Directed Neural Differentiation of Mouse Embryonic Stem Cells Is a Sensitive System for the Identification of Novel Hox Gene Effectors

The evolutionarily conserved Hox family of homeodomain transcription factors plays fundamental roles in regulating cell specification along the anterior posterior axis during development of all bilaterian animals by controlling cell fate choices in a highly localized, extracellular signal and cell context dependent manner. Some studies have established downstream target genes in specific systems but their identification is insufficient to explain either the ability of Hox genes to direct homeotic transformations or the breadth of their patterning potential. To begin delineating Hox gene function in neural development we used a mouse ES cell based system that combines efficient neural differentiation with inducible Hoxb1 expression. Gene expression profiling suggested that Hoxb1 acted as both activator and repressor in the short term but predominantly as a repressor in the long run. Activated and repressed genes segregated in distinct processes suggesting that, in the context examined, Hoxb1 blocked differentiation while activating genes related to early developmental processes, wnt and cell surface receptor linked signal transduction and cell-to-cell communication. To further elucidate aspects of Hoxb1 function we used loss and gain of function approaches in the mouse and chick embryos. We show that Hoxb1 acts as an activator to establish the full expression domain of CRABPI and II in rhombomere 4 and as a repressor to restrict expression of Lhx5 and Lhx9. Thus the Hoxb1 patterning activity includes the regulation of the cellular response to retinoic acid and the delay of the expression of genes that commit cells to neural differentiation. The results of this study show that ES neural differentiation and inducible Hox gene expression can be used as a sensitive model system to systematically identify Hox novel target genes, delineate their interactions with signaling pathways in dictating cell fate and define the extent of functional overlap among different Hox genes

Leptin Administration Favors Muscle Mass Accretion by Decreasing FoxO3a and Increasing PGC-1α in ob/ob Mice

Absence of leptin has been associated with reduced skeletal muscle mass in leptin-deficient ob/ob mice. The aim of our study was to examine the effect of leptin on the catabolic and anabolic pathways regulating muscle mass. Gastrocnemius, extensor digitorum longus and soleus muscle mass as well as fiber size were significantly lower in ob/ob mice compared to wild type littermates, being significantly increased by leptin administration (P<0.001). This effect was associated with an inactivation of the muscle atrophy-related transcription factor forkhead box class O3 (FoxO3a) (P<0.05), and with a decrease in the protein expression levels of the E3 ubiquitin-ligases muscle atrophy F-box (MAFbx) (P<0.05) and muscle RING finger 1 (MuRF1) (P<0.05). Moreover, leptin increased (P<0.01) protein expression levels of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), a regulator of muscle fiber type, and decreased (P<0.05) myostatin protein, a negative regulator of muscle growth. Leptin administration also activated (P<0.01) the regulators of cell cycle progression proliferating cell nuclear antigen (PCNA) and cyclin D1, and increased (P<0.01) myofibrillar protein troponin T. The present study provides evidence that leptin treatment may increase muscle mass of ob/ob mice by inhibiting myofibrillar protein degradation as well as enhancing muscle cell proliferation

Development of a Framework to Compare Low-Altitude Unmanned Air Traffic Management Systems

Presented at the AIAA SciTech 2021 ForumSeveral reports forecast a very high demand for Urban Air Mobility services such as package delivery and air taxi. This would lead to very dense low-altitude operations which cannot be safely accommodated by the current air traffic management system. Many different architectures for low-altitude air traffic management have been proposed in the literature, however, the lack of a common framework makes it difficult to compare strategies. The work presented here establishes efficiency, safety and capacity metrics, defines the components of an automated traffic management system architecture and introduces a preliminary framework to compare different alternatives. This common framework allows for the evaluation and comparison of different alternatives for unmanned traffic management. The framework is showcased on different strategies with different architectures. The impact of algorithmic choices and airspace architectures is evaluated. A decoupled approach to 4D trajectory planning is shown to scale poorly with agents density. The impact of segregating traffic by heading is shown to be very different depending on the algorithms and airspace access rules chosen

Steric Manipulation of the Reductive Reactivity of Ytterbocenes toward 2-(((2,6-Diisopropylphenyl)imino)methyl)pyridine: Insertion of the N:C Bond into the Yb-Indenyl Bond or Oxidative Cleavage of the h5 Yb-Cp (Cp = C13H9, Cp) Bond.

International audienceUnprecedented N=C bond insertion into the 5 Yb-C9H7 bond occurs in the reaction of 2-(((2,6-diisopropylphenyl)imino)methyl)pyridine with (C9H7)2Yb(THF)2 and affords the Yb(III) derivative [Yb(5-C9H7){N(2,6-i-Pr2C6H3)CH(C9H7)(C5H4N)}{2,6-i-Pr2C6H3NCH(C5H4N)-}]. For the complexes Cp2Yb(THF)2 (Cp = C13H9, Cp*) coordinated by bulkier 5 ligands the same reaction results in an oxidative cleavage of the 5 Yb-Cp (Cp = C13H9, Cp*) bond and formation of [Yb{(2,6-i-Pr2C6H5NCH(C5H4N)-}3] and [Yb(C5Me5){(2,6-i-Pr2C6H3NCH(C5H4N)-}2], respectively

Ytterbocenes as one- and two-electron reductants in their reactions with diazadienes: YbIII mixed-ligand bent-sandwich complexes containing a dianion of diazabutadiene

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Energy analysis within process simulation software to enhance process energy management

Energy analysis within process simulation software to enhance process energy management. Journée Thermodynamique et Bioprocédé

Mesoporous Silica Nanoparticles Combining Two-Photon Excited Fluorescence and Magnetic Properties

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