Anàlisi de polimorfismes en el gen APOE en una població de malalts d'Alzheimer de Mallorca

Objectiu: Verificar l'associació entre l'al ·lel APOE4, el polimorfisme del promotor APOE -491 T/A i el desenvolupament de malaltia d'Al zheimer. Pacients i mètodes: S'analitza el genotip APOE i el genotip del polimorfisme -491 T/A del promotor del gen APOE mitjançant peR seguida de digestió amb un enzim de restricció, en 34 pacients de Mallorca afectats de probable Malaltia d'Al zheimer i en 57 conh·ols sans. Resultats: A la nosh·a població, la freqüència de l'al·lel APOE4 va ser significativament superior en els pacients respecte dels controls (p=O,02; OR: 2,55). També la freqüència del genotip -491 AA mosh ·à una diferencia estadísticament significativa respecte de la població conh·ol (p=O,026; OR: 3,5). Quan es va analitzar la presència conjunta d'ambdós polimorfismes es comprovà com la possessió de l'al·lel APOE4 en un context d'alt nivell de producció de la proteïna ApoE, tal com ve determinat pel polimorfisme -491 AA, s'associà al major risc de desenvolupar la malaltia d'Alzheimer (p=O,0039; OR:4.73). Conclusions: Tant l'al·lel APOE-4 com el polimorfisme -491 A i molt mes la seva presencia conjunta constitueixen un factor important en el desenvolupament de malaltia d'Alzheimer

Solution design for low-fluorine trifluoroacetate route to YBa2Cu3O7 films

We present our work in the preparation of metallorganic precursor solutions with reduced fluorine content, able to fulfil the requirements for high-performance superconducting YBCO epitaxial layers as a promising approach to low cost and scalable coated conductors. Six different solutions using different quantities of fluorine and non-fluorine carboxylate precursors with a total amount of fluorine from 10 to 50% that of standard trifluoroacetic acid (TFA) solutions. For stabilization purposes different coordinating agents have been used and the solution rheology has been modified for proper substrate wettability. Thermal decomposition analysis and infrared spectroscopy performed directly in films, have revealed that the decomposition takes place in two consecutive stages around 265 and 310 °C respectively, and nuclear magnetic resonance (NMR) analysis could unveil the chemical reactions taking place in the solution. Using the solutions with 20% fluorine and upon optimization of the growth process parameters, YBCO layers with T and J (77 K) of 90 K and 4 MA cm are obtained.The authors acknowledge the financial support from MICINN (Consolider NANOSELECT, CSD2007-00041, MAT 2011- 28874-C02, MAT2014-51778-C2-2-R also with FEDER support); Generalitat de Catalunya (Pla de Recerca 2014- SGR-753 and XaRMAE), and EU (FP7 NMP-LA-2012- 280432 EUROTAPES project and MP1201 Cost action).Peer Reviewe

Rebuilding the hematopoietic stem cell niche: Recent developments and future prospects

