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Embarking on a boat trip to escape boredom, intrepid best friends Bob and Joss share an adventure when they become shipwrecked on a tropical island

Accumulated precipitation forecasts are of high socioeconomic importance for agriculturally dominated societies in northern tropical Africa. In this study, the performance of nine operational global ensemble prediction systems (EPSs) is analyzed relative to climatology-based forecasts for 1–5-day accumulated precipitation based on the monsoon seasons during 2007–14 for three regions within northern tropical Africa. To assess the full potential of raw ensemble forecasts across spatial scales, state-of-the-art statistical postprocessing methods were applied in the form of Bayesian model averaging (BMA) and ensemble model output statistics (EMOS), and results were verified against station and spatially aggregated, satellite-based gridded observations. Raw ensemble forecasts are uncalibrated and unreliable, and often underperform relative to climatology, independently of region, accumulation time, monsoon season, and ensemble. The differences between raw ensemble and climatological forecasts are large and partly stem from poor prediction for low precipitation amounts. BMA and EMOS postprocessed forecasts are calibrated, reliable, and strongly improve on the raw ensembles but, somewhat disappointingly, typically do not outperform climatology. Most EPSs exhibit slight improvements over the period 2007–14, but overall they have little added value compared to climatology. The suspicion is that parameterization of convection is a potential cause for the sobering lack of ensemble forecast skill in a region dominated by mesoscale convective systems.

While out camping, Bob and Joss become bored and decide to take a hike and end up getting lost in the woods when they forget to bring their map.

Highly pathogenic avian influenza A(H5N1) viruses of clade 2.3.4.4b underwent an explosive geographic expansion in 2021 among wild birds and domestic poultry across Asia, Europe, and Africa. By the end of 2021, 2.3.4.4b viruses were detected in North America, signifying further intercontinental spread. Here we show that the western movement of clade 2.3.4.4b was quickly followed by reassortment with viruses circulating in wild birds in North America, resulting in the acquisition of different combinations of ribonucleoprotein genes. These reassortant A(H5N1) viruses are genotypically and phenotypically diverse, with many causing severe disease with dramatic neurologic involvement in mammals. The proclivity of the current A(H5N1) 2.3.4.4b virus lineage to reassort and target the central nervous system warrants concerted planning to combat the spread and evolution of the virus within the continent and to mitigate the impact of a potential influenza pandemic that could originate from similar A(H5N1) reassortants. Highly pathogenic avian influenza A(H5N1) viruses of clade 2.3.4.4b underwent an explosive geographic expansion in 2021 among wild birds and domestic poultry. Here, Kandeil et al. show that the Western movement of this clade was followed by reassortment with viruses circulating in wild birds in North America which resulted in different genotypes exhibiting a wide range of disease severity in mammal models (mice, ferrets, chicken) ranging from asymptomatic disease to severe neurological pathology.

\"Meet the Bishnoi, followers of the only religion with nature conservation at its heart. Today, Bishnois remain fierce defenders of trees and animals, living by principles set by their guru Jambhoji in the fifteenth century. They chase down armed poachers, rescue and care for injured animals, save endangered species, and lead heroic reforestation efforts in the Rajasthani desert. In a time of biodiversity loss and climate change, what lessons do they have to teach us? The story of the Bishnoi is true, though it reads like a fable. In 1730, the Maharajah of Jodhpur sent his troops to chop down a forest in northwest India. When 363 local villagers, led by Amrita Devi, hugged the trees to protect them, the Maharajah's men chopped off their heads. Who are these people who love trees so much that they would give their lives to save them? Martin Goodman was invited deep into the world of the Bishnoi, who asked him to share their message. My Head for a Tree takes us from temples, homes, and schoolrooms to animal sanctuaries, farms, and desert forests, revealing a thriving community of eco-warriors. Their stories inspire and challenge readers to live more kindly and defend nature with a passion. While you can only be born a Bishnoi, Goodman writes, we can all follow their example.\"-- Provided by publisher.

