physical health-related domains post laparoscopic intracorporeal hemicolectomy. The relationship between QoL domains and operative outcomes specific to this anastomotic technique was also assessed. RESULTS: The SF-36 scores at six weeks and six months postoperation revealed shifts in the overall QoL following ICA. Notably, physical function showed significant improvement, while bodily pain remained a significant concern. The correlation analysis found operative blood loss and the length of the extraction site to be significantly correlated with postoperative physical role. CONCLUSION: The study determined that decreased operative blood loss and a shorter extraction site were associated with improved postoperative physical role. It showed the overall QoL improved within six months of the procedure, with the bodily pain domain still an area requiring attention. Understanding the impact of laparoscopic ICA on patient-reported outcomes may help in tailoring patient-cantred approaches and enhancing the overall quality of care. KEY WORDS: Intracorporeal, Right hemicolectomy, Patient-reported outcome measures, Colorectal anastomosis.
Subject(s)
Colonic Neoplasms , Laparoscopy , Humans , Quality of Life , Blood Loss, Surgical , Colectomy/methods , Anastomosis, Surgical/methods , Laparoscopy/methods , Patient Reported Outcome Measures , Pain , Patient Outcome Assessment , Colonic Neoplasms/surgery , Retrospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: Despite representing 4% of the global population, the US has the fifth highest number of intentional homicides in the world. Peripartum people represent a unique and vulnerable subset of homicide victims. This study aimed to understand the risk factors for peripartum homicide. STUDY DESIGN: We used data from the 2018 to 2020 National Violent Death Reporting System to compare homicide rates of peripartum and nonperipartum people capable of becoming pregnant (12 to 50 years of age). Peripartum was defined as currently pregnant or within 1-year postpartum. We additionally compared state-level peripartum homicide rates between states categorized as restrictive, neutral, or protective of abortion. Pearson's chi-square and Wilcoxon rank-sum tests were used. RESULTS: There were 496 peripartum compared with 8,644 nonperipartum homicide victims. The peripartum group was younger (27.4 ± 71 vs 33.0 ± 9.6, p < 0.001). Intimate partner violence causing the homicide was more common in the peripartum group (39.9% vs 26.4%, p < 0.001). Firearms were used in 63.4% of homicides among the peripartum group compared with 49.5% in the comparison (p < 0.001). A significant difference was observed in peripartum homicide between states based on policies regarding abortion access (protective 0.37, neutral 0.45, restrictive 0.64; p < 0.01); the same trend was not seen with male homicides. CONCLUSIONS: Compared with nonperipartum peers, peripartum people are at increased risk for homicide due to intimate partner violence, specifically due to firearm violence. Increasing rates of peripartum homicide occur in states with policies that are restrictive to abortion access. There is a dire need for universal screening and interventions for peripartum patients. Research and policies to reduce violence against pregnant people must also consider the important role that abortion access plays in protecting safety.
Subject(s)
Firearms , Intimate Partner Violence , Suicide , Female , Humans , Male , Pregnancy , United States/epidemiology , Homicide/prevention & control , Peripartum Period , Violence , Intimate Partner Violence/prevention & controlABSTRACT
Hepatocellular carcinoma (HCC) is one of the most common malignancies and is a major cause of cancer-related mortalities worldwide (Forner et al., 2018; He et al., 2023). Sarcopenia is a syndrome characterized by an accelerated loss of skeletal muscle (SM) mass that may be age-related or the result of malnutrition in cancer patients (Cruz-Jentoft and Sayer, 2019). Preoperative sarcopenia in HCC patients treated with hepatectomy or liver transplantation is an independent risk factor for poor survival (Voron et al., 2015; van Vugt et al., 2016). Previous studies have used various criteria to define sarcopenia, including muscle area and density. However, the lack of standardized diagnostic methods for sarcopenia limits their clinical use. In 2018, the European Working Group on Sarcopenia in Older People (EWGSOP) renewed a consensus on the definition of sarcopenia: low muscle strength, loss of muscle quantity, and poor physical performance (Cruz-Jentoft et al., 2019). Radiological imaging-based measurement of muscle quantity or mass is most commonly used to evaluate the degree of sarcopenia. The gold standard is to measure the SM and/or psoas muscle (PM) area using abdominal computed tomography (CT) at the third lumbar vertebra (L3), as it is linearly correlated to whole-body SM mass (van Vugt et al., 2016). According to a "North American Expert Opinion Statement on Sarcopenia," SM index (SMI) is the preferred measure of sarcopenia (Carey et al., 2019). The variability between morphometric muscle indexes revealed that they have different clinical relevance and are generally not applicable to broader populations (Esser et al., 2019).
