Regulation of proteinaceous effector expression in phytopathogenic fungi

Effectors are molecules used by microbial pathogens to facilitate infection via effector-triggered susceptibility or tissue necrosis in their host. Much research has been focussed on the identification and elucidating the function of fungal effectors during plant pathogenesis. By comparison, knowledge of how phytopathogenic fungi regulate the expression of effector genes has been lagging. Several recent studies have illustrated the role of various transcription factors, chromosome-based control, effector epistasis, and mobilisation of endosomes within the fungal hyphae in regulating effector expression and virulence on the host plant. Improved knowledge of effector regulation is likely to assist in improving novel crop protection strategies

Development and validation of a weather-based model for predicting infection of loquat fruit by Fusicladium eriobotryae

A mechanistic, dynamic model was developed to predict infection of loquat fruit by conidia of Fusicladium eriobotryae, the causal agent of loquat scab. The model simulates scab infection periods and their severity through the sub-processes of spore dispersal, infection, and latency (i.e., the state variables); change from one state to the following one depends on environmental conditions and on processes described by mathematical equations. Equations were developed using published data on F. eriobotryae mycelium growth, conidial germination, infection, and conidial dispersion pattern. The model was then validated by comparing model output with three independent data sets. The model accurately predicts the occurrence and severity of infection periods as well as the progress of loquat scab incidence on fruit (with concordance correlation coefficients .0.95). Model output agreed with expert assessment of the disease severity in seven loquatgrowing seasons. Use of the model for scheduling fungicide applications in loquat orchards may help optimise scab management and reduce fungicide applications.This work was funded by Cooperativa Agricola de Callosa d'En Sarria (Alicante, Spain). Three months' stay of E. Gonzalez-Dominguez at the Universita Cattolica del Sacro Cuore (Piacenza, Italy) was supported by the Programa de Apoyo a la Investigacion y Desarrollo (PAID-00-12) de la Universidad Politecnica de Valencia. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.González Domínguez, E.; Armengol Fortí, J.; Rossi, V. (2014). Development and validation of a weather-based model for predicting infection of loquat fruit by Fusicladium eriobotryae. PLoS ONE. 9(9):1-12. https://doi.org/10.1371/journal.pone.0107547S11299Sánchez-Torres, P., Hinarejos, R., & Tuset, J. J. (2009). Characterization and Pathogenicity ofFusicladium eriobotryae, the Fungal Pathogen Responsible for Loquat Scab. Plant Disease, 93(11), 1151-1157. doi:10.1094/pdis-93-11-1151Gladieux, P., Caffier, V., Devaux, M., & Le Cam, B. (2010). Host-specific differentiation among populations of Venturia inaequalis causing scab on apple, pyracantha and loquat. Fungal Genetics and Biology, 47(6), 511-521. doi:10.1016/j.fgb.2009.12.007González-Domínguez, E., Rossi, V., Armengol, J., & García-Jiménez, J. (2013). Effect of Environmental Factors on Mycelial Growth and Conidial Germination ofFusicladium eriobotryae, and the Infection of Loquat Leaves. Plant Disease, 97(10), 1331-1338. doi:10.1094/pdis-02-13-0131-reGonzález-Domínguez, E., Rossi, V., Michereff, S. J., García-Jiménez, J., & Armengol, J. (2014). Dispersal of conidia of Fusicladium eriobotryae and spatial patterns of scab in loquat orchards in Spain. European Journal of Plant Pathology, 139(4), 849-861. doi:10.1007/s10658-014-0439-0Becker, C. M. (1994). Discontinuous Wetting and Survival of Conidia ofVenturia inaequalison Apple Leaves. Phytopathology, 84(4), 372. doi:10.1094/phyto-84-372Hartman, J. R., Parisi, L., & Bautrais, P. (1999). Effect of Leaf Wetness Duration, Temperature, and Conidial Inoculum Dose on Apple Scab Infections. Plant Disease, 83(6), 531-534. doi:10.1094/pdis.1999.83.6.531Holb, I. J., Heijne, B., Withagen, J. C. M., & Jeger, M. J. (2004). Dispersal of Venturia inaequalis Ascospores and Disease Gradients from a Defined Inoculum Source. Journal of Phytopathology, 152(11-12), 639-646. doi:10.1111/j.1439-0434.2004.00910.xRossi, V., Giosue, S., & Bugiani, R. (2003). Influence of Air Temperature on the Release of Ascospores of Venturia inaequalis. Journal of Phytopathology, 151(1), 50-58. doi:10.1046/j.1439-0434.2003.00680.xStensvand, A., Gadoury, D. M., Amundsen, T., Semb, L., & Seem, R. C. (1997). Ascospore Release and Infection of Apple Leaves by Conidia and Ascospores ofVenturia inaequalisat Low Temperatures. Phytopathology, 87(10), 1046-1053. doi:10.1094/phyto.1997.87.10.1046Machardy WE (1996) Apple scab. Biology, epidemiology and management. St. Paul: APS Press. 545.James, J. R. (1982). Environmental Factors Influencing Pseudothecial Development and Ascospore Maturation ofVenturia inaequalis. Phytopathology, 72(8), 1073. doi:10.1094/phyto-72-1073Li, B., Zhao, H., Li, B., & Xu, X.-M. (2003). Effects of temperature, relative humidity and duration of wetness period on germination and infection by conidia of the pear scab pathogen (Venturia nashicola). Plant Pathology, 52(5), 546-552. doi:10.1046/j.1365-3059.2003.00887.xLi, B.-H., Xu, X.-M., Li, J.-T., & Li, B.-D. (2005). Effects of temperature and continuous and interrupted wetness on the infection of pear leaves by conidia of Venturia nashicola. Plant Pathology, 54(3), 357-363. doi:10.1111/j.1365-3059.2005.01207.xUMEMOTO, S. 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Phytopathology, 72(10), 1339. doi:10.1094/phyto-72-1339MARZO, L., FRISULLO, S., LOPS, F., & ROSSI, V. (1993). Possible dissemination of Spilocaea oleagina conidia by insects (Ectopsocus briggsi). EPPO Bulletin, 23(3), 389-391. doi:10.1111/j.1365-2338.1993.tb01341.xLOPS, F., FRISULLO, S., & ROSSI, V. (1993). Studies on the spread of the olive scab pathogen, Spilocaea oleagina. EPPO Bulletin, 23(3), 385-387. doi:10.1111/j.1365-2338.1993.tb01340.xObanor, F. O., Walter, M., Jones, E. E., & Jaspers, M. V. (2007). Effect of temperature, relative humidity, leaf wetness and leaf age on Spilocaea oleagina conidium germination on olive leaves. European Journal of Plant Pathology, 120(3), 211-222. doi:10.1007/s10658-007-9209-6Obanor, F. O., Walter, M., Jones, E. E., & Jaspers, M. V. (2010). Effects of temperature, inoculum concentration, leaf age, and continuous and interrupted wetness on infection of olive plants by Spilocaea oleagina. Plant Pathology, 60(2), 190-199. doi:10.1111/j.1365-3059.2010.02370.xViruega, J. R., Moral, J., Roca, L. F., Navarro, N., & Trapero, A. (2013). Spilocaea oleaginain Olive Groves of Southern Spain: Survival, Inoculum Production, and Dispersal. Plant Disease, 97(12), 1549-1556. doi:10.1094/pdis-12-12-1206-reViruega, J. R., Roca, L. F., Moral, J., & Trapero, A. (2011). Factors Affecting Infection and Disease Development on Olive Leaves Inoculated withFusicladium oleagineum. Plant Disease, 95(9), 1139-1146. doi:10.1094/pdis-02-11-0126Eikemo, H., Gadoury, D. M., Spotts, R. A., Villalta, O., Creemers, P., Seem, R. C., & Stensvand, A. (2011). Evaluation of Six Models to Estimate Ascospore Maturation in Venturia pyrina. Plant Disease, 95(3), 279-284. doi:10.1094/pdis-02-10-0125Li, B.-H., Yang, J.-R., Dong, X.-L., Li, B.-D., & Xu, X.-M. (2007). A dynamic model forecasting infection of pear leaves by conidia of Venturia nashicola and its evaluation in unsprayed orchards. European Journal of Plant Pathology, 118(3), 227-238. doi:10.1007/s10658-007-9138-4Rossi, V., Giosuè, S., & Bugiani, R. (2007). A-scab (Apple-scab), a simulation model for estimating risk of Venturia inaequalis primary infections. EPPO Bulletin, 37(2), 300-308. doi:10.1111/j.1365-2338.2007.01125.xXU, X.-M., BUTT, D. J., & SANTEN, G. (1995). A dynamic model simulating infection of apple leaves by Venturia inaequalis. Plant Pathology, 44(5), 865-876. doi:10.1111/j.1365-3059.1995.tb02746.xRoubal, C., Regis, S., & Nicot, P. C. (2012). Field models for the prediction of leaf infection and latent period ofFusicladium oleagineumon olive based on rain, temperature and relative humidity. Plant Pathology, 62(3), 657-666. doi:10.1111/j.1365-3059.2012.02666.xPayne, A. F., & Smith, D. L. (2012). Development and Evaluation of Two Pecan Scab Prediction Models. 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Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

