Sustainable coffee: A review of the diverse initiatives and governance dimensions of global coffee supply chains.

With a global footprint of 10 million hectares across 12.5 million farms, coffee is among the world's most traded commodities. The coffee industry has launched a variety of initiatives designed to reduce coffee's contribution to climate change and biodiversity loss and enhance the socio-economic conditions of coffee producers. We systematically reviewed the literature on the sustainability and governance of coffee production and developed a typology of eleven sustainability initiatives. Our review shows that coffee sustainability research has focused primarily on the economic outcomes of certification schemes. The typology expands our knowledge of novel sustainability initiatives being led by coffee farming communities themselves, allowing for an improved consideration of power dynamics in sustainability governance. Sustainability initiatives governed by local actors can improve sustainability outcomes by empowering local decision makers to assess direct risks and benefits of sustainable practices to the local environment, economy, and culture.

Ensembl 2024.

Ensembl (https://www.ensembl.org) is a freely available genomic resource that has produced high-quality annotations, tools, and services for vertebrates and model organisms for more than two decades. In recent years, there has been a dramatic shift in the genomic landscape, with a large increase in the number and phylogenetic breadth of high-quality reference genomes, alongside major advances in the pan-genome representations of higher species. In order to support these efforts and accelerate downstream research, Ensembl continues to focus on scaling for the rapid annotation of new genome assemblies, developing new methods for comparative analysis, and expanding the depth and quality of our genome annotations. This year we have continued our expansion to support global biodiversity research, doubling the number of annotated genomes we support on our Rapid Release site to over 1700, driven by our close collaboration with biodiversity projects such as Darwin Tree of Life. We have also strengthened support for key agricultural species, including the first regulatory builds for farmed animals, and have updated key tools and resources that support the global scientific community, notably the Ensembl Variant Effect Predictor. Ensembl data, software, and tools are freely available.

GENCODE: reference annotation for the human and mouse genomes in 2023.

GENCODE produces high quality gene and transcript annotation for the human and mouse genomes. All GENCODE annotation is supported by experimental data and serves as a reference for genome biology and clinical genomics. The GENCODE consortium generates targeted experimental data, develops bioinformatic tools and carries out analyses that, along with externally produced data and methods, support the identification and annotation of transcript structures and the determination of their function. Here, we present an update on the annotation of human and mouse genes, including developments in the tools, data, analyses and major collaborations which underpin this progress. For example, we report the creation of a set of non-canonical ORFs identified in GENCODE transcripts, the LRGASP collaboration to assess the use of long transcriptomic data to build transcript models, the progress in collaborations with RefSeq and UniProt to increase convergence in the annotation of human and mouse protein-coding genes, the propagation of GENCODE across the human pan-genome and the development of new tools to support annotation of regulatory features by GENCODE. Our annotation is accessible via Ensembl, the UCSC Genome Browser and https://www.gencodegenes.org.

Ensembl 2023.

Ensembl (https://www.ensembl.org) has produced high-quality genomic resources for vertebrates and model organisms for more than twenty years. During that time, our resources, services and tools have continually evolved in line with both the publicly available genome data and the downstream research and applications that utilise the Ensembl platform. In recent years we have witnessed a dramatic shift in the genomic landscape. There has been a large increase in the number of high-quality reference genomes through global biodiversity initiatives. In parallel, there have been major advances towards pangenome representations of higher species, where many alternative genome assemblies representing different breeds, cultivars, strains and haplotypes are now available. In order to support these efforts and accelerate downstream research, it is our goal at Ensembl to create high-quality annotations, tools and services for species across the tree of life. Here, we report our resources for popular reference genomes, the dramatic growth of our annotations (including haplotypes from the first human pangenome graphs), updates to the Ensembl Variant Effect Predictor (VEP), interactive protein structure predictions from AlphaFold DB, and the beta release of our new website.

A joint NCBI and EMBL-EBI transcript set for clinical genomics and research.

