Smart phone, smart science: how the use of smartphones can revolutionize research in cognitive science

Investigating human cognitive faculties such as language, attention, and memory most often relies on testing small and homogeneous groups of volunteers coming to research facilities where they are asked to participate in behavioral experiments. We show that this limitation and sampling bias can be overcome by using smartphone technology to collect data in cognitive science experiments from thousands of subjects from all over the world. This mass coordinated use of smartphones creates a novel and powerful scientific "instrument" that yields the data necessary to test universal theories of cognition. This increase in power represents a potential revolution in cognitive science

MEGALEX:A megastudy of visual and auditory word recognition

Using the megastudy approach, we report a new database (MEGALEX) of visual and auditory lexical decision times and accuracy rates for tens of thousands of words. We collected visual lexical decision data for 28,466 French words and the same number of pseudowords, and auditory lexical decision data for 17,876 French words and the same number of pseudowords (synthesized tokens were used for the auditory modality). This constitutes the first large-scale database for auditory lexical decision, and the first database to enable a direct comparison of word recognition in different modalities. Different regression analyses were conducted to illustrate potential ways to exploit this megastudy database. First, we compared the proportions of variance accounted for by five word frequency measures. Second, we conducted item-level regression analyses to examine the relative importance of the lexical variables influencing performance in the different modalities (visual and auditory). Finally, we compared the similarities and differences between the two modalities. All data are freely available on our website ( https://sedufau.shinyapps.io/megalex/ ) and are searchable at www.lexique.org , inside the Open Lexique search engine

The role of vitamin D metabolism in regulating bone turnover in adolescents with perinatally-acquired HIV in southern Africa:a cross-sectional study in Zimbabwe and Zambia

Vitamin D dysregulation can occur in people living with HIV, disrupting calcium homeostasis and bone turnover. We aimed to investigate the potential mechanisms by which vitamin D regulates bone turnover in adolescents living with perinatally-acquired HIV (ALWH) in southern Africa. A pre-planned secondary analysis was performed of baseline data from the VITALITY trial [PACTR20200989766029] which enrolled ALWH (11-19 years) taking antiretroviral therapy for ≥6 months, and recorded socio-demographic, clinical and dietary data. After over-night fasting, vitamin D metabolites [25(OH)D, 1,25(OH)2D, 24,25(OH)2D], intact parathyroid hormone (PTH) and bone turnover markers (BTMs) [CTX and P1NP] were measured. Tandem Mass Spectrometry measured vitamin D metabolites, whilst intact PTH and BTMs were analysed by electrochemiluminescence immunoassay. Stratified by 25(OH)D [<75 vs ≥75 nmol/L], associations between standardized concentrations (β = standard deviations) of vitamin D metabolites, intact PTH and BTMs were assessed using structural equations modelling (SEM) adjusted for age, sex and country (Zimbabwe/Zambia). Among the 842 ALWH enrolled, the median dietary calcium intake was 100 mg [IQR:55-145]. The SEM showed PTH was positively associated [β 0.21, 95%CI: 0.1,0.32] with 1,25(OH)2D, only when 25(OH)D was <75 nmol/L vs ≥75 nmol/L [β 0.23, 95%CI: -0.13,0.59], with evidence of an interaction [β -0.11, 95%CI: -0.20,-0.02]. A positive relationship between 25(OH)D and 24,25(OH)2D was seen irrespective of 25(OH)D concentration. 24,25(OH)2D was inversely related to BTMs, particularly when 25(OH)D was <75 nmol/L [CTX: β -0.15, 95%CI: -0.24,-0.06, and P1NP: β -0.14, 95%CI: -0.22,-0.06]. There was interaction between dietary calcium and 25(OH)D on PTH [β -0.15, 95% CI: -0.22,-0.07] suggesting an interaction between low 25(OH)D and low dietary calcium which increases PTH. In conclusion, associations between 25(OH)D, PTH, 1,25(OH)2D and BTMs in ALWH appear dependent upon 25(OH)D concentrations <75 nmol/L and calcium intake. A novel, potentially causal pathway between 25(OH)D, 24,25(OH)2D and BTMs was seen. Findings enhance understanding of vitamin D metabolism in people living with HIV

Patterns of volatile diversity yield insights into the genetics and biochemistry of the date palm fruit volatilome

Volatile organic compounds are key components of the fruit metabolome that contribute to traits such as aroma and taste. Here we report on the diversity of 90 flavor-related fruit traits in date palms (Phoenix dactylifera L.) including 80 volatile organic compounds, which collectively represent the fruit volatilome, as well as 6 organic acids, and 4 sugars in tree-ripened fruits. We characterize these traits in 148 date palms representing 135 varieties using headspace solid-phase microextraction gas chromatography. We discovered new volatile compounds unknown in date palm including 2-methoxy-4-vinylphenol, an attractant of the red palm weevil (Rhynchophorus ferrugineus Olivier), a key pest that threatens the date palm crop. Associations between volatile composition and sugar and moisture content suggest that differences among fruits in these traits may be characterized by system-wide differences in fruit metabolism. Correlations between volatiles indicate medium chain and long chain fatty acid ester volatiles are regulated independently, possibly reflecting differences in the biochemistry of fatty acid precursors. Finally, we took advantage of date palm clones in our analysis to estimate broad-sense heritabilities of volatiles and demonstrate that at least some of volatile diversity has a genetic basis

Multimorbidity research in Sub-Saharan Africa: Proceedings of an interdisciplinary workshop

