Population genetics of trypanosoma brucei rhodesiense: clonality and diversity within and between foci

African trypanosomes are unusual among pathogenic protozoa in that they can undergo their complete morphological life cycle in the tsetse fly vector with mating as a non-obligatory part of this development. Trypanosoma brucei rhodesiense, which infects humans and livestock in East and Southern Africa, has classically been described as a host-range variant of the non-human infective Trypanosoma brucei that occurs as stable clonal lineages. We have examined T. b. rhodesiense populations from East (Uganda) and Southern (Malawi) Africa using a panel of microsatellite markers, incorporating both spatial and temporal analyses. Our data demonstrate that Ugandan T. b. rhodesiense existed as clonal populations, with a small number of highly related genotypes and substantial linkage disequilibrium between pairs of loci. However, these populations were not stable as the dominant genotypes changed and the genetic diversity also reduced over time. Thus these populations do not conform to one of the criteria for strict clonality, namely stability of predominant genotypes over time, and our results show that, in a period in the mid 1990s, the previously predominant genotypes were not detected but were replaced by a novel clonal population with limited genetic relationship to the original population present between 1970 and 1990. In contrast, the Malawi T. b. rhodesiense population demonstrated significantly greater diversity and evidence for frequent genetic exchange. Therefore, the population genetics of T. b. rhodesiense is more complex than previously described. This has important implications for the spread of the single copy T. b. rhodesiense gene that allows human infectivity, and therefore the epidemiology of the human disease, as well as suggesting that these parasites represent an important organism to study the influence of optional recombination upon population genetic dynamics

Discovery of mating in the major African livestock pathogen Trypanosoma congolense

The protozoan parasite, Trypanosoma congolense, is one of the most economically important pathogens of livestock in Africa and, through its impact on cattle health and productivity, has a significant effect on human health and well being. Despite the importance of this parasite our knowledge of some of the fundamental biological processes is limited. For example, it is unknown whether mating takes place. In this paper we have taken a population genetics based approach to address this question. The availability of genome sequence of the parasite allowed us to identify polymorphic microsatellite markers, which were used to genotype T. congolense isolates from livestock in a discrete geographical area of The Gambia. The data showed a high level of diversity with a large number of distinct genotypes, but a deficit in heterozygotes. Further analysis identified cryptic genetic subdivision into four sub-populations. In one of these, parasite genotypic diversity could only be explained by the occurrence of frequent mating in T. congolense. These data are completely inconsistent with previous suggestions that the parasite expands asexually in the absence of mating. The discovery of mating in this species of trypanosome has significant consequences for the spread of critical traits, such as drug resistance, as well as for fundamental aspects of the biology and epidemiology of this neglected but economically important pathogen

Aggressive vs. conservative phototherapy for infants with extremely low birth weight.

BACKGROUND: It is unclear whether aggressive phototherapy to prevent neurotoxic effects of bilirubin benefits or harms infants with extremely low birth weight (1000 g or less). METHODS: We randomly assigned 1974 infants with extremely low birth weight at 12 to 36 hours of age to undergo either aggressive or conservative phototherapy. The primary outcome was a composite of death or neurodevelopmental impairment determined for 91% of the infants by investigators who were unaware of the treatment assignments. RESULTS: Aggressive phototherapy, as compared with conservative phototherapy, significantly reduced the mean peak serum bilirubin level (7.0 vs. 9.8 mg per deciliter [120 vs. 168 micromol per liter], P\u3c0.01) but not the rate of the primary outcome (52% vs. 55%; relative risk, 0.94; 95% confidence interval [CI], 0.87 to 1.02; P=0.15). Aggressive phototherapy did reduce rates of neurodevelopmental impairment (26%, vs. 30% for conservative phototherapy; relative risk, 0.86; 95% CI, 0.74 to 0.99). Rates of death in the aggressive-phototherapy and conservative-phototherapy groups were 24% and 23%, respectively (relative risk, 1.05; 95% CI, 0.90 to 1.22). In preplanned subgroup analyses, the rates of death were 13% with aggressive phototherapy and 14% with conservative phototherapy for infants with a birth weight of 751 to 1000 g and 39% and 34%, respectively (relative risk, 1.13; 95% CI, 0.96 to 1.34), for infants with a birth weight of 501 to 750 g. CONCLUSIONS: Aggressive phototherapy did not significantly reduce the rate of death or neurodevelopmental impairment. The rate of neurodevelopmental impairment alone was significantly reduced with aggressive phototherapy. This reduction may be offset by an increase in mortality among infants weighing 501 to 750 g at birth. (ClinicalTrials.gov number, NCT00114543.