Background Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period. Methods 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution. Findings Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations. Interpretation Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic

Diagnostic Value of Serum and Saliva Matrix Metalloproteinase13 (MMP13) in Oral Squamous Cell Carcinoma

BACKGROUND AND OBJECTIVE: Matrix metalloproteinases (MMPs) are a group of enzymes responsible for extracellular matrix breakdown. Increased activity of type 13 is involved in invasion of oral squamous cell carcinoma. This study was performed to compare the level of matrix metalloproteinase13 (MMP13) in saliva and serum of patients with oral squamous cell carcinoma and healthy controls. METHODS: In this experimental in vitro study, 24 saliva and 24 serum samples were collected from patients with primary oral squamous cell carcinoma after histopathologic confirmation, whereas 21 saliva samples and 21 serum samples were collected from healthy subjects with mucosal health confirmation. Clinical examination was done for MMP-13 levels in saliva and serum, and the results were compared by ELISA. FINDINGS: MMP-13 levels in serum (7.47±2.36) and saliva (8.42±2.69) of patients with oral squamous cell carcinoma compared to healthy subjects increased respectively by 5.39±1.90 and 6.72±2.11 (P= 0.002 and P= 0.025, respectively). The levels of MMP13 in saliva and serum to determine the existence of oral squamous cell carcinoma has a "good" diagnostic value, with sensitivity and specificity of 88% and 86% respectively for serum, and 88% and 71% respectively for saliva. CONCLUSION: According to the results of this study, the levels of MMP13 in saliva and serum of patients with oral squamous cell carcinoma was higher than in healthy individuals and this biomarker had good diagnostic value in the diagnosis of oral squamous cell carcinoma

Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

BackgroundEstimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period.Methods22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution.FindingsGlobal all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations.InterpretationGlobal adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic