Miracle-dz/UniFAR-FTUs huggingface dataset:
Suitability of resampled multispectral datasets for mapping flowering plants in the Kenyan savannah

Pollination services and honeybee health in general are important in the African savannahs particularly to farmers who often rely on honeybee products as a supplementary source of income. Therefore, it is imperative to understand the floral cycle, abundance and spatial distribution of melliferous plants in the African savannah landscapes. Furthermore, placement of apiaries in the landscapes could benefit from information on spatiotemporal patterns of flowering plants, by optimising honeybees’ foraging behaviours, which could improve apiary productivity. This study sought to assess the suitability of simulated multispectral data for mapping melliferous (flowering) plants in the African savannahs. Bi-temporal AISA Eagle hyperspectral images, resampled to four sensors (i.e. WorldView-2, RapidEye, Spot-6 and Sentinel-2) spatial and spectral resolutions, and a 10-cm ultra-high spatial resolution aerial imagery coinciding with onset and peak flowering periods were used in this study. Ground reference data was collected at the time of imagery capture. The advanced machine learning random forest (RF) classifier was used to map the flowering plants at a landscape scale and a classification accuracy validated using 30% independent test samples. The results showed that 93.33%, 69.43%, 67.52% and 82.18% accuracies could be achieved using WorldView-2, RapidEye, Spot-6 and Sentinel-2 data sets respectively, at the peak flowering period. Our study provides a basis for the development of operational and cost-effective approaches for mapping flowering plants in an African semiarid agroecological landscape. Specifically, such mapping approaches are valuable in providing timely and reliable advisory tools for guiding the implementation of beekeeping systems at a landscape scale.
Analysis of Treponema pallidum strains from China using improved methods for whole-genome sequencing from primary syphilis chancres

Whole-genome sequencing (WGS) of Treponema pallidum subsp. pallidum (TPA) has been constrained by the lack of in vitro cultivation methods for isolating spirochetes from patient samples. We built upon recently developed enrichment methods to sequence TPA directly from primary syphilis chancre swabs collected in Guangzhou, China. By combining parallel, pooled whole-genome amplification (ppWGA) with hybrid selection, we generated high quality genomes from four of eight chancre-swab samples and two of two rabbit-passaged isolates, all subjected to challenging storage conditions. This approach enabled the first WGS of Chinese samples without rabbit passage and provided insights into TPA genetic diversity in China.
Ongoing outbreak of COVID-19 in Iran: challenges and signs of concern

Since the first outbreak in China, the Coronavirus Disease 2019 (COVID-19) has rapidly spread around the world. Iran was one of the first countries outside of China to report infections with COVID-19. With nearly 100 exported cases to various other countries, it has since been the epicentre of the outbreak in the Middle east. By examining the age-stratified COVID-19 case fatality rates across the country and 14 university hospitals in Tehran, we find that, in younger age groups, the reported cases on 13/03/2020 only capture less than 10% of symptomatic cases in the population. This indicates significant levels of under-reporting in Iran. Using the 18 full-genome sequences from cases with a travel history or link to Iran, as well as the one full genome sequence obtained from within the country, we estimate the time to the most recent common ancestor of sequences which suggests the likely start of the outbreak on 21/01/2020 (95% HPD: 05/12/2019 - 14/02/2020) with an approximate doubling time of 3.07 (95% HPD: 1.68 - 16.27). Also, based on known exported cases to Oman, Kuwait, Lebanon, and China, we estimate the outbreak size on 25 February and 6 March to be around 13,700 (95% CI: 7,600 - 33,300) and 60,500 (43,200 - 209,200), respectively. Knowing the size of the outbreak at two time points and the typical doubling times associated with the COVID-19 epidemics in countries across Europe and North America, we can independently verify that the likely start of epidemic in Iran is around 15/01/2020 (27/12/2019 - 24/01/2020). Our assessment of the fate of the epidemic based on current levels of non-pharmaceutical interventions implemented by the government suggests upward of 10 million cases (IQR: 6.7M - 18M) and 100,000 ICU beds required (IQR: 77K - 140K) during the peak of the epidemic with more than 100,000 cumulative deaths (IQR: 180K - 240K). We also predict a peak in demand for ICU beds on 21/04/2020 (IQR: 06/04/2020 - 23/05/2020). The large span of the peak of the ICU demand is a result of two separate peaks, with the first occurring at around 15/4/2020 and the second in approximately a months time. The latter is also expected to last longer and is based on the relatively relaxed social distancing measures in place. The exact magnitude and timing of the peaks strictly depends on levels of interventions and can change significantly upon new information or change of policy. We caution that a lack of, or relaxed, stringent intervention measures, during a period of highly under-reported spread, would likely lead to the healthcare system becoming overwhelmed in the next few months.
Cyclopamine sensitizes Glioblastoma cells to Temozolomide treatment through Sonic Hedgehog pathway