Comprehensive genome annotation is essential to understand the impact of clinically relevant variants. However, the absence of a standard for clinical reporting and browser display complicates the process of consistent interpretation and reporting. To address these challenges, Ensembl/GENCODE1 and RefSeq2 launched a joint initiative, the Matched Annotation from NCBI and EMBL-EBI (MANE) collaboration, to converge on human gene and transcript annotation and to jointly define a high-value set of transcripts and corresponding proteins. Here, we describe the MANE transcript sets for use as universal standards for variant reporting and browser display. The MANE Select set identifies a representative transcript for each human protein-coding gene, whereas the MANE Plus Clinical set provides additional transcripts at loci where the Select transcripts alone are not sufficient to report all currently known clinical variants. Each MANE transcript represents an exact match between the exonic sequences of an Ensembl/GENCODE transcript and its counterpart in RefSeq such that the identifiers can be used synonymously. We have now released MANE Select transcripts for 97% of human protein-coding genes, including all American College of Medical Genetics and Genomics Secondary Findings list v3.0 (ref. 3) genes. MANE transcripts are accessible from major genome browsers and key resources. Widespread adoption of these transcript sets will increase the consistency of reporting, facilitate the exchange of data regardless of the annotation source and help to streamline clinical interpretation.

Impact of cocoa agricultural intensification on bird diversity and community composition.

To meet the growing demand for chocolate, cocoa (Theobroma cacao) agriculture is expanding and intensifying. Although this threatens tropical forests, cocoa sustainability initiatives largely overlook biodiversity conservation. To inform these initiatives, we analyzed how cocoa agriculture affects bird diversity at farm and landscape scales with a meta-analysis of 23 studies. We extracted 214 Hedges' g* comparisons of bird diversity and 14 comparisons of community similarity between a forest baseline and 4 farming systems that cover an intensification gradient in landscapes with high and low forest cover, and we summarized 119 correlations between cocoa farm features and bird diversity. Bird diversity declined sharply in low shade cocoa. Cocoa with >30% canopy cover from diverse trees retained bird diversity similar to nearby primary or mature secondary forest but held a different community of birds. Diversity of endemic species, frugivores, and insectivores (agriculture avoiders) declined, whereas diversity of habitat generalists, migrants, nectarivores, and granivores (agriculture associates) increased. As forest decreased on the landscape, the difference in bird community composition between forest and cocoa also decreased, indicating agriculture associates replaced agriculture avoiders in forest patches. Our results emphasize the need to conserve forested landscapes (land sparing) and invest in mixed-shade agroforestry (land sharing) because each strategy benefits a diverse and distinct biological community.

Impacto de la Intensificación Agrícola del Cacao sobre la Diversidad y Composición de la Comunidad de Aves Resumen Para responder a la demanda creciente de chocolate, el cultivo de cacao (Theobroma cacao) se ha expandido e intensificado. Aunque esto es una amenaza para los bosques tropicales, las iniciativas de cacao sustentable en gran medida pasan por alto la conservación de la biodiversidad. Para proporcionar información a estas iniciativas, analizamos como la agricultura del cacao afecta a la diversidad de aves a escala de rancho y de paisaje mediante un metaanálisis de 23 estudios. Extrajimos 214 comparaciones de Hedges g* de la diversidad de aves y 14 comparaciones de la similitud de comunidades entre una línea de base de bosque y 4 sistemas de cultivo que cubren un gradiente de intensificación en paisajes con cobertura de bosque alta a baja, y sintetizamos 119 correlaciones entre características de cultivos de cacao y la diversidad de aves. La diversidad de aves declinó claramente en cultivos con poca sombra. Cultivos con >30% de cobertura de diversos árboles retuvieron una diversidad de aves similar a la de bosques primarios o maduros cercanos, pero presentaron una comunidad diferente. La diversidad de especies endémicas, frugívoras e insectívoras (evasoras de agricultura) declinó, mientras que la diversidad de generalistas de hábitat, migrantes, nectarívoras y granívoras (asociadas a agricultura) incrementó. A medida que decreció el bosque en el paisaje, la diferencia en la composición de la comunidad de aves entre bosque y cacao también decreció, lo que indica que las especies asociadas a la agricultura reemplazaron a las evasoras de la agricultura en los fragmentos de bosque. Nuestros resultados enfatizan la necesidad de conservar paisajes boscosos (conservación de tierras) e invertir en agroforestería de sombra mixta (compartición de tierras) porque cada estrategia beneficia a una comunidad biológica diversa y distinta.

