Explore the vast range of titles available.

Women’s underrepresentation in science, technology, engineering, and mathematics (STEM) impedes progress in solving Africa’s complex development problems. As in other regions, women’s participation in STEM drops progressively moving up the education and career ladder, with women currently constituting 30% of Africa’s STEM researchers. This study elucidates gender-based differences in PhD performance using new survey data from 227 alumni of STEM PhD programs in 17 African countries. We find that, compared to their male counterparts, sampled women had about one less paper accepted for publication during their doctoral studies and took about half a year longer to finish their PhD training. Negative binomial regression models provide insights on the observed differences in women’s and men’s PhD performance. Results indicate that the correlates of publication productivity and time to PhD completion are very similar for women and men, but some gender-based differences are observed. For publication output, we find that good supervision had a stronger impact for men than women; and getting married during the PhD reduced women’s publication productivity but increased that of men. Becoming a parent during the PhD training was a key reason that women took longer to complete the PhD, according to our results. Findings suggest that having a female supervisor, attending an institution with gender policies in place, and pursuing the PhD in a department where sexual harassment by faculty was perceived as uncommon were enabling factors for women’s timely completion of their doctoral studies. Two priority interventions emerge from this study: (1) family-friendly policies and facilities that are supportive of women’s roles as wives and mothers and (2) fostering broader linkages and networks for women in STEM, including ensuring mentoring and supervisory support that is tailored to their specific needs and circumstances.

Gender disparities in science, technology, engineering, and mathematics (STEM) remain pronounced in many African countries, particularly at the postgraduate level. This study explores the experiences of African women in STEM postgraduate education by integrating data from an online survey of 163 female PhD alumni from 40 African universities in 17 countries and seven focus group discussions (FGDs) with 39 current postgraduate students across three countries. Through a mixed-methods approach, we examine both the challenges women face and the factors that enable their persistence and success. Over 60% of respondents reported financial stress during their PhD, and more than half felt unprepared at the time of program entry. Yet 95% expressed confidence in their ability to succeed, reflecting strong self-efficacy despite structural barriers. In the FGDs, women highlighted the burden of caregiving responsibilities, lack of role models, and cultural norms that pressure them to prioritize family over academic careers. Contrary to common assumptions, most FGD participants preferred male supervisors, citing competitiveness or lack of support from some senior women. Despite these obstacles, participants demonstrated high levels of resilience, often driven by a passion for science and strong family support. Our findings highlight the need for family-friendly policies, structured and tailored mentoring, and flexible, gender-responsive institutional reforms to ensure more inclusive and equitable STEM postgraduate environments in Africa.

Metabolism underpins the pathogenic strategy of the causative agent of TB, Mycobacterium tuberculosis (Mtb), and therefore metabolic pathways have recently re-emerged as attractive drug targets. A powerful approach to study Mtb metabolism as a whole, rather than just individual enzymatic components, is to use a systems biology framework, such as a Genome-Scale Metabolic Network (GSMN) that allows the dynamic interactions of all the components of metabolism to be interrogated together. Several GSMNs networks have been constructed for Mtb and used to study the complex relationship between the Mtb genotype and its phenotype. However, the utility of this approach is hampered by the existence of multiple models, each with varying properties and performances. Here we systematically evaluate eight recently published metabolic models of Mtb-H37Rv to facilitate model choice. The best performing models, sMtb2018 and iEK1011, were refined and improved for use in future studies by the TB research community.

The Mycobacterium tuberculosis complex includes bovine and human strains of the tuberculosis bacillus, including Mycobacterium tuberculosis, Mycobacterium bovis and the Mycobacterium bovis BCG vaccine strain. M. bovis has evolved from a M. tuberculosis-like ancestor and is the ancestor of the BCG vaccine. The pathogens demonstrate distinct differences in virulence, host range and metabolism, but the role of metabolic differences in pathogenicity is poorly understood. Systems biology approaches have been used to investigate the metabolism of M. tuberculosis, but not to probe differences between tuberculosis strains. In this study genome scale metabolic networks of M. bovis and M. bovis BCG were constructed and interrogated, along with a M. tuberculosis network, to predict substrate utilisation, gene essentiality and growth rates. The models correctly predicted 87-88% of high-throughput phenotype data, 75-76% of gene essentiality data and in silico-predicted growth rates matched measured rates. However, analysis of the metabolic networks identified discrepancies between in silico predictions and in vitro data, highlighting areas of incomplete metabolic knowledge. Additional experimental studies carried out to probe these inconsistencies revealed novel insights into the metabolism of these strains. For instance, that the reduction in metabolic capability observed in bovine tuberculosis strains, as compared to M. tuberculosis, is not reflected by current genetic or enzymatic knowledge. Hence, the in silico networks not only successfully simulate many aspects of the growth and physiology of these mycobacteria, but also provide an invaluable tool for future metabolic studies.

