FLT3L governs the development of partially overlapping hematopoietic lineages in humans and mice.

FMS-related tyrosine kinase 3 ligand (FLT3L), encoded by FLT3LG, is a hematopoietic factor essential for the development of natural killer (NK) cells, B cells, and dendritic cells (DCs) in mice. We describe three humans homozygous for a loss-of-function FLT3LG variant with a history of various recurrent infections, including severe cutaneous warts. The patients' bone marrow (BM) was hypoplastic, with low levels of hematopoietic progenitors, particularly myeloid and B cell precursors. Counts of B cells, monocytes, and DCs were low in the patients' blood, whereas the other blood subsets, including NK cells, were affected only moderately, if at all. The patients had normal counts of Langerhans cells (LCs) and dermal macrophages in the skin but lacked dermal DCs. Thus, FLT3L is required for B cell and DC development in mice and humans. However, unlike its murine counterpart, human FLT3L is required for the development of monocytes but not NK cells.

Human inherited CCR2 deficiency underlies progressive polycystic lung disease.

We describe a human lung disease caused by autosomal recessive, complete deficiency of the monocyte chemokine receptor C-C motif chemokine receptor 2 (CCR2). Nine children from five independent kindreds have pulmonary alveolar proteinosis (PAP), progressive polycystic lung disease, and recurrent infections, including bacillus Calmette Guérin (BCG) disease. The CCR2 variants are homozygous in six patients and compound heterozygous in three, and all are loss-of-expression and loss-of-function. They abolish CCR2-agonist chemokine C-C motif ligand 2 (CCL-2)-stimulated Ca2+ signaling in and migration of monocytic cells. All patients have high blood CCL-2 levels, providing a diagnostic test for screening children with unexplained lung or mycobacterial disease. Blood myeloid and lymphoid subsets and interferon (IFN)-γ- and granulocyte-macrophage colony-stimulating factor (GM-CSF)-mediated immunity are unaffected. CCR2-deficient monocytes and alveolar macrophage-like cells have normal gene expression profiles and functions. By contrast, alveolar macrophage counts are about half. Human complete CCR2 deficiency is a genetic etiology of PAP, polycystic lung disease, and recurrent infections caused by impaired CCL2-dependent monocyte migration to the lungs and infected tissues.

Cytotoxic T Cells Use Mechanical Force to Potentiate Target Cell Killing.

The immunological synapse formed between a cytotoxic T lymphocyte (CTL) and an infected or transformed target cell is a physically active structure capable of exerting mechanical force. Here, we investigated whether synaptic forces promote the destruction of target cells. CTLs kill by secreting toxic proteases and the pore forming protein perforin into the synapse. Biophysical experiments revealed a striking correlation between the magnitude of force exertion across the synapse and the speed of perforin pore formation on the target cell, implying that force potentiates cytotoxicity by enhancing perforin activity. Consistent with this interpretation, we found that increasing target cell tension augmented pore formation by perforin and killing by CTLs. Our data also indicate that CTLs coordinate perforin release and force exertion in space and time. These results reveal an unappreciated physical dimension to lymphocyte function and demonstrate that cells use mechanical forces to control the activity of outgoing chemical signals.

A magnetar giant flare in the nearby starburst galaxy M82.

Magnetar giant flares are rare explosive events releasing up to 1047 erg in gamma rays in less than 1 second from young neutron stars with magnetic fields up to 1015-16 G (refs. 1,2). Only three such flares have been seen from magnetars in our Galaxy3,4 and in the Large Magellanic Cloud5 in roughly 50 years. This small sample can be enlarged by the discovery of extragalactic events, as for a fraction of a second giant flares reach luminosities above 1046 erg s-1, which makes them visible up to a few tens of megaparsecs. However, at these distances they are difficult to distinguish from short gamma-ray bursts (GRBs); much more distant and energetic (1050-53 erg) events, originating in compact binary mergers6. A few short GRBs have been proposed7-11, with different amounts of confidence, as candidate giant magnetar flares in nearby galaxies. Here we report observations of GRB 231115A, positionally coincident with the starburst galaxy M82 (ref. 12). Its spectral properties, along with the length of the burst, the limits on its X-ray and optical counterparts obtained within a few hours, and the lack of a gravitational wave signal, unambiguously qualify this burst as a giant flare from a magnetar in M82.

