Miracle-dz/UniFAR-FTUs huggingface dataset:
DNA Thermo-Protection Facilitates Whole-Genome Sequencing of Mycobacteria Direct from Clinical Samples

Mycobacterium tuberculosis is the leading cause of death from bacterial infection. Improved rapid diagnosis and antimicrobial resistance determination, such as by whole-genome sequencing, are required. Our aim was to develop a simple, low-cost method of preparing DNA for sequencing direct from M. tuberculosis-positive clinical samples (without culture). Simultaneous sputum liquefaction, bacteria heat inactivation (99°C/30 min), and enrichment for mycobacteria DNA were achieved using an equal volume of thermo-protection buffer (4 M KCl, 0. ABSTRACT Mycobacterium tuberculosis is the leading cause of death from bacterial infection. Improved rapid diagnosis and antimicrobial resistance determination, such as by whole-genome sequencing, are required. Our aim was to develop a simple, low-cost method of preparing DNA for sequencing direct from M. tuberculosis-positive clinical samples (without culture). Simultaneous sputum liquefaction, bacteria heat inactivation (99°C/30 min), and enrichment for mycobacteria DNA were achieved using an equal volume of thermo-protection buffer (4 M KCl, 0.05 M HEPES buffer, pH 7.5, 0.1% dithiothreitol [DTT]). The buffer emulated intracellular conditions found in hyperthermophiles, thus protecting DNA from rapid thermodegradation, which renders it a poor template for sequencing. Initial validation experiments employed mycobacteria DNA, either extracted or intracellular. Next, mock clinical samples (infection-negative human sputum spiked with 0 to 105 Mycobacterium bovis BCG cells/ml) underwent liquefaction in thermo-protection buffer and heat inactivation. DNA was extracted and sequenced. Human DNA degraded faster than mycobacteria DNA, resulting in target enrichment. Four replicate experiments achieved M. tuberculosis detection at 101 BCG cells/ml, with 31 to 59 M. tuberculosis complex reads. Maximal genome coverage (>97% at 5× depth) occurred at 104 BCG cells/ml; >91% coverage (1× depth) occurred at 103 BCG cells/ml. Final validation employed M. tuberculosis-positive clinical samples (n = 20), revealing that initial sample volumes of ≥1 ml typically yielded higher mean depths of M. tuberculosis genome coverage, with an overall range of 0.55 to 81.02. A mean depth of 3 gave >96% 1-fold tuberculosis (TB) genome coverage (in 15/20 clinical samples). A mean depth of 15 achieved >99% 5-fold genome coverage (in 9/20 clinical samples). In summary, direct-from-sample sequencing of M. tuberculosis genomes was facilitated by a low-cost thermo-protection buffer.
Invasion and maintenance of spore killers in populations of ascomycete fungi

Meiotic drivers are selfish genetic elements that have the ability to become over-represented among the products of meiosis. This transmission advantage makes it possible for them to spread in a population even when they impose fitness costs on their host organisms. Whether a meiotic driver can invade a population, and subsequently reach fixation or coexist in a stable polymorphism, depends on the one hand on the biology of the host organism, including its life-cycle, mating system, and population structure, and on the other hand on the specific fitness effects of the driving allele on the host. Here, we present a population genetics model for spore killing, a type of drive specific to fungi. We show how ploidy level, rate of selfing, and efficiency of spore killing affect the invasion probability of a driving allele and the conditions for its stable coexistence with the non-driving allele. Our model can be adapted to different fungal life-cycles, and is applied here to two well-studied genera of filamentous ascomycetes known to harbor spore killing elements, Podospora and Neurospora. We discuss our results in the light of recent empirical findings for these two systems.
Influence of historical and human factors on genetic structure and diversity patterns in peripheral populations: implications for the conservation of Moroccan trout

The brown trout s.l. has been the focus of numerous phylogeographic and conservation studies due to its socioeconomic importance, its marked genetic and phenotypic differentiation and its broad distribution range. Especially interesting evolutionary patterns are observed for populations occupying peripheral areas of a distribution range, such as in the case of the highly isolated trout populations in Morocco. Continuous stocking programs may conceal natural genetic patterns, making it challenging to discern evolutionary patterns. In Morocco, trout stocking programs have been implemented to increase the genetic diversity of native populations by pooling fish of different origins in the Ras el Ma hatchery (Azrou region) and then stocking them in the different basins. In this study, phylogenetic and phylogeographic patterns, as well as genetic structure and diversity, of Moroccan trout populations were analyzed to evaluate the impact of continuous fish stocking on evolutionary processes in order to better distinguish between natural and human-mediated patterns. Two mitochondrial and nine microsatellite markers were analyzed for all populations along the entire distribution range of brown trout in Morocco. Phylogenetic and phylogeographic analyses rendered two highly divergent evolutionary lineages, one comprising populations in the Drâa Basin and a second grouping the remaining Moroccan populations. Divergence of the Drâa lineage occurred during the Upper Pliocene, whilst differentiation within the second lineage coincided with the onset of the Pleistocene. Genetic structuring among populations was evident. Nevertheless, populations exhibiting higher levels of genetic diversity were those affected by human-mediated processes, making it difficult to associate this diversity with natural processes. In fact, highly geographically isolated, not stocked populations showed the lowest values of genetic diversity. Although stocking management may increase the genetic diversity of these populations, it could also lead to the loss of local adaptive genotypes. Hence, current trout conservation programs should be revised.
Distribution of disease-causing germline mutations in coiled-coils suggests essential role of their N-terminal region

