The nuclear mitotic apparatus protein NuMA controls rDNA transcription and mediates the nucleolar stress response in a p53-independent manner.

The nuclear mitotic apparatus protein, NuMA, is involved in major cellular events such as DNA damage response, apoptosis and p53-mediated growth-arrest, all of which are under the control of the nucleolus upon stress. Proteomic investigation has identified NuMA among hundreds of nucleolar proteins. Yet, the precise link between NuMA and nucleolar function remains undetermined. We confirm that NuMA is present in the nucleolus and reveal redistribution of NuMA upon actinomycin D or doxorubicin-induced nucleolar stress. NuMA coimmunoprecipitates with RNA polymerase I, with ribosomal proteins RPL26 and RPL24, and with components of B-WICH, an ATP-dependent chromatin remodeling complex associated with rDNA transcription. NuMA also binds to 18S and 28S rRNAs and localizes to rDNA promoter regions. Downregulation of NuMA expression triggers nucleolar stress, as shown by decreased nascent pre-rRNA synthesis, fibrillarin perinucleolar cap formation and upregulation of p27kip1, but not p53. Physiologically relevant nucleolar stress induction with reactive oxygen species reaffirms a p53-independent p27kip1 response pathway and leads to nascent pre-rRNA reduction. It also promotes the decrease in the amount of NuMA. This previously uncharacterized function of NuMA in rDNA transcription and p53-independent nucleolar stress response supports a central role for this nuclear structural protein in cellular homeostasis.

NuMA promotes homologous recombination repair by regulating the accumulation of the ISWI ATPase SNF2h at DNA breaks.

Chromatin remodeling factors play an active role in the DNA damage response by shaping chromatin to facilitate the repair process. The spatiotemporal regulation of these factors is key to their function, yet poorly understood. We report that the structural nuclear protein NuMA accumulates at sites of DNA damage in a poly[ADP-ribose]ylation-dependent manner and functionally interacts with the ISWI ATPase SNF2h/SMARCA5, a chromatin remodeler that facilitates DNA repair. NuMA coimmunoprecipitates with SNF2h, regulates its diffusion in the nucleoplasm and controls its accumulation at DNA breaks. Consistent with NuMA enabling SNF2h function, cells with silenced NuMA exhibit reduced chromatin decompaction after DNA cleavage, lesser focal recruitment of homologous recombination repair factors, impaired DNA double-strand break repair in chromosomal (but not in episomal) contexts and increased sensitivity to DNA cross-linking agents. These findings reveal a structural basis for the orchestration of chromatin remodeling whereby a scaffold protein promotes genome maintenance by directing a remodeler to DNA breaks.

3D photogrammetry as a tool for studying erosive processes at a Roman coastal site: the case of the Roman fish-salting plant at Sobreira (Vigo, Spain).

Rising sea levels, along with other biological and human factors, have increased erosion rates at a number of important sites located along the Atlantic coastline. Project GaltFish implemented a series of contingency measures to record some of these sites before they degraded further or totally disappeared. This process involved detailed photogrammetric recording of some of the sites under threat over a set period of time. One of the sites selected for this project was Sobreira (Vigo, Galicia): a Roman fish-salting factory which was partially destroyed by building activity in the 1980s and the remains of which are under threat from marine erosion and human action. In order to study the site, two photogrammetric models were created to examine the effect of erosive processes across the course of one year. The results illustrate that photogrammetry is an efficient tool for recording and analysing the issue of erosion. The data compiled helped in designing additional action in the factory, which was subject to a rescue excavation to record and help protect the site from further damage. This paper presents the results of this project, as well as the methodology used to produce the models, the data generated and their analysis. It is argued that the methodology can be used to collect and analyse data from other sites, and that this data could inform the political/administrative decision-making processes which concern the future management and preservation of archaeological sites under threat.

NuMA influences higher order chromatin organization in human mammary epithelium.

The coiled-coil protein NuMA is an important contributor to mitotic spindle formation and stabilization. A potential role for NuMA in nuclear organization or gene regulation is suggested by the observations that its pattern of nuclear distribution depends upon cell phenotype and that it interacts and/or colocalizes with transcription factors. To date, the precise contribution of NuMA to nuclear function remains unclear. Previously, we observed that antibody-induced alteration of NuMA distribution in growth-arrested and differentiated mammary epithelial structures (acini) in three-dimensional culture triggers the loss of acinar differentiation. Here, we show that in mammary epithelial cells, NuMA is present in both the nuclear matrix and chromatin compartments. Expression of a portion of the C terminus of NuMA that shares sequence similarity with the chromatin regulator HPC2 is sufficient to inhibit acinar differentiation and results in the redistribution of NuMA, chromatin markers acetyl-H4 and H4K20m, and regions of deoxyribonuclease I-sensitive chromatin compared with control cells. Short-term alteration of NuMA distribution with anti-NuMA C-terminus antibodies in live acinar cells indicates that changes in NuMA and chromatin organization precede loss of acinar differentiation. These findings suggest that NuMA has a role in mammary epithelial differentiation by influencing the organization of chromatin.

