Miracle-dz/UniFAR-FTUs huggingface dataset:
Recombination may occur in the absence of transcription in the immunoglobulin heavy chain recombination centre

Abstract Developing B cells undergo V(D)J recombination to generate a vast repertoire of Ig molecules. V(D)J recombination is initiated by the RAG1/RAG2 complex in recombination centres (RCs), where gene segments become accessible to the complex. Whether transcription is the causal factor of accessibility or whether it is a side product of other processes that generate accessibility remains a controversial issue. At the IgH locus, V(D)J recombination is controlled by Eμ enhancer, which directs the transcriptional, epigenetic and recombinational events in the IgH RC. Deletion of Eμ enhancer affects both transcription and recombination, making it difficult to conclude if Eμ controls the two processes through the same or different mechanisms. By using a mouse line carrying a CpG-rich sequence upstream of Eμ enhancer and analyzing transcription and recombination at the single-cell level, we found that recombination could occur in the RC in the absence of detectable transcription, suggesting that Eμ controls transcription and recombination through distinct mechanisms. Moreover, while the normally Eμ-dependent transcription and demethylating activities were impaired, recruitment of chromatin remodeling complexes was unaffected. RAG1 was efficiently recruited, thus compensating for the defective transcription-associated recruitment of RAG2, and providing a mechanistic basis for RAG1/RAG2 assembly to initiate V(D)J recombination.
Detection of Gait From Continuous Inertial Sensor Data Using Harmonic Frequencies

Mobile gait analysis using wearable inertial measurement units (IMUs) provides valuable insights for the assessment of movement impairments in different neurological and musculoskeletal diseases, for example Parkinson's disease (PD). The increase in data volume due to arising long-term monitoring requires valid, robust and efficient analysis pipelines. In many studies an upstream detection of gait is therefore applied. However, current methods do not provide a robust way to successfully reject non-gait signals. Therefore, we developed a novel algorithm for the detection of gait from continuous inertial data of sensors worn at the feet. The algorithm is focused not only on a high sensitivity but also a high specificity for gait. Sliding windows of IMU signals recorded from the feet of PD patients were processed in the frequency domain. Gait was detected if the frequency spectrum contained specific patterns of harmonic frequencies. The approach was trained and evaluated on 150 clinical measurements containing standardized gait and cyclic movement tests. The detection reached a sensitivity of 0.98 and a specificity of 0.96 for the best sensor configuration (angular rate around the medio-lateral axis). On an independent validation data set including 203 unsupervised, semi-standardized gait tests, the algorithm achieved a sensitivity of 0.97. Our algorithm for the detection of gait from continuous IMU signals works reliably and showed promising results for the application in the context of free-living and non-standardized monitoring scenarios.
Pathogen-Associated Molecular Pattern-Triggered Immunity Involves Proteolytic Degradation of Core Nonsense-Mediated mRNA Decay Factors During the Early Defense Response[OPEN]

Nonsense-mediated mRNA decay is a major regulatory process by which pattern recognition receptors fine-tune resistance gene transcript levels to reduce fitness costs and achieve effective immunity. Nonsense-mediated mRNA decay (NMD), an mRNA quality control process, is thought to function in plant immunity. A subset of fully spliced (FS) transcripts of Arabidopsis (Arabidopsis thaliana) resistance (R) genes are upregulated during bacterial infection. Here, we report that 81.2% and 65.1% of FS natural TIR-NBS-LRR (TNL) and CC-NBS-LRR transcripts, respectively, retain characteristics of NMD regulation, as their transcript levels could be controlled posttranscriptionally. Both bacterial infection and the perception of bacteria by pattern recognition receptors initiated the destruction of core NMD factors UP-FRAMESHIFT1 (UPF1), UPF2, and UPF3 in Arabidopsis within 30 min of inoculation via the independent ubiquitination of UPF1 and UPF3 and their degradation via the 26S proteasome pathway. The induction of UPF1 and UPF3 ubiquitination was delayed in mitogen-activated protein kinase3 (mpk3) and mpk6, but not in salicylic acid-signaling mutants, during the early immune response. Finally, previously uncharacterized TNL-type R transcripts accumulated in upf mutants and conferred disease resistance to infection with a virulent Pseudomonas strain in plants. Our findings demonstrate that NMD is one of the main regulatory processes through which PRRs fine-tune R transcript levels to reduce fitness costs and achieve effective immunity.
Long-Chain acyl-CoA Synthetase LACS2 Contributes to Submergence Tolerance by Modulating Cuticle Permeability in Arabidopsis

