Regulation of dormancy during tumor dissemination: the role of the ECM.

The study of the metastatic cascade has revealed the complexity of the process and the multiple cellular states that disseminated cancer cells must go through. The tumor microenvironment and in particular the extracellular matrix (ECM) plays an important role in regulating the transition from invasion, dormancy to ultimately proliferation during the metastatic cascade. The time delay from primary tumor detection to metastatic growth is regulated by a molecular program that maintains disseminated tumor cells in a non-proliferative, quiescence state known as tumor cell dormancy. Identifying dormant cells and their niches in vivo and how they transition to the proliferative state is an active area of investigation, and novel approaches have been developed to track dormant cells during dissemination. In this review, we highlight the latest research on the invasive nature of disseminated tumor cells and their link to dormancy programs. We also discuss the role of the ECM in sustaining dormant niches at distant sites.

Functional insight into multi-omics-based interventions for climatic resilience in sorghum (Sorghum bicolor): a nutritionally rich cereal crop.

MAIN CONCLUSION: The article highlights omics-based interventions in sorghum to combat food and nutritional scarcity in the future. Sorghum with its unique ability to thrive in adverse conditions, has become a tremendous highly nutritive, and multipurpose cereal crop. It is resistant to various types of climatic stressors which will pave its way to a future food crop. Multi-omics refers to the comprehensive study of an organism at multiple molecular levels, including genomics, transcriptomics, proteomics, and metabolomics. Genomic studies have provided insights into the genetic diversity of sorghum and led to the development of genetically improved sorghum. Transcriptomics involves analysing the gene expression patterns in sorghum under various conditions. This knowledge is vital for developing crop varieties with enhanced stress tolerance. Proteomics enables the identification and quantification of the proteins present in sorghum. This approach helps in understanding the functional roles of specific proteins in response to stress and provides insights into metabolic pathways that contribute to resilience and grain production. Metabolomics studies the small molecules, or metabolites, produced by sorghum, provides information about the metabolic pathways that are activated or modified in response to environmental stress. This knowledge can be used to engineer sorghum varieties with improved metabolic efficiency, ultimately leading to better crop yields. In this review, we have focused on various multi-omics approaches, gene expression analysis, and different pathways for the improvement of Sorghum. Applying omics approaches to sorghum research allows for a holistic understanding of its genome function. This knowledge is invaluable for addressing challenges such as climate change, resource limitations, and the need for sustainable agriculture.

The current scenario and future perspectives of transgenic oilseed mustard by CRISPR-Cas9.

PURPOSE: Production of a designer crop having added attributes is the primary goal of all plant biotechnologists. Specifically, development of a crop with a simple biotechnological approach and at a rapid pace is most desirable. Genetic engineering enables us to displace genes among species. The newly incorporated foreign gene(s) in the host genome can create a new trait(s) by regulating the genotypes and/or phenotypes. The advent of the CRISPR-Cas9 tools has enabled the modification of a plant genome easily by introducing mutation or replacing genomic fragment. Oilseed mustard varieties (e.g., Brassica juncea, Brassica nigra, Brassica napus, and Brassica carinata) are one such plants, which have been transformed with different genes isolated from the wide range of species. Current reports proved that the yield and value of oilseed mustard has been tremendously improved by the introduction of stably inherited new traits such as insect and herbicide resistance. However, the genetic transformation of oilseed mustard remains incompetent due to lack of potential plant transformation systems. To solve numerous complications involved in genetically modified oilseed mustard crop varieties regeneration procedures, scientific research is being conducted to rectify the unwanted complications. Thus, this study provides a broader overview of the present status of new traits introduced in each mentioned varieties of oilseed mustard plant by different genetical engineering tools, especially CRISPR-Cas9, which will be useful to improve the transformation system of oilseed mustard crop plants. METHODS: This review presents recent improvements made in oilseed mustard genetic engineering methodologies by using CRISPR-Cas9 tools, present status of new traits introduced in oilseed mustard plant varieties. RESULTS: The review highlighted that the transgenic oilseed mustard production is a challenging process and the transgenic varieties of oilseed mustard provide a powerful tool for enhanced mustard yield. Over expression studies and silencing of desired genes provide functional importance of genes involved in mustard growth and development under different biotic and abiotic stress conditions. Thus, it can be expected that in near future CRISPR can contribute enormously in improving the mustard plant's architecture and develop stress resilient oilseed mustard plant species.

