Selective autophagy: the fulcrum of plant-virus interaction.

Selective autophagy receptors play both proviral and antiviral roles during plant-virus interaction. However, little is known about the balance between such contradictory dual roles of these receptors. Tong et al. have deciphered the temporal regulation of antiviral and antiplant roles of a selective autophagy receptor, a virus-induced small peptide 1 (VISP1).

The Real DAPSI: A Real-World Retrospective Study on Assessing the Efficacy and Safety of a Fixed-Dose Combination of Dapagliflozin and Sitagliptin in the Indian Population.

Introduction Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder affecting millions of individuals worldwide. Effective management of T2DM is crucial to prevent complications. Dapagliflozin and sitagliptin are oral anti-diabetic agents that have been shown to provide synergistic effects in controlling blood glucose levels. However, there is limited data on the efficacy and safety of the dapagliflozin-sitagliptin fixed-dose combination (FDC) in the Indian population. This study aimed to evaluate the real-world effectiveness and safety of the dapagliflozin-sitagliptin FDC in the Indian population. Methods This was a retrospective study conducted at healthcare centers in India. The study included patients with T2DM who were prescribed a FDC of dapagliflozin and sitagliptin. Data were collected from the medical health records of patients, including demographics, baseline glycated hemoglobin (HbA1c), blood glucose levels, BMI, blood pressure, and adverse events. The primary outcome was the change in HbA1c, postprandial plasma glucose (PPG), and fasting plasma glucose (FPG) from baseline to 12 weeks after treatment initiation. Results A total of 358 patients were included in the study, with a mean age of 56.2 years. The majority of the patients were male (68.2%), and the mean baseline HbA1c was 8.9 ± 0.87%. After 12 weeks of treatment with dapagliflozin and sitagliptin, there was a significant reduction in HbA1c levels from 8.9 to 7.2 (p <0.0001). There was also a significant reduction in fasting blood glucose levels from 178.8 to 124.0 (p <0.0001) and postprandial blood glucose levels from 273.9 to 176.0 (p <0.0001). There were no serious adverse events reported during the study period. Conclusion The FDC of dapagliflozin and sitagliptin is effective and safe in reducing blood glucose levels and BMI in the Indian population with T2DM. This real-world retrospective study provides valuable insights into the clinical effectiveness and safety of dapagliflozin-sitagliptin FDC in the Indian population. These findings highlight the potential benefits of this combination therapy in managing T2DM and pave the way for optimized treatment strategies and improved patient outcomes in the Indian healthcare landscape. Clinicians may consider dapagliflozin-sitagliptin FDC as a viable treatment option for T2DM patients.

Post translational modifications at the verge of plant-geminivirus interaction.

Plant-virus interaction is a complex phenomenon and involves the communication between plant and viral factors. Viruses have very limited coding ability yet, they are able to cause infection which results in huge agro-economic losses throughout the globe each year. Post-translational modifications (PTMs) are covalent modifications of proteins that have a drastic effect on their conformation, stability and function. Like the host proteins, geminiviral proteins are also subject to PTMs and these modifications greatly expand the diversity of their functions. Additionally, these viral proteins can also interact with the components of PTM pathways and modulate them. Several studies have highlighted the importance of PTMs such as phosphorylation, ubiquitination, SUMOylation, myristoylation, S-acylation, acetylation and methylation in plant-geminivirus interaction. PTMs also regulate epigenetic modifications during geminivirus infection which determines viral gene expression. In this review, we have summarized the role of PTMs in regulating geminiviral protein function, influence of PTMs on viral gene expression and how geminiviral proteins interact with the components of PTM pathways to modulate their function.

Healthcare Practitioners' Perspective of Prevailing Awareness on Diabetes Complications: A Questionnaire-Based Pan-India Study.

The increasing prevalence rate of diabetes mellitus (DM) and the associated long-term complications warrant a need to improve awareness of DM-related complications in the Indian population. Our questionnaire-based pan-India study (April 2021-March 2022) aims to capture the observations of healthcare practitioners (HCPs) on the prevailing level of knowledge and awareness regarding diabetes among their patients. We refer to this as the 90:90:90 program. It aims to achieve 90% awareness, 90% screening and detection of diabetes and prediabetes, and 90% achievement of effective treatment and control. A structured questionnaire was circulated to 1800 HCPs using Google Forms (Google, Mountain View, CA) and Zoom poll questions (Zoom Video Communications, Inc., San Jose, CA) during 125 symposiums. About half (48.6%) of the HCPs observe that less than 40% of their patients are aware of the risk factors of diabetes, and less than 60% of the patients were aware of its cardiovascular complications. About 92-95% of the HCPs recommend screening for diabetes in adults over 30 years of age and suggest the inclusion of a blood glucose estimate as a fifth vital to be tested during doctor visits. Less than 40% of patients fail to achieve the treatment goal, possibly due to lack of adherence, access to medicines, and financial constraints. Therefore, spreading awareness of DM complications and early screening for DM among adults (>30 years) could help achieve better management and treatment outcomes.