Aim Glioblastoma is an extremely aggressive glioma, resistant to radio and chemotherapy usually performed with temozolomide. One of the main reasons for glioblastoma resistance to conventional therapies is due to the presence of cancer stem-like cells. These cells could recapitulate some signaling pathways important for embryonic development, such as Sonic hedgehog. Here, we investigated if the inhibitor of the Sonic hedgehog pathway, cyclopamine, could potentiate the temozolomide effect in cancer stem-like cells and glioblastoma cell lines in vitro. Main methods The viability of glioblastoma cells exposed to cyclopamine and temozolomide treatment was evaluated by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay while the induction of apoptosis was assessed by western blot. The stemness properties of glioma cells were verified by clonogenic and differentiation assay and the expression of stem cell markers were measured by fluorescence microscopy and western blot. Key findings The glioblastoma viability was reduced by cyclopamine treatment. Cyclopamine potentiated temozolomide treatment in glioblastoma cell lines by inducing apoptosis through activation of caspase-3 cleaved. Conversely, the combined treatment of cyclopamine and temozolomide potentiated the stemness properties of glioblastoma cells by inducing the expression of SOX-2 and OCT-4. Significance Cyclopamine plays an effect on glioblastoma cell lines but also sensibilize them to temozolomide treatment. Thus, first-line treatment with Sonic hedgehog inhibitor followed by temozolomide could be used as a new therapeutic strategy for glioblastoma patients.
Vesicular GABA-transporter neurons in the zona incerta are maximally active during non rapid-eye movement (NREM) and rapid-eye movement (REM) sleep

Sleep and wake are opposing behavioral states controlled by the activity of specific neurons. The neurons responsible for sleep/wake control have not been fully identifed due to the lack of in-vivo high throughput technology. We use the deep-brain calcium (Ca2+) imaging method to identify activity of hypothalamic neurons expressing the vesicular GABA transporter (vGAT), a marker of GABAergic neurons. vGAT-cre mice (n=5) were microinjected with rAAV-FLEX-GCaMP6M into the lateral hypothalamus and 21d later the Ca2+ influx in vGAT neurons (n=372) was recorded in freely-behaving mice during waking (W), NREM and REM sleep. Post-mortem analysis revealed the lens tip located in the zona incerta/lateral hypothalamus (ZI-LH) and the change in fluorescence of neurons in the field of view was as follows: 54.9% of the vGAT neurons had peak fluorescence during REM sleep (REM-max), 17.2% were NREM-max, 22.8% were wake-max while 5.1% were both wake+REM max. Thus, three quarters of the recorded vGAT neurons in the ZI-LH were most active during sleep. In the NREM-max group Ca2+ fluorescence anticipated the initiation of NREM sleep onset and remained high throughout sleep (NREM and REM sleep). In the REM-max neurons Ca2+fluorescence increased before the onset of REM sleep and stayed elevated during the episode. Activation of the vGAT NREM-max neurons in the zona incerta and dorsal lateral hypothalamus would inhibit the arousal neurons to initiate and maintain sleep.
Repairing neural damage in a C. elegans chemosensory circuit using genetically engineered synapses

Neuronal loss can considerably diminish neural circuit function, impairing normal behavior by disrupting information flow in the circuit. We reasoned that by rerouting the flow of information in the damaged circuit it may be possible to offset these negative outcomes. We examined this possibility using the well-characterized chemosensory circuit of the nematode worm C. elegans. In this circuit, a main sensory neuron class sends parallel outputs to several interneuron classes. We found that the removal of one of these interneuron classes impairs chemotaxis to attractive odors, revealing a prominent path for information flow in the circuit. To alleviate these deficiencies, we sought to reinforce a remaining neural pathway. We used genetically engineered electrical synapses for this purpose, and observed the successful recovery of chemotaxis performance. However, we were surprised to find that the recovery was largely mediated by inadvertently formed left-right lateral electrical connections within individual neuron classes. Our analysis suggests that these additional electrical synapses help restore circuit function by amplifying weakened neuronal signals in the damaged circuit. These results demonstrate the power of genetically engineered synapses to regulate information flow and signal intensity in damaged neural circuits.
Identification of functionally-distinct macrophage subpopulations regulated by efferocytosis in Drosophila

