Namur Research Institute for Life Sciences

MOTIVATION: Homology or comparative modeling is currently the most accurate method to predict the three-dimensional structure of proteins. It generally consists in four steps: (1) databanks searching to identify the structural homolog, (2) target-template alignment, (3) model building and optimization, and (4) model evaluation. The target-template alignment step is generally accepted as the most critical step in homology modeling. RESULTS: We present here ESyPred3D, a new automated homology modeling program. The method gets benefit of the increased alignment performances of a new alignment strategy. Alignments are obtained by combining, weighting and screening the results of several multiple alignment programs. The final three-dimensional structure is build using the modeling package MODELLER. ESyPred3D was tested on 13 targets in the CASP4 experiment (Critical Assessment of Techniques for Proteins Structural Prediction). Our alignment strategy obtains better results compared to PSI-BLAST alignments and ESyPred3D alignments are among the most accurate compared to those of participants having used the same template. AVAILABILITY: ESyPred3D is available through its web site at http://www.fundp.ac.be/urbm/bioinfo/esypred/ CONTACT: christophe.lambert@fundp.ac.be; http://www.fundp.ac.be/~lambertc

The first human members of the MAGE gene family that have been described are expressed in tumor cells but silent in normal adult tissues except in the male germ line. Hence, they encode strictly tumor-specific antigens that represent attractive targets for cancer immunotherapy. However, other members of the family were recently found to be expressed in normal cells, indicating that the family is larger and more disparate than initially expected. We therefore performed a database screening to identify all of the recorded members of both classes of human MAGE genes. This report provides an overview of the MAGE family and proposes a general nomenclature for all of the MAGE genes identified thus far. We found that the MAGE-D genes were particularly well conserved between man and mouse, suggesting that they exert important functions. In addition, the genomic structure of the MAGE-D genes indicates that one of them corresponds to the founder member of the family, and that all of the other MAGE genes are retrogenes derived from that common ancestral gene. Intriguingly, the COOH-terminal domain of MAGE-D3 was found to be identical to trophinin, a previously described protein believed to be involved in embryo implantation.

The genome of the asexual rotifer Adineta vaga lacks homologous chromosomes; instead, its allelic regions are rearranged and sometimes found on the same chromosome in a palindromic fashion, a structure reminiscent of the primate Y chromosome and of other mitotic lineages such as cancer cells. Bdelloid rotifers are thought to have persisted and diversified asexually for millions of years, which is odd because loss of sexual reproduction is widely considered to be an evolutionary dead end for metazoans. The suspicion remained that they might engage in sex on rare occasions. But here Olivier Jaillon and colleagues sequence the genome of a bdelloid rotifer, Adineta vaga, and show that its structure is incompatible with conventional meiosis, the type of cell division associated with sexual reproduction. The genome has undergone abundant gene conversion, which may limit the accumulation of deleterious mutations in the absence of meiosis. Up to 8% of the genes are of probable non-metazoan origin, probably acquired through horizontal gene transfer. These findings demonstrate positive evidence for asexual evolution, supporting the hypothesis of ancient asexuality among bdelloid rotifers. Loss of sexual reproduction is considered an evolutionary dead end for metazoans, but bdelloid rotifers challenge this view as they appear to have persisted asexually for millions of years1. Neither male sex organs nor meiosis have ever been observed in these microscopic animals: oocytes are formed through mitotic divisions, with no reduction of chromosome number and no indication of chromosome pairing2. However, current evidence does not exclude that they may engage in sex on rare, cryptic occasions. Here we report the genome of a bdelloid rotifer, Adineta vaga (Davis, 1873)3, and show that its structure is incompatible with conventional meiosis. At gene scale, the genome of A. vaga is tetraploid and comprises both anciently duplicated segments and less divergent allelic regions. However, in contrast to sexual species, the allelic regions are rearranged and sometimes even found on the same chromosome. Such structure does not allow meiotic pairing; instead, we find abundant evidence of gene conversion, which may limit the accumulation of deleterious mutations in the absence of meiosis. Gene families involved in resistance to oxidation, carbohydrate metabolism and defence against transposons are significantly expanded, which may explain why transposable elements cover only 3% of the assembled sequence. Furthermore, 8% of the genes are likely to be of non-metazoan origin and were probably acquired horizontally. This apparent convergence between bdelloids and prokaryotes sheds new light on the evolutionary significance of sex.