Ensembl 2022.

Ensembl (https://www.ensembl.org) is unique in its flexible infrastructure for access to genomic data and annotation. It has been designed to efficiently deliver annotation at scale for all eukaryotic life, and it also provides deep comprehensive annotation for key species. Genomes representing a greater diversity of species are increasingly being sequenced. In response, we have focussed our recent efforts on expediting the annotation of new assemblies. Here, we report the release of the greatest annual number of newly annotated genomes in the history of Ensembl via our dedicated Ensembl Rapid Release platform (http://rapid.ensembl.org). We have also developed a new method to generate comparative analyses at scale for these assemblies and, for the first time, we have annotated non-vertebrate eukaryotes. Meanwhile, we continually improve, extend and update the annotation for our high-value reference vertebrate genomes and report the details here. We have a range of specific software tools for specific tasks, such as the Ensembl Variant Effect Predictor (VEP) and the newly developed interface for the Variant Recoder. All Ensembl data, software and tools are freely available for download and are accessible programmatically.

Assessment with clinical data of a coupled bio-hemodynamics numerical model to predict leukocyte adhesion in coronary arteries.

Numerical simulations of coupled hemodynamics and leukocyte transport and adhesion inside coronary arteries have been performed. Realistic artery geometries have been obtained for a set of four patients from intravascular ultrasound and angiography images. The numerical model computes unsteady three-dimensional blood hemodynamics and leukocyte concentration in the blood. Wall-shear stress dependent leukocyte adhesion is also computed through agent-based modeling rules, fully coupled to the hemodynamics and leukocyte transport. Numerical results have a good correlation with clinical data. Regions where high adhesion is predicted by the simulations coincide to a good approximation with artery segments presenting plaque increase, as documented by clinical data from baseline and six-month follow-up exam of the same artery. In addition, it is observed that the artery geometry and, in particular, the tortuosity of the centerline are a primary factor in determining the spatial distribution of wall-shear stress, and of the resulting leukocyte adhesion patterns. Although further work is required to overcome the limitations of the present model and ultimately quantify plaque growth in the simulations, these results are encouraging towards establishing a predictive methodology for atherosclerosis progress.

Ensembl 2021.

The Ensembl project (https://www.ensembl.org) annotates genomes and disseminates genomic data for vertebrate species. We create detailed and comprehensive annotation of gene structures, regulatory elements and variants, and enable comparative genomics by inferring the evolutionary history of genes and genomes. Our integrated genomic data are made available in a variety of ways, including genome browsers, search interfaces, specialist tools such as the Ensembl Variant Effect Predictor, download files and programmatic interfaces. Here, we present recent Ensembl developments including two new website portals. Ensembl Rapid Release (http://rapid.ensembl.org) is designed to provide core tools and services for genomes as soon as possible and has been deployed to support large biodiversity sequencing projects. Our SARS-CoV-2 genome browser (https://covid-19.ensembl.org) integrates our own annotation with publicly available genomic data from numerous sources to facilitate the use of genomics in the international scientific response to the COVID-19 pandemic. We also report on other updates to our annotation resources, tools and services. All Ensembl data and software are freely available without restriction.

Ensembl 2020.