Macrophages are a highly heterogeneous population of cells, with this diversity stemming in part from the existence of tissue resident populations and an ability to adopt a variety of activation states in response to stimuli. Drosophila blood cells (hemocytes) are dominated by a lineage of cells considered to be the functional equivalents of mammalian macrophages (plasmatocytes). Until very recently plasmatocytes were thought to be a homogeneous population. Here, we identify enhancer elements that label subpopulations of plasmatocytes, which vary in abundance across the lifecourse of the fly. We demonstrate that these plasmatocyte subpopulations behave in a functionally-distinct manner when compared to the overall population, including more potent migratory responses to injury and decreased clearance of apoptotic cells within the developing embryo. Additionally, these subpopulations display differential localisation and dynamics in pupae and adults, hinting at the presence of tissue-resident macrophages in the fly. Our enhancer analysis also allows us to identify novel candidate genes involved in plasmatocyte behaviour in vivo. Misexpression of one such enhancer-linked gene (calnexin14D) in all plasmatocytes improves wound responses, causing the overall population to behave more like the subpopulation marked by the calnexin14D-associated enhancer. Finally, we show that, we are able to modulate the number of cells within some subpopulations via exposure to increased levels of apoptotic cell death, thereby decreasing the number of plasmatocytes within more wound-responsive subpopulations. Taken together our data demonstrates the existence of macrophage heterogeneity in Drosophila and identifies mechanisms involved in the specification and function of these plasmatocyte subpopulations. Furthermore, this work identifies key molecular tools with which Drosophila can be used as a highly genetically-tractable, in vivo system to study the biology of macrophage heterogeneity.
Degradation levels of continuous speech affect neural speech tracking and alpha power differently

Understanding degraded speech, e.g. following a hearing damage, can pose a challenge. Previous attempts to quantify speech intelligibility in neural terms have usually focused on one of two measures, namely low-frequency speech-brain synchronization or alpha power modulations. However, reports have been mixed concerning the modulation of these measures, an issue aggravated by the fact that they have normally been studied separately. Using a parametric speech degradation approach, we present MEG studies that overcome this shortcoming. In a first study, participants listened to unimodal auditory speech with three different levels of degradation (original, 7-channel and 3-channel vocoding). Intelligibility declined with declining clarity, implemented by fewer vocoding channels but was still intelligible to some extent even for the lowest clarity level used (3-channel vocoding). Low- frequency (1-7 Hz) speech tracking suggested a u-shaped relationship with strongest effects for the medium degraded speech (7-channel) in bilateral auditory and left frontal regions. To follow up on this finding, we implemented three additional vocoding levels (5-channel, 2- channel, 1-channel) in a second MEG study. Using this wider range of degradation, the speech-brain synchronization showed a similar pattern for the degradation levels used in the first study but further shows that when speech becomes unintelligible, synchronization declines again. The relationship differed for alpha power, which continued to decrease across vocoding levels reaching a floor effect for 5-channel vocoding. Predicting subjective intelligibility based on models either combining both measures or each measure alone, showed superiority of the combined model. Our findings underline that speech tracking and alpha power are modified differently by the degree of degradation of continuous speech but together contribute to the subjective understanding of speech.
The Beginning of the End: A Chromosomal Assembly of the New World Malaria Mosquito Ends with a Novel Telomere

Chromosome level assemblies are accumulating in various taxonomic groups including mosquitoes. However, even in the few reference-quality mosquito assemblies, a significant portion of the heterochromatic regions including telomeres remain unresolved. Here we produce a de novo assembly of the New World malaria mosquito, Anopheles albimanus by integrating Oxford Nanopore sequencing, Illumina, Hi-C and optical mapping. This 172.6 Mbps female assembly, which we call AalbS3, is obtained by scaffolding polished large contigs (contig N50=13.7 Mbps) into three chromosomes. All chromosome arms end with telomeric repeats, which is the first in mosquito assemblies and represents a significant step towards the completion of a genome assembly. These telomeres consist of tandem repeats of a novel 30-32 bp telomeric repeat unit (TRU) and are confirmed by analysing the termini of long reads and through both chromosomal in situ hybridization and a Bal31 sensitivity assay. The AalbS3 assembly included previously uncharacterized centromeric and rDNA clusters and more than doubled the content of transposable elements and other repetitive sequences. This telomere-to-telomere assembly, although still containing gaps, represents a significant step towards resolving biologically important but previously hidden genomic components. The comparison of different scaffolding methods will also inform future efforts to obtain reference-quality genomes for other mosquito species. 100-word Article Summary We report AalbS3, a telomere-to-telomere assembly of the Anopheles albimanus genome produced by integrating advancing technologies including Oxford Nanopore and Bionano optical mapping. AalbS3 features much of the difficult-to-assemble genomic ‘dark matters’ including previously missed transposons, centromeres and rDNA clusters. We describe novel telomeric repeats that are confirmed by analysis of long reads and by telomere hybridization assays. This reference-quality assembly represents a significant step towards completing the genomic puzzle pieces and informs efforts to improve the assembly of other mosquito species. Future research into the relationship between telomere and mosquito life span may have significant implications to disease control.
Genomics of experimental diversification of Pseudomonas aeruginosa in cystic fibrosis lung-like conditions