Next-generation sequencing resulted in the identification of a huge number of naturally occurring variations in human proteins. The correct interpretation of the functional effects of these variations necessitates the understanding of how they modulate protein structure. Coiled-coils are α-helical structures responsible for a diverse range of functions, but most importantly, they facilitate the structural organization of macromolecular scaffolds via oligomerization. In this study, we analyzed a comprehensive set of disease-associated germline mutations in coiled-coil structures. Our results highlight the essential role of residues near the N-terminal part of coiled-coil regions, possibly critical for superhelix assembly and folding in some cases. We also show that coiled-coils of different oligomerization states exhibit characteristically distinct patterns of disease-causing mutations. Our study provides structural and functional explanations on how disease emerges through the mutation of these structural motifs.
Spatio-temporal responses of butterflies to global warming on a Mediterranean island over two decades

In recent decades, efforts have been made to understand how global warming affects biodiversity and in this regard butterflies have emerged as a model group. The most conspicuous sign that warming is affecting the ecology of butterflies are the phenological advances occurring in many species. Moreover, rising temperatures are having a notable impact – both negative and positive – on population abundances. To date, patterns have generally been analysed at species level without taking into account possible differences between populations, which, when they are noted, are mostly attributed to large-scale climate differences across a latitudinal gradient. In this work, we use a long-term database of butterflies from the island of Menorca (Balearic Islands, Spain) to investigate how phenology and population dynamics have been affected by climate warming during the past two decades. In addition, we assess how responses are modulated by habitat characteristics and by species’ biological cycles. Our results show that species respond differently to warming at a local scale depending on season and habitat, and that coastal habitats in the Mediterranean region are particularly sensitive to the effects of climate change. Furthermore, our findings suggest that the effects of temperature could be partially offset in more inland habitats such as forests and deep ravines. The positive effect of temperature on ravine populations during the summer suggests that butterflies disperse across habitats as a response to rising temperatures during the season. This type of dispersal behaviour as a response to warming could be especially important in island ecosystems where the possibilities of modifying altitudinal or latitudinal distributions are often severely limited.
ProteinGCN: Protein model quality assessment using Graph Convolutional Networks

Blind estimation of local (per-residue) and global (for the whole structure) accuracies in protein structure models is an essential step in many protein modeling applications. With the recent developments in deep-learning, single-model quality assessment methods have been also advanced, primarily through the use of 2D and 3D convolutional deep neural networks. Here we explore an alternative approach and train a graph convolutional network with nodes representing protein atoms and edges connecting spatially adjacent atom pairs on the dataset Rosetta-300k which contains a set of 300k conformations from 2,897 proteins. We show that our proposed architecture, ProteinGCN, is capable of predicting both local and global accuracies in protein models at state-of-the-art levels. Further, the number of free parameters in ProteinGCN is almost 1-2 orders of magnitude smaller compared to the 3D convolutional networks proposed earlier. We provide the source code of our work to encourage reproducible research.1
GUNGEN-Heartbeat: A Support System for High Quality Idea Generation Using Heartbeat Variance

SUMMARY We propose an idea generation support system known as the “GUNGEN-Heartbeat” that uses heartbeat variations for creating high quality ideas during brainstorming. This system shows “An indication of a check list” or “An indication to promote deep breathing” at time beyond a value with variance of heart rates. We also carried out comparison experiments to evaluate the usefulness of the system.
Density and Kinetics of IKr and IKs in Guinea Pig and Rabbit Ventricular Myocytes Explain Different Efficacy of IKs Blockade at High Heart Rate in Guinea Pig and Rabbit

Background— Class III antiarrhythmic agents commonly exhibit reverse frequency-dependent prolongation of the action potential duration (APD). This is undesirable because of the danger of bradycardia-related arrhythmias and the limited protection against ventricular tachyarrhythmias. The effects of blockade of separate components of delayed rectifier K+ current (IK) may help to develop agents effective at high heart rate. Methods and Results— We assessed the density and kinetics of the 2 components of the delayed rectifier K+ current, IKr and IKs, in rabbit and guinea pig ventricular myocytes. The effects of their specific blockers (chromanol 293B for IKs and E-4031 for IKr) on the action potential was studied at different heart rates by use of whole-cell patch-clamp techniques. In guinea pig ventricular myocytes only, blockade of IKs causes APD prolongation in a frequency-independent manner, whereas blockade of IKs in rabbit ventricular myocytes shows reverse frequency dependence, as does blockade of IKr .
Improving Seeded k-Means Clustering with Deviation- and Entropy-Based Term Weightings