The Ensembl (https://www.ensembl.org) is a system for generating and distributing genome annotation such as genes, variation, regulation and comparative genomics across the vertebrate subphylum and key model organisms. The Ensembl annotation pipeline is capable of integrating experimental and reference data from multiple providers into a single integrated resource. Here, we present 94 newly annotated and re-annotated genomes, bringing the total number of genomes offered by Ensembl to 227. This represents the single largest expansion of the resource since its inception. We also detail our continued efforts to improve human annotation, developments in our epigenome analysis and display, a new tool for imputing causal genes from genome-wide association studies and visualisation of variation within a 3D protein model. Finally, we present information on our new website. Both software and data are made available without restriction via our website, online tools platform and programmatic interfaces (available under an Apache 2.0 license) and data updates made available four times a year.

Ensembl 2019.

The Ensembl project (https://www.ensembl.org) makes key genomic data sets available to the entire scientific community without restrictions. Ensembl seeks to be a fundamental resource driving scientific progress by creating, maintaining and updating reference genome annotation and comparative genomics resources. This year we describe our new and expanded gene, variant and comparative annotation capabilities, which led to a 50% increase in the number of vertebrate genomes we support. We have also doubled the number of available human variants and added regulatory regions for many mouse cell types and developmental stages. Our data sets and tools are available via the Ensembl website as well as a through a RESTful webservice, Perl application programming interface and as data files for download.

Sixteen diverse laboratory mouse reference genomes define strain-specific haplotypes and novel functional loci.

We report full-length draft de novo genome assemblies for 16 widely used inbred mouse strains and find extensive strain-specific haplotype variation. We identify and characterize 2,567 regions on the current mouse reference genome exhibiting the greatest sequence diversity. These regions are enriched for genes involved in pathogen defence and immunity and exhibit enrichment of transposable elements and signatures of recent retrotransposition events. Combinations of alleles and genes unique to an individual strain are commonly observed at these loci, reflecting distinct strain phenotypes. We used these genomes to improve the mouse reference genome, resulting in the completion of 10 new gene structures. Also, 62 new coding loci were added to the reference genome annotation. These genomes identified a large, previously unannotated, gene (Efcab3-like) encoding 5,874 amino acids. Mutant Efcab3-like mice display anomalies in multiple brain regions, suggesting a possible role for this gene in the regulation of brain development.

Conservation of Neotropical migratory birds in tropical hardwood and oil palm plantations.

Tropical forests in the Americas are undergoing rapid conversion to commercial agriculture, and many migratory bird species that use these forests have experienced corresponding populations declines. Conservation research for migratory birds in the tropics has focused overwhelmingly on shade coffee plantations and adjacent forest, but both cover types are now in decline, creating an urgent need to evaluate conservation opportunities in other agricultural systems. Here we compare how a community of 42 Neotropical migratory bird species and a subset of five conservation-priority species differ in usage and habitat associations among a secondary forest baseline and four expanding commercial plantation systems in Guatemala: African oil palm, teak, rubber, and mixed-native hardwoods. We found that mixed-native hardwood plantations supported the highest richness and diversity of all migrants and that the three hardwood plantation types generally outperformed oil palm in richness and diversity metrics. Despite this, oil palm supported high abundance of several common and widespread species also experiencing range-wide population declines and may therefore play an important role in conserving common species. Mature secondary forest hosted low abundance and diversity of the full migratory community, but high abundance and richness of conservation priority migrants along with native hardwood and teak plantations. Likewise, the percentage of forest cover on the landscape was positively associated with priority migrant abundance and richness but negatively associated with the abundance of migrants in general, highlighting how individual species within the broad group of Neotropical migratory landbirds respond differently to anthropogenic changes in land use. Across all cover types, the retention of tall overstory trees increased the abundance, richness, and diversity of all migrants, which indicates that vertical structural diversity and remnant trees are important habitat features for birds in agricultural landscapes. Our findings show that conservation opportunities exist in hardwood and oil palm plantations, though the species likely to benefit from conservation action will vary among plantation types. For the subset of conservation priority migrants, our results suggest that conservation efforts should combine strategies that retain and restore secondary forest, promote the adoption of native hardwood and teak plantations, and promote the retention of tall, remnant trees in agricultural landscapes.