Hematopoietic stem cells (HSCs) have proven their clinical relevance in stem cell transplantation to cure patients with hematological disorders. Key to their regenerative potential is their natural microenvironment – their niche – in the bone marrow (BM). Developments in the field of biomaterials enable the recreation of such environments with increasing preciseness in the laboratory. Such artificial niches help to gain a fundamental understanding of the biophysical and biochemical processes underlying the interaction of HSCs with the materials in their environment and the disturbance of this interplay during diseases affecting the BM. Artificial niches also have the potential to multiply HSCs in vitro, to enable the targeted differentiation of HSCs into mature blood cells or to serve as drug-testing platforms. In this review, we will introduce the importance of artificial niches followed by the biology and biophysics of the natural archetype. We will outline how 2D biomaterials can be used to dissect the complexity of the natural niche into individual parameters for fundamental research and how 3D systems evolved from them. We will present commonly used biomaterials for HSC research and their applications. Finally, we will highlight two areas in the field of HSC research, which just started to unlock the possibilities provided by novel biomaterials, in vitro blood production and studying the pathophysiology of the niche in vitro. With these contents, the review aims to give a broad overview of the different biomaterials applied for HSC research and to discuss their potentials, challenges and future directions in the field. Statement of significance Hematopoietic stem cells (HSCs) are multipotent cells responsible for maintaining the turnover of all blood cells. They are routinely applied to treat patients with hematological diseases. This high clinical relevance explains the necessity of multiplication or differentiation of HSCs in the laboratory, which is hampered by the missing natural microenvironment – the so called niche. Biomaterials offer the possibility to mimic the niche and thus overcome this hurdle. The review introduces the HSC niche in the bone marrow and discusses the utility of biomaterials in creating artificial niches. It outlines how 2D systems evolved into sophisticated 3D platforms, which opened the gateway to applications such as, expansion of clinically relevant HSCs, in vitro blood production, studying niche pathologies and drug testing

Genomic diversity of human papillomavirus-16, 18, 31, and 35 isolates in a Mexican population and relationship to European, African, and Native American variants

AbstractCervical cancer, mainly caused by infection with human papillomaviruses (HPVs), is a major public health problem in Mexico. During a study of the prevalence of HPV types in northeastern Mexico, we identified, as expected from worldwide comparisons, HPV-16, 18, 31, and 35 as highly prevalent. It is well known that the genomes of HPV types differ geographically because of evolution linked to ethnic groups separated in prehistoric times. As HPV intra-type variation results in pathogenic differences, we analyzed genomic sequences of Mexican variants of these four HPV types. Among 112 HPV-16 samples, 14 contained European and 98 American Indian (AA) variants. This ratio is unexpected as people of European ethnicity predominate in this part of Mexico. Among 15 HPV-18 samples, 13 contained European and 2 African variants, the latter possibly due to migration of Africans to the Caribbean coast of Mexico. We constructed phylogenetic trees of HPV-31 and 35 variants, which have never been studied. Forty-six HPV-31 isolates from Mexico, Europe, Africa, and the United States (US) contained a total of 35 nucleotide exchanges in a 428-bp segment, with maximal distances between any two variants of 16 bp (3.7%), similar to those between HPV-16 variants. The HPV-31 variants formed two branches, one apparently the European, the other one an African branch. The European branch contained 13 of 29 Mexican isolates, the African branch 16 Mexican isolates. These may represent the HPV-31 variants of American Indians, as a 55% prevalence of African variants in Mexico seems incomprehensible. Twenty-seven HPV-35 samples from Mexico, Europe, Africa, and the US contained 11 mutations in a 893-bp segment with maximal distances between any two variants of only 5 mutations (0.6%), including a characteristic 16-bp insertion/deletion. These HPV-35 variants formed several phylogenetic clusters rather than two- or three-branched trees as HPV-16, 18, and 31. An HPV-35 variant typical for American Indians was not identifiable. Our research suggests type specific patterns of evolution and spread of HPV-16, 18, 31, and 35 both before and after the worldwide migrations of the last four centuries. The high prevalence of highly carcinogenic HPV-16 AA variants, and the extensive diversity of HPV-18, 31, and 35 variants with unknown pathogenic properties raise the possibility that HPV intra-type variation contributes to the high cervical cancer burden in Mexico

Variations in childbirth interventions in high-income countries: protocol for a multinational cross-sectional study