SUMMARY The outcome of document clustering depends on the scheme used to assign a weight to each term in a document. While recent works have tried to use distributions related to class to enhance the discrimination ability. It is worth exploring whether a deviation approach or an entropy approach is more e ﬀ ective. This paper presents a comparison be-tween deviation-based distribution and entropy-based distribution as constraints in term weighting. In addition, their potential combinations are investigated to ﬁnd optimal solutions in guiding the clustering process. In the experiments, the seeded k-means method is used for clustering, and the performances of deviation-based, entropy-based, and hybrid approaches, are analyzed using two English and one Thai text datasets. The result showed that the deviation-based distribution outperformed the entropy-based distribution, and a suitable combination of these distributions increases the clustering accuracy by 10%.
The Effect of Axis-Wise Triaxial Acceleration Data Fusion in CNN-Based Human Activity Recognition

SUMMARY The triaxial accelerometer is one of the most important sensors for human activity recognition (HAR). It has been observed that the relations between the axes of a triaxial accelerometer plays a signiﬁ-cant role in improving the accuracy of activity recognition. However, the existing research rarely focuses on these relations, but rather on the fusion of multiple sensors. In this paper, we propose a data fusion-based convolutional neural network (CNN) approach to e ﬀ ectively use the relations between the axes. We design a single-channel data fusion method and multichannel data fusion method in consideration of the diversiﬁed formats of sensor data. After obtaining the fused data, a CNN is used to extract the features and perform classiﬁcation. The experiments show that the proposed approach has an advantage over the CNN in accuracy. Moreover, the single-channel model achieves an accuracy of 98.83% with the WISDM dataset, which is higher than that of state-of-the-art methods.
A temperate endotherm trades thermoregulation for self-preservation: stress-induced changes in surface temperature as thermoregulatory trade-offs

Coping with stressors can require substantial energetic investment, and when resources are limited, such investment can preclude simultaneous expenditure on other biological processes. Among endotherms, energetic demands of thermoregulation can be immense, yet whether a stress response is sufficient to induce changes in thermoregulatory investment appears unexplored. We tested the hypothesis that stress-induced changes in surface temperature, a well-documented phenomenon across vertebrates, stem from a trade-off between thermoregulation and stress responsiveness, whereby individuals seek to reduce energetic expenditure on thermoregulation in challenging environments (the “Thermoprotective Hypothesis”). We predicted that surface temperature and dry heat loss of individuals that are resource-limited would fall under stress exposure at low ambient temperatures and rise under stress exposure at high ambient temperatures when compared with non-resource limited individuals. To test our predictions, we exposed Black-capped Chickadees to rotating stressors and control treatments (ndays/treatment = 30; paired treatments) across an ambient temperature gradient whilst remotely monitoring both feeding behaviour and surface temperature. Supporting the Thermoprotective Hypothesis, our results showed that: 1) social subordinates (n = 12), who fed less than social dominants and alone suffered stress-induced declines in mass, displayed significantly larger changes in surface temperature following stress exposure than social dominants (n = 8), and 2) stress-induced changes in surface temperature significantly increased heat conservation at low ambient temperature, and heat dissipation at high ambient temperature among social subordinates alone. These results suggest that Black-capped Chickadees adjust their thermoregulatory strategies under stress when resources are limited and support the hypothesis that stress-induced changes in temperature are functionally significant. Data Availability Statement: All data and R code used for the construction of this study are available at: https://datadryad.org/stash/share/QzmRV875_S5IYpMT0jxOYIsoO-ua0T3LX6AA9u-XpdQ.
Modulating functional amyloid formation via alternative splicing of the premelanosomal protein PMEL17

