Pub Date : 2024-08-22DOI: 10.1007/s12038-024-00454-7
Caglar Berkel, Ercan Cacan
Circadian clocks, biochemical oscillators that are regulated by environmental time cues including the day/night cycle, have a central function in the majority of biological processes. The disruption of the circadian clock can alter breast biology negatively and may promote the development of breast tumors. The expression status of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) were used to classify breast cancer into different molecular subtypes such as triple-negative breast cancer (TNBC). Receptor status-dependent expression of circadian clock genes have been previously studied in breast cancer using relatively small sample sizes in a particular population. Here, using TCGA-BRCA data (n=1119), we found that the expressions of CRY1, PER1, PER2, PER3, BMAL1, CLOCK, RORA, RORB, RORC, NR1D1, NR1D2, and FBXL3 were higher in ER+ breast cancer cells compared with those of ER− status. Similarly, we showed that transcript levels of CRY2, PER1, PER2, PER3, BMAL1, RORA, RORB, RORC, NR1D1, NR1D2, and FBXL3 were higher in PR+ breast cancer cells than in PR− breast cancer cells. We report that the expressions of CRY2, PER1, BMAL1, and RORA were lower, and the expression of NR1D1 was higher, in HER2+ breast cancer cells compared with HER2− breast cancer cells. Moreover, we studied these receptor status-dependent changes in the expressions of circadian clock genes also based on the race and age of breast cancer patients. Lastly, we found that the expressions of CRY2, PER1, PER2, PER3, and CLOCK were higher in non-TNBC than in TNBC, which has the worst prognosis among subtypes. We note that our findings are not always parallel to the observations reported in previous studies with smaller sample sizes performed in different populations and organisms. Our study suggests that receptor status in breast cancer (thus, subtype of breast cancer) might be more important than previously shown in terms of its influence on the expression of circadian clock genes and on the disruption of the circadian clock, and that ER or PR might be important regulators of breast cancer chronobiology that should be taken into account in personalized chronotherapies.
{"title":"A majority of circadian clock genes are expressed in estrogen receptor and progesterone receptor status-dependent manner in breast cancer","authors":"Caglar Berkel, Ercan Cacan","doi":"10.1007/s12038-024-00454-7","DOIUrl":"https://doi.org/10.1007/s12038-024-00454-7","url":null,"abstract":"<p>Circadian clocks, biochemical oscillators that are regulated by environmental time cues including the day/night cycle, have a central function in the majority of biological processes. The disruption of the circadian clock can alter breast biology negatively and may promote the development of breast tumors. The expression status of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) were used to classify breast cancer into different molecular subtypes such as triple-negative breast cancer (TNBC). Receptor status-dependent expression of circadian clock genes have been previously studied in breast cancer using relatively small sample sizes in a particular population. Here, using TCGA-BRCA data (<i>n</i>=1119), we found that the expressions of <i>CRY1</i>, <i>PER1</i>, <i>PER2</i>, <i>PER3</i>, <i>BMAL1</i>, <i>CLOCK</i>, <i>RORA</i>, <i>RORB</i>, <i>RORC</i>, <i>NR1D1</i>, <i>NR1D2</i>, and <i>FBXL3</i> were higher in ER+ breast cancer cells compared with those of ER− status. Similarly, we showed that transcript levels of <i>CRY2</i>, <i>PER1</i>, <i>PER2</i>, <i>PER3</i>, <i>BMAL1</i>, <i>RORA</i>, <i>RORB</i>, <i>RORC</i>, <i>NR1D1</i>, <i>NR1D2</i>, and <i>FBXL3</i> were higher in PR+ breast cancer cells than in PR− breast cancer cells. We report that the expressions of <i>CRY2</i>, <i>PER1</i>, <i>BMAL1</i>, and <i>RORA</i> were lower, and the expression of <i>NR1D1</i> was higher, in HER2+ breast cancer cells compared with HER2− breast cancer cells. Moreover, we studied these receptor status-dependent changes in the expressions of circadian clock genes also based on the race and age of breast cancer patients. Lastly, we found that the expressions of <i>CRY2</i>, <i>PER1</i>, <i>PER2</i>, <i>PER3</i>, and <i>CLOCK</i> were higher in non-TNBC than in TNBC, which has the worst prognosis among subtypes. We note that our findings are not always parallel to the observations reported in previous studies with smaller sample sizes performed in different populations and organisms. Our study suggests that receptor status in breast cancer (thus, subtype of breast cancer) might be more important than previously shown in terms of its influence on the expression of circadian clock genes and on the disruption of the circadian clock, and that ER or PR might be important regulators of breast cancer chronobiology that should be taken into account in personalized chronotherapies.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"79 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142187587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-06DOI: 10.1007/s12038-024-00464-5
