Functional expression of TRPV4 in human periodontal ligament cells

Background: Periodontal ligament (PDL) cells are exposed to physical forces in vivo in response to mastication, parafunction, speech and orthodontic tooth movement. Although it has been shown that PDL cells perceive and respond directly to mechanical stimulation, the nature of the ion channels that mediate this mechanotransduction remain to be fully elucidated. The transient receptor potential (TRP) superfamily of ion channels is believed to play a critical role in sensory physiology, where they act as transducers for thermal, chemical and mechanical stimuli. Recent studies have shown that members of the vanilloid (TRPV) and ankyrin (TRPA) subfamilies encode mechanosensitive TRPs. The vanilloid family member TRPV4 is one such non selective calcium permeable cationic channel which has been shown to be activated by chemical ligands, hypotonicity, and mechanical stimuli. Objectives: The objective of the current study was to investigate functional expression of TRPV4 in cultured human PDL cells. Methods: Human PDL cells were grown in Dulbecco's Modified Eagle Medium with L-glutamine supplemented with 10% fetal bovine serum (FBS), 100UI/ml penicillin and 100μg/ml streptomycin. Cells in passage 4-6 were used in all experiments. TRPV4 functional expression was determined using ratiometric calcium imaging. Cultured cells were loaded with intracellular Ca2+ probe fura-2 and cells were then stimulated with the TRPV4 agonists, 4alpha-phorbol 12,13-didecanoate (4alpha-PDD), GSK1016790A or hypotonic solution. The TRPV4 antagonist RN 1734 was used to block the corresponding agonist responses. Results: PDL fibroblasts responded to application of TRPV4 agonists and hypotonic stimuli by an increase in intracellular calcium which was attenuated in the presence of the TRPV4 antagonist. Conclusions: We have shown for the first time the functional expression of the mechanosensitive TRPV4 channel in human PDL cells. The molecular identity and mechanisms of activation of mechanosensitive TRP channels in PDL cells merit further investigation.

Radioimmunoassay Quantitation of Neuropeptide Y (NPY) in Human Dental Pulps

Neuropeptide Y (NPY) is a 36 amino acid peptide that is abundantly expressed in both the central and peripheral nervous systems. NPY has previously been shown to be present in human dental pulp although its exact role in pulpal health and disease remains to be fully elucidated. In addition to serving a neurotransmitter role, NPY may also have a role in modulating the pulpal response to injury and inflammation. Indeed NPY is known to be a potent vasoconstrictor in a range of tissues. Recent work by our research group has demonstrated changes in sensory neuropeptide levels measured by radioimmunoassay (RIA) in healthy and carious teeth. In addition to elevated levels of sensory neuropeptides, it is also possible that the carious process is associated with increased levels of autonomic neuropeptides such as NPY. Objectives: The aim of the present study was to undertake a comprehensive quantitative RIA analysis of NPY expression in human dental pulps from carious and non-carious teeth. Methods: A total of 22 non-carious and 46 carious teeth were included in the study. NPY was measured in all samples using RIA. Briefly, the RIA system consisted of a total volume of 400 ul, comprising 100 ul anti-NPY antibody (Peninsula Laboratories), 200 ul human NPY synthetic standard or pulp sample, and 100 ul of 125I-labelled NPY as radioactive tracer. Results: The mean concentration of NPY in non-carious teeth was found to be 4.28 ng/g (4.34 SD) compared to 9.57 ng/g (9.39 SD) in carious teeth. Using ANOVA the difference in NPY levels between the non-carious group and the carious group was found to be statistically significant (p= 0.003). Conclusion: The significant increase in the levels of NPY in carious dental pulps reported in this study provides evidence for a role for NPY in the pulpal response to caries.

Domestic Violence as a Human Rights Issue: Rumor v. Italy

The article focuses on the recent developments as regards domestic violence within the context of the Council of Europe. Since 2007 the European Court of Human Rights has issued a series of important judgments in cases involving domestic violence. The most recent of these is Rumor v. Italy, in which the Court issued its judgment on 27 May 2014. The article analyses this case in the context of the Court’s previous jurisprudence on domestic violence. In addition, on 1 August 2014 the Council of Europe Convention on preventing and combating violence against women and domestic violence entered into force, and the article will include a number of reflections on the potential held by this Convention. No violation of the European Convention on Human Rights was found in Rumor, however the question of whether Italy would have been in breach of the provisions of the new Convention, to which it is a party, had this Convention been in force at the time of the relevant events, will be examined.

