Unidad de Investigación

• Professionals from Navarrabiomed and the University Hospital of Navarra have participated in this multicentre project led by the Cima of the University of Navarra

The Department of Economic and Business Development has subsidized, through the call for Grants for Strategic R&D Projects for the period 2020-2022, the Linterna project, which seeks to advance immunotherapy techniques to fight cancer. Specifically, the project has managed to identify a biomarker that may be effective in stopping the progression of lung cancer. In addition, genomic analysis techniques have been used in subjects with tobacco-induced lung cancer under this project. This has allowed both to advance in the identification and to develop new therapeutic approaches. 

The main objective of the Linterna project (Leadership and INnovation in Cancer immunoTHErapy from NAvarra) is to bring together the work of different institutions that are developing immunotherapy strategies to fight cancer. This technique is based on enhancing the body's own defences versus, for example, techniques that are based on supplying chemicals outside the body.

The whole development has been carried out by a consortium led by the Cima - University of Navarra and in which  University Hospital of Navarra (Medical Oncology Service), the University of Navarra Clinic, Navarrabiomed (Units of Oncoimmunology and of Translational Medical Oncology), ADItech and the pharmaceutical company Medibiopharma have also participated.

During the development of the project, non-cellular markers have been searched for in plasma samples from patients. For this, high-performance analytical techniques have been used. Thanks to this work, fractalkine has been identified, which is a small protein that helps control the growth and activity of other cells, as a biomarker of response to immunotherapy. This discovery will make it possible to develop new, more effective treatments by combining this protein with current therapies.
 

• See project video (spanish)

The European network APTITUDE - Acting for Trans-Pyrenees Prevention of Dependency in Seniors – is gathering in Pamplona on Wednesday, 3 July for a scientific seminar that is expected to draw more than 200 experts in active ageing and frailty. The seminar will take place at the Tres Reyes Hotel in Pamplona, starting at 8.15am. In addition, there will be side workshops organised with the Navarra Red Cross for the general public, at Rincón de la Aduana and Paseo del Doctor Arazuri, starting at 10am.

These events were introduced this morning at the biomedical research centre Navarrabiomed, the network’s leading institution in Navarra, along with the Public University of Navarre (UPNA), the Navarra Hospital Complex (CHN) and the Navarra Red Cross. At the press conference were Nicolás Martínez Velilla, APTITUDE Coordinator in Navarra and Head of the Geriatrics Unit at CHN, Juan José San Martín Baquedano, Coordinator of the Navarra Red Cross, and Jorge Marín Vidondo, Project Manager at Navarrabiomed.

Martínez Velilla said the seminar would be the third APTITUDE meeting – and the first to take place in Pamplona. It will gather primary health care professionals and representatives of hospitals and research centres, universities, nursing homes and businesses from Occitanie in France, Catalonia and Navarra in Spain, and Andorra.
At the seminar, experts will discuss the concept of intrinsic capacity in older individuals – that is, the set of physical and mental skills an individual can apply at any given moment, plus the functional capacity, which is the way in which an individual relates to and interacts with the environment – proposed by the World Health Organisation (WHO). Also, they will talk about the multi-component training offered by the project, targeted at health and social care practitioners working with frail seniors, so that they can prescribe the adequate physical activity routines, make cognitive stimulation interventions, give healthy diet guidelines, make psycho-social interventions, etc.

Keynote speakers include Norman Lazarus and Stephen Harridge, from King’s College London, who have broad experience in physical activity, anti-ageing and muscle deterioration in geriatric care and other sectors, like aerospace, where they have worked with NASA.

Open workshops

On Wednesday, between 10am and 2pm, there will be open workshops at Rincón de la Aduana and Paseo del Doctor Arazuri, Pamplona. Under the title ‘Active, healthy seniors/Tailerrak: Adineko aktibo eta osasuntsuak’, they are targeted at people over 65, but they can also be of interest to caretakers, relatives or volunteers. The workshops are free and no prior registration is required.

In addition, there will be APTITUDE-Red Cross Tents, hosting functional assessment, cognitive stimulation and adapted leisure activities for the elderly, giving information about support devices and healthy habits, and giving out supplementary material with workout routines.