Karishma Bhatia, Sandhya Tiwari, Vikas Kumar Gupta, Neerav M Sapariya, Sanjeev K Upadhyay
Obesity-related chronic low-grade inflammation plays a central role in the development of insulin resistance. Macrophages are key players in adipose tissue homeostasis, and their phenotypic shift from the anti-inflammatory or alternatively activated (M2) form to the pro-inflammatory, classically activated (M1) form is a hallmark of insulin resistance. However, adipose tissue macrophages (ATMs) have been identified as a distinct subpopulation of macrophages in several recent studies. These ATMs, described as metabolically activated macrophages (MMe), differ from M1 and are primarily found in the adipose tissue of obese individuals. In our study, we developed an in vitro model of MMe macrophages to establish a simple and reproducible system to understand their characteristics and role in the pathophysiology of insulin resistance. We examined their characteristics such as inflammatory patterns, surface markers, and metabolic features, and compared them with M1 and M2 macrophages. We found that a cell line-based in vitro model effectively mirrors the characteristics of ATMs, highlighting distinct inflammatory phenotypes, metabolism, surface markers, altered lysosomal activity, and ER stress akin to macrophages in vivo. This model captures the subtle distinctions between MMe and M1, and can be effectively used to study several features of macrophage–adipose interactions of therapeutic importance.
{"title":"An in vitro model of adipose tissue-associated macrophages","authors":"Karishma Bhatia, Sandhya Tiwari, Vikas Kumar Gupta, Neerav M Sapariya, Sanjeev K Upadhyay","doi":"10.1007/s12038-024-00464-5","DOIUrl":"https://doi.org/10.1007/s12038-024-00464-5","url":null,"abstract":"<p>Obesity-related chronic low-grade inflammation plays a central role in the development of insulin resistance. Macrophages are key players in adipose tissue homeostasis, and their phenotypic shift from the anti-inflammatory or alternatively activated (M2) form to the pro-inflammatory, classically activated (M1) form is a hallmark of insulin resistance. However, adipose tissue macrophages (ATMs) have been identified as a distinct subpopulation of macrophages in several recent studies. These ATMs, described as metabolically activated macrophages (MMe), differ from M1 and are primarily found in the adipose tissue of obese individuals. In our study, we developed an <i>in vitro</i> model of MMe macrophages to establish a simple and reproducible system to understand their characteristics and role in the pathophysiology of insulin resistance. We examined their characteristics such as inflammatory patterns, surface markers, and metabolic features, and compared them with M1 and M2 macrophages. We found that a cell line-based <i>in vitro</i> model effectively mirrors the characteristics of ATMs, highlighting distinct inflammatory phenotypes, metabolism, surface markers, altered lysosomal activity, and ER stress akin to macrophages <i>in vivo</i>. This model captures the subtle distinctions between MMe and M1, and can be effectively used to study several features of macrophage–adipose interactions of therapeutic importance.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"35 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141932372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-06DOI: 10.1007/s12038-024-00447-6
Manaswita Saikia, Dhruba K Bhattacharyya, Jugal K Kalita
Single-cell RNA sequencing (scRNA-Seq) technology provides the scope to gain insight into the interplay between intrinsic cellular processes as well as transcriptional and behavioral changes in gene–gene interactions across varying conditions. The high level of scarcity of scRNA-seq data, however, poses a significant challenge for analysis. We propose a complete differential co-expression (DCE) analysis framework for scRNA-Seq data to extract network modules and identify hub-genes. The performance of our method has been shown to be satisfactory after validation using an scRNA-Seq esophageal squamous cell carcinoma (ESCC) dataset. From comparison with four other existing hub-gene finding methods, it has been observed that our method performs better in the majority of cases and has the ability to identify unique potential biomarkers that were not detected by the other methods. The potential biomarker genes identified by our framework, differential co-expression analysis method for single-cell RNA sequencing data (scDiffCoAM), have been validated both statistically and biologically.
