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The study of rare families with inherited pain insensitivity can identify new human-validated analgesic drug targets. Here, a 66-yr-old female presented with nil requirement for postoperative analgesia after a normally painful orthopaedic hand surgery (trapeziectomy). Further investigations revealed a lifelong history of painless injuries, such as frequent cuts and burns, which were observed to heal quickly. We report the causative mutations for this new pain insensitivity disorder: the co-inheritance of (i) a microdeletion in dorsal root ganglia and brain-expressed pseudogene, FAAH-OUT, which we cloned from the fatty-acid amide hydrolase (FAAH) chromosomal region; and (ii) a common functional single-nucleotide polymorphism in FAAH conferring reduced expression and activity. Circulating concentrations of anandamide and related fatty-acid amides (palmitoylethanolamide and oleoylethanolamine) that are all normally degraded by FAAH were significantly elevated in peripheral blood compared with normal control carriers of the hypomorphic single-nucleotide polymorphism. The genetic findings and elevated circulating fatty-acid amides are consistent with a phenotype resulting from enhanced endocannabinoid signalling and a loss of function of FAAH. Our results highlight previously unknown complexity at the FAAH genomic locus involving the expression of FAAH-OUT, a novel pseudogene and long non-coding RNA. These data suggest new routes to develop FAAH-based analgesia by targeting of FAAH-OUT, which could significantly improve the treatment of postoperative pain and potentially chronic pain and anxiety disorders.


Biological responses to climate change have been widely documented across taxa and regions, but it remains unclear whether species are maintaining a good match between phenotype and environment, i.e. whether observed trait changes are adaptive. Here we reviewed 10,090 abstracts and extracted data from 71 studies reported in 58 relevant publications, to assess quantitatively whether phenotypic trait changes associated with climate change are adaptive in animals. A meta-analysis focussing on birds, the taxon best represented in our dataset, suggests that global warming has not systematically affected morphological traits, but has advanced phenological traits. We demonstrate that these advances are adaptive for some species, but imperfect as evidenced by the observed consistent selection for earlier timing. Application of a theoretical model indicates that the evolutionary load imposed by incomplete adaptive responses to ongoing climate change may already be threatening the persistence of species.


This paper studies differences in the effect of temperature on cognitive performance by gender in a large controlled lab experiment (N = 543). We study performance in math, verbal and cognitive reflection tasks and find that the effects of temperature vary significantly across men and women. At higher temperatures, women perform better on a math and verbal task while the reverse effect is observed for men. The increase in female performance in response to higher temperature is significantly larger and more precisely estimated than the corresponding decrease in male performance. In contrast to math and verbal tasks, temperature has no impact on a measure of cognitive reflection for either gender. Our findings suggest that gender mixed workplaces may be able to increase productivity by setting the thermostat higher than current standards.


The 28,000-year-old remains of a woolly mammoth, named ‘Yuka’, were found in Siberian permafrost. Here we recovered the less-damaged nucleus-like structures from the remains and visualised their dynamics in living mouse oocytes after nuclear transfer. Proteomic analyses demonstrated the presence of nuclear components in the remains. Nucleus-like structures found in the tissue homogenate were histone- and lamin-positive by immunostaining. In the reconstructed oocytes, the mammoth nuclei showed the spindle assembly, histone incorporation and partial nuclear formation; however, the full activation of nuclei for cleavage was not confirmed. DNA damage levels, which varied among the nuclei, were comparable to those of frozen-thawed mouse sperm and were reduced in some reconstructed oocytes. Our work provides a platform to evaluate the biological activities of nuclei in extinct animal species.


Urban residence is associated with a higher risk of some psychiatric disorders, but the underlying drivers remain unknown. There is increasing evidence that the level of exposure to natural environments impacts mental health, but few large-scale epidemiological studies have assessed the general existence and importance of such associations. Here, we investigate the prospective association between green space and mental health in the Danish population. Green space presence was assessed at the individual level using high-resolution satellite data to calculate the normalized difference vegetation index within a 210 × 210 m square around each person’s place of residence (∼1 million people) from birth to the age of 10. We show that high levels of green space presence during childhood are associated with lower risk of a wide spectrum of psychiatric disorders later in life. Risk for subsequent mental illness for those who lived with the lowest level of green space during childhood was up to 55% higher across various disorders compared with those who lived with the highest level of green space. The association remained even after adjusting for urbanization, socioeconomic factors, parental history of mental illness, and parental age. Stronger association of cumulative green space presence during childhood compared with single-year green space presence suggests that presence throughout childhood is important. Our results show that green space during childhood is associated with better mental health, supporting efforts to better integrate natural environments into urban planning and childhood life.


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.


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.


In this study, we used large-scale representative panel data to disentangle the between-person and within-person relations linking adolescent social media use and well-being. We found that social media use is not, in and of itself, a strong predictor of life satisfaction across the adolescent population. Instead, social media effects are nuanced, small at best, reciprocal over time, gender specific, and contingent on analytic methods.


As of April 26, 2019, CDC had reported 704 cases of measles in the United States since the beginning of 2019, representing the largest number of cases reported in the country in a single year since 1994, when 963 cases occurred, and since measles was declared eliminated* in 2000 (1,2). Measles is a highly contagious, acute viral illness characterized by fever and a maculopapular rash; complications include pneumonia, encephalitis, and death. Among the 704 cases, 503 (71%) were in unvaccinated persons and 689 (98%) occurred in U.S. residents. Overall, 66 (9%) patients were hospitalized. Thirteen outbreaks have been reported in 2019, accounting for 663 cases, 94% of all reported cases. Six of the 13 outbreaks were associated with underimmunized close-knit communities and accounted for 88% of all cases. High 2-dose measles vaccination coverage in the United States has been critical to limiting transmission (3). However, increased global measles activity poses a risk to U.S. elimination, particularly when unvaccinated travelers acquire measles abroad and return to communities with low vaccination rates (4). Health care providers should ensure persons are up to date with measles, mumps, rubella (MMR) vaccine, including before international travel, and rapidly report all suspected cases of measles to public health authorities.


Generation of thick vascularized tissues that fully match the patient still remains an unmet challenge in cardiac tissue engineering. Here, a simple approach to 3D-print thick, vascularized, and perfusable cardiac patches that completely match the immunological, cellular, biochemical, and anatomical properties of the patient is reported. To this end, a biopsy of an omental tissue is taken from patients. While the cells are reprogrammed to become pluripotent stem cells, and differentiated to cardiomyocytes and endothelial cells, the extracellular matrix is processed into a personalized hydrogel. Following, the two cell types are separately combined with hydrogels to form bioinks for the parenchymal cardiac tissue and blood vessels. The ability to print functional vascularized patches according to the patient’s anatomy is demonstrated. Blood vessel architecture is further improved by mathematical modeling of oxygen transfer. The structure and function of the patches are studied in vitro, and cardiac cell morphology is assessed after transplantation, revealing elongated cardiomyocytes with massive actinin striation. Finally, as a proof of concept, cellularized human hearts with a natural architecture are printed. These results demonstrate the potential of the approach for engineering personalized tissues and organs, or for drug screening in an appropriate anatomical structure and patient-specific biochemical microenvironment.