Ageing and functional decline

According to INE data from 2018, the population of Navarra amounts to 647,219 people, 19.5 per cent are 65 or above. The region has one of the longest life expectancies in Europe: 86.6 years for women and 81 years for men. However, the quality of life varies: whereas women tend to live longer lives, they become more dependent than men after 65.

According to the World Health Organisation, the main causes of mild or severe disability in old age are sensory impairment, back or neck pain, chronic obstructive pulmonary disease (COPD), depression, falls, diabetes mellitus, dementia and osteoarthritis. Moreover, more than 50 per cent of the elderly suffer from a combination of illnesses and take three to five medicines together.

Initiatives like APTITUDE advocate a change of paradigm in elderly care. Caretakers should face the challenge of setting illness aside to focus on functional capacity and its maintenance or improvement. APTITUDE promotes healthy habits, physical activity and cross-generational, adapted leisure both in urban centres and rural environments, in an effort to combat loneliness, depopulation in rural areas and the stereotypes associated with ageing.

About APTITUDE

APTITUDE was established in 2018 as a three-year network to foster cross-border cooperation in four regions (Occitanie, Catalonia, Navarra and Andorra) by building its own local networks with a total budget of 2 million Euro.
The APTITUDE project, which includes the APTITUDE network in Navarra, gets 65 per cent of its funds from the European Regional Development Fund (ERDF), through the Interreg V-A Spain-France-Andorra (POCTEFA) cooperation programme, aimed at the development of cross-border economic, social and environmental action by means of joint strategies to promote sustainable territorial development.

APTITUDE partners:

Gérontopôle - Centre Hospitalier Universitaire (CHU) de Toulouse
Fundació Salut i Envelliment - Universitat Autònoma de Barcelona (UAB)
Servei Andorrà d’Atenció Sanitària
Complejo Hospitalario de Navarra (CHN) - Navarrabiomed

More information: www.aptitude-net.com

Photo: From left to right: Jorge Marín (Navarrabiomed), Nicolás Martínez (CHN-Navarrabiomed) and Juan José San Martín (Navarra Red Cross).

Professionals at the Navarra Hospital Complex (CHN) from the Public University of Navarra (UPNA) and Navarrabiomed are participating in the establishment of a European network for preventing old-age dependency and promoting active ageing. Hospitals and research centres from France, Spain (Navarra and Catalonia) and Andorra are part of this project, named APTITUDE (Acting for Trans-Pyrenees Prevention of Dependency in Seniors). As announced today, the network in Navarra is being coordinated by Navarrabiomed-Miguel Servet Foundation.

The three-year cross-border project will develop local networks in France, Navarra, Catalonia and Andorra. The project has been assigned a 2-million-Euro budget, with 1 million going to Spain (and 400,000 to Navarra). 65 per cent of the funds are being contributed by the European Regional Development Fund (ERDF) through the Interreg V-A Spain programme.

Through training programmes, awareness-raising activities and scientific evidence, the project is aimed at improving the quality of life of elderly people, encouraging the adoption of healthy habits and reducing the loss of functional autonomy, as explained by Antonio Merino Díaz de Cerio, CHN Managing Director, and Nicolás Martínez Velilla, Head of the Geriatrics Department, researcher at the Geriatrics Unit in Navarrabiomed and leader of APTITUDE in Navarra. In the words of Martínez Velilla, ‘the primary goal of the network is to prevent old-age dependency by trying to mitigate frailty in the elderly population.’

Antonio Merino stressed the importance of this type of European projects where protocols, good practices and procedures are shared for the benefit of all the participating institutions and society at large.

Specific actions by APTITUDE Navarra

Álvaro Casas Herrero, geriatrician at CHN and President of the Spanish Geriatrics Society, and Maite Soria Sarnago, Nursing Director at CHN, announced the actions to be undertaken in our community in the forthcoming months.

On Tuesday, 20 November, the project will be presented at a talk in the function room of the School of Medical Sciences, titled ‘Active and healthy seniors: Keys for adopting healthy habits’. The talk will start at 4pm and finish at 6.30pm. Admission is free, but there will be a limited number of seats available. It will also be streamed on the Navarrabiomed YouTube channel.