{"title":"scDiffCoAM: A complete framework to identify potential biomarkers for esophageal squamous cell carcinoma using scRNA-Seq data analysis","authors":"Manaswita Saikia, Dhruba K Bhattacharyya, Jugal K Kalita","doi":"10.1007/s12038-024-00447-6","DOIUrl":"https://doi.org/10.1007/s12038-024-00447-6","url":null,"abstract":"<p>Single-cell RNA sequencing (scRNA-Seq) technology provides the scope to gain insight into the interplay between intrinsic cellular processes as well as transcriptional and behavioral changes in gene–gene interactions across varying conditions. The high level of scarcity of scRNA-seq data, however, poses a significant challenge for analysis. We propose a complete differential co-expression (DCE) analysis framework for scRNA-Seq data to extract network modules and identify hub-genes. The performance of our method has been shown to be satisfactory after validation using an scRNA-Seq esophageal squamous cell carcinoma (ESCC) dataset. From comparison with four other existing hub-gene finding methods, it has been observed that our method performs better in the majority of cases and has the ability to identify unique potential biomarkers that were not detected by the other methods. The potential biomarker genes identified by our framework, differential co-expression analysis method for single-cell RNA sequencing data (scDiffCoAM), have been validated both statistically and biologically.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"303 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141932494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-26DOI: 10.1007/s12038-024-00450-x
Ricardo A Fochi, Thalles F R Ruiz, Mariana M Jesus, Lucas R Azevedo, Luiz R Falleiros-Júnior, Silvana G P Campos, Rejane M Góes, Sonia M Oliani, Patricia S L Vilamaior, Sebastião R Taboga
Paradoxical sleep deprivation (PSD) presents different effects on metabolism and neurological functions. In addition, over long duration, sleep restriction (SR) can promote permanent changes. The prostate is an endocrine-dependent organ with homeostatic regulation directly related to hormone levels. Our study proposed to demonstrate the experimental prostatic effects of PSD (96 h), PSD with recovery (PSR – 96/96 h), and sleep restriction (SR – 30 PSD cycles/recovery). PSD and SR promoted decrease in serum testosterone and significant increase in serum and intraprostatic corticosterone. In agreement, androgen receptors (AR) were less expressed and glucocorticoid receptors (GR) were enhanced in PSR and SR. Thus, the prostate, especially under SR, demonstrates a castration-like effect due to loss of responsiveness and sensitization by androgens. SR triggered an important inflammatory response through enhancement of serum and intraprostatic pro- (IL-1α, IL-6, TNF-α) and anti-inflammatory (IL-10) cytokines. Furthermore, the respective receptors of anti-inflammatory cytokines (IL-1RI and TNF-R) were highly expressed in the prostatic epithelium and stroma. PSR can partially restore prostate homeostasis, as it restores testosterone and the prostate proliferation index, in addition to promoting balance in the inflammatory response that is considered protective. PSD and SR are key factors in the endocrine axis that coordinate prostatic homeostasis, and significant changes in these factors have consequences on prostate functionality.
