Sumoylation Promotes the Stability of the DNA Sensor cGAS and the Adaptor STING to Regulate the Kinetics of Response to DNA Virus.

During viral infection, sensing of cytosolic DNA by the cyclic GMP-AMP synthase (cGAS) activates the adaptor protein STING and triggers an antiviral response. Little is known about the mechanisms that determine the kinetics of activation and deactivation of the cGAS-STING pathway, ensuring effective but controlled innate antiviral responses. Here we found that the ubiquitin ligase Trim38 targets cGas for sumoylation in uninfected cells and during the early phase of viral infection. Sumoylation of cGas prevented its polyubiquitination and degradation. Trim38 also sumoylated Sting during the early phase of viral infection, promoting both Sting activation and protein stability. In the late phase of infection, cGas and Sting were desumoylated by Senp2 and subsequently degraded via proteasomal and chaperone-mediated autophagy pathways, respectively. Our findings reveal an essential role for Trim38 in the innate immune response to DNA virus and provide insight into the mechanisms that ensure optimal activation and deactivation of the cGAS-STING pathway.

The Modulation of Trehalose Metabolism by 20-Hydroxyecdysone in Antheraea pernyi (Lepidoptera: Saturniidae) During its Diapause Termination and Post-Termination Period.

Trehalose plays a crucial role in the diapause process of many insects, serving as an energy source and a stress protectant. Trehalose accumulation has been reported in diapause pupae of Antheraea pernyi; however, trehalose metabolic regulatory mechanisms associated with diapause termination remain unclear. Here, we showed that the enhanced trehalose catabolism was associated with an increase in endogenous 20-hydroxyecdysone (20E) in hemolymph of A. pernyi pupae during their diapause termination and posttermination period. Injection of 20E increased the mRNA level of trehalase 1A (ApTre-1A) and trehalase 2 (ApTre-2) of A. pernyi diapause pupae in a dose-dependent manner but did not affect the mRNA level of trehalase 1B (ApTre-1B). Meanwhile, exogenous 20E increased the enzyme activities of soluble and membrane-bound trehalase, leading to a decline in hemolymph trehalose. Conversely, the expression of ApTre-1A and ApTre-2 were down-regulated after the ecdysone receptor gene (ApEcRB1) was silenced by RNA interference or by injection of an ecdysone receptor antagonist cucurbitacin B (CucB), which inhibits the 20E pathway. Moreover, CucB treatment delayed adult emergence, which suggests that ApEcRB1 might be involved in regulating pupal-adult development of A. pernyi by mediating ApTre-1A and ApTre-2 expressions. This study provides an overview of the changes in the expression and activity of different trehalase enzymes in A. pernyi in response to 20E, confirming the important role of 20E in controlling trehalose catabolism during A. pernyi diapause termination and posttermination period.

TRIM38 Negatively Regulates TLR3/4-Mediated Innate Immune and Inflammatory Responses by Two Sequential and Distinct Mechanisms.

Tripartite motif (TRIM)38 is an E3 ubiquitin ligase that was reported to regulate signaling in innate immune and inflammatory responses in certain cell lines. In this study, we show that Trim38 deficiency markedly increased TLR3- and TLR4-mediated induction of type I IFNs and proinflammatory cytokines, such as TNF-α, IL-1ß, and IL-6, in immune cells and in vivo. Trim38 deficiency also caused the mice to be more susceptible to death triggered by polyinosinic-polycytidylic acid, LPS, and Salmonella typhimurium. Mechanistically, TRIM38 catalyzed K48-linked polyubiquitination of the TLR3/4 adapter protein TIR domain-containing adapter-inducing IFN-ß at K228 and promoted its proteasomal degradation in immune cells. Moreover, Trim38 was highly induced by type I IFNs, which then negatively regulated TNF-α/IL-1ß signaling in IFN-ß-primed immune cells, but not unprimed immune cells, by mediating degradation of Tab2 in a lysosomal-dependent process. These results suggest that Trim38 negatively regulates TLR3/4-mediated innate immune and inflammatory responses by two sequential and distinct mechanisms. This study increases our understanding of how the innate immune response is initiated during the early phase of infection to defend against microbial invasion and is efficiently terminated during the late phase to prevent excessive and harmful inflammatory responses.