A sensitive assay for measuring whole-blood responses to type I IFNs.

Human inborn errors of the type I IFN response pathway and auto-Abs neutralizing IFN-α, -ß, and/or -ω can underlie severe viral illnesses. We report a simple assay for the detection of both types of condition. We stimulate whole blood from healthy individuals and patients with either inborn errors of type I IFN immunity or auto-Abs against type I IFNs with glycosylated human IFN-α2, -ß, or -ω. As controls, we add a monoclonal antibody (mAb) blocking the type I IFN receptors and stimulated blood with IFN-γ (type II IFN). Of the molecules we test, IP-10 (encoded by the interferon-stimulated gene (ISG) CXCL10) is the molecule most strongly induced by type I and type II IFNs in the whole blood of healthy donors in an ELISA-like assay. In patients with inherited IFNAR1, IFNAR2, TYK2, or IRF9 deficiency, IP-10 is induced only by IFN-γ, whereas, in those with auto-Abs neutralizing specific type I IFNs, IP-10 is also induced by the type I IFNs not neutralized by the auto-Abs. The measurement of type I and type II IFN-dependent IP-10 induction therefore constitutes a simple procedure for detecting rare inborn errors of the type I IFN response pathway and more common auto-Abs neutralizing type I IFNs.

Evaluating the Frequency of Mole Checks by a Dermatologist and Correlated Variables in a Global Survey across 17 Countries: HELIOS Project.

Secondary prevention of skin cancer consists in early detection of malignant lesions through patients' mole self-examination and medical examination. The objective of this study was to assess the self-reported  frequency of mole examination in a large, representative sample of the adult general population of 17 countries from all continents. Of a total of 17,001 participants, 4.8% had their moles checked by a dermatologist more than once a year, 11.3% once a year, 8.4% every 2-3 years, 12.4% once in a while, 10.3% once in lifetime, and 52.6% of participants had never performed a mole examination. Egypt was the country with the highest prevalence of people who performed a moles check more than once a year (15.9%), followed by Brazil and the USA. A higher frequency of mole checks was associated with sex (man vs woman), higher education, higher income, fair phototype, history of skin cancer, medical insurance, and sun-protective behaviours. Despite recommendations by health providers, it appears that the frequency of mole checks in the general population is still low. It is necessary for dermatologists to keep informing at-risk populations about the importance of moles check, with particular care regarding categories that less frequently adhere to secondary prevention measures.

Safety and Tolerance Evaluation of a Suncare Product in Ethnically Diverse Children With Atopic Dermatitis-Prone Skin

Atopic Dermatitis (AD) is a common chronic inflammatory skin condition, with high prevalence in children. Sun protection is important for children with eczema and AD-prone skin, yet many sunscreens can cause skin irritation due to their formulations. In this study, we evaluated the safety and tolerance of an SPF 50 sunscreen in ethnically diverse children with a history of AD over 4 weeks of product use. A total of 45 children from diverse racial/ethnic backgrounds, aged 3 to 12 years old with skin phototypes I-VI, plus a history of eczema and perceived sensitive skin completed the study. All participants applied sunscreen daily on the face and body, at least 15 minutes prior to sun exposure and as needed. After 4 weeks, evaluations were performed by a dermatologist and by participants for tolerability. Product performance questionnaires were also completed by parents/guardians of pediatric participants. After 4 weeks of sunscreen application, tolerability assessments of skin dryness, peeling, erythema, and edema were all absent in children participants. Parent/guardian evaluations of sunscreen tolerability for their child also revealed no perceived skin issues. These results were consistent with no adverse event being observed throughout the study. Parents/guardians reported that sunscreen application on children was smooth and even, with the absence of a white cast appearance on children with skin of color. We conclude from this study that this SPF 50 sunscreen is safe to use in ethnically diverse children with a history of AD and sensitive skin. J Drugs Dermatol. 2024;23(8):669-673.  doi:10.36849/JDD.8282.