Graphical abstract
矛盾性剥夺睡眠(PSD)会对新陈代谢和神经功能产生不同的影响。此外,长期限制睡眠(SR)会导致永久性变化。前列腺是一个依赖内分泌的器官,其平衡调节与激素水平直接相关。我们的研究拟证明 PSD(96 小时)、PSD 与恢复(PSR - 96/96 小时)和睡眠限制(SR - 30 PSD 周期/恢复)对前列腺的实验性影响。PSD 和 SR 会导致血清睾酮下降,血清和前列腺内皮质酮显著增加。同样,在 PSR 和 SR 中,雄激素受体(AR)表达较少,糖皮质激素受体(GR)表达增强。因此,前列腺,尤其是在 SR 条件下,由于对雄激素失去反应性和敏感性,表现出类似阉割的效应。SR通过增强血清和前列腺内促炎症(IL-1α、IL-6、TNF-α)和抗炎症(IL-10)细胞因子,引发了重要的炎症反应。此外,抗炎细胞因子的相应受体(IL-1RI 和 TNF-R)在前列腺上皮细胞和基质中高度表达。PSR 能部分恢复前列腺的平衡,因为它能恢复睾酮和前列腺增生指数,此外还能促进被认为具有保护作用的炎症反应的平衡。PSD和SR是协调前列腺稳态的内分泌轴的关键因素,这些因素的显著变化会对前列腺功能产生影响。
{"title":"Paradoxical sleep deprivation and restriction promote castration-like effects and local inflammatory responses in male gerbil prostate","authors":"Ricardo A Fochi, Thalles F R Ruiz, Mariana M Jesus, Lucas R Azevedo, Luiz R Falleiros-Júnior, Silvana G P Campos, Rejane M Góes, Sonia M Oliani, Patricia S L Vilamaior, Sebastião R Taboga","doi":"10.1007/s12038-024-00450-x","DOIUrl":"https://doi.org/10.1007/s12038-024-00450-x","url":null,"abstract":"<p>Paradoxical sleep deprivation (PSD) presents different effects on metabolism and neurological functions. In addition, over long duration, sleep restriction (SR) can promote permanent changes. The prostate is an endocrine-dependent organ with homeostatic regulation directly related to hormone levels. Our study proposed to demonstrate the experimental prostatic effects of PSD (96 h), PSD with recovery (PSR – 96/96 h), and sleep restriction (SR – 30 PSD cycles/recovery). PSD and SR promoted decrease in serum testosterone and significant increase in serum and intraprostatic corticosterone. In agreement, androgen receptors (AR) were less expressed and glucocorticoid receptors (GR) were enhanced in PSR and SR. Thus, the prostate, especially under SR, demonstrates a castration-like effect due to loss of responsiveness and sensitization by androgens. SR triggered an important inflammatory response through enhancement of serum and intraprostatic pro- (IL-1α, IL-6, TNF-α) and anti-inflammatory (IL-10) cytokines. Furthermore, the respective receptors of anti-inflammatory cytokines (IL-1RI and TNF-R) were highly expressed in the prostatic epithelium and stroma. PSR can partially restore prostate homeostasis, as it restores testosterone and the prostate proliferation index, in addition to promoting balance in the inflammatory response that is considered protective. PSD and SR are key factors in the endocrine axis that coordinate prostatic homeostasis, and significant changes in these factors have consequences on prostate functionality.</p><h3 data-test=\"abstract-sub-heading\">Graphical abstract</h3>\u0000","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"26 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141770881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-23DOI: 10.1007/s12038-024-00463-6
Vivek Nityananda
Bees have been excellent model systems to study social learning – the ability of animals to change their behaviour based on observations of other individuals. Researchers have investigated several aspects of social learning in bees, including how it can lead to cultural traditions. A recent study also argues that bees have the capacity to socially learn behaviours that they could not innovate on their own. To understand these findings better, I review what we know about the mechanisms underlying social learning in bees and use these findings to compare social learning and culture in bees and humans. The findings suggest that the seemingly complex social behaviours of bees could arise from simple mechanisms underlying learning in general. I highlight the importance of investigating cognitive mechanisms and how they might differ across animals.
{"title":"Social learning and culture in bees: Simple mechanisms, complex outcomes","authors":"Vivek Nityananda","doi":"10.1007/s12038-024-00463-6","DOIUrl":"https://doi.org/10.1007/s12038-024-00463-6","url":null,"abstract":"<p>Bees have been excellent model systems to study social learning – the ability of animals to change their behaviour based on observations of other individuals. Researchers have investigated several aspects of social learning in bees, including how it can lead to cultural traditions. A recent study also argues that bees have the capacity to socially learn behaviours that they could not innovate on their own. To understand these findings better, I review what we know about the mechanisms underlying social learning in bees and use these findings to compare social learning and culture in bees and humans. The findings suggest that the seemingly complex social behaviours of bees could arise from simple mechanisms underlying learning in general. I highlight the importance of investigating cognitive mechanisms and how they might differ across animals.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"25 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141770882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rice production is severely affected by various diseases such as bacterial leaf blight (BLB), brown spot (BS), false smut (FS), foot rot (FR), rice blast (RB), and sheath blight (SB). In recent years, several quantitative trait loci (QTLs) studies involving different populations have been carried out, resulting in the identification of hundreds of resistance QTLs for each disease. These QTLs can be integrated and analyzed using meta-QTL (MQTL) analysis for better understanding of the genetic architecture underlying multiple disease resistance (MDR). This study involved an MQTL analysis on 661 QTLs (378, 161, 21, 41, 44, and 16 QTLs for SB, RB, BLB, BS, FS, and FR, respectively) retrieved from 50 individual studies published from 1995 to 2021. Of these, 503 QTLs were projected finally onto the consensus map saturated with 6,275 markers, resulting in 73 MQTLs, including 27 MDR-MQTLs conferring resistance to three or more diseases. Forty-seven MQTLs were validated using marker-trait associations identified in published genome-wide association studies. A total of 3,310 genes, including both R and defense genes, were also identified within some selected high-confidence MQTL regions that were investigated further for the syntenic relationship with barley, wheat, and maize genomes. Thirty-nine high-confidence candidate genes were selected based on their expression patterns and recommended for future studies involving functional validation, genetic engineering, and gene editing. Nineteen MQTLs were co-localized with 39 known R genes for BLB and RB diseases. These results could pave the way to utilize candidate genes in a marker-assisted breeding program for MDR in rice.
