SciCombinator

Discover the most talked about and latest scientific content & concepts.

Journal: Wellcome open research

3

Background: Relative blood flow in the two middle cerebral arteries can be measured using functional transcranial Doppler sonography (fTCD) to give an index of lateralisation as participants perform a specific task. Language laterality has mostly been studied with fTCD using a word generation task, but it is not clear whether this is optimal. Methods: Using fTCD, we evaluated a sentence generation task that has shown good reliability and strong left lateralisation in fMRI. We interleaved trials of word generation, sentence generation and list generation and assessed agreement of these tasks in 31 participants (29 right-handers). Results: Although word generation and sentence generation both gave robust left-lateralisation, Bland-Altman analysis showed that these two methods were not equivalent. The comparison list generation task was not systematically lateralised, but nevertheless laterality indices (LIs) from this task were significantly correlated with the other two tasks. Subtracting list generation LI from sentence generation LI did not affect the strength of the laterality index. Conclusions: This was a pre-registered methodological study designed to explore novel approaches to optimising measurement of language lateralisation using fTCD. It confirmed that sentence generation gives robust left lateralisation in most people, but is not equivalent to the classic word generation task. Although list generation does not show left-lateralisation at the group level, the LI on this task was correlated with left-lateralised tasks. This suggests that word and sentence generation involve adding a constant directional bias to an underlying continuum of laterality that is reliable in individuals but not biased in either direction. In future research we suggest that consistency of laterality across tasks might have more functional significance than strength or direction of laterality on any one task.

0

Background: Mosquito-borne flaviviruses, such as dengue and Japanese encephalitis virus (JEV), cause life-threatening diseases, particularly in the tropics. Methods: Here we performed unbiased metagenomic sequencing of RNA extracted from the serum of four patients and the plasma of one patient, all hospitalized at a tertiary care centre in South India with severe or prolonged febrile illness, together with the serum from one healthy control, in 2014. Results: We identified and assembled a complete dengue virus type 3 sequence from a case of severe dengue fever. We also identified a small number of JEV sequences in the serum of two adults with febrile illness, including one with severe dengue. Phylogenetic analysis revealed that the dengue sequence belonged to genotype III. It has an estimated divergence time of 13.86 years from the most highly related Indian strains. In total, 11 amino acid substitutions were predicted for this strain in the antigenic envelope protein, when compared to the parent strain used for development of the first commercial dengue vaccine.  Conclusions: We demonstrate that both genome assembly and detection of a low number of viral sequences are possible through the unbiased sequencing of clinical material. These methods may help ascertain causal agents for febrile illnesses with no known cause.

0

Background: The arbovirus vector, Aedes albopictus, originating from Asia, has recently invaded African countries, including the Republic of the Congo, where it was associated with a chikungunya outbreak. Up until now, little was known about its distribution in relation to the native Aedes aegypti and how the invasion will modify the epidemiology of arboviral diseases. Here, we assessed the current distribution of Ae. albopictus and Ae. aegypti in the Republic of the Congo and explored the genetic diversity of the invading species, Ae. albopictus. Methods: Immature stages of Aedes were collected in nine locations in the Republic of the Congo in 2017 following a north-south transect and reared to adult stage. Adults were morphologically identified, counted and grouped according to species and location. Genetic diversity of Ae. albopictus was assessed by analyzing the cytochrome oxidase I ( COI) gene. Results:Ae.albopictus and Ae. aegypti were found together across the country in all the locations investigated. The invasive species is predominant over the native species in all locations except Brazzaville, suggesting that Ae. albopictus is displacing Ae. aegypti across Congo. When comparing the species distributions across the two largest cities, Brazzaville and Pointe Noire, Ae. albopictus was more prevalent than Ae. aegypti in the suburbs whereas the opposite situation was reported in the city centre. Mitochondrial DNA analysis revealed very low genetic diversity of Ae. albopictus with only three haplotypes recorded across the country supporting the recent introduction of this species in the Republic of the Congo. Phylogenetic tree analysis revealed that Ae. albopictus from Congo originated from other tropical Asian countries such as China, likely as a result of increasing trade links. Conclusion: These findings are important for the implementation of vector control strategies and can serve as a foundation for further research on these vectors in the country.