In Arabidopsis thaliana, LONG-CHAIN ACYL-COA SYNTHETASEs (LACSs) catalyze the synthesis of long-chain acyl-CoAs and function in diverse biological processes. We have recently revealed that LACS2 is primarily involved in the production of polyunsaturated linolenoyl-CoA, essential for the activation of ethylene response transcription factors-mediated hypoxia signaling. Here, we further reported the dual role of LACS2 in the regulation of submergence tolerance by modulating cuticle permeability in Arabidopsis cells. LACS2-overexpressors (LACS2-OEs) showed improved tolerance to submergence, with higher accumulation of cuticular wax and cutin in their rosettes. In contrast, knockout of LACS2 in the lacs2-3 mutant resulted in hypersensitivity to submergence with reduced wax crystals and thinner cutin layer. By analyses of plant surface permeability, we observed that the hypoxic sensitivities in the LACS2-OEs and lacs2-3 mutant were physiologically correlated with chlorophyll leaching, water loss rates, ionic leakage, and gas exchange. Thus, our findings suggest the role of LACS2 in plant response to submergence by modulating cuticle permeability in plant cells.
Structural sequence evolution and Computational Modeling Approaches of the Complement System in Leishmaniasis

The complement system acts as central arm of innate immunity that is critical to host defense as well as the development of adaptive immunity. The origins of the complement system have so far been traced, which correlates to near to the beginnings of multi-cellular animal life. Owing to the difficulty in obtaining crystal structures of GPCRs in either inactive or active state, accurate structural modeling is still highly desirable for the majority of GPCRs. In an attempt to dissect the conformational changes associated with GPCR activation, computational modeling approaches is being pursued in this paper along with the evolutionary divergence to deal with the structural variability.
Rotatable source crossed molecular beams apparatus with pulsed ultraviolet/vacuum ultraviolet photoionization detection

A newly constructed universal crossed molecular beams apparatus for studies of bimolecular chemical reaction dynamics is described. The apparatus employs two rotatable molecular beam sources and a fixed ultrahigh vacuum (UHV) quadrupole mass spectrometer with electron impact or pulsed photoionization of reaction products. Electronically cold neutral supersonic transition metal atomic beams are produced in one of the rotatable sources using laser vaporization. The beams are characterized by laser induced fluorescence spectroscopy, photodepletion spectroscopy, and time-of-flight analysis. Photoionization of the ZrC2H2 products from the crossed beam reaction Zr+C2H4→ZrC2H2+H2 is carried out using the pulsed 157 nm radiation from a F2 excimer laser in the UHV region of the mass spectrometer. Compared to conventional electron impact ionization, 157 nm photoionization improves signal-to-noise ratios by more than two orders of magnitude for experiments using pulsed beam sources where cross correlation methods ca.
Transforming Ocean Conservation: Applying the Genetic Rescue Toolkit

Although oceans provide critical ecosystem services and support the most abundant populations on earth, the extent of damage impacting oceans and the diversity of strategies to protect them is disconcertingly, and disproportionately, understudied. While conventional modes of conservation have made strides in mitigating impacts of human activities on ocean ecosystems, those strategies alone cannot completely stem the tide of mounting threats. Biotechnology and genomic research should be harnessed and developed within conservation frameworks to foster the persistence of viable ocean ecosystems. This document distills the results of a targeted survey, the Ocean Genomics Horizon Scan, which assessed opportunities to bring novel genetic rescue tools to marine conservation. From this Horizon Scan, we have identified how novel approaches from synthetic biology and genomics can alleviate major marine threats. While ethical frameworks for biotechnological interventions are necessary for effective and responsible practice, here we primarily assessed technological and social factors directly affecting technical development and deployment of biotechnology interventions for marine conservation. Genetic insight can greatly enhance established conservation methods, but the severity of many threats may demand genomic intervention. While intervention is controversial, for many marine areas the cost of inaction is too high to allow controversy to be a barrier to conserving viable ecosystems. Here, we offer a set of recommendations for engagement and program development to deploy genetic rescue safely and responsibly.
Cas3 Protein—A Review of a Multi-Tasking Machine