Image Analysis of Xerosis and Atopic Dermatitis Following Prebiotic Skincare Regimen in Ethnically Diverse Patients.

Variations in the epidemiology, clinical presentation, and disease course in atopic dermatitis (AD) patients with Skin of Color (SOC) compared with white counterparts have been reported. In this study, we evaluated the capability of a new imaging device (SkinCam) in quantifying skin texture changes in diverse patients, presenting with AD or xerosis, after using a prebiotic skincare routine over 10 weeks.  A total of 39 subjects from diverse racial/ethnic backgrounds, aged 3 to 76 years old, with Fitzpatrick skin phototypes I to VI, presenting with mild AD and moderate to severe xerosis, were enrolled in the study. All subjects used a prebiotic cleanser on its own for 2 weeks, followed by a prebiotic moisturizer in conjunction for an additional 8 weeks. Standardized images of the subjects' legs were taken with SkinCam at several time points (baseline, week 2, and week 10), and analyzed for skin texture parameters. Our results demonstrate that both skin texture irregularity and skin color patterns significantly improve over time with a prebiotic skincare regimen in AD (n=12) and xerosis (n=24) subjects. Interestingly, image analyses showed more improvement over time in xerosis and AD SOC patients (n=18, Fitzpatrick IV-VI). Lastly, skin texture analyses from SkinCam imaging correlated with clinical assessments, showing significant improvement by prebiotic skincare regimen in all subjects by week 10. In summary, our results demonstrate that the SkinCam imaging device has the capability to effectively monitor skin texture parameters over time in both AD and xerosis patients with lightly and darkly pigmented skin. J Drugs Dermatol. 2024;23(7):557-563.  doi:10.36849/JDD.8371.

BID expression determines the apoptotic fate of cancer cells after abrogation of the spindle assembly checkpoint by AURKB or TTK inhibitors.

BACKGROUND: Drugs targeting the spindle assembly checkpoint (SAC), such as inhibitors of Aurora kinase B (AURKB) and dual specific protein kinase TTK, are in different stages of clinical development. However, cell response to SAC abrogation is poorly understood and there are no markers for patient selection. METHODS: A panel of 53 tumor cell lines of different origins was used. The effects of drugs were analyzed by MTT and flow cytometry. Copy number status was determined by FISH and Q-PCR; mRNA expression by nCounter and RT-Q-PCR and protein expression by Western blotting. CRISPR-Cas9 technology was used for gene knock-out (KO) and a doxycycline-inducible pTRIPZ vector for ectopic expression. Finally, in vivo experiments were performed by implanting cultured cells or fragments of tumors into immunodeficient mice. RESULTS: Tumor cells and patient-derived xenografts (PDXs) sensitive to AURKB and TTK inhibitors consistently showed high expression levels of BH3-interacting domain death agonist (BID), while cell lines and PDXs with low BID were uniformly resistant. Gene silencing rendered BID-overexpressing cells insensitive to SAC abrogation while ectopic BID expression in BID-low cells significantly increased sensitivity. SAC abrogation induced activation of CASP-2, leading to cleavage of CASP-3 and extensive cell death only in presence of high levels of BID. Finally, a prevalence study revealed high BID mRNA in 6% of human solid tumors. CONCLUSIONS: The fate of tumor cells after SAC abrogation is driven by an AURKB/ CASP-2 signaling mechanism, regulated by BID levels. Our results pave the way to clinically explore SAC-targeting drugs in tumors with high BID expression.

IL-4 and IL-13, not eosinophils, drive type 2 airway inflammation, remodeling and lung function decline.

