Microarrayed human bone marrow organoids for modeling blood stem cell dynamics

In many leukemia patients, a poor prognosis is attributed either to the development of chemotherapy resistance by leukemic stem cells (LSCs) or to the inefficient engraftment of transplanted hematopoietic stem/progenitor cells (HSPCs) into the bone marrow (BM). Here, we build a 3D in vitro model system of bone marrow organoids (BMOs) that recapitulate several structural and cellular components of native BM. These organoids are formed in a high-throughput manner from the aggregation of endothelial and mesenchymal cells within hydrogel microwells. Accordingly, the mesenchymal compartment shows partial maintenance of its self-renewal and multilineage potential, while endothelial cells self-organize into an interconnected vessel-like network. Intriguingly, such an endothelial compartment enhances the recruitment of HSPCs in a chemokine ligand/receptor-dependent manner, reminiscent of HSPC homing behavior in vivo. Additionally, we also model LSC migration and nesting in BMOs, thus highlighting the potential of this system as a well accessible and scalable preclinical model for candidate drug screening and patient-specific assays

In Situ Formed Sn1 xInx In1 ySnyOz Core Shell Nanoparticles as Electrocatalysts for CO2 Reduction to Formate

Electrochemical reduction of CO2 CO2RR driven by renewable energy has gained increasing attention for sustainable production of chemicals and fuels. Catalyst design to overcome large overpotentials and poor product selectivity remains however challenging. Sn SnOx and In InOx composites have been reported active for CO2RR with high selectivity toward formate formation. In this work, the CO2RR activity and selectivity of metal metal oxide composite nanoparticles formed by in situ reduction of bimetallic amorphous SnInOx thin films are investigated. It is shown that during CO2RR the amorphous SnInOx pre catalyst thin films are reduced in situ into Sn1 XInX In1 YSnYOz core shell nanoparticles composed of Sn rich SnIn alloy nanocores with x lt; 0.2 surrounded by InOx rich bimetallic InSnOx shells with 0.3 lt; y lt; 0.4 and z amp; 8776; 1 . The in situ formed particles catalyze the CO2RR to formate with high faradaic efficiency 80 and outstanding formate mass activity 437 A gIn Sn amp; 8722;1 amp; 8722;1.0 V vs RHE in 0.1 m KHCO3 . While extensive structural investigation during CO2RR reveals pronounced dynamics in terms of particle size, the core shell structure is observed for the different electrolysis conditions essayed, with high surface oxide contents favoring formate over hydrogen selectivit

Potential impacts of climate change on agriculture and fisheries production in 72 tropical coastal communities

Climate change is expected to profoundly affect key food production sectors, including fisheries and agriculture. However, the potential impacts of climate change on these sectors are rarely considered jointly, especially below national scales, which can mask substantial variability in how communities will be affected. Here, we combine socioeconomic surveys of 3,008 households and intersectoral multi-model simulation outputs to conduct a sub-national analysis of the potential impacts of climate change on fisheries and agriculture in 72 coastal communities across five Indo-Pacific countries (Indonesia, Madagascar, Papua New Guinea, Philippines, and Tanzania). Our study reveals three key findings: First, overall potential losses to fisheries are higher than potential losses to agriculture. Second, while most locations (> 2/3) will experience potential losses to both fisheries and agriculture simultaneously, climate change mitigation could reduce the proportion of places facing that double burden. Third, potential impacts are more likely in communities with lower socioeconomic status

L-Plastin nanobodies perturb matrix degradation, podosome formation, stability and lifetime in THP-1 macrophages

Podosomes are cellular structures acting as degradation ‘hot-spots’ in monocytic cells. They appear as dot-like structures at the ventral cell surface, enriched in F-actin and actin regulators, including gelsolin and L-plastin. Gelsolin is an ubiquitous severing and capping protein, whereas L-plastin is a leukocyte-specific actin bundling protein. The presence of the capping protein CapG in podosomes has not yet been investigated. We used an innovative approach to investigate the role of these proteins in macrophage podosomes by means of nanobodies or Camelid single domain antibodies. Nanobodies directed against distinct domains of gelsolin, L-plastin or CapG were stably expressed in macrophage-like THP-1 cells. CapG was not enriched in podosomes. Gelsolin nanobodies had no effect on podosome formation or function but proved very effective in tracing distinct gelsolin populations. One gelsolin nanobody specifically targets actin-bound gelsolin and was effectively enriched in podosomes. A gelsolin nanobody that blocks gelsolin-G-actin interaction was not enriched in podosomes demonstrating that the calcium-activated and actin-bound conformation of gelsolin is a constituent of podosomes. THP-1 cells expressing inhibitory L-plastin nanobodies were hampered in their ability to form stable podosomes. Nanobodies did not perturb Ser5 phosphorylation of L-plastin although phosphorylated L-plastin was highly enriched in podosomes. Furthermore, nanobody-induced inhibition of L-plastin function gave rise to an irregular and unstable actin turnover of podosomes, resulting in diminished degradation of the underlying matrix. Altogether these results indicate that L-plastin is indispensable for podosome formation and function in macrophages