At the event, the leaders of the project will talk about healthy habits and good practices for improving the quality of life of old people. The President of Club Atlético Osasuna, Luis Sabalza Iriarte, will talk about ‘Working beyond retirement age’. He will share experiences from his career in the Club.

In addition, three strategic actions will take place in the upcoming months in Navarra. Firstly, a cross-border record will be established of people aged 65 and over who are interested in getting information or taking part in gerontechnology and clinical research programmes.

Simultaneously, Clinical and Innovation Research Travelling Teams will be established where professionals specialising in various medical fields will transfer clinical and research practice to urban and rural areas, thus ensuring broader penetration and larger participation for the population. The teams will be made of doctors, nurses, physiotherapists and occupational therapists.

Also, a database will be created with data provided voluntarily by frail old people and old adults with memory disorders, which will be used to design research projects involving all the centres participating in the project.

Lastly, the members of the project will participate in the validation of a new concept, ‘intrinsic capacity’, as defined by the World Health Organisation (WHO), which might be used in the clinical assessment of old people.

Recently published studies

The actions framed within the project are in line with the conclusions drawn in a study published recently in JAMA Internal Medicine, the peer-reviewed medical journal of the American Medical Association.

Professor Mikel Izquierdo Redín, Director of the Department of Medical Sciences at UPNA and senior researcher from the Physical Exercise and Frailty Research Unit at Navarrabiomed, presented a study that shows that a tailored physical activity plan for in-patients aged 75 or older reduces functional decline. The clinical trial consisted in a three-year follow-up of 370 patients in the Geriatrics Service of CHN.

The study reveals that preadmission health and functional status can indicate the risk of functional decline associated with hospitalisation. This clinical sign might be negatively affected by bed rest during hospitalisation.

Simultaneously, the team is participating in the DIABFRAIL LATAM European project, funded by the European Commission in the context of the Horizon 2020 European research project. DIABFRAIL LATAM focuses on pre-frail and frail old people with diabetes in Latin America. At present, 40 per cent of people aged 65 and older are affected by diabetes.

The project’s goal is to implement a treatment model in Colombia, Chile, Mexico, Peru and Argentina, consisting of physical exercise, education and a nutrition plan, plus blood sugar level and blood pressure goals adjusted to old adults with diabetes, who are particularly vulnerable as a result of their frailty. More than 1000 pre-frail and frail old people with type 2 diabetes are taking part in the clinical trial.

www.aptitude-net.com / aptitude@navarra.es

• Four Catalan institutions are also participating in this project to develop molecules with coronavirus-neutralizing properties

The Supera COVID-19 Fund launched by Banco Santander through Santander Universities, in collaboration with Crue Spanish Universities and the Spanish National Research Council (CSIC), has granted €160,000 in funding to a research project on COVID-19 designed by a consortium made up of Navarrabiomed researchers and four Catalan institutions coordinated by the Universidad Pública de Navarra (UPNA). This project seeks to develop molecules with SARS-CoV-2-neutralizing properties for the treatment of patients requiring hospitalization and clinical supervision due to the infection’s severity.

These molecules are based on peptides specific to the ACE2 receptor that can reduce or halt the ability of SARS-CoV-2 to cause infection. “These molecules reproduce the human receptor region the virus attaches to,” explained project leader Jacinto López Sagaseta, from the Protein Crystallography Unit at the Navarrabiomed Biomedical Research Center. “We are trying to create molecules from this region that have a greater capacity to bind to the viral particle, which would hinder the virus’s ability to attach to the natural receptor and thus slow down infection.” According to López, these molecules may “help chemists design drugs that can mitigate the process and speed of infection and thereby facilitate patients’ clinical recovery”.