Adapting to time: duration channels do not mediate human time perception

Accurately encoding the duration and temporal order of events is essential for survival and important to everyday activities, from holding conversations to driving in fast flowing traffic. Although there is a growing body of evidence that the timing of brief events (< 1s) is encoded by modality-specific mechanisms, it is not clear how such mechanisms register event duration. One approach gaining traction is a channel-based model; this envisages narrowly-tuned, overlapping timing mechanisms that respond preferentially to different durations. The channel-based model predicts that adapting to a given event duration will result in overestimating and underestimating the duration of longer and shorter events, respectively. We tested the model by having observers judge the duration of a brief (600ms) visual test stimulus following adaptation to longer (860ms) and shorter (340ms) stimulus durations. The channel-based model predicts perceived duration compression of the test stimulus in the former condition and perceived duration expansion in the latter condition. Duration compression occurred in both conditions, suggesting that the channel-based model does not adequately account for perceived duration of visual events.

Acid-labile protein-adducted heterocyclic aromatic amines in human blood are not viable biomarkers of dietary exposure: A systematic study.

Heterocyclic aromatic amines (HCA) are carcinogenic mutagens formed during cooking of protein-rich foods. HCA residues adducted to blood proteins have been postulated as biomarkers of HCA exposure. However, the viability of quantifying HCAs following hydrolytic release from adducts in vivo and correlation with dietary intake are unproven. To definitively assess the potential of labile HCA-protein adducts as biomarkers, a highly sensitive UPLC-MS/MS method was validated for four major HCAs: 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx) and 2-amino-3,7,8-trimethylimidazo[4,5-f]quinoxaline (7,8-DiMeIQx). Limits of detection were 1e5 pg/ml plasma and recoveries 91e115%. Efficacy of hydrolysis was demonstrated by HCA-protein adducts synthesised in vitro. Plasma and 7-day food diaries were collected from 122 fasting adults consuming their habitual diets. Estimated HCA intakes ranged from 0 to 2.5 mg/day. An extensive range of hydrolysis conditions was examined for release of adducted HCAs in plasma. HCA was detected in only one sample (PhIP, 9.7 pg/ml), demonstrating conclusively for the first time that acid-labile HCA adducts do not reflect dietary HCA intake and are present at such low concentrations that they are not feasible biomarkers of exposure. Identification of biomarkers remains important. The search should concentrate on stabilised HCA peptide markers and use of untargeted proteomic and metabolomic approaches.

Human melioidosis, Malawi, 2011

A case of human melioidosis caused by a novel sequence type of Burkholderia pseudomallei occurred in a child in Malawi, southern Africa. A literature review showed that human cases reported from the continent have been increasing.

Aflatoxin Exposure and Associated Human Health Effects, a Review of Epidemiological Studies

flatoxins are fungal toxins that possess acute life threatening toxicity, carcinogenic properties and other potential chronic adverse effects. Dietary exposure to aflatoxins is considered a major public health concern, especially for subsistence farming communities in sub-Saharan Africa and South Asia, where dietary staple food crops such as groundnuts and maize are often highly contaminated with aflatoxin due to hot and humid climates and poor storage, together with low awareness of risk and lack of enforcement of regulatory limits. Biomarkers have been developed and applied in many epidemiological studies assessing aflatoxin exposure and the associated health effects in these high-risk population groups. This review discusses the recent epidemiological evidence for aflatoxin exposure, co-exposure with other mycotoxins and associated health effects in order to provide evidence on risk assessment, and highlight areas where further research is necessary. Aflatoxin exposure can occur at any stage of life and is a major risk factor for hepatocellular carcinoma, especially when hepatitis B infection is present. Recent evidence suggests that aflatoxin may be an underlying determinant of stunted child growth, and may lower cell-mediated immunity, thereby increasing disease susceptibility. However, a causal relationship between aflatoxin exposure and these latter adverse health outcomes has not been established, and the biological mechanisms for these have not been elucidated, prompting further research. Furthermore, there is a dearth of information regarding the health effects of co-exposure to aflatoxin with other mycotoxins. Recent developments of biomarkers provide opportunities for important future research in this area.

