Miracle-dz/UniFAR-FTUs huggingface dataset:
Quantifying flight aptitude variation in wild A. gambiae s.l. in order to identify long-distance migrants

Background In the West African Sahel, during the 5-7 month-long dry season mosquito reproduction is halted due to the absence of surface waters required for larval development. Recent studies have suggested that both Anopheles gambiae s.s and A. arabiensis persist in this region by migration from distant locations where larval sites are perennial, and A. coluzzii engages in long-distance migration, presumably within the Sahel, following shifting resources due to the ever-changing patterns of Sahelian rainfall. Understanding mosquito migration is key to malaria control, a disease that still kills >400,000 people, mostly children in Africa. Methods We used a new tethered-flight assay to characterize flight in the three primary malaria vectors mentioned above and evaluated seasonal differences in their flight activity. The flight of tethered wild mosquitoes was audio-recorded from 21:00h to 05:00h in the following morning and three flight aptitude indices were examined: total flight duration, longest flight bout, and the number of flight bouts during the assay. Based on recent studies, we predicted that (i) the distribution of the flight aptitude indices would exhibit bi-modality and/or marked skewness, indicating a subpopulation of high flight activity (HFA) associated with long-distance migrants, in contrast to low flight activity (LFA) in appetitive flyers. Additionally, flight aptitude would (ii) increase in the wet season, (iii) increase in gravid females, and (iv) vary among the vector species. Results The distributions of all flight indices departed sharply from a normal curve, and were strongly skewed to the right, consistent with the division of the population into a majority of LFAs and a minority of HFAs, e.g., the median total flight was 586 seconds, and its maximum value was 16,110 seconds (~4.5 h). As predicted, flight aptitude peaked in the wet season and was higher in gravid females than in non-bloodfed females. Flight aptitude was higher in A. coluzzii than in A. arabiensis, but A. gambiae s.s. was not statistically different from either. We evaluated differences in wing size and shape between LFAs and HFAs. During the wet season, wing size of HFA A. coluzzii was larger than that of LFAs; it was wider than predicted by its length, indicating a shape change. However, no statistically significant differences were found in wings of A. gambiae s.s. or A. arabiensis. Conclusions The partial agreement between the assay results and predictions suggest a degree of discrimination between appetitive flyers and long-distance migrants. Wing size and shape seems to indicate higher flight activity in A. coluzzii during the wet season.
Dynamic localization of SPO11-1 and conformational changes of meiotic axial elements during recombination initiation of maize meiosis

Meiotic double-strand breaks (DSBs) are generated by the evolutionarily conserved SPO11 complex in the context of chromatin loops that are organized along axial elements (AEs) of chromosomes. However, how DSBs are formed with respect to chromosome axes and the SPO11 complex remains unclear in plants. Here, we confirm that DSB and bivalent formation are defective in maize spo11-1 mutants. Super-resolution microscopy demonstrates dynamic localization of SPO11-1 during recombination initiation, with variable numbers of SPO11-1 foci being distributed in nuclei but similar numbers of SPO11-1 foci being found on AEs. Notably, cytological analysis of spo11-1 meiocytes revealed an aberrant AE structure. At leptotene, AEs of wild-type and spo11-1 meiocytes were similarly curly and discontinuous. However, during early zygotene, wild-type AEs become uniform and exhibit shortened axes, whereas the elongated and curly AEs persisted in spo11-1 mutants, suggesting that loss of SPO11-1 compromised AE structural maturation. Our results reveal an interesting relationship between SPO11-1 loading onto AEs and the conformational remodeling of AEs during recombination initiation.
The evolution of suppressed recombination between sex chromosomes by chromosomal inversions