In 2023, Mycobacterium tuberculosis (Mtb) caused 10.6 million new tuberculosis cases and 1.3 million deaths. The WHO proscribed treatment is not always successful, even when strains were sensitive to the antibiotics.as clinical Mtb populations contain phenotypically tolerant subpopulations, termed persisters . Here a Mtb transposon library was challenged with rifampicin (RIF) and streptomycin (STM) under conditions designed to identify genes that modulate persister frequency. Mutants with reduced survival in RIF were predominantly in genes associated with membrane integrity e.g . arabinogalactan assembly genes cpsA/lytR/Psr , whilst for STM, reduced survival was associated with toxin/antitoxin genes. Some mutations enhanced survival. For RIF these included the methyl citrate cycle genes prpC, prpD and prpR , and the trkA-C K + uptake system genes ceoB and Rv2690 , and for STM, the resistance associated gene, gidB , and anion-transport genes Rv3679c and Rv3680c . Few genes overlapped the RIF and STM selections, demonstrating that survival mechanisms were antibiotic-specific. Directed deletions of Δ prpD and Δ fadE5 confirmed their predicted enhanced and reduced RIF fitness respectively. The study identified genes that modulate not only persister frequency but also resistance and tolerance, and demonstrates that the mechanisms that produce these phenotypes are diverse and antibiotic-specific.

The co‐catabolism of multiple host‐derived carbon substrates is required by Mycobacterium tuberculosis (Mtb) to successfully sustain a tuberculosis infection. However, the metabolic plasticity of this pathogen and the complexity of the metabolic networks present a major obstacle in identifying those nodes most amenable to therapeutic interventions. It is therefore critical that we define the metabolic phenotypes of Mtb in different conditions. We applied metabolic flux analysis using stable isotopes and lipid fingerprinting to investigate the metabolic network of Mtb growing slowly in our steady‐state chemostat system. We demonstrate that Mtb efficiently co‐metabolises either cholesterol or glycerol, in combination with two‐carbon generating substrates without any compartmentalisation of metabolism. We discovered that partitioning of flux between the TCA cycle and the glyoxylate shunt combined with a reversible methyl citrate cycle is the critical metabolic nodes which underlie the nutritional flexibility of Mtb. These findings provide novel insights into the metabolic architecture that affords adaptability of bacteria to divergent carbon substrates and expand our fundamental knowledge about the methyl citrate cycle and the glyoxylate shunt. Synopsis Quantitative metabolic analysis using stable isotopes, lipid fingerprinting, and mathematical modelling are applied to investigate the metabolic network of Mycobacterium tuberculosis growing slowly in a steady state chemostat system. The tubercle bacillus efficiently co‐metabolises cholesterol or glycerol, in combination with two‐carbon generating substrates without compartmentalisation of metabolism. Metabolic flux profiles of M . tuberculosis growing slowly on the dual carbon sources are described using an expanded 13C isotopomer model. Partitioning of metabolite flux between the TCA cycle and the glyoxylate shunt combined with a reversible methyl citrate cycle are critical nodes underlying the metabolic flexibility of M. tuberculosis . Graphical Abstract Quantitative metabolic analysis using stable isotopes, lipid fingerprinting, and mathematical modelling are applied to investigate the metabolic network of Mycobacterium tuberculosis growing slowly in a steady state chemostat system.

Despite the introduction of conjugated polysaccharide vaccines for many of the Neisseria meningitidis serogroups, neisserial infections continue to cause septicaemia and meningitis across the world. This is in part due to the difficulties in developing a, cross-protective vaccine that is effective against all serogroups, including serogroup B meningococci. Although convalescent N. meningitidis patients develop a natural long-lasting cross-protective immunity, the antigens that mediate this response remain unknown. To help define the target of this protective immunity we identified the proteins recognized by IgG in sera from meningococcal patients by a combination of 2D protein gels, western blots and mass spectrometry. Although a number of outer membrane antigens were identified the majority of the antigens were cytoplasmic, with roles in cellular processes and metabolism. When recombinant proteins were expressed and used to raise sera in mice, none of the antigens elicited a positive SBA result, however flow cytometry did demonstrate that some, including the ribosomal protein, RplY were localised to the neisserial cell surface.

Leprosy was endemic in Europe until the Middle Ages. Using DNA array capture, we have obtained genome sequences of Mycobacterium leprae from skeletons of five medieval leprosy cases from the United Kingdom, Sweden, and Denmark. In one case, the DNA was so well preserved that full de novo assembly of the ancient bacterial genome could be achieved through shotgun sequencing alone. The ancient M. leprae sequences were compared with those of 11 modern strains, representing diverse genotypes and geographic origins. The comparisons revealed remarkable genomic conservation during the past 1000 years, a European origin for leprosy in the Americas, and the presence of an M. leprae genotype in medieval Europe now commonly associated with the Middle East. The exceptional preservation of M. leprae biomarkers, both DNA and mycolic acids, in ancient skeletons has major implications for palaeomicrobiology and human pathogen evolution.