Consensus coding sequence (CCDS) database: a standardized set of human and mouse protein-coding regions supported by expert curation.

The Consensus Coding Sequence (CCDS) project provides a dataset of protein-coding regions that are identically annotated on the human and mouse reference genome assembly in genome annotations produced independently by NCBI and the Ensembl group at EMBL-EBI. This dataset is the product of an international collaboration that includes NCBI, Ensembl, HUGO Gene Nomenclature Committee, Mouse Genome Informatics and University of California, Santa Cruz. Identically annotated coding regions, which are generated using an automated pipeline and pass multiple quality assurance checks, are assigned a stable and tracked identifier (CCDS ID). Additionally, coordinated manual review by expert curators from the CCDS collaboration helps in maintaining the integrity and high quality of the dataset. The CCDS data are available through an interactive web page (https://www.ncbi.nlm.nih.gov/CCDS/CcdsBrowse.cgi) and an FTP site (ftp://ftp.ncbi.nlm.nih.gov/pub/CCDS/). In this paper, we outline the ongoing work, growth and stability of the CCDS dataset and provide updates on new collaboration members and new features added to the CCDS user interface. We also present expert curation scenarios, with specific examples highlighting the importance of an accurate reference genome assembly and the crucial role played by input from the research community.

The role of cardiac biomarkers for predicting left ventricular dysfunction and cardiovascular mortality in acute exacerbations of COPD.

The presence of cardiovascular comorbidities is frequently associated with poor outcomes in chronic obstructive pulmonary disease (COPD). No clear role has been defined for cardiac biomarkers in acute exacerbations of COPD (AECOPD). The aim of this systematic review was to examine the prognostic value of brain natriuretic peptide (BNP) and troponins in patients with AECOPD. Two independent authors searched the PubMed and Cochrane Library to collect clinical trials, observational studies and meta-analyses studying the prognostic value of cardiac biomarkers in AECOPD. The reference lists of all the included studies were also reviewed. A total of 14 studies were included in the review, of which 10 measured troponins, 7 measured BNP or NT-proBNP, and 3 measured both. Of the studies that used mortality in AECOPD as an end point, some but not all found that elevated BNP and/or troponins were associated with increased mortality. Of the studies that used left ventricular (LV) dysfunction in AECOPD as an end point, all found a significant association between elevated BNP and troponins in the diagnosis of LV dysfunction. In summary, it appears that there may be a link between an elevated level of BNP or NT-proBNP and increased cardiovascular mortality in AECOPD, although the data currently available are not conclusive. The inconsistencies in biomarkers measured, time points of measurements and the variability in outcome measured preclude more robust analysis.

Current status and new features of the Consensus Coding Sequence database.

The Consensus Coding Sequence (CCDS) project (http://www.ncbi.nlm.nih.gov/CCDS/) is a collaborative effort to maintain a dataset of protein-coding regions that are identically annotated on the human and mouse reference genome assemblies by the National Center for Biotechnology Information (NCBI) and Ensembl genome annotation pipelines. Identical annotations that pass quality assurance tests are tracked with a stable identifier (CCDS ID). Members of the collaboration, who are from NCBI, the Wellcome Trust Sanger Institute and the University of California Santa Cruz, provide coordinated and continuous review of the dataset to ensure high-quality CCDS representations. We describe here the current status and recent growth in the CCDS dataset, as well as recent changes to the CCDS web and FTP sites. These changes include more explicit reporting about the NCBI and Ensembl annotation releases being compared, new search and display options, the addition of biologically descriptive information and our approach to representing genes for which support evidence is incomplete. We also present a summary of recent and future curation targets.