Recent perspective of non-coding RNAs at the nexus of plant-pathogen interaction.

In natural habitats, plants are exploited by pathogens in biotrophic or necrotrophic ways. Concurrently, plants have evolved their defense systems for rapid perception of pathogenic effectors and begin concerted cellular reprogramming pathways to confine the pathogens at the entry sites. During the reorganization of cellular signaling mechanisms following pathogen attack, non-coding RNAs serves an indispensable role either as a source of resistance or susceptibility. Besides the well-studied functions of non-coding RNAs related to plant development and abiotic stress responses, previous and recent discoveries have established that non-coding RNAs like miRNAs, siRNAs, lncRNAs and phasi-RNAs can fine tune plant defense responses by targeting various signaling pathways. In this review, recapitulation of previous reports associated with non-coding RNAs as a defense responder against virus, bacteria and fungus attacks and insightful discussion will lead us to conceive innovative ideas to fight against approaching threats of resistant breaking pathogens.

Suppressing plant defense: Scavenge the ROS!

Reactive oxygen species (ROS)-mediated defense against fungal pathogens is an essential arm of plant immunity. As a counter defense, these pathogens synthesize antioxidant enzymes that scavenge the ROS produced by plants. The molecular mechanism behind the upregulation of these enzymes in fungal pathogens was unknown. A recent study by Zhang et al. (2023, https://doi.org/10.15252/embj.2022112634) has shed light on the mechanism, and it has been shown that deacetylation of FolSrpk1 protein on the K304 residue following oxidative stress is an important event in the signaling cascade leading to ROS detoxification in Fusarium oxysporum f. sp. lycopersici. Deacetylated FolSrpk1 moves to the nucleus where it hyperphosphorylates FolSr1, which further regulates the transcription of antioxidant enzymes. This mechanism of ROS detoxification is conserved in Botrytis cinerea as well. Several other phytopathogenic fungi have a corresponding K304 site and NLS present in their Srpk1, suggesting a similar mechanism of ROS detoxification and suppression of plant defense. In this article, we have presented our views on how future studies can be synthesized based on the pathway deciphered by Zhang et al. (2023, https://doi.org/10.15252/embj.2022112634).

Mycoviral gene-incorporating phytopathogenic fungi: a biocontrol agent.

Fungal pathogens cause devastating agroeconomic losses. Chemical fungicides are used to control fungal diseases, although this is not an ecofriendly approach. A recent study by Liu et al. highlighted the use of mycoviral gene-incorporating phytopathogenic fungi as biocontrol agents for disease management.

Ubiquitination from the perspective of plant pathogens.

The constant battle of survival between pathogens and host plants has played a crucial role in shaping the course of their co-evolution. However, the major determinants of the outcome of this ongoing arms race are the effectors secreted by pathogens into host cells. These effectors perturb the defense responses of plants to promote successful infection. In recent years, extensive research in the area of effector biology has reported an increase in the repertoire of pathogenic effectors that mimic or target the conserved ubiquitin-proteasome pathway. The role of the ubiquitin-mediated degradation pathway is well known to be indispensable for various aspects of a plant's life, and thus targeting or mimicking it seems to be a smart strategy adopted by pathogens. Therefore, this review summarizes recent findings on how some pathogenic effectors mimic or act as one of the components of the ubiquitin-proteasome machinery while others directly target the plant's ubiquitin-proteasome system.

Osmosensing in plants: mystery unveiled.

Osmotic stress limits plant growth and productivity. The downstream signaling components involved in osmotic adjustments are well known, but our knowledge of the perception of osmotic stress is far too limited. Wang et al. have recently identified a lesser-known mechanism of bimolecular condensation that underlies osmotic stress perception in plants.

Unraveling the mystery of viroid nuclear import.

Viroids are closed-circular infectious RNAs that are known to infect plants. Despite their small noncoding genome, they have the ability to cause disease. The nuclear import mechanism of nucleus replicating viroids is not well understood. Ma et al. have recently highlighted the route of viroid entry into the nucleus.