{"title":"Defining genomic landscape for identification of potential candidate resistance genes associated with major rice diseases through MetaQTL analysis","authors":"Simran Goyal, Dinesh Kumar Saini, Pankaj Kumar, Gurwinder Kaur, Umesh Preethi Praba, Krishna Sai Karnatam, Gautam Chhabra, Rajveer Singh, Yogesh Vikal","doi":"10.1007/s12038-024-00460-9","DOIUrl":"https://doi.org/10.1007/s12038-024-00460-9","url":null,"abstract":"<p>Rice production is severely affected by various diseases such as bacterial leaf blight (BLB), brown spot (BS), false smut (FS), foot rot (FR), rice blast (RB), and sheath blight (SB). In recent years, several quantitative trait loci (QTLs) studies involving different populations have been carried out, resulting in the identification of hundreds of resistance QTLs for each disease. These QTLs can be integrated and analyzed using meta-QTL (MQTL) analysis for better understanding of the genetic architecture underlying multiple disease resistance (MDR). This study involved an MQTL analysis on 661 QTLs (378, 161, 21, 41, 44, and 16 QTLs for SB, RB, BLB, BS, FS, and FR, respectively) retrieved from 50 individual studies published from 1995 to 2021. Of these, 503 QTLs were projected finally onto the consensus map saturated with 6,275 markers, resulting in 73 MQTLs, including 27 MDR-MQTLs conferring resistance to three or more diseases. Forty-seven MQTLs were validated using marker-trait associations identified in published genome-wide association studies. A total of 3,310 genes, including both R and defense genes, were also identified within some selected high-confidence MQTL regions that were investigated further for the syntenic relationship with barley, wheat, and maize genomes. Thirty-nine high-confidence candidate genes were selected based on their expression patterns and recommended for future studies involving functional validation, genetic engineering, and gene editing. Nineteen MQTLs were co-localized with 39 known R genes for BLB and RB diseases. These results could pave the way to utilize candidate genes in a marker-assisted breeding program for MDR in rice.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"32 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141770885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-18DOI: 10.1007/s12038-024-00453-8
Meenakshi Tellis, Sharada Mohite, Rakesh Joshi
Trehalose serves as a primary circulatory sugar in insects which is crucial in energy metabolism and stress recovery. It is hydrolyzed into two glucose molecules by trehalase. Silencing or inhibiting trehalase results in reduced fitness, developmental defects, and insect mortality. Despite its importance, the molecular response of insects to trehalase inhibition is not known. Here, we performed transcriptomic analyses of Helicoverpa armigera treated with validamycin A (VA), a trehalase inhibitor. VA ingestion resulted in increased mortality, developmental delay, and reduced ex vivo trehalase activity. Pathway enrichment and gene ontology analyses suggest that key genes involved in carbohydrate, protein, fatty acid, and mitochondria-related metabolisms are deregulated. The activation of protein and fat degradation may be necessary to fulfil energy requirements, evidenced by the dysregulated expression of critical genes in these metabolisms. Co-expression analysis supports the notion that trehalase inhibition leads to putative interaction with key regulators of other pathways. Metabolomics correlates with transcriptomics to show reduced levels of key energy metabolites. VA generates an energy-deficient condition, and insects activate alternate pathways to facilitate the energy demand. Overall, this study provides insights into the molecular mechanisms underlying the response of insects to trehalase inhibition and highlights potential targets for insect control.