RATIONALE: Type 2 (T2) asthma is characterized by airflow limitations and elevated levels of blood and sputum eosinophils, fractional exhaled nitric oxide, IgE, and periostin. While eosinophils are associated with exacerbations, the contribution of eosinophils to lung inflammation, remodeling and function remains largely hypothetical. OBJECTIVES: To determine the effect of T2 cytokines IL-4, IL-13 and IL-5 on eosinophil biology and compare the impact of depleting just eosinophils versus inhibiting all aspects of T2 inflammation on airway inflammation. METHODS: Human eosinophils or endothelial cells stimulated with IL-4, IL-13 or IL-5 were assessed for gene changes or chemokine release.Mice exposed to house dust mite extract received anti-IL-4Rα (dupilumab), anti-IL-5 or control antibodies and were assessed for changes in lung histological and inflammatory endpoints. MEASUREMENTS AND MAIN RESULTS: IL-4 or IL-13 stimulation of human eosinophils and endothelial cells induced gene expression changes related to granulocyte migration; whereas, IL-5 induced changes reflecting granulocyte differentiation.In a mouse model, blocking IL-4Rα improved lung function by impacting multiple effectors of inflammation and remodeling, except peripheral eosinophil counts, thereby disconnecting blood eosinophils from airway inflammation, remodeling and function. Blocking IL-5 globally reduced eosinophil counts but did not impact inflammatory or functional measures of lung pathology. Whole lung transcriptome analysis revealed that IL-5 or IL-4Rα blockade impacted eosinophil associated genes, whereas IL-4Rα blockade also impacted genes associated with multiple cells, cytokines and chemokines, mucus production, cell:cell adhesion and vascular permeability. CONCLUSIONS: Eosinophils are not the sole contributor to asthma pathophysiology or lung function decline and emphasizes the need to block additional mediators to modify lung inflammation and impact lung function.

Challenges and Opportunities in Cancer Drug Resistance.

There has been huge progress in the discovery of targeted cancer therapies in recent years. However, even for the most successful and impactful cancer drugs which have been approved, both innate and acquired mechanisms of resistance are commonplace. These emerging mechanisms of resistance have been studied intensively, which has enabled drug discovery scientists to learn how it may be possible to overcome such resistance in subsequent generations of treatments. In some cases, novel drug candidates have been able to supersede previously approved agents; in other cases they have been used sequentially or in combinations with existing treatments. This review summarizes the current field in terms of the challenges and opportunities that cancer resistance presents to drug discovery scientists, with a focus on small molecule therapeutics. As part of this review, common themes and approaches have been identified which have been utilized to successfully target emerging mechanisms of resistance. This includes the increase in target potency and selectivity, alternative chemical scaffolds, change of mechanism of action (covalents, PROTACs), increases in blood-brain barrier permeability (BBBP), and the targeting of allosteric pockets. Finally, wider approaches are covered such as monoclonal antibodies (mAbs), bispecific antibodies, antibody drug conjugates (ADCs), and combination therapies.

A blend of functional amino acids and grape polyphenols improves the pig capacity to cope with an inflammatory challenge caused by poor hygiene of housing conditions.

