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1.
NAR Cancer ; 6(2): zcae024, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38751936

RESUMO

In this review, we explore the transformative impact of next generation sequencing technologies in the realm of translatomics (the study of how translational machinery acts on a genome-wide scale). Despite the expectation of a direct correlation between mRNA and protein content, the complex regulatory mechanisms that affect this relationship remark the limitations of standard RNA-seq approaches. Then, the review characterizes crucial techniques such as polysome profiling, ribo-seq, trap-seq, proximity-specific ribosome profiling, rnc-seq, tcp-seq, qti-seq and scRibo-seq. All these methods are summarized within the context of cancer research, shedding light on their applications in deciphering aberrant translation in cancer cells. In addition, we encompass databases and bioinformatic tools essential for researchers that want to address translatome analysis in the context of cancer biology.

2.
Life Sci Alliance ; 7(3)2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38176727

RESUMO

Activating transcription factor 4 (Atf4), which is modulated by the protein kinase RNA-like ER kinase (PERK), is a stress-induced transcription factor responsible for controlling the expression of a wide range of adaptive genes, enabling cells to withstand stressful conditions. However, the impact of the Atf4 signaling pathway on airway regeneration remains poorly understood. In this study, we used mouse airway epithelial cell culture models to investigate the role of PERK/Atf4 in respiratory tract differentiation. Through pharmacological inhibition and silencing of ATF4, we uncovered the crucial involvement of PERK/Atf4 in the differentiation of basal stem cells, leading to a reduction in the number of secretory cells. ChIP-seq analysis revealed direct binding of ATF4 to regulatory elements of genes associated with osteoblast differentiation and secretory cell function. Our findings provide valuable insights into the role of ATF4 in airway epithelial differentiation and its potential involvement in innate immune responses and cellular adaptation to stress.


Assuntos
Estresse do Retículo Endoplasmático , eIF-2 Quinase , Animais , Camundongos , eIF-2 Quinase/genética , Estresse do Retículo Endoplasmático/genética , Fator 4 Ativador da Transcrição/genética , Fator 4 Ativador da Transcrição/metabolismo , Diferenciação Celular/genética , Sistema Respiratório/metabolismo
3.
Nurs Rep ; 13(4): 1706-1720, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38133117

RESUMO

BACKGROUND: The end of life and death have changed from being issues managed within the family, assumed as part of life, to occur within health institutions for the majority of patients. The amount of patients dying at home has decreased, and the roles of families and communities in death and dying have become involuted, threatening related traditions and knowledge. As a result, a need to promote the end of life at home in this new self-serving society has arisen. In that context, the main objective of this study was to find out what patients and their families need during the end-of-life process in order to feel effectively accompanied at this time. METHODS: With that objective, a descriptive qualitative study was conducted via the content analysis of data from semi-structured interviews and focus groups. This research adhered to the COREQ guidelines. The sample consisted of 36 informants selected via intentional sampling of family members and patients integrated into the Comprehensive Palliative Care Process (PAI Paliativos). RESULTS: The results suggest the existence of several common needs such as communication and presence, including the conspiracy of silence as an important factor generating suffering for both. However, there are specific needs such as autonomy, dignity, and respect for patients, which must be taken into account. CONCLUSIONS: The results of this study will allow us to establish intervention strategies for effective accompaniment of patients' family members at the end of life and the avoidance of ethnocentrism in this process. This study was retrospectively registered with the (nursrep-1194226) on the (21 April 2023).