Genome sequencing and comparative transcriptomics of the model entomopathogenic fungi Metarhizium anisopliae and M. acridum.

Metarhizium spp. are being used as environmentally friendly alternatives to chemical insecticides, as model systems for studying insect-fungus interactions, and as a resource of genes for biotechnology. We present a comparative analysis of the genome sequences of the broad-spectrum insect pathogen Metarhizium anisopliae and the acridid-specific M. acridum. Whole-genome analyses indicate that the genome structures of these two species are highly syntenic and suggest that the genus Metarhizium evolved from plant endophytes or pathogens. Both M. anisopliae and M. acridum have a strikingly larger proportion of genes encoding secreted proteins than other fungi, while ~30% of these have no functionally characterized homologs, suggesting hitherto unsuspected interactions between fungal pathogens and insects. The analysis of transposase genes provided evidence of repeat-induced point mutations occurring in M. acridum but not in M. anisopliae. With the help of pathogen-host interaction gene database, ~16% of Metarhizium genes were identified that are similar to experimentally verified genes involved in pathogenicity in other fungi, particularly plant pathogens. However, relative to M. acridum, M. anisopliae has evolved with many expanded gene families of proteases, chitinases, cytochrome P450s, polyketide synthases, and nonribosomal peptide synthetases for cuticle-degradation, detoxification, and toxin biosynthesis that may facilitate its ability to adapt to heterogeneous environments. Transcriptional analysis of both fungi during early infection processes provided further insights into the genes and pathways involved in infectivity and specificity. Of particular note, M. acridum transcribed distinct G-protein coupled receptors on cuticles from locusts (the natural hosts) and cockroaches, whereas M. anisopliae transcribed the same receptor on both hosts. This study will facilitate the identification of virulence genes and the development of improved biocontrol strains with customized properties.

Predicting coronary heart disease in Chinese diabetics using machine learning.

Diabetes, a common chronic disease worldwide, can induce vascular complications, such as coronary heart disease (CHD), which is also one of the main causes of human death. It is of great significance to study the factors of diabetic patients complicated with CHD for understanding the occurrence of diabetes/CHD comorbidity. In this study, by analyzing the risk of CHD in more than 300,000 diabetes patients in southwest China, an artificial intelligence (AI) model was proposed to predict the risk of diabetes/CHD comorbidity. Firstly, we statistically analyzed the distribution of four types of features (basic demographic information, laboratory indicators, medical examination, and questionnaire) in comorbidities, and evaluated the predictive performance of three traditional machine learning methods (eXtreme Gradient Boosting, Random Forest, and Logistic regression). In addition, we have identified nine important features, including age, WHtR, BMI, stroke, smoking, chronic lung disease, drinking and MSP. Finally, the model produced an area under the receiver operating characteristic curve (AUC) of 0.701 on the test samples. These findings can provide personalized guidance for early CHD warning for diabetic populations.

Differentiated functions of Ras1 and Ras2 proteins in regulating the germination, growth, conidiation, multi-stress tolerance and virulence of Beauveria bassiana.

Ras1 and Ras2 are two distinct Ras GTPases in Beauveria bassiana, an entomopathogenic fungus whose biocontrol potential against insect pests depends largely on virulence and multi-stress tolerance. The functions of both proteins were characterized for the first time by constructing dominant-active (GTP-bound) Ras1(G19V) and dominant-negative (GDP-bound) Ras1(D126A) and integrating them and normal Ras1 into wild type and ΔRas2 for a series of phenotypic and transcriptional analyses. The resultant mutants showed gradient changes of multiple phenotypes but little difference in conidial thermotolerance. Expression of Ras1(D126A) caused vigorous hyphal growth, severely defective conidiation, and increased tolerances to oxidation, cell wall disturbance, fungicide and UV-A/UV-B irradiations, but affected slightly germination, osmosensitivity and virulence. These phenotypes were antagonistically altered by mRas1(G19V) expressed in either wild type or ΔRas2, which was severely defective in conidial germination and hyphal growth and displayed intermediate changes in other mentioned phenotypes between paired mutants expressing Ras1(G19V) or Ras1(D126A) in wild type and ΔRas2. Their growth, UV tolerance or virulence was significantly correlated with cellular response to oxidation or cell wall disturbance. Transcriptional changes of 35 downstream effector genes involved in conidiation and multi-stress responses also related to most of the phenotypic changes among the mutants. Our findings highlight that Ras1 and Ras2 regulate differentially or antagonistically the germination, growth, conidiation, multi-stress tolerance and virulence of B. bassiana, thereby exerting profound effects on the fungal biocontrol potential.