BACKGROUND: Dietary supplementation with a blend of functional amino acids (AA) and grape extract polyphenols contributes to preserve intestinal health and growth performance of piglets during the post-weaning period. In the present experiment, we assessed if a supplementation with a mix of AA and grape extract polyphenols during the post-weaning period would persist to improve the pig capacity to cope with a subsequent challenge caused by poor hygiene of housing conditions. Eighty pigs weaned at 28 days of age were fed a standard diet supplemented (AAP) or not (CNT) with 0.2% of a blend of AA (glutamine, arginine, cystine, valine, isoleucine, and leucine) and grape extract polyphenols during the post-weaning period (from week 0 to 6). At week 6, pigs were transferred to a growing unit where 50% of pigs previously fed AAP and CNT diets were housed in good and the other 50% in poor hygiene conditions for 3 weeks (from week 7 to 9; challenge period). All pigs were fed a standard growing diet that was not supplemented with AAP. We measured pig growth performance, plasma indicators of inflammation, digestive integrity, and oxidative status, and scored fecal consistency. Differences were considered significant at P ≤ 0.05. RESULTS: One week post-weaning, pigs fed AAP had lower plasma concentrations of haptoglobin than CNT pigs (P = 0.03). Six weeks post-weaning, plasma concentrations of diamine oxidase (DAO) were lower (P = 0.03) whereas those of vitamin E and A were greater (P ≤ 0.05) in pigs fed AAP compared to CNT pigs. The prevalence of diarrhea was higher in CNT pigs compared to AAP pigs (P < 0.01). During the challenge period, only pigs previously fed CNT diet had lower growth rate in poor than good conditions (P ≤ 0.05). They had also greater plasma concentrations of haptoglobin and oxidative stress index (OSI) and lower plasma concentrations of vitamin E in poor than good hygiene conditions (P ≤ 0.05). CONCLUSIONS: Pigs fed AAP diet during post-weaning had less diarrhea and plasma concentrations of a digestive integrity marker, as well as greater plasma concentrations of antioxidant indicators during the post-weaning period. The beneficial effects of AAP supplementation persisted after the post-weaning period as evidenced by the absence of effects of the hygiene challenge on growth and health indicators in pigs previously fed APP. This clearly indicated a greater ability of pigs fed AAP to cope with the poor hygiene conditions.

The impact of visible scars on well-being and quality of life: An international epidemiological survey in adults.

INTRODUCTION: Scars are visible marks from various causes, including surgery, skin injury, burning or dermatological disease, and may impact the quality of life. OBJECTIVE: To assess the impact of scars on quality of life (QoL). MATERIAL AND METHODS: Data about sociodemography, presence, origin, and symptoms of scars were collected using an Internet survey between April and May 2020. Overall, 11,100 individuals answered the survey. In total, 48.5% of the responders had at least one scar of less than 1 year of age. Scars were mainly reported on the abdomen and face. Globally, 28.9% of subjects with recent scars reported pain, 23.7% reported burning, 35.0% reported itching, and 44.1% reported redness. Subjects were most frequently bothered by the visibility of their scars and the presence of marks. Incidences were significantly higher than for those with older scars. The average DLQI score was 7.44; it decreased to 2.90 after 1 year. Subjects with scars aged less than 3 months had their QoL more frequently impacted (33.9%) than those with scars aged 12 months or more (10.2%). In subjects reporting skin discomfort, clinical symptoms significantly impacted body movement, choice of clothes, leisure activities, and sexual life more than in those reporting no skin discomfort. Moreover, subjects felt significantly more impacted in their daily lives due to their skin discomfort. When feeling bothered by the visibility of their scars, significantly more subjects were also impacted in their body movement, choice of clothes, leisure activities, and sexual life than those subjects who did not feel bothered. Moreover, significantly more subjects felt embarrassed. CONCLUSION: Scars significantly impact the subjects' quality of life. This impact is even more important when caused by recent and visible scars, with a lower DLQI score in subjects with more aged than in those with recent scars.

Sun exposure behaviours as a compromise to paradoxical injunctions: Insight from a worldwide survey.

BACKGROUND: Behavioural interventions can improve attitudes towards sun protection but the impact remains inconsistent worldwide. OBJECTIVE: To assess awareness of and attitudes towards the multiple facets of sun exposure and suggest ways to improve prevention from overexposure to the sun in all geographical zones and multiple skin types. METHODS: Online survey was conducted from 28 September to 18 October 2021. Study population was selected from the Ipsos online Panel (3,540,000 panellists), aged ≥18 years, from 17 countries around the five continents. Demographics, sun-exposure habits and practices, understanding of risks and information on phototypes were documented and analysed using descriptive statistics. RESULTS: Eighty-eight per cent of participants knew that sunlight can cause skin health problems (90% phototypes I-II, 82% phototypes V-VI, >90% in American and European countries, 72% in Asia and 85% in Africa). Eighty-five per cent used some form of protection against sunlight, predominantly: Seeking shade (77%), avoiding the midday sun (66%), facial application of sunscreen (60%) and wearing protective clothing (44%). The perception of sunlight itself is positive ('it gives energy' for 82%; 'tanned skin looks attractive' for 72%), although less in Asian countries and among individuals with dark skin phototypes. Eighty-three per cent reported having experienced sunburn, mainly in Australia, Canada, USA, Germany, France and Russia, and among individuals with dark skin phototypes. Only 12% systematically/often used all types of protection during exposure to the sun and 23% believed it is safe to go out in the sun with no protection when their skin is already tanned. From 13% (skin phototype I) to 26% (phototype VI) reported not using any form of protection against the sun. Knowledge and habits were significantly superior among people who are accustomed to seeing a dermatologist for a complete skin exam. CONCLUSIONS: Dermatologists could play a crucial role in relaying novel prevention messages, more finely tailored to specific risks, populations and areas of the world.

