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Brain development and function depend on the precise regulation of gene expression. However, our understanding of the complexity and dynamics of the transcriptome of the human brain is incomplete. Here we report the generation and analysis of exon-level transcriptome and associated genotyping data, representing males and females of different ethnicities, from multiple brain regions and neocortical areas of developing and adult post-mortem human brains. We found that 86 per cent of the genes analysed were expressed, and that 90 per cent of these were differentially regulated at the whole-transcript or exon level across brain regions and/or time. The majority of these spatio-temporal differences were detected before birth, with subsequent increases in the similarity among regional transcriptomes. The transcriptome is organized into distinct co-expression networks, and shows sex-biased gene expression and exon usage. We also profiled trajectories of genes associated with neurobiological categories and diseases, and identified associations between single nucleotide polymorphisms and gene expression. This study provides a comprehensive data set on the human brain transcriptome and insights into the transcriptional foundations of human neurodevelopment. Gene expression in the human brain Gene expression controls and dictates everything from development and plasticity to ongoing neurogenesis in the brain, yet the temporal dynamics of transcription throughout the brain's lifetime have been mostly unknown. Here, two groups present a large gene-expression database from a variety of human brain samples ranging from before birth to over 80 years in age. Colantuoni et al . focus on the prefrontal cortex. Although they note significant expression pattern dynamics throughout development, they identify a consistent molecular architecture of transcription across subjects from different races despite the large number of genetic polymorphisms among them. Kang et al . produce a more comprehensive time course, exploring expression in 16 different brain areas, determining that the largest spatiotemporal variability occurs before birth, with transcriptomes in brain regions converging as we age.

The brains of humans and other mammals are highly vulnerable to interruptions in blood flow and decreases in oxygen levels. Here we describe the restoration and maintenance of microcirculation and molecular and cellular functions of the intact pig brain under ex vivo normothermic conditions up to four hours post-mortem. We have developed an extracorporeal pulsatile-perfusion system and a haemoglobin-based, acellular, non-coagulative, echogenic, and cytoprotective perfusate that promotes recovery from anoxia, reduces reperfusion injury, prevents oedema, and metabolically supports the energy requirements of the brain. With this system, we observed preservation of cytoarchitecture; attenuation of cell death; and restoration of vascular dilatory and glial inflammatory responses, spontaneous synaptic activity, and active cerebral metabolism in the absence of global electrocorticographic activity. These findings demonstrate that under appropriate conditions the isolated, intact large mammalian brain possesses an underappreciated capacity for restoration of microcirculation and molecular and cellular activity after a prolonged post-mortem interval. A specialized technology can restore and preserve microcirculation and cellular functions hours post-mortem in an isolated pig brain.

The use of sunscreens is an established and recommended practice to protect skin from solar-induced damage. Around 30 UV filters can be used in sunscreen products in the European Union, which ought to follow the requirements of the regulation 1223/2009 to ensure their efficacy and safety for humans. Nevertheless, low photostability and putative toxicity for humans and environment have been reported for some UV filters. Particularly, the negative impact in marine organisms has recently raised concern on the scientific community. Therefore, it is important to develop new UV filters with improved safety profile and photostability. Over the last two decades, nearly 200 new compounds have revealed promising photoprotection properties. The explored compounds were obtained through different approaches, including exploration of natural sources, synthetic pathways, and nanotechnology. Almost 50 natural products and around 140 synthetic derivatives, such as benzimidazoles, benzotriazoles, hydroxycinnamic acids, xanthones, triazines, among others, have been studied aiming the discovery of novel, effective, and safer future photoprotective agents. Herein, we provide the reader with an overview about UV filters’ challenges and prospects, offering a forward-looking to the next-generation of UV filters.

Human nervous system development is an intricate and protracted process that requires precise spatiotemporal transcriptional regulation. We generated tissue-level and single-cell transcriptomic data from up to 16 brain regions covering prenatal and postnatal rhesus macaque development. Integrative analysis with complementary human data revealed that global intraspecies (ontogenetic) and interspecies (phylogenetic) regional transcriptomic differences exhibit concerted cup-shaped patterns, with a late fetal-to-infancy (perinatal) convergence. Prenatal neocortical transcriptomic patterns revealed transient topographic gradients, whereas postnatal patterns largely reflected functional hierarchy. Genes exhibiting heterotopic and heterochronic divergence included those transiently enriched in the prenatal prefrontal cortex or linked to autism spectrum disorder and schizophrenia. Our findings shed light on transcriptomic programs underlying the evolution of human brain development and the pathogenesis of neuropsychiatric disorders.

