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\"The most celebrated Andean artwork in the world is a five-hundred-year-old Inca tunic made famous through theories about the meanings of its intricate designs, including attempts to read them as a long-lost writing system. But very little is really known about it. The Royal Inca Tunic reconstructs the history of this enigmatic object, presenting significant new findings about its manufacture and symbolism in Inca visual culture. Andrew James Hamilton draws on meticulous physical examinations of the garment conducted over a decade, wide-ranging studies of colonial Peruvian manuscripts, and groundbreaking research into the tunic's provenance. He methodically builds a case for the textile having been woven by two women who belonged to the very highest echelon of Inca artists for the last emperor of the Inca Empire on the eve of the Spanish invasion in 1532. Hamilton reveals for the first time that this imperial vestment remains unfinished and has suffered massive dye fading that transforms its appearance today, and he proposes a bold new conception of what this radiant masterpiece originally looked like. Featuring stunning photography of the tunic and Hamilton's own beautiful illustrations, The Royal Inca Tunic demonstrates why this object holds an important place in the canon of art history as a deft creation by Indigenous women artists, a reminder of the horrors of colonialism, and an emblem of contemporary Andean identity.\"-- Publisher's website.

Significance Many suggest we are approaching a sixth mass extinction event, and yet estimates of how many species exist, and thus how many might become extinct, vary by as much as an order of magnitude. There are few statistically robust methods to estimate global species richness, and here we introduce several new methods, including one that builds on the observation that larger species are often described before smaller species. We combine these, giving equal weight to each, to provide mean global species estimates for the most speciose order, class, and phylum on Earth, beetles, insects, and arthropods (terrestrial). We attempt to aid conservation planning by broadening the range of methods used and bringing greater stability to global estimates for these taxa. It has been suggested that we do not know within an order of magnitude the number of all species on Earth [May RM (1988) Science 241(4872):1441–1449]. Roughly 1.5 million valid species of all organisms have been named and described [Costello MJ, Wilson S, Houlding B (2012) Syst Biol 61(5):871–883]. Given Kingdom Animalia numerically dominates this list and virtually all terrestrial vertebrates have been described, the question of how many terrestrial species exist is all but reduced to one of how many arthropod species there are. With beetles alone accounting for about 40% of all described arthropod species, the truly pertinent question is how many beetle species exist. Here we present four new and independent estimates of beetle species richness, which produce a mean estimate of 1.5 million beetle species. We argue that the surprisingly narrow range (0.9–2.1 million) of these four autonomous estimates—derived from host-specificity relationships, ratios with other taxa, plant:beetle ratios, and a completely novel body-size approach—represents a major advance in honing in on the richness of this most significant taxon, and is thus of considerable importance to the debate on how many species exist. Using analogous approaches, we also produce independent estimates for all insects, mean: 5.5 million species (range 2.6–7.8 million), and for terrestrial arthropods, mean: 6.8 million species (range 5.9–7.8 million), which suggest that estimates for the world’s insects and their relatives are narrowing considerably.

This is a business history of the first 25 years of nationalized railways in Britain. Commissioned by the British Railways Board and based on the Board's extensive archives, it fully analyses the dynamics of nationalized industry management and the complexities of the vital relationship with government.

Plastic waste has been documented in nearly all types of marine environments and has been found in species spanning all levels of marine food webs. Within these marine environments, deep pelagic waters encompass the largest ecosystems on Earth. We lack a comprehensive understanding of the concentrations, cycling, and fate of plastic waste in sub-surface waters, constraining our ability to implement effective, large-scale policy and conservation strategies. We used remotely operated vehicles and engineered purpose-built samplers to collect and examine the distribution of microplastics in the Monterey Bay pelagic ecosystem at water column depths ranging from 5 to 1000 m. Laser Raman spectroscopy was used to identify microplastic particles collected from throughout the deep pelagic water column, with the highest concentrations present at depths between 200 and 600 m. Examination of two abundant particle feeders in this ecosystem, pelagic red crabs ( Pleuroncodes planipes ) and giant larvaceans ( Bathochordaeus stygius ), showed that microplastic particles readily flow from the environment into coupled water column and seafloor food webs. Our findings suggest that one of the largest and currently underappreciated reservoirs of marine microplastics may be contained within the water column and animal communities of the deep sea.

