Molecular Mechanism & Structure-Zooming in on Plant Immunity.

The first of three International Society for Molecular Plant-Microbe Interactions (IS-MPMI) eSymposia was convened on 12 and 13 July 2021, with the theme "Molecular Mechanism & Structure-Zooming in on Plant Immunity". Hosted by Jian-Min Zhou (Beijing, China) and Jane Parker (Cologne, Germany), the eSymposium centered on "Top 10 Unanswered Questions in MPMI" number five: Does effector-triggered immunity (ETI) potentiate and restore pattern-triggered immunity (PTI)-or is there really a binary distinction between ETI and PTI? Since the previous International Congress of IS-MPMI in 2019, substantial progress has been made in untangling the complex signaling underlying plant immunity, including a greater understanding of the structure and function of key proteins. A clear need emerged for the MPMI community to come together virtually to share new knowledge around plant immunity. Over the course of two synchronous, half days of programming, participants from 32 countries attended two plenary sessions with engaging panel discussions and networked through interactive hours and poster breakout rooms. In this report, we summarize the concerted effort by multiple laboratories to study the molecular mechanisms underlying ETI and PTI, highlighting the essential role of plant resistosomes in the formation of calcium channels during an immune response. We conclude our report by forming new questions about how overlapping signaling mechanisms are controlled.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

The crystal structure of SnTox3 from the necrotrophic fungus Parastagonospora nodorum reveals a unique effector fold and provides insight into Snn3 recognition and pro-domain protease processing of fungal effectors.

Plant pathogens cause disease through secreted effector proteins, which act to promote infection. Typically, the sequences of effectors provide little functional information and further targeted experimentation is required. Here, we utilized a structure/function approach to study SnTox3, an effector from the necrotrophic fungal pathogen Parastagonospora nodorum, which causes cell death in wheat-lines carrying the sensitivity gene Snn3. We developed a workflow for the production of SnTox3 in a heterologous host that enabled crystal structure determination and functional studies. We show this approach can be successfully applied to study effectors from other pathogenic fungi. The ß-barrel fold of SnTox3 is a novel fold among fungal effectors. Structure-guided mutagenesis enabled the identification of residues required for Snn3 recognition. SnTox3 is a pre-pro-protein, and the pro-domain of SnTox3 can be cleaved in vitro by the protease Kex2. Complementing this, an in silico study uncovered the prevalence of a conserved motif (LxxR) in an expanded set of putative pro-domain-containing fungal effectors, some of which can be cleaved by Kex2 in vitro. Our in vitro and in silico study suggests that Kex2-processed pro-domain (designated here as K2PP) effectors are common in fungi and this may have broad implications for the approaches used to study their functions.

The structural repertoire of Fusarium oxysporum f. sp. lycopersici effectors revealed by experimental and computational studies.

Plant pathogens secrete proteins, known as effectors, that function in the apoplast or inside plant cells to promote virulence. Effector recognition by cell-surface or cytosolic receptors results in the activation of defence pathways and plant immunity. Despite their importance, our general understanding of fungal effector function and recognition by immunity receptors remains poor. One complication often associated with effectors is their high sequence diversity and lack of identifiable sequence motifs precluding prediction of structure or function. In recent years, several studies have demonstrated that fungal effectors can be grouped into structural classes, despite significant sequence variation and existence across taxonomic groups. Using protein X-ray crystallography, we identify a new structural class of effectors hidden within the secreted in xylem (SIX) effectors from Fusarium oxysporum f. sp. lycopersici (Fol). The recognised effectors Avr1 (SIX4) and Avr3 (SIX1) represent the founding members of the Fol dual-domain (FOLD) effector class, with members containing two distinct domains. Using AlphaFold2, we predicted the full SIX effector repertoire of Fol and show that SIX6 and SIX13 are also FOLD effectors, which we validated experimentally for SIX6. Based on structural prediction and comparisons, we show that FOLD effectors are present within three divisions of fungi and are expanded in pathogens and symbionts. Further structural comparisons demonstrate that Fol secretes effectors that adopt a limited number of structural folds during infection of tomato. This analysis also revealed a structural relationship between transcriptionally co-regulated effector pairs. We make use of the Avr1 structure to understand its recognition by the I receptor, which leads to disease resistance in tomato. This study represents an important advance in our understanding of Fol-tomato, and by extension plant-fungal interactions, which will assist in the development of novel control and engineering strategies to combat plant pathogens.

The Prevalence of p16 Expression in Urothelial Bladder Cancer in a Tertiary Care Hospital of Chattogram, Bangladesh.

