Lack of routine surveillance in countries endemic for bovine tuberculosis (tB) and limited laboratory support contributes to the inability to differentiate the Mycobacterium tuberculosis complex species, leading to an underestimated burden of the disease. Here, Whole-Genome Sequencing of Mycobacterium bovis isolated from tissues with TB-like lesions obtained from cattle and buffalos at Marajó Island, Brazil, demonstrates that recent transmission of M. bovis is ongoing at distinct sites. Moreover, the M. bovis epidemiology in this setting is herein found to be dominated by an endemic and unique clade composed of strains evolved from a common ancestor that are now genetically differentiated from other M. bovis clades. Additionally, envisioning a rapid strain differentiation and tracing across multiple settings, 28 globally validated strain-specific SNPs were identified, three of which considered as robust markers for the M. bovis Marajó strain. In conclusion, this study contributes with data regarding the identification of a novel M. bovis phylogenetic clade responsible for ongoing transmission events in both cattle and buffalo species in Brazil, provides a framework to investigate the dissemination of this highly prevalent strain and, holds the potential to inform TB control strategies that may help to prevent the spread of bovine and zoonotic TB. Tuberculosis (TB) is a worldwide important infectious disease in humans and other animals resulting in substantial morbidity and mortality caused by the Mycobacterium tuberculosis Complex (MTBC) pathogens 1,2. Among these, Mycobacterium bovis is the main etiological agent of bovine TB (bTB) in herds and is associated with a decreased livestock productivity due to early disposal of animals of high zootechnical value with subsequent economic impact 3. The impact of bTB and M. bovis is not only restricted to economic aspects of livestock production. Although the economic losses can ascend to, e.g., US$18 200 in a single region as reported for Makurdi in Nigeria

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is one of the deadliest infectious diseases worldwide. Multidrug and extensively drug-resistant strains are making disease control difficult, and exhausting treatment options. New anti-TB drugs bedaquiline (BDQ), delamanid (DLM) and pretomanid (PTM) have been approved for the treatment of multi-drug resistant TB, but there is increasing resistance to them. Nine genetic loci strongly linked to resistance have been identified (mmpR5, atpE, and pepQ for BDQ; ddn, fgd1, fbiA, fbiB, fbiC, and fbiD for DLM/PTM). Here we investigated the genetic diversity of these loci across >33,000 M. tuberculosis isolates. In addition, epistatic mutations in mmpL5-mmpS5 as well as variants in ndh, implicated for DLM/PTM resistance in M. smegmatis, were explored. Our analysis revealed 1,227 variants across the nine genes, with the majority (78%) present in isolates collected prior to the roll-out of BDQ and DLM/PTM. We identified phylogenetically-related mutations, which are unlikely to be resistance associated, but also high-impact variants such as frameshifts (e.g. in mmpR5, ddn) with likely functional effects, as well as non-synonymous mutations predominantly in MDR-/XDR-TB strains with predicted protein destabilising effects. Overall, our work provides a comprehensive mutational catalogue for BDQ and DLM/PTM associated genes, which will assist with establishing associations with phenotypic resistance; thereby, improving the understanding of the causative mechanisms of resistance for these drugs, leading to better treatment outcomes.

Portugal is a low incidence country for tuberculosis (TB) disease. Now figuring among TB low incidence countries, it has since the 1990s reported multidrug resistant and extensively drug resistant (XDR) TB cases, driven predominantly by two strain-types: Lisboa3 and Q1. This study describes the largest characterization of the evolutionary trajectory of M/XDR-TB strains in Portugal, spanning a time-period of two decades. By combining whole-genome sequencing and phenotypic susceptibility data for 207 isolates, we report the geospatial patterns of drug resistant TB, particularly the dispersion of Lisboa3 and Q1 clades, which underly 64.2% and 94.0% of all MDR-TB and XDR-TB isolates, respectively. Genomic-based similarity and a phylogenetic analysis revealed multiple clusters (n = 16) reflecting ongoing and uncontrolled recent transmission of M/XDR-TB, predominantly associated with the Lisboa3 and Q1 clades. These clades are now thought to be evolving in a polycentric mode across multiple geographical districts. The inferred evolutionary history is compatible with MDR-and XDR-TB originating in Portugal in the 70's and 80's, respectively, but with subsequent multiple emergence events of MDR and XDR-TB particularly involving the Lisboa3 clade. A SNP barcode was defined for Lisboa3 and Q1 and comparison with a phylogeny of global strain-types (n = 28 385) revealed the presence of Lisboa3 and Q1 strains in Europe, South America and Africa. In summary, Portugal displays an unusual and unique epidemiological setting shaped by >40 years of uncontrolled circulation of two main phylogenetic clades, leading to a sympatric evolutionary trajectory towards XDR-TB with the potential for global reach. Multidrug-resistant (MDR) tuberculosis (TB) poses a serious threat to the WHO goal of eliminating TB by 2035 1. In Europe alone, the number of MDR-TB notified cases amounted to 35 224 cases in 2017 2. MDR-TB treatment involves using second-line drugs which are more expensive, have longer treatment regimens and currently have lower success rates 1. Extensively Drug Resistant (XDR) TB, which is MDR-TB with concomitant resistance to a fluoroquinolone and an injectable second-line drug, is associated with a much worse outcome 1. Portugal recently became a low TB incidence country by reporting a notification rate below 20 cases per 100 000 habitants (17.5/100 000 in 2017) 2. Nonetheless, it still reports the highest incidence rate in Western Europe and while this rate shows a steady decline averaged at −7.9% per year, treatment success rates are decreasing. Additionally, according to the most recent data from the WHO, it is estimated that Portugal had 24 new incident cases per 100 000 habitants in 2018 1. Ten MDR-TB cases were reported in 2017, but this is thought to be an underestimate, as only 61.4% of all TB cases are laboratory-confirmed, and only 66.7% of those underwent drug