Subject(s)
Carcinoma, Hepatocellular , Deep Learning , Liver Neoplasms , Sarcopenia , Humans , Aged , Sarcopenia/diagnosis , Sarcopenia/diagnostic imaging , Carcinoma, Hepatocellular/complications , Carcinoma, Hepatocellular/diagnostic imaging , Muscle, Skeletal/diagnostic imaging , Prognosis , Radiomics , Liver Neoplasms/complications , Liver Neoplasms/diagnostic imaging , Retrospective StudiesABSTRACT
The objective of this research was to produce the smallest possible ZnO nanoparticles through an adapted wet chemical process and subsequently, to fabricate a core-shell structure utilizing polyethylene glycol (PEG) as the shell component. The synthesis, size, and shape of the NPs were confirmed using advanced techniques. The resulting clustered NPs were round and had a size of 9.8 nm. Both plain and core-shell NPs were tested for their antibacterial properties against multi-drug resistant bacteria strains (E. cloacae, E. amnigenus, S. flexneri, S. odorifacae, Citrobacter, and E. coli), with concentrations of 500, 1000, and 1500 µg ml-1 used for testing. Both types of NPs demonstrated antibacterial activity against the tested pathogens, with the core-shell NPs being more effective. The synthesized NPs were biocompatible with human red blood cells, with a low level of hemolysis observed. The biocompatibility of the core-shell NPs was significantly enhanced by the presence of the PEG added as the shell. In addition, their effectiveness as photosensitizers for cancer treatment via photodynamic therapy (PDT) was evaluated. MTT assay was used to evaluate the cytotoxicity of ZnO and PEG-ZnO, and the results showed that these NPs were able to generate ROS inside tumor cells upon irradiation, leading to apoptosis and cell death, making them a promising candidate for PDT.
ABSTRACT
Plant NAC transcription factors play a crucial role in enhancing cold stress tolerance, yet the precise molecular mechanisms underlying cold stress remain elusive. In this study, we identified and characterized CaNAC035, an NAC transcription factor isolated from pepper (Capsicum annuum) leaves. We observed that the expression of the CaNAC035 gene is induced by both cold and abscisic acid (ABA) treatments, and we elucidated its positive regulatory role in cold stress tolerance. Overexpression of CaNAC035 resulted in enhanced cold stress tolerance, while knockdown of CaNAC035 significantly reduced resistance to cold stress. Additionally, we discovered that CaSnRK2.4, a SnRK2 protein, plays an essential role in cold tolerance. In this study, we demonstrated that CaSnRK2.4 physically interacts with and phosphorylates CaNAC035 both in vitro and in vivo. Moreover, the expression of two ABA biosynthesis-related genes, CaAAO3 and CaNCED3, was significantly upregulated in the CaNAC035-overexpressing transgenic pepper lines. Yeast one-hybrid, Dual Luciferase, and electrophoretic mobility shift assays provided evidence that CaNAC035 binds to the promoter regions of both CaAAO3 and CaNCED3 in vivo and in vitro. Notably, treatment of transgenic pepper with 50 µm Fluridone (Flu) enhanced cold tolerance, while the exogenous application of ABA at a concentration of 10 µm noticeably reduced cold tolerance in the virus-induced gene silencing line. Overall, our findings highlight the involvement of CaNAC035 in the cold response of pepper and provide valuable insights into the molecular mechanisms underlying cold tolerance. These results offer promising prospects for molecular breeding strategies aimed at improving cold tolerance in pepper and other crops.
Subject(s)
Abscisic Acid , Capsicum , Abscisic Acid/metabolism , Cold-Shock Response , Capsicum/physiology , Stress, Physiological/genetics , Phosphorylation , Plant Leaves/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Gene Expression Regulation, Plant , Plants, Genetically Modified/geneticsABSTRACT
Histone methyltransferases play essential roles in the organization and function of chromatin. They are also frequently mutated in human diseases including cancer1. One such often mutated methyltransferase, SETD2, associates co-transcriptionally with RNA polymerase II and catalyzes histone H3 lysine 36 trimethylation (H3K36me3) - a modification that contributes to gene transcription, splicing, and DNA repair2. While studies on SETD2 have largely focused on the consequences of its catalytic activity, the non-catalytic functions of SETD2 are largely unknown. Here we report a catalysis-independent function of SETD2 in maintaining nuclear lamina stability and genome integrity. We found that SETD2, via its intrinsically disordered N-terminus, associates with nuclear lamina proteins including lamin A/C, lamin B1, and emerin. Depletion of SETD2, or deletion of its N-terminus, resulted in widespread nuclear morphology abnormalities and genome stability defects that were reminiscent of a defective nuclear lamina. Mechanistically, the N-terminus of SETD2 facilitates the association of the mitotic kinase CDK1 with lamins, thereby promoting lamin phosphorylation and depolymerization required for nuclear envelope disassembly during mitosis. Taken together, our findings reveal an unanticipated link between the N-terminus of SETD2 and nuclear lamina organization that may underlie how SETD2 acts as a tumor suppressor.
