African Swine Fever Virus L83L Negatively Regulates the cGAS-STING-Mediated IFN-I Pathway by Recruiting Tollip To Promote STING Autophagic Degradation.

African swine fever (ASF) is a devastating infectious disease of pigs caused by the African swine fever virus (ASFV), which poses a great danger to the global pig industry. Many viral proteins can suppress with interferon signaling to evade the host's innate immune responses. Therefore, the development of an effective vaccine against ASFV has been dampened. Recent studies have suggested that the L83L gene may be integrated into the host genome, weakening the host immune system, but the underlying mechanism is unknown. Our study found that L83L negatively regulates the cGAS-STING-mediated type I interferon (IFN-I) signaling pathway. Overexpression of L83L inhibited IFN-ß promoter and ISRE activity, and knockdown of L83L induced higher transcriptional levels of interferon-stimulated genes (ISGs) and phosphorylation levels of IRF3 in primary porcine alveolar macrophages. Mechanistically, L83L interacted with cGAS and STING to promote autophagy-lysosomal degradation of STING by recruiting Tollip, thereby blocking the phosphorylation of the downstream signaling molecules TBK1, IRF3, and IκBα and reducing IFN-I production. Altogether, our study reveals a negative regulatory mechanism involving the L83L-cGAS-STING-IFN-I axis and provides insights into an evasion strategy involving autophagy and innate signaling pathways employed by ASFV. IMPORTANCE African swine fever virus (ASFV) is a large double-stranded DNA virus that primarily infects porcine macrophages. The ASFV genome encodes a large number of immunosuppressive proteins. Current options for the prevention and control of this pathogen remain pretty limited. Our study showed that overexpression of L83L inhibited the cGAS-STING-mediated type I interferon (IFN-I) signaling pathway. In contrast, the knockdown of L83L during ASFV infection enhanced IFN-I production in porcine alveolar macrophages. Additional analysis revealed that L83L protein downregulated IFN-I signaling by recruiting Tollip to promote STING autophagic degradation. Although L83L deletion has been reported to have little effect on viral replication, its immune evade mechanism has not been elucidated. The present study extends our understanding of the functions of ASFV-encoded pL83L and its immune evasion strategy, which may provide a new basis for developing a live attenuated vaccine for ASF.

Does Proximity to Fast Food Cause Childhood Obesity? Evidence from Public Housing.

We examine the causal link between proximity to fast food and the incidence of childhood obesity among low-income households in New York City. Using individual-level longitudinal data on students living in public housing linked to restaurant location data, we exploit the naturally occurring within-development variation in distance to fast food restaurants to estimate the impact of proximity on obesity. Since the assignment of households to specific buildings is based upon availability at the time of assignment to public housing, the distance between student residence and retail outlets-including fast food restaurants, wait-service restaurants, supermarkets, and corner stores-is plausibly random. Our credibly causal estimates suggest that childhood obesity increases with proximity to fast food, with larger effects for younger children who attend neighborhood schools.

Distribution of human papillomavirus type 16 variants in Lithuanian women with cervical cancer.

BACKGROUND AND OBJECTIVE: Cervical cancer usually is caused by HPV 16. However, HPV 16 varies within type; different genotypes are described as prototype or variants. Prevalence of different variants differ according the geographic regions and has an unequal impact for cervical cancer development. Our study aimed to identify which variant of HPV 16 was most prevalent in biological samples taken from Lithuanian women with cervical cancer. MATERIALS AND METHODS: A total of 122 HPV 16 positive cervical samples (invasive cancer and cervical intraepithelial neoplasia) were investigated and sequenced to identify different variants. HPV 16 was detected using type specific PCR, exact sequence of the virus was obtained by viral DNA sequencing. RESULTS: Adequate HPV sequence was detected in 106 cases from 122 (86.9% of all cases). After histological confirmation, 96 cases were included in the final analysis. In 33 cases (34.4%) HPV 16 prototype was detected; in 50 cases (52.1%), L83V variant; and in remaining 13 cases (13.5%), multivariant of HPV 16. The frequency of L83V variant in invasive cancer and carcinoma in situ samples was the same (66.7% and 62.0%, respectively; P=0.696). Of analyzed multivariants, 10 were attributed to the European phylogenetic line; 1, to the North American, and 1, to the Asian-American. One sample was not attributed to any of the known phylogenetic lines. CONCLUSIONS: The European HPV 16 L83V variant is usually associated with high risk of cervical cancer among women. However, statistically significant difference was not achieved when comparing difference of L83V variants between investigated groups and in HPV 16 L83V variant and prototype distribution in CIN3/Ca in situ and cancer.

The impact of government failure on tourism in the Philippines.

