Calpain restrains the stem cells compartment in breast cancer

CAPNS1 is essential for the stability and function of ubiquitous CAPN1 and CAPN2. Calpain modulates by proteolytic cleavage many cellular substrates and its activity is often deregulated in cancer cells, therefore calpain inhibition has been proposed as a therapeutical strategy for a number of malignancies. Here we show that CAPNS1 depletion is coupled to impairment of MCF7 and MCF10AT cell lines growth on plate and defective architecture of mammary acini derived from MCF10A cells. In soft agar CAPNS1 depletion leads to cell growth increase in MCF7, and decrease in MCF10AT cells. In both MCF7 and MCF10AT, CAPNS1 depletion leads to the enlargement of the stem cell compartment, as demonstrated by mammosphere formation assays and evaluation of stem cell markers by means of FACS and western blot analysis. Accordingly, activation of calpain by thapsigargin treatment leads to a decrease in the stem cell reservoir. The expansion of the cancer stem cell population in CAPNS1 depleted cells is coupled to a defective shift from symmetric to asymmetric division during mammosphere growth coupled to a decrease in NUMB protein level

First Record of the Invasive Asian Fish Tapeworm \u3ci\u3eBothriocephalus acheilognathi\u3c/i\u3e in Honduras, Central America

This paper provides the first report of the invasive Asian fish tapeworm, Bothriocephalus acheilognathi Yamaguti, 1934, in Honduras. The cestode was found in Profundulus portillorum (Cyprinodontiformes: Profundulidae), which represents a new host record, and which is a member of a genus faced with a variety of conservation challenges, now potentially complicated by the presence of this pathogenic cestode. Nearly complete sequence data from the ITS-1 5.8S and ITS-2 regions corroborate the determination based on morphological characteristics. Several species of carp were introduced to Honduras for aquaculture purposes in the early 1980s and the presence of the Asian fish tapeworm in Honduras may be related to these introductions. In addition, this report documents the currently known geographical distribution of this parasite in Central America, first recorded from Panamá and now from Honduras

Detection and analysis of tumour biomarkers to strengthen the diagnosis of acute and chronic leukaemias

AbstractMolecular markers in leukaemia are essential to diagnose, establish prognosis factors and determine the correct treatment of patients; therefore, it is imperative to include molecular biology studies, so that, combined with cytomorphology and immunophenotyping studies, they constitute the differential diagnosis of these neoplasias. It is extremely important to implement a panel of molecular markers that allows us to detect oncogenes derived from chromosomal translocations, genes derived from epigenetic alterations and drug-resistant genes.A panel of molecular markers that included 11 genes derived from chromosomal translocations BCR-ABL major and minor breakpoints, E2A-PBX1, MLL-AF4, TEL-AML1, PML-RARα, AML1-ETO was standardised; cancer testis antigens (CTA) derived from NY-ESO1 and MAGE-A3 epigenetic alterations and multi-drug-resistant genes ABCB1 and ABCG2. 30 patients diagnosed with leukaemia from Mexico's General Hospital (Hospital General de Mexico) were included. They suffered from acute lymphoblastic leukaemia (ALL) and acute myeloblastic leukaemia (AML); bone marrow mononuclear cells were used, from which RNA was extracted for the synthesis of cDNA and RT-PCR for each of the markers. In acute lymphoblastic leukaemia (ALL), BCR-ABL biomarkers expressed under 30% (3/10), E2A-PBX1 10% (1/10), ABC-B1 80% (8/10), and ABC-G2 60% (6/10). Patients with acute myeloblastic leukaemia (AML) expressed 30% PML-RARα (3/10), 40% ABC-B1 (4/10), and 10% ABC-G2 (1/10). Lastly, in patients with chronic myeloid leukaemia (CML), BCR-ABL was over 100% (10/10), ABC-B1 20% (2/10), and ABC-G2 50% (5/10). The presence of transcripts from chimeric genes minor BCR-ABL and E2A-PBX1 in ALL; PML-RARα in AML; and major BCR-ABL in CML, confirms the importance that the panel of molecular markers has in strengthening the diagnosis and prognosis of these conditions