Pancreatic adenocarcinoma cells drive autophagy in tumour microenvironment-associated stellate cells, which release alanine that is used by the cancer cells as a carbon source for a variety of metabolic processes in an otherwise nutrient-poor environment. A cancer cell support network dissected Cancer cells generally have metabolic needs that differ from those of neighbouring normal cells, and hence display rewired metabolic networks. Cristovão Sousa et al . show that, in pancreatic cancers, stellate cells in the tumour environment supply cancer cells with the amino acid alanine as the carbon needed for anabolic processes when other sources are scarce. Tumour cells in turn stimulate autophagy in stellate cells, which is needed for alanine secretion. This cross-talk allows pancreatic cancer cells to fulfil their metabolic requirements in an environment lacking in other essential nutrients. Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease characterized by an intense fibrotic stromal response and deregulated metabolism 1 , 2 , 3 , 4 . The role of the stroma in PDAC biology is complex and it has been shown to play critical roles that differ depending on the biological context 5 , 6 , 7 , 8 , 9 , 10 . The stromal reaction also impairs the vasculature, leading to a highly hypoxic, nutrient-poor environment 4 , 11 , 12 . As such, these tumours must alter how they capture and use nutrients to support their metabolic needs 11 , 13 . Here we show that stroma-associated pancreatic stellate cells (PSCs) are critical for PDAC metabolism through the secretion of non-essential amino acids (NEAA). Specifically, we uncover a previously undescribed role for alanine, which outcompetes glucose and glutamine-derived carbon in PDAC to fuel the tricarboxylic acid (TCA) cycle, and thus NEAA and lipid biosynthesis. This shift in fuel source decreases the tumour’s dependence on glucose and serum-derived nutrients, which are limited in the pancreatic tumour microenvironment 4 , 11 . Moreover, we demonstrate that alanine secretion by PSCs is dependent on PSC autophagy, a process that is stimulated by cancer cells. Thus, our results demonstrate a novel metabolic interaction between PSCs and cancer cells, in which PSC-derived alanine acts as an alternative carbon source. This finding highlights a previously unappreciated metabolic network within pancreatic tumours in which diverse fuel sources are used to promote growth in an austere tumour microenvironment.

As the push for carbon-neutral transport continues, the aviation sector is facing increasing pressure to reduce its carbon footprint. Furthermore, commercial air traffic is expected to resume the continuous growth experienced until the pandemic, highlighting the need for reduced emissions. The use of alternative fuels plays a key role in achieving future emission goals, while also lowering the dependency on fossil fuels. The so-called sustainable aviation fuels (SAF), which encompass bio and synthetic fuels, are currently the most viable option, but hydrogen is also being considered as a long-term solution. The present paper reviews the production methods, logistical and technological barriers, and potential for future mass implementation of these alternative fuels. In general, biofuels currently present higher technological readiness levels than other alternatives. Sustainable mass production faces critical feedstock-related challenges that synthetic fuels, together with other solutions, can overcome. All conventional fuel replacements, though with different scopes, will be important in meeting long-term goals. Government support will play an important role in accelerating and facilitating the transition towards sustainable aviation.

The kidney arises from two types of progenitors; here, the signalling conditions that induce the production of collecting ducts and functional nephrons from human pluripotent stem cells are determined, and organoids that recapitulate the functional regionalization of the kidney are produced. Human kidney organoids with all renal components The development of the human kidney in the embryo depends on two different stem cell types, one to generate collecting ducts and the other to generate functional nephrons. Melissa Little, Minoru Takasato and colleagues showed previously that human pluripotent stem cells (hPSCs) can differentiate into both types of progenitors. They have now identified the signalling conditions required to induce not only these structures but also the surrounding cell types including interstitium and blood vessels. Using this approach, they have grown kidney organoids that recapitulate the functional regionalization of the embryonic kidney. The tissue complexity and degree of functionalization achieved in these organoids are not on a par with a working kidney, but replicate the normal human embryonic kidney. Importantly, they provide evidence of their potential in screening drugs for toxicity, modelling genetic kidney disease or perhaps to provide specific kidney cell types for cellular therapy. The human kidney contains up to 2 million epithelial nephrons responsible for blood filtration. Regenerating the kidney requires the induction of the more than 20 distinct cell types required for excretion and the regulation of pH, and electrolyte and fluid balance. We have previously described the simultaneous induction of progenitors for both collecting duct and nephrons via the directed differentiation of human pluripotent stem cells 1 . Paradoxically, although both are of intermediate mesoderm in origin, collecting duct and nephrons have distinct temporospatial origins. Here we identify the developmental mechanism regulating the preferential induction of collecting duct versus kidney mesenchyme progenitors. Using this knowledge, we have generated kidney organoids that contain nephrons associated with a collecting duct network surrounded by renal interstitium and endothelial cells. Within these organoids, individual nephrons segment into distal and proximal tubules, early loops of Henle, and glomeruli containing podocytes elaborating foot processes and undergoing vascularization. When transcription profiles of kidney organoids were compared to human fetal tissues, they showed highest congruence with first trimester human kidney. Furthermore, the proximal tubules endocytose dextran and differentially apoptose in response to cisplatin, a nephrotoxicant. Such kidney organoids represent powerful models of the human organ for future applications, including nephrotoxicity screening, disease modelling and as a source of cells for therapy.