Relatively little is known of leprosy in Medieval Ireland; as an island located at the far west of Europe it has the potential to provide interesting insights in relation to the historical epidemiology of the disease. To this end the study focuses on five cases of probable leprosy identified in human skeletal remains excavated from inhumation burials. Three of the individuals derived from the cemetery of St Michael Le Pole, Golden Lane, Dublin, while single examples were also identified from Ardreigh, Co. Kildare, and St Patrick's Church, Armoy, Co. Antrim. The individuals were radiocarbon dated and examined biomolecularly for evidence of either of the causative pathogens, M. leprae or M. lepromatosis. Oxygen and strontium isotopes were measured in tooth enamel and rib samples to determine where the individuals had spent their formative years and to ascertain if they had undertaken any recent migrations. We detected M. leprae DNA in the three Golden Lane cases but not in the probable cases from either Ardreigh Co. Kildare or Armoy, Co. Antrim. M. lepromatosis was not detected in any of the burals. DNA preservation was sufficiently robust to allow genotyping of M. leprae strains in two of the Golden Lane burials, SkCXCV (12-13th century) and SkCCXXX (11-13th century). These strains were found to belong on different lineages of the M. leprae phylogenetic tree, namely branches 3 and 2 respectively. Whole genome sequencing was also attempted on these two isolates with a view to gaining further information but poor genome coverage precluded phylogenetic analysis. Data from the biomolecular study was combined with osteological, isotopic and radiocarbon dating to provide a comprehensive and multidisciplinary study of the Irish cases. Strontium and oxygen isotopic analysis indicate that two of the individuals from Golden Lane (SkCXLVIII (10-11th century) and SkCXCV) were of Scandinavian origin, while SkCCXXX may have spent his childhood in the north of Ireland or central Britain. We propose that the Vikings were responsible for introducing leprosy to Ireland. This work adds to our knowledge of the likely origins of leprosy in Medieval Ireland and will hopefully stimulate further research into the history and spread of this ancient disease across the world.

Leprosy remains a major problem in the world today, particularly affecting the poorest and most disadvantaged sections of society in the least developed countries of the world. The long-term aim of research is to develop new treatments and vaccines, and these aims are currently hampered by our inability to grow the pathogen in axenic culture. In this study, we probed the metabolism of M. leprae while it is surviving and replicating inside its primary host cell, the Schwann cell, and compared it to a related pathogen, M. tuberculosis , replicating in macrophages. Our analysis revealed that unlike M. tuberculosis , M. leprae utilized host glucose as a carbon source and that it biosynthesized its own amino acids, rather than importing them from its host cell. We demonstrated that the enzyme phosphoenolpyruvate carboxylase plays a crucial role in glucose catabolism in M. leprae . Our findings provide the first metabolic signature of M. leprae in the host Schwann cell and identify novel avenues for the development of antileprosy drugs. New approaches are needed to control leprosy, but understanding of the biology of the causative agent Mycobacterium leprae remains rudimentary, principally because the pathogen cannot be grown in axenic culture. Here, we applied 13 C isotopomer analysis to measure carbon metabolism of M. leprae in its primary host cell, the Schwann cell. We compared the results of this analysis with those of a related pathogen, Mycobacterium tuberculosis , growing in its primary host cell, the macrophage. Using 13 C isotopomer analysis with glucose as the tracer, we show that whereas M. tuberculosis imports most of its amino acids directly from the host macrophage, M. leprae utilizes host glucose pools as the carbon source to biosynthesize the majority of its amino acids. Our analysis highlights the anaplerotic enzyme phosphoenolpyruvate carboxylase required for this intracellular diet of M. leprae , identifying this enzyme as a potential antileprosy drug target. IMPORTANCE Leprosy remains a major problem in the world today, particularly affecting the poorest and most disadvantaged sections of society in the least developed countries of the world. The long-term aim of research is to develop new treatments and vaccines, and these aims are currently hampered by our inability to grow the pathogen in axenic culture. In this study, we probed the metabolism of M. leprae while it is surviving and replicating inside its primary host cell, the Schwann cell, and compared it to a related pathogen, M. tuberculosis , replicating in macrophages. Our analysis revealed that unlike M. tuberculosis , M. leprae utilized host glucose as a carbon source and that it biosynthesized its own amino acids, rather than importing them from its host cell. We demonstrated that the enzyme phosphoenolpyruvate carboxylase plays a crucial role in glucose catabolism in M. leprae . Our findings provide the first metabolic signature of M. leprae in the host Schwann cell and identify novel avenues for the development of antileprosy drugs.