We have investigated the fundamental mechanism underlying the hydrogen-induced exfoliation of silicon, using a combination of spectroscopic and microscopic techniques. We have studied the evolution of the internal defect structure as a function of implanted hydrogen concentration and annealing temperature and found that the mechanism consists of a number of essential components in which hydrogen plays a key role. Specifically, we show that the chemical action of hydrogen leads to the formation of (100) and (111) internal surfaces above 400 °C via agglomeration of the initial defect structure. In addition, molecular hydrogen is evolved between 200 and 400 °C and subsequently traps in the microvoids bounded by the internal surfaces, resulting in the build-up of internal pressure. This, in turn, leads to the observed “blistering” of unconstrained silicon samples, or complete layer transfer for silicon wafers joined to a supporting (handle) wafer which acts as a mechanical “stiffener.”

Apixaban does not require monitoring nor frequent dose adjustment. However, searching for the optimal dose for the individual patient may be useful in some situations. Moreover, there is a need for clinicians to know whether coagulation assays are influenced by apixaban use. The aim of this study was to determine which coagulation assay could be used to assess the impact of apixaban on haemostasis and provide good laboratory recommendations for the accurate interpretation of haemostasis assays. Apixaban is spiked at concentrations ranging from 5 to 500 ng/mlin platelet-poor plasma. Routinely used or more specific coagulation assays are tested. Results show a concentration dependent prolongation of aPTT, PT and dilute PT. The sensitivity mainly depends on the reagent, but none of these tests is sensitive enough to ensure an accurate estimation of the pharmacodynamic effect of apixaban. FXa chromogenic assays show high sensitivity and a linear correlation depending on the reagent and/or the methodology. Immunological assays and assays acting below the FXa are not influenced by apixaban. In conclusion, PT and/or dilute PT cannot be used to assess apixaban pharmacodynamic properties. More specific and sensitive assays such as chromogenic FXa assays using specific calibrators are required. In case of thrombophilia or in the exploration of a haemorrhagic event, immunological assays should be recommended, when applicable. Standardisation of the time between the last intake of apixaban and the sampling is mandatory.

The virulence functions of Yersinia enterocolitica include the pYV-encoded Yop proteins and YadA adhesin as well as the chromosome-encoded enterotoxin, Yst. The yop and yadA genes form a temperature-activated regulon controlled by the transcriptional activator VirF. Gene virF, also localized on pYV, is itself thermoinduced in the absence of other pYV genes. The enterotoxin yst gene is silent in some collection strains including strain W22703. This paper describes two Tn5-Tc1 chromosomal insertion mutants of W22703 transcribing virF, and hence the yop and yadA genes, at low temperature. These mutants also resumed their production of Yst, with its typical temperature dependence. Both mutations were insertions in the same gene called ymoA for 'Yersinia modulator'. The cloned ymoA gene fully complemented the two mutations. Several properties of the mutants suggest that ymoA encodes a histone-like protein. According to the nucleic acid sequence, the product of ymoA is an 8064 Da protein rich in aspartic acid (9%), glutamic acid (9%) and lysine (10.5%), but the predicted amino acid sequence shows no similarity with any described histone-like protein. This work supports recent reports which propose a role for DNA topology and bacterial chromatin structure in thermoregulation of virulence functions.

IMPORTANCE: A phase 3 trial with ponatinib in patients with chronic myeloid leukemia (CML) was interrupted due to an important increase of vascular occlusive events. A similar risk was also suspected with nilotinib, another BCR-ABL tyrosine kinase inhibitor (TKI) used in patients with CML. OBJECTIVE: To assess the risk of vascular occlusive events in patients with CML treated by new generations of TKIs and provide an overall assessment of the clinical benefit. DATA SOURCES: Two independent reviewers selected studies from PubMed, Scopus, and the Cochrane library database from their inception to October 21, 2014. Abstracts published during the past 3 years at international congresses and a trial register were also searched. STUDY SELECTION: Two independent reviewers screened abstracts and titles against inclusion and exclusion criteria published previously in the PROSPERO 2014 protocol: CRD42014014147. Among the 249 abstracts identified, 10 studies fulfilled the established criteria. DATA EXTRACTION AND SYNTHESIS: Two investigators independently extracted data using a standard form. MAIN OUTCOMES AND MEASURES: Information extracted included study and patients characteristics, type of intervention and data on vascular occlusive events, overall survival, and major molecular response (MMR). The meta-analysis was performed using a fixed-effects model. Odds ratios (ORs) with 95% CIs were computed using the Peto method. RESULTS: Ten randomized clinical trials (3043 patients) were analyzed. Risk of vascular occlusive events was increased with dasatinib (OR, 3.86; 95% CI, 1.33-11.18), nilotinib (OR, 3.42; 95% CI, 2.07-5.63), and ponatinib (OR, 3.47; 95% CI, 1.23-9.78) compared with imatinib in patients with CML. No significant difference was found with bosutinib (OR, 2.77; 95% CI, 0.39-19.77). New-generation TKIs increased the rate of MMR at 1 year compared with imatinib (overall OR, 2.22; 95% CI, 1.87 to 2.63). No statistical difference in overall survival at 1 year was found (overall OR, 1.20; 95% CI, 0.63-2.29). Inaccessibility to individual data and time-to-event data and differences in evaluation criteria between studies could have introduced bias. CONCLUSIONS AND RELEVANCE: Dasatinib, nilotinib, and ponatinib increase vascular occlusive events. New-generation TKIs improve MMR but not the overall survival at 1 year in patients with CML.