Neratinib overcomes trastuzumab resistance in HER2 amplified breast cancer.

Trastuzumab has been shown to improve the survival outcomes of HER2 positive breast cancer patients. However, a significant proportion of HER2-positive patients are either inherently resistant or develop resistance to trastuzumab. We assessed the effects of neratinib, an irreversible panHER inhibitor, in a panel of 36 breast cancer cell lines. We further assessed its effects with or without trastuzumab in several sensitive and resistant breast cancer cells as well as a BT474 xenograft model. We confirmed that neratinib was significantly more active in HER2-amplified than HER2 non-amplified cell lines. Neratinib decreased the activation of the 4 HER receptors and inhibited downstream pathways. However, HER3 and Akt were reactivated at 24 hours, which was prevented by the combination of trastuzumab and neratinib. Neratinib also decreased pHER2 and pHER3 in acquired trastuzumab resistant cells. Neratinib in combination with trastuzumab had a greater growth inhibitory effect than either drug alone in 4 HER2 positive cell lines. Furthermore, trastuzumab in combination with neratinib was growth inhibitory in SKBR3 and BT474 cells which had acquired resistance to trastuzumab as well as in a BT474 xenograft model. Innately trastuzumab resistant cell lines showed sensitivity to neratinib, but the combination did not enhance response compared to neratinib alone. Levels of HER2 and phospho-HER2 showed a direct correlation with sensitivity to neratinib. Our data indicate that neratinib is an effective anti-HER2 therapy and counteracted both innate and acquired trastuzumab resistance in HER2 positive breast cancer. Our results suggest that combined treatment with trastuzumab and neratinib is likely to be more effective than either treatment alone for both trastuzumab-sensitive breast cancer as well as HER2-positive tumors with acquired resistance to trastuzumab.

Potential of PET to predict the response to trastuzumab treatment in an ErbB2-positive human xenograft tumor model.

UNLABELLED: Currently, an alteration in the gross volume of a tumor is used to assess its response to trastuzumab; however, this approach provides only a late indication of response. Tissue-sample ex vivo assays are potentially valuable, but their procurement through biopsies is invasive and might be biased by tumor heterogeneity. We studied the feasibility of using PET to quantify changes in ErbB2 (HER2/neu) expression and to predict the response to trastuzumab in BT474 breast cancer xenografts with N-[2-(4-(18)F-fluorobenzamido)ethyl]maleimide ((18)F-FBEM)-HER(2:342) Affibody. METHODS: Mice bearing BT474 tumors were given trastuzumab (50 mg/kg loading dose, 25 mg/kg maintenance dose, administered intraperitoneally twice a week) or saline (control) for a total of 5 doses. Tumor size was monitored twice a week. Animals were scanned before the treatment, at 48 h, and 2 wk after the beginning of therapy. After the final scan, PET results were correlated with tumor response and immunohistochemical assessment of ErbB2 level, as well as with vasculature in the treated tumors. RESULTS: Analysis of PET images indicated that tracer uptake was significantly reduced after 1 dose of trastuzumab, compared with baseline, suggesting applicability as an early indicator of changes in ErbB2 expression. After 5 doses of trastuzumab, the overall decrease in (18)F-FBEM-HER(2:342) Affibody uptake also correlated with tumor response and downregulation of ErbB2 expression by immunohistochemical assessment. However, individual animals had different responses. There was a correlation between bigger PET changes and a higher vessel count in the tumors, suggesting that an increased number of vessels could lead to better trastuzumab delivery. We confirmed that the difference in average vessel count in the tumors was not related to the size of the tumors and therefore was not due to the selection of more vascular tumors. This finding is consistent with previous findings demonstrating that the number of vessels in a tumor could be a useful prognostic marker for treatment response. CONCLUSION: Our data suggest that Affibody-based PET can noninvasively provide specific information on changes in receptor expression and could be a valuable strategy for predicting tumor response to trastuzumab.