In order to implement the 12-month project, a consortium was set up of researchers from different disciplines, including chemical synthesis, protein engineering, structural analysis and cell biology, as well as specialists in the conditions of biosafety level three (BSL3, for laboratories, on a scale of one to four), to test the potential of these molecules. Specifically, besides Navarrabiomed and the UPNA, four Barcelona research institutions are also participating in the project: IRB Barcelona (Institute for Research in Biomedicine), IQAC-CSIC (Institute for Advanced Chemistry of Catalonia), CIBER-BBN (Bioengineering, Biomaterials and Nanomedicine Subject Area of the CIBER Biomedical Research Center), and IRTA (Institute of Agrifood Research and Technology). Besides Jacinto López Sagaseta, other Navarrabiomed researchers taking part in this research project include Gilda Dichiara Rodríguez, Elena Erausquin Arrondo and Ane Ochoa Echevarría, who are members of the Protein Crystallography Unit.
The consortium members hope that “the availability of molecules with a strong inhibitory effect will significantly mitigate the socioeconomic impact of the pandemic due to the persistence of current and/or future SARS-CoV-2 outbreaks, as well as outbreaks of other potentially harmful coronaviruses with similar entry routes,” said López.

€8.5 million fund

The €8.5 million Supera COVID-19 Fund has been earmarked for projects of different organizations that are based on the fund’s three-pronged strategic approach against COVID-19: research on the virus and its prevention, research on its social impact, and strengthening universities’ technological capacity and reducing the digital divide. A total of 700 grant applications were submitted, of which 35 were selected and received funding to the tune of €5 million to carry out applied research against the virus. Nearly €1 million was also distributed to twelve projects on the social impact of the virus. Finally, €2.5 million will be allocated to supply young university students in unfavorable socioeconomic situations throughout Spain with nearly 5,000 computers and 15,000 Internet connectivity solutions and webcams.

• The Government of Navarre provided €1.1 million in funding for eight research projects and has now added two more Navarre initiatives to the list of recipients of funding from the Carlos III Health Institute

María Chivite, the President of the Government of Navarre, recognized “the good work” being done at research centers and institutes in the Region of Navarre to find alternatives that help alleviate the effects of COVID-19. She spoke in the context of a meeting she attended this morning with ten researchers in charge of their own publicly funded studies on this disease, which has caused 515 deaths in Navarre and more than 27,000 in all of Spain.

The meeting was also attended by Santos Induráin, the Minister of Health, and Juan Cruz Cigudosa, the Minister of University, Innovation and Digital Transformation, and provided a firsthand opportunity to learn about the research purpose of the projects that have received grants from the Navarre COVI+D Fund. Created by the Government of Navarre to promote research on this topic, the fund paid out €1.1 million in May to eight projects that had received a favorable assessment from the Carlos III Health Institute. The Carlos III Health Institute has also provided direct funding of €232,000 for two other Navarre research projects.

Chivite took advantage of the forum to remind the participants of the Government of Navarre’s commitment to innovation and research “as a model of economic and social development,” not just through these grants, but also by means of the R&D&i Emergency Plan, presented last week, and the Reactivate Navarre Plan / Nafarroa Suspertu 2020-2023. The Government is also committed to improving technological infrastructure and promoting supra-regional cooperation. “We want Navarre to lead the way in biomedicine because we have the talent and skills to do just that. It’s one of the strategic areas we’re working on. We have to be able to transfer knowledge and research to favor industrial and technological development,” she said, before expressing her confidence that Navarre will become “a key stop on the R&D&i map.”

Chivite confirmed that the goal of the Government of Navarre is “to keep increasing investment and setting up strong pillars for the model of growth.” Navarre will thus be prepared for future challenges of the likes of COVID-19.

Chivite informed the researchers of the public support of their research work, though “people are aware of the pressure you’re under when you’re studying this coronavirus, because of the high expectations about finding a vaccine, treatments and other aspects that could alleviate the effects of a virus that has had a major impact on our society.” She asked for respect “for the time frames, rigor and meticulousness” of the researcher’s work, and also expressed hope that this work would promote “true and instructive information” that avoids fake news and disinformation in society as a whole.
 

Ten projects

In addition to President Chivite, the meeting was attended by Rosario Martínez, the Director General for Innovation. Also attending were the researchers from the ten projects that received public funding: Luis Martínez de Morentin, Fermín Mallor Giménez, Borja Sáez Ochoa, Natalia Ramírez Huerto, Jacinto López Sagaseta, Pablo Sarobe Ugarriza, Patricia Fanlo Mateo, David Escors Murugarren, Jesús Castilla Catalán and Leyre Ruete Ibarrola, who attended in representation of Beatriz Lacruz Escalada. They were joined by the heads of the different research centers where the projects are being carried out. This group included María Rosario Luquin, the Scientific Director of  the Navarre Health Research Institute (IdiSNA), Claudio Fernández, the Director of the Lurederra Foundation, and Íñigo Lasa Uzcudun, the Director of Navarrabiomed.

