Mouse transcriptome reveals potential signatures of protection and pathogenesis in human tuberculosis

Although mouse infection models have been extensively used to study the host response to Mycobacterium tuberculosis, their validity in revealing determinants of human tuberculosis (TB) resistance and disease progression has been heavily debated. Here, we show that the modular transcriptional signature in the blood of susceptible mice infected with a clinical isolate of M. tuberculosis resembles that of active human TB disease, with dominance of a type I interferon response and neutrophil activation and recruitment, together with a loss in B lymphocyte, natural killer and T cell effector responses. In addition, resistant but not susceptible strains of mice show increased lung B cell, natural killer and T cell effector responses in the lung upon infection. Notably, the blood signature of active disease shared by mice and humans is also evident in latent TB progressors before diagnosis, suggesting that these responses both predict and contribute to the pathogenesis of progressive M. tuberculosis infection

Structural and temporal patterns of the first global trading market

Little is known about the structural patterns and dynamics of the first global trading market (FGTM), which emerged during the sixteenth century as a result of the Iberian expansion, let alone how it compares to today's global financial markets. Here we build a representative network of the FGTM using information contained in 8725 (handwritten) Bills of Exchange from that time-which were (human) interpreted and digitalized into an online database. We show that the resulting temporal network exhibits a hierarchical, highly clustered and disassortative structure, with a power-law dependence on the connectivity that remains remarkably robust throughout the entire period investigated. Temporal analysis shows that, despite major turnovers in the number and nature of the links-suggesting fast adaptation in response to the geopolitical and financial turmoil experienced at the time-the overall characteristics of the FGTM remain robust and virtually unchanged. The methodology developed here demonstrates the possibility of building and analysing complex trading and finance networks originating from pre-statistical eras, enabling us to highlight the striking similarities between the structural patterns of financial networks separated by centuries in time.This research was supported by FCT-Portugal through grant nos FCT-TECH/0002/2007 (A.S.R. and A.P.), SFRH/BD/77389/2011 (F.L.P.), SFRH/BPD/76278/2011 (A.S.R.), PTDC/MAT-STA/3358/2014 (F.L.P., F.C.S. and J.M.P.), PTDC/EEI-SII/5081/2014 (F.L.P., F.C.S. and J.M.P.), UID/BIA/04050/2013 (J.M.P.) and UID/CEC/50021/2013 (F.C.S.), and by the European Science Foundation through grant no. DynCoopNet-06-TECT-FP-004 (A.S.R. and A.P.)

Capacidade combinatória de híbridos de tomateiro de crescimento determinado, resistentes a Begomovirus e Tospovirus

O objetivo deste trabalho foi avaliar a capacidade combinatória de linhagens de tomateiro com hábito de crescimento determinado, com resistência múltipla a espécies dos gêneros Begomovirus e Tospovirus, e identificar combinações híbridas superiores. O experimento foi realizado em casa de vegetação, com 14 híbridos obtidos do cruzamento de sete linhagens femininas (grupo I) com duas linhagens masculinas (grupo II), em um dialelo parcial. As seguintes características agronômicas foram avaliadas: produção total, produção precoce, massa média de frutos, formato, firmeza inicial e firmeza na meia-vida. As linhagens genitoras TOM-680 e TOM-682, do grupo I, se destacaram por exibir as maiores estimativas de capacidade geral de combinação (CGC) quanto às características produção total, produção precoce e massa média de frutos, enquanto a linhagem TOM-585 se destacou quanto aos maiores valores de produção total e massa média de frutos. No grupo II, a linhagem TOM-698 apresentou estimativas superiores de CGC para as características de produção total, produção precoce, massa média dos frutos e firmeza inicial dos frutos. O híbrido TOM-682xTOM-698 apresenta as maiores estimativas de capacidade geral e específica de combinação para produção total, produção precoce e meia-vida da firmeza, e é o genótipo mais promissor entre os materiais testados

From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways

The human body hosts an enormous abundance and diversity of microbes, which perform a range of essential and beneficial functions. Our appreciation of the importance of these microbial communities to many aspects of human physiology has grown dramatically in recent years. We know, for example, that animals raised in a germ-free environment exhibit substantially altered immune and metabolic function, while the disruption of commensal microbiota in humans is associated with the development of a growing number of diseases. Evidence is now emerging that, through interactions with the gut-brain axis, the bidirectional communication system between the central nervous system and the gastrointestinal tract, the gut microbiome can also influence neural development, cognition and behaviour, with recent evidence that changes in behaviour alter gut microbiota composition, while modifications of the microbiome can induce depressive-like behaviours. Although an association between enteropathy and certain psychiatric conditions has long been recognized, it now appears that gut microbes represent direct mediators of psychopathology. Here, we examine roles of gut microbiome in shaping brain development and neurological function, and the mechanisms by which it can contribute to mental illness. Further, we discuss how the insight provided by this new and exciting field of research can inform care and provide a basis for the design of novel, microbiota-targeted, therapies.GB Rogers, DJ Keating, RL Young, M-L Wong, J Licinio, and S Wesseling

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

The Accuracy of the Papanicolaou Smear in the Screening and Diagnostic Settings

Objective. We evaluated the performance of the Papanicolaou smear in screening and diagnostic settings. Study Design. We analyzed Papanicolaou smear results of 1,850 women recruited into a clinical trial to evaluate an emerging technology for the detection of cervical cancer. Screening and diagnosis groups were based on the history of previous Papanicolaou smear results. We calculated sensitivities, specificities, positive and negative likelihood ratios (LR+ and LRj), receiver operating characteristic curves, and areas under the receiver operating characteristic curve (AUC). Results. In the screening group, by defining disease as cervical intraepithelial neoplasia (CIN) 2,3/cancer or worse and using high-grade squamous intraepithelial lesion (HSIL) as the test cutpoint, the AUC was 0.689, and the LR+ and LRj were 39.25 and 0.67, respectively. In the diagnosis group, the AUC was 0.764, and the LR+ and LRj were 3.79 and 0.56, respectively. By defining disease as human papillomavirus/CIN 1 or worse and HSIL as the test cutpoint, the AUC was 0.586, and the LR+ and LRj were 17.01 and 0.92 in the screening group; in the diagnosis group, the AUC was 0.686, and the LR+ and LRj were 2.77 and 0.75, respectively. Conclusions. In a screening setting, a Papanicolaou smear result of HSIL or worse is 39 times more likely in a patient with CIN 2,3/cancer than in a patient without it. This compares to 4 times more likely in the diagnostic setting. The magnitude of the positive likelihood ratio observed in the screening group indicated that abnormal Papanicolaou smear results obtained in the screening setting should have more impact on clinical decision making than those from results obtained in the diagnostic setting.