The autophagy gene BbATG5, involved in the formation of the autophagosome, contributes to cell differentiation and growth but is dispensable for pathogenesis in the entomopathogenic fungus Beauveria bassiana.

Autophagy is a highly conserved process, representing the major eukaryotic degradative pathway of cellular components. Autophagy-mediated recycling of cellular materials contributes to cell differentiation, tissue remodelling and proper development. In fungi, autophagy is required for normal growth and cell differentiation. The entomopathogenic fungus Beauveria bassiana and its invertebrate targets represent a unique model system with which to examine host-pathogen interactions. The ATG5 gene is one of 17 involved in autophagosome formation, and the B. bassiana homologue (BbATG5) was identified. The role of autophagy in B. bassiana growth and virulence was investigated via construction of a targeted gene knockout of BbATG5. The mutant strain displayed increased sensitivity to nutrient limitation, with decreased germination and growth as compared with the wild-type parent. Conidiation was severely compromised and conidia derived from the ΔBbATG5 strain were altered in morphology. Cell differentiation into blastospores was also greatly reduced. Despite the significant growth and developmental defects, insect bioassays using the oriental leafworm moth, Spodoptera litura, indicated a modest (~40 %) decrease in virulence in the ΔBbATG5 strain. The phenotypic defects of the ΔBbATG5 strain could be restored by introduction of an intact copy of BbATG5. These data suggest that unlike several plant and animal pathogenic fungi, where ATG5 is required for infection, in B. bassiana it is dispensable for pathogenesis.

iRNA-ac4C: A novel computational method for effectively detecting N4-acetylcytidine sites in human mRNA.

RNA N4-acetylcytidine (ac4C) is the acetylation of cytidine at the nitrogen-4 position, which is a highly conserved RNA modification and involves a variety of biological processes. Hence, accurate identification of genome-wide ac4C sites is vital for understanding regulation mechanism of gene expression. In this work, a novel predictor, named iRNA-ac4C, was established to identify ac4C sites in human mRNA based on three feature extraction methods, including nucleotide composition, nucleotide chemical property, and accumulated nucleotide frequency. Subsequently, minimum-Redundancy-Maximum-Relevance combined with incremental feature selection strategies was utilized to select the optimal feature subset. According to the optimal feature subset, the best ac4C classification model was trained by gradient boosting decision tree with 10-fold cross-validation. The results of independent testing set indicated that our proposed method could produce encouraging generalization capabilities. For the convenience of other researchers, we established a user-friendly web server which is freely available at http://lin-group.cn/server/iRNA-ac4C/. We hope that the tool could provide guide for wet-experimental scholars.

[The epidemiology of out-of-hospital deaths due to acute coronary events in young Beijing adults].

OBJECTIVES: To explore the characteristics of status and different populations of prehospital death associated with acute coronary events among young adults in Beijing. METHODS: Data of acute coronary events of hospitalization or death were obtained from the Hospital Discharge Information System from Beijing Public Health Information Center and Death Register System from Beijing Center for Disease Control in Beijing. The total case fatality rate of acute coronary events and proportion of prehospital coronary heart disease (CHD) death were compared upon gender, area, occupation and marital status among people aged between 25 - 45 years old. RESULTS: A total of 3489 cases were identified during 2007 to 2009 with acute coronary events (male: 3183, female: 306), with a mean age of (40.5 ± 4.3) years old. The 3-years' overall mortality was 26.0%, with female's higher than male's (51.0% vs 23.6%, P < 0.05); and it was higher in rural area than in urban areas (28.9% vs 22.9%, P < 0.05). Ninety-five percent of death due to acute coronary events occurred prehospital, with the proportion of 95.2% in male and 94.2% in female. Among the people with different occupations, self-employed people had the highest rate of prehospital death. Majority of prehospital deaths (64.8%) occurred at home. CONCLUSION: More than 90% of deaths caused by acute coronary events among young adults aged between 25-45 years old occurred before been admitted into hospital, and the site of prehospital deaths was mainly at home.