Feeding intact proteins, peptides, or free amino acids to monogastric farm animals.

For terrestrial farm animals, intact protein sources like soybean meal have been the main ingredients providing the required amino acids (AA) to sustain life. However, in recent years, the availability of hydrolysed protein sources and free AA has led to the use of other forms of AA to feed farm animals. The advent of using these new forms is especially important to reduce the negative environmental impacts of animal production because these new forms allow reducing the dietary crude protein content and provide more digestible materials. However, the form in which dietary AA are provided can have an effect on the dynamics of nutrient availability for protein deposition and tissue growth including the efficiency of nutrient utilization. In this literature review, the use of different forms of AA in animal diets is explored, and their differences in digestion and absorption rates are focused on. These differences affect the postprandial plasma appearance of AA, which can have metabolic consequences, like greater insulin response when free AA or hydrolysates instead of intact proteins are fed, which can have a profound effect on metabolism and growth performance. Nevertheless, the use and application of the different AA forms in animal diets are important to achieve a more sustainable and efficient animal production system in the future, as they allow for a more precise diet formulation and reduced negative environmental impact. It is, therefore, important to differentiate the physiological and metabolic effects of different forms of AA to maximize their nutritional value in animal diets.

Inter-Kingdom Networks of Canola Microbiome Reveal Bradyrhizobium as Keystone Species and Underline the Importance of Bulk Soil in Microbial Studies to Enhance Canola Production.

The subterranean microbiota of plants is of great importance for plant growth and health, as root-associated microbes can perform crucial ecological functions. As the microbial environment of roots is extremely diverse, identifying keystone microorganisms in plant roots, rhizosphere, and bulk soil is a necessary step towards understanding the network of influence within the microbial community associated with roots and enhancing its beneficial elements. To target these hot spots of microbial interaction, we used inter-kingdom network analysis on the canola growth phase of a long-term cropping system diversification experiment conducted at four locations in the Canadian Prairies. Our aims were to verify whether bacterial and fungal communities of canola roots, rhizosphere, and bulk soil are related and influenced by diversification of the crop rotation system; to determine whether there are common or specific core fungi and bacteria in the roots, rhizosphere, and bulk soil under canola grown in different environments and with different levels of cropping system diversification; and to identify hub taxa at the inter-kingdom level that could play an important ecological role in the microbiota of canola. Our results showed that fungi were influenced by crop diversification, which was not the case on bacteria. We found no core microbiota in canola roots but identified three core fungi in the rhizosphere, one core mycobiota in the bulk soil, and one core bacterium shared by the rhizosphere and bulk soil. We identified two bacterial and one fungal hub taxa in the inter-kingdom networks of the canola rhizosphere, and one bacterial and two fungal hub taxa in the bulk soil. Among these inter-kingdom hub taxa, Bradyrhizobium sp. and Mortierella sp. are particularly influential on the microbial community and the plant. To our knowledge, this is the first inter-kingdom network analysis utilized to identify hot spots of interaction in canola microbial communities.

Physiological response to the weaning in two pig lines divergently selected for residual feed intake.