4.
Vet Res ; 54(1): 91, 2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37845774

RESUMO

The microbiota in humans and animals play crucial roles in defense against pathogens and offer a promising natural source for immunomodulatory products. However, the development of physiologically relevant model systems and protocols for testing such products remains challenging. In this study, we present an experimental condition where various natural products derived from the registered lactic acid bacteria Ligilactobacillus salivarius CECT 9609, known for their immunomodulatory activity, were tested. These products included live and inactivated bacteria, as well as fermentation products at different concentrations and culture times. Using our established model system, we observed no morphological changes in the airway epithelium upon exposure to Pasteurella multocida, a common respiratory pathogen. However, early molecular changes associated with the innate immune response were detected through transcript analysis. By employing diverse methodologies ranging from microscopy to next-generation sequencing (NGS), we characterized the interaction of these natural products with the airway epithelium and their potential beneficial effects in the presence of P. multocida infection. In particular, our discovery highlights that among all Ligilactobacillus salivarius CECT 9609 products tested, only inactivated cells preserve the conformation and morphology of respiratory epithelial cells, while also reversing or altering the natural immune responses triggered by Pasteurella multocida. These findings lay the groundwork for further exploration into the protective role of these bacteria and their derivatives.


Assuntos
Produtos Biológicos , Ligilactobacillus salivarius , Infecções por Pasteurella , Pasteurella multocida , Humanos , Animais , Imunidade Inata , Células Epiteliais , Produtos Biológicos/farmacologia , Infecções por Pasteurella/microbiologia , Infecções por Pasteurella/veterinária
5.
Int J Mol Sci ; 24(19)2023 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-37834236

RESUMO

The airway epithelium is a critical component of the respiratory system, serving as a barrier against inhaled pathogens and toxins. It is composed of various cell types, each with specific functions essential to proper airway function. Chronic respiratory diseases can disrupt the cellular composition of the airway epithelium, leading to a decrease in multiciliated cells (MCCs) and an increase in secretory cells (SCs). Basal cells (BCs) have been identified as the primary stem cells in the airway epithelium, capable of self-renewal and differentiation into MCCs and SCs. This review emphasizes the role of transcription factors in the differentiation process from BCs to MCCs and SCs. Recent advancements in single-cell RNA sequencing (scRNAseq) techniques have provided insights into the cellular composition of the airway epithelium, revealing specialized and rare cell types, including neuroendocrine cells, tuft cells, and ionocytes. Understanding the cellular composition and differentiation processes within the airway epithelium is crucial for developing targeted therapies for respiratory diseases. Additionally, the maintenance of BC populations and the involvement of Notch signaling in BC self-renewal and differentiation are discussed. Further research in these areas could provide valuable insights into the mechanisms underlying airway epithelial homeostasis and disease pathogenesis.


Assuntos
Células Epiteliais , Doenças Respiratórias , Humanos , Células Epiteliais/metabolismo , Mucosa Respiratória/metabolismo , Diferenciação Celular/genética , Regulação da Expressão Gênica , Doenças Respiratórias/metabolismo
6.
Int J Paleopathol ; 43: 22-30, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37717498

RESUMO

OBJECTIVE: This article analyses new prehistoric evidence of trepanation from a collective burial site in the south-eastern Iberian Peninsula. MATERIALS: The trepanned individual was documented in the Chalcolithic burial site of Camino del Molino, where 1348 individuals (30.7 % non-adults and 69.3 % adults) were deposited in two contiguous funerary phases, making it a reference site for the knowledge of Recent Prehistoric populations. METHODS: The individual has been sexed using traditional anthropological methods and ancient DNA. C14 dating has also been obtained. The lesion has been analysed macroscopically and microscopically using SEM. RESULTS: The skull under study belonged to an adult female deposited in the second burial phase (2566-2239 years cal BCE). It exhibits in the anterior region of the right temporal fossa two contiguous and partially overlapping holes that correspond to two trepanations performed using the scraping technique. CONCLUSIONS: It is a double cranial trepanation with signs of bone remodelling suggesting survival from surgery. No pathological signs were identified potentially associated with the intervention. SIGNIFICANCE: This is the second case of surgical interventions in the geographical area of study and one of the few evidences of this practice in women during prehistoric times. LIMITATIONS: So far only the articulated skeletons from this burial have been thoroughly analysed. SUGGESTIONS FOR FURTHER RESEARCH: Further intensive review of skull collection is advised to learn more about these surgical interventions in Copper Age and to go deeper into the causes that motivated their execution.