The premelanosomal protein (PMEL17) forms functional amyloid fibrils involved in melanin biosynthesis. Multiple PMEL17 isoforms are produced, two of which arise from excision of a cryptic intron within the amyloid-forming repeat (RPT) domain, leading to long (lRPT) and short (sRPT) isoforms with 10 and 7 imperfect repeats, respectively. Both lRPT and sRPT isoforms undergo similar pH-dependent mechanisms of amyloid formation and fibril dissolution. Here, using human PMEL17, we tested the hypothesis that the minor, but more aggregation-prone, sRPT facilitates amyloid formation of lRPT. We observed that cross-seeding by sRPT fibrils accelerates the rate of lRPT aggregation, resulting in propagation of an sRPT-like twisted fibril morphology, unlike the rodlike structure that lRPT normally adopts. This templating was specific, as the reversed reaction inhibited sRPT fibril formation. Despite displaying ultrastructural differences, self- and cross-seeded lRPT fibrils had a similar β-sheet structured core, revealed by Raman spectroscopy, limited-proteolysis, and fibril disaggregation experiments, suggesting the fibril twist is modulated by N-terminal residues outside the amyloid core. Interestingly, bioinformatics analysis of PMEL17 homologs from other mammals uncovered that long and short RPT isoforms are conserved among members of this phylogenetic group. Collectively, our results indicate that the short isoform of RPT serves as a “nucleator” of PMEL17 functional amyloid formation, mirroring how bacterial functional amyloids assemble during biofilm formation. Whereas bacteria regulate amyloid assembly by using individual genes within the same operon, we propose that the modulation of functional amyloid formation in higher organisms can be accomplished through alternative splicing.
Oral Charcoal Adsorbents Attenuate Neointima Formation of Arteriovenous Fistulas

Chronic kidney disease (CKD) accelerates the development of neointima formation at the anastomosis site of arteriovenous (AV) fistulas. Accumulation of certain uremic toxins has a deleterious effect on the cardiovascular system. The oral charcoal adsorbent, AST-120, reduces circulating and tissue uremic toxins, but its effect on neointima formation at an AV fistula is unknown. To understand the effect of CKD and AST-120 on neointima formation, we created AV fistulas (common carotid artery to the external jugular vein in an end-to-side anastomosis) in mice with and without CKD. AST-120 was administered in chow before and after AV fistula creation. Administration of AST-120 significantly decreased serum indoxyl sulfate levels in CKD mice. CKD mice had a larger neointima area than non-CKD mice, and administration of AST-120 in CKD mice attenuated neointima formation. Both smooth muscle cell and fibrin components were increased in CKD mice, and AST-120 decreased both. RNA expression of MMP-2, MMP-9, TNFα, and TGFβ was increased in neointima tissue of CKD mice, and AST-120 administration neutralized the expression. Our results provided in vivo evidence to support the role of uremic toxin-binding therapy on the prevention of neointima formation. Peri-operative AST-120 administration deserves further investigation as a potential therapy to improve AV fistula patency.
SAT0114 Trends in the incidence of solid tumors in patients with rheumatoid arthritis in spain. a national observational cohort study.

Background During the last 20 years, the rheumatoid arthritis (RA) treatment has changed. Considering the increasing use of biological immunomodulators to treat this desease and the concern that immunomodulation may alter cancer risk, it’s important to know the tumors incidence in RA. Objectives To analyze the incidence and trend of hospital admissions for solid tumors in patients with RA in Spain during the period between 1999 and 2015. Methods This is a retrospective population based study. We analized a national administrative database that includes a Minimum Basic Data Set (MBDS) of all hospital admissions of RA patients. Period: 1999 to 2015. We selected the MBDS for solid tumors. Cases were identified by the presence in primary and secondary diagnosis of ICD 9 codes. The population at risk was estimated through the population census of the National Institute of Statistics, with an estimated prevalence of RA of 0,5% (women: 0,8%, men:0,2%). Crude and adjusted rates of the solid tumors were calculated. The trend was analyzed by Generalized Linear Model (GLM). Results 338.343 RA hospital admissions were detected in the study period, being 18.401 (5,4%) due to solid tumors. The main clinical-demographic characteristics are shown in the next table. Total Women Men P value N (%) 18.401 (5,4) 8689 (3,8) 9712 (8,6) P<0,001 Age, mean (SD) 69,98 (11,21) 68,62 (12,3) 71,20 (9,99) P<0,001 In-hospital exitus n (%) 2455 (13,34) 1035 (11,9) 1420 (14,62) P<0,001 Charlson Index, mean (SD) 5,72 (2,95) 5,63 (2,95) 5,80 (2,95) P<0,001 Stay, mean (SD) 10,94 (11,6) 10,76 (11,6) 11,1 (11,77) P=0,051 The solid tumor adjusted rate during the study period was 647,53/105 inhabitants/yr (366,97/105 in women and 1792,99/105 in men; relative risk men:women =4,8). This rate increased from 305,65/105 in 1999 to 993,19/105 inhabitants/yr in 2015 (from 814,06/105 in 1999 to 2535,5/105 in 2015 in men; from 181,68/105 in 1999 to 607,71/105 in 2015 in women). The annual age-adjusted rate increased significantly: 7,37% (6,52% in men and 8,02% in women; p≤0,001). figure1 Conclusions There was an increasing incidence of hospital admissions due to solid tumors in RA in Spain during the period 1999-2015. An annual rate increase of 7.37%, is estimated. Disclosure of Interest: None declared