Breeding efficient pigs is a way to reduce dietary costs and environmental waste. However, optimization of feed efficiency must not be linked to a decrease of the ability of animals to cope with stress, such as the weaning. This study characterizes the response after weaning of pigs from two lines divergently selected for residual feed intake (RFI) during growth. Animals of the low (L) RFI line are more efficient than animals from the high (H) RFI line. Thirty-six piglets from each line weaned at 28 days of age were individually housed and fed a conventional dietary sequence. Their performance, behaviour, health and oxidative status, immune and nutritional parameters were followed during three weeks. Daily feed intake and growth rate of pigs from the LRFI line were 35% and 40% lower compared with HRFI (p < 0.001). Pigs from the LRFI-line had lower total tract apparent digestibility (-6% for OM) and suffered more from undernutrition with a 167 and 55% higher plasmatic concentration of NEFA and urea compared with HRFI (p < 0.01). In the first week after the weaning, they had more diarrhoea and had a higher inflammatory status with concentration of haptoglobin 52% higher (p < 0.001). These piglets then seemed to adapt to the weaning conditions and to recover during the second and third weeks. Both lines had similar zootechnical performance and physiological characteristics at the end of the post-weaning period. To conclude, the physiological responses to the weaning differed between lines. Pigs from the LRFI line, selected for greater feed efficiency, were more sensitive to the weaning stress. They were also more resilient as they finally adapted to the new condition and recovered to show similar performance results as pigs of the HRFI line.

Simplification, not "tropicalization", of temperate marine ecosystems under ocean warming and acidification.

Ocean warming is altering the biogeographical distribution of marine organisms. In the tropics, rising sea surface temperatures are restructuring coral reef communities with sensitive species being lost. At the biogeographical divide between temperate and tropical communities, warming is causing macroalgal forest loss and the spread of tropical corals, fishes and other species, termed "tropicalization". A lack of field research into the combined effects of warming and ocean acidification means there is a gap in our ability to understand and plan for changes in coastal ecosystems. Here, we focus on the tropicalization trajectory of temperate marine ecosystems becoming coral-dominated systems. We conducted field surveys and in situ transplants at natural analogues for present and future conditions under (i) ocean warming and (ii) both ocean warming and acidification at a transition zone between kelp and coral-dominated ecosystems. We show that increased herbivory by warm-water fishes exacerbates kelp forest loss and that ocean acidification negates any benefits of warming for range extending tropical corals growth and physiology at temperate latitudes. Our data show that, as the combined effects of ocean acidification and warming ratchet up, marine coastal ecosystems lose kelp forests but do not gain scleractinian corals. Ocean acidification plus warming leads to overall habitat loss and a shift to simple turf-dominated ecosystems, rather than the complex coral-dominated tropicalized systems often seen with warming alone. Simplification of marine habitats by increased CO2 levels cascades through the ecosystem and could have severe consequences for the provision of goods and services.

An extremely young massive clump forming by gravitational collapse in a primordial galaxy.

When cosmic star formation history reaches a peak (at about redshift z ≈ 2), galaxies vigorously fed by cosmic reservoirs are dominated by gas and contain massive star-forming clumps, which are thought to form by violent gravitational instabilities in highly turbulent gas-rich disks. However, a clump formation event has not yet been observed, and it is debated whether clumps can survive energetic feedback from young stars, and afterwards migrate inwards to form galaxy bulges. Here we report the spatially resolved spectroscopy of a bright off-nuclear emission line region in a galaxy at z = 1.987. Although this region dominates star formation in the galaxy disk, its stellar continuum remains undetected in deep imaging, revealing an extremely young (less than ten million years old) massive clump, forming through the gravitational collapse of more than one billion solar masses of gas. Gas consumption in this young clump is more than tenfold faster than in the host galaxy, displaying high star-formation efficiency during this phase, in agreement with our hydrodynamic simulations. The frequency of older clumps with similar masses, coupled with our initial estimate of their formation rate (about 2.5 per billion years), supports long lifetimes (about 500 million years), favouring models in which clumps survive feedback and grow the bulges of present-day galaxies.