Heightened miR6024-NLR interactions facilitate necrotrophic pathogenesis in tomato.

KEY MESSAGE: miR6024 acts as a negative regulator of R genes, hence of Tomato plant immunity, and facilitates disease by the necrotrophic pathogen A. solani. Plant resistance genes or Nucleotide-binding leucine-rich repeat (NLR) genes, integral components of plant disease stress-signaling are targeted by variable groups of miRNAs. However, the significance of miRNA-mediated regulation of NLRs during a pathogen stress response, specifically for necrotrophic fungus, is poorly understood. A thorough examination of Tomato NLRs and miRNAs could map substantial interactions of which half the annotated NLRs were targets of Solanaceae-specific and conserved miRNAs, at the NB subdomain. The Solanaceae-specific miR6024 and its NLR targets analysed in different phytopathogenic stresses revealed differential and mutually antagonistic regulation. Interestingly, miR6024-targeted cleavage of a target NLR also triggered the generation of secondary phased siRNAs which could potentially amplify the defense signal. RNA-seq analysis of leaf tissues from miR6024 overexpressing Tomato plants evidenced a perturbation in the defense transcriptome with the transgenics showing unwarranted immune response-related genes' expression with or without infection with necrotrophic Alternaria solani, though no adverse effect could be observed in the growth and development of the transgenic plants. Transgenic plants exhibited constitutive downregulation of the target NLRs, aggravated disease phenotype with an enhanced lesion, greater ROS generation and hypersusceptibility to A. solani infection, thus establishing that miR6024 negatively impacts plant immune response during necrotrophic pathogenesis. Limited knowledge about the outcome of NLR-miRNA interaction during necrotrophic pathogenesis is a hindrance to the deployment of miRNAs in crop improvement programs. With the elucidation of the necrotrophic disease-synergistic role played by miR6024, it becomes a potent candidate for biotechnological manipulation for the rapid development of pathogen-tolerant solanaceous plants.

Disruption of tomato TGS machinery by ToLCNDV causes reprogramming of vascular tissue-specific TORNADO1 gene expression.

MAIN CONCLUSION: Vascular development-related TRN1 transcription is suppressed by cytosine methylation in fully developed leaves of tomato. ToLCNDV infection disrupts methylation machinery and reactivates TRN1 expression - likely causing abnormal leaf growth pattern. Leaf curl disease of tomato caused by tomato leaf curl New Delhi virus (ToLCNDV) inflicts huge economical loss. Disease symptoms resemble leaf developmental defects including abnormal vein architecture. Leaf vein patterning-related TORNADO1 gene's (SlTRN1) transcript level is augmented in virus-infected leaves. To elucidate the molecular mechanism of the upregulation of SlTRN1 in vivo, we have deployed SlTRN1 promoter-reporter transgenic tomato plants and investigated the gene's dynamic expression pattern in leaf growth stages and infection. Expression of the gene was delimited in the vascular tissues and suppressed in fully developed leaves. WRKY16 transcription factor readily activated SlTRN1 promoter in varied sized leaves and upon virus infection, while silencing of WRKY16 gene resulted in dampened promoter activity. Methylation-sensitive PCR analyses confirmed the accumulation of CHH methylation at multiple locations in the SlTRN1 promoter in older leaves. However, ToLCNDV infection reverses the methylation status and restores expression level in the leaf vascular bundle. The virus dampens the level of key maintenance and de novo DNA methyltransferases SlDRM5, SlMET1, SlCMT2 with concomitant augmentation of two DNA demethylases, SlDML1 and SlDML2 levels in SlTRN1 promoter-reporter transgenics. Transient overexpression of SlDML2 mimics the virus-induced hypomethylation state of the SlTRN1 promoter in mature leaves, while silencing of SlDML2 lessens promoter activity. Furthermore, in line with the previous studies, we confirm the crucial role of viral suppressors of RNA silencing AC2 and AC4 proteins in promoting DNA demethylation and directing it to restore activated transcription of SlTRN1. Unusually elevated expression of SlTRN1 may negatively impact normal growth of leaves.