ANOLEA (Atomic Non-Local Environment Assessment) is a www server that performs energy calculations at the atomic level in protein structures. The calculations involve the non-local interactions between all the heavy atoms of the twenty standard amino acids in the molecule. The input of the server is a PDB file containing one or more protein chains. The output is an energy profile, which gives an energy value for each amino acid of the protein. High energy zones (HEZs) in the profile correlate with errors or with potential interacting zones of proteins. The output of the server also displays the structure in three dimensions, pointing out the high energy amino acids in the protein. This option requires the CHIME plug-in, which is freely available on Internet and makes possible, in real time, to rotate, translate and change the point of view and presentation of the molecule in three dimensions. Thus, a fast analysis of a protein structure can be done using a personal computer connected to Internet. The server is available at: http:@www.fundp.ac.be/pub/ANOLEA.html.

Modified nucleosides close to the anticodon are important for the proper decoding of mRNA by the ribosome. Particularly, the uridine at the first anticodon position (U34) of glutamate, lysine, and glutamine tRNAs is universally thiolated (S(2)U34), which is proposed to be crucial for both restriction of wobble in the corresponding split codon box and efficient codon-anticodon interaction. Here we show that the highly conserved complex Ctu1-Ctu2 (cytosolic thiouridylase) is responsible for the 2-thiolation of cytosolic tRNAs in the nematode and fission yeast. In both species, inactivation of the complex leads to loss of thiolation on tRNAs and to a thermosensitive decrease of viability associated with marked ploidy abnormalities and aberrant development. Increased level of the corresponding tRNAs suppresses the fission yeast defects, and our data suggest that these defects could result from both misreading and frame shifting during translation. Thus, a translation defect due to unmodified tRNAs results in severe genome instability.

This roadmap outlines the potential roles of metallic nanoparticles (MNPs) in the field of radiation therapy. MNPs made up of a wide range of materials (from Titanium, Z = 22, to Bismuth, Z = 83) and a similarly wide spectrum of potential clinical applications, including diagnostic, therapeutic (radiation dose enhancers, hyperthermia inducers, drug delivery vehicles, vaccine adjuvants, photosensitizers, enhancers of immunotherapy) and theranostic (combining both diagnostic and therapeutic), are being fabricated and evaluated. This roadmap covers contributions from experts in these topics summarizing their view of the current status and challenges, as well as expected advancements in technology to address these challenges.

Glycyl-L-phenylalanine 2-naphthylamide (Gly-L-Phe-2-NNap), a cathepsin C substrate, induces an increase of the free and unsedimentable activities of this enzyme when incubated with a total mitochondrial fraction of rat liver. 1 mM-ZnSO4 considerably inhibits the cathepsin C total activity, measured with Gly-L-Phe-2-NNap as the substrate, in the presence of Triton X-100. The inhibition is markedly less pronounced when the free activity is determined; a high activity remains that depends on the integrity of the lysosomes; it decreases as the free activity of N-acetylglucosaminidase increases when lysosomes are subjected to treatments able to disrupt their membrane. Cathepsin C activity is reduced when thioethylamine hydrochloride is omitted from the incubation medium. Under these conditions at 37 degrees C, the free activity equals the total activity, although the lysosomes are intact, as indicated by the low free activity of N-acetylglucosaminidase. 1 mM-ZnSO4 strikingly inhibits the total activity, whereas more than 80% of the free activity remains. These observations are presented as evidence that Gly-L-Phe-2-NNap can possibly cause a disruption of the lysosomes as a result of its hydrolysis inside these organelles. In the presence of ZnSO4, intralysosomal hydrolysis becomes apparent, owing to a preferential inhibition by Zn2+ of extralysosomal hydrolysis; in the absence of thioethylamine hydrochloride, it is measurable because the disruption of lysosomes by Gly-L-Phe-2-NNap is delayed as a result of a slow-down of the reaction. The usefulness of Gly-L-Phe-2-NNap and related dipeptidyl naphthylamides in lysosomal-membrane-permeability studies is emphasized.