曲哈糖是昆虫体内的主要循环糖,对能量代谢和应激恢复至关重要。它通过曲哈糖酶水解成两个葡萄糖分子。沉默或抑制三卤糖酶会导致昆虫体能下降、发育缺陷和死亡。尽管trehalase很重要,但昆虫对trehalase抑制的分子反应还不清楚。在这里,我们对用三卤酶抑制剂有效霉素 A(VA)处理的 Helicoverpa armigera 进行了转录组分析。摄入 VA 会导致死亡率上升、发育迟缓以及体内外三卤酶活性降低。通路富集和基因本体分析表明,参与碳水化合物、蛋白质、脂肪酸和线粒体相关代谢的关键基因发生了失调。激活蛋白质和脂肪降解可能是满足能量需求的必要条件,这些代谢过程中关键基因的表达失调就是证明。共表达分析支持这样一种观点,即三卤素酶抑制会导致与其他通路的关键调控因子发生假定的相互作用。代谢组学与转录组学相互关联,显示出关键能量代谢产物水平的降低。VA 会产生能量不足的情况,昆虫会激活其他途径来满足能量需求。总之,这项研究深入揭示了昆虫对曲卤酶抑制反应的分子机制,并突出了昆虫控制的潜在目标。
{"title":"Trehalase inhibition in Helicoverpa armigera activates machinery for alternate energy acquisition","authors":"Meenakshi Tellis, Sharada Mohite, Rakesh Joshi","doi":"10.1007/s12038-024-00453-8","DOIUrl":"https://doi.org/10.1007/s12038-024-00453-8","url":null,"abstract":"<p>Trehalose serves as a primary circulatory sugar in insects which is crucial in energy metabolism and stress recovery. It is hydrolyzed into two glucose molecules by trehalase. Silencing or inhibiting trehalase results in reduced fitness, developmental defects, and insect mortality. Despite its importance, the molecular response of insects to trehalase inhibition is not known. Here, we performed transcriptomic analyses of <i>Helicoverpa armigera</i> treated with validamycin A (VA), a trehalase inhibitor. VA ingestion resulted in increased mortality, developmental delay, and reduced <i>ex vivo</i> trehalase activity. Pathway enrichment and gene ontology analyses suggest that key genes involved in carbohydrate, protein, fatty acid, and mitochondria-related metabolisms are deregulated. The activation of protein and fat degradation may be necessary to fulfil energy requirements, evidenced by the dysregulated expression of critical genes in these metabolisms. Co-expression analysis supports the notion that trehalase inhibition leads to putative interaction with key regulators of other pathways. Metabolomics correlates with transcriptomics to show reduced levels of key energy metabolites. VA generates an energy-deficient condition, and insects activate alternate pathways to facilitate the energy demand. Overall, this study provides insights into the molecular mechanisms underlying the response of insects to trehalase inhibition and highlights potential targets for insect control.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"61 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141740144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-10DOI: 10.1007/s12038-024-00455-6
Prakash Paraseth, Kakoli Banerjee
The Kunming–Montreal Global Biodiversity Framework (GBF) is a recently signed protocol by the conference of the parties (COP 15) with an aim to protect biodiversity from risks imposed by biological threats such as invasive alien species (IAS). The present work is an effort to meet target 6 of GBF which directly deals with IAS by assessing the current and future distribution of Ageratum species in regions of the Eastern Ghats of India. Prediction of Ageratum distribution was done based on greenhouse gas emission levels, namely RCP 4.5, 6.0 and 8.5 for the climatic years 2030, 2050 and 2080. Of a total of 23 environmental parameters (19 bioclimatic, 1 land use land cover (LULC) and 3 topographic) seven were selected for species distribution modeling (SDM) considering value inflation factor (VIF) scores <3 by using maximum entropy. In the current climatic scenario, 40.09% of the geographical area (TGA) is covered by Ageratum species which will reach 76.51%, 77.44%, 82.58% for RCP 4.5, 6.0 and 8.5 respectively by the end of 2100. Both the AUC value (0.884) and Jackknife test have shown a good model performance. The Eastern Ghats, being a biodiversity-rich zone, needs efficient conservation and management strategies to decrease the extent of invaded areas to maximize biodiversity returns.