ABSTRACT
The ribosomal protein contains complex structures that belong to polypeptide glycoprotein family, which are involved in plant growth and responses to various stresses. In this study, we found that capsicum annuum 40S ribosomal protein SA-like (CaSLP) was extensively accumulated in the cell nucleus and cell membrane, and the expression level of CaSLP was up-regulated by Salicylic acid (SA) and drought treatment. Significantly fewer peppers plants could withstand drought stress after CaSLP gene knockout. The transient expression of CaSLP leads to drought tolerance in pepper, and Arabidopsis's ability to withstand drought stress was greatly improved by overexpressing the CaSLP gene. Exogenous application of SA during spraying season enhanced drought tolerance. CaSLP-knockdown pepper plants demonstrated a decreased resistance of Pseudomonas syringae PV.tomato (Pst) DC3000 (Pst.DC3000), whereas ectopic expression of CaSLP increased the Pst.DC3000 stress resistance in Arabidopsis. Yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) results showed that CaNAC035 physically interacts with CaSLP in the cell nucleus. CaNAC035 was identified as an upstream partner of the CaPR1 promoter and activated transcription. Collectively the findings demonstrated that CaSLP plays an essential role in the regulation of drought and Pst.DC3000 stress resistance.
ABSTRACT
BACKGROUND: Hepatic ischemia-reperfusion (IR) injury is the primary reason for complications following hepatectomy and liver transplantation (LT). Insulin-induced gene 2 (Insig2) is one of several proteins that anchor the reticulum in the cytoplasm and is essential for metabolism and inflammatory responses. However, its function in IR injury remains ambiguous. METHODS: Insig2 global knock-out (KO) mice and mice with adeno-associated-virus8 (AAV8)-delivered Insig2 hepatocyte-specific overexpression were subjected to a 70% hepatic IR model. Liver injury was assessed by monitoring hepatic histology, inflammatory responses, and apoptosis. Hypoxia/reoxygenation stimulation (H/R) of primary hepatocytes and hypoxia model induced by cobalt chloride (CoCl2) were used for in vitro experiments. Multi-omics analysis of transcriptomics, proteomics, and metabolomics was used to investigate the molecular mechanisms underlying Insig2. RESULTS: Hepatic Insig2 expression was significantly reduced in clinical samples undergoing LT and the mouse IR model. Our findings showed that Insig2 depletion significantly aggravated IR-induced hepatic inflammation, cell death and injury, whereas Insig2 overexpression caused the opposite phenotypes. The results of in vitro H/R experiments were consistent with those in vivo. Mechanistically, multi-omics analysis revealed that Insig2 is associated with increased antioxidant pentose phosphate pathway (PPP) activity. The inhibition of glucose-6-phosphate-dehydrogenase (G6PD), a rate-limiting enzyme of PPP, rescued the protective effect of Insig2 overexpression, exacerbating liver injury. Finally, our findings indicated that mouse IR injury could be attenuated by developing a nanoparticle delivery system that enables liver-targeted delivery of substrate of PPP (glucose 6-phosphate). CONCLUSIONS: Insig2 has a protective function in liver IR by upregulating the PPP activity and remodeling glucose metabolism. The supplementary glucose 6-phosphate (G6P) salt may serve as a viable therapeutic target for alleviating hepatic IR.
Subject(s)
Hepatocytes , Insulins , Liver Diseases , Reperfusion Injury , Animals , Mice , Antioxidants/metabolism , Apoptosis/genetics , Glucose/metabolism , Hepatectomy/adverse effects , Hepatocytes/metabolism , Hepatocytes/pathology , Hypoxia/complications , Hypoxia/genetics , Hypoxia/metabolism , Insulins/metabolism , Liver/blood supply , Liver/injuries , Liver/metabolism , Liver/pathology , Liver Diseases/genetics , Liver Diseases/metabolism , Liver Diseases/pathology , Liver Diseases/surgery , Liver Transplantation/adverse effects , Phosphates/metabolism , Phosphates/pharmacology , Reperfusion Injury/genetics , Reperfusion Injury/metabolism , Reperfusion Injury/pathology , Reperfusion Injury/prevention & controlABSTRACT
Background: Mental illness stigma is universally prevalent and a significant barrier to achieving global mental health goals. Mental illness stigma in Bangladesh has gained little attention despite its widespread impact on seeking mental health care in rural and urban areas. This study aimed to investigate mental illness stigma and the associated factors in rural and urban areas of Bangladesh. Methods: The study areas were divided into several clusters from which 325 participants (≥18 years) were recruited with systematic random sampling. The Bangla version of the Days' Mental Illness Stigma Scale was used to collect data. Independent-samples t-test, ANOVA, and multiple regression were performed. Results: Results suggest that gender, age, geographical location, socioeconomic status, and occupation significantly differed across subscales of stigma. Age, gender, seeking treatment of mental illness, having knowledge on mental health, and socioeconomic status were predictive factors of mental illness stigma. The results also showed a high treatment gap in both rural and urban areas. Conclusion: This study supports that mental illness stigma is prevalent in Bangladesh, requiring coordinated efforts. Results can inform the development of contextually tailored mental health strategies to reduce stigma and contribute to the promotion of mental health of individuals and communities across Bangladesh.