Cas3 has essential functions in CRISPR immunity but its other activities and roles, in vitro and in cells, are less widely known. We offer a concise review of the latest understanding and questions arising from studies of Cas3 mechanism during CRISPR immunity, and highlight recent attempts at using Cas3 for genetic editing. We then spotlight involvement of Cas3 in other aspects of cell biology, for which understanding is lacking—these focus on CRISPR systems as regulators of cellular processes in addition to defense against mobile genetic elements.
Early Screening of the Autism Spectrum Disorders: Validity Properties and Cross-Cultural Generalizability of the First Year Inventory in Italy

This study examined the cross-cultural generalisability of the First Year Inventory (FYI) on an Italian sample, testing its construct validity, consistency, and structural validity. Six hundred ninety-eight parents of children aged 11–13 months completed the questionnaire. Similarities between analyses of Italian and American/Israeli samples were found, as were demonstrations of the instrument’s construct validity and internal consistency with both groups. The original factorial structure was not demonstrated; thus, a new factorial structure was tested, and a short version of the FYI was demonstrated via confirmatory factor analysis. The findings supported the generalisability of the Italian version of the FYI and its validity. The FYI may aid in medical decision-making on further steps for referral of the child to an early diagnostic assessment.
CRISPR/Cas9-Mediated Mutagenesis of RCO in Cardamine hirsuta

The small crucifer Cardamine hirsuta bears complex leaves divided into leaflets. This is in contrast to its relative, the reference plant Arabidopsis thaliana, which has simple leaves. Comparative studies between these species provide attractive opportunities to study the diversification of form. Here, we report on the implementation of the CRISPR/Cas9 genome editing methodology in C. hirsuta and with it the generation of novel alleles in the RCO gene, which was previously shown to play a major role in the diversification of form between the two species. Thus, genome editing can now be deployed in C. hirsuta, thereby increasing its versatility as a model system to study gene function and evolution.
Preprocessing, analysis and quantification in single‐voxel magnetic resonance spectroscopy: experts' consensus recommendations

Once an MRS dataset has been acquired, several important steps must be taken to obtain the desired metabolite concentration measures. First, the data must be preprocessed to prepare them for analysis. Next, the intensity of the metabolite signal(s) of interest must be estimated. Finally, the measured metabolite signal intensities must be converted into scaled concentration units employing a quantitative reference signal to allow meaningful interpretation. In this paper, we review these three main steps in the post‐acquisition workflow of a single‐voxel MRS experiment (preprocessing, analysis and quantification) and provide recommendations for best practices at each step.
Comparative effects of two heat acclimation protocols consisting of high-intensity interval training in the heat on aerobic performance and thermoregulatory responses in exercising rats

Acclimation resulting from low- to moderate-intensity physical exertion in the heat induces several thermoregulatory adaptations, including slower exercise-induced increases in core body temperature. However, few studies have investigated the thermoregulatory adaptations induced by high-intensity interval training (HIIT) protocols. Thus, the present study aimed to compare the adaptations in rats’ thermoregulatory parameters and aerobic performance observed after two different heat acclimation regimens consisting of HIIT protocols performed in a hot environment. Twenty-three adult male Wistar rats were initially subjected to an incremental-speed exercise at 32°C until they were fatigued and then randomly assigned to one of the following three heat acclimation strategies: passive heat exposure without any exercise (untrained controls–UN; n = 7), HIIT performed at the maximal aerobic speed (HIIT100%; n = 8) and HIIT performed at a high but submaximal speed (HIIT85%; n = 8). Following the two weeks of interventions, the rats were again subjected to a fatiguing incremental exercise at 32°C, while their colonic temperature (TCOL) was recorded. The workload performed by the rats and their thermoregulatory efficiency were calculated. After the intervention period, rats subjected to both HIIT protocols attained greater workloads (HIIT100%: 313.7 ± 21.9 J vs. HIIT85%: 318.1 ± 32.6 J vs. UN: 250.8 ± 32.4 J; p < 0.01) and presented a lower ratio between the change in TCOL and the distance travelled (HIIT100%: 4.95 ± 0.42°C/km vs. HIIT85%: 4.33 ± 0.59°C/km vs. UN: 6.14 ± 1.03°C/km; p < 0.001) when compared to UN rats. The latter finding indicates better thermoregulatory efficiency in trained animals. No differences were observed between rats subjected to the two HIIT regimens. In conclusion, the two HIIT protocols induce greater thermoregulatory adaptations and performance improvements than passive heat exposure. These adaptations do not differ between the two training protocols investigated in the present study.
Self-Supervised Multi-View Person Association and its Applications