{"title":"Goat weed (Ageratum conyzoides L.): A biological threat to plant diversity in Eastern Ghats of India","authors":"Prakash Paraseth, Kakoli Banerjee","doi":"10.1007/s12038-024-00455-6","DOIUrl":"https://doi.org/10.1007/s12038-024-00455-6","url":null,"abstract":"<p>The Kunming–Montreal Global Biodiversity Framework (GBF) is a recently signed protocol by the conference of the parties (COP 15) with an aim to protect biodiversity from risks imposed by biological threats such as invasive alien species (IAS). The present work is an effort to meet target 6 of GBF which directly deals with IAS by assessing the current and future distribution of <i>Ageratum</i> species in regions of the Eastern Ghats of India. Prediction of <i>Ageratum</i> distribution was done based on greenhouse gas emission levels, namely RCP 4.5, 6.0 and 8.5 for the climatic years 2030, 2050 and 2080. Of a total of 23 environmental parameters (19 bioclimatic, 1 land use land cover (LULC) and 3 topographic) seven were selected for species distribution modeling (SDM) considering value inflation factor (VIF) scores <3 by using maximum entropy. In the current climatic scenario, 40.09% of the geographical area (TGA) is covered by <i>Ageratum</i> species which will reach 76.51%, 77.44%, 82.58% for RCP 4.5, 6.0 and 8.5 respectively by the end of 2100. Both the AUC value (0.884) and Jackknife test have shown a good model performance. The Eastern Ghats, being a biodiversity-rich zone, needs efficient conservation and management strategies to decrease the extent of invaded areas to maximize biodiversity returns.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"25 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141569606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nitric oxide (NO) and iNOS are crucial host factors in innate immunity against intracellular pathogens. However, the role of NO in Mycobacterium tuberculosis (M. tb) infection in humans remains controversial, unlike in the murine model of TB. To investigate this, levels of NO, iNOS, and L-arginine, as well as the NOS2A gene polymorphism rs57234985 at the promoter region of NOS2A, were evaluated in pulmonary TB (PTB) patients and their household contacts (HHCs). Increased levels of NO and iNOS expression in HHCs indicated exposure to M. tb infection which was confirmed by higher levels of iNOS and NO in Mantoux-positive individuals. Furthermore, higher levels of arginine were detected in HHCs, suggesting its potential role in promoting optimal NO synthesis. PTB patients had higher levels of these analytes due to ongoing active infection. Interestingly, iNOS and NO levels were inversely related to bacterial burden, suggesting their antimicrobial role. NOS2A gene polymorphism was found to be associated with disease susceptibility, with the TT genotype linked to increased iNOS expression. To conclude, iNOS plays a crucial role in controlling early M. tb infection in HHCs by inducing optimal NO production with help of L-arginine. Further longitudinal studies are needed to better understand the role of these host factors upon disease activation.
一氧化氮(NO)和 iNOS 是先天性免疫中抵抗细胞内病原体的关键宿主因子。然而,与小鼠结核病模型不同,一氧化氮在人类结核分枝杆菌(M. tb)感染中的作用仍存在争议。为了研究这个问题,我们对肺结核(PTB)患者及其家庭接触者(HHCs)体内的 NO、iNOS 和 L-精氨酸水平以及 NOS2A 启动子区的 NOS2A 基因多态性 rs57234985 进行了评估。HHCs 中 NO 和 iNOS 表达水平的升高表明他们受到了结核杆菌的感染,而 Mantoux 阳性者体内较高水平的 iNOS 和 NO 也证实了这一点。此外,在 HHCs 中还检测到了较高水平的精氨酸,这表明精氨酸在促进最佳 NO 合成方面具有潜在作用。由于持续的活动性感染,肺结核患者体内这些分析物的水平更高。有趣的是,iNOS 和 NO 的水平与细菌负荷成反比,这表明它们具有抗菌作用。研究发现,NOS2A 基因多态性与疾病易感性有关,TT 基因型与 iNOS 表达增加有关。总之,iNOS 在 L-精氨酸的帮助下诱导产生最佳的 NO,从而在控制 HHC 早期 M. tb 感染方面发挥了关键作用。要更好地了解这些宿主因素在疾病激活时的作用,还需要进一步的纵向研究。
{"title":"Nitric oxide brings innate immune resistance to M. tuberculosis infection among high-risk household contacts of pulmonary tuberculosis patients","authors":"Sudhasini Panda, Ambrish Tiwari, Kalpana Luthra, Kuldeep Kumar, Archana Singh","doi":"10.1007/s12038-024-00459-2","DOIUrl":"https://doi.org/10.1007/s12038-024-00459-2","url":null,"abstract":"<p>Nitric oxide (NO) and iNOS are crucial host factors in innate immunity against intracellular pathogens. However, the role of NO in <i>Mycobacterium tuberculosis</i> (M. tb) infection in humans remains controversial, unlike in the murine model of TB. To investigate this, levels of NO, iNOS, and