Introduction There are growing concerns about the increase in rates of commonly used childbirth interventions. When indicated, childbirth interventions are crucial for preventing maternal and perinatal morbidity and mortality, but their routine use in healthy women and children leads to avoidable maternal and neonatal harm. Establishing ideal rates of interventions can be challenging. This study aims to describe the range of variations in the use of commonly used childbirth interventions in high-income countries around the world, and in outcomes in nulliparous and multiparous women. Methods and analysis This multinational cross-sectional study will use data from births in 2013 with national population data or representative samples of the population of pregnant women in high-income countries. Data from women who gave birth to a single child from 37 weeks gestation onwards will be included and the results will be presented for nulliparous and multiparous women separately. Anonymised individual level data will be analysed. Primary outcomes are rates of commonly used childbirth interventions, including induction and/or augmentation of labour, intrapartum antibiotics, epidural and pharmacological pain relief, episiotomy in vaginal births, instrument-assisted birth (vacuum or forceps), caesarean section and use of oxytocin postpartum. Secondary outcomes are maternal and perinatal mortality, Apgar score below 7 at 5 min, postpartum haemorrhage and obstetric anal sphincter injury. Univariable and multivariable logistic regression analyses will be conducted to investigate variations among countries, adjusted for maternal age, body mass index, gestational weight gain, ethnic background, socioeconomic status and infant birth weight. The overall mean rates will be considered as a reference category, weighted for the size of the study population per country. Ethics and dissemination The Medical Ethics Review Committee of VU University Medical Center Amsterdam confirmed that an official approval of this study was not required. Results will be disseminated at national and international conferences and published in peer-reviewed journals.The study was developed during a meeting with COST-members (European Cooperation in Science and Technology). These meetings are funded by the COST Action IS1405 ‘BIRTH’ (European Cooperation in Science and Technology). There is no other external funding for this study.Peer Reviewe

NF-κB/Rel-Mediated Regulation of the Neural Fate in Drosophila

Two distinct roles are described for Dorsal, Dif and Relish, the three NF-κB/Rel proteins of Drosophila, in the development of the peripheral nervous system. First, these factors regulate transcription of scute during the singling out of sensory organ precursors from clusters of cells expressing the proneural genes achaete and scute. This effect is possibly mediated through binding sites for NF-κB/Rel proteins in a regulatory module of the scute gene required for maintenance of scute expression in precursors as well as repression in cells surrounding precursors. Second, genetic evidence suggests that the receptor Toll-8, Relish, Dif and Dorsal, and the caspase Dredd pathway are active over the entire imaginal disc epithelium, but Toll-8 expression is excluded from sensory organ precursors. Relish promotes rapid turnover of transcripts of the target genes scute and asense through an indirect, post-transcriptional mechanism. We propose that this buffering of gene expression levels serves to keep the neuro-epithelium constantly poised for neurogenesis

Correction : variations in childbirth interventions in high-income countries : protocol for a multinational cross-sectional study

Original article can be fount at: https://www.um.edu.mt/library/oar/handle/123456789/58714Correction issued for the article Variations in childbirth interventions in highincome countries: protocol for a multinational cross-sectional study (10.1136/bmjopen-2017-017993)peer-reviewe

Late presentation of chronic HBV and HCV patients seeking first time specialist care in Spain: a 2-year registry review

Chronic viral hepatitis infection affects an estimated 325 million people globally. People who initiate treatment after significant disease progression face increased risk of severe liver complications and death. Data are scarce on the characteristics and risk factors of people who present late to care in Spain and globally. Data were collected from January 2018 to December 2019 to report late presentation (LP) to specialist care at 11 large university hospitals in Spain to assess related risk factors using a multivariable logistic regression model. 2290 (CHB = 505, CHC = 1785) patients were analysed, with 581 (25.2%) presenting late. Hepatitis C patients more frequently reported LP compared to hepatitis B patients (28.1% vs 15.0%; p < 0.001). Older age (p < 0.001), being male (p < 0.001), being Spanish-born (p < 0.001), and having an unknown origin of referral (p = 0.08) were associated with a higher likelihood of LP. Advanced liver disease was identified in 533 (23%) patients and late-stage liver disease in 124 (5.4%). LP, including with irreversible liver damage, to viral hepatitis specialist care is frequent in Spain, despite being a country with unrestricted treatment access. Initiatives to reduce LP should specifically target men, older individuals, foreign-born populations for CHB, and Spanish nationals for CHC.AP, TMW, JVL acknowledge support to ISGlobal from the Spanish Ministry of Science, Innovation and Universities through the “Centro de Excelencia Severo Ochoa 2019–2023” Programme (CEX2018-000806-S), and support from the Government of Catalonia through the CERCA Programme. CAP acknowledges support from the Secretaria d’Universitats i Recerca de la Generalitat de Catalunya and the European Social Fund as an AGAUR-funded PhD fellow