The idea that sex-differences in selection drive the evolution of suppressed recombination between sex chromosomes is well-developed in population genetics. Yet, despite a now classic body of theory, empirical evidence that sexual antagonism drives the evolution of recombination suppression remains meagre and alternative hypotheses underdeveloped. We investigate whether the length of ‘evolutionary strata’ formed by chromosomal inversions that expand the non-recombining sex determining region (SDR) on recombining sex chromosomes can offer an informative signature of whether, and how, selection influenced their fixation. We develop population genetic models that determine how the length of a chromosomal inversion that expands the SDR affects its fixation probability for three categories of inversions: (i) neutral, (ii) directly beneficial (i.e., due to breakpoint or position effects), and (iii) indirectly beneficial (especially those capturing sexually antagonistic loci). Our models predict that neutral inversions should leave behind a unique signature of large evolutionary strata, and that it will often be difficult or impossible to distinguish between smaller strata created by directly or indirectly beneficial inversions. An interesting and unexpected prediction of our models is that the physical location of the ancestral SDR on the sex chromosomes is the most important factor influencing the relation between inversion size and the probability of expanding the SDR. Our findings raise a suite of new questions about how physical as well as selective processes influence the evolution of recombination suppression between sex chromosomes.
Synthetic hypermutation: gene-drug mutation rate synergy reveals a translesion synthesis mechanism

Gene-gene or gene-drug interactions are typically quantified using fitness as readout because the data is continuous and easily measured in high-throughput. However, to what extent fitness captures the range of other phenotypes that show synergistic effects is usually unknown. Using Saccharomyces cerevisiae, and focusing on a matrix of DNA repair mutants and genotoxic drugs, we quantify 76 gene-drug interactions based on both mutation rate and fitness and find that these parameters are not necessarily overlapping. Independent of fitness defects we identified six cases of synthetic hypermutation, where the combined effect of the drug and mutant on mutation rate was greater than predicted. One example occurred when yeast lacking RAD1 were exposed to cisplatin and we characterized this interaction using whole-genome sequencing. Our sequencing results indicate mutagenesis by cisplatin in rad1Δ cells appeared to depend almost entirely on interstrand crosslinks at GpCpN motifs. Interestingly, our data suggests that the 3’ base in these motifs templates the addition of the mutated base. This result differs from cisplatin mutation signatures in XPF-deficient C. elegans and supports a model in which translesion synthesis polymerases perform a slippage and realignment extension across from the damaged base. Accordingly, DNA polymerase ζ activity was essential for mutagenesis in cisplatin treated rad1Δ cells. Together these data reveal the potential to gain new mechanistic insights from non-fitness measures of gene-drug interactions and extend the use of mutation accumulation and whole-genome sequencing analysis to define DNA repair mechanisms.
Cleavage modification did not alter early blastomere fates during bryozoan evolution

Stereotypic cleavage patterns play a crucial role in cell fate determination by precisely positioning early embryonic blastomeres. Although misplaced cell divisions can alter blastomere fates and cause embryonic defects, cleavage patterns have changed several times during animal evolution. Here, we analyze the evolutionary transition from spiral cleavage – a stereotypic pattern remarkably conserved in many protostomes – to the biradial cleavage of bryozoans. We characterize the cell lineage, MAPK signaling and expression of several developmental genes in the bryozoan Membranipora membranacea, and found that the fate and the genes expressed in the early bryozoan blastomeres are similar to their putative homologous blastomeres in spiral-cleaving embryos. The data indicate that cleavage geometry evolved independent from other developmental traits during the transition from spiral to biradial cleavage in the bryozoan lineage, revealing that stereotypic cleavage patterns can be evolutionarily modified without major changes to the molecular identity and fate of embryonic blastomeres.
Heterotrophic Thaumarchaeota with ultrasmall genomes are widespread in the ocean