L-arginine, as well as the <i>NOS2A</i> gene polymorphism rs57234985 at the promoter region of <i>NOS2A</i>, were evaluated in pulmonary TB (PTB) patients and their household contacts (HHCs). Increased levels of NO and iNOS expression in HHCs indicated exposure to M. tb infection which was confirmed by higher levels of iNOS and NO in Mantoux-positive individuals. Furthermore, higher levels of arginine were detected in HHCs, suggesting its potential role in promoting optimal NO synthesis. PTB patients had higher levels of these analytes due to ongoing active infection. Interestingly, iNOS and NO levels were inversely related to bacterial burden, suggesting their antimicrobial role. <i>NOS2A</i> gene polymorphism was found to be associated with disease susceptibility, with the TT genotype linked to increased iNOS expression. To conclude, iNOS plays a crucial role in controlling early M. tb infection in HHCs by inducing optimal NO production with help of L-arginine. Further longitudinal studies are needed to better understand the role of these host factors upon disease activation.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"83 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141569607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amyloids interact with plasma membranes. Extracellular amyloids cross the plasma membrane barrier. Internalized extracellular amyloids are reported to trigger amyloidogenesis of endogenous proteins in recipient cells. To what extent these extracellular and intracellular amyloids perturb the plasma membrane proteome is not investigated. Using α-synuclein as a model amyloid protein, we performed membrane shaving followed by mass spectrometry experiments to identify the conformational changes in cell surface proteins after extracellular amyloid challenge. We also performed membrane proteomics after the biogenesis of intracellular α-synuclein amyloids. Our results suggest that promiscuous interactions with extracellular amyloids stochastically alter the conformation of plasma membrane proteins. This affects the biological processes through the plasma membrane and results in loss of cell viability. Cells that survive the extracellular amyloid shock can grow normally and gradually develop intracellular amyloids which do not directly impact the plasma membrane proteome and associated biological processes. Thus, our results suggest that α-synuclein amyloids can damage the plasma membrane and related processes during cell-to-cell transfer and not during their intracellular biogenesis.
{"title":"Cell membrane proteome analysis in HEK293T cells challenged with α-synuclein amyloids","authors":"Harshit Vaish, Shemin Mansuri, Aanchal Jain, Swasti Raychaudhuri","doi":"10.1007/s12038-024-00457-4","DOIUrl":"https://doi.org/10.1007/s12038-024-00457-4","url":null,"abstract":"<p>Amyloids interact with plasma membranes. Extracellular amyloids cross the plasma membrane barrier. Internalized extracellular amyloids are reported to trigger amyloidogenesis of endogenous proteins in recipient cells. To what extent these extracellular and intracellular amyloids perturb the plasma membrane proteome is not investigated. Using α-synuclein as a model amyloid protein, we performed membrane shaving followed by mass spectrometry experiments to identify the conformational changes in cell surface proteins after extracellular amyloid challenge. We also performed membrane proteomics after the biogenesis of intracellular α-synuclein amyloids. Our results suggest that promiscuous interactions with extracellular amyloids stochastically alter the conformation of plasma membrane proteins. This affects the biological processes through the plasma membrane and results in loss of cell viability. Cells that survive the extracellular amyloid shock can grow normally and gradually develop intracellular amyloids which do not directly impact the plasma membrane proteome and associated biological processes. Thus, our results suggest that α-synuclein amyloids can damage the plasma membrane and related processes during cell-to-cell transfer and not during their intracellular biogenesis.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"37 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141547708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}