A new approach for the treatment of CLL using chlorambucil/hydroxychloroquine-loaded anti-CD20 nanoparticles

Current approaches for the treatment of chronic lymphocytic leukemia (CLL) have greatly improved the prognosis for survival, but some patients remain refractive to these therapeutic regimens. Hence, in addition to reducing the long-term sideeffects of therapeutics for all leukemia patients, there is an urgent need for novel therapeutic strategies for difficult-to-treat leukemia cases. Due to the cytotoxicity of drugs, the major challenge currently is to deliver the therapeutic agents to neoplastic cells while preserving the viability of non-malignant cells. In this study, we propose a therapeutic approach in which high doses of hydroxychloroquine and chlorambucil were loaded into biodegradable polymeric nanoparticles coated with an anti-CD20 antibody.We first demonstrated the ability of the nanoparticles to target and internalize in tumor B-cells. Moreover, these nanoparticles could kill not only p53-mutated/deleted leukemia cells expressing a low amount of CD20, but also circulating primary cells isolated from chronic lymphocytic leukemia patients. The safety of these nanoparticles was also demonstrated in healthy mice, and their therapeutic effects were shown in a new model of aggressive leukemia. These results showed that anti-CD20 nanoparticles containing hydroxychloroquine and chlorambucil can be effective in controlling aggressive leukemia and provided a rationale for adopting this approach for the treatment of other B-cell disorders. [Figure not available: see fulltext.

Evaluación física y clínica de sementales bovinos en dos municipios de la costa chica de Guerrero, México

Objective: To evaluate the reproductive physical characteristics and general health of stallions in two municipalities of Costa Chica of Guerrero, Mexico. Design/methodology/approach: The study was carried out in the municipalities of Ometepec and Cuajinicuilapa. Thirty bulls between 2 and 10 years of age were evaluated. In the physical reproductive and clinical examination were performed by direct observation, using ultrasound to evaluate attached reproductive glands and testicular parenchyma. Blood samples were taken to determine the blood profile. Descriptive statistics was used to present the results. Results: The 86% of the bulls had adequate legs and feet as well as preputial length. Scrotal circumference was according to the age and breed of the animals. Testicular defects were showed for 30% of the bulls, the most common was hypoplasia and unilateral tumors of testicular parenchyma and epididymis, as well as calcifications of the testicular parenchyma. The 93% of the bulls had normal accessory genital glands. Clinically 24% of the bulls with signs suggestive of anaplasmosis were found. The 76% of the bulls, apparently healthy, presented monocytosis, thrombocytopenia and anemia. Limitations on study/implications: the lack of knowledge of the producers about the need for a comprehensive evaluation of the bulls allows them to suffer from diseases without receiving any type of treatment, decreasing their reproductive efficiency. Findings/conclusions: Most of the bulls evaluated had the minimum physical characteristics required, although the presence of anemia and respiratory diseases may have an indirect negative impact on the reproductive efficiency of the bulls.Objetivo: Evaluar las características físicas reproductivas y la salud general de los sementales en dos municipios de Costa Chica de Guerrero, México. Diseño/metodología/aproximación: Se evaluaron reproductiva y clínicamente 30 sementales, de entre 2 y 10 años. El examen reproductivo, se realizó por observación directa, empleándose ecografía para evaluar glándulas reproductivas anexas y el parénquima testicular. La evaluación clínica se realizó por medio del examen físico y perfil hemático. Se empleó estadística descriptiva para la presentación de los resultados. Resultados: El 86% de los sementales tuvieron aplomos y largo prepucial adecuado, así como circunferencia escrotal acorde a la edad y raza de los animales. El 30% de los sementales presentaron defectos testiculares, siendo los más comunes, hipoplasia y tumores unilaterales de parénquima testicular y epidídimos, así como calcificaciones del parénquima testicular. El 93% de las glándulas anexas fueron normales. Clínicamente se encontró un 24% de los sementales con signos sugerentes a anaplasmosis. El 76% de los toros, aparentemente sanos, presentaron monocitosis, trombocitopenia y anemia. Limitaciones del estudio/implicaciones: El desconocimiento de los productores sobre la necesidad de una evaluación integral de los sementales permite que éstos padezcan enfermedades que no son tratadas, disminuyendo su eficiencia reproductiva. Hallazgos/conclusiones: La mayoría de los sementales evaluados tuvieron las características físicas mínimas requeridas, aunque la presencia de anemia y enfermedades respiratorias pueden tener incidencia negativa indirecta sobre la eficiencia reproductiva de los sementales

