The challenges associated with analyzing rare cells are dependent on a series of factors, which usually require large numbers of cells per sample for successful resolution. Among these is determining ...the minimum number of total events needed to be acquired as defined by the expected frequency of the target cell population. The choice of markers that identify the target population, as well as the event rate and the number of aborted events/second, will also determine the statistically significant detection of rare cell events. Sample preparation is another important but often overlooked factor in rare cell analysis, and in this study we examine Poisson theory and methods to determine the effect of sample manipulation on rare cell detection. After verifying the applicability of this theory, we have evaluated the potential impact of red cell lysis on rare cell analysis, and how cell rarity can be underestimated or overestimated based on erythrolytic sensitivity or resistance of healthy leukocytes and pathological rare cells.
We have evaluated the potential impact of red cell lysis on rare cell analysis, and how cell rarity can be underestimated or overestimated based on erythrolytic sensitivity or resistance of healthy leukocytes and pathological rare cells.
The marine microbiome contains many billions of genes with the ability to express an unimaginable arsenal of small molecules, as well as proteins, lipids and others classes of products with ...ecological functions that can be ‘humanized’ for the discovery of new pharmaceuticals, improved enzymes, biopolymers and novel biomaterials, as well as new resources for food and feed stocks, nutraceuticals, diagnostic devices, personal care and cosmetic products and an ever‐increasing list of marine natural products. Metagenome approaches, including next‐generation gene sequencing, bioinformatics, functional genomics, transcriptomics, metabolomics and other OMICS technologies, including the efficient engineering of bacteria chassis for heterologous expression as well as knowledge of cell‐to‐cell communication are all transversal disciplines that can be used outside the realm of the human body to interpret the role of other global microbiomes, including the marine microbiome. New research strategies to mimic natural conditions through the use of elicitors, co‐cultures, quorum sensing signalling and the specific modulation of the genomic regulation systems are innovative applications of modern synthetic biology that will provide a new and more rational approach for drug discovery. Deep‐sea sampling, metagenomics, next‐generation sequencing, genome mining and bioinformatics, innovative chassis for heterologous expression of large gene clusters, culture of fastidious organisms, induction of silent biosynthetic gene clusters, new analytical technologies, development of new screening platforms for unknown mechanism of actions and a large list of transversal biotechnologies provide just a few examples of the many developing technologies that will unlock the potential of the marine microbiome and play a crucial role in future marine science.
En Colombia, de conformidad con el artículo 374, la Constitución Política podrá ser reformada por el Congreso mediante un acto legislativo, por una asamblea constituyente o por el pueblo mediante ...referendo; sin embargo, la Corte Constitucional realiza actos de construcción jurídica cuya consecuencia es una mutación en la Constitución a través de la creación de normas implícitas como es el caso del estado de cosas inconstitucional, que da lugar al establecimiento de una nueva regla constitucional. Lejos de considerar que la interpretación del derecho es abiertamente discrecional o que, como lo manifiestan algunos autores (Suárez-Parra, 2007; López, 2011), la Corte Constitucional colombiana “legisle” o genere inseguridad jurídica, la creación de derecho en sede interpretativa es algo que no genera incompatibilidad con nuestra cultura jurídica, tal como lo indican Kelsen (1982), Tarello (2013) y Gómez (2018). La tesis planteada consiste en comprobar que los argumentos de la interpretación de la Corte corresponden con la teoría del escepticismo interpretativo del realismo genovés, aplicado a la figura de declaratoria de estado de cosas inconstitucional, cuyo fin es proteger los derechos fundamentales de la población Wayúu en La Guajira, especialmente el derecho a la alimentación en las sentencias de la Corte Constitucional de Colombia (T-302 de 2017, T-359 de 2018).
Two new bioactive polyhydroxyl macrolide lactones PM100117 (1) and PM100118 (2) were isolated from the culture broth of the marine-derived Streptomyces caniferus GUA-06-05-006A. Their structures were ...elucidated by a combination of spectroscopic methods, mainly one-dimensional and 2D NMR and HRESI-MS. They consist of 36-membered macrolides with a side chain containing three deoxy sugars and a 1,4-naphthoquinone chromophore. Compounds 1 and 2 displayed potent cytotoxicity against three human tumor cell lines with GI50 values in the micromolar range, as well as slight antifungal activity against Candida albicans ATCC10231. In addition, both compounds alter the plasma membrane of tumor cells, inducing loss of membrane integrity and subsequent cell permeabilization leading to a fast and dramatic necrotic cell death.
Bone cement, frequently based on poly (methyl methacrylate), is commonly used in different arthroplasty surgical procedures and its use is essential for prosthesis fixation. However, its ...manufacturing process reaches high temperatures (up to 120 °C), producing necrosis in the patients’ surrounding tissues. To help avoid this problem, the addition of graphene could delay the polymerisation of the methyl methacrylate as it could, simultaneously, favour the optimisation of the composite material’s properties. In this work, we address the effect of different percentages of highly reduced graphene oxide with different wt.% (0.10, 0.50, and 1.00) and surface densities (150, 300, 500, and 750 m2/g) on the physical, mechanical, and thermal properties of commercial poly (methyl methacrylate)-based bone cement and its processing. It was noted that a lower sintering temperature was achieved with this addition, making it less harmful to use in surgery and reducing its adverse effects. In contrast, the variation of the density of the materials did not introduce significant changes, which indicates that the addition of highly reduced graphene oxide would not significantly increase bone porosity. Lastly, the mechanical properties (strength, elastic modulus, and fracture toughness) were reduced by almost 20%. Nevertheless, their typical values are high enough that these new materials could still fulfil their structural function. In conclusion, this paper presents a way to control the sintering temperature, without significant degradation of the mechanical performance, by adding highly reduced graphene oxide so that local necrosis of bone cement based on poly (methyl methacrylate) used in surgery is avoided.