Assuntos
Crânio , Trepanação , Adulto , Humanos , Feminino , Espanha , Crânio/patologia , Sepultamento/métodos , Europa (Continente)
7.
Front Psychiatry ; 14: 1132581, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37520236

RESUMO

Spirituality is defined as the meaning of life, being the very essence of life made up of all of the aspects inherent to it. During end-of-life processes, this need is shown to be particularly altered in patients and yet it is an aspect that the health professionals accompanying patients in this situation report being least equipped to address, alongside therapies that could help to meet these needs, such as art therapy. An exploratory qualitative study was conducted, adheres to the guidelines of COREQ (41). The study population were final year students undertaking a nursing degree at the University of Huelva, Spain. The sample was selected via intentional sampling using snowball recruitment from the study population. Stratification according to gender was performed due to the feminised nature of the population. Sample size was determined progressively during the research, with recruitment ceasing at 13 informants once information saturation was achieved. Inclusion criteria required that participants were to be final year students enrolled on a nursing degree who had provided consent to participate voluntarily in the research. The analysis Realized was interpretive phenomenological (IPA) as described by Smith (43-45). The present study revealed that students perceive their training on spiritual care to be deficient. Despite them reporting that they possess the skills and tools to provide end-of-life care, this is not enough to provide effective accompaniment, given that this moment brings them into touch with their own insecurities. Students verbalized the need to learn strategies to address this shortcoming regarding final accompaniment, for instance, through art, with creativity being one of the skills with the potential to uncover the meaning of life.

8.
Medicine (Baltimore) ; 102(2): e32495, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36637943

RESUMO

RATIONALE: Chronic graft versus host disease (cGVHD) is a systemic immune-mediated complication that occurs in approximately half of patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HCT), and remains the leading cause of late morbidity and mortality. cGVHD involves a heterogeneous group of organic manifestations, many of which mimic autoimmune diseases such as scleroderma, primary biliary cholangitis, Sjögren syndrome and polymyositis. PATIENT CONCERNS: A 60-years-old female with a history of allo-HCT developed de novo cGVHD 11 months after allo-HCT with isolated liver involvement. The patient presented with jaundice, cytolysis, cholestasis and concomitant acute digital ischemia. Liver biopsy and autoimmunity tests were performed and were found to be compatible with immune-mediated liver damage. Nailfold capillaroscopy revealed microangiopathy, characterized by avascular areas and some enlarged capillaries resembled an early systemic sclerosis pattern. DIAGNOSIS: Biliary cholangitis-like and digital ischemia related to cGVHD. INTERVENTIONS: The patient was treated with high-dose prednisone and ursodeoxycholic acid, and extracorporeal photopheresis. The patient required hospital admission for administration of intravenous prostacyclin due to refractory Raynaud syndrome. OUTCOMES: After 6 to 8 weeks, the patient achieved a good response, with evident clinical improvement and progressive normalization of liver function. LESSONS: cGVHD is a multiorgan pathological condition, and this case emphasizes that a multidisciplinary team, including rheumatologists, should be involved in the follow-up of allo-transplant patients to ensure that the clinical complications are adequately addressed. Early intervention is critical for improving patient' prognosis.In addition, we performed a systemic literature review based on published case articles on hepatic cGVHD and digital ischemia published up to August 2022. To the best of our knowledge, this is the first reported case of such an association.