Yield estimation of forage oat (Avena sativa L.) Chihuahua variety: ruler and plate methods

Objetive: To analyze forage estimations with the direct method and the plant height. Diseño/Metodología/Aproximación: The treatments were the plants age, assessed in a random block design, with three repetitions. Simple linear regressions were carried out and adjusted using the SPSS statistical software. Resultados: The highest and lowest yields occurred at 105 and 30 days after sowing (DAS), with 5,412 and 783 kg DM ha-1, respectively. Height with the rule had a significant effect on forage production, with an R2 of 0.83. For each increase per cm the plants increased 56,134 kg DM ha-1. The height with the plate had an R2 of 0.97, so that 65.032 kg DM ha-1 are produced for each cm in height. Limitaciones del estudio/implicaciones: None Hallazgos/conclusiones: The forage accumulation in Avena sativa L., var. Chihuahua varied depending on the age of the plant. The heights calculated with the plate method, had greater reliability for the forage yield estimate, compared to the graduated rule method

Effect of graphene oxide on bacteria and peripheral blood mononuclear cells

"Background Driven by the potential biological applications of graphene, many groups have studied the response of cells exposed to graphene oxide (GO). In particular, investigations of bacteria indicate that there are 2 crucial parameters, which so far have only been investigated separately: GO size and exposure methodology. Our study took into account both parameters. We carefully characterized the samples to catalog sizes and structural properties, and tested different exposure methodologies: exposure in saline solution and in the presence of growth media. Furthermore, we performed experiments with peripheral blood mononuclear cells exposed to our GO materials. Methods Atomic force microscopy, scanning electron microscopy, Raman spectroscopy, X-ray photoelectron spectroscopy and transmission electron microscopy were used to characterize the morphology and composition of different samples of GO: GO-H2O, GO-PBS and GO-MG. Our samples had 2D sizes of ?100 nm (GO-H2O and GO-PBS) and >2 µm (GO-MG). We tested antibacterial activity and cytotoxicity toward peripheral blood mononuclear cells of 3 different GO samples. Results A size-dependent growth inhibition of Escherichia coli (DH5 ?) in suspension was found, which proved that this effect depends strongly on the protocol followed for exposure. Hemocompatibility was confirmed by exposing peripheral blood mononuclear cells to materials for 24 hours; viability and apoptosis tests were also carried out. Conclusions Our experiments provide vital information for future applications of GO in suspension. If its antibacterial properties are to be potentiated, care should be taken to select 2D sizes in the micrometer range, and exposure should not be carried out in the presence of grow media.

A prominent β-hairpin structure in the winged-helix domain of RECQ1 is required for DNA unwinding and oligomer formation

RecQ helicases have attracted considerable interest in recent years due to their role in the suppression of genome instability and human diseases. These atypical helicases exert their function by resolving a number of highly specific DNA structures. The crystal structure of a truncated catalytic core of the human RECQ1 helicase (RECQ149–616) shows a prominent β-hairpin, with an aromatic residue (Y564) at the tip, located in the C-terminal winged-helix domain. Here, we show that the β-hairpin is required for the DNA unwinding and Holliday junction (HJ) resolution activity of full-length RECQ1, confirming that it represents an important determinant for the distinct substrate specificity of the five human RecQ helicases. In addition, we found that the β-hairpin is required for dimer formation in RECQ149–616 and tetramer formation in full-length RECQ1. We confirmed the presence of stable RECQ149–616 dimers in solution and demonstrated that dimer formation favours DNA unwinding; even though RECQ1 monomers are still active. Tetramers are instead necessary for more specialized activities such as HJ resolution and strand annealing. Interestingly, two independent protein–protein contacts are required for tetramer formation, one involves the β-hairpin and the other the N-terminus of RECQ1, suggesting a non-hierarchical mechanism of tetramer assembly