154 research outputs found
Swimming by spinning: spinning-top type rotations regularize sperm swimming into persistently symmetric paths in 3D
Sperm modulate their flagellar symmetry to navigate through complex
physico-chemical environments and achieve reproductive function. Yet it remains
elusive how sperm swim forwards despite the inherent asymmetry of several
components that constitutes the flagellar engine. Despite the critical
importance of symmetry, or the lack of it, on sperm navigation and its
physiological state, there is no methodology to date that can robustly detect
the symmetry state of the beat in free-swimming sperm in 3D.How does symmetric
progressive swimming emerge even for asymmetric beating, and how can beating
(a)symmetry be inferred experimentally? Here, we numerically resolve the fluid
mechanics of swimming around asymmetrically beating spermatozoa. This reveals
that sperm spinning critically regularizes swimming into persistently symmetric
paths in 3D, allowing sperm to swim forwards despite any imperfections on the
beat. The sperm orientation in three-dimensions, and not the swimming path, can
inform the symmetry state of the beat, eliminating the need of tracking the
flagellum in 3D. We report a surprising correspondence between the movement of
sperm and spinning-top experiments, indicating that the flagellum drives
''spinning-top'' type rotations during sperm swimming, and that this parallel
is not a mere analogy. These results may prove essential in future studies on
the role of (a)symmetry in spinning and swimming microorganisms and
micro-robots, as body orientation detection has been vastly overlooked in
favour of swimming path detection. Altogether, sperm rotation may provide a
foolproof mechanism for forward propulsion and navigation in nature that would
otherwise not be possible for flagella with broken symmetry
PromotionLens: Inspecting Promotion Strategies of Online E-commerce via Visual Analytics
Promotions are commonly used by e-commerce merchants to boost sales. The
efficacy of different promotion strategies can help sellers adapt their
offering to customer demand in order to survive and thrive. Current approaches
to designing promotion strategies are either based on econometrics, which may
not scale to large amounts of sales data, or are spontaneous and provide little
explanation of sales volume. Moreover, accurately measuring the effects of
promotion designs and making bootstrappable adjustments accordingly remains a
challenge due to the incompleteness and complexity of the information
describing promotion strategies and their market environments. We present
PromotionLens, a visual analytics system for exploring, comparing, and modeling
the impact of various promotion strategies. Our approach combines
representative multivariant time-series forecasting models and well-designed
visualizations to demonstrate and explain the impact of sales and promotional
factors, and to support "what-if" analysis of promotions. Two case studies,
expert feedback, and a qualitative user study demonstrate the efficacy of
PromotionLens.Comment: IEEE Transactions on Visualization and Computer Graphics (Proc. IEEE
VIS 2022
Agricultural vulnerability to drought in southern Alberta : a quantitative assessment
xii, 127 leaves : ill. ; 29 cm.Agricultural vulnerability is generally referred to as the degree to which agricultural systems are likely to experience harm due to a stress. In this study, an existing analytical method to quantify vulnerability was adopted to assess the magnitude as well as the spatial pattern of agricultural vulnerability to varying drought conditions in Southern Alberta. Based on the farm reported data and remote sensing imagery, two empirical approaches were developed to implement vulnerability assessment in Southern Alberta at the quarter-section and 30 meter by 30 meter pixel levels. Cereal crop yield and the Standardized Precipitation Index (SPI) were specified as the agricultural wellbeing and stress pair in the study. Remote sensing data were used to generate cereal crop yield estimations, which were then implemented in vulnerability quantification. The utility of the remote sensing data source for vulnerability assessment were proved. The spatial pattern of agricultural vulnerability to different severity and duration of drought were mapped
Forkhead box F2 Regulation of Platelet-Derived Growth Factor and myocardin/Serum Response Factor Signaling is Essential for Intestinal Development
Alterations in the forkhead box F2 gene expression have been reported in numerous pathologies, and Foxf2−/− mice are perinatal lethal with multiple malformations; however, molecular mechanisms pertaining to Foxf2 signaling are severely lacking. In this study, Foxf2 requirements in murine smooth muscle cells were examined using a conditional knock-out approach. We generated novel Foxf2-floxed mice, which we bred to smMHC-Cre-eGFP mice to generate a mouse line with Foxf2 deleted specifically from smooth muscle. These mice exhibited growth retardation due to reduced intestinal length as well as inflammation and remodeling of the small intestine. Colons of Tg(smMHC-Cre-eGFP+/−);Foxf2−/− mice had expansion of the myenteric nerve plexus and increased proliferation of smooth muscle cells leading to thickening of the longitudinal smooth muscle layer. Foxf2 deficiency in colonic smooth muscle was associated with increased expression of Foxf1, PDGFa, PDGFb, PDGF receptor α, and myocardin. FOXF2 bound to promoter regions of these genes indicating direct transcriptional regulation. Foxf2 repressed Foxf1 promoter activity in co-transfection experiments. We also show that knockdown of Foxf2 in colonic smooth muscle cells in vitro and in transgenic mice increased myocardin/serum response factor signaling and increased expression of contractile proteins. Foxf2 attenuated myocardin/serum response factor signaling in smooth muscle cells through direct binding to the N-terminal region of myocardin. Our results indicate that Foxf2 signaling in smooth muscle cells is essential for intestinal development and serum response factor signaling
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Deletion of Forkhead Box M1 Transcription Factor from Respiratory Epithelial Cells Inhibits Pulmonary Tumorigenesis
