Miracle-dz/UniFAR-FTUs huggingface dataset:
Stitching together the Multiple Dimensions of Autophagy Using Metabolomics and Transcriptomics Reveals Impacts on Metabolism, Development, and Plant Responses to the Environment in Arabidopsis[C][W]

We performed transcriptomic and metabolomic analysis of rosette leaves of Arabidopsis autophagy mutants to elucidate the housekeeping process of autophagy, which plays a key role in immunity, senescence, nutrient recycling, and environmental adaptation. We deciphered the wide range of effects generated by autophagy defects in plants and uncovered links between autophagy, metabolism, and signaling. Autophagy is a fundamental process in the plant life story, playing a key role in immunity, senescence, nutrient recycling, and adaptation to the environment. Transcriptomics and metabolomics of the rosette leaves of Arabidopsis thaliana autophagy mutants (atg) show that autophagy is essential for cell homeostasis and stress responses and that several metabolic pathways are affected. Depletion of hexoses, quercetins, and anthocyanins parallel the overaccumulation of several amino acids and related compounds, such as glutamate, methionine, glutathione, pipecolate, and 2-aminoadipate. Transcriptomic data show that the pathways for glutathione, methionine, raffinose, galacturonate, and anthocyanin are perturbed. Anthocyanin depletion in atg mutants, which was previously reported as a possible defect in flavonoid trafficking to the vacuole, appears due to the downregulation of the master genes encoding the enzymes and regulatory proteins involved in flavonoid biosynthesis. Overexpression of the PRODUCTION OF ANTHOCYANIN PIGMENT1 transcription factor restores anthocyanin accumulation in vacuoles of atg mutants. Transcriptome analyses reveal connections between autophagy and (1) salicylic acid biosynthesis and response, (2) cytokinin perception, (3) oxidative stress and plant defense, and possible interactions between autophagy and the COP9 signalosome machinery. The metabolic and transcriptomic signatures identified for the autophagy mutants are discussed and show consistencies with the observed phenotypes.
Female influence on pre‐ and post‐copulatory sexual selection and its genetic basis in Drosophila melanogaster

Genetic variation among females is likely to influence the outcome of both pre‐ and post‐copulatory sexual selection in Drosophila melanogaster. Here we use association testing to survey natural variation in 10 candidate female genes for their effects on female reproduction. Females from 91 chromosome two substitution lines were scored for phenotypes affecting pre‐ and post‐copulatory sexual selection such as mating and remating rate, propensity to use sperm from the second male to mate, and measures of fertility. There were significant genetic contributions to phenotypic variation for all the traits measured. Resequencing of the 10 candidate genes in the 91 lines yielded 68 non‐synonymous polymorphisms which were tested for associations with the measured phenotypes. Twelve significant associations (markerwise P < 0.01) were identified. Polymorphisms in the putative serine protease homolog CG9897 and the putative odorant binding protein CG11797 associated with female propensity to remate and met an experimentwise significance of P < 0.05. Several other associations, including those impacting both fertility and female remating rate suggest that sperm storage might be an important factor mitigating female influence on sexual selection.
Different rates of DNA replication at early versus late S‐phase sections: Multiscale modeling of stochastic events related to DNA content/EdU (5‐ethynyl‐2′deoxyuridine) incorporation distributions

Mathematical modeling allows relating molecular events to single‐cell characteristics assessed by multiparameter cytometry. In the present study we labeled newly synthesized DNA in A549 human lung carcinoma cells with 15–120 min pulses of EdU. All DNA was stained with DAPI and cellular fluorescence was measured by laser scanning cytometry. The frequency of cells in the ascending (left) side of the “horseshoe”‐shaped EdU/DAPI bivariate distributions reports the rate of DNA replication at the time of entrance to S phase while their frequency in the descending (right) side is a marker of DNA replication rate at the time of transition from S to G2 phase. To understand the connection between molecular‐scale events and scatterplot asymmetry, we developed a multiscale stochastic model, which simulates DNA replication and cell cycle progression of individual cells and produces in silico EdU/DAPI scatterplots. For each S‐phase cell the time points at which replication origins are fired are modeled by a non‐homogeneous Poisson Process (NHPP). Shifted gamma distributions are assumed for durations of cell cycle phases (G1, S and G2M), Depending on the rate of DNA synthesis being an increasing or decreasing function, simulated EdU/DAPI bivariate graphs show predominance of cells in left (early‐S) or right (late‐S) side of the horseshoe distribution. Assuming NHPP rate estimated from independent experiments, simulated EdU/DAPI graphs are nearly indistinguishable from those experimentally observed. This finding proves consistency between the S‐phase DNA‐replication rate based on molecular‐scale analyses, and cell population kinetics ascertained from EdU/DAPI scatterplots and demonstrates that DNA replication rate at entrance to S is relatively slow compared with its rather abrupt termination during S to G2 transition. Our approach opens a possibility of similar modeling to study the effect of anticancer drugs on DNA replication/cell cycle progression and also to quantify other kinetic events that can be measured during S‐phase. © 2014 International Society for Advancement of Cytometry
Construct and criterion validity of several proposed DAS28-based rheumatoid arthritis flare criteria: an OMERACT cohort validation study