The Thaumarchaeota comprise a diverse archaeal phylum including numerous lineages that play key roles in global biogeochemical cycling, particularly in the ocean. To date, all genomically-characterized marine Thaumarchaeota are reported to be chemolithoautotrophic ammonia-oxidizers. In this study, we report a group of heterotrophic marine Thaumarchaeota (HMT) with ultrasmall genome sizes that is globally abundant in deep ocean waters, apparently lacking the ability to oxidize ammonia. We assemble five HMT genomes from metagenomic data derived from both the Atlantic and Pacific Oceans, including two that are >95% complete, and show that they form a deeply-branching lineage sister to the ammonia-oxidizing archaea (AOA). Metagenomic read mapping demonstrates the presence of this group in mesopelagic samples from all major ocean basins, with abundances reaching up to 6% that of AOA. Surprisingly, the predicted sizes of complete HMT genomes are only 837-908 Kbp, and our ancestral state reconstruction indicates this lineage has undergone substantial genome reduction compared to other related archaea. The genomic repertoire of HMT indicates a highly reduced metabolism for aerobic heterotrophy that, although lacking the carbon fixation pathway typical of AOA, includes a divergent form III-a RuBisCO that potentially functions in a nucleotide scavenging pathway. Despite the small genome size of this group, we identify 13 encoded pyrroloquinoline quinone (PQQ)-dependent dehydrogenases that are predicted to shuttle reducing equivalents to the electron transport chain, suggesting these enzymes play an important role in the physiology of this group. Our results suggest that heterotrophic Thaumarchaeota are widespread in the ocean and potentially play key roles in global chemical transformations. Importance It has been known for many years that marine Thaumarchaeota are abundant constituents of dark ocean microbial communities, where their ability to couple ammonia oxidation and carbon fixation plays a critical role in nutrient dynamics. In this study we describe an abundant group of heterotrophic marine Thaumarchaeota (HMT) in the ocean with physiology distinct from their ammonia-oxidizing relatives. HMT lack the ability to oxidize ammonia and fix carbon via the 3-hydroxypropionate/4-hydroxybutyrate pathway, but instead encode a form III-a RuBisCO and diverse PQQ-dependent dehydrogenases that are likely used to generate energy in the dark ocean. Our work expands the scope of known diversity of Thaumarchaeota in the ocean and provides important insight into a widespread marine lineage.
SLC45A2 protein stability and regulation of melanosome pH determine melanocyte pigmentation

SLC45A2 encodes a putative transporter expressed primarily in pigment cells. SLC45A2 mutations and polymorphisms cause oculocutaneous albinism (OCA) and pigmentation variation, but neither SLC45A2 localization and function nor how gene variants affect these properties are known. We show that SLC45A2 localizes to mature melanosomes that only partially overlap with a cohort expressing the chloride channel OCA2. SLC45A2 expressed ectopically in HeLa cells localizes to lysosomes and raises lysosomal pH, suggesting that, like OCA2, SLC45A2 in melanocytes de-acidifies maturing melanosomes to support melanin synthesis. Analyses of SLC45A2- and OCA2-deficient mouse melanocytes show that SLC45A2 functions later during melanosome maturation than OCA2, and that OCA2 overexpression compensates for loss of SLC45A2 expression in pigmentation. The light skin-associated SLC45A2 allelic F374 variant restores only moderate pigmentation to SLC45A2-deficient melanocytes because of low level expression in melanosomes due to rapid proteasome-independent degradation. Our data indicate that SLC45A2 maintains melanosome neutralization – initially orchestrated by transient OCA2 activity – to support melanization at late stages of melanosome maturation, and that a common variant imparts reduced activity due to protein instability.
The pathogenesis of retinal damage in human eye under impact and blast load

Human eye subjected to non penetrating impact (blunt-impact) may experience severe damage. The most common type is partial tearing of the retina at specific eye locations. In ophthalmology, based on impact experiment performed by Delori et al. (1967), it is commonly accepted that the mechanism responsible for retinal damage is the vitreous pull-traction action and the equatorial expansion of the sclera. Based on the evidence of a vitrectomized patient who reported retinal damage after blunt impact, an investigation on the possible role of shockwave dynamics in the retinal damage has been performed by means of hydrocode numerical simulation. A FEM model of the eye has been developed and the experiment of Delori et al. has been reproduced. Soft tissues constitutive response has been determined by means of reverse engineering approach. It has been demonstrated that release waves at the retina-choroid interface are generated in the early time of the blunt impact and can cause retina tearing when the eye bulb .
Mitochondrial dysfunction underlying sporadic inclusion body myositis is ameliorated by the mitochondrial homing drug MA-5