Marine ingredients are a source of new chemical entities with biological action, which is the reason why they have gained relevance in the cosmetic industry. The facial care category is the most relevant in this industry, and within it, the sensitive skin segment occupies a prominent position. This work analyzed the use of marine ingredients in 88 facial cosmetics for sensitive skin from multinational brands, as well as their composition and the scientific evidence that supports their efficacy. Marine ingredients were used in 27% of the cosmetic products for sensitive skin and included the species Laminaria ochroleuca, Ascophyllum nodosum (brown macroalgae), Asparagopsis armata (red macroalgae), and Chlorella vulgaris (microalgae). Carotenoids, polysaccharides, and lipids are the chemical classes highlighted in these preparations. Two ingredients, namely the Ascophyllum nodosum extract and Asparagopsis armata extracts, present clinical evidence supporting their use for sensitive skin. Overall, marine ingredients used in cosmetics for sensitive skin are proposed to reduce skin inflammation and improve the barrier function. Marine-derived preparations constitute promising active ingredients for sensitive skin cosmetic products. Their in-depth study, focusing on the extracted metabolites, randomized placebo-controlled studies including volunteers with sensitive skin, and the use of extraction methods that are more profitable may provide a great opportunity for the cosmetic industry.

Nerve myelination facilitates saltatory action potential conduction and exhibits spatiotemporal variation during development associated with the acquisition of behavioral and cognitive maturity. Although human cognitive development is unique, it is not known whether the ontogenetic progression of myelination in the human neocortex is evolutionarily exceptional. In this study, we quantified myelinated axon fiber length density and the expression of myelin-related proteins throughout postnatal life in the somatosensory (areas 3b/3a/1/2), motor (area 4), frontopolar (prefrontal area 10), and visual (areas 17/18) neocortex of chimpanzees (N = 20) and humans (N = 33). Our examination revealed that neocortical myelination is developmentally protracted in humans compared with chimpanzees. In chimpanzees, the density of myelinated axons increased steadily until adult-like levels were achieved at approximately the time of sexual maturity. In contrast, humans displayed slower myelination during childhood, characterized by a delayed period of maturation that extended beyond late adolescence. This comparative research contributes evidence crucial to understanding the evolution of human cognition and behavior, which arises from the unfolding of nervous system development within the context of an enriched cultural environment. Perturbations of normal developmental processes and the decreased expression of myelin-related molecules have been related to psychiatric disorders such as schizophrenia. Thus, these species differences suggest that the human-specific shift in the timing of cortical maturation during adolescence may have implications for vulnerability to certain psychiatric disorders.

The appearance of cognitive deficits and altered brain morphology in newborns with Down syndrome (DS) suggests that these features are driven by disruptions at the earliest stages of brain development. Despite its high prevalence and extensively characterized cognitive phenotypes, relatively little is known about the cellular and molecular mechanisms that drive the changes seen in DS. Recent technical advances, such as single-cell omics and the development of induced pluripotent stem cell (iPSC) models of DS, now enable in-depth analyses of the biochemical and molecular drivers of altered brain development in DS. Here, we review the current state of knowledge on brain development in DS, focusing primarily on data from human post-mortem brain tissue. We explore the biological mechanisms that have been proposed to lead to intellectual disability in DS, assess the extent to which data from studies using iPSC models supports these hypotheses, and identify current gaps in the field.Trisomy 21, the genetic cause of Down syndrome, is associated with both cognitive deficits and altered brain structure. Here, Anita Bhattacharyya and colleagues discuss our current understanding of the neurodevelopmental mechanisms that are disrupted in Down syndrome and that underlie these changes.