Assuntos
Síndrome de Bronquiolite Obliterante , Colangite , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Escleroderma Sistêmico , Humanos , Feminino , Pessoa de Meia-Idade , Transplante Homólogo/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Enxerto-Hospedeiro/complicações , Doença Enxerto-Hospedeiro/diagnóstico , Colangite/complicações , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/terapia , Isquemia/complicações , Doença Crônica
9.
Artigo em Inglês | MEDLINE | ID: mdl-36011982

RESUMO

The current demographic panorama in Spain corresponds to an aging population; this situation is characterized by the need to care for an elderly population, which contains polymedicated and pluripathological individuals. Polymedication is a criterion of frailty in the elderly and a risk factor for mortality and morbidity due to the increased risk of drug interactions and medication errors. There are numerous studies that measure reconciliation at hospital discharge and at admission, and even the methodology of reconciliation, but we have not found many studies that measure reconciliation in the context of the COVID-19 pandemic from the point of view of health professionals regarding difficulties and the strategies carried out, which is essential to begin to glimpse solutions. METHODS: This was a qualitative study based on 21 in-depth interviews and two discussion groups, conducted between January and April 2021 (13 nurses and 8 doctors, in rural and urban areas). The discourse was analyzed according to the Taylor-Bodgan model and processed using Atlas.ti software. RESULTS: The areas altered by the health crisis were access to patients, their reconciliation of medication, and changes in the care modality, including the greater use of telephone communication, changes in work organization, and time dedicated to patient care and family work. Difficulties encountered during COVID-19: change in medication format, the specific characteristics of the patient and their pathologies, and difficulties arising from communication with the patient and their family. The strategies applied: the collaboration of home assistants and caregivers, emphasis on patient-health professional communication, and the use of Information and Communication Technologies (ICT). CONCLUSION: The discharge was interrupted by the health crisis caused by COVID-19, in terms of both the traditional access of patients and by the remote care modalities generated by telemedicine.


Assuntos
COVID-19 , Telemedicina , Idoso , COVID-19/epidemiologia , Idoso Fragilizado , Hospitais , Humanos , Reconciliação de Medicamentos/métodos , Pandemias , Alta do Paciente , Percepção
10.
Front Cell Dev Biol ; 10: 820255, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35652095

RESUMO

Characterization of pluripotent states, in which cells can both self-renew or differentiate, with the irreversible loss of pluripotency, are important research areas in developmental biology. Although microRNAs (miRNAs) have been shown to play a relevant role in cellular differentiation, the role of miRNAs integrated into gene regulatory networks and its dynamic changes during these early stages of embryonic stem cell (ESC) differentiation remain elusive. Here we describe the dynamic transcriptional regulatory circuitry of stem cells that incorporate protein-coding and miRNA genes based on miRNA array expression and quantitative sequencing of short transcripts upon the downregulation of the Estrogen Related Receptor Beta (Esrrb). The data reveals how Esrrb, a key stem cell transcription factor, regulates a specific stem cell miRNA expression program and integrates dynamic changes of feed-forward loops contributing to the early stages of cell differentiation upon its downregulation. Together these findings provide new insights on the architecture of the combined transcriptional post-transcriptional regulatory network in embryonic stem cells.

11.
Sci Rep ; 12(1): 2537, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-35169184

RESUMO

Archaeological research in the Dolmen of El Pendón (Reinoso, Burgos, Spain) has brought to light the complex biography of a megalithic monument used throughout the 4th millennium cal. BC. The ossuary of this burial holds the bones of nearly a hundred individuals who suffered from diverse pathologies and injuries. This study presents the discovery of a skull with two bilateral perforations on both mastoid bones. These evidences point to a mastoidectomy, a surgical procedure possibly performed to relieve the pain this prehistoric individual may have suffered as a result of otitis media and mastoiditis. The hypothesis of surgical intervention is also supported by the presence of cut marks at the anterior edge of the trepanation made in the left ear. Furthermore, the results of this paper demonstrate the survival of the individual to both interventions. Given the chronology of this dolmen, this find would be the earliest surgical ear intervention in the history of mankind.