Background To describe rheumatoid arthritis (RA) worsening that leads to change or re-initiation of treatment, several Disease Activity Score 28 (DAS28)-based flare criteria have been described, but none validated. Methods Six previously published DAS28-based flare criteria ((1) increase in DAS28 >1.2, or >0.6 if DAS28 >5.1; (2) increase in DAS28 >1.2, or >0.6 if DAS28 ≥3.2; (3) increase >0.6 or DAS28 >3.2; (4) increase in DAS28 >1.2; (5) DAS28 >3.2; (6) DAS28 >2.6) were tested against five hypotheses concerning criterion and construct validity: (1+2) Sensitivity and specificity >70% compared with patient's/physician's judgment; (3) difference in proportion with disease modifying anti-rheumatic drug/corticosteroid initiation/increase >0.2; (4) mean difference in C-reactive protein (CRP) >10 mg/l; and (5) no statistical difference in Short Form-36 Mental Health subscale change. Three different RA patient databases in which flare might occur were used. Sensitivity/specificity, χ2 and two-sample student t test analyses were done. Results The analyses included 51, 147 and 744 RA patients, from the three databases. Criterion 2 fulfilled most hypotheses: 4 out of 5. Sensitivity and specificity varied between 63%–78% and 84%–92%. Construct validity was demonstrated with 23% more treatment change, higher mean CRP (11.4 mg/l) and depression scale change of −5. Criteria 3, 5 and 6 were more sensitive, criteria 1, 2 and 4 more specific. Conclusions An increase in DAS28 >1.2 or >0.6 if DAS28 ≥3.2 appears most discriminating and valid by our predefined validation criteria. Considering the other criteria, sensitivity and specificity shown here might facilitate use in different settings.
Clinical Trials of Therapeutic Ocular Surface Medium for Moderate to Severe Dry Eye

Purpose: To investigate therapeutic ocular surface medium (TOSM), a potential physiological tear replacement therapy, for moderate to severe dry eye. Methods: Forty-six patients with symptoms of moderate to severe dry eye despite maximal standard therapy were enrolled in a prospective pilot study of TOSM over 1 month (n = 10) and a randomized, double-masked, controlled trial of TOSM versus saline (placebo) over 2 months (n = 36). The primary outcome measure was conjunctival rose bengal staining. Results: An improvement in conjunctival rose bengal staining by ≥3 points occurred in 7 of 10 patients receiving TOSM in the pilot study (P = 0.017) and in 8 of 18 patients (44%) in the randomized trial (P = 0.982). In the pilot study, subjective dry eye symptoms significantly improved (P = 0.005). TOSM significantly improved the blepharitis score (P = 0.002) and conjunctival impression cytology (P = 0.028) in the randomized controlled trial. There were no serious or irreversible side effects with TOSM. Conclusions: TOSM is a physiological tear replacement for dry eye that, unlike autologous serum, can be easily manufactured, could be widely available, and may also be beneficial for blepharitis.
Association of hormone replacement therapy to estrogen and progesterone receptor status in invasive breast carcinoma

Observational studies and randomized trials have demonstrated that hormone replacement therapy (HRT) increases the recipient's risk of developing breast carcinoma. Because it is known that some breast malignancies are hormonally responsive and that others are not, it has been hypothesized that HRT may be associated with the development of estrogen receptor (ER)‐positive/progesterone receptor (PR)‐positive breast carcinoma more so than with the development of ER‐negative/PR‐negative breast carcinoma.
Simultaneous imaging of Ca2+ signals in interstitial cells of Cajal and longitudinal smooth muscle cells during rhythmic activity in mouse ileum