The Forkhead Box m1 (Foxm1) protein is induced in a majority of human non-small cell lung cancers and its expression is associated with poor prognosis. However, specific requirements for the Foxm1 in each cell type of the cancer lesion remain unknown. The present study provides the first genetic evidence that the Foxm1 expression in respiratory epithelial cells is essential for lung tumorigenesis. Using transgenic mice, we demonstrated that conditional deletion of Foxm1 from lung epithelial cells (epFoxm1−/− mice) prior to tumor initiation caused a striking reduction in the number and size of lung tumors, induced by either urethane or 3-methylcholanthrene (MCA)/butylated hydroxytoluene (BHT). Decreased lung tumorigenesis in epFoxm1−/− mice was associated with diminished proliferation of tumor cells and reduced expression of Topoisomerase-2α (TOPO-2α), a critical regulator of tumor cell proliferation. Depletion of Foxm1 mRNA in cultured lung adenocarcinoma cells significantly decreased TOPO-2α mRNA and protein levels. Moreover, Foxm1 directly bound to and induced transcription of the mouse TOPO-2α promoter region, indicating that TOPO-2α is a direct target of Foxm1 in lung tumor cells. Finally, we demonstrated that a conditional deletion of Foxm1 in pre-existing lung tumors dramatically reduced tumor growth in the lung. Expression of Foxm1 in respiratory epithelial cells is critical for lung cancer formation and TOPO-2α expression in vivo, suggesting that Foxm1 is a promising target for anti-tumor therapy.</p
Key Role of the Membrane Trafficking of Nav1.5 Channel Protein in Antidepressant-Induced Brugada Syndrome
Anti-depressant treatment has been found to be associated with the development of Brugada syndrome (BrS) through poorly defined mechanisms. Herein, this study aimed to explore the molecular basis for amitriptyline-induced BrS. The effects of long-term treatments of amitriptyline on Nav1.5 were investigated using neonatal rat ventricular myocytes. The electrophysiological properties, expression and distribution of Nav1.5 were studied using the patch clamp, Western blot and confocal laser microscopy assays. Interactions between Nav1.5 and its interacting proteins, including ankyrin-G and dystrophin, were evaluated by co-immunoprecipitation. A larger decrease in the peak INa occurred after long-term treatments to amitriptyline (56.64%) than after acute exposure to amitriptyline (28%). Slow recovery from inactivation of Nav1.5 was observed after acute or long-term treatments to amitriptyline. The expression of Nav1.5 on the cell membrane showed a larger decrease by long-term treatments to amitriptyline than by acute exposure to amitriptyline. After long-term treatments to amitriptyline, we observed reduced Nav1.5 proteins on the cell membrane and the disrupted co-localization of Nav1.5 and ankyrin-G or dystrophin. Co-immunoprecipitation experiments further testified that the combination of Nav1.5 and ankyrin-G or dystrophin was severely weakened after long-term treatments to amitriptyline, implying the failed interaction between Nav1.5 and ankyrin-G or dystrophin. Our data suggest that the long-term effect of amitriptyline serves as an important contribution to BrS induced by amitriptyline. The mechanisms of BrS induced by amitriptyline were related to Nav1.5 trafficking and could be explained by the disrupted interaction of ankyrin-G, dystrophin and Nav1.5
Prompt-to-afterglow transition of optical emission in a long gamma-ray burst consistent with a fireball
Long gamma-ray bursts (GRBs), which signify the end-life collapsing of very
massive stars, are produced by extremely relativistic jets colliding into
circumstellar medium. Huge energy is released both in the first few seconds,
namely the internal dissipation phase that powers prompt emissions, and in the
subsequent self-similar jet-deceleration phase that produces afterglows
observed in broad-band electromagnetic spectrum. However, prompt optical
emissions of GRBs have been rarely detected, seriously limiting our
understanding of the transition between the two phases. Here we report
detection of prompt optical emissions from a gamma-ray burst (i.e. GRB 201223A)
using a dedicated telescope array with a high temporal resolution and a wide
time coverage. The early phase coincident with prompt {\gamma}-ray emissions
show a luminosity in great excess with respect to the extrapolation of
{\gamma}-rays, while the later luminosity bump is consistent with onset of the
afterglow. The clearly detected transition allows us to differentiate physical
processes contributing to early optical emissions and to diagnose the
composition of the jetComment: Authors' version of article published in Nature Astronomy, see their
website for official versio
Evaluación de los factores determinantes del recuento de plaquetas en pacientes con cirrosis
Thrombocytopenia is considered one of the hallmarks of patients with cirrhosis. Several mechanisms have been implicated in the pathophysiology of thrombocytopenia in cirrhosis. Hypersplenism caused by splenomegay, classically regarded as an indirect marker of portal hypertension has been considered the main factor implicated [200]. Nevertheless, portal hypertension is best estimated by the hepatic venous pressure gradient (HVPG) [32, 189], although contradictory results have been reported regarding the association between HVPG and platelet count [195-197]. The identification of thrombopoietin (TPO), a growth factor that enhances the maturation of megakaryocytes and the release of platelets from the bone marrow, has shed new light on the physiolgy of platelets [217]. In normal conditions in adults, TPO is mainly produced in the liver [93, 96] and the circulating leves of platelets are controlled by a negative feedback mechanism [99], so there is an inverse relationship between the amount of circulating platelets, and the amount of TPO that can reach the bone marrow to stimulate thrombopoiesis. In liver cirrhosis perhaps a decreased syntehesis of TPO could be implicated in the development of thrombocytopenia. Controversial findings regarding the role of each mechanism in thrombocytopenia of liver cirrhosis have been reported [142, 146, 160-161, 184] and no study has simultaneously evaluated the influence of the different mechanisms including portal hypertension and TPO production nor whether their influence could change in different stages of the disease..
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