Pressure Behavior of the Zero Thermal Expansion Material Sc<inf>1.5</inf>Al<inf>0.5</inf>W<inf>3</inf>O<inf>12</inf>

Zero thermal expansion materials have a unique ability to withstand thermal shock over varied temperature ranges, enabling potential applications as components of high precision devices. The zero thermal expansion material Sc1.5Al0.5W3O12 exhibits zero thermal expansion over the largest temperature range reported to date, from 4 to 1400 K (Liu et al. Chem. Mater. 2021, 33, 3823). In this work, the pressure stability of this material is investigated using high-pressure neutron and X-ray powder diffraction as well as Raman spectroscopy and supported with density functional theory (DFT) calculations. Sc1.5Al0.5W3O12 shows an orthorhombic to monoclinic transition with the application of a small amount of pressure which is similar to that reported for other compositions in this family. Additional peak splitting is noted above 3.4 GPa which may indicate an additional phase transition. A pressure induced amorphization is found between 4.3 and 5.7 GPa and an amorphous to amorphous phase transition is further evidenced at around 15 GPa. The tungsten coordination sphere evolves from WO4 to WO6 as pressure is increased, which is evidenced by both DFT calculations and Raman spectroscopy. The <3.4 GPa monoclinic phase has a bulk modulus, B0, of 17.4(14) GPa determined with X-ray powder diffraction by second order Birch-Murnaghan. This work demonstrates the importance of understanding structural changes under pressure for zero thermal expansion materials, as changes in pressure impart a more significant impact on the crystallographic volume compared to temperature

The Achievement of a Decentralized Water Management Through Stakeholder Participation: An Example from the Drôme River Catchment Area in France (1981–2008)

International audienceDifferent water Acts (e.g., the European Water Framework Directive) and stakeholders involved in aquatic affairs have promoted integrated river basin management (IRBM) over recent decades. However, few studies have provided feedback on these policies. The aim of the current article is to fill this gap by exploring how local newspapers reflect the implementation of a broad public participation within a catchment of France known for its innovation with regard to this domain. The media coverage of a water management strategy in the Drôme watershed from 1981 to 2008 was investigated using a content analysis and a geographic information system (GIS). We sought to determine what public participation and decentralized decision-making can be in practice. The results showed that this policy was integrated because of its social perspective, the high number of involved stakeholders, the willingness to handle water issues, and the local scale suitable for participation. We emphasized the prominence of the watershed scale guaranteed by the local water authority. This area was also characterized by compromise, arrangements, and power dynamics on a fine scale. We examined the most politically engaged writings regarding water management, which topics each group emphasized, and how the groups agreed and disagreed on issues based on their values and context. The temporal pattern of participation implementation was progressive but worked by fits and starts

Oxidative stress-driven parvalbumin interneuron impairment as a common mechanism in models of schizophrenia.

Parvalbumin inhibitory interneurons (PVIs) are crucial for maintaining proper excitatory/inhibitory balance and high-frequency neuronal synchronization. Their activity supports critical developmental trajectories, sensory and cognitive processing, and social behavior. Despite heterogeneity in the etiology across schizophrenia and autism spectrum disorder, PVI circuits are altered in these psychiatric disorders. Identifying mechanism(s) underlying PVI deficits is essential to establish treatments targeting in particular cognition. On the basis of published and new data, we propose oxidative stress as a common pathological mechanism leading to PVI impairment in schizophrenia and some forms of autism. A series of animal models carrying genetic and/or environmental risks relevant to diverse etiological aspects of these disorders show PVI deficits to be all accompanied by oxidative stress in the anterior cingulate cortex. Specifically, oxidative stress is negatively correlated with the integrity of PVIs and the extracellular perineuronal net enwrapping these interneurons. Oxidative stress may result from dysregulation of systems typically affected in schizophrenia, including glutamatergic, dopaminergic, immune and antioxidant signaling. As convergent end point, redox dysregulation has successfully been targeted to protect PVIs with antioxidants/redox regulators across several animal models. This opens up new perspectives for the use of antioxidant treatments to be applied to at-risk individuals, in close temporal proximity to environmental impacts known to induce oxidative stress