12.
Metab Brain Dis ; 37(3): 607-617, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35000053

RESUMO

Mitochondria are a primary source and a target of reactive oxygen species (ROS). Increased mitochondrial production of ROS is associated with bioenergetics decline, cell death, and inflammation. Here we investigated whether a pretreatment (for 24 h) with sesamol (SES; at 12.5-50 µM) would be efficient in preventing the mitochondrial collapse induced by hydrogen peroxide (H2O2, at 300 µM) in the human neuroblastoma SH-SY5Y cell line. We have found that a pretreatment with SES at 25 µM decreased the effects of H2O2 on lipid peroxidation, protein carbonylation, and protein nitration in membranes obtained from the mitochondria isolated from the SH-SY5Y cells. In this regard, SES pretreatment decreased the production of superoxide anion radical (O2-•) by the mitochondria of H2O2-treated cells. SES also prevented the mitochondrial dysfunction induced by H2O2, as assessed by analyzing the activity of the complexes I and V. The H2O2-induced reduction in the production of adenosine triphosphate (ATP) was also prevented by SES. The levels of the pro-inflammatory cytokines interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α), as well as the activity of the transcription factor nuclear factor-κB (NF-κB) were downregulated by the SES pretreatment in the H2O2-challenged cells. Silencing of the nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factor abolished the protection induced by SES regarding mitochondrial function and inflammation. Thus, SES depends on Nrf2 to promote mitochondrial protection in cells facing redox impairment.


Assuntos
Fator 2 Relacionado a NF-E2 , Neuroblastoma , Benzodioxóis , Linhagem Celular Tumoral , Sobrevivência Celular , Humanos , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/toxicidade , Mitocôndrias/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Neuroblastoma/metabolismo , Fenóis , Espécies Reativas de Oxigênio/metabolismo
13.
Enferm Clin ; 31: S112-S116, 2021 Feb.
Artigo em Espanhol | MEDLINE | ID: mdl-34629857

RESUMO

OBJECTIVE: The objective of this review was to synthesize the possible evidence to establish recommendations on the approach of mourning and death in relatives of COVID-19 patients, as well as offering substitute resources for the necessary rituals and procedures in order to build up functional griefs and prevent complicated bereavements. METHOD: A bibliographic research was conducted in MEDLINE, EMBASE, SCIENCEDIRECT, WOS, CINAHL and CUIDEN databases, using MeSH terms, (family, patient, isolation hospitals, grief, death, ceremonial behavior, self-care, affects and social networks) with its corresponding boolean equation. The selected articles have been published in a critical reading through the Critical Assessment Skills Program in Spanish (CASPe). RESULTS: A total of 560 articles were initially found, after applying the selection criteria, 13 studies were included in the analysis, of which 8 were systematic reviews, 3 qualitative studies, 1 cross-sectional prospective pilot study and 1 clinical guide, which allowed identifying strategies for the approach grief and death attending to this moment of exceptionality covid19, influencing the competence management of health professionals in emotional support and accompaniment as well as the monitoring throughout the process, as well as in the communication with the family. CONCLUSION: In the final process of life in COVID-19's time, health professionals must work farewells, alternative funeral rites, spiritual care and early coping that will allow the prevention of complicated grief.


Assuntos
COVID-19 , Estudos Transversais , Família , Pesar , Humanos , Projetos Piloto , Estudos Prospectivos , SARS-CoV-2
14.
PLoS One ; 16(1): e0244139, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33406086

RESUMO

Sheep remains constitute the main archaeozoological evidence for the presence of Early Neolithic human groups in the highlands of the Southern Pyrenees but understanding the role of herding activities in the Neolithisation process of this mountain ecosystem calls for the analysis of large and well-dated faunal assemblages. Cova de Els Trocs (Bisaurri, Huesca, Spain), a cave located at 1564 m a.s.l on the southern slopes of the Central Pyrenees, is an excellent case study since it was seasonally occupied throughout the Neolithic (ca. 5312-2913 cal. BC) and more than 4000 caprine remains were recovered inside. The multi-proxy analytical approach here presented has allowed us to offer new data elaborating on vertical mobility practices and herd management dynamics as has not been attempted up until now within Neolithic high-mountain sites in the Iberian Peninsula. For the first time, δ18O and δ13C stable isotope analyses offer direct evidence on both the regular practice of altitudinal movements of sheep flocks and the extended breeding season of sheep. Autumn births are recorded from the second half of the fifth millennium cal. BC onwards. Age-at-death distributions illustrate the progressive decline in caprine perinatal mortality together with the rising survival rate of individuals older than six months of age and the larger frequency of adults. This trend alongside the 'off-season' lambing signal at the implementation of husbandry techniques over time, probably aiming to increase the size of the flocks and their productivity. Palaeoparasitological analyses of sediment samples document also the growing reliance on herding activities of the human groups visiting the Els Trocs cave throughout the Neolithic sequence. In sum, our work provides substantial arguments to conclude that the advanced herding management skills of the Early Neolithic communities arriving in Iberia facilitated the anthropisation process of the subalpine areas of the Central Pyrenees.