0

Background: Human visceral leishmaniasis, caused by infection with Leishmania donovani or L. infantum, is a potentially fatal disease affecting 50,000-90,000 people yearly in 75 disease endemic countries, with more than 20,000 deaths reported. Experimental models of infection play a major role in understanding parasite biology, host-pathogen interaction, disease pathogenesis, and parasite transmission. In addition, they have an essential role in the identification and pre-clinical evaluation of new drugs and vaccines. However, our understanding of these models remains fragmentary. Although the immune response to Leishmania donovani infection in mice has been extensively characterized, transcriptomic analysis capturing the tissue-specific evolution of disease has yet to be reported. Methods: We provide an analysis of the transcriptome of spleen, liver and peripheral blood of BALB/c mice infected with L. donovani. Where possible, we compare our data in murine experimental visceral leishmaniasis with transcriptomic data in the public domain obtained from the study of L. donovani-infected hamsters and patients with human visceral leishmaniasis. Digitised whole slide images showing the histopathology in spleen and liver are made available via a dedicated website, www.leishpathnet.org. Results: Our analysis confirms marked tissue-specific alterations in the transcriptome of infected mice over time and identifies previously unrecognized parallels and differences between murine, hamster and human responses to infection. We show commonality of interferon-regulated genes whilst confirming a greater activation of type 2 immune pathways in infected hamsters compared to mice. Cytokine genes and genes encoding immune checkpoints were markedly tissue specific and dynamic in their expression, and pathways focused on non-immune cells reflected tissue specific immunopathology. Our data also addresses the value of measuring peripheral blood transcriptomics as a potential window into underlying systemic disease.  Conclusions: Our transcriptomic data, coupled with histopathologic analysis of the tissue response, provide an additional resource to underpin future mechanistic studies and to guide clinical research.

0

Background: Malaria parasite species differ greatly in the harm they do to humans. While P. falciparum kills hundreds of thousands per year, P. vivax kills much less often and P. malariae is relatively benign. Strains of the rodent malaria parasite Plasmodium chabaudi show phenotypic variation in virulence during infections of laboratory mice. This make it an excellent species to study genes which may be responsible for this trait. By understanding the mechanisms which underlie differences in virulence we can learn how parasites adapt to their hosts and how we might prevent disease. Methods: Here we present a complete reference genome sequence for a more virulent P. chabaudi strain, PcCB, and perform a detailed comparison with the genome of the less virulent PcAS strain. Results: We found the greatest variation in the subtelomeric regions, in particular amongst the sequences of the pir gene family, which has been associated with virulence and establishment of chronic infection. Despite substantial variation at the sequence level, the repertoire of these genes has been largely maintained, highlighting the requirement for functional conservation as well as diversification in host-parasite interactions. However, a subset of pir genes, previously associated with increased virulence, were more highly expressed in PcCB, suggesting a role for this gene family in virulence differences between strains. We found that core genes involved in red blood cell invasion have been under positive selection and that the more virulent strain has a greater preference for reticulocytes, which has elsewhere been associated with increased virulence. Conclusions: These results provide the basis for a mechanistic understanding of the phenotypic differences between Plasmodium chabaudi strains, which might ultimately be translated into a better understanding of malaria parasites affecting humans.

0

Cryptococcal meningitis is a leading cause of morbidity and mortality among HIV-infected persons, accounting for 15% of AIDS-related deaths. Visual disturbance is commonly reported, and a wide range of ophthalmic signs may be present on examination. There is limited published literature to date describing the range and incidence of ophthalmic signs in HIV-associated cryptococcal meningitis. Nested within the Adjunctive Sertraline for the Treatment of HIV-Associated Cryptococcal Meningitis (ASTRO-CM) trial (ClinicalTrials.gov number: NCT01802385), we conducted an observational study of 696 Ugandan adults with HIV-associated cryptococcal meningitis. Patients were screened for visual disturbance and external ophthalmic signs at initial presentation and at follow-up appointments over 18 weeks. Assessment comprised simple clinical history and basic examination and required no specialist equipment. More than a quarter of our cohort demonstrated ocular signs or symptoms, which were observed throughout the study period.  A broad range of ocular signs were demonstrated: these included neurological signs (10.9%), localized ocular pathology (4.5%), and evidence of concurrent systemic disease (12.9%). The range of signs observed demonstrates the complexities of case management in patients with advanced HIV and cryptococcosis and also the importance of basic ocular examination in low resource settings. There remains an urgent need for studies conducting comprehensive ocular examination in patients with HIV-associated cryptococcal meningitis; these studies should include formal assessment of visual acuity, slit lamp examination and dilated indirect ophthalmoscopy. Prospective studies should investigate whether there is a correlation between reported visual disturbance and objective signs, in order to further clarify the underlying mechanisms and to guide effective diagnosis, follow-up and management.