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To assess the associations between the consumption of sugary drinks (such as sugar sweetened beverages and 100% fruit juices), artificially sweetened beverages, and the risk of cancer.


Elimination of HIV-1 requires clearance and removal of integrated proviral DNA from infected cells and tissues. Here, sequential long-acting slow-effective release antiviral therapy (LASER ART) and CRISPR-Cas9 demonstrate viral clearance in latent infectious reservoirs in HIV-1 infected humanized mice. HIV-1 subgenomic DNA fragments, spanning the long terminal repeats and the Gag gene, are excised in vivo, resulting in elimination of integrated proviral DNA; virus is not detected in blood, lymphoid tissue, bone marrow and brain by nested and digital-droplet PCR as well as RNAscope tests. No CRISPR-Cas9 mediated off-target effects are detected. Adoptive transfer of human immunocytes from dual treated, virus-free animals to uninfected humanized mice fails to produce infectious progeny virus. In contrast, HIV-1 is readily detected following sole LASER ART or CRISPR-Cas9 treatment. These data provide proof-of-concept that permanent viral elimination is possible.


Combating climate change requires unified action across all sectors of society. However, this collective action is precluded by the ‘consensus gap’ between scientific knowledge and public opinion. Here, we test the extent to which the iconic cities around the world are likely to shift in response to climate change. By analyzing city pairs for 520 major cities of the world, we test if their climate in 2050 will resemble more closely to their own current climate conditions or to the current conditions of other cities in different bioclimatic regions. Even under an optimistic climate scenario (RCP 4.5), we found that 77% of future cities are very likely to experience a climate that is closer to that of another existing city than to its own current climate. In addition, 22% of cities will experience climate conditions that are not currently experienced by any existing major cities. As a general trend, we found that all the cities tend to shift towards the sub-tropics, with cities from the Northern hemisphere shifting to warmer conditions, on average ~1000 km south (velocity ~20 km.year-1), and cities from the tropics shifting to drier conditions. We notably predict that Madrid’s climate in 2050 will resemble Marrakech’s climate today, Stockholm will resemble Budapest, London to Barcelona, Moscow to Sofia, Seattle to San Francisco, Tokyo to Changsha. Our approach illustrates how complex climate data can be packaged to provide tangible information. The global assessment of city analogues can facilitate the understanding of climate change at a global level but also help land managers and city planners to visualize the climate futures of their respective cities, which can facilitate effective decision-making in response to on-going climate change.


Brown adipose tissue (BAT) is able to rapidly generate heat and metabolise macronutrients, such as glucose and lipids, through activation of mitochondrial uncoupling protein 1 (UCP1). Diet can modulate UCP1 function but the capacity of individual nutrients to promote the abundance and activity of UCP1 is not well established. Caffeine consumption has been associated with loss of body weight and increased energy expenditure, but whether it can activate UCP1 is unknown. This study examined the effect of caffeine on BAT thermogenesis in vitro and in vivo. Stem cell-derived adipocytes exposed to caffeine (1 mM) showed increased UCP1 protein abundance and cell metabolism with enhanced oxygen consumption and proton leak. These functional responses were associated with browning-like structural changes in mitochondrial and lipid droplet content. Caffeine also increased peroxisome proliferator-activated receptor gamma coactivator 1-alpha expression and mitochondrial biogenesis, together with a number of BAT selective and beige gene markers. In vivo, drinking coffee (but not water) stimulated the temperature of the supraclavicular region, which co-locates to the main region of BAT in adult humans, and is indicative of thermogenesis. Taken together, these results demonstrate that caffeine can promote BAT function at thermoneutrality and may have the potential to be used therapeutically in adult humans.