[Hospitalization rates for coronary heart disease from 2007 to 2009 in Beijing].

OBJECTIVE: To examine the distribution and trends of hospitalization rates for coronary heart disease (CHD) from 2007 to 2009 in Beijing. METHODS: We calculated hospitalization rates for CHD using data from Beijing Hospital Discharge Information System. Information of census registered population in Beijing was obtained from Beijing Municipal Bureau of Statistics. CHD includes acute myocardial infarction, unstable angina and other forms of CHD. Age-standardized hospitalization rates for CHD per 100 000 population aged 25 years or more were calculated. RESULTS: During 2007 - 2009, a total of 248 049 patients aged 25 years or more hospitalized in Beijing with the primary discharge diagnosis of CHD were enrolled, of whom 73.7% were permanent registered Beijing citizens. The average hospitalization rate for CHD in 2007 - 2009 was 651.2/100 000 for the permanent residences in Beijing (741.2/100 000 in men, 560.9/100 000 in women). The highest average hospitalization rate (671.9/100 000) was seen in exurban area compared to other areas in Beijing. The average hospitalization rate for acute myocardial infarction, unstable angina, and other CHD was 126.4/100 000, 226.4/100 000 and 298.4/100 000, respectively. The hospitalization rate for CHD increased 18.1% from 2007 to 2009 (from 598.1/100 000 to 706.5/100 000). The same trend was seen in women (20.2%) and men (16.6%). The hospitalization rates of CHD in the urban, suburban, and exurban areas of Beijing all increased in the three years, and the greatest increase (36.6%) was found in exurban area. Hospitalization rates of acute myocardial infarction and unstable angina increased 24.5% and 55.3%, respectively, in the three years, while hospitalization rates of other CHD decreased 5.7%. CONCLUSIONS: The hospitalization rate of CHD is higher in men than in women in Beijing. The hospitalization rates for CHD increased from the observation period, especially in those living in exurban area. Awareness of the magnitudes and trends of CHD hospitalization rates is of great importance in evaluating the burden of cardiovascular disease, allocating and utilizing health care resources, and estimating the health insurance for Beijing.

[Surveillance on the incidence of acute coronary events in the permanent residents of Beijing aged 25 years and more from 2007 to 2009].

OBJECTIVE: To survey the incidence of acute coronary events and its trend in three years, and explore the distribution of the incidence across Beijing residents aged 25 years and more from 2007 to 2009. METHODS: The present study incorporated and linked the routinely collected data from the Hospital Discharge Information System and Cause of Death Register System in Beijing, estimated the incidence of acute coronary events, and analyzed the distribution of the incidence across gender, age groups and regions. Acute coronary event was defined as non-fatal myocardial infarction and death from coronary heart disease. Numbers of residents by age, gender and area were obtained from the Beijing Statistics Bureau. RESULTS: A total of 68 390 acute coronary events were identified among permanent residents of Beijing aged 25 years and more from 2007 to 2009. The age-standardized incidence was 166.4 per 100 000 people in overall population, with 218.5 in males and 115.2 in females. The age-standardized incidence was 144.3, 154.7, and 195.8 per 100 000 people in urban, suburban, and exurban area, respectively. The incidence was the highest in Huairou district (263.8 per 100 000), while was the lowest in Haidian district (121.5 per 100 000). The age-standardized incidence was 158.4, 169.4, and 171.2 per 100 000 in 2007, 2008, and 2009, respectively. The age-standardized incidence increased by 8.1% in 2009 compared to 2007, increase in men (11.1%) was greater than in women (2.5%). The incidence increased significantly with age in each year. The incidence raised by 30.3% in 2009 compared to 2007 for men aged 35 - 44 years. In 2009, the incidence was 146.7, 155.9, and 207.4 per 100 000 people in urban, suburban, and exurban area, respectively. The rates increased by 3.2% in both urban and suburban areas, and 16.4% in exurban areas in 2009 compared to 2007. CONCLUSION: The incidence of acute coronary events increased from 2007 to 2009 among the permanent residents of Beijing aged 25 years and over, especially in young men, and people living in the exurban areas.