The directors of the ten research projects presented their lines of research, which include the study of possible vaccines, the use of specific drugs, resource management, the development of preventive measures and products, and the analysis of incidence bearing in mind sociodemographic characteristics and other conditioning factors.

The Government of Navarre aims to promote Navarre innovation and national prominence through the COVI+D Fund grants. But the goal is also to attract scientific talent, given the fact that these grants include staff payroll expenses.

• Vanessa Arrieta Paniagua, predoctoral researcher at the Translational Cardiology Unit of Navarrabiomed - IdiSNA will present her doctoral thesis by the Public University of Navarra next Monday, November 28, at 12:00, in the Assembly Hall of Navarrabiomed. 

The doctoral work, entitled "Role of sST2 in myocardial fibrosis in severe aortic stenosis”, has been developed at the University Hospital of Navarra and Navarrabiomed under the direction of Natalia López Andrés, Principal investigator of the Translational Cardiology Unit.

Aortic stenosis is the most common valvular heart disease in Europe and North America affecting 2-7%, depending on the region, in population over 65 years of age. To date, there is no medical treatment that can slow down or reverse the evolution of the disease, so aortic valve replacement (surgical or percutaneous) is the only treatment when symptoms or ventricular dysfunction appear.

This disease produces an abnormal progressive narrowing of the aortic valve that, as a result of pressure overload, causes hypertrophy of the left ventricle. In this process, myocardial fibrosis has an important pathophysiological role, as well as a prognostic role. Initially, myocardial fibrosis is part of a compensatory mechanism, but in advanced stages a focal replacement fibrosis appears, leading to ventricular dysfunction and heart failure. The pathophysiological mechanisms underlying these processes are not fully understood. 

Focal replacement fibrosis can be detected and quantified by cardiac magnetic resonance imaging (MRI) with the delayed enhancement (DE) sequences. The presence of DE in patients with severe aortic stenosis has been shown to be an independent predictor of mortality and unfavourable clinical outcome in this group of patients. However, MRI is an expensive technique with limited availability, so it is not used in the follow-up of this group of patients in routine clinical practice.

The hypothesis of this thesis is that as the levels of soluble ST2 (sST2), a biomarker associated with the process of fibrosis and myocardial remodelling, are elevated in case of aortic stenosis, they may have a prognostic value. Specifically, this study addresses the role of sST2 in myocardial fibrosis in severe aortic stenosis. 
 

Research development 

The work is proposed from a translational point of view, and has a dual goal. First of all, to delve into the pathophysiological role of tSS2 in severe aortic stenosis. To this end, a proteomic study has been carried out to assess the proteins modulated by sST2 in human cardiac fibroblasts and the in vitro effects of sST2 on human cardiac fibroblasts have been investigated. The results have been validated in vitro in a rat model with pressure overload and in myocardial biopsies of patients with aortic stenosis that underwent surgery. 

Likewise, it has been demonstrated that sST2 exerts a deleterious role in human cardiac fibroblasts, on the one hand, affecting the mitochondrial function of the cell and thus increasing oxidative stress and the synthesis of proinflammatory molecules and on the other hand, promoting differentiation to myofibroblasts and increasing the synthesis of profibrotic molecules. These findings were validated in the animal model and in myocardial biopsies of patients with aortic stenosis.

Secondly, from the clinical point of view, a cohort of patients with severe aortic stenosis with surgical indication was analysed to check if the blood levels of sST2 are associated with the DE evaluated by MRI in patients with severe aortic stenosis. Thus, it is observed that patients with severe aortic stenosis with cardiac MRI DE have significantly higher blood levels of sST2 than those without RT. Blood sST2 levels are positively correlated with DE mass and with VI mass in patients with severe aortic stenosis. High levels of sST2 make it possible to identify patients with severe aortic stenosis with DE, without having to perform cardiac MRI, in a simple way that can be applied in routine clinical practice.
 