Humans create vast quantities of wastewater through inefficiencies and poor management of water systems. The wasting of water poses sustainability challenges, depletes energy reserves, and undermines human water security and ecosystem health. Here we review emerging approaches for reusing wastewater and minimizing its generation. These complementary options make the most of scarce freshwater resources, serve the varying water needs of both developed and developing countries, and confer a variety of environmental benefits. Their widespread adoption will require changing how freshwater is sourced, used, managed, and priced.

The reticuloruminal function is central to the digestive efficiency in ruminants. For cattle, collar- and ear tag-based accelerometer monitors have been developed to assess the time spent ruminating on an individual animal. Cattle that are ill feed less and so ruminate less, thus, the estimation of the time spent ruminating provides insights into the health of individual animals. pH boluses directly provide information on the reticuloruminal function within the rumen and extended (three hours or more) periods during which the ruminal pH value remains below 5.6 is an indicator that dysfunction and poor welfare are likely. Accelerometers, incorporated into the pH boluses, have been used to indicate changes in behaviour patterns (high/low activity), utilised to detect the onset of oestrus. The paper demonstrates for the first time that by processing the reticuloruminal motion, it is possible to recover rumination periods. Reticuloruminal motion energy and the time between reticuloruminal contractions are used as inputs to a Support Vector Machine (SVM) to identify rumination periods with an overall accuracy of 86.1%, corroborated by neck mounted rumination collars.

Key Points Post-translational modifications with the lipids farnesyl or geranylgeranyl (together referred to as prenyl) are catalysed by farnesyltransferase (FT) or geranylgeranyltransferase 1 (GGT1) and are required for the cellular localization, function and cancer-causing activities of some proteins. Among the hundreds of proteins that are estimated to be prenylated most are either exclusively farnesylated (for example, HRAS and RAS homologue enriched in brain (RHEB)) or geranylgeranylated (for example, RHOA, RHOC, RALA and RALB); some are both farnesylated and geranylgeranylated (RHOB), and others are naturally farnesylated but become geranylgeranylated when FT is inhibited (for example, KRAS and NRAS). These and other important observations prompted the design and development of inhibitors of FT (FTIs) and GGT1 (GGTIs) as potential anticancer drugs. Several FTIs have been tested clinically but only one GGTI has recently entered clinical trials. Further validation of FT and GGT1 as anticancer drug targets was recently provided by genetic mouse models: conditional loss of FT and/or GGT1 hampers mutant KRAS-induced tumorigenesis and extends the lifespan of mice. FTI treatment results in the reversal of several hallmarks of cancer, including mitotic arrest at prometaphase, induction of apoptosis, inhibition of anchorage-dependent and anchorage-independent growth, invasion, angiogenesis and tumour growth, as well as induction of tumour regression in animal models. These effects seem to be mediated by interference with aberrant signal transduction pathways such as RAF–MEK–ERK, PI3K–AKT, and other oncogenic and survival pathways. GGTI treatment also results in the reversal of the cancer hallmarks mentioned above except that they block cells in the G1 phase of the cell cycle, and this seems to be owing to their ability to induce the accumulation of the cyclin-dependent kinase (CDK) inhibitors p21 and p27 and to inhibit CDKs and induce hypophosphorylation of RB. GGTI treatment also decreases the levels of phospho-AKT and survivin, and this seems to mediate their ability to induce apoptosis. Although in preclinical models FTIs are highly effective as antitumour agents, in clinical trials limited efficacy was observed. This is primarily due to poor patient selection. This in turn is due to our lack of understanding of the mechanism of action of FTIs. In the future, a major effort must be dedicated to identifying the prenylated proteins the inhibition of which is responsible for the antitumour effects of PTIs. This will be of great value not only for enhancing our understanding of the mechanism of action of FTIs and GGTIs, but also for selecting patients whose tumours are addicted to specific prenylated proteins and who are more likely to respond to these agents. Recent advances in techniques to characterize the human prenylome are likely to accelerate achieving these crucial goals in the prenylation field. It was hoped that targeting protein prenylation would inhibit the oncogenic signalling of RAS family members. However, preclinical and clinical trials of prenyltransferase inhibitors have conflicting results. This Review discusses why these differences might occur and the future of targeting prenylation. Protein farnesylation and geranylgeranylation, together referred to as prenylation, are lipid post-translational modifications that are required for the transforming activity of many oncogenic proteins, including some RAS family members. This observation prompted the development of inhibitors of farnesyltransferase (FT) and geranylgeranyltransferase 1 (GGT1) as potential anticancer drugs. In this Review, we discuss the mechanisms by which FT and GGT1 inhibitors (FTIs and GGTIs, respectively) affect signal transduction pathways, cell cycle progression, proliferation and cell survival. In contrast to their preclinical efficacy, only a small subset of patients responds to FTIs. Identifying tumours that depend on farnesylation for survival remains a challenge, and strategies to overcome this are discussed. One GGTI has recently entered the clinic, and the safety and efficacy of GGTIs await results from clinical trials.