Horizontal gene transfer and the evolution of land plants.

Horizontal gene transfer (HGT) is the transfer of genetic material between organisms. It has been known for some time that HGT in eukaryotes is not a rare phenomenon. A recent study by Ma et al. has shown that HGT has played a crucial role in shaping the evolution of land plants.

Shedding light on immune suppression at high temperature.

Rising temperatures pose a threat to agriculture in the present times. Salicylic acid (SA) accumulation and signaling is repressed at high temperatures leading to a compromise in plant immunity against pathogens. The mechanism behind this suppression was unknown. Recent evidence from Kim et al. suggests that CBP60g transcription is the key thermosensitive step.

Resistance genes on the verge of plant-virus interaction.

Viruses are acellular pathogens that cause severe infections in plants, resulting in worldwide crop losses every year. The lack of chemical agents to control viral diseases exacerbates the situation. Thus, to devise proper management strategies, it is important that the defense mechanisms of plants against viruses are understood. Resistance (R) genes regulate plant defense against invading pathogens by eliciting a hypersensitive response (HR). Compatible interaction between plant R gene and viral avirulence (Avr) protein activates the necrotic cell death response at the site of infection, resulting in the cessation of disease. Here, we review different aspects of R gene-mediated dominant resistance against plant viruses in dicotyledonous plants and possible ways for developing crops with better disease resistance.

DNA methylation dynamics in response to abiotic and pathogen stress in plants.

DNA methylation is a dynamic epigenetic mechanism that plays a significant role in gene expression and also maintains chromatin stability. The process is conserved in both plants and animals, and crucial for development and stress responses. Differential DNA methylation during adverse environmental conditions or pathogen attack facilitates the selective expression of defense-related genes. Both stress-induced DNA hypomethylation and hypermethylation play beneficial roles in activating the defense response. These DNA marks may be carried to the next generation making the progenies 'primed' for abiotic and biotic stress responses. Over the recent years, rapid advancements in the area of high throughput sequencing have enabled the detection of methylation status at genome levels in several plant species. Epigenotyping offers an alternative tool to plant breeders in addition to conventional markers for the selection of the desired offspring. In this review, we briefly discuss the mechanism of DNA methylation, recent understanding of DNA methylation-mediated gene regulation during abiotic and biotic stress responses, and stress memory in plants.

Interaction of ToLCNDV TrAP with SlATG8f marks it susceptible to degradation by autophagy.

Tomato leaf curl New Delhi virus (ToLCNDV) is a devastating plant pathogen which causes significant losses in tomato yield. According to previous reports, proteins of geminiviruses like ßC1 of Cotton leaf curl Multan virus and C1 of Tomato leaf curl Yunnan virus are degraded by the autophagy pathway. There are no reports on the role of autophagy in ToLCNDV pathogenesis. In this study, we have shown that SlATG8f interacts with the ToLCNDV Transcription activator protein (TrAP; AC2) to mediate its degradation by the autophagy pathway. Silencing of SlATG8f in a ToLCNDV tolerant tomato cultivar; H-88-78-1 resulted in enhanced viral symptoms and ToLCNDV accumulation suggesting an anti-viral role for SlATG8f against ToLCNDV. TrAP is a nucleus localized protein, but it interacts with SlATG8f in and outside the nucleus indicating its nuclear export. This export might be mediated by Exportin1 as treatment with Exportin1 inhibitor inhibits TrAP export outside the nucleus. ToLCNDV TrAP is known to possess host RNA silencing suppression (RSS) activity. Degradation of TrAP results in the attenuation of its RSS activity. To the best of our knowledge, we have shown for the first time that SlATG8f-TrAP interaction leads to TrAP degradation providing defence against ToLCNDV.

Role of the Sw5 Gene Cluster in the Fight against Plant Viruses.

The Sw5 gene cluster furnishes robust resistance to Tomato spotted wilt virus in tomato, which has led to its widespread applicability in agriculture. Among the five orthologs, Sw5b functions as a resistance gene against a broad-spectrum tospovirus and is linked with tospovirus resistance. However, its paralog Sw5a has been recently implicated in providing resistance against Tomato leaf curl New Delhi virus, broadening the relevance of the Sw5 gene cluster in promoting defense against plant viruses. We propose that plants have established modifications within the homologs of R genes that permit identification of different effector proteins and provide broad and robust resistance against different pathogens through activation of the hypersensitive response and cell death.