Beneficial Effects of Berberine on Oxidized LDL-induced Cytotoxicity in Human Retinal Müller Cells

PURPOSE. Limited mechanistic understanding of diabetic retinopathy (DR) has hindered therapeutic advances. Berberine, an isoquinolone alkaloid, has shown favorable effects on glucose and lipid metabolism in animal and human studies, but effects on DR are unknown. We previously demonstrated intraretinal extravasation and modification of LDL in human diabetes, and toxicity of modified LDL to human retinal M¨uller cells. We now explore pathogenic effects of modified LDL on M¨uller cells, and the efficacy of berberine in mitigating this cytotoxicity. METHODS. Confluent human M¨uller cells were exposed to in vitro–modified ‘highly oxidized, glycated (HOG-) LDL versus native-LDL (N-LDL; 200 mg protein/L) for 6 or 24 hours, with/ without pretreatment with berberine (5 lM, 1 hour) and/or the adenosine monophosphate (AMP)-activated protein kinase (AMPK) inhibitor, Compound C (5 lM, 1 hour). Using techniques including Western blots, reactive oxygen species (ROS) detection assay, and quantitative real-time PCR, the following outcomes were assessed: cell viability (CCK-8 assay), autophagy (LC3, Beclin-1, ATG-5), apoptosis (cleaved caspase 3, cleaved poly-ADP ribose polymerase), oxidative stress (ROS, nuclear factor erythroid 2-related factor 2, glutathione peroxidase 1, NADPH oxidase 4), angiogenesis (VEGF, pigment epithelium-derived factor), inflammation (inducible nitric oxide synthase, intercellular adhesion molecule 1, IL-6, IL-8, TNF-a), and glial cell activation (glial fibrillary acidic protein). RESULTS. Native-LDL had no effect on cultured human M¨uller cells, but HOG-LDL exhibited marked toxicity, significantly decreasing viability and inducing autophagy, apoptosis, oxidative stress, expression of angiogenic factors, inflammation, and glial cell activation. Berberine attenuated all the effects of HOG-LDL (all P < 0.05), and its effects were mitigated by AMPK inhibition (P < 0.05). CONCLUSIONS. Berberine inhibits modified LDL-induced M¨uller cell injury by activating the AMPK pathway, and merits further study as an agent for preventing and/or treating DR.

Schizophrenia risk from complex variation of complement component 4

Schizophrenia is a heritable brain illness with unknown pathogenic mechanisms. Schizophrenia's strongest genetic association at a population level involves variation in the major histocompatibility complex (MHC) locus, but the genes and molecular mechanisms accounting for this have been challenging to identify. Here we show that this association arises in part from many structurally diverse alleles of the complement component 4 (C4) genes. We found that these alleles generated widely varying levels of C4A and C4B expression in the brain, with each common C4 allele associating with schizophrenia in proportion to its tendency to generate greater expression of C4A. Human C4 protein localized to neuronal synapses, dendrites, axons, and cell bodies. In mice, C4 mediated synapse elimination during postnatal development. These results implicate excessive complement activity in the development of schizophrenia and may help explain the reduced numbers of synapses in the brains of individuals with schizophrenia.

Low-pathogenicity Mycoplasma spp. alter human monocyte and macrophage function and are highly prevalent among patients with ventilator-acquired pneumonia

Background
Ventilator-acquired pneumonia (VAP) remains a significant problem within intensive care units (ICUs). There is a growing recognition of the impact of critical-illness-induced immunoparesis on the pathogenesis of VAP, but the mechanisms remain incompletely understood. We hypothesised that, because of limitations in their routine detection, Mycoplasmataceae are more prevalent among patients with VAP than previously recognised, and that these organisms potentially impair immune cell function.
Methods and setting
159 patients were recruited from 12 UK ICUs. All patients had suspected VAP and underwent bronchoscopy and bronchoalveolar lavage (BAL). VAP was defined as growth of organisms at >104 colony forming units per ml of BAL fluid on conventional culture. Samples were tested for Mycoplasmataceae (Mycoplasma and Ureaplasma spp.) by PCR, and positive samples underwent sequencing for speciation. 36 healthy donors underwent BAL for comparison. Additionally, healthy donor monocytes and macrophages were exposed to Mycoplasma salivarium and their ability to respond to lipopolysaccharide and undertake phagocytosis was assessed.