Pseudomonas aeruginosa is among the most problematic opportunistic pathogens for adults with cystic fibrosis (CF), causing repeated and resilient infections in the lung and surrounding airways. Evidence suggests that long-term infections are associated with diversification into specialized types but the underlying cause of that diversification and the effect it has on the persistence of infections remains poorly understood. Here, we use evolve and resequence experiments to investigate the genetic changes accompanying rapid, de novo phenotypic diversification in lab environments designed to mimic two aspects of human lung ecology: spatial structure and complex nutritional content. After ∼220 generations of evolution, we find extensive genetic variation present in all environments, including those that most closely resemble the CF lung, attributable to a combination of high mutation supply rates resulting from large population sizes and the complex ecological conditions imposed by resource complexity and spatial structure. We use the abundance and frequency of nonsynonymous and synonymous mutations to estimate the ratio of mutations that are selectively neutral (hitchhikers) to those that are under selection (drivers). A significantly lower proportion of driver mutations in spatially structured populations suggests that reduced dispersal generates subpopulations with reduced effective population size, decreasing the supply of beneficial mutations and causing more divergent evolutionary trajectories. The genes most commonly mutated tend to impact regulatory functions linked to a range of CF-associated phenotypes, including one gene that confers antibiotic resistance despite the absence of antibiotic selection in our experiment, but do not appear to be specific to CF-like conditions arising from antimicrobial treatment, immune system suppression, or competition from other microbial species. Our results are consistent with models of adaptation that see the first mutations fixed during adaptation to a stressful environment being those that are broadly beneficial across a range of environments.
A nucleoid-associated protein bends and bridges DNA in a multiplicity of topological states with varying specificity

Nucleoid-associated proteins are crucial in compacting prokaryotic DNA, but how they generate higher-order structures is unclear. Integration host factor, IHF, is a key nucleoid-associated protein in bacteria, creating sharp bends in DNA. We show that the IHF–DNA complex structural multimodality is far more elaborate than previously proposed and provide insights into how this enables mechanical molecular switching. Using single-molecule atomic force microscopy and all-atom molecular dynamics simulations we find three topological modes in roughly equal proportions: “associated” (73° of DNA bend), “half-wrapped” (107°) and “fully-wrapped” (147°), with only the latter occurring with sequence specificity. DNA bridging is seen in the presence of multiple binding sites, with simulations showing this occurs through another recognition mode that does not depend on sequence and gives IHF a stoichiometry greater than one. We present a model of these states and propose a crucial biological role for these observed behaviors.
Using prior information from humans to prioritize genes and gene-associated variants for complex traits in livestock

Genome-Wide Association Studies (GWAS) in large human cohorts have identified thousands of loci associated with complex traits and diseases. For identifying the genes and gene-associated variants that underlie complex traits in livestock, especially where sample sizes are limiting, it may help to integrate the results of GWAS for equivalent traits in humans as prior information. In this study, we sought to investigate the usefulness of results from a GWAS on human height as prior information for identifying the genes and gene-associated variants that affect stature in cattle, using GWAS summary data on samples sizes of 700,000 and 58,265 for humans and cattle, respectively. Using Fisher’s exact test, we observed a significant proportion of cattle stature-associated genes (30/77) that are also associated with human height (odds ratio = 5.1, p = 3.1e-10). Result of randomized sampling tests showed that cattle orthologs of human height-associated genes, hereafter referred to as candidate genes (C-genes), were more enriched for cattle stature GWAS signals than random samples of genes in the cattle genome (p=0.01). Randomly sampled SNPs within the C-genes also tend to explain more genetic variance for cattle stature (up to 13.2%) than randomly sampled SNPs within random cattle genes (p=0.09). The most significant SNPs from a cattle GWAS for stature within the C-genes did not explain more genetic variance for cattle stature than the most significant SNPs within random cattle genes (p=0.87). Altogether, our findings support previous studies that suggest a similarity in the genetic regulation of height across mammalian species. However, with the availability of a powerful GWAS for stature that combined data from 8 cattle breeds, prior information from human-height GWAS does not seem to provide any additional benefit with respect to the identification of genes and gene-associated variants that affect stature in cattle. Author Summary Provided that there is a similarity in the biological control of complex traits in different species, the results of genome-wide association study for a given trait in a model species can be utilized as prior information to identify genes and gene-associated variants that affect the same trait in a non-model species. Here we report that the number of genes found to be affecting height in both humans and cattle is more than can be expected by chance, suggesting a similarity in the biology of height in both species. In addition, genes that are associated with height in humans were found to be highly enriched with variants that are strongly associated with height in cattle. Using height as a model trait, we demonstrated that across-species prior information cannot compete with a within-species prior information, with respect to the identification of genes and the gene-associated variants that affect a complex trait. Across-species prior information can be useful, however, when within-species prior information is either unavailable or poor.