IBPred: A sequence-based predictor for identifying ion binding protein in phage.

Ion binding proteins (IBPs) can selectively and non-covalently interact with ions. IBPs in phages also play an important role in biological processes. Therefore, accurate identification of IBPs is necessary for understanding their biological functions and molecular mechanisms that involve binding to ions. Since molecular biology experimental methods are still labor-intensive and cost-ineffective in identifying IBPs, it is helpful to develop computational methods to identify IBPs quickly and efficiently. In this work, a random forest (RF)-based model was constructed to quickly identify IBPs. Based on the protein sequence information and residues' physicochemical properties, the dipeptide composition combined with the physicochemical correlation between two residues were proposed for the extraction of features. A feature selection technique called analysis of variance (ANOVA) was used to exclude redundant information. By comparing with other classified methods, we demonstrated that our method could identify IBPs accurately. Based on the model, a Python package named IBPred was built with the source code which can be accessed at https://github.com/ShishiYuan/IBPred.

A new manganese superoxide dismutase identified from Beauveria bassiana enhances virulence and stress tolerance when overexpressed in the fungal pathogen.

A superoxide dismutase (SOD) was characterized from Beauveria bassiana, a fungal entomopathogen widely applied to insect control. This 209-aa enzyme (BbSod2) showed no more than 71% sequence identity to other fungal Mn-SODs, sharing all conserved residues with the Mn-SOD family and lacking a mitochondrial signal. The SOD activity of purified BbSod2 was significantly elevated by Mn(2+), suppressed by Cu(2+) and Zn(2+) but inhibited by Fe(3+). Overexpressing the enzyme in a BbSod2-absent B. bassiana strain enhanced its SOD activity (107.2 +/- 6.1 U mg(-1) protein) by 4-10-fold in different transformants analyzed. The best BbSod2-transformed strain with the SOD activity of 1,157.9 +/- 74.7 U mg(-1) was 93% and 61% more tolerant to superoxide-generating menadione in both colony growth (EC(50) = 2.41 +/- 0.03 versus 1.25 +/- 0.01 mM) and conidial germination (EC(50) = 0.89 +/- 0.06 versus 0.55 +/- 0.07 mM), and 23% more tolerant to UV-B irradiation (LD(50) = 0.49 +/- 0.02 versus 0.39 +/- 0.01 J cm(-2)). Its virulence to Spodoptera litura larvae was enhanced by 26% [LT(50) = 4.5 (4.2-4.8) versus 5.7 (5.2-6.4) days]. Our study highlights for the first time that the Mn(2+)-cofactored, cytosolic BbSod2 contributes significantly to the virulence and stress tolerance of B. bassiana and reveals possible means to improving field persistence and efficacy of a fungal formulation by manipulating the antioxidant enzymes of a candidate strain.

Impact of reimbursement program on liver-related mortality in patients with chronic hepatitis B in Beijing, China.