Mucoadhesive polymers: Synthesis and in vitro characterization of thiolated poly(vinyl alcohol).

The aim of this study was to synthesize thiolated poly(vinyl alcohol) (PVA) and to evaluate its mucoadhesive properties. Thiourea and 3-mercaptopropionic acid were utilized in order to obtain thiolated PVAs, namely, TPVA1 and TPVA2, respectively. TPVA1 and TPVA2 displayed 130.44 ± 14.99 and 958.35 ± 155.27 µmol immobilized thiol groups per gram polymer, respectively, which were then evaluated regarding reactivity of thiol groups, swelling behavior and mucoadhesive properties. Both thiolated PVAs exhibited the highest reactivity at pH 8.0 whereas more than 95% of free thiol groups were preserved at pH 5.0. Thiolation of PVA decelerated water uptake and prolonged disintegration time of test discs compared to unmodified PVA. Contact time of TPVA1- and TPVA2-based test discs on porcine intestinal mucosa was 3.2- and 15.8-fold prolonged, respectively, in comparison to non-thiolated PVA as measured by rotating cylinder method. According to tensile studies on mucosa, the total work of adhesion (TWA) and the maximum detachment force (MDF) were increased when compared to PVA. Furthermore, thiolated PVAs preserved higher percentage of viable cells compared to unmodified PVA within 24h as evaluated by MTT assay. Accordingly, thiolated PVA represents a novel excipient that can likely improve the mucoadhesive properties of various pharmaceutical formulations.

El embarazo en mujeres con lupus eritematoso sistémico: una revisión integrativa / Pregnancy in women with systemic lupus erythematosus: an integrative review

INTRODUCCIÓN: En la actualidad, se conoce que el lupus eritematoso sistémico no afecta a la fertilidad; sin embargo, el embarazo en mujeres que lo padecen se asocia a riesgos, tanto maternos como fetales. OBJETIVO: Determinar las variables que intervienen en la preparación y control de la gestación en mujeres con lupus eritematoso sistémico, así como las medidas de enfermería más importantes. MATERIAL Y MÉTODO: Se ha realizado una revisión integrativa mediante una búsqueda en las bases de datos Proquest, Pubmed y Web of Science. Se incluyeron artículos científicos originales, observacionales y de revisión, en inglés y español, excluyendo aquellos artículos anteriores a 2009 o que no estuviesen en texto completo. RESULTADOS: Se han incluido 15 artículos publicados entre el año 2009 y 2019. El embarazo en pacientes con lupus eritematoso sistémico es complejo, ya que necesita de un control exhaustivo y continuo para conseguir buenos resultados. Un cambio de tratamiento, test de laboratorio cada cierto tiempo y la vigilancia de un equipo multidisciplinar, harán que la enfermedad se encuentre controlada y los riesgos de complicaciones maternas y fetales disminuyan. CONCLUSIONES: En la actualidad, la mayoría de las mujeres con lupus eritematoso sistémico pueden conseguir el objetivo de la maternidad, siempre y cuando la enfermedad se encuentre controlada al menos 6 meses antes de la concepción y durante todo el embarazo. Las variables más determinantes en el embarazo de la mujer con lupus eritematoso sistémico son la fertilidad, las complicaciones o el tratamiento, que influyen de forma directa sobre el embarazo

INTRODUCTION: At present, it is known that systemic lupus erythematosus does not affect fertility; however, pregnancy in these women is associated with risks, both maternal and fetal. OBJECTIVE: To determine the variables involved in the preparation and control of pregnancy in women with systemic lupus erythematosus, as well as the most important nursing actions. MATERIAL AND METHOD: An integrative review has been carried out through a search in the ProQuest, PubMed and Web of Science databases. Original, observational and review scientific articles were included, in English and Spanish, excluding those articles published before 2009 or that were not in full text in the databases. RESULTS: 15 articles published between 2009 and 2019 have been included. Pregnancy in patients with systemic lupus erythematosus is complex. Comprehensive and continuous control is required to achieve good results. A change of treatment, laboratory tests from time to time and the monitoring of a multidisciplinary team will control the disease and will reduce the risk of maternal and fetal complications. CONCLUSIONS: Currently, most women with systemic lupus erythematosus can achieve the goal of motherhood, if the disease is controlled at least 6 months before conception and throughout pregnancy. The most determinant variables in pregnancy of women with systemic lupus erythematosus are fertility, complications or treatment, which directly influence pregnancy