Reliable markerless motion tracking of people participating in a complex group activity from multiple moving cameras is challenging due to frequent occlusions, strong viewpoint and appearance variations, and asynchronous video streams. To solve this problem, reliable association of the same person across distant viewpoints and temporal instances is essential. We present a self-supervised framework to adapt a generic person appearance descriptor to the unlabeled videos by exploiting motion tracking, mutual exclusion constraints, and multi-view geometry. The adapted discriminative descriptor is used in a tracking-by-clustering formulation. We validate the effectiveness of our descriptor learning on WILDTRACK T. Chavdarova et al., “WILDTRACK: A multi-camera HD dataset for dense unscripted pedestrian detection,” in Proc. IEEE Conf. Comput. Vis. Pattern Recognit. , 2018, pp. 5030–5039. and three new complex social scenes captured by multiple cameras with up to 60 people “in the wild”. We report significant improvement in association accuracy (up to 18 percent) and stable and coherent 3D human skeleton tracking (5 to 10 times) over the baseline. Using the reconstructed 3D skeletons, we cut the input videos into a multi-angle video where the image of a specified person is shown from the best visible front-facing camera. Our algorithm detects inter-human occlusion to determine the camera switching moment while still maintaining the flow of the action well. Website: http://www.cs. cmu.edu/~ILIM/projects/IM/Association4Tracking.
HNRNPA1-induced spliceopathy in a transgenic mouse model of myotonic dystrophy

Significance Myotonic dystrophy type 1 (DM1) is a model for RNA-mediated disease in microsatellite expansion disorders. DM1 is caused by CTG expansions (CTGexp) and expression of CUGexp RNAs that sequester muscleblind-like (MBNL) proteins, while also triggering hyperphosphorylation of CUGBP1/ETR3-like factor 1 (CELF1). These proteins regulate developmental transitions in RNA processing, so DM1 is characterized by retention of fetal RNA processing patterns in adults. Although current evidence indicates that CELF1 is a specific antagonist of MBNL activity, this study reveals that another protein, HNRNPA1, is also downregulated during normal development but upregulated in DM1, where it also induces fetal splicing shifts. Thus, DM1 disease results from an imbalance in the expression of multiple RNA processing factors important for both proliferation and differentiation. Studies on myotonic dystrophy type 1 (DM1) have led to the RNA-mediated disease model for hereditary disorders caused by noncoding microsatellite expansions. This model proposes that DM1 disease manifestations are caused by a reversion to fetal RNA processing patterns in adult tissues due to the expression of toxic CUG RNA expansions (CUGexp) leading to decreased muscleblind-like, but increased CUGBP1/ETR3-like factor 1 (CELF1), alternative splicing activities. Here, we test this model in vivo, using the mouse HSALR poly(CUG) model for DM1 and recombinant adeno-associated virus (rAAV)-mediated transduction of specific splicing factors. Surprisingly, systemic overexpression of HNRNPA1, not previously linked to DM1, also shifted DM1-relevant splicing targets to fetal isoforms, resulting in more severe muscle weakness/myopathy as early as 4 to 6 wk posttransduction, whereas rAAV controls were unaffected. Overexpression of HNRNPA1 promotes fetal exon inclusion of representative DM1-relevant splicing targets in differentiated myoblasts, and HITS-CLIP of rAAV-mycHnrnpa1-injected muscle revealed direct interactions of HNRNPA1 with these targets in vivo. Similar to CELF1, HNRNPA1 protein levels decrease during postnatal development, but are elevated in both regenerating mouse muscle and DM1 skeletal muscle. Our studies suggest that CUGexp RNA triggers abnormal expression of multiple nuclear RNA binding proteins, including CELF1 and HNRNPA1, that antagonize MBNL activity to promote fetal splicing patterns.
Performance under pressure in skill tasks: An analysis of professional darts