Ways to monitor dabigatran etexilate (DE) therapy would be useful in certain situations. Functional assays such as aPTT or Hemoclot® Thrombin Inhibitor (HTI) have been proposed to evaluate dabigatran concentrations, but previous findings are based on in vitro studies and results must be confirmed in clinical samples. The aim of this study was to compare aPTT and HTI measurements with liquid chromatography-tandem mass spectrometry (LC-MS/MS) measurements of dabigatran in plasma samples from DE treated patients. Seventy-one plasma samples were included. aPTT was performed using STA-CKPrest® and SynthASil®. HTI was performed according to instructions from the manufacturer. The LC-MS/MS method utilised dabigatran-d3 as internal standard. The plasma concentration range was 0 to 645 ng/ml as measured by LC-MS/MS. Overall, the HTI and LC-MS/MS analyses correlated well (r²=0.97). The Bland-Altman analysis showed a mean difference of 9 ng/ml (SD: 20 ng/ml). However, the HTI performed poorly at concentrations <50 ng/ml. LC-MS/MS was sensitive (limit of quantification 1.1 ng/ml) and specific for dabigatran. The aPTT methods did not correlate well with plasma concentrations measured by LC-MS/MS (r² = 0.59 with SynthASil® and 0.50 with STA-CKPrest®). In conclusion, the poor sensitivity, the important inter-individual variability, and the poor correlation with LC-MS/MS preclude the use of aPTT to estimate dabigatran concentrations. Due to its small inter-individual variability and good agreement with LC-MS/MS measurements, we recommend the use of HTI assays to rather accurately estimate concentrations of dabigatran >50 ng/ml. Quantification of lower dabigatran levels in DE-treated patients requires the "reference" LC-MS/MS method.

BACKGROUND: Signals of an increased risk of myocardial infarction (MI) have been identified with dabigatran etexilate in randomized controlled trials (RCTs). METHODS AND RESULES: We conducted searches of the published literature and a clinical trials registry maintained by the drug manufacturer. Criteria for inclusion in our meta-analysis included all RCTs and the availability of outcome data for MI, other cardiovascular events, major bleeding, and all-cause mortality. Among the 501 unique references identified, 14 RCTs fulfilled the inclusion criteria. Stratification analyses by comparators and doses of dabigatran etexilate were conducted. Peto odds ratio (ORPETO) values using the fixed-effect model (FEM) for MI, other cardiovascular events, major bleeding, and all-cause mortality were 1.34 (95% CI 1.08 to 1.65, P=0.007), 0.93 (95%CI 0.83 to 1.06, P=0.270), 0.88 (95% CI 0.79 to 0.99, P=0.029), and 0.89 (95% CI 0.80 to 1.00, P=0.041). When compared with warfarin, ORPETO values using FEM were 1.41 (95% CI 1.11 to 1.80, P=0.005), 0.94 (95%CI 0.83 to 1.06, P=0.293), 0.85 (95% CI 0.76 to 0.96, P=0.007), and 0.90 (95% CI 0.81 to 1.01, P=0.061), respectively. In RCTs using the 150-mg BID dosage, the ORPETO values using FEM were 1.45 (95% CI 1.11 to 1.91, P=0.007), 0.95 (95% CI 0.82 to 1.09, P=0.423), 0.92 (95% CI 0.81 to 1.05, P=0.228), and 0.88 (95% CI 0.78 to 1.00, P=0.045), respectively. The results of the 110-mg BID dosage were mainly driven by the RE-LY trial. CONCLUSIONS: This meta-analysis provides evidence that dabigatran etexilate is associated with a significantly increased risk of MI. This increased risk should be considered taking into account the overall benefit in terms of major bleeding and all-cause mortality.