Background & Objective: p16 is a tumor suppressor gene, loss of which is usually associated with poor epithelial differentiation, resulting in tumor progression, which correlates with aggressive clinical behavior and poor prognosis. CDK 4/6 inhibitors can be used as a therapeutic target in p16 negative cases. Bladder cancer is one of the most prevalent cancers, prognosis of which depends not only upon the histopathological type, grade, and invasiveness but also on many other factors. The purpose of this study was to examine p16 expression in bladder urothelial carcinoma among the people who receive treatment at a tertiary care facility in Chattogram, Bangladesh. Methods: At the Department of Pathology, Chittagong Medical College we did this cross-sectional study from July 2019 to September 2021. The study included fifty-one cases of primary urothelial bladder cancer for histopathological examinations. Immunostaining was done by using a primary antibody against p16. Results: Among the 51 cases, twenty-six cases (51%) showed positive p16 expression. The proportion of patients with high-grade (66.7%) and muscle-invasive (86.4%) tumors were more prone to show p16 negativity. Conclusion: The result of this study shows the high grade and muscle-invasive urothelial bladder cancer is linked to reduction of p16 expression, which may provide additional prognostic information to stratify the high-risk patients and can also guide treatment plans, being a therapeutic target.

Screening of plasma IL-6 and IL-17 in Bangladeshi lung cancer patients.

Lung cancer is responsible for causing one of the highest numbers of cancer deaths. In Bangladesh, both men and women are affected by lung cancer, and environmental contaminants are believed to be one of the main risk factors apart from smoking. The diagnosis of lung cancer is difficult due to the delicate structure and complexity of the lungs. Diagnosis in later stages results in a poor prognosis of the disease. Tissue biopsy is the most reliable way of identifying lung cancer, but it is invasive and requires identification of the primary neoplasm within the lungs. As inflammation is involved in carcinogenesis, circulating levels of cytokines might be elevated in patients during the early stages of cancer. Increased IL-6 levels have been associated with the promotion of tumor growth, and IL-17 is believed to aid metastasis of lung cancer. In this study, the use of IL-6 and IL-17 was investigated as diagnostic markers for lung cancer. IL-6 and IL-17 levels were compared between 35 lung cancer patients and 19 healthy individuals. IL-6 levels were markedly elevated (7.417 pg/mL) in lung cancer cases compared to the controls (0.970 pg/mL), indicating a positive correlation (p < 0.05). IL-17 levels were only slightly higher in lung cancer patients (9.400 pg/mL) compared to healthy individuals (8.922 pg/mL). Both IL-6 and IL-17 levels were higher in patients with adenocarcinoma compared with other subtypes of lung cancer. Treatment with chemotherapy and radiotherapy did not significantly affect IL-6 levels. However, IL-17 levels were reduced due to cancer treatment. Further studies with larger sample sizes assessing the IL-6 and IL-17 in lung cancer patients are needed to establish the diagnostic role of the two cytokines.

COVID-19 vaccine hesitancy among the adult population in Bangladesh: A nationwide cross-sectional survey.

INTRODUCTION: Studies related to the COVID-19 vaccine hesitancy are scanty in Bangladesh, despite the growing necessity of understanding the population behavior related to vaccination. Thus, the present study was conducted to assess the prevalence of the COVID-19 vaccine hesitancy and its associated factors in Bangladesh to fill the knowledge gap. METHODS AND MATERIALS: This study adopted a cross-sectional design to collect data from 1497 respondents using online (Google forms) and face-to-face interviews from eight administrative divisions of Bangladesh between 1-7 February 2021. We employed descriptive statistics and multiple logistic regression analysis. RESULTS: The prevalence of vaccine hesitancy was 46.2%. The Muslims (aOR = 1.80, p ≤ 0.01) and the respondents living in the city corporation areas (aOR = 2.14, p ≤0.001) had more hesitancy. There was significant variation in vaccine hesitancy by administrative divisions (geographic regions). Compared to the Sylhet division, the participants from Khulna (aOR = 1.31, p ≤0.001) had higher hesitancy. The vaccine hesitancy tended to decrease with increasing knowledge about the vaccine (aOR = 0.88, p≤0.001) and the vaccination process (aOR = 0.91, p ≤ 0.01). On the other hand, hesitancy increased with the increased negative attitudes towards the vaccine (aOR = 1.17, p≤0.001) and conspiracy beliefs towards the COVID-19 vaccine (aOR = 1.04, p≤0.01). The perceived benefits of COVID-19 vaccination (aOR = 0.85, p≤0.001) were negatively associated with hesitancy, while perceived barriers (aOR = 1.16, p ≤0.001) were positively associated. The participants were more hesitant to accept the vaccine from a specific country of origin (India, USA, Europe). CONCLUSIONS: Our findings warrant that a vigorous behavior change communication campaign should be designed and implemented to demystify negative public attitudes and conspiracy beliefs regarding the COVID-19 Vaccine in Bangladesh. The policymakers should also think about revisiting the policy of the online registration process to receive the COVID-19 vaccine, as online registration is a key structural barrier for many due to the persistent digital divide in the country. Finally, the government should consider the population's preference regarding vaccines' country of manufacture to reduce the COVID-19 vaccine hesitancy.