Following over 3 decades of gradual but uneven increases in sea ice coverage, the yearly average Antarctic sea ice extents reached a record high of 12.8 × 106 km2 in 2014, followed by a decline so precipitous that they reached their lowest value in the 40-y 1979-2018 satellite multichannel passive-microwave record, 10.7 × 106 km2, in 2017. In contrast, it took the Arctic sea ice cover a full 3 decades to register a loss that great in yearly average ice extents. Still, when considering the 40-y record as a whole, the Antarctic sea ice continues to have a positive overall trend in yearly average ice extents, although at 11,300 ± 5,300 km2⋅y-1, this trend is only 50% of the trend for 1979-2014, before the precipitous decline. Four of the 5 sectors into which the Antarctic sea ice cover is divided all also have 40-y positive trends that are well reduced from their 2014-2017 values. The one anomalous sector in this regard, the Bellingshausen/Amundsen Seas, has a 40-y negative trend, with the yearly average ice extents decreasing overall in the first 3 decades, reaching a minimum in 2007, and exhibiting an overall upward trend since 2007 (i.e., reflecting a reversal in the opposite direction from the other 4 sectors and the Antarctic sea ice cover as a whole).


To assess the prospective associations of baseline and long term trajectories of physical activity on mortality from all causes, cardiovascular disease, and cancer.


Girls and women need effective, safe, and affordable menstrual products. Single-use products are regularly selected by agencies for resource-poor settings; the menstrual cup is a less known alternative. We reviewed international studies on menstrual cup leakage, acceptability, and safety and explored menstrual cup availability to inform programmes.


Background Systemic iron status has been implicated in atherosclerosis and thrombosis. The aim of this study was to investigate the effect of genetically determined iron status on carotid intima-media thickness, carotid plaque, and venous thromboembolism using Mendelian randomization. Methods and Results Genetic instrumental variables for iron status were selected from a genome-wide meta-analysis of 48 972 subjects. Genetic association estimates for carotid intima-media thickness and carotid plaque were obtained using data from 71 128 and 48 434 participants, respectively, and estimates for venous thromboembolism were obtained using data from a study incorporating 7507 cases and 52 632 controls. Conventional 2-sample summary data Mendelian randomization was performed for the main analysis. Higher genetically determined iron status was associated with increased risk of venous thromboembolism. Odds ratios per SD increase in biomarker levels were 1.37 (95% CI 1.14-1.66) for serum iron, 1.25 (1.09-1.43) for transferrin saturation, 1.92 (1.28-2.88) for ferritin, and 0.76 (0.63-0.92) for serum transferrin (with higher transferrin levels representing lower iron status). In contrast, higher iron status was associated with lower risk of carotid plaque. Corresponding odds ratios were 0.85 (0.73-0.99) for serum iron and 0.89 (0.80-1.00) for transferrin saturation, with concordant trends for serum transferrin and ferritin that did not reach statistical significance. There was no Mendelian randomization evidence of an effect of iron status on carotid intima-media thickness. Conclusions These findings support previous work to suggest that higher genetically determined iron status is protective against some forms of atherosclerotic disease but increases the risk of thrombosis related to stasis of blood.


Bluehead wrasses undergo dramatic, socially cued female-to-male sex change. We apply transcriptomic and methylome approaches in this wild coral reef fish to identify the primary trigger and subsequent molecular cascade of gonadal metamorphosis. Our data suggest that the environmental stimulus is exerted via the stress axis and that repression of the aromatase gene (encoding the enzyme converting androgens to estrogens) triggers a cascaded collapse of feminizing gene expression and identifies notable sex-specific gene neofunctionalization. Furthermore, sex change involves distinct epigenetic reprogramming and an intermediate state with altered epigenetic machinery expression akin to the early developmental cells of mammals. These findings reveal at a molecular level how a normally committed developmental process remains plastic and is reversed to completely alter organ structures.


Evidence from humans suggests that the expression of emotions can regulate social interactions and promote coordination within a group. Despite its evolutionary importance, social communication of emotions in non-human animals is still not well understood. Here, we combine behavioural and physiological measures, to determine if animals can distinguish between vocalisations linked to different emotional valences (positive and negative). Using a playback paradigm, goats were habituated to listen to a conspecific call associated with positive or negative valence (habituation phase) and were subsequently exposed to a variant of the same call type (contact call) associated with the opposite valence (dishabituation phase), followed by a final call randomly selected from the habituation phase as control (rehabituation phase). The effects of the calls on the occurrence of looking and cardiac responses in these phases were recorded and compared.