Modulation of human endogenous retrovirus (HERV) transcription during persistent and de novo HIV-1 infection

Background: The human genome contains multiple LTR elements including human endogenous retroviruses (HERVs) that together account for approximately 8–9% of the genomic DNA. At least 40 different HERV groups have been assigned to three major HERV classes on the basis of their homologies to exogenous retroviruses. Although most HERVs are silenced by a variety of genetic and epigenetic mechanisms, they may be reactivated by environmental stimuli such as exogenous viruses and thus may contribute to pathogenic conditions. The objective of this study was to perform an in-depth analysis of the influence of HIV-1 infection on HERV activity in different cell types. Results: A retrovirus-specific microarray that covers major HERV groups from all three classes was used to analyze HERV transcription patterns in three persistently HIV-1 infected cell lines of different cellular origins and in their uninfected counterparts. All three persistently infected cell lines showed increased transcription of multiple class I and II HERV groups. Up-regulated transcription of five HERV taxa (HERV-E, HERV-T, HERV-K (HML-10) and two ERV9 subgroups) was confirmed by quantitative reverse transcriptase PCR analysis and could be reversed by knock-down of HIV-1 expression with HIV-1-specific siRNAs. Cells infected de novo by HIV-1 showed stronger transcriptional up-regulation of the HERV-K (HML-2) group than persistently infected cells of the same origin. Analysis of transcripts from individual members of this group revealed up-regulation of predominantly two proviral loci (ERVK-7 and ERVK-15) on chromosomes 1q22 and 7q34 in persistently infected KE37.1 cells, as well as in de novo HIV-1 infected LC5 cells, while only one single HML-2 locus (ERV-K6) on chromosome 7p22.1 was activated in persistently infected LC5 cells. Conclusions: Our results demonstrate that HIV-1 can alter HERV transcription patterns of infected cells and indicate a correlation between activation of HERV elements and the level of HIV-1 production. Moreover, our results suggest that the effects of HIV-1 on HERV activity may be far more extensive and complex than anticipated from initial studies with clinical material

Taxonomy based on science is necessary for global conservation

Peer reviewe

The Influence of Manga on the Graphic Novel

This material has been published in The Cambridge History of the Graphic Novel edited by Jan Baetens, Hugo Frey, Stephen E. Tabachnick. This version is free to view and download for personal use only. Not for re-distribution, re-sale or use in derivative works. © Cambridge University PressProviding a range of cogent examples, this chapter describes the influences of the Manga genre of comics strip on the Graphic Novel genre, over the last 35 years, considering the functions of domestication, foreignisation and transmedia on readers, markets and forms

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

L’alimentation de la Sarre en électricité sous l’influence de la libéralisation du marché européen de l’énergie

Ayant succédé à l’exploitation des mines de charbon, la production d’électricité en Sarre continue à être fondée presque exclusivement sur le charbon. La libéralisation européenne du marché de l’énergie y a été mise en place plus tôt et d’une manière plus large qu’en France. Pour pouvoir réaliser la réduction des émissions de CO2, fixée par le protocole de Kyoto (1997), il faudra économiser la consommation de courant, favoriser la co-production d’électricité et de chauffage (co-génération) aussi bien que les énergies renouvelables. Ces dernières sont soutenues par deux nouvelles lois depuis 2000. Des technologies avancées vont également améliorer la compétitivité des centrales au charbon par rapport à celles au gaz. Il est vrai que la co-génération aura besoin de subventions, mais elle pourra profiter de l’existence de l’axe du chauffage urbain sarrois. Par contre, les énergies renouvelables ne se développent que lentement : jusqu’à ce jour, on ne compte que 21 éoliennes (12,5 MW), et, compte tenu du relief peu approprié, la capacité ne pourra que tripler dans un proche avenir. Si la génération d’électricité photovoltaïque par habitant dépasse de 25 % la moyenne allemande, elle, reste quand même modeste. Comme il faudra encore beaucoup de temps pour augmenter la production d’énergie renouvelable d’une manière considérable, la Sarre demeurera une localisation importante pour la transformation du charbon en électricité.As a secondary industry succeeding coal mining, electricity generation in Saarland continues to be almost exclusively upon coal. In Germany the European liberalization of the energy market has been implemented earlier and more comprehensibly than in France. The reduction of CO2 emissions, as specified by the Kyoto protocol, will be achievable only by the decrease of energy consumption, the increased use of renewable energy resources and co-generation. Since 2000 both are being supported in Germany by two new statutes. Advanced technologies in the domain of co-generation will enhance the competitivity of coal power plants as compared to power stations fuelled by natural gas. Co-generation on the basis of coal will need significant subsidies, but at the same time it will profit from the existing « Saar-district heating-axis ». In contrast, renewable energies are developing only very slowly. Until now, only 21 wind generators with an installed power of 12.5 MW have been constructed. Due to the inappropriate topography, the installed power of wind mills will at best triple in the near future. The generation by photovoltaics which currently exceeds the German mean by 25 % will remain very low. Since the comprehensive developement of renewable energy resources will require a considerable period of time, the Saarland will continue to be an important region of coal-based electricity generation.Die Stromerzeugung im Saarland beruht als Folge des Steinkohlenbergbaus fast ausschließlich auf heimischer Kohle. Die europäische Liberalisierung des Energiemarkts wurde in Deutschland früher und umfassender umgesetzt als in Frankreich. Die Umsetzung der im Kyoto-Protokoll (1997) festgelegten Reduzierung der CO2-Emissionen wird nur über Stromsparmaßnahmen, Kraft-Wärme-Kopplung (KWK) und den Einsatz erneuerbarer Energien möglich sein. Neue Gesetze fördern seit dem Jahr 2000 KWK und vor allem erneuerbare Energien. Neue technologische Entwicklungen werden die Konkurrenzfähigkeit der Steinkohleverstromung gegenüber Gas verbessern. KWK erfordert den Einsatz von Subventionen, kann aber im Saarland von der vorhandenen Infrastruktur der Fernwärmeschiene Saar profitieren. Erneuerbare Energien entwickeln sich nur langsam. Im Saarland wurden bisher nur 21 Windkraftanlagen mit 12,5 MW installiert, aufgrund der wenigen geeigneten Flächen ist in absehbarer Zeit nicht mehr als eine Verdreifachung zu erwarten. Bescheiden ist auch die Erzeugung von Photovoltaikstrom, auch wenn sie um 25 % über dem deutschen Durchschnitt liegt. Insgesamt wird der Ausbau erneuerbarer Energien viel Zeit brauchen, so daß das Saarland auch in Zukunft ein wichtiger Standort für die Steinkohleverstromung bleiben wird