Electrical rhythmicity in smooth muscle cells is essential for the movement of the gastrointestinal tract. Interstitial cells of Cajal (ICC) lie adjacent to smooth muscle layers and are implicated as the pacemaker cells. However, the pace making mechanism remains unclear. To study the intercellular interaction during electrical rhythm generation, we visualized changes in intracellular Ca2+ concentration ([Ca2+]i) in smooth muscle cells and myenteric ICC within segments of mouse ileum loaded with a fluorescent Ca2+ indicator, fluo‐3. We observed rhythmic [Ca2+]i changes in longitudinal smooth muscle cells travelling rapidly through the smooth muscle cell layer. Between the rhythmic Ca2+ transients, we found brief Ca2+ transients localized to small areas within smooth muscle cells. The amplitude but not the periodicity of rhythmic [Ca2+]i transients in both cell types was partially inhibited by nicardipine, an L‐type Ca2+ channel antagonist, suggesting that the rhythmic [Ca2+]i transients reflect membrane potential depolarizations corresponding to both slow waves and triggered Ca2+ spikes. Longitudinal smooth muscle cells and myenteric ICC showed synchronous spontaneous [Ca2+]i transients in eight out of 21 ileac preparations analysed. In the remaining preparations, the synchrony between ICC and smooth muscle cells was absent, although the rhythmicity of the smooth muscle cells was not disturbed. These results suggest that myenteric ICC may play multiple roles including pace making for physiological bowel movement.
Real-time multi-people tracking by greedy likelihood maximization

Unlike tracking rigid targets, the task of tracking multiple people is very challenging because the appearance and the shape of a person varies depending on the target's location and orientation. This paper presents a new approach to track multiple people with high accuracy using a calibrated monocular camera. Our approach recursively updates the positions of all persons based on the observed foreground image and previously known location of each person. This is done by maximizing the likelihood of observing the foreground image given the positions of all persons. Since the computational complexity of our approach is low, it is possible to run in real time on smart cameras. When a network of multiple smart cameras overseeing the scene is available, local position estimates from smart cameras can be fused to produced more accurate joint position estimates. The performance evaluation of our approach on very challenging video sequences from public datasets shows that our tracker achieves high accuracy. When comparing to other state-of-the-art tracking systems, our method outperforms in terms of Multiple Object Tracking Accuracy (MOTA).
Mode and commodity perspectives on U.S. freight energy consumption and CO2 emissions: Insights and directions for improvement

Abstract In the United States, freight transportation consumes 9% of all energy consumed and emits 12% of all CO2 emissions in the entire economy. Freight energy consumption and CO2 emissions have also been growing faster than those of other economic sectors since 1980. In response, this paper surveys freight energy consumption trends from both a modal-disaggregate (e.g. truck, rail, ship, etc.) and commodity-disaggregate (e.g. food products, wood products, consumer electronics, etc.) perspective. A systems approach is used to delineate the boundary between the freight systems and other economic systems with which it interacts, and to provide a framework for understanding the structure of freight. From a modal perspective, it is found that the amount of freight energy consumed by trucks has remained at about two-thirds of the total for the past two decades. However, there are also some recent examples of growing use of rail, which can be expanded to make U.S. freight less energy intensive. On the commodity side, freight energy use is found to be concentrated in a limited number of products, such as food products, farm products, and nonmetallic minerals, so that collaboration with these industries can provide a focal point for reducing freight energy. The subsequent discussion considers other factors such as changes to supply chains, impact of geographic patterns of freight, dematerialization of products, and transitioning to low-carbon fuels.
Differential expression of Homer family proteins in the developing mouse brain