ABSTRACT
Heat stress, which is caused by global warming, threatens crops yield and quality across the world. As a kind of post-translation modification, SUMOylation involves in plants heat stress response with a rapid and wide pattern. Here, we identified small ubiquitin modifiers (SUMO), which affect drought tolerance in apple, also participated in thermotolerance. Six isoforms of SUMOs located on six chromosomes in apple genome, and all the SUMOs were up-regulated in response to heat stress condition. The MdSUMO2 RNAi transgenic apple plants exhibited higher survival rate, lower ion leakage, higher catalase (CAT) activity, and Malondialdehyde (MDA) content under heat stress. MdDREB2A, the substrate of MdSUMO2 in apple, was accumulated in MdSUMO2 RNAi transgenic plants than the wild type GL-3 at the protein level in response to heat stress treatment. Further, the inhibited SUMOylation level of MdDREB2A in MdSUMO2 RNAi plants might repress its ubiquitination, too. The accumulated MdDREB2A in MdSUMO2 RNAi plants further induced heat-responsive genes expression to strengthen plants thermotolerance, including MdHSFA3, MdHSP26.5, MdHSP18.2, MdHSP70, MdCYP18-1 and MdTLP1. In summary, these findings illustrate that interfering small ubiquitin modifiers (SUMO) in apple improves plants thermotolerance, partly by facilitating the stability and activity of MdDREB2A.
ABSTRACT
Isochromosomes are mirror-imaged chromosomes with simultaneous duplication and deletion of genetic material which may contain two centromeres to create isodicentric chromosomes. Although isochromosomes commonly occur in cancer and developmental disorders and promote genome instability, mechanisms that prevent isochromosomes are not well understood. We show here that the tumor suppressor and methyltransferase SETD2 is essential to prevent these errors. Using cellular and cytogenetic approaches, we demonstrate that loss of SETD2 or its epigenetic mark, histone H3 lysine 36 trimethylation (H3K36me3), results in the formation of isochromosomes as well as isodicentric and acentric chromosomes. These defects arise during DNA replication and are likely due to faulty homologous recombination by RAD52. These data provide a mechanism for isochromosome generation and demonstrate that SETD2 and H3K36me3 are essential to prevent the formation of this common mutable chromatin structure known to initiate a cascade of genomic instability in cancer.
Subject(s)
Isochromosomes , Humans , Centromere , Chromosome Aberrations , Cytogenetics , DNA Replication , Genomic InstabilityABSTRACT
[This corrects the article DOI: 10.1039/D3RA02640J.].
ABSTRACT
We investigated the physical behavior of SrMO3 (M = Hf and Pt) compounds, which are strontium-based oxide perovskites. We utilized the WIEN2k software to simulate and investigate their physical properties. The structural stability of SrHfO3 and SrPtO3 was verified using the Birch-Murnaghan equation of states for optimization. We also checked the elastic stability through the computation of elastic constants using the IRelast software. Our results indicate the stability of these compounds and showed their anisotropic, ductility, scratch-resistive, and plastic strain-resistant characteristics. Using the TB-mBJ potential approach, we determined that SrHfO3 is an insulator, whereas SrPtO3 is a metal in nature. The density of states computations was used to find the band structure as well as the contribution of different electronic states. Optical property research was conducted using the band gap energies of these substances. Our findings suggest that these crystals have low energy absorption and reflectivity of up to 65%, making them suitable for use in high-frequency UV devices. Specifically, SrHfO3 is more transparent before the energy point 2.80 eV, while the compound SrPtO3 after 6.50 eV to 12.0 eV and SrHfO3 from 12.0 and 14.0 eV. This study represents the first DFT-based investigation of these discussed crystals according to the best of our knowledge.