HIF-1 is the main transcription factor responsible for increased gene expression in hypoxia: VEGF, erythropoietin, GLUT-1, and glycolytic enzymes are such target genes and all participate in the adaptative response of cells to hypoxia. AP-1 activation by hypoxia has also been demonstrated in several cell lines and it cooperates with HIF-1 for increasing VEGF gene transcription in hypoxia. Both HIF-1 and AP-1 activation by hypoxia seems to involve members of the MAP kinase family. Here, we summarize the data indicating that ERK and JNK are needed for activation of HIF-1 and AP-1, respectively.

Heteroepitaxial growth of BaSnO3 and Ba1−xLaxSnO3 (x = 7%) lanthanum doped barium stannate thin films on different perovskite single crystal (SrTiO3 (001) and SmScO3 (110)) substrates has been achieved by pulsed laser deposition under optimized deposition conditions. X-ray diffraction measurements indicate that the films on either of these substrates are relaxed due to the large mismatch and present a high degree of crystallinity with narrow rocking curves and smooth surface morphology while analytical quantification by proton induced X-ray emission confirms the stoichiometric La transfer from a polyphasic target, producing films with measured La contents above the bulk solubility limit. The films show degenerate semiconducting behavior on both substrates, with the observed room temperature resistivities, Hall mobilities, and carrier concentrations of 4.4 mΩ cm, 10.11 cm2 V−1 s−1, and 1.38 × 1020 cm−3 on SmScO3 and 7.8 mΩ cm, 5.8 cm2 V−1 s−1, and 1.36 × 1020 cm−3 on SrTiO3 ruling out any extrinsic contribution from the substrate. The superior electrical properties observed on the SmScO3 substrate are attributed to reduction in dislocation density from the lower lattice mismatch.

Antibody-labeled gold nanoparticles represent a promising novel tool regarding cancer imaging and therapy. Nevertheless, the characterization of biodistribution of such immunonanocarriers has been poorly documented. In this study, the biodistribution of (89)Zr-labeled cetuximab before and after the coupling reaction to gold nanoparticles (AuNPs) was compared and the quantitative imaging performance of (89)Zr immuno-PET was evaluated. Cetuximab was functionalized with the desferal moiety and labeled with (89)Zr ((89)Zr-Df-Bz-NCS-cetuximab). AuNPs with a mean diameter of 5 nm were synthesized according a new method developed in the laboratory, and conjugated to (89)Zr-Df-Bz-NCS-cetuximab using carbodiimide chemistry (AuNPs-PPAA-cetuximab-(89)Zr). The two tracers were injected in A431 xenograft-bearing mice. Tumor and liver uptakes were assessed at different times after injection using quantitative PET imaging. The in vivo specificity of the binding was investigated using a saturating dose of unlabeled cetuximab. Radiolabeled cetuximab was conjugated to AuNPs with a coupling reaction yield >75%. All conjugates were stable in vitro and to a lesser extent in plasma. In vivo distribution studies revealed no significant difference in tumor uptake for cetuximab conjugated to nanoparticles up to 72 h after injection, compared with unconjugated cetuximab. Immuno-PET studies showed that AuNPs-PPAA-cetuximab-(89)Zr provided high tumor-to-background ratio. The liver uptake of AuNPs-PPAA-cetuximab-(89)Zr was higher, compared with (89)Zr-Df-Bz-NCS-cetuximab. In vivo blocking experiments demonstrated selective tumor targeting after coupling reaction. This study showed that the conjugation of AuNPs to cetuximab did not affect its tumor accumulation and that the efficacy of EGFR-targeted nanoparticles was unaltered. The (89)Zr-labeled cetuximab-targeted gold nanoparticles could be a valuable tool for theranostic purposes.

Background: A previous meta-analysis demonstrated that 3 of the new-generation BCR-ABL tyrosine kinase inhibitors (TKIs) (dasatinib, nilotinib and ponatinib) are associated with an increased risk of vascular occlusive events in patients with Ph+ chronic myeloid leukemia compared with imatinib. This meta-analysis of randomized controlled trials aims at assessing these risks separately.Methods: The literature search was performed by two independent reviewers following the previous protocol (PROSPERO 2014:CRD42014014147). A random-effects model and a fixed-effect model were used according to the characteristics of the included studies. Peto odds ratios with 95%CI were computed.Results: Overall, 4.78% of patients developed arterial occlusive events with new generation TKIs compared with 0.96% with imatinib. Ponatinib (ORPETO:3.26; 95%CI:1.12 to 9.50), nilotinib (ORPETO: 3.69; 95%CI:2.29 to 5.95) and dasatinib (ORPETO:3.32; 95%CI:1.37 to 8.01) are all associated with a higher risk of arterial occlusive events than imatinib. Venous occlusive events occur in 0.72% of patients treated with new generation TKIs and in 0.27% of imatinib-treated patients. Overall, a trend toward an increase of the rate of venous occlusive events with new-generation TKIs (ORPETO:2.17; 95%CI:0.90 to 5.25) was highlighted but stratifications by treatment gave nonsignificant results.Conclusions: Vascular occlusive events associated with new-generation BCR-ABL TKIs are driven by arterial occlusive events.