Thylakoid localized bestrophin-like proteins are essential for the CO2 concentrating mechanism of Chlamydomonas reinhardtii.

The green alga Chlamydomonas reinhardtii possesses a CO2 concentrating mechanism (CCM) that helps in successful acclimation to low CO2 conditions. Current models of the CCM postulate that a series of ion transporters bring HCO3- from outside the cell to the thylakoid lumen, where the carbonic anhydrase 3 (CAH3) dehydrates accumulated HCO3- to CO2, raising the CO2 concentration for Ribulose bisphosphate carboxylase/oxygenase (Rubisco). Previously, HCO3- transporters have been identified at both the plasma membrane and the chloroplast envelope, but the transporter thought to be on the thylakoid membrane has not been identified. Three paralogous genes (BST1, BST2, and BST3) belonging to the bestrophin family have been found to be up-regulated in low CO2 conditions, and their expression is controlled by CIA5, a transcription factor that controls many CCM genes. YFP fusions demonstrate that all 3 proteins are located on the thylakoid membrane, and interactome studies indicate that they might associate with chloroplast CCM components. A single mutant defective in BST3 has near-normal growth on low CO2, indicating that the 3 bestrophin-like proteins may have redundant functions. Therefore, an RNA interference (RNAi) approach was adopted to reduce the expression of all 3 genes at once. RNAi mutants with reduced expression of BST1-3 were unable to grow at low CO2 concentrations, exhibited a reduced affinity to inorganic carbon (Ci) compared with the wild-type cells, and showed reduced Ci uptake. We propose that these bestrophin-like proteins are essential components of the CCM that deliver HCO3- accumulated in the chloroplast stroma to CAH3 inside the thylakoid lumen.

Contraceptive behavior and unmet need among the tribal married women aged 15-49 years: A cross-sectional study in a community development block of paschim Bardhaman District, West Bengal.

BACKGROUND: Contraceptive behavior and unmet need for family planning, particularly among the tribal women of reproductive age in India, still remains a public health concern. This needs to be explored in different geographical regions. OBJECTIVES: : This study aimed to ascertain the contraceptive behavior of tribal married women of 15-49 years and to assess the unmet need for family planning and its determinants. METHODS: : A descriptive, cross-sectional study was conducted during May 2019 to April 2020 in Barabani Block of Paschim Bardhaman District, West Bengal. A calculated sample of 530 study participants was selected from the study area by the simple random sampling. Required data on contraceptive behavior characteristics, unmet need, and correlates were collected by interviewing them with a predesigned schedule. Bivariate analysis and multivariable logistic regression were done. Data were analyzed using the SPSS software v. 20. RESULTS: : All study participants were Hindu and belonged to Santhal ethnicity; 53.4% were illiterate; 51.7% had early marriage, and 52.4% had adolescent pregnancy. Only 41.1% women were found currently using any contraceptives, another 14.5% ever used and 44.4% never used any methods. Apprehension of side effects and spouse disapproval were reported as two common reasons for never using contraceptives. The age of the women appeared as a significant predictor of current contraceptive use. Overall, unmet need for family planning was 19.4% and age of the women, socioeconomic status, and type of the family were found as significant predictors. CONCLUSION: Issues contributing to unsatisfactory contraceptive behavior and high unmet need for family planning need to be addressed appropriately.