"Más que dolor": experiencia de pacientes dializados respecto a su punción en hemodiálisis / "More than pain": experiences of dialyzed patients regarding their puncture in hemodialysis

INTRODUCCIÓN: El dolor a la punción de la fístula arteriovenosa es una constante en todos los pacientes en hemodiálisis. OBJETIVO: El propósito del estudio fue explorar la percepción del dolor a la punción en los pacientes en hemodiálisis, analizando tanto emociones como ideas sobre su calidad de vida. MATERIAL Y MÉTODO: Se realizó un estudio cualitativo, de carácter fenomenológico, en el Hospital Universitario Reina Sofía de Córdoba, en la Unidad de Nefrología y en el Servicio de Consultas Externas "El Perpetuo Socorro" (que también pertenece al mismo hospital). Se realizaron entrevistas semiestructuradas a diez pacientes, hombres y mujeres, que sufrían de Insuficiencia Renal Crónica bajo tratamiento de hemodiálisis. RESULTADOS: Se llevó a cabo un análisis de contenido del que emergieron tres categorías principales asociadas a distintas subcategorías: 1) Doler, duele ¿eh? Pero… (Mejora con el tiempo; Cuando duele lo hace de verdad; ¿Duele? Ni te enteras); 2) Ansiedad y miedos relacionados con la intervención (Cuestión de mentalizarse; Ansiedad anticipatoria; Desesperación e inseguridad ante complicaciones y desinformación; ¡Por Dios, que no se rompa la fístula!; Las manos de la enfermera); 3) Una calidad de vida comprometida (Muchas limitaciones; Pero no tiene tanto impacto; ¿Catéter o fístula?). CONCLUSIONES: El estudio permitió describir las percepciones de los pacientes en hemodiálisis en torno a la punción, su contexto y consecuencias, posibilitando, primero, una mayor comprensión y empatía en los profesionales de la salud y, después, una base para otras aproximaciones indagatorias al fenómeno en cuestión

INTRODUCTION: Pain during puncture of the arteriovenous fistula is a constant in all hemodialysis patients. OBJECTIVE: The purpose of the study was to explore the perception of pain during puncture in hemodialysis patients, analyzing both emotions and ideas about their quality of life. MATERIAL AND METHOD: A qualitative study with a phenomenological approach was carried out at the Reina Sofía University Hospital in Córdoba, at the Nephrology Unit and at the External Consultation Service "El Perpetuo Socorro" (which also belongs to the same hospital). Semi-structured interviews were conducted with ten patients, men and women suffering from chronic renal failure on hemodialysis. RESULTS: A content analysis was carried out from which three main categories associated with different subcategories emerged: 1) It hurts, it hurts, huh? But... (Improves over time; When it hurts, it does; Does it hurt? You don't even know); 2) Anxiety and fears related to the intervention (Question of make aware; Anticipatory anxiety; Despair and insecurity in the face of complications and misinformation; For God's sake, do not break the fistula!; The nurse's hands); 3) A compromised quality of life (Many limitations; But it doesn't have that much impact; catheter or fistula?). CONCLUSIONS: The study allowed describing the perceptions of hemodialysis patients regarding puncture, context and consequences, allowing, first, a greater understanding and empathy in health professionals and, later, a basis for other approaches to the phenomenon

The C terminus of the nuclear protein NuMA: phylogenetic distribution and structure.

The C terminus of the nuclear protein NuMA, NuMA-CT, has a well-known function in mitosis via its proximal segment, but it seems also involved in the control of differentiation. To further investigate the structure and function of NuMA, we exploited established computational techniques and tools to collate and characterize proteins with regions similar to the distal portion of NuMA-CT (NuMA-CTDP). The phylogenetic distribution of NuMA-CTDP was examined by PSI-BLAST- and TBLASTN-based analysis of genome and protein sequence databases. Proteins and open reading frames with a NuMA-CTDP-like region were found in a diverse set of vertebrate species including mammals, birds, amphibia, and early teleost fish. The potential structure of NuMA-CTDP was investigated by searching a database of protein sequences of known three-dimensional structure with a hidden Markov model (HMM) estimated using representative (human, frog, chicken, and pufferfish) sequences. The two highest scoring sequences that aligned to the HMM were the extracellular domains of beta3-integrin and Her2, suggesting that NuMA-CTDP may have a primarily beta fold structure. These data indicate that NuMA-CTDP may represent an important functional sequence conserved in vertebrates, where it may act as a receptor to coordinate cellular events.