L’alimentation de la Sarre en électricité sous l’influence de la libéralisation du marché européen de l’énergie

Ayant succédé à l’exploitation des mines de charbon, la production d’électricité en Sarre continue à être fondée presque exclusivement sur le charbon. La libéralisation européenne du marché de l’énergie y a été mise en place plus tôt et d’une manière plus large qu’en France. Pour pouvoir réaliser la réduction des émissions de CO2, fixée par le protocole de Kyoto (1997), il faudra économiser la consommation de courant, favoriser la co-production d’électricité et de chauffage (co-génération) aussi bien que les énergies renouvelables. Ces dernières sont soutenues par deux nouvelles lois depuis 2000. Des technologies avancées vont également améliorer la compétitivité des centrales au charbon par rapport à celles au gaz. Il est vrai que la co-génération aura besoin de subventions, mais elle pourra profiter de l’existence de l’axe du chauffage urbain sarrois. Par contre, les énergies renouvelables ne se développent que lentement : jusqu’à ce jour, on ne compte que 21 éoliennes (12,5 MW), et, compte tenu du relief peu approprié, la capacité ne pourra que tripler dans un proche avenir. Si la génération d’électricité photovoltaïque par habitant dépasse de 25 % la moyenne allemande, elle, reste quand même modeste. Comme il faudra encore beaucoup de temps pour augmenter la production d’énergie renouvelable d’une manière considérable, la Sarre demeurera une localisation importante pour la transformation du charbon en électricité.As a secondary industry succeeding coal mining, electricity generation in Saarland continues to be almost exclusively upon coal. In Germany the European liberalization of the energy market has been implemented earlier and more comprehensibly than in France. The reduction of CO2 emissions, as specified by the Kyoto protocol, will be achievable only by the decrease of energy consumption, the increased use of renewable energy resources and co-generation. Since 2000 both are being supported in Germany by two new statutes. Advanced technologies in the domain of co-generation will enhance the competitivity of coal power plants as compared to power stations fuelled by natural gas. Co-generation on the basis of coal will need significant subsidies, but at the same time it will profit from the existing « Saar-district heating-axis ». In contrast, renewable energies are developing only very slowly. Until now, only 21 wind generators with an installed power of 12.5 MW have been constructed. Due to the inappropriate topography, the installed power of wind mills will at best triple in the near future. The generation by photovoltaics which currently exceeds the German mean by 25 % will remain very low. Since the comprehensive developement of renewable energy resources will require a considerable period of time, the Saarland will continue to be an important region of coal-based electricity generation.Die Stromerzeugung im Saarland beruht als Folge des Steinkohlenbergbaus fast ausschließlich auf heimischer Kohle. Die europäische Liberalisierung des Energiemarkts wurde in Deutschland früher und umfassender umgesetzt als in Frankreich. Die Umsetzung der im Kyoto-Protokoll (1997) festgelegten Reduzierung der CO2-Emissionen wird nur über Stromsparmaßnahmen, Kraft-Wärme-Kopplung (KWK) und den Einsatz erneuerbarer Energien möglich sein. Neue Gesetze fördern seit dem Jahr 2000 KWK und vor allem erneuerbare Energien. Neue technologische Entwicklungen werden die Konkurrenzfähigkeit der Steinkohleverstromung gegenüber Gas verbessern. KWK erfordert den Einsatz von Subventionen, kann aber im Saarland von der vorhandenen Infrastruktur der Fernwärmeschiene Saar profitieren. Erneuerbare Energien entwickeln sich nur langsam. Im Saarland wurden bisher nur 21 Windkraftanlagen mit 12,5 MW installiert, aufgrund der wenigen geeigneten Flächen ist in absehbarer Zeit nicht mehr als eine Verdreifachung zu erwarten. Bescheiden ist auch die Erzeugung von Photovoltaikstrom, auch wenn sie um 25 % über dem deutschen Durchschnitt liegt. Insgesamt wird der Ausbau erneuerbarer Energien viel Zeit brauchen, so daß das Saarland auch in Zukunft ein wichtiger Standort für die Steinkohleverstromung bleiben wird