Homer acts as a postsynaptic adaptor protein that links multiple targets, such as proteins involved in glutamate receptor signaling. We report the differential expression of the long form of Homer proteins produced from three distinctive genes during postnatal development of the mouse brain. Homer 1b/c and Cupidin/Homer 2a/b are widespread throughout the developing brain and are down‐regulated in hindbrain‐origin regions, such as the cerebellum, pons, and medulla oblongata. In contrast, Homer 3a/b is restricted to the cerebellum, hippocampus, and neonatal olfactory bulb. In the cerebellum, Homer 1b/c and Cupidin/Homer 2a/b predominate in the postsynapses of developing granule cells, whereas Homer 3a/b is concentrated in the dendritic spines of Purkinje cells and their axons. The down‐regulation of Homer 1b/c and Cupidin/Homer 2a/b is in marked contrast to the up‐regulation of Homer 3a/b between the first and the second postnatal weeks. In the hippocampus, Homer 1b/c and Cupidin/Homer 2a/b are largely located in the CA1 region and the CA1–CA2 region, respectively, whereas Homer 3a/b is largely distributed in the CA2–CA3 region and peaks around the third postnatal week. In hippocampal cell cultures, Homer 1b/c and Cupidin/Homer 2a/b are expressed in inhibitory and excitatory neurons, whereas Homer 3a/b is largely expressed in excitatory neurons but not in inhibitory neurons. In the developing olfactory bulb, Homer 1b/c and Cupidin/Homer 2a/b are up‐regulated in the granular, external plexiform, and glomerular layers, whereas Homer 3a/b drastically decreases in these regions within the first postnatal week. Cupidin/Homer 2a/b is also expressed in olfactory sensory neurons within a distinct olfactory epithelial zone and is then widely distributed to both the axons in the olfactory nerve layer and the cilia in the olfactory epithelium. These results demonstrate that Homer family members have distinct regional, cellular, and subcellular distributions in time and space during postnatal brain development. J. Comp. Neurol. 473:582–599, 2004. © 2004 Wiley‐Liss, Inc.
Neural basis of imprinting behavior in chicks

Newly hatched chicks memorize the characteristics of the first moving object they encounter, and subsequently show a preference for it. This “imprinting” behavior is an example of infant learning and is elicited by visual and/or auditory cues. Visual information of imprinting stimuli in chicks is first processed in the visual Wulst (VW), a telencephalic area corresponding to the mammalian visual cortex, congregates in the core region of the hyperpallium densocellulare (HDCo) cells, and transmitted to the intermediate medial mesopallium (IMM), a region similar to the mammalian association cortex. The imprinting memory is stored in the IMM, and activities of IMM neurons are altered by imprinting. Imprinting also induces functional and structural plastic changes of neurons in the circuit that links the VW and the IMM. Of these neurons, the activity of the HDCo cells is strongly influenced by imprinting. Expression and modulation of NR2B subunit‐containing N‐methyl‐D‐aspartate (NMDA) receptors in the HDCo cells are crucial for plastic changes in this circuit as well as the process of visual imprinting. Thus, elucidation of cellular and molecular mechanisms underlying the plastic changes that occurred in the HDCo cells may provide useful knowledge about infant learning.
Comprehensive Proteomic Analysis of Human Par Protein Complexes Reveals an Interconnected Protein Network*

The polarization of eukaryotic cells is controlled by the concerted activities of asymmetrically localized proteins. The PAR proteins, first identified in Caenorhabditis elegans, are common regulators of cell polarity conserved from nematode and flies to man. However, little is known about the molecular mechanisms by which these proteins and protein complexes establish cell polarity in mammals. We have mapped multiprotein complexes formed around the putative human Par orthologs MARK4 (microtubule-associated protein/microtubule affinity-regulating kinase 4) (Par-1), Par-3, LKB1 (Par-4), 14-3-3ζ and η (Par-5), Par-6a, -b, -c, and PKCλ (PKC3). We employed a proteomic approach comprising tandem affinity purification (TAP) of protein complexes from cultured cells and protein sequencing by tandem mass spectrometry. From these data we constructed a highly interconnected protein network consisting of three core complex “modules” formed around MARK4 (Par-1), Par-3·Par-6, and LKB1 (Par-4). The network confirms most previously reported interactions. In addition we identified more than 50 novel interactors, some of which, like the 14-3-3 phospho-protein scaffolds, occur in more than one distinct complex. We demonstrate that the complex formation between LKB1·Par-4, PAPK, and Mo25 results in the translocation of LKB1 from the nucleus to the cytoplasm and to tight junctions and show that the LKB1 complex may activate MARKs, which are known to introduce 14-3-3 binding sites into several substrates. Our findings suggest co-regulation and/or signaling events between the distinct Par complexes and provide a basis for further elucidation of the molecular mechanisms that govern cell polarity.
Physical activity in the prevention of coronary heart disease: implications for the clinician