Trastornos del sueño en el paciente con enfermedad renal crónica avanzada / Sleep disorders in advanced chronic kidney disease patients

Objetivo: Conocer las alteraciones y/o trastornos del sueño en los pacientes con Enfermedad Renal Crónica Avanzada. Material y Método: Se realizó una búsqueda en las bases de datos Google Académico, Scielo, Science Direct, PubMed y Scopus. Se incluyeron artículos científicos en español e inglés y texto completo disponible. Se analizaron aquellos artículos que trataban sobre alteraciones del sueño en los pacientes en prediálisis, y en tratamiento renal sustitutivo: Hemodiálisis, Diálisis Peritoneal y Trasplante Renal. Resultados: Se han incluido 30 artículos publicados entre los años 2013 y 2018. Los pacientes con Enfermedad Renal Crónica Avanzada presentan una alta prevalencia de alteraciones del sueño, llegando a alcanzar una prevalencia de casi el 90% en pacientes en hemodiálisis y diálisis peritoneal, y 62% en pacientes con trasplante renal; y entre el 44% y el 77% en la etapa prediálisis. Las alteraciones del sueño más frecuentes encontradas, fueron: insomnio, síndrome de piernas inquietas, apnea del sueño y somnolencia diurna excesiva. Como principales medidas y tratamientos utilizados para las alteraciones del sueño en estos pacientes se han encontrado terapias tanto farmacológicas, como no farmacológicas y la combinación de ambas. Conclusiones: Las alteraciones del sueño tienen una alta prevalencia en los pacientes con Enfermedad Renal Crónica Avanzada, tanto en prediálisis como en tratamiento renal sustitutivo; siendo las más frecuentes el insomnio, el síndrome de piernas inquietas, la apnea obstructiva del sueño y la somnolencia diurna excesiva. Entre los factores de riesgo más influyentes destacan: ansiedad y depresión, Diabetes Mellitus, hipertensión arterial, problemas respiratorios y tiempo en diálisis

Objective: To know the disturbances and/or sleep disorders in Advanced Chronic Kidney Disease patients. Material and Method: A search was made in the Google Scholar, Scielo, Science Direct, PubMed and Scopus databases. Scientific articles in Spanish and English and full-text available were included. Those articles dealing with sleep disorders in patients on pre-dialysis and renal replacement therapy were analyzed: Hemodialysis, Peritoneal Dialysis and Renal Transplantation. Results: 30 articles published between 2013 and 2018 were included. Patients with Advanced Chronic Kidney Disease have a high prevalence of sleep disturbances, reaching a prevalence of almost 90% in patients on hemodialysis and peritoneal dialysis, and 62% in patients with renal transplantation; and between 44% and 77% in the pre-dialysis stage. The most frequent sleep disorders found were: insomnia, restless legs syndrome, sleep apnea and excessive daytime sleepiness. Pharmacological and non-pharmacological therapies and its combination were found as main measures and treatments for sleep disorders in these patients. Conclusions: Sleep disorders have a high prevalence in patients with Advanced Chronic Kidney Disease, both in pre-dialysis and in renal replacement therapy; being the most frequent insomnia, restless legs syndrome, obstructive sleep apnea and excessive daytime sleepiness. Among the most influential risk factors include: anxiety and depression, diabetes mellitus, high blood pressure, respiratory problems and dialysis time

The control of tissue architecture over nuclear organization is crucial for epithelial cell fate.

The remodeling of nuclear organization during differentiation and the dramatic alteration of nuclear organization associated with cancer development are well documented. However, the importance of tissue architecture in the control of nuclear organization remains to be determined. Differentiation of mammary epithelial cells into functional tissue structures, in three-dimensional culture, is characterized by a specific tissue architecture (i.e. a basoapical polarity axis), cell cycle exit and maintenance of cell survival. Here we show that induction of partial differentiation (i.e. basal polarity only, cell cycle exit and cell survival) by epigenetic mechanisms in malignant breast cells is sufficient to restore features of differentiation-specific nuclear organization, including perinucleolar heterochromatin, large splicing factor speckles, and distinct nuclear mitotic apparatus protein (NuMA) foci. Upon alteration of nuclear organization using an antibody against NuMA, differentiated non-neoplastic cells undergo apoptosis, whereas partially differentiated malignant cells enter the cell cycle. Non-neoplastic cells cultured under conditions that prevent the establishment of apical polarity also enter the cell cycle upon NuMA antibody treatment. These findings demonstrate that the differentiation status rather than the non-neoplastic or neoplastic origin of cells controls nuclear organization and suggest a link between nuclear organization and epigenetic mechanisms dictated by tissue architecture for the control of cell behavior.