Assuntos
Arqueologia , Artiodáctilos/fisiologia , Criação de Animais Domésticos/história , Animais , Artiodáctilos/parasitologia , Teorema de Bayes , Isótopos de Carbono/química , Cavernas , Fósseis , História Antiga , Dente Serotino/química , Nematoides/crescimento & desenvolvimento , Nematoides/isolamento & purificação , Óvulo/química , Isótopos de Oxigênio/química , Espanha
15.
Artigo em Inglês | MEDLINE | ID: mdl-35010487

RESUMO

Spirituality is the most unknown aspect of palliative care despite being the need that is most altered in the last moments of life. OBJECTIVE: To identify on the one hand the spiritual needs of patients who are at the end of life and on the other hand, the way in which nursing professionals can work to provide effective accompaniment in this process. METHOD: A qualitative study was conducted which applied different data collection techniques. This was done to describe the phenomenon from a holistic perspective in relation to experts' perceptions of the competencies required by health professionals and palliative patients' spiritual needs. Semi-structured interviews were conducted within both populations. In order to analyze the qualitative data collected through interviews, discourse was analyzed according to the Taylor-Bodgan model and processed using Atlas.ti software. RESULTS: Three well-differentiated lines of argument are extracted from the discourse in each of the groups, on the one hand in the group of patients they define the concept of spirituality, system of values and beliefs, and the Factors that influence the spirituality of patients at the end of life (differentiating palliative care areas/other areas) and on the other, the professionals agree with the patients in the line of argument of concept of spirituality although they define more metaphysical categories and the other two lines of argument that result are the spiritual attention in this process and the need for formation in spirituality. CONCLUSIONS: The provision of spiritual care gives meaning to the actions of nursing professionals when it comes to providing end-of-life care, achieving holistic care, humanizing death, and promoting a dignified end.


Assuntos
Cuidados Paliativos na Terminalidade da Vida , Terapias Espirituais , Assistência Terminal , Humanos , Cuidados Paliativos , Espiritualidade
16.
Life Sci Alliance ; 3(5)2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32284354

RESUMO

BMAL1 is essential for the regulation of circadian rhythms in differentiated cells and adult stem cells, but the molecular underpinnings of its function in pluripotent cells, which hold a great potential in regenerative medicine, remain to be addressed. Here, using transient and permanent loss-of-function approaches in mouse embryonic stem cells (ESCs), we reveal that although BMAL1 is dispensable for the maintenance of the pluripotent state, its depletion leads to deregulation of transcriptional programs linked to cell differentiation commitment. We further confirm that depletion of Bmal1 alters the differentiation potential of ESCs in vitro. Mechanistically, we demonstrate that BMAL1 participates in the regulation of energy metabolism maintaining a low mitochondrial function which is associated with pluripotency. Loss-of-function of Bmal1 leads to the deregulation of metabolic gene expression associated with a shift from glycolytic to oxidative metabolism. Our results highlight the important role that BMAL1 plays at the exit of pluripotency in vitro and provide evidence implicating a non-canonical circadian function of BMAL1 in the metabolic control for cell fate determination.