Understanding and predicting how individuals perform in high-pressure situations is of importance in designing and managing workplaces. We investigate performance under pressure in professional darts as a near-ideal setting with no direct interaction between players and a high number of observations per subject. Analyzing almost one year of tournament data covering 32,274 dart throws, we find no evidence in favor of either choking or excelling under pressure.
Pollinator visitation rate and effectiveness vary with flowering phenology.

PREMISE Flowering time may influence pollination success and seed set through a variety of mechanisms, including seasonal changes in total pollinator visitation or the composition and effectiveness of pollinator visitors. METHODS We investigated mechanisms by which changes in flowering phenology influence pollination and reproductive success of Mertensia ciliata (Boraginaceae). We manipulated flowering onset of potted plants and assessed the frequency and composition of pollinator visitors, as well as seed set. We tested whether floral visitors differed in their effectiveness as pollinators by measuring pollen receipt and seed set resulting from single visits to virgin flowers. RESULTS Despite a five-fold decrease in pollinator visitation over four weeks, we detected no significant difference in seed set among plants blooming at different times. On a per-visit basis, each bumblebee transferred more conspecific pollen than did a solitary bee or a fly. The proportion of visits by bumblebees increased over the season, countering the decrease in visitation rate so that flowering time had little net effect on seed set. CONCLUSIONS This work illustrates the need to consider pollinator effectiveness, along with changes in pollinator visitation and species composition to understand the mechanisms by which phenology affects levels of pollination.
Aging Biomarkers: From Functional Tests to Multi‐Omics Approaches

Aging results in various deleterious changes in the human body that may lead to loss of function and the manifestation of chronic diseases. While diseases can generally be reliably diagnosed, the aging process itself requires more sophisticated approaches to evaluate its progression. Numerous attempts have been made to establish biomarkers to quantify human aging at the cellular, tissue, and organismal level. Here, an up‐to‐date overview of biomarkers related to human aging with an emphasis on biomarkers that take into account different mechanisms of aging between individuals is provided. Classical discrete molecular and non‐molecular biomarkers handpicked by researches on the base of their strong correlation with age, as well as emerging omics‐based biomarkers, are discussed and potential future directions and developments in the field of aging assessment are outlined.
Reduction in lignin content and increase in the antioxidant capacity of corn and sugarcane silages treated with an enzymatic complex produced by white rot fungus

The objective was to evaluate the effect of the addition of 0, 10, 20, and 30 mg.kg-1 of natural matter of a lignocellulosic enzymatic complex produced by the white rot fungus on the chemical composition, cumulative gas production in vitro, and antioxidant compounds of corn and sugarcane silages. After being chopped and treated with the enzymatic complex, the plants were packed in vacuum-sealed bags. After 60 days, the mini silos were opened and the samples were dried in a forced ventilation oven at 55 °C for analysis of the proposed parameters. The experiment was conducted in a completely randomized design with four replicates per treatment. In the corn silage, there was a linear reduction in the lignin concentration. In the sugarcane silage showed a reduction of 12% in the lignin concentration, a linear reduction in the hemicellulose content, and a decrease of 8% in the cellulose concentration compared to the control treatment. The lignin monomers had linear increases in the syringyl:guaiacil ratio. This reflected on significant increases in the concentration of the non-fibrous carbohydrates and the A + B1 fraction of the carbohydrates, and a reduction in the C fraction. The in vitro gas production increased, the time of colonization and initiation of in vitro fermentation linearly decreased in both silages. The phenolic compounds and the antioxidant capacity increased linearly with the addition of the enzymes in both silages. The addition of the lignocellulolytic enzymes to the silages caused changes in the cell wall, resulting in improvements in the in vitro fermentative parameters, besides the additional effect on the antioxidant capacity. There was an effect of the addition of the enzymes on the evaluated fodder, and the best concentration was, on average, 20 mg kg-1 MN for corn silage and 10 mg kg-1 NM for sugarcane silage.