CASP7 (caspase 7, apoptosis-related cysteine peptidase)

Review on CASP7 (caspase 7, apoptosis-related cysteine peptidase), with data on DNA, on the protein encoded, and where the gene is implicated

Colchicine and amiprophos-methyl (APM) in polyploidy induction in banana plant

The objective was to assess the colchicine and amiprophos-methyl (APM) concentration and exposure period in the chromosome duplication of breed banana plants diploids. Banana stem tips were used from the following genotypes: breed diploids (1304-04 [Malaccensis x Madang (Musa acuminata spp. banksii)] and 8694-15 [0337-02 (Calcutta x Galeo) x SH32-63]). Colchicine was used at concentrations of 0 (control treatment), 1.25, 2.5 and 5.0 mM, while APM was used at 0 (control treatment), 40 and 80 μM, in solution under agitation (20 rpm), for 24 and 48 h periods. With the use of APM, 66.67% tetraploid plants were obtained in the 1304-04 genotype using 40 μM for 24 h and 18.18% in 80 μM for 48 h, while in the 8694-15 genotype using 40 and 80 μM colchicine for 48 h, 27.27 and 21.43% tetraploid plants were observed, respectively. For colchicine, in the 1304-04 genotype, only the 1.25 mM treatment for 48 h presented 25% tetraploid plants and in the 8694-15 genotype, the 5.0 mM concentration for 48 h produced 50% tetraploid plants. APM for 24 h enabled the tetraploid plant of the 1304-04 genotype to be obtained, while colchicine for 48 h resulted in tetraploid plants in the 8694-15 genotype.Key words: Musa acuminata, antimitotic, flow cytometry, tissue culture

Entropic Upper Bound on Gravitational Binding Energy

We prove that the gravitational binding energy {\Omega} of a self gravitating system described by a mass density distribution {\rho}(x) admits an upper bound B[{\rho}(x)] given by a simple function of an appropriate, non-additive Tsallis' power-law entropic functional Sq evaluated on the density {\rho}. The density distributions that saturate the entropic bound have the form of isotropic q-Gaussian distributions. These maximizer distributions correspond to the Plummer density profile, well known in astrophysics. A heuristic scaling argument is advanced suggesting that the entropic bound B[{\rho}(x)] is unique, in the sense that it is unlikely that exhaustive entropic upper bounds not based on the alluded Sq entropic measure exit. The present findings provide a new link between the physics of self gravitating systems, on the one hand, and the statistical formalism associated with non-additive, power-law entropic measures, on the other hand

Cholesteryl hemiazelate causes lysosome dysfunction impacting vascular smooth muscle cell homeostasis

In atherosclerotic lesions, vascular smooth muscle cells (VSMCs) represent half of the foam cell population, which is characterized by an aberrant accumulation of undigested lipids within lysosomes. Loss of lysosome function impacts VSMC homeostasis and disease progression. Understanding the molecular mechanisms underlying lysosome dysfunction in these cells is, therefore, crucial. We identify cholesteryl hemiazelate (ChA), a stable oxidation end-product of cholesteryl-polyunsaturated fatty acid esters, as an inducer of lysosome malfunction in VSMCs. ChA-treated VSMCs acquire a foam-cell-like phenotype, characterized by enlarged lysosomes full of ChA and neutral lipids. The lysosomes are perinuclear and exhibit degradative capacity and cargo exit defects. Lysosome luminal pH is also altered. Even though the transcriptional response machinery and autophagy are not activated by ChA, the addition of recombinant lysosomal acid lipase (LAL) is able to rescue lysosome dysfunction. ChA significantly affects VSMC proliferation and migration, impacting atherosclerosis. In summary, this work shows that ChA is sufficient to induce lysosomal dysfunction in VSMCs, that, in ChA-treated VSMCs, neither lysosome biogenesis nor autophagy are triggered, and, finally, that recombinant LAL can be a therapeutic approach for lysosomal dysfunction

Geo-environmental mapping using physiographic analysis: constraints on the evaluation of land instability and groundwater pollution hazards in the Metropolitan District of Campinas, Brazil

Geo-environmental terrain assessments and territorial zoning are useful tools for the formulation and implementation of environmental management instruments (including policy-making, planning, and enforcement of statutory regulations). They usually involve a set of procedures and techniques for delimitation, characterisation and classification of terrain units. However, terrain assessments and zoning exercises are often costly and time-consuming, particularly when encompassing large areas, which in many cases prevent local agencies in developing countries from properly benefiting from such assessments. In the present paper, a low-cost technique based on the analysis of texture of satellite imagery was used for delimitation of terrain units. The delimited units were further analysed in two test areas situated in Southeast Brazil to provide estimates of land instability and the vulnerability of groundwater to pollution hazards. The implementation incorporated procedures for inferring the influences and potential implications of tectonic fractures and other discontinuities on ground behaviour and local groundwater flow. Terrain attributes such as degree of fracturing, bedrock lithology and weathered materials were explored as indicators of ground properties. The paper also discusses constraints on- and limitations of- the approaches taken

ERBB4 confers metastatic capacity in Ewing sarcoma.