Results
Mycoplasmataceaewerefoundin49%(95%CI 33% to 65%) of patients with VAP, compared with 14% (95% CI 9% to 25%) of patients without VAP. Patients with sterile BAL fluid had a similar prevalence to healthy donor BAL fluid (10% (95% CI 4% to 20%) vs 8% (95% CI 2% to 22%)). The most common organism identified was M. salivarium. Blood monocytes from healthy volunteers incubated with M. salivarium displayed an impaired TNF-α response to lipopolysaccharide ( p=0.0003), as did monocyte-derived macrophages (MDMs) (p=0.024). MDM exposed to M. salivarium demonstrated impaired phagocytosis ( p=0.005).

Discussion and conclusions
This study demonstrates a high prevalence of Mycoplasmataceae among patients with VAP, with a markedly lower prevalence among patients with suspected VAP in whom subsequent cultures refuted the diagnosis. The most common organism found, M. salivarium, is able to alter the functions of key immune cells. Mycoplasmataceae may contribute to VAP pathogenesis.

Characterizing Human Cysticercosis In Portugal

Abstract text Introduction: Cysticercosis results from the ingestion Taenia solium eggs directly by faecal-oral route or contaminated food or water. While, still considered a leading cause of acquired epilepsy in developed countries, this zoonosis has been controlled or eradicated in industrialized countries due to significant improvements in sanitation, pig rearing and slaughterhouse control systems. Objectives: the health burden of human cysticercosis in Portugal. Material and Metodes: We developed a retrospective study on human neurocysticercosis (NCC) hospitalisations based on the national database resulting from National Health Service (NHS) hospital episodes except those of Madeira and Azores Islands. Results: Between 2006 and 2013 there were 357 hospitalized NCC cases in Portugal. Annual frequency of cases between 2006-2013 kept stable (mean 45). NCC was most frequent in those aged 25-34 years (59; 16,5%) and those >75 years (65; 18,2%). Overall, mean age was 47,3 years (median age 45, standard deviation 41,1, mode 28) and 176 cases were in males (49,3%); no significant differences were observed between age and gender (t-student, p>0,05). In Norte Region cases tended to be older than in Lisboa and Vale do Tejo Region. Conclusions: The Directorate-General of Health established the National Observatory of Cysticercosis and Teniiasis which will define criteria for NCC cases monitoring and surveillance (hospitalized and non-hospitalized cases).