Climate-sensitive health priorities in Nunatsiavut, Canada

Background: This exploratory study used participatory methods to identify, characterize, and rank climate-sensitive health priorities in Nunatsiavut, Labrador, Canada. Methods: A mixed method study design was used and involved collecting both qualitative and quantitative data at regional, community, and individual levels. In-depth interviews with regional health representatives were conducted throughout Nunatsiavut (n = 11). In addition, three PhotoVoice workshops were held with Rigolet community members (n = 11), where participants took photos of areas, items, or concepts that expressed how climate change is impacting their health. The workshop groups shared their photographs, discussed the stories and messages behind them, and then grouped photos into re-occurring themes. Two community surveys were administered in Rigolet to capture data on observed climatic and environmental changes in the area, and perceived impacts on health, wellbeing, and lifestyles (n = 187). Results: Climate-sensitive health pathways were described in terms of inter-relationships between environmental and social determinants of Inuit health. The climate-sensitive health priorities for the region included food security, water security, mental health and wellbeing, new hazards and safety concerns, and health services and delivery. Conclusions: The results highlight several climate-sensitive health priorities that are specific to the Nunatsiavut region, and suggest approaching health research and adaptation planning from an EcoHealth perspective

South Asian individuals' experiences on the NHS low-calorie diet programme: a qualitative study in community settings in England.

BACKGROUND: Existing literature examines barriers to the provision of ethnically diverse dietary advice, however, is not specific to total diet replacement (TDR). There is a lack of literature from the UK, limiting the potential applicability of existing findings and themes to the UK context. This study addresses this gap in research by interviewing participants of South Asian ethnicity who have undertaken the National Health Service (NHS) low-calorie diet programme (LCD) for people with type 2 diabetes living with overweight or obesity. This study explores factors that may affect the uptake and acceptability of its TDR, food reintroduction and weight maintenance stages. This aims to provide rich data that can inform effective tailoring of future programmes with South Asian participants. OBJECTIVE: To explore the perspectives of individuals of South Asian ethnicity on an NHS programme using TDR approaches for the management of type 2 diabetes (T2D). DESIGN: Qualitative study. SETTING: Individuals in the community undertaking the NHS LCD programme. PARTICIPANTS: Twelve one-to-one interviews were conducted with individuals from a South Asian ethnicity participating in the NHS LCD. MAIN OUTCOME MEASURES: Qualitative semistructured interviews conducted through different stages of the programme. Reflexive thematic analysis was used to analyse the transcripts. RESULTS: Key themes highlighted positive and negative experiences of the programme: (1) more work is needed in the programme for person centeredness; (2) it is not the same taste; (3) needing motivation to make changes and feel better; (4) a mixed relationship with the coach; (5) social experiences; (6) culture-related experiences. CONCLUSION: This study provides important experience-based evidence of the need for culturally tailored T2D programmes. Action to address these findings and improve the tailoring of the NHS LCD may improve experience, retention and outcomes on the programme for people of South Asian ethnicity and thereby reduce inequalities

A barrier to homologous recombination between sympatric strains of the cooperative soil bacterium Myxococcus xanthus

The bacterium Myxococcus xanthus glides through soil in search of prey microbes, but when food sources run out, cells cooperatively construct and sporulate within multicellular fruiting bodies. M. xanthus strains isolated from a 16 × 16-cm-scale patch of soil were previously shown to have diversified into many distinct compatibility types that are distinguished by the failure of swarming colonies to merge upon encounter. We sequenced the genomes of 22 isolates from this population belonging to the two most frequently occurring multilocus sequence type (MLST) clades to trace patterns of incipient genomic divergence, specifically related to social divergence. Although homologous recombination occurs frequently within the two MLST clades, we find an almost complete absence of recombination events between them. As the two clades are very closely related and live in sympatry, either ecological or genetic barriers must reduce genetic exchange between them. We find that the rate of change in the accessory genome is greater than the rate of amino-acid substitution in the core genome. We identify a large genomic tract that consistently differs between isolates that do not freely merge and therefore is a candidate region for harbouring gene(s) responsible for self/non-self discrimination

Communication in bacteria: an ecological and evolutionary perspective

Individual bacteria can alter their behaviour through chemical interactions between organisms in microbial communities - this is generally referred to as quorum sensing. Frequently, these interactions are interpreted in terms of communication to mediate coordinated, multicellular behaviour. We show that the nature of interactions through quorum-sensing chemicals does not simply involve cooperative signals, but entails other interactions such as cues and chemical manipulations. These signals might have a role in conflicts within and between species. The nature of the chemical interaction is important to take into account when studying why and how bacteria react to the chemical substances that are produced by other bacteria