Metastatic spread is the single-most powerful predictor of poor outcome in Ewing sarcoma (ES). Therefore targeting pathways that drive metastasis has tremendous potential to reduce the burden of disease in ES. We previously showed that activation of the ERBB4 tyrosine kinase suppresses anoikis, or detachment-induced cell death, and induces chemoresistance in ES cell lines in vitro. We now show that ERBB4 is transcriptionally overexpressed in ES cell lines derived from chemoresistant or metastatic ES tumours. ERBB4 activates the PI3K-Akt cascade and focal adhesion kinase (FAK), and both pathways contribute to ERBB4-mediated activation of the Rac1 GTPase in vitro and in vivo. ERBB4 augments tumour invasion and metastasis in vivo, and these effects are blocked by ERBB4 knockdown. ERBB4 expression correlates significantly with reduced disease-free survival, and increased expression is observed in metastatic compared to primary patient-matched ES biopsies. Our findings identify a novel ERBB4-PI3K-Akt-FAK-Rac1 pathway associated with aggressive disease in ES. These results predict that therapeutic targeting of ERBB4, alone or in combination with cytotoxic agents, may suppress the metastatic phenotype in ES

A selective p53 activator and anticancer agent to improve colorectal cancer therapy

Impairment of the p53 pathway is a critical event in cancer. Therefore, reestablishing p53 activity has become one of the most appealing anticancer therapeutic strategies. Here, we disclose the p53-activating anticancer drug (3S)-6,7-bis(hydroxymethyl)-5-methyl-3-phenyl-1H,3H-pyrrolo[1,2-c]thiazole (MANIO). MANIO demonstrates a notable selectivity to the p53 pathway, activating wild-type (WT)p53 and restoring WT-like function to mutant (mut)p53 in human cancer cells. MANIO directly binds to the WT/mutp53 DNA-binding domain, enhancing the protein thermal stability, DNA-binding ability, and transcriptional activity. The high efficacy of MANIO as an anticancer agent toward cancers harboring WT/mutp53 is further demonstrated in patient-derived cells and xenograft mouse models of colorectal cancer (CRC), with no signs of undesirable side effects. MANIO synergizes with conventional chemotherapeutic drugs, and in vitro and in vivo studies predict its adequate drug-likeness and pharmacokinetic properties for a clinical candidate. As a single agent or in combination, MANIO will advance anticancer-targeted therapy, particularly benefiting CRC patients harboring distinct p53 status.We thank PT national funds (FCT/MCTES , Fundação para a Ciência e a Tecnologia , and Ministério da Ciência, Tecnologia e Ensino Superior ) through grants UIDB/50006/2020 , UID/BIO/04469/2019 , UIDB/04539/2020 , and UIDP/04539/2020 ( CIBB ); BioTecNorte operation ( NORTE-01-0145-FEDER-000004 ) and Porto Neurosciences and Neurologic Disease Research Initiative at I3S ( Norte-01-0145-FEDER-000008 ) funded by the European Regional Development Fund under the scope of Norte2020 - Programa Operacional Regional do Norte ; Masaryk University ( Project MUNI/A/1127/2019 ) and Ministry of Education, Youth and Sports of the Czech Republic (project nos. LQ1605 and LM2018125 ); FCT financial support through the fellowships SFRH/BD/119144/2016 (H.R.) and SFRH/BD/117949/2016 (L.R.); Fondazione AIRC ( IG#18985 , A.I.); and the Programa Operacional Potencial Humano (POCH), specifically the BiotechHealth Programme (Doctoral Programme on Cellular and Molecular Biotechnology Applied to Health Sciences , PD/00016/2012 ). We thank Dario Rizzotto for assistance in preparing the libraries for RNA sequencing. Funding: This work was supported by PT National Funds (FCT/MCTES, Fundação para a Ciência e Tecnologia , and Ministério da Ciência, Tecnologia e Ensino Superior ) via the projects UIDB/50006/2020 ( LAQV/REQUIMTE ), UIDB/00313/2020 , and UIDP/00313/2020 , co-funded by COMPETE2020-UE