This protocol describes an improved northern blot method that enhances detection of small RNA molecules (<40 nt) including regulatory species such as microRNA (miRNA), short-interfering RNA (siRNA) and Piwi-interacting RNA. Northern blot analysis involves the separation of RNA molecules by denaturing gel electrophoresis followed by transfer and cross-linking of the separated molecules to nylon membrane. RNA of interest is then detected by hybridization with labeled complementary nucleic acid probes. We have replaced conventional UV-cross-linking of RNA to nylon membranes with a novel, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)-mediated, chemical cross-linking step that enhances detection of small RNA by up to 50-fold. This requires no specialized equipment, is relatively inexpensive and is technically straightforward. Northern blotting can be done in 2 d, but detection of a specific RNA can vary from minutes to days. Although chemical cross-linking takes longer (15 min to 2 h) than UV cross-linking, improved sensitivity means shorter periods of exposure are required to detect signal after hybridization.

The ocean supplies large quantities of thermal energy to tidewater glaciers, but the mechanisms behind the heat delivery are not fully understood. To examine heat flux dynamics in glacial fjords, we run an 8‐year realistic numerical simulation of Milne Fiord, validated with observations. We leverage the duration and spatial resolution of the simulation to calculate ice melt, offshore density variations, average fjord temperature, and heat fluxes at different locations along‐fjord. Correlations between these quantities reveal that heat fluxes near the grounding line (<5 km) are linked to buoyancy‐driven circulation while offshore forcing is linked to heat fluxes along the remainder of the fjord. Comparison to a simulation with constant offshore boundary conditions reveals that offshore forcing enhances the exchange between the coastal shelf and the fjord, increasing glacier melt rates by 18%. Including offshore forcing into numerical and box models of glacial fjords is essential for accurate melting predictions. Plain Language Summary In high latitude coastal regions, glaciers can flow into the ocean. These glaciers, called tidewater glaciers, are therefore exposed to the warming ocean which can drive submarine melting and glacier retreat. Since most tidewater glaciers terminate in fjords, understanding the mechanisms that regulate the exchange of heat between the ice and the ocean in glacial fjords is important for accurate estimates of glacier melt rates and retreat. In this study we recreate Milne Fiord in a numerical model to study these mechanisms. First, we find that the heat transport near the glacier is regulated by the freshwater released at the glacier face. Second, we find that further than 5 km from the glacier, offshore density variations are responsible for the heat exchange, with a net effect of increasing the exchange between the fjord and the open ocean, which enhances the melting of the tidewater glacier. Key Points 8‐year high‐resolution realistic numerical model of Milne Fiord, validated with observations Heat fluxes are linked to offshore density variations, except within 5 km of the grounding line where they are linked to buoyancy forcing Offshore density variations act to enhance coastal shelf‐fjord exchange, increasing tidewater glacier melt rates by 18%

Missense mutations in p53 are severely deleterious and occur in over 50% of all human cancers. The majority of these mutations are located in the inherently unstable DNA-binding domain (DBD), many of which destabilize the domain further and expose its aggregation-prone hydrophobic core, prompting self-assembly of mutant p53 into inactive cytosolic amyloid-like aggregates. Screening an oligopyridylamide library, previously shown to inhibit amyloid formation associated with Alzheimer’s disease and type II diabetes, identified a tripyridylamide, ADH-6, that abrogates self-assembly of the aggregation-nucleating subdomain of mutant p53 DBD. Moreover, ADH-6 targets and dissociates mutant p53 aggregates in human cancer cells, which restores p53’s transcriptional activity, leading to cell cycle arrest and apoptosis. Notably, ADH-6 treatment effectively shrinks xenografts harboring mutant p53, while exhibiting no toxicity to healthy tissue, thereby substantially prolonging survival. This study demonstrates the successful application of a bona fide small-molecule amyloid inhibitor as a potent anticancer agent. Amyloid aggregation of mutant p53 contributes to its loss of tumor suppressor function and oncogenic gain-of-function. Here, the authors use a protein mimetic to abrogate mutant p53 aggregation and rescue p53 function, which inhibits cancer cell proliferation in vitro and halts tumor growth in vivo.