Assuntos
Fatores de Transcrição ARNTL/metabolismo , Células-Tronco Pluripotentes/metabolismo , Fatores de Transcrição ARNTL/fisiologia , Animais , Diferenciação Celular/fisiologia , Ritmo Circadiano/genética , Metabolismo Energético/fisiologia , Expressão Gênica/genética , Glicólise , Células HEK293 , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Camundongos , Mitocôndrias/genética , Células-Tronco Embrionárias Murinas/citologia , Células-Tronco Embrionárias Murinas/metabolismo , Células-Tronco Pluripotentes/citologia
17.
R Soc Open Sci ; 7(2): 191754, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32257332

RESUMO

We monitored northern bat Eptesicus nilssonii (Keyserling & Blasius, 1839) acoustically along a 27 km road transect at weekly intervals in 1988, 1989 and 1990, and again in 2016 and 2017. The methodology of data collection and the transect were the same throughout, except that the insect-attracting mercury-vapour street-lights along parts of the road were replaced by sodium lights between the two survey periods. Counts along sections of the transect with and without street-lights were analysed separately. The frequency of bat encounters in unlit sections showed an average decline of 3.0% per year, corresponding to a reduction of 59% between 1988 and 2017. Sections with street-lights showed an 85% decline over the same period (6.3% per year). The decline represents a real reduction in the abundance of bats rather than an artefact of changed distribution of bats away from roads. Our study conforms with another long-term survey of the same species on the Baltic island of Gotland. Our results agree with predictions based on climate change models. They also indicate that the decline was caused directly by the disuse of the insect-attracting mercury-vapour street-lights, which may have resulted in lower availability of preferred prey (moths). In the 1980s, E. nilssonii was considered the most common bat in Sweden, but the subsequent decline would rather qualify it for vulnerable or endangered status in the national Red List of Threatened Species.

18.
IEEE/ACM Trans Comput Biol Bioinform ; 17(4): 1093-1104, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30530369

RESUMO

FM-index is a compact data structure suitable for fast matches of short reads to large reference genomes. The matching algorithm using this index exhibits irregular memory access patterns that cause frequent cache misses, resulting in a memory bound problem. This paper analyzes different FM-index versions presented in the literature, focusing on those computing aspects related to the data access. As a result of the analysis, we propose a new organization of FM-index that minimizes the demand for memory bandwidth, allowing a great improvement of performance on processors with high-bandwidth memory, such as the second-generation Intel Xeon Phi (Knights Landing, or KNL), integrating ultra high-bandwidth stacked memory technology. As the roofline model shows, our implementation reaches 95 percent of the peak random access bandwidth limit when executed on the KNL and almost all of the available bandwidth when executed on other Intel Xeon architectures with conventional DDR memory. In addition, the obtained throughput in KNL is much higher than the results reported for GPUs in the literature.


Assuntos
Genômica , Alinhamento de Sequência , Algoritmos , Computadores , DNA/genética , Genoma Humano/genética , Genômica/instrumentação , Genômica/métodos , Humanos , Alinhamento de Sequência/instrumentação , Alinhamento de Sequência/métodos
19.
J Proteome Res ; 19(1): 194-203, 2020 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-31657576

RESUMO

Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative neoplasm of early childhood with a poor survival rate, thus there is a requirement for improved treatment strategies. Induced pluripotent stem cells offer the ability to model disease and develop new treatment strategies. JMML is frequently associated with mutations in PTPN11. Children with Noonan syndrome, a development disorder, have an increased incidence of JMML associated with specific germline mutations in PTPN11. We undertook a proteomic assessment of myeloid cells derived from induced pluripotent stem cells obtained from Noonan syndrome patients with PTPN11 mutations, either associated or not associated with an increased incidence of JMML. We report that the proteomic perturbations induced by the leukemia-associated PTPN11 mutations are associated with TP53 and NF-Kκb signaling. We have previously shown that MYC is involved in the differential gene expression observed in Noonan syndrome patients associated with an increased incidence of JMML. Thus, we employed drugs to target these pathways and demonstrate differential effects on clonogenic hematopoietic cells derived from Noonan syndrome patients, who develop JMML and those who do not. Further, we demonstrated these small molecular inhibitors, JQ1 and CBL0137, preferentially extinguish primitive hematopoietic cells from sporadic JMML patients as opposed to cells from healthy individuals.