As life expectancies rise globally, the number of people living with multiple chronic health conditions – commonly referred to as ‘multimorbidity’ – is rising. Multimorbidity has been recognised as especially challenging to respond to in countries whose health systems are under-funded, fragmented, and designed primarily for acute care, including in sub-Saharan Africa. A growing body of research in sub-Saharan Africa has sought to better understand the particular challenges multimorbidity poses in the region and to develop context-sensitive responses. However, with multimorbidity still crystallising as a subject of enquiry, there remains considerable heterogeneity in conceptualising multimorbidity across disciplines and fields, hindering coordinated action. In June 2022, 60 researchers, practitioners, and stakeholders with regional expertise from nine sub-Saharan African countries gathered in Blantyre, Malawi to discuss ongoing multimorbidity research across the region. Drawing on insights from disciplines including epidemiology, public health, clinical medicine, anthropology, history, and sociology, participants critically considered the meaning, singular potential, and limitations of the concept of multimorbidity in sub-Saharan Africa. The workshop emphasised the need to move beyond a disease-centred concept of multimorbidity to one foregrounding patients’ values, needs, and social context; the importance of foregrounding structures and systems rather than behaviour and lifestyles; the value of a flexible (rather than standard) definition of multimorbidity; and the need to leverage local knowledge, expertise, resources, and infrastructure. The workshop further served as a platform for exploring opportunities for training, writing, and ongoing collaboration

Cre-dependent DNA recombination activates a STING-dependent innate immune response

Gene-recombinase technologies, such as Cre/loxP-mediated DNA recombination, are important tools in the study of gene function, but have potential side effects due to damaging activity on DNA. Here we show that DNA recombination by Cre instigates a robust antiviral response in mammalian cells, independent of legitimate loxP recombination. This is due to the recruitment of the cytosolic DNA sensor STING, concurrent with Cre-dependent DNA damage and the accumulation of cytoplasmic DNA. Importantly, we establish a direct interplay between this antiviral response and cell-cell interactions, indicating that low cell densities in vitro could be useful to help mitigate these effects of Cre. Taking into account the wide range of interferon stimulated genes that may be induced by the STING pathway, these results have broad implications in fields such as immunology, cancer biology, metabolism and stem cell research. Further, this study sets a precedent in the field of gene-engineering, possibly applicable to other enzymatic-based genome editing technologies

Cre-dependent DNA recombination activates a STING-dependent innate immune response

Gene-recombinase technologies, such as Cre/loxP-mediated DNA recombination, are important tools in the study of gene function, but have potential side effects due to damaging activity on DNA. Here we show that DNA recombination by Cre instigates a robust antiviral response in mammalian cells, independent of legitimate loxP recombination. This is due to the recruitment of the cytosolic DNA sensor STING, concurrent with Cre-dependent DNA damage and the accumulation of cytoplasmic DNA. Importantly, we establish a direct interplay between this antiviral response and cell-cell interactions, indicating that low cell densities in vitro could be useful to help mitigate these effects of Cre. Taking into account the wide range of interferon stimulated genes that may be induced by the STING pathway, these results have broad implications in fields such as immunology, cancer biology, metabolism and stem cell research. Further, this study sets a precedent in the field of gene-engineering, possibly applicable to other enzymatic-based genome editing technologies

Sequence-dependent off-target inhibition of TLR7/8 sensing by synthetic microRNA inhibitors

Anti-microRNA (miRNA) oligonucleotides (AMOs) with 2\u27-O-Methyl (2\u27OMe) residues are commonly used to study miRNA function and can achieve high potency, with low cytotoxicity. Not withstanding this, we demonstrate the sequence-dependent capacity of 2\u27OMe AMOs to inhibit Toll-like receptor (TLR) 7 and 8 sensing of immunostimulatory RNA, independent of their miRNA-targeting function. Through a screen of 29 AMOs targeting common miRNAs, we found a subset of sequences highly inhibitory to TLR7 sensing in mouse macrophages. Interspecies conservation of this inhibitory activity was confirmed on TLR7/8 activity in human peripheral blood mononuclear cells. Significantly, we identified a core motif governing the inhibitory activity of these AMOs, which is present in more than 50 AMOs targeted to human miRNAs in miRBaseV20. DNA/locked nucleic acids (LNA) AMOs synthesized with a phosphorothioate backbone also inhibited TLR7 sensing in a sequence-dependent manner, demonstrating that the off-target effects of AMOs are not restricted to 2\u27OMe modification. Taken together, our work establishes the potential for off-target effects of AMOs on TLR7/8 function, which should be taken into account in their therapeutic development and in vivo application

Genome-wide association mapping of date palm fruit traits

Date palms (Phoenix dactylifera) are an important fruit crop of arid regions of the Middle East and North Africa. Despite its importance, few genomic resources exist for date palms, hampering evolutionary genomic studies of this perennial species. Here we report an improved long-read genome assembly for P. dactylifera that is 772.3 Mb in length, with contig N50 of 897.2 Kb, and use this to perform genome-wide association studies (GWAS) of the sex determining region and 21 fruit traits. We find a fruit color GWAS at the R2R3-MYB transcription factor VIRESCENS gene and identify functional alleles that include a retrotransposon insertion and start codon mutation. We also find a GWAS peak for sugar composition spanning deletion polymorphisms in multiple linked invertase genes. MYB transcription factors and invertase are implicated in fruit color and sugar composition in other crops, demonstrating the importance of parallel evolution in the evolutionary diversification of domesticated species