Health Belief Model, Theory of Planned Behavior, or Psychological Antecedents: What Predicts COVID-19 Vaccine Hesitancy Better Among the Bangladeshi Adults?

This study aimed to determine the prevalence and investigate the constellations of psychological determinants of the COVID-19 vaccine hesitancy among the Bangladeshi adult population utilizing the health belief model-HBM (perceived susceptibility to and severity of COVID-19, perceived benefits of and barriers to COVID-19 vaccination, and cues to action), the theory of planned behavior-TPB (attitude toward COVID-19 vaccine, subjective norm, perceived behavioral control, and anticipated regret), and the 5C psychological antecedents (confidence, constraints, complacency, calculation, and collective responsibility). We compared the predictability of these theoretical frameworks to see which framework explains the highest variance in COVID-19 vaccine hesitancy. This study adopted a cross-sectional research design. We collected data from a nationally representative sample of 1,497 respondents through both online and face-to-face interviews. We employed multiple linear regression analysis to assess the predictability of each model of COVID-19 vaccine hesitancy. We found a 41.1% prevalence of COVID-19 vaccine hesitancy among our study respondents. After controlling the effects of socio-economic, demographic, and other COVID-19 related covariates, we found that the TPB has the highest predictive power (adjusted R 2 = 0.43), followed by the 5C psychological antecedents of vaccination (adjusted R 2 = 0.32) and the HBM (adjusted R 2 = 0.31) in terms of explaining total variance in the COVID-19 vaccine hesitancy among the adults of Bangladesh. This study provides evidence that theoretical frameworks like the HBM, the TPB, and the 5C psychological antecedents can be used to explore the psychological determinants of vaccine hesitancy, where the TPB has the highest predictability. Our findings can be used to design targeted interventions to reduce vaccine hesitancy and increase vaccine uptake to prevent COVID-19.

Population-Level Preparedness About Preventive Practices Against Coronavirus Disease 2019: A Cross-Sectional Study Among Adults in Bangladesh.

This study assessed the preparedness regarding the preventive practices toward the coronavirus disease 2019 (COVID-19) among the adult population in Bangladesh. Data were collected through an online survey with a sample size of 1,056. We constructed four variables (individual, household, economic, and community and social distancing) related to preparedness based on the principal component analysis of eight items. We employed descriptive statistics and multiple linear regression analysis. The results showed that the accuracy rate of the overall preparedness scale was 68.9%. The preparedness level related to economic, individual, household, and community and social distancing was 64.9, 77.1, 50.4, and 83.2%, respectively. However, the economic preparedness significantly varied by sex, education, occupation, attitude, and worries related to COVID-19. Individual preparedness was significantly associated with education, residence, and attitudes. The household preparedness significantly varied by education, residence, and worries, while the respondent's community and social distancing-related preparedness significantly varied by sex, region, residence, and attitude. This study implies the necessity of the coverage of financial schemes for the vulnerable group. Increased coverage of health education regarding personal hygiene targeting the less educated and rural population should be ensured.

Do knowledge and attitudes matter for preventive behavioral practices toward the COVID-19? A cross-sectional online survey among the adult population in Bangladesh.

The Government of Bangladesh has adopted several non-therapeutic measures to tackle the pandemic of SARS-CoV-2. However, the curve of COVID-19 positive cases has not significantly flattened yet, as the adoption of preventive measures by the general population is predominantly a behavioral phenomenon that is often influenced by people's knowledge and attitudes. This study aimed to assess the levels of knowledge, attitudes, and preventive behavioral practices toward COVID-19 and their interrelationships among the population of Bangladesh aged 18 years and above. This study adopted a web-based cross-sectional survey design and collected data from 1056 respondents using the online platform Google Form. We employed the independent sample t-test, one-way ANOVA, Pearson's product-moment correlation, and Spearman rank-order correlation to produce the bivariate level statistics. We also run multiple linear and logistic regression models to identify the factors affecting knowledge, attitudes, and preventive behavioral practices toward COVID-19. The respondents had an average knowledge score of 17.29 (Standard Deviation (SD) = 3.30). The average score for attitude scale toward COVID-19 was 13.6 (SD = 3.7). The respondents had excellent preventive behavioral practices toward COVID-19 (mean 7.7, SD = 0.72). However, this study found that knowledge and attitudes did not matter for preventive behavioral practices toward COVID-19. Instead, education appeared as a sole predictor for preventive behavioral practices toward COVID-19; that means preventive behavioral practices toward COVID-19 was lower among the less educated respondents. This study suggests increasing education as a long-term strategy and taking immediate action to increase knowledge and decrease negative attitudes toward COVID-19 through targeted health education initiatives as a short-term strategy.