Cardiovascular disease (CVD) continues to be a leading cause of death worldwide. Because regular physical activity (PA) independently decreases the risk of coronary heart disease (CHD) while also having a positive, dose-related impact on other cardiovascular (CV) risk factors, it has increasingly become a focus of CHD prevention. Current guidelines recommend 30 min of moderate-intensity PA 5 days a week, but exercise regimens remain underused. PA adherence can be fostered with a multilevel approach that involves active individual participation, physician counselling and health coaching, community involvement, and policy change, with incorporation of cardiac rehabilitation for patients requiring secondary prevention. Viewing exercise quantity as a vital sign, prescribing PA like a medication, and using technology, such as smartphone applications, encourage a global shift in focus from CVD treatment to prevention. Community-wide, home-based and internet-based prevention initiatives may also offer a developing pool of resources that can be tapped into to promote education and PA compliance. This review summarises the underlying rationale, current guidelines for and recommendations to cultivate a comprehensive focus in the endorsement of PA in the primary and secondary prevention of CHD.
Managing and Documenting Legacy Scientific Workflows

Summary Scientific legacy workflows are often developed over many years, poorly documented and implemented with scripting languages. In the context of our cross-disciplinary projects we face the problem of maintaining such scientific workflows. This paper presents the Workflow Instrumentation for Structure Extraction (WISE) method used to process several ad-hoc legacy workflows written in Python and automatically produce their workflow structural skeleton. Unlike many existing methods, WISE does not assume input workflows to be preprocessed in a known workflow formalism. It is also able to identify and analyze calls to external tools. We present the method and report its results on several scientific workflows.
Induction of a selective and persistent extravasation of neutrophils into the peritoneal cavity by tryptase mouse mast cell protease 6.

Recombinant mouse mast cell protease 6 (mMCP-6) was generated to study the role of this tryptase in inflammatory reactions. Seven to forty-eight hours after the i.p. injection of recombinant mMCP-6 into BALB/c, mast cell-deficient WCB6F1-Sl/Sl(d), C5-deficient, or mMCP-5-null mice, the number of neutrophils in the peritoneal cavity of each animal increased significantly by >50-fold. The failure of the closely related recombinant tryptase mMCP-7 to induce a comparable peritonitis indicates that the substrate specificities of the two tryptases are very different. Unlike most forms of acute inflammation, the mMCP-6-mediated peritonitis was relatively long lasting and neutrophil specific. Mouse MCP-6 did not induce neutrophil chemotaxis directly in an in vitro assay, but did promote chemotaxis of the leukocyte in the presence of endothelial cells. Mouse MCP-6 did not induce cultured human endothelial cells to express TNF-alpha, RANTES, IL-1alpha, or IL-6. However, the tryptase induced endothelial cells to express large amounts of IL-8 continually over a 40-h period. Neither enzymatically active mMCP-7 nor enzymatically inactive pro-mMCP-6 was able to induce endothelial cells to increase their expression of IL-8. Although the mechanism by which mMCP-6 induces neutrophil accumulation in tissues remains to be determined, the finding that mMCP-6 induces cultured human endothelial cells to selectively release large amounts of IL-8 raises the possibility that this tryptase regulates the steady state levels of neutrophil-specific chemokines in vivo during mast cell-mediated inflammatory events.
A model proposal to determine a crowd-credit-scoring

DOI: 10.14254/2071789X.2018/11-4/4 ABSTRACT. Crowdlending is gaining importance as a financial option and is democratizing access to capital markets. However, the key factors that drive investors to choose a given project requires further research. Some authors have identified certain isolated factors, but a holistic approach is needed. To fill this gap, we identified 10 success factors allowing us to build a crowdlending success model. The model leads to establishing the concept of crowd-credit-scoring, in others words, understanding which criteria “crowds” follow when lending money and how different these criteria are from those applied by banking executives. Results will be very useful to establish the crowd-credit-scoring concept. In others words, which are the criteria follow by the “crowd” to lend money and how different are this criteria to the banking executives’ ones.