Assuntos
Células-Tronco Pluripotentes Induzidas , Leucemia Mielomonocítica Juvenil , Síndrome de Noonan , Criança , Pré-Escolar , Humanos , Leucemia Mielomonocítica Juvenil/tratamento farmacológico , Leucemia Mielomonocítica Juvenil/genética , Mutação , Proteômica
20.
Enferm. clín. (Ed. impr.) ; 30: 0-0, 2020. graf
Artigo em Espanhol | IBECS | ID: ibc-191716

RESUMO

OBJETIVO: Realizar una síntesis de la evidencia disponible para establecer recomendaciones sobre el abordaje del duelo y la muerte en familiares de pacientes con COVID-19, así como ofrecer recursos sustitutivos de los rituales y procedimientos necesarios con el fin de favorecer duelos funcionales y prevenir duelos complicados. MÉTODO: Se realizó búsqueda bibliográfica en bases de datos MEDLINE, EMBASE, SCIENCEDIRECT, WOS, CINAHL y CUIDEN, utilizando términos MeSH (family, patient, isolation hospitals, grief, death, ceremonial behavior, self care, affects y social networking) con su ecuación booleana correspondiente. Los artículos seleccionados se sometieron a una lectura crítica a través del Critical Apraisal Skill Programme en español. RESULTADOS: Se encontraron 560 artículos atingentes; tras aplicar los criterios de selección 13 estudios se incluyeron en el análisis, de los cuales 8 eran revisiones sistemáticas, 3 estudios cualitativos, un estudio piloto prospectivo transversal y una guía clínica, que permitieron identificar estrategias para el abordaje del duelo y la muerte atendiendo a este momento de excepcionalidad de la COVID-19, incidiendo en el manejo competencial de los profesionales sanitarios en apoyo emocional y en el acompañamiento, así como en el seguimiento durante todo el proceso y en la comunicación con la familia. CONCLUSIÓN. En el proceso final de la vida en tiempos de la COVID-19 los profesionales sanitarios deben trabajar despedidas, los ritos fúnebres alternativos, la atención espiritual y el afrontamiento precoz que permitirán a su vez la prevención del duelo complicado


OBJECTIVE: The objective of this review was to synthesize the possible evidence to establish recommendations on the approach of mourning and death in relatives of COVID-19 patients, as well as offering substitute resources for the necessary rituals and procedures in order to build up functional griefs and prevent complicated bereavements. METHOD: A bibliographic research was conducted in MEDLINE, EMBASE, SCIENCEDIRECT, WOS, CINAHL and CUIDEN databases, using MeSH terms, (family, patient, isolation hospitals, grief, death, ceremonial behavior, self-care, affects and social networks) with its corresponding boolean equation. The selected articles have been published in a critical reading through the Critical Assessment Skills Program in Spanish (CASPe). RESULTS: A total of 560 articles were initially found, after applying the selection criteria, 13 studies were included in the analysis, of which 8 were systematic reviews, 3 qualitative studies, 1 cross-sectional prospective pilot study and 1 clinical guide, which allowed identifying strategies for the approach grief and death attending to this moment of exceptionality covid19, influencing the competence management of health professionals in emotional support and accompaniment as well as the monitoring throughout the process, as well as in the communication with the family. CONCLUSION: In the final process of life in COVID-19's time, health professionals must work farewells, alternative funeral rites, spiritual care and early coping that will allow the prevention of complicated grief


Assuntos
Humanos , Pesar , Morte , Saúde da Família , Infecções por Coronavirus/psicologia , Pneumonia Viral/psicologia , Enfermagem Baseada em Evidências/normas , Pessoal de Saúde/psicologia , Cuidados Críticos/psicologia
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