Pathogenesis of rheumatoid arthritis depends critically on the NLRP3 inflammasome/interleukin-1 signalling axis. Inflammasome-related rheumatoid arthritis model Mutations in the human NLRP3 inflammasome, a multiprotein complex involved in innate immunity through the production of certain interleukins, were previously linked to rheumatoid arthritis. Further work on the nature of this relationship has been hampered by the lack of a relevant mouse model. This study shows that the pathology in the mouse model of inflammatory arthritis induced by myeloid-specific deletion of the rheumatoid susceptibility gene A20 depends critically on the NLRP3 inflammasome and interleukin-1 signalling axis. Thus, A20 myel-KO mice provide an experimental model for the study of the role of inflammasomes in rheumatoid arthritis pathology and for testing therapies targeting inflammasomes and related cellular pathways. Rheumatoid arthritis is a chronic autoinflammatory disease that affects 1–2% of the world’s population and is characterized by widespread joint inflammation. Interleukin-1 is an important mediator of cartilage destruction in rheumatic diseases 1 , but our understanding of the upstream mechanisms leading to production of interleukin-1β in rheumatoid arthritis is limited by the absence of suitable mouse models of the disease in which inflammasomes contribute to pathology. Myeloid-cell-specific deletion of the rheumatoid arthritis susceptibility gene A20/Tnfaip3 in mice ( A20 myel-KO mice) triggers a spontaneous erosive polyarthritis that resembles rheumatoid arthritis in patients 2 . Rheumatoid arthritis in A20 myel-KO mice is not rescued by deletion of tumour necrosis factor receptor 1 (ref. 2 ). Here we show, however, that it crucially relies on the Nlrp3 inflammasome and interleukin-1 receptor signalling. Macrophages lacking A20 have increased basal and lipopolysaccharide-induced expression levels of the inflammasome adaptor Nlrp3 and proIL-1β. As a result, A20-deficiency in macrophages significantly enhances Nlrp3 inflammasome-mediated caspase-1 activation, pyroptosis and interleukin-1β secretion by soluble and crystalline Nlrp3 stimuli. In contrast, activation of the Nlrc4 and AIM2 inflammasomes is not altered. Importantly, increased Nlrp3 inflammasome activation contributes to the pathology of rheumatoid arthritis in vivo , because deletion of Nlrp3, caspase-1 and the interleukin-1 receptor markedly protects against rheumatoid-arthritis-associated inflammation and cartilage destruction in A20 myel-KO mice. These results reveal A20 as a novel negative regulator of Nlrp3 inflammasome activation, and describe A20 myel-KO mice as the first experimental model to study the role of inflammasomes in the pathology of rheumatoid arthritis.

The mechanisms that control activation of the AIM2 inflammasome by cytosolic bacteria are unclear. Kanneganti and colleagues demonstrate that a pathway involving the transcription factor IRF1 is required for the activation of AIM2. Inflammasomes are critical for mounting host defense against pathogens. The molecular mechanisms that control activation of the AIM2 inflammasome in response to different cytosolic pathogens remain unclear. Here we found that the transcription factor IRF1 was required for activation of the AIM2 inflammasome during infection with the Francisella tularensis subspecies novicida ( F. novicida ), whereas engagement of the AIM2 inflammasome by mouse cytomegalovirus (MCMV) or transfected double-stranded DNA did not require IRF1. Infection of F. novicida detected by the DNA sensor cGAS and its adaptor STING induced type I interferon–dependent expression of IRF1, which drove the expression of guanylate-binding proteins (GBPs); this led to intracellular killing of bacteria and DNA release. Our results reveal a specific requirement for IRF1 and GBPs in the liberation of DNA for sensing by AIM2 depending on the pathogen encountered by the cell.

