The lymphocyte function-associated antigen-1 (LFA-1) (also known as CD11a/CD18 and α
β₂), is just one of many integrins in the human body, but its significance is derived from its exclusive presence ...in leukocytes. In this review, we summarize the studies relating LFA-1 and its major ligand ICAM-1 (or CD54) with cancer, through the function of lymphocytes and myeloid cells on tumor cells. We consider how LFA-1 mediates the interaction of leukocytes with tumors and the role of ICAM-1 in tumor dynamics, which can be independent of its interaction with LFA-1. We also offer a more detailed examination of the role of LFA-1 within B-cell chronic lymphocytic leukemia. Finally, we discuss the role that exosomes harboring LFA-1 play in tumor growth and metastasis.
The topological partition theory states that icosahedral group affine extensions (fullerenes symmetry) are the most effective way to energetically optimize the surface covering. In recent decades, ...potential applications of fullerene symmetry have emerged in the major fields of biology, like enzyme inhibition and antiviral therapy. This research suggests a novel perspective to interpret the underlying spatial organization of cell populations in tissues from the polyhedral graph theory. We adopted this theoretical framework to study HUVEC cell in vitro angiogenesis assays on Matrigel. This work underscores the importance of extracellular Ca2+ gradients, both from conditioned BJ and pretreated HUVEC cells, in angiogenesis fullerene-rule spatial minimization.
E-scooter vibrations are a problem recently studied. Theoretical models based on dynamic simulations and also real measurements have confirmed the high impact of e-scooter vibrations on driver ...comfort and health. Some authors recommend improving e-scooter damping systems, including tyres. However, it has not been suggested nor has any research been published studying how to improve e-scooter frame design for reducing driver vibrations and improving comfort. In this paper, we have modelled a real e-scooter to have a reference. Then, we have developed a multibody dynamic model for running dynamic simulations studying the influence of mass geometry parameters of the e-scooter frame (mass, centre of gravity and inertia moment). Acceleration results have been analysed based on the UNE-2631 standard for obtaining comfort values. Based on results, a qualitative e-scooter frame design guide for mitigating vibrations and increasing the comfort of e-scooter driver has been developed. Some application cases have been running on the multibody dynamic simulation model, finding improvements of comfort levels higher than 9% in comparison with the e-scooter reference model. The dynamic model has been qualitatively validated from real measurements. In addition, a basic sensor proposal and comfort colour scale is proposed for giving feedback to e-scooter drivers.
Assessing the role of the WT1 transcription factor (WT1) during early gonad differentiation and its impact on adult sex development has been difficult due to the complete gonadal agenesis and ...embryonic lethality exhibited by Wt1KO mouse models. Here, we generated Wt1LoxP/GFP;Wt1Cre mice, the first Wt1KO mouse model that reaches adulthood with a dramatically reduced Wt1 expression during early gonadogenesis. Wt1LoxP/GFP;Wt1Cre mice lacked mature gonads and displayed genital tracts containing both male and female genital structures and ambiguous genitalia. We found that WT1 is necessary for the activation of both male and female sex-determining pathways, as embryonic mutant gonads failed to upregulate the expression of the genes specific for each genetic programme. The gonads of Wt1LoxP/GFP;Wt1Cre mice showed a lack of production of Sertoli and pre-granulosa cells and a reduced number of germ cells. NR5A1 and the steroidogenic genes expression was modulated differently in XY and XX Wt1LoxP/GFP;Wt1Cre gonads, explaining the mutant phenotypes. Further studies of the XX Wt1LoxP/GFP;Wt1Cre gonads revealed that deletion of WT1 at an early stage impaired the differentiation of several cell types including somatic cells and the ovarian epithelium. Through the characterisation of this Wt1KO mouse model, we show that the deletion of Wt1 during early gonadogenesis produces dramatic defects in adult sex development.
One of the most common applications of glass fiber composite materials (GFRP) is the manufacturing of the hulls of high-speed boats. During navigation, the hull of these boats is subjected to ...repetitive impacts against the free surface of the water (slamming effect), which can cause severe damage to the material. To better understand the behavior of the composite material under this effect, in the present work, an experimental test has been carried out to reproduce the slamming phenomenon in GFRP panels by means of a novel device that allows this cyclic impact to be obtained while the panels are always in contact with water. By means of non-destructive ultrasound inspection in immersion, it has been possible to establish the evolution of the damage according to the number of impacts received by each panel. Destructive tests in the affected zone, specifically shear tests (Iosipescu test), allow determination of the loss of mechanical properties experienced by the material after receiving a high number of impacts in the presence of water (up to 900,000 impact cycles in some panels). The behavior of the material was found to be very different in wet and dry conditions. Under dry conditions, the material loses stiffness as the damage density increases and its shear strength also decreases, as does displacement at maximum load. For wet conditions, the material shows higher displacements at maximum load, while the shear strength decreases with increasing stiffness.
Synaptic activity is the main energy-consuming process in the central nervous system. We are beginning to understand how energy is supplied and used during synaptic activity by neurons. However, the ...long-term metabolic adaptations associated with a previous episode of synaptic activity are not well understood. Herein, we show that an episode of synaptic activity increases mitochondrial bioenergetics beyond the duration of the synaptic activity by transcriptionally inducing the expression of iron metabolism genes with the consequent enhancement of cellular and mitochondrial iron uptake. Iron is a necessary component of the electron transport chain complexes, and its chelation or knockdown of mitochondrial iron transporter Mfrn1 blocks the activity-mediated bioenergetics boost. We found that Mfrn1 expression is regulated by the well-known regulator of synaptic plasticity CREB, suggesting the coordinated expression of synaptic plasticity programs with those required to meet the associated increase in energetic demands.
