LATS1 controls CTCF chromatin occupancy and hormonal response of 3D-grown breast cancer cells.

The cancer epigenome has been studied in cells cultured in two-dimensional (2D) monolayers, but recent studies highlight the impact of the extracellular matrix and the three-dimensional (3D) environment on multiple cellular functions. Here, we report the physical, biochemical, and genomic differences between T47D breast cancer cells cultured in 2D and as 3D spheroids. Cells within 3D spheroids exhibit a rounder nucleus with less accessible, more compacted chromatin, as well as altered expression of ~2000 genes, the majority of which become repressed. Hi-C analysis reveals that cells in 3D are enriched for regions belonging to the B compartment, have decreased chromatin-bound CTCF and increased fusion of topologically associating domains (TADs). Upregulation of the Hippo pathway in 3D spheroids results in the activation of the LATS1 kinase, which promotes phosphorylation and displacement of CTCF from DNA, thereby likely causing the observed TAD fusions. 3D cells show higher chromatin binding of progesterone receptor (PR), leading to an increase in the number of hormone-regulated genes. This effect is in part mediated by LATS1 activation, which favors cytoplasmic retention of YAP and CTCF removal.

Choosing the right partner in hormone-dependent gene regulation: Glucocorticoid and progesterone receptors crosstalk in breast cancer cells.

Steroid hormone receptors (SHRs) belong to a large family of ligand-activated nuclear receptors that share certain characteristics and possess others that make them unique. It was thought for many years that the specificity of hormone response lay in the ligand. Although this may be true for pure agonists, the natural ligands as progesterone, corticosterone and cortisol present a broader effect by simultaneous activation of several SHRs. Moreover, SHRs share structural and functional characteristics that range from similarities between ligand-binding pockets to recognition of specific DNA sequences. These properties are clearly evident in progesterone (PR) and glucocorticoid receptors (GR); however, the biological responses triggered by each receptor in the presence of its ligand are different, and in some cases, even opposite. Thus, what confers the specificity of response to a given receptor is a long-standing topic of discussion that has not yet been unveiled. The levels of expression of each receptor, the differential interaction with coregulators, the chromatin accessibility as well as the DNA sequence of the target regions in the genome, are reliable sources of variability in hormone action that could explain the results obtained so far. Yet, to add further complexity to this scenario, it has been described that receptors can form heterocomplexes which can either compromise or potentiate the respective hormone-activated pathways with its possible impact on the pathological condition. In the present review, we summarized the state of the art of the functional cross-talk between PR and GR in breast cancer cells and we also discussed new paradigms of specificity in hormone action.

NOMAD spectrometer on the ExoMars trace gas orbiter mission: part 2-design, manufacturing, and testing of the ultraviolet and visible channel.

NOMAD is a spectrometer suite on board the ESA/Roscosmos ExoMars Trace Gas Orbiter, which launched in March 2016. NOMAD consists of two infrared channels and one ultraviolet and visible channel, allowing the instrument to perform observations quasi-constantly, by taking nadir measurements at the day- and night-side, and during solar occultations. Here, in part 2 of a linked study, we describe the design, manufacturing, and testing of the ultraviolet and visible spectrometer channel called UVIS. We focus upon the optical design and working principle where two telescopes are coupled to a single grating spectrometer using a selector mechanism.

Técnica de lavado pulmonar en lactante con proteinosis alveolar / A lung lavage technique in an infant with pulmonary alveolar proteinosis

No disponible

NOMAD spectrometer on the ExoMars trace gas orbiter mission: part 1--design, manufacturing and testing of the infrared channels.

NOMAD is a spectrometer suite on board ESA's ExoMars trace gas orbiter due for launch in January 2016. NOMAD consists of two infrared channels and one ultraviolet and visible channel allowing the instrument to perform observations quasi-constantly, by taking nadir measurements at dayside and nightside, and during solar occultations. In this paper, the design, manufacturing, and testing of the two infrared channels are described. We focus upon the optical working principle in these channels, where an echelle grating, used as a diffractive element, is combined with an acousto-optical tunable filter, used as a diffraction order sorter.