Summary
Glutarimide‐containing polyketides are known as potent antitumoral and antimetastatic agents. The associated gene clusters have only been identified in a few Streptomyces producers and ...Burkholderia gladioli symbiont. The new glutarimide‐family polyketides, denominated sesbanimides D, E and F along with the previously known sesbanimide A and C, were isolated from two marine alphaproteobacteria Stappia indica PHM037 and Labrenzia aggregata PHM038. Structures of the isolated compounds were elucidated based on 1D and 2D homo and heteronuclear NMR analyses and ESI‐MS spectrometry. All compounds exhibited strong antitumor activity in lung, breast and colorectal cancer cell lines. Subsequent whole genome sequencing and genome mining revealed the presence of the trans‐AT PKS gene cluster responsible for the sesbanimide biosynthesis, described as sbn cluster. Strikingly, the modular architecture of downstream mixed type PKS/NRPS, SbnQ, revealed high similarity to PedH in pederin and Lab13 in labrenzin gene clusters, although those clusters are responsible for the production of structurally completely different molecules. The unexpected presence of SbnQ homologues in unrelated polyketide gene clusters across phylogenetically distant bacteria, raises intriguing questions about the evolutionary relationship between glutarimide‐like and pederin‐like pathways, as well as the functionality of their synthetic products.
Self-heating effects in AlGaN/GaN high-electron mobility transistors grown on three different substrates have been evaluated for ambient temperatures between 0 ° C and 225 ° C. A simple and accurate ...electrical method for the estimation of channel temperature is proposed. This technique is based on the difference in drain current between dc and short-pulsed conditions. Being an electrical method, neither special geometry nor expensive equipments are required. Simulations have also been performed to confirm the results. We have applied our technique to different device structures and geometries, demonstrating its sensitivity and validity at different ambient temperatures.
Resumen: Este trabajo tiene por objeto demostrar la existencia de la obligación y del derecho a la protección contra el desplazamiento forzado por factores medioambientales, a partir del derecho al ...medio ambiente sano, en el marco del Sistema Interamericano de Derechos Humanos. Para tal fin, la hermenéutica jurídica contribuye, en primer lugar, a definir el concepto de desplazamiento por factores medioambientales y sus categorías. En segundo lugar, desde la caracterización del derecho al medio ambiente sano como un Derecho Económico, Social, Cultural y Ambiental se relata el debate jurisprudencial y doctrinal de la exigibilidad de esta última categoría, haciendo énfasis en el método de derivación de derechos del artículo 26 de la Convención Americana sobre Derechos Humanos. Luego, se sugiere recurrir al artículo 25.1 de la Convención a fin de complementar el método de derivación de derechos del artículo 26 convencional con base en la derivación de derechos a partir del marco legal de los Estados parte. Finalmente, se analizan las obligaciones internacionales, para verificar la viabilidad de la exigencia de protección contra el desplazamiento por factores medioambientales.
Cassava (Manihot esculenta, Crantz) is an important food security crop, but it is becoming an important raw material for different industrial applications. Cassava is the second most important source ...of starch worldwide. Novel starch properties are of interest to the starch industry, and one them is the recently identified amylose-free (waxy) cassava starch. Waxy mutants have been found in different crops and have been often associated with a yield penalty. There are ongoing efforts to develop commercial cassava varieties with amylose-free starch. However, little information is available regarding the biological and agronomic implications of starch mutations in cassava, nor in other root and tuber crops. In this study, siblings from eight full-sib families, segregating for the waxy trait, were used to determine if the mutation has implications for yield, dry matter content (DMC) and harvest index in cassava. A total of 87 waxy and 87 wild-type starch genotypes from the eight families were used in the study. The only significant effect of starch type was on DMC (p < 0.01), with waxy clones having a 0.8% lower content than their wild type counterparts. There was no effect of starch type on fresh root yield (FRY), adjusted FRY and harvest index. It is not clear if lower DMC is a pleiotropic effect of the waxy starch mutation or else the result of linked genes introgressed along with the mutation. It is expected that commercial waxy cassava varieties will have competitive FRYs but special efforts will be required to attain adequate DMCs. This study contributes to the limited knowledge available of the impact of starch mutations on the agronomic performance of root and tuber crops.
Three novel lipopeptides, PM130391 (1), PM130392 (2), and PM140293 (3) were obtained from cultures of Streptomyces tuirus PHM034 isolated from a marine sediment. Structural elucidation of the three ...compounds showed they belong to the nonribosomal peptides family, and they all contain an acylated alanine, three piperazic acids, a methylated glycine, and an N-hydroxylated alanine. The difference between the three compounds resides in the acyl chain bound to the alanine residue. All three compounds showed cytotoxic activity against human cancer cell lines. Genome sequence and bioinformatics analysis allowed the identification of the gene cluster responsible for the biosynthesis. Inactivation of a nonribosomal peptide synthase of this cluster abolished the biosynthesis of the three compounds, thus demonstrating the involvement of this cluster in the biosynthesis of these lipopeptides.
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