Metabonomics of human amniotic fluid for prenatal diagnostics

O trabalho apresentado nesta tese teve como principais objectivos contribuir para o conhecimento da composição do líquido amniótico humano (LA), colhido no 2º trimestre de gravidez, assim como investigar possíveis alterações na sua composição devido à ocorrência de patologias pré-natais, recorrendo à metabonómica e procurando, assim, definir novos biomarcadores de doenças da grávida e do feto. Após uma introdução descrevendo o estado da arte relacionado com este trabalho (Capítulo 1) e os princípios das metodologias analíticas usadas (Capítulo 2), seguida de uma descrição dos aspectos experimentais associados a esta tese (Capítulo 3), apresentam-se os resultados da caracterização da composição química do LA (gravidez saudável) por espectroscopia de ressonância magnética nuclear (RMN), assim como da monitorização da sua estabilidade durante o armazenamento e após ciclos de congelamento-descongelamento (Capítulo 4). Amostras de LA armazenadas a -20°C registaram alterações significativas, tornando-se estas menos pronunciadas (mas ainda mensuráveis) a -70°C, temperatura recomendada para o armazenamento de LA. Foram também observadas alterações de composição após 1-2 ciclos de congelamento-descongelamento (a ter em conta aquando da reutilização de amostras), assim como à temperatura ambiente (indicando um período máximo de 4h para a manipulação e análise de LA). A aquisição de espectros de RMN de 1H de alta resolução e RMN acoplado (LC-NMR/MS) permitiu a detecção de 75 compostos no LA do 2º trimestre, 6 dos quais detectados pela primeira vez no LA. Experiências de difusão (DOSY) permitiram ainda a caracterização das velocidades de difusão e massas moleculares médias das proteínas mais abundantes. O Capítulo 5 descreve o estudo dos efeitos de malformações fetais (FM) e de cromossomopatias (CD) na composição do LA do 2º trimestre de gravidez. A extensão deste trabalho ao estudo dos efeitos de patologias no LA que ocorrem no 3º trimestre de gravidez é descrita no Capítulo 6, nomeadamente no que se refere ao parto pré-termo (PTD), pré-eclampsia (PE), restrição do crescimento intra-uterino (IUGR), ruptura prematura de membranas (PROM) e diabetes mellitus gestacional (GDM). Como complemento a estes estudos, realizou-se uma análise preliminar da urina materna do 2º trimestre para o estudo de FM e GDM, descrita no Capítulo 7. Para interpretação dos dados analíticos, obtidos por espectroscopia RMN de 1H, cromatografia líquida de ultra eficiência acoplada a espectrometria de massa (UPLC-MS) e espectroscopia do infravermelho médio (MIR), recorreu-se à análise discriminante pelos métodos dos mínimos quadrados parciais e o método dos mínimos quadrados parciais ortogonal (PLS-DA e OPLS-DA) e à correlação espectral. Após análise por validação cruzada de Monte-Carlo (MCCV), os modelos PLS-DA de LA permitiram distinguir as FM dos controlos (sensibilidades 69-85%, especificidades 80-95%, taxas de classificação 80-90%), revelando variações metabólicas ao nível do metabolismo energético, dos metabolismos dos aminoácidos e glícidos assim como possíveis alterações ao nível do funcionamento renal. Observou-se também um grande impacto das FM no perfil metabólico da urina materna (medido por UPLC-MS), tendo no entanto sido registados modelos PLS-DA com menor sensibilidade (40-60%), provavelmente devido ao baixo número de amostras e maior variabilidade da composição da urina (relativamente ao LA). Foram sugeridos possíveis marcadores relacionados com a ocorrência de FM, incluindo lactato, glucose, leucina, valina, glutamina, glutamato, glicoproteínas e conjugados de ácido glucurónico e/ou sulfato e compostos endógenos e/ou exógenos (<1 M) (os últimos visíveis apenas na urina). No LA foram também observadas variações metabólicas devido à ocorrência de vários tipos de cromossomopatias (CD), mas de menor magnitude. Os perfis metabólicos de LA associado a pré- PTD produziram modelos que, apesar do baixo poder de previsão, sugeriram alterações precoces no funcionamento da unidade fetoplacentária, hiperglicémia e stress oxidativo. Os modelos obtidos para os grupos pré- IUGR pré- PE, pré- PROM e pré-diagnóstico GDM (LA e urina materna) registaram baixo poder de previsão, indicando o pouco impacto destas condições na composição do LA e/ou urina do 2º trimestre. Os resultados obtidos demonstram as potencialidades da análise dos perfis metabólicos do LA (e, embora com base em menos estudos, da urina materna) do 2º trimestre para o desenvolvimento de novos e complementares métodos de diagnóstico, nomeadamente para FM e PTD.

Metabolic signature of lung cancer: a metabolomic study of human tissues and biofluids