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Magnetic fields in red giant stars remain a poorly understood topic, particularly in what concerns their intensity in regions far below the surface. In this work, we propose that gravity-dominated mixed modes of high absolute radial order and low angular degree can be used to probe the magnetic field in their radiative cores. Using two poloidal, axisymmetric configurations for the field in the core and the classical perturbative approach, we derive an analytical expression for the magnetic frequency splitting of these oscillation modes. Considering three distinct red giant models, with masses of 1.3, 1.6, and 2.0 M⊙, we find that a field strength of 105 G is necessary in the core of these stars to induce a frequency splitting of the order of a μHz in dipole and quadrupole oscillation modes. Moreover, taking into account observational limits, we estimate that magnetic fields in the cores of red giants that do not present observable magnetic splittings cannot exceed 104 G. Given the general absence of observable splittings in the oscillation spectra of these stars, and assuming that present mode suppression mechanisms are not biased towards certain azimuthal orders and retain all peaks in each multiplet, our results lead us to conclude that internal fields with the considered configurations and strengths above 104 G are not prevalent in red giants.

ResumoEste artigo propõe-se refletir sobre a relação entre o processo de 'desportivização' do automobilismo e as motivações que a elite local projetava sobre a modalidade, averiguando de que forma se coadunavam com a ideia da unidade do império. Procura-se explicar como os critérios sociais de entrada neste desporto foram evoluindo e como isso era revelador de rivalidades e dinâmicas económicas mais amplas que moviam os investidores a apostarem na modalidade para promover as suas marcas. A construção do Autódromo de Luanda e a internacionalização das '6 horas de Nova Lisboa' ajudaram a popularizar a modalidade incentivando vínculos identitários locais que ora se articularam com os interesses do governo ora com interesses autonomistas de uma elite local. Palavras-chavesautomobilismo -autódromo de Luanda -Angola colonial -sportsman -pilotos Colonialisme, classe et nation dans l'histoire du sport automobile angolais (1957-1975) Résumé Cet article veut réfléchir sur le processus de 'sportivisation' du sport automobile et sur les motivations que l'élite locale projetait sur ce sport, pour savoir en quoi elles s'intégraient dans l'idée d'unité de l'empire. Il cherche à expliquer comment les critères 13 Colonialismo, classe e nação Lusotopie 18 (2019) 12-39 sociaux d'entrée dans ce sport ont évolué et en quoi cela révélait des rivalités et une dynamique économique plus larges qui poussaient les investisseurs à parier sur le sport pour promouvoir leurs marques. La construction du Circuit de Luanda et l'internationalisation des '6 Heures de Nova Lisboa (Huambo)' ont contribué à populariser la modalité en stimulant les liens identitaires locaux qui étaient articulés avec les intérêts du gouvernement ou avec les intérêts autonomes d'une élite locale. AbstractThis article proposes to reflect upon the relation between the 'sportisation' process of motorsport and the motivations that the local elite projected on this practice, ascertaining how they were in line with the idea of the empire's unity. It seeks to explain how the social criteria to enter into this sport had evolved and how this was revealing of wider rivalries and economic dynamics that moved investors to wager on motorsport to promote their brands. Luanda's Race Track construction and the internationalization of the '6 Hours of Nova Lisboa (Huambo)' helped to popularize this modality by instigating local identity bonds which could be articulated with the interests of the government or with the autonomous interests of local elites.