Técnica del catéter de analgesia intraincisional. Una alternativa para el control del dolor postoperatorio en cirugía de la mama / Intraincisional analgesia catheter techniques. An alternative for managing postoperative pain in breast surgery

Objetivo: La analgesia postoperatoria en cirugía de la mama sigue siendo un reto. Presentamos la técnica de colocación de un catéter para la perfusión continua de anestésicos locales en cirugía de mama como alternativa a los métodos analgésicos actuales. Casos clínicos: Caso 1. Mujer de 59 años con un carcinoma en la mama derecha con ganglios axilares negativos. Se realizó mastectomía derecha y se colocó catéter de analgesia interpectoral. Caso 2. Mujer de 52 años con un carcinoma en la mama derecha y ganglios axilares positivos. Se realizó mastectomía tipo Madden y se colocó catéter de analgesia interpectoral y axilar derecho. Se retiró el catéter a las 48 horas sin complicaciones. Conclusiones: El uso de perfusión continua de anestésico local en la herida quirúrgica mediante catéter multiperforado es una alternativa eficaz para el control del dolor postoperatorio en cirugía de la mama, lo cual disminuye los requerimientos y los efectos secundarios de antiinflamatorios sistémicos y opioides(AU)

Introduction: Postoperative analgesia in breast surgery is still a challenge. We present a technique for continuous perfusion of anaesthetics through an "in situ" placed catheter, as an alternative to the current analgesic methods in breast surgery. Case reports: Case 1. A 59 year old woman with carcinoma in the right breast and negative axillary nodes had a right mastectomy and an interpectoral analgesia catheter was inserted. Case 2. A 52 year old woman with carcinoma in the right breast and positive axillary nodes. A right Madden mastectomy was performed and an interpectoral and right axillary analgesia catheter was inserted. The catheter was removed 48 hours later with no complications. Conclusions: The use of continuous perfusion in surgical wounds by means of a multiperforated catheter is an effective option for the treatment of post-surgical pain in breast surgery. This technique reduces the requirements, and potential side effects, of systemic anti-inflammatory drugs and opioids(AU)

Catalase deficiency in Staphylococcus aureus subsp. anaerobius is associated with natural loss-of-function mutations within the structural gene.

Degenerate oligonucleotide primers based on internal peptide sequences obtained by HPLC from purified Staphylococcus aureus catalase were used to locate the S. aureus and S. aureus subsp. anaerobius kat regions by PCR. Southern hybridization analysis with a probe derived from a 1.1 kb PCR-amplified fragment showed that a single copy of the putative catalase gene was present in the S. aureus and S. aureus subsp. anaerobius chromosome. The nucleotide sequence of S. aureus katA revealed a 1518 bp open reading frame for a protein with 505 amino acids and a predicted molecular mass of 58347 Da, whereas S. aureus subsp. anaerobius katB is 1368 nt long and encodes a polypeptide of 455 amino acids with a predicted molecular mass of 52 584 Da. These catalases are highly homologous to typical monofunctional catalases from prokaryotes. The active-site residues, proximal and distal haem-binding ligands and NADPH-binding residues of the bovine liver catalase-type enzyme were highly conserved in S. aureus KatA. Escherichia coli cells carrying cloned katA had a catalase activity approximately 1000 times that of untransformed E. coli, but no detectable increase in catalase activity was observed with E. coli carrying cloned katB. Northern blotting showed the presence of a kat-specific transcript in S. aureus subsp. anaerobius, suggesting that the lack of catalase activity in this bacterium is due to a post-transcriptional alteration. Compared to the nucleotide sequence of katA, katB showed a single base-pair deletion and six mis-sense mutations, and these alterations were present in three other S. aureus subsp. anaerobius strains analysed. The deletion, located at 1338 bp from the initiation codon, originates a shift of the nucleotide reading frame and is responsible for the premature translation termination at 1368 bp, generating a KatB polypeptide 50 amino acid residues shorter than KatA. Moreover, four of the mis-sense mutations present in katB lead to non-conservative amino acid replacements, the most significant being that located at residue 317 (Pro in KatA-->Ser in KatB) because the affected amino acid is involved in determining the proximal haem-binding site. Both the main alterations found in KatB (the deletion and the substitution in residue 317) seem to contribute to the lack of catalase activity in S. aureus subsp. anaerobius, as deduced from results obtained with chimeric catalase constructs.

Estudio sobre el comportamiento de dos nuevas bolsas cerradas de ostomía, de diseño único y con dos tipos diferentes de protector cutáneo / Study on the performance of two new ostomy closed bags of unique design with two different types of cutaneous protector

Se estudia el comportamiento de las bolsas cerradas Almarys Optima(R) y Almaris Quiet(R), en personas ostomizadas, en el ámbito geográfico del estado español. Se analiza el comportamiento de los dos protectores cutáneos de dichas bolsas en función de las características de las personas ostomizadas; se valora su nivel de seguridad, discreción, comodidad; se analiza si las características de los pacientes ostomizados influyen en la valoración efectuada de estas nuevas bolsas. El estudio ha sido prospectivo a simple ciego y multicéntrico. se concluye que la valoración de ambas bolsas es muy positiva tanto por los usuarios como por los profesionales sanitarios encargados de efectuar el estudio, aunque se destaca la oportunidad de abordar la utilización de una u otra de las bolsas en función del tipo de piel y de la actividad física realizada por el usuario (AU)