This thesis reports the application of metabolomics to human tissues and biofluids (blood plasma and urine) to unveil the metabolic signature of primary lung cancer. In Chapter 1, a brief introduction on lung cancer epidemiology and pathogenesis, together with a review of the main metabolic dysregulations known to be associated with cancer, is presented. The metabolomics approach is also described, addressing the analytical and statistical methods employed, as well as the current state of the art on its application to clinical lung cancer studies. Chapter 2 provides the experimental details of this work, in regard to the subjects enrolled, sample collection and analysis, and data processing. In Chapter 3, the metabolic characterization of intact lung tissues (from 56 patients) by proton High Resolution Magic Angle Spinning (HRMAS) Nuclear Magnetic Resonance (NMR) spectroscopy is described. After careful assessment of acquisition conditions and thorough spectral assignment (over 50 metabolites identified), the metabolic profiles of tumour and adjacent control tissues were compared through multivariate analysis. The two tissue classes could be discriminated with 97% accuracy, with 13 metabolites significantly accounting for this discrimination: glucose and acetate (depleted in tumours), together with lactate, alanine, glutamate, GSH, taurine, creatine, phosphocholine, glycerophosphocholine, phosphoethanolamine, uracil nucleotides and peptides (increased in tumours). Some of these variations corroborated typical features of cancer metabolism (e.g., upregulated glycolysis and glutaminolysis), while others suggested less known pathways (e.g., antioxidant protection, protein degradation) to play important roles. Another major and novel finding described in this chapter was the dependence of this metabolic signature on tumour histological subtype. While main alterations in adenocarcinomas (AdC) related to phospholipid and protein metabolisms, squamous cell carcinomas (SqCC) were found to have stronger glycolytic and glutaminolytic profiles, making it possible to build a valid classification model to discriminate these two subtypes. Chapter 4 reports the NMR metabolomic study of blood plasma from over 100 patients and near 100 healthy controls, the multivariate model built having afforded a classification rate of 87%. The two groups were found to differ significantly in the levels of lactate, pyruvate, acetoacetate, LDL+VLDL lipoproteins and glycoproteins (increased in patients), together with glutamine, histidine, valine, methanol, HDL lipoproteins and two unassigned compounds (decreased in patients). Interestingly, these variations were detected from initial disease stages and the magnitude of some of them depended on the histological type, although not allowing AdC vs. SqCC discrimination. Moreover, it is shown in this chapter that age mismatch between control and cancer groups could not be ruled out as a possible confounding factor, and exploratory external validation afforded a classification rate of 85%. The NMR profiling of urine from lung cancer patients and healthy controls is presented in Chapter 5. Compared to plasma, the classification model built with urinary profiles resulted in a superior classification rate (97%). After careful assessment of possible bias from gender, age and smoking habits, a set of 19 metabolites was proposed to be cancer-related (out of which 3 were unknowns and 6 were partially identified as N-acetylated metabolites). As for plasma, these variations were detected regardless of disease stage and showed some dependency on histological subtype, the AdC vs. SqCC model built showing modest predictive power. In addition, preliminary external validation of the urine-based classification model afforded 100% sensitivity and 90% specificity, which are exciting results in terms of potential for future clinical application. Chapter 6 describes the analysis of urine from a subset of patients by a different profiling technique, namely, Ultra-Performance Liquid Chromatography coupled to Mass Spectrometry (UPLC-MS). Although the identification of discriminant metabolites was very limited, multivariate models showed high classification rate and predictive power, thus reinforcing the value of urine in the context of lung cancer diagnosis. Finally, the main conclusions of this thesis are presented in Chapter 7, highlighting the potential of integrated metabolomics of tissues and biofluids to improve current understanding of lung cancer altered metabolism and to reveal new marker profiles with diagnostic value.

Synthesis in the human evolutionary behavioural sciences

Over the last three decades, the application of evolutionary theory to the human sciences has shown remarkable growth. This growth has also been characterised by a ‘splitting’ process, with the emergence of distinct sub-disciplines, most notably: Human Behavioural Ecology (HBE), Evolutionary Psychology (EP) and studies of Cultural Evolution (CE). Multiple applications of evolutionary ideas to the human sciences are undoubtedly a good thing, demonstrating the usefulness of this approach to human affairs. However, this fracture has been associated with considerable tension, a lack of integration, and sometimes outright conflict between researchers. In recent years however, there have been clear signs of hope that a synthesis of the human evolutionary behavioural sciences is underway. Here, we briefly review the history of the debate, both its theoretical and practical causes; then provide evidence that the field is currently becoming more integrated, as the traditional boundaries between sub-disciplines become blurred. This article constitutes the first paper under the new editorship of the Journal of Evolutionary Psychology, which aims to further this integration by explicitly providing a forum for integrated work.

The PREDICTS database: a global database of how local terrestrial biodiversity responds to human impacts

Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species’ threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project – and avert – future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups – including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems – www.predicts.org.uk). We make site-level summary data available alongside this article. The full database will be publicly available in 2015.