The bdelloid rotifer lineage Adineta vaga inhabits temporary habitats subjected to frequent episodes of drought. The recently published draft sequence of the genome of A. vaga revealed a peculiar genomic structure incompatible with meiosis and suggesting that DNA damage induced by desiccation may have reshaped the genomic structure of these organisms. However, the causative link between DNA damage and desiccation has never been proven to date in rotifers. To test for the hypothesis that desiccation induces DNA double-strand breaks (DSBs), we developed a protocol allowing a high survival rate of desiccated A. vaga. Using pulsed-field gel electrophoresis to monitor genomic integrity, we followed the occurrence of DSBs in dried bdelloids and observed an accumulation of these breaks with time spent in dehydrated state. These DSBs are gradually repaired upon rehydration. Even when the genome was entirely shattered into small DNA fragments by proton radiation, A. vaga individuals were able to efficiently recover from desiccation and repair a large amount of DSBs. Interestingly, when investigating the influence of UV-A and UV-B exposure on the genomic integrity of desiccated bdelloids, we observed that these natural radiations also caused important DNA DSBs, suggesting that the genome is not protected during the desiccated stage but that the repair mechanisms are extremely efficient in these intriguing organisms.

A benzylic amide macrocycle containing a pyridine moiety (macrocycle 2) and a related benzylic amide macrocycle-based molecular shuttle (naphthalimide rotaxane) with two pyridine moieties on the macrocyclic unit were grafted onto a self-assembled monolayer (SAM) of 11-mercaptoundecanoic acid (11-MUA) on gold. X-ray photoelectron spectroscopy (XPS) indicates that the molecules are linked to the SAM by hydrogen-bonding. Electrochemical investigations show that the self-assembled monolayer is densely packed and well ordered and allows the estimation of the average thickness of the SAM alone and of the SAM functionalized with either macrocycle 2 or with naphthalimide rotaxane. The estimated thickness values suggest that the 11-MUA chains in the SAM are tilted with respect to the surface normal, as expected for ordered and stable SAMs, whereas the rotaxane molecules are oriented with the thread parallel to the SAM surface and macrocycle plan preferentially perpendicular to the surface. The photophysical studies of the naphthalimide rotaxane grafted onto the SAM on gold demonstrated that fluorescence is partially quenched but still remains easily measurable because the presence of the SAM reduces the quenching effect of the metal substrate. Moreover, the photophysical analysis clearly indicates that the naphthalimide part of the rotaxane strongly interacts with the carboxylic groups of the SAM, in agreement with the orientation of the molecule obtained from the electrochemistry.

One Health is an interdisciplinary collaboration that aims at mitigating risks to human health arising from microorganisms present in non-human animal species, which have the potential to be transmitted and cause disease in humans. Different degrees of scientific collaboration and sectoral integration are needed for different types of zoonotic diseases, depending on the health and associated economic gains that can be expected from a One Health approach. Indeed, mitigating zoonotic risks related to emerging diseases with pandemic potential is different from mitigating risks related to endemic zoonotic diseases like brucellosis. Likewise, management of brucellosis at the wildlife-livestock interface in wildlife conservation areas is in essence different from mitigating transmission of a given Brucella species within its preferential host species, which in turn is different from mitigating the spillover of a given Brucella species to non-preferential host species, humans included. Brucellosis economic models often oversimplify and/or wrongly assess transmission between reservoir hosts and spillover hosts. Moreover,they may not properly value non-market outcomes, such as avoidance of human disease, consumer confidence and conservation biology issues. As a result, uncertainty is such that the economic predictions of these models can be questionable. Therefore, understanding the infection biology of Brucella species is a prerequisite. This paper reviews and highlights important features of the infection biology of Brucella species and the changing epidemiology of brucellosis that need to be integrated into a true One Health perspective of brucellosis.