Identification and characterization of a solute carrier, CIA8, involved in inorganic carbon acclimation in Chlamydomonas reinhardtii.

The supply of inorganic carbon (Ci) at the site of fixation by Rubisco is a key parameter for efficient CO2 fixation in aquatic organisms including the green alga, Chlamydomonas reinhardtii. Chlamydomonas reinhardtii cells, when grown on limiting CO2, have a CO2-concentrating mechanism (CCM) that functions to concentrate CO2 at the site of Rubisco. Proteins thought to be involved in inorganic carbon uptake have been identified and localized to the plasma membrane or chloroplast envelope. However, current CCM models suggest that additional molecular components are involved in Ci uptake. In this study, the gene Cia8 was identified in an insertional mutagenesis screen and characterized. The protein encoded by Cia8 belongs to the sodium bile acid symporter subfamily. Transcript levels for this gene were significantly up-regulated when the cells were grown on low CO2. The cia8 mutant exhibited reduced growth and reduced affinity for Ci when grown in limiting CO2 conditions. Prediction programs localize this protein to the chloroplast. Ci uptake and the photosynthetic rate, particularly at high external pH, were reduced in the mutant. The results are consistent with the model that CIA8 is involved in Ci uptake in C. reinhardtii.

Menstrual hygiene behaviour among the tribal married women aged 15 to 49 years: A cross-sectional study in a community development block of Paschim Bardhaman District, West Bengal.

Background: Menstrual hygiene management is integrally associated with reproductive health of women. Menstrual health and hygiene needs, particularly of tribal women still remain unmet for many reasons. Inappropriate menstrual behaviour leads to adverse health consequences. Objectives: This study aimed to ascertain the menstrual hygiene behaviour of tribal married women aged 15 to 49 years and its correlates. Methods: A descriptive cross-sectional study was conducted from May 2019 to April 2020 in the Barabani block of Paschim Bardhaman district, West Bengal. A calculated sample of 530 women was selected randomly from 10 tribal villages of the study area; they were interviewed through a pre-designed schedule for socio-demographic and menstrual hygiene behaviour characteristics. Menstrual hygiene management score was derived based on five essential components- hygienic absorbents, hygienic disposal of absorbents, frequency of changing of absorbents, cleaning of external genitalia and source of water for cleaning; menstrual hygiene behaviour was categorised as favourable and unfavourable. Bivariate and multivariable logistic regression was performed using SPSS v. 20. Results: All 530 women were Hindu and belonged to Santhal ethnicity; 53.4% were illiterate. Sanitary pads were used by 43.8% of women; 63% practised indiscriminate throwing for disposal of absorbents; 86% practised appropriate changing of absorbents. Overall, 63% had favourable menstrual hygiene management behaviour, and the literacy status of women was found to be a significant predictor. Conclusion: Unfavourable menstrual practices are still widely prevalent among tribal women, mainly attributable to lack of knowledge. Awareness generation should be focused on improving those practices, which would also result in the improvement of general health conditions.

Serum Chemerin Levels Correlate With Severity of Dysglycemia in Young Adult Women With Polycystic Ovary Syndrome.

