Estudio comparativo de piedras canteras en Las Banderas y Diriamba

Como materia prima, la piedra se extrae generalmente de canteras, explotaciones mineras a cielo abierto. La cantería es uno de los oficios de más antigua tradición. La piedra es tallada por los maestros tallistas, dedicados a este oficio en el municipio de Las Banderas y Diriamba. La piedra cantera cuenta con una producción artesanal e industrial en nuestro país, así como su calidad depende del lugar de su extracción, tipo, corte y ubicación de estos yacimientos. La influencia económica que tiene en sus municipios se caracteriza por la zona de ubicación y demanda de esta. En el siguiente trabajo se aborda el estudio comparativo de piedras cantera en el municipio de Las Banderas departamento de Managua y el municipio de Diriamba departamento de Caraz

ROCK1/2 signaling contributes to corticosteroid-refractory acute graft-versus-host disease

Patients with corticosteroid-refractory acute graft-versus-host disease (aGVHD) have a low one-year survival rate. Identification and validation of novel targetable kinases in patients who experience corticosteroid-refractory-aGVHD may help improve outcomes. Kinase-specific proteomics of leukocytes from patients with corticosteroid-refractory-GVHD identified rho kinase type 1 (ROCK1) as the most significantly upregulated kinase. ROCK1/2 inhibition improved survival and histological GVHD severity in mice and was synergistic with JAK1/2 inhibition, without compromising graft-versus-leukemia-effects. ROCK1/2-inhibition in macrophages or dendritic cells prior to transfer reduced GVHD severity. Mechanistically, ROCK1/2 inhibition or ROCK1 knockdown interfered with CD80, CD86, MHC-II expression and IL-6, IL-1β, iNOS and TNF production in myeloid cells. This was accompanied by impaired T cell activation by dendritic cells and inhibition of cytoskeletal rearrangements, thereby reducing macrophage and DC migration. NF-κB signaling was reduced in myeloid cells following ROCK1/2 inhibition. In conclusion, ROCK1/2 inhibition interferes with immune activation at multiple levels and reduces acute GVHD while maintaining GVL-effects, including in corticosteroid-refractory settings

Validation of a SARS-CoV-2 Surrogate Virus Neutralization Test in Recovered and Vaccinated Healthcare Workers

Vaccination against COVID-19 is the main public health approach to fight against the pandemic. The Spike (S) glycoprotein of SARS-CoV-2 is the principal target of the neutralizing humoral response. We evaluated the analytical and clinical performances of a surrogate virus neutralization test (sVNT) compared to conventional neutralization tests (cVNTs) and anti-S eCLIA assays in recovered and/or vaccinated healthcare workers. Our results indicate that sVNTs displayed high specificity and no cross-reactivity. Both eCLIA and sVNT immunoassays were good at identifying cVNT serum dilutions ≥1:16. The optimal thresholds when identifying cVNT titers ≥1:16, were 74.5 U/mL and 49.4 IU/mL for anti-S eCLIA and sVNT, respectively. Our data show that neutralizing antibody titers (Nab) differ from one individual to another and may diminish over time. Specific assays such as sVNTs could offer a reliable complementary tool to routine anti-S serological assays

Amotl2a interacts with the hippo effector yap1 and the Wnt/β-catenin effector lef1 to control tissue size in zebrafish

During development, proliferation must be tightly controlled for organs to reach their appropriate size. While the Hippo signaling pathway plays a major role in organ growth control, how it senses and responds to increased cell density is still unclear. In this study, we use the zebrafish lateral line primordium (LLP), a group of migrating epithelial cells that form sensory organs, to understand how tissue growth is controlled during organ formation. Loss of the cell junctionassociated Motin protein Amotl2a leads to overproliferation and bigger LLP, affecting the final pattern of sensory organs. Amotl2a function in the LLP is mediated together by the Hippo pathway effector Yap1 and the Wnt/β-catenin effector Lef1. Our results implicate for the first time the Hippo pathway in size regulation in the LL system. We further provide evidence that the Hippo/Motin interaction is essential to limit tissue size during development

Le Courrier

06 mars 18511851/03/06 (N65)

Reaction media of 44I12 cytoplasmic extract incubated with Impranil at 30°C and pH 7.0 during 24h.

<p>Negative control: <i>E</i>. <i>coli</i> host strain Epi100 transformed with the empty pCC1FOS fosmid. For 44I12, the reaction medium, in and out of the tube, is showed, since a solid aggregate could be obtained.</p

ORFs of interest from the sequenced clones, annotated as putative esterases or proteases.

<p>ORFs of interest from the sequenced clones, annotated as putative esterases or proteases.</p

Graphical representation of the metagenomic sequence of clone 44I12, and RAST annotation of the identified ORFs.

<p>Red arrow: CE_Ubrb encoding gene.</p

Phylogenetic tree of sequences characteristic of the first 8 lipolytic families described by Arpigny et Jaeger [51], along with the characterized CE_Ubrb blast hits against the NCBI-NR database and the first blast hits against the ESTHER database.

<p>In red: biochemically characterized enzymes.</p

MicroRNA-146a regulates immune-related adverse events caused by immune checkpoint inhibitors

Immune checkpoint inhibitor (ICI) therapy has shown a significant benefit in the treatment of a variety of cancer entities. However, immune-related adverse events (irAEs) occur frequently and can lead to ICI treatment termination. MicroRNA-146a (miR-146a) has regulatory functions in immune cells. We observed that mice lacking miR-146a developed markedly more severe irAEs compared with WT mice in several irAE target organs in 2 different murine models. miR-146a-/- mice exhibited increased T cell activation and effector function upon ICI treatment. Moreover, neutrophil numbers in the spleen and the inflamed intestine were highly increased in ICI-treated miR-146a-/- mice. Therapeutic administration of a miR-146a mimic reduced irAE severity. To validate our preclinical findings in patients, we analyzed the effect of a SNP in the MIR146A gene on irAE severity in 167 patients treated with ICIs. We found that the SNP rs2910164 leading to reduced miR-146a expression was associated with an increased risk of developing severe irAEs, reduced progression-free survival, and increased neutrophil counts both at baseline and during ICI therapy. In conclusion, we characterized miR-146a as a molecular target for preventing ICI-mediated autoimmune dysregulation. Furthermore, we identified the MIR146A SNP rs2910164 as a biomarker to predict severe irAE development in ICI-treated patients