The formation of neurites is an important process affecting the cognitive abilities of an organism. Neurite growth requires the addition of new membranes, but the metabolic remodeling necessary to ...supply lipids for membrane expansion is poorly understood. Here, we show that synaptic activity, one of the most important inducers of neurite growth, transcriptionally regulates the expression of neuronal glucose transporter Glut3 and rate‐limiting enzymes of glycolysis, resulting in enhanced glucose uptake and metabolism that is partly used for lipid synthesis. Mechanistically, CREB regulates the expression of Glut3 and Siah2, the latter and LDH activity promoting the normoxic stabilization of HIF‐1α that regulates the expression of rate‐limiting genes of glycolysis. The expression of dominant‐negative HIF‐1α or Glut3 knockdown blocks activity‐dependent neurite growth in vitro while pharmacological inhibition of the glycolysis and specific ablation of HIF‐1α in early postnatal mice impairs the neurite architecture. These results suggest that the manipulation of neuronal glucose metabolism could be used to treat some brain developmental disorders.
Synopsis
Neuronal membrane expansion required for neurite outgrowth upon synaptic stimulation involves concomitant upregulation of glucose uptake and metabolism, supporting lipid biosynthesis.
Glucose metabolism is necessary for activity‐dependent neurite outgrowth.
Synaptic activity induces glucose uptake and metabolism at transcriptional level.
Induction of glycolysis genes depends on HIF‐1α stabilization mediated by Siah2 and LDH.
Glut3 and Siah2 expression is regulated by CREB.
Neuronal membrane expansion required for neurite outgrowth upon synaptic stimulation involves concomitant upregulation of glucose uptake and metabolism, supporting lipid biosynthesis.
Encrustation of ureteral double J stents is a common complication that may affect its removal. The aim of the proposed study is to evaluate the efficacy and safety of a new oral composition to ...prevent double J stent encrustation in indwelling times up to 8 weeks.
A double-blinded, multicenter, placebo-controlled trial was conducted with 105 patients with indwelling double J stents enrolled across 9 public hospitals in Spain. The patients were randomly assigned (1:1) into intervention (53 patients) or placebo (52 patients) groups for 3 to 8 weeks and both groups self-monitored daily their morning urine pH levels. The primary outcome of analysis was the degree of stent ends encrustation, defined by a 4-point score (0 - none; 3 - global encrustation) using macroscopic and electron microscopy analysis of crystals, after 3 to 8-w indwelling period. Score was exponentially transformed according to calcium levels. Secondary endpoints included urine pH decrease, stent removal, and incidence of adverse events.
The intervention group benefits from a lower global encrustation rate of stent ends than placebo group (1% vs 8.2%; p < 0.018). Mean encrustation score was 85.12 (274.5) in the placebo group and 18.91 (102.27) in the intervention group (p < 0.025). Considering the secondary end points, treated patients reported greater urine pH decreases (p = 0.002). No differences in the incidence of adverse events were identified between the groups.
Our data suggest that the use of this new oral composition is beneficial in the context of ureteral double J indwelling by decreasing mean, as well as global encrustation.
This trial was registered at www.clinicaltrials.gov under the name "Combined Use of a Medical Device and a Dietary Complement in Patient Urinary pH Control in Patients With an Implanted Double J Stent" with date 2nd November 2017, code NCT03343275, and URL.
The epicardium plays a crucial role in embryonic heart development and adult heart repair; however, the molecular events underlying its maturation remain unknown.
, one of the main markers of the ...embryonic epicardium, is essential for epicardial development and function. Here, we analyse the transcriptomic profile of epicardial-enriched cells at different stages of development and from control and epicardial-specific
knockout (
) mice. Transcriptomic and cell morphology analyses of epicardial cells from epicardial-specific
mice revealed a defect in the maturation process of the mutant epicardium, including sustained upregulation of
expression and the inability of mutant epicardial cells to transition into a mature squamous phenotype. We identified
as a transcriptional target of Wt1, thus providing a molecular basis for the retention of the cuboidal cell shape observed in the
epicardium. Accordingly, inhibition of the Bmp4 signalling pathway both
and
rescued the cuboidal phenotype of the mutant epicardium. Our findings indicate the importance of the cuboidal-to-squamous transition in epicardial maturation, a process regulated by Wt1.
There are numerous studies describing the signaling mechanisms that mediate oligodendrocyte precursor cell (OPC) proliferation and differentiation, although the contribution of the cellular prion ...protein (PrP(c)) to this process remains unclear. PrP(c) is a glycosyl-phosphatidylinositol (GPI)-anchored glycoprotein involved in diverse cellular processes during the development and maturation of the mammalian central nervous system (CNS). Here we describe how PrP(c) influences oligodendrocyte proliferation in the developing and adult CNS. OPCs that lack PrP(c) proliferate more vigorously at the expense of a delay in differentiation, which correlates with changes in the expression of oligodendrocyte lineage markers. In addition, numerous NG2-positive cells were observed in cortical regions of adult PrP(c) knockout mice, although no significant changes in myelination can be seen, probably due to the death of surplus cells.
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