Sporadic inclusion body myositis (sIBM) is the most common idiopathic inflammatory myopathy, and several reports have suggested that mitochondrial abnormalities are involved in its etiology. We recruited 9 sIBM patients and found significant histological changes and an elevation of growth differential factor 15 (GDF15), a marker of mitochondrial disease, strongly suggesting the involvement of mitochondrial dysfunction. Bioenergetic analysis of sIBM patient myoblasts revealed impaired mitochondrial function. Decreased ATP production, reduced mitochondrial size and reduced mitochondrial dynamics were also observed in sIBM myoblasts. Cell vulnerability to oxidative stress also suggested the existence of mitochondrial dysfunction. Mitochonic acid-5 (MA-5) increased the cellular ATP level, reduced mitochondrial ROS, and provided protection against sIBM myoblast death. MA-5 also improved the survival of sIBM skin fibroblasts as well as mitochondrial morphology and dynamics in these cells. The reduction in the gene expression levels of Opa1 and Drp1 was also reversed by MA-5, suggesting the modification of the fusion/fission process. These data suggest that MA-5 may provide an alternative therapeutic strategy for treating not only mitochondrial diseases but also sIBM.
Beyond the limitation of randomized controlled trials (RCTs)-current drug repositioning by using human induced pluripotent stem (iPS) cells technology-

To ensure the clinical value of medical interventions, randomized controlled trials (RCTs) are necessary. However, the results of conventional RCTs cannot show individual therapeutic efficacy and safety for medical intervention to a targeted patient. It is the most important weak point of conventional RCTs. Here I show that the new clinical research method by using human induced pluripotent stem (iPS) cells technology will be able to complement the most important weak point of conventional RCTs. As the representative examples, I show the new clinical values of statins (inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase) found by using human iPS cells technology in achondroplasia or hanatophoric dysplasia (type 1) case and hepatitis C virus (HCV) infection case. Furthermore, they are also important examples for drug repositioning. Therefore, my article would be valuable as a scientific communication for physicians and/or scientists.
Extracellular mycobacterial DNA triggers Caspase-11-dependent pyroptosis of infected macrophages and drives disease progression

Deregulated inflammation is a serious complication of life-threatening microbial infections, including tuberculosis (TB). The pathological hallmark of TB, the granuloma, is an inflammatory structure crucial for containing infection. However, excessive inflammation in granulomas can cause tissue damage and promote bacterial proliferation and dissemination. The assembly of multiprotein inflammasome complexes is an important trigger of inflammation, but it remains unknown how inflammasome activation impacts TB granuloma progression. Here, by in vivo imaging using the zebrafish TB model, we found that inflammasomes and ensuing pyroptotic cell death of infected macrophages drive granuloma expansion and disease progression. We show that different types of inflammasomes are activated during granuloma formation, with host-protective roles for Asc-dependent inflammasome activation and Il1b secretion. In contrast, an Asc-independent pathway induces macrophage pyroptosis and impairs host resistance. Complementary research in ASC-deficient murine macrophages reveals that extracellular bacterial DNA induces CASP11-dependent pyroptosis in a manner dependent on phagosome permeabilization. Finally, we show that mycobacteria induce pyroptosis to escape from cell-in-cell structures that form within granulomas when living infected cells are engulfed by newly attracted macrophages. This study provides new insights into the role of pyroptosis in TB pathogenesis and unravels a novel link between nucleic acid sensing and CASP11-dependent pyroptosis.
Development and Use of miRNA-derived SSR Markers to Study Genetic Diversity, Population Structure and Characterization of Genotypes for Heat Tolerance Breeding in Bread Wheat (Triticum aestivum L.)