Tuberculosis is associated with expansion of a motile, permissive and immunomodulatory CD16(+) monocyte population via the IL-10/STAT3 axis

The human CD14+ monocyte compartment is composed by two subsets based on CD16 expression. We previously reported that this compartment is perturbed in tuberculosis (TB) patients, as reflected by the expansion of CD16+ monocytes along with disease severity. Whether this unbalance is beneficial or detrimental to host defense remains to be elucidated. Here in the context of active TB, we demonstrate that human monocytes are predisposed to differentiate towards an anti-inflammatory (M2-like) macrophage activation program characterized by theCD16+CD163+MerTK+pSTAT3+ phenotype and functional properties such as enhanced protease-dependent motility, pathogen permissivity and immunomodulation. This process is dependent on STAT3 activation, and loss-of-function experiments point towards a detrimental role in host defense against TB. Importantly, we provide a critical correlation between the abundance of the CD16+CD163+MerTK+pSTAT3+ cells and the progression of the disease either at the local level in a non-human primate tuberculous granuloma context, or at the systemic level through the detection of the soluble form of CD163 in human sera. Collectively, this study argues for the pathogenic role of the CD16+CD163+MerTK+pSTAT3+ monocyte-to-macrophage differentiation program and its potential as a target for TB therapy,and promotes the detection of circulating CD163 as a potential biomarker for disease progression and monitoringof treatment efficacy.Fil: Lastrucci, Claire. Centre National de la Recherche Scientifique; FranciaFil: Bénard, Alan. Centre National de la Recherche Scientifique; FranciaFil: Balboa, Luciana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Pingris, Karine. Centre National de la Recherche Scientifique; FranciaFil: Souriant, Shanti. Centre National de la Recherche Scientifique; FranciaFil: Poincloux, Renaud. Centre National de la Recherche Scientifique; FranciaFil: Al Saati, Talal. Inserm; FranciaFil: Rasolofo, Voahangy. Pasteur Institute in Antananarivo; MadagascarFil: González Montaner, Pablo. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas ; ArgentinaFil: Inwentarz, Sandra. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas ; ArgentinaFil: Moraña, Eduardo José. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas ; ArgentinaFil: Kondova, Ivanela. Biomedical Primate Research Centre; Países BajosFil: Verreck, Franck A. W.. Biomedical Primate Research Centre; Países BajosFil: Sasiain, María del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Neyrolles, Olivier. Centre National de la Recherche Scientifique; FranciaFil: Maridonneau Parini, Isabel. Centre National de la Recherche Scientifique; FranciaFil: Lugo Villarino, Geanncarlo. Centre National de la Recherche Scientifique; FranciaFil: Cougoule, Celine. Centre National de la Recherche Scientifique; Franci

Natural Convection of Nanofluids in a Square Enclosure with a Protruding Heater

This paper reports a numerical study on natural convection from a protruding heater located at the bottom of a square cavity filled with a copper-water nanofluid. The vertical walls of the cavity are cooled isothermally; the horizontal ones are adiabatic, and the heater is attached to the bottom wall. The heat source is assumed either to be isothermal or to have a constant heat flux. The effective viscosity and thermal conductivity of the nanofluid are modeled according to Brinkman and Patel, respectively. Numerical solutions of the full-governing equations, based on the lattice Boltzmann method, are obtained for a wide range of the governing parameters: the Rayleigh number, Ra; the Prandtl number, Pr; the geometrical parameters specifying the heater; the volume fraction of nanoparticles, Φ. For a particular geometry, it has been found that, for a given Ra, heat transfer is enhanced with increasing Φ, independently of the thermal boundary condition applied on the heater

c-FLIP efficiently rescues TRAF-2(-/-) cells from TNF-induced apoptosis

For the past 20 years, it has been known that preparations of Tumor Necrosis Factor alpha (TNF) fail to induce apoptosis due to cytoprotective responses that render cells resistant to its cytotoxic activity. Here we show that TRAF-2(-/-) embryonic fibroblasts express reduced levels of the anti-apoptotic molecule c-FLIP due to extensive degradation of the protein. Reconstitution of TRAF-2(-/-) EF with c-FLIP is sufficient for resistance to TNF toxicity. Our results strengthen the role of c-FLIP in protecting cells from the cytotoxic effect of TNF and have implication for the treatment of inflammatory and proliferative disorders