While the Philippines aspires to be one of the top tourist destinations in Southeast Asia, self-inflicted wounds like the failure of the government to comply with international aviation safety standards may derail the country from achieving its goals. This article estimates the short- and long-term impact of the US FAA downgrade of the Philippine civil aviation system in 2008 and the EU ban of Philippine carriers in 2010 on tourist expenditures, arrivals, and length of stay using monthly time series data. The econometric model, consisting of three equations due to the endogeneity of the tourist arrivals and length of stay variables in the tourist expenditures equation, is estimated simultaneously using the generalized method of moments. The results indicate that the US FAA downgrade and the EU ban impact monthly tourist receipts negatively in the short term while the downgrade also impacts tourist expenditures in the long term. Moreover, the ban impacts length of stay negatively in the short and long term while the downgrade impacts length of stay negatively only in the long term. The substantial decline in tourism receipts from 2008 to 2010 despite an increasing trend in tourist arrivals is due to the shorter stay of tourists, indicating that high-spending tourists have not returned following the downgrade and ban.

Carbon footprint of tourism in Spain: Covid-19 impact and a look forward to recovery.

Tourism is very vulnerable to climate change and the disruption of Covid-19, facing two challenges: fighting climate change pursuing its carbon emissions goals, and recovering from the complex pandemic effects. We contribute to the incomplete understanding of tourism emissions pandemic impact and in different post-covid recovery scenarios. Using official data on tourists' consumption, we calculate the carbon footprint of tourism in Spain in 2019 and 2020 under different recovery pathways, including changes in consumption patterns and emissions efficiency, using a multiregional input-output model. Results show that the carbon footprint of tourism in Spain fell by 63% in 2020 compared to pre-pandemic levels, which would be aligned with the current sectoral decarbonisation target. However, the new tourists' consumption patterns resulting from the pandemic are insufficient to increase tourism sustainability if they imply pre-pandemic consumption levels. The results provide empirical ground for the binary debate on "recovery or reform".

Impact of Toxic Leadership on Employee Performance.

This research intends to shed additional light on the effects of toxic leadership on employee satisfaction, motivation, and performance. Such a study on toxic leadership is required since, to date, no research in Indonesia have sought to quantify the consequences of toxic leadership on organizational leaders. Using surveys and structural equation modeling, a quantitative strategy was adopted (SEM). The research sample amounted to 400 taken from 8 locations in Indonesia. Using Google Forms, questionnaires were distributed to 400 employees and analyzed using the Lisrel 8.5 program. The results show that toxic leadership has an effect on job satisfaction (p > 0.00), toxic leadership has an effect on work motivation (p > 0.00), toxic leadership has no effect on employee performance (p < 0.00), job satisfaction has an effect on work motivation (p > 0.00), job satisfaction has effect on employee performance (p > 0.00) work motivation has no effect on employee performance (p < 0.00). The consequences of the study findings for organizations range from the process of screening and selection of leaders to creating stress management and self-resilience training to help employees deal with their emotions in healthy ways and strengthen their defenses.

A Market for Snow: Modeling Winter Recreation Patterns Under Current and Future Climate.

Throughout the winter months across the globe, mountain communities and snow-enthusiasts alike anxiously monitor ever-changing snowpack conditions. We model the behavioral response to this climate amenity by pairing a unique panel of 12 million short-term property rental transactions with daily local weather, daily local snowpack, and daily local snowfall in every major ski resort market across the United States. Matching the spatial and temporal variation in the level of the amenity with that of related market transactions, we derive market-specific demand elasticities, explicitly accounting for substitution, to model recreation patterns throughout a typical season. Lastly, we combine downscaled projections of local snowpack under future climate scenarios to estimate within and across season trends in visitation during mid and late-century conditions. Our model predicts reductions in snow-related visitation of -40% to -60%, almost twice as large as previous estimates suggest. This translates to a lower-bound on the annual willingness to pay to avoid reductions in snowpack between $1.23 billion (RCP4.5) and $2.05 billion (RCP8.5) by the end of the century.

Can international elite sport success trickle down to mass sport participation? Evidence from Danish team handball.

Many scholars do not find evidence of a trickle-down effect from elite sport success to mass sport participation. Contrary to what is assumed by the trickle-down effect "theorem", successful elite sportspeople do not seem to inspire amateurs to take up sport themselves. However, recent studies present evidence that elite sport can have an influence. In this article, we apply regression models on time series data from one of the most successful Danish sports, team handball. Our findings are mixed, but lean towards supporting scholars who argue that trickle-down effects are not necessarily an inherent part of international sporting success. Further studies should examine more sports to identify where trickle-down effects occur and why.