Context: A subset of polycystic ovary syndrome (PCOS) individuals also have type 2 diabetes (T2D); an unmet need to identify this subgroup exists. Objective: We looked at the potential role of serum chemerin, a proinflammatory adipokine, in identifying dysglycemic PCOS. Methods: A total of 93 PCOS and 33 healthy controls were classified, based on fasting and 2-hour plasma glucose levels (2hPGPG) and glycated hemoglobin A1c (HbA1c) (%) into normoglycemic (n = 34), dysglycemic (n = 33), and T2D (n = 26). Serum chemerin were measured by enzyme-linked immunosorbent assay. Homeostatic model 2 assessment of insulin resistance (HOMA-2IR) and homeostatic model 2 assessment of ß-cell function (HOMA-2ß) were computed using serum C-peptide. Results: Metabolic syndrome was present in 9.7% (National Cholesterol Education Program) of PCOS. Waist circumference, body fat (%), 2hPGPG, and HbA1c levels were significantly higher in T2D group. Serum triglycerides/high-density lipoprotein cholesterol (TGs/HDL-c) ratio was increased in PCOS individuals with T2D; no significant changes in total cholesterol and LDL-c levels were seen. Serum chemerin levels were significantly higher (P < .001) in the PCOS group. Total body fat (%), 2hPGPG, HbA1c, and TG/HDL-c ratio correlated positively with chemerin levels. Serum chemerin levels correlated positively with HOMA2IR and negatively with HOMA-2ß. On receiver operating characteristic curve analysis, a serum chemerin cutoff level of greater than 309.3 ng/mL differentiated PCOS individuals with dysglycemia from those without (sensitivity 85.71%, specificity 89.47%). The Cohen kappa test revealed a substantial agreement (P < .001) between chemerin cutoff and 2hPGPG levels greater than 200 mg/dL. The present study is arguably the first ever to define a serum chemerin cutoff to distinguish PCOS individuals with T2D from those without. Conclusion: Elevated serum chemerin levels reliably identify PCOS individuals with dysglycemia. Further, longitudinal studies with larger samples are required to confirm this association.

An assessment of the potential environmental effects of bridge construction in Boga, Patuakhali, Bangladesh.

Bangladesh Road Transport Authority announced a plan to build a bridge over the Lohalia River in Boga, Patuakhali, which will significantly modify the entire communication system and lead to significant economic empowerment in the southeastern part of Bangladesh. This study was designed to help decision-makers through the identification and evaluation of all potential social and environmental consequences of this proposed project using an integrated methodology combining GIS mapping, environmental impact value assessment, and critical evaluation of the environmental impact through the Leopold matrix. The necessary information required for this study has been collected through questionnaire surveys, participatory community risk assessments (CRA), focused group discussions, key informant interviews, and reviews of previously published documents. According to this study, the proposed Boga Bridge construction will have some adverse environmental consequences including agricultural land and productivity loss, the decline of ecosystem health, extinction of endangered species, deterioration of water, air and soil quality, sedimentation and changes in river flow. Despite these adverse impacts this project will improve the life and livelihood of the coastal community and foster economic growth and industrialization over the long run through easily assessable road transportation. Additionally, the estimated overall environmental impact value (-2) and Leopold matrix's impact value (-1.51) revealed that this project has low adverse effects on the surrounding environment. Moreover, the majority of the environmental consequences were found to be transient because they were only limited to the construction phase which makes it simple to control with the proper implementation of appropriate mitigation strategies. Therefore, this study furnished some effective mitigation strategies incorporating mitigation hierarchy principals to avoid and minimize adverse impacts as well as enhance the positive impacts of this project. Finally, this study recommends constructing the proposed Boga Bridge after ensuring rigorous implementation and monitoring of all impact mitigation strategies proposed in this study.

Multi-apical polarity of alveolar stem cells and their dynamics during lung development and regeneration.

Epithelial cells of diverse tissues are characterized by the presence of a single apical domain. In the lung, electron microscopy studies have suggested that alveolar type-2 epithelial cells (AT2s) en face multiple alveolar sacs. However, apical and basolateral organization of the AT2s and their establishment during development and remodeling after injury repair remain unknown. Thick tissue imaging and electron microscopy revealed that a single AT2 can have multiple apical domains that enface multiple alveoli. AT2s gradually establish multi-apical domains post-natally, and they are maintained throughout life. Lineage tracing, live imaging, and selective cell ablation revealed that AT2s dynamically reorganize multi-apical domains during injury repair. Single-cell transcriptome signatures of residual AT2s revealed changes in cytoskeleton and cell migration. Significantly, cigarette smoke and oncogene activation lead to dysregulation of multi-apical domains. We propose that the multi-apical domains of AT2s enable them to be poised to support the regeneration of a large array of alveolar sacs.