Regulatory T (T reg ) cells derived from the thymus (tT reg ) and periphery (pT reg ) have central and distinct functions in immunosuppression, but mechanisms for the generation and activation of T reg subsets in vivo are unclear. Here, we show that mechanistic target of rapamycin (mTOR) unexpectedly supports the homeostasis and functional activation of tT reg and pT reg cells. mTOR signaling is crucial for programming activated T reg -cell function to protect immune tolerance and tissue homeostasis. T reg -specific deletion of mTOR drives spontaneous effector T-cell activation and inflammation in barrier tissues and is associated with reduction in both thymic-derived effector T reg (eT reg ) and pT reg cells. Mechanistically, mTOR functions downstream of antigenic signals to drive IRF4 expression and mitochondrial metabolism, and accordingly, deletion of mitochondrial transcription factor A (Tfam) severely impairs T reg -cell suppressive function and eT reg -cell generation. Collectively, our results show that mTOR coordinates transcriptional and metabolic programs in activated T reg subsets to mediate tissue homeostasis. The authors previously showed that mTOR controls the function of regulatory T cells. Here they show how this mTOR signaling orchestrates homeostasis of T reg -cell subsets and prevents fatal autoimmunity.

Precipitation forecasts are of large societal value in the tropics. Here, we compare 1–5-day ensemble predictions from the European Centre for Medium-Range Weather Forecasts (ECMWF, 2009–17) and the Meteorological Service of Canada (MSC, 2009–16) over 30°S–30°N with an extended probabilistic climatology based on the Tropical Rainfall Measuring Mission 3 B42 gridded dataset. Both models predict rainfall occurrence better than the reference only over about half of all land points, with a better performance by MSC. After applying the postprocessing technique ensemble model output statistics, this fraction increases to 87% (ECMWF) and 82% (MSC). For rainfall amount there is skill in many tropical areas (about 60% of land points), which can be increased by postprocessing to 97% (ECMWF) and 88% (MSC). Forecasts for extremes (>20 mm) are only marginally worse than those of occurrence but do not improve as much through postprocessing, particularly over dry areas. Forecast performance is generally best over arid Australia and worst over oceanic deserts, the Andes and Himalayas, as well as over tropical Africa, where models misrepresent the high degree of convective organization, such that even postprocessed forecasts are hardly better than climatology. Skill of 5-day accumulated forecasts often exceeds that of shorter ranges, as timing errors matter less. An increase in resolution and major model update in 2010 has significantly improved ECMWF predictions. Especially over tropical Africa new techniques such as convection-permitting models or combined statistical-dynamical forecasts may be needed to generate skill beyond the climatological reference.

Chronic inflammation during many diseases is associated with bone loss. While interferons (IFNs) are often inhibitory to osteoclast formation, the complex role that IFN and interferon-stimulated genes (ISGs) play in osteoimmunology during inflammatory diseases is still poorly understood. We show that mice deficient in IFN signaling components including IFN alpha and beta receptor 1 (IFNAR1), interferon regulatory factor 1 (IRF1), IRF9, and STAT1 each have reduced bone density and increased osteoclastogenesis compared to wild type mice. The IFN-inducible guanylate-binding proteins (GBPs) on mouse chromosome 3 (GBP1, GBP2, GBP3, GBP5, GBP7) are required to negatively regulate age-associated bone loss and osteoclastogenesis. Mechanistically, GBP2 and GBP5 both negatively regulate in vitro osteoclast differentiation, and loss of GBP5, but not GBP2, results in greater age-associated bone loss in mice. Moreover, mice deficient in GBP5 or chromosome 3 GBPs have greater LPS-mediated inflammatory bone loss compared to wild type mice. Overall, we find that GBP5 contributes to restricting age-associated and inflammation-induced bone loss by negatively regulating osteoclastogenesis. The innate immune system and inflammation modulate bone homeostasis through complex regulation of bone remodelling cells including osteoblasts and osteoclasts. Here, the authors show that the type I interferon pathway and guanylate binding proteins functionally limit bone loss by inhibiting osteoclast functions.