OBJECTIVE: Since July 1, 2011 antiviral therapy for hepatitis B virus infection has been listed as a reimbursable expense for medical insurance in Beijing. This study aimed to assess the impact of this program on liver-related death for patients with chronic hepatitis B (CHB). METHODS: Profiles of patients with CHB discharged between January 2008 and December 2015 were retrieved from the Beijing hospital discharge database. Liver-related deaths in these patients occurring between January 2008 and December 2017 were retrieved by linking them to the death certification database. Liver-related mortality (number of deaths divided by the observed person-years) before and after this program was launched was calculated and compared. A Poisson regression was performed to assess the strength of association (risk ratio [RR]) between the reimbursement program and liver-related mortality. RESULTS: Information on 35 943 discharged patients (17 114 patients with non-cirrhotic and 18 829 with compensated cirrhotic CHB) was retrieved. Altogether 3 832 liver-related deaths during the 190 695 person-years were observed. After the reimbursement program was launched, liver-related mortality per 100 person-years dropped from 0.38% to 0.16% for patients with non-cirrhotic CHB, and from 4.03% to 3.39% for those with compensated cirrhosis. The program was associated with a lower risk of developing liver-related death for patients with non-cirrhotic CHB (RR 0.40, 95% confidence interval [CI] 0.30-0.52) and those with compensated cirrhosis (RR 0.84, 95% CI 0.78-0.89). CONCLUSION: Coverage of antiviral therapy by basic medical insurance reduced the risk of developing liver-related death for patients with non-cirrhotic and with compensated cirrhotic CHB.

[Analysis of the quality of notifiable infectious disease report in Beijing medical treatment organizations].

OBJECTIVE: To evaluate the quality of the infectious diseases reporting via network in Beijing hospitals and to filtrate factors that affect the reporting quality. METHODS: We collected 5536 infectious disease cases randomly and investigated 52 medical treatment organizations. Information was collected by field questionnaire survey, interview and gathering routine reporting data for analyzing the quality. RESULTS: The result showed that the timeliness of the 52 medical treatment organizations was 94.18%, the consistency was 80.84%, the completeness was 88.47%, and the misreport was 13.73%. The reporting quality of the second level hospitals was higher than that of the first level hospitals, township health centers and the third level hospitals. The reporting quality of urban hospitals was higher than that of the suburb hospitals. The reporting quality of outpatient and inpatient departments was higher than that of the laboratory. The laboratory was the primary part of underreporting. CONCLUSION: Strengthening guidance, training and paying attention to each weak portion would certainly ameliorate the quality of infectious diseases reporting via network.

Innate immunity to RNA virus is regulated by temporal and reversible sumoylation of RIG-I and MDA5.

Sensing of viral RNA by the cytosolic receptors RIG-I and melanoma differentiation-associated gene 5 (MDA5) leads to innate antiviral response. How RIG-I and MDA5 are dynamically regulated in innate antiviral response is not well understood. Here, we show that TRIM38 positively regulates MDA5- and RIG-I-mediated induction of downstream genes and acts as a SUMO E3 ligase for their dynamic sumoylation at K43/K865 and K96/K888, respectively, before and after viral infection. The sumoylation of MDA5 and RIG-I suppresses their K48-linked polyubiquitination and degradation in uninfected or early-infected cells. Sumoylation of the caspase recruitment domains of MDA5 and RIG-I is also required for their dephosphorylation by PP1 and activation upon viral infection. At the late phase of viral infection, both MDA5 and RIG-I are desumoylated by SENP2, resulting in their K48-linked polyubiquitination and degradation. These findings suggest that dynamic sumoylation and desumoylation of MDA5 and RIG-I modulate efficient innate immunity to RNA virus and its timely termination.

Risk factors for SARS-related deaths in 2003, Beijing.

OBJECTIVE: To study the potential risk factors for severe acute respiratory syndromes (SARS)-related deaths in Beijing. METHODS: Epidemiological data were collected among the confirmed SARS patients officially reported by Beijing Centers for Disease Control and Prevention (BCDC), and information was also supplemented by a follow-up case survey. Chi-square test and multivariate stepwise logistic regression analysis were performed. RESULTS: Old age (over 60 years) was found to be significantly associated with SARS-related deaths in the univariate analysis. Also, history of contacting SARS patients within 2 weeks prior to the onset of illness, health occupation, and inferior hospital ranking as well as longer interval of clinic consulting (longer than 1 day) were the risk factors for SARS-related deaths. Multivariate stepwise logistic regression analysis found four risk factors for SARS-related deaths. CONCLUSION: Old age (over 60 years) is the major risk factor for SARS-related deaths. Moreover, hospital health workers, the designated hospitals for SARS clinical services and the interval of consulting doctors (less than 1 day) are protective factors for surviving from SARS.