Wheat is one of the most important cereal crop in the world. Heat stress is an important abiotic stress limiting wheat production and productivity in the world including south-east Asia. The importance of miRNAs in gene expression under various biotic and abiotic stresses is well documented. Molecular markers, especially SSR markers, plays an important role for the success in molecular plant breeding programs. The discovery of SSRs from non-coding regions has been a challenging task. Therefore, development of novel miRNA-based SSRs from the conserved portions of the genome will prove useful for the study of genetic diversity of heat-responsive miRNA-genes in wheat. In the present study, efforts are made to mine SSR markers from 96 members of heat-responsive miRNA-genes of wheat followed by their validation using 37 contrasting (heat tolerance/susceptible) wheat genotypes. Among a set of 13 miRNA-SSRs used,7 SSRs were found polymorphic. Among these polymorphic SSR markers, three found to be very informative SSRs (HT-169j, HT-160a and HT-160b) and could largely discriminate heat tolerant genotypes from the heat susceptible ones. Further analysis based on Polymorphism Information Content (PIC) revealed that miRNA genes were more diverse in susceptible genotypes compared to tolerant genotypes. Ours is the first report that the genic/miRNA markers could be successfully used to study wheat diversity, population structure and characterization of trait specific germplasm. The important and useful miRNA-based SSRs, therefore, would serve as best markers in the marker-assisted breeding programs aimed at enhancing heat tolerance of Indian wheat.
Acute stressors experienced by layer breeders do not affect measures of stress and fear in their offspring

Stressors experienced by layer breeders during egg production can lead to changes in the egg hormone content, potentially impacting their offspring, the commercial layers. Genetic differences might also affect the offspring’s susceptibility to maternal experiences. In this study, we tested if maternal stress affects measures of stress and fear in five strains of layer breeders: commercial brown 1 & 2, commercial white 1 & 2 and a pure line White Leghorn. Each strain was equally separated into two groups: “Maternal Stress” (MS), where hens were subjected to a series of 8 consecutive days of acute psychological stressors, and “Control,” which received routine husbandry. Additional eggs from Control were injected either with corticosterone diluted in a vehicle solution (“CORT”) or just “Vehicle. ” Stress- and fear-responses of the offspring were measured in a plasma corticosterone test and a combined human approach and novel object test. Both MS and CORT treatments failed to affect the measured endpoints in the offspring, but significant strain differences were found. The offspring of the white strains showed a higher physiological response compared to brown strains, but the White 2 offspring was consistently the least fearful strain in the behaviour tests. Our study found that the acute psychological stressors experienced by layer breeders did not affect the parameters tested in their offspring and that corticosterone does not seem to be the primary mediator of maternal stress in laying hens. This is highly important, as in poultry production, layer breeders are often subjected to short-term stressors. In addition, we successfully dissociated the physiological and behavioural parameters of stress response in laying hens, showing that increased concentrations of plasma corticosterone in response to stress is not directly associated with high levels of fear.
Highly diverse mesophotic reef fish communities in Raja Ampat, West Papua

Mesophotic coral ecosystems (MCEs; reefs 30–150 m depth) are poorly studied, with existing research heavily geographically biased away from the most species-rich reef regions. Yet, MCEs are of high interest because of their unique species and potential to act as refuges from the impacts of fishing. Using baited remote underwater video systems, we surveyed reef fish communities from 2 to 85 m depths throughout the Raja Ampat archipelago in West Papua, Indonesia—an area considered the heart of the Coral Triangle where coral reef biodiversity is greatest. We sought to provide the first assessment of fish communities across this depth gradient in the region and identify whether human population density and market access differently affected fish abundance based on depth. Here we show that—similar to shallow reefs—Raja Ampat MCEs are exceptionally diverse, with 152 fish species recorded at depths greater than 40 m. We found that fish community structures were highly depth driven, with declines in fish abundance at increased depth. In contrast to previous studies elsewhere in the world, we found that the proportion of planktivores declined across the shallow reef to MCE depth gradient. While greater human population density correlated with lower Epinephelidae and Lutjanidae abundance (two key fisheries families), we did not find evidence that MCEs provide a depth refuge from fishing. Surprisingly, we also found that fish abundance declined at greater distances from the major regional market—likely caused by historical fisheries pressure in more remote areas. These results both expand upon and contrast some previously established MCE-depth patterns and human impact patterns on fish communities, suggesting that regional context and historical pressures matters. Our findings highlight the need for future MCE studies within the Coral Triangle region.