Analytical tools for the multiplex rapid detection of SARS-CoV-2

There is a high demand for analytical tools that can readily be applied to effectively diagnose the Covid-19 but also to carry out screening and surveillance detection with enough frequency to get the transmission rates under control and thus help to timely tackling the disease. On the one hand, high throughput analytical benchtop approaches are still highly demanding for accelerating diagnostics. Such platforms are required to show multiplexed capabilities while in turn reducing the turnaround times of currently applied techniques such as the RT-PCR gold standard. On the other hand, massive screening and surveillance protocols still require for effective tools at the point of need that could reliably detect the virus in individuals after being exposed or the likelihood of being immunized after suffering from the disease. The rapid detection of coronavirus biomarkers, including RNA as well as spike and nucleocapsid proteins in nasopharyngeal and oropharyngeal samples, together with host biomarkers such as immunoglobulins and cytokines in serum has been addressed in this work. We aim to produce tools that provided with a global response to the diagnosis, prognosis and follow-up of the disease (Figure 1). All the biocomponents and corresponding bioassay protocols required for measuring these biomarkers have been tailored made and implemented in three different platforms. A calorimetric device based on a lateral flow assay format [1, 2] and a multiplex electrochemical platform comprising an electrochemical transducer array and a paper microfluidic component [3] have been adapted to produce tools to be used at the point of care. Likewise, a fluorescence microarray platform has been set up with the potential for high-throughput screening by recording molecular signatures thanks to the its multiplexing and miniaturization capabilities. REFERENCES [1] E. Polo et al. PCT, ES2013/070549 [2] E. Polo et al. Chem. Commun., 49 (2013) 3676 [3] C. Fernández-Sánchez et al. Application no. EP20382721.

The transcribed pseudogene RPSAP52 enhances the oncofetal HMGA2-IGF2BP2-RAS axis through LIN28B-dependent and independent let-7 inhibition

Altres ajuts: We thank CERCA Program/Generalitat de Catalunya for their institutional support. This work was also supported by the Fundació La Marató de TV3, grant number #20131610 (S.G.), the AECC-Junta de Barcelona (S.G.), the Fundación Científica de la AECC under grant GCB13131578DEÁ (O.M.T.), the Health and Science Departments of the Catalan Government (Gen-eralitat de Catalunya). C.O.-M. is a pre-doctoral fellow funded by the Basque Government (PRE_2013_1_1009).One largely unknown question in cell biology is the discrimination between inconsequential and functional transcriptional events with relevant regulatory functions. Here, we find that the oncofetal HMGA2 gene is aberrantly reexpressed in many tumor types together with its antisense transcribed pseudogene RPSAP52. RPSAP52 is abundantly present in the cytoplasm, where it interacts with the RNA binding protein IGF2BP2/IMP2, facilitating its binding to mRNA targets, promoting their translation by mediating their recruitment on polysomes and enhancing proliferative and self-renewal pathways. Notably, downregulation of RPSAP52 impairs the balance between the oncogene LIN28B and the tumor suppressor let-7 family of miRNAs, inhibits cellular proliferation and migration in vitro and slows down tumor growth in vivo. In addition, high levels of RPSAP52 in patient samples associate with a worse prognosis in sarcomas. Overall, we reveal the roles of a transcribed pseudogene that may display properties of an oncofetal master regulator in human cancers