Severe acute respiratory syndrome--retrospect and lessons of 2004 outbreak in China.

OBJECTIVE: To summarize lessons learned from an outbreak of severe acute respiratory syndrome (SARS) in China during the spring of 2004. METHODS: Data of SARS cases were officially reported by Beijing Municipal Center for Disease Control and Prevention (BCDC) and Anhui Provincial Center for Disease Control and Prevention (APCDC) and results of epidemiological investigations were collected and analyzed. RESULTS: Three generations of 11 cases of SARS were identified during the outbreak. Initial two cases were most likely to be infected in Diarrhea Virus Laboratory of National Institute of Virology, China Centers for Disease Control and Prevention and main mode of transmission was direct contact with SARS patients. Delay in detecting initial case resulted in spread of the illness at hospitals and communities with two generations of secondary cases. CONCLUSIONS: SARS outbreak in 2004 has yielded following lessons for public health globally. (1) Lab bio-safety programs should be made and should be strictly abided by. Studies in highly pathogenic viruses such as SARS coronavirus should be utmost cautious. (2) Management systems of occupational exposure to virus and disease surveillance need to be strengthened to take all risk factors into account so as to detect potential patients with infectious disease as early as possible.

The autophagy-related genes BbATG1 and BbATG8 have different functions in differentiation, stress resistance and virulence of mycopathogen Beauveria bassiana.

Autophagy-related proteins play significantly different roles in eukaryotes. In the entomopathogenic fungus Beauveria bassiana, autophagy is associated with fungal growth and development. BbATG1 (a serine/threonine protein kinase) and BbATG8 (a ubiquitin-like protein) have similar roles in autophagy, but different roles in other processes. Disruption mutants of BbATG1 and BbATG8 had impaired conidial germination under starvation stress. The mutant ΔBbATG8 exhibited enhanced sensitivity to oxidative stress, while a ΔBbATG1 mutant did not. BbATG1 and BbATG8 showed different roles in spore differentiation. The blastospore yield was reduced by 70% and 92% in ΔBbATG1 and ΔBbATG8 mutants, respectively, and the double mutant had a reduction of 95%. Conidial yield was reduced by approximately 90% and 50% in ΔBbATG1 and ΔBbATG8 mutants, respectively. A double mutant had a reduction similar to ΔBbATG1. Additionally, both BbATG1 and BbATG8 affected the levels of conidial protein BbCP15p required for conidiation. The virulence of each autophagy-deficient mutant was considerably weakened as indicated in topical and intrahemocoel injection assays, and showed a greater reduction in topical infection. However, BbATG1 and BbATG8 had different effects on fungal virulence. Our data indicate that these autophagy-related proteins have different functions in fungal stress response, asexual development and virulence.

Specific features of the contact history of probable cases of severe acute respiratory syndrome.

OBJECTIVE: To describe the specific features of the contact history of probable cases of severe acute respiratory syndrome (SARS) in Beijing. METHODS: Data of SARS cases notified from the Beijing Municipal Center for Disease Control and Prevention (BCDC) and supplemented by other channels were collected. All the data were analyzed by descriptive epidemiology. RESULTS: (1) The number of probable cases with contact history was significantly higher than the excluded cases. (2) The proportion of probable cases with contact history descended with epidemic development, but this situation did not occur in health care workers (HCWs). (3) The fatality rate of probable cases with contact history was significantly higher than the cases without contact history (OR = 1.489). (4) The proportion of probable cases with contact history was 85.86% among health care workers, which was significantly higher than that of non-health care workers (85.86% v.s. 56.44%, OR=4.69). CONCLUSIONS: (1) The susceptible persons with contact history may not get infected, and the contact history is just a sufficient condition of infecting SARS; (2) There are 3 conceivable reasons for the descending trend of the proportion in probable cases with contact history; (3) The contact history is one of the risk factors of the death of SARS cases; (4) The risk of contacting with SARS among health care workers is approximately 5 times higher than that of non-HCWs.