Dissemination of results 

The work carried out has led to several scientific publications: in 2019, in the journal Clinical Science, “Soluble ST2 promotes oxidative stress and inflammation in cardiac fibroblasts: an in vitro and in vivo study in aortic stenosis”, and in 2020 in the journal Cells, “Soluble St2 Induces Cardiac Fibroblast Activation and Collagen Synthesis via Neuropilin-1”.   

In addition, the results have been disclosed at several national and international congresses such as the SEC Congress in Bilbao (in 2015 and in 2017), at the 29th EACTS Annual Meeting in Amsterdam, in 2015 or at the Heart Failure Congress in Paris, in 2017.

Biochemist Jaime Ibarrola Ulzurrun (Pamplona, 1991) has shown for the first time that a hormone is involved in mitral valve prolapse, a heart valve disease that leads to heart failure, and that a series of drugs can have positive effects on this condition. ‘The drugs known as antimineralocorticoids or mineralocorticoid receptor antagonists (MCRAs) are a promising option to reduce mitral valve remodelling. The only existing solution to date was surgery,’ Ibarrola explains. This was the subject of his doctoral thesis at the Public University of Navarra (UPNA).

The mitral valve is the valve between the left atrium and the left ventricle of the heart. Mitral valve prolapse is a condition in which the two valve flaps of the mitral valve do not close smoothly or evenly, but instead bulge (prolapse) upward into the left atrium. Sometimes, the mitral valve does not close tightly, allowing blood to flow backward in the heart. This condition is known as mitral valve regurgitation or mitral insufficiency. Most people with mitral valve prolapse – one of the most common heart conditions, affecting 176 million people around the world – never have problems. They do not need treatment or lifestyle changes. Some, however, do need to be treated. ‘To date, no drugs have been developed for this condition, so the only viable solution is surgery,’ Ibarrola explains. His doctoral advisor was Natalia López Andrés, senior researcher at the Cardiovascular Translational Research Unit of Navarrabiomed, a joint centre of the Government of Navarra and the Public University of Navarra (UPNA).

New therapeutic targets

Ibarrola’s research responds to the need to study ‘new mechanisms and new therapeutic targets in order to find drug treatments for mitral valve prolapse.’ ‘Mineralocorticoids are a class of hormones produced by the human body. The primary mineralocorticoid is aldosterone. The aldosterone/mineralocorticoid receptor (Aldo/MR) pathway can cause cardiac fibrosis. In addition, a large number of studies have shown that the Aldo/MR pathway is involved in a number of heart conditions. MCRA drugs can block the effects of the Aldo/MR pathway. Moreover, significant clinical studies show that they can also improve cardiac function by reducing cardiac fibrosis,’ Ibarrola explains. He conducted his doctoral research project with financial aid from UPNA and a European programme.

Ibarrola worked on the hypothesis that the Aldo/MR pathway could play a role ‘in the development of mitral valve prolapse, modulating cell activation and cellular differentiation.’ ‘Furthermore, the Aldo/MR pathway could become a new therapeutic target in this disease, and blocking this pathway with MCRA drugs could prevent the alterations associated with mitral valve prolapse. For the first time, we were able to show that the Aldo/MR pathway is involved in the development of mitral valve prolapse and that the drugs could have a positive effect on this condition,’ Ibarrola concludes. His doctoral thesis got an A-grade cum laude.

Ibarrola’s résumé

Jaime Ibarrola holds a degree in Biochemistry and a master’s degree in Biomedical Research from the University of Navarra. At present, he is a postdoctoral researcher at the Molecular Cardiology Research Institute (MCRI) at Tufts University (Massachusetts, USA).

As a doctoral student, Ibarrola was twice a visiting scholar at the Cordeliers Research Centre, Sorbonne University, in Paris. He shared his results in eight international conferences in Germany, Spain, France and Ireland. Ibarrola is the author of about a dozen papers published in international scientific journals.

Experts gathered at the Public University of Navarra (UPNA) have urged health and sports professionals to become ‘health agents’ by promoting physical activity among young people and pregnant women. Their goal is to improve the health and fitness of the population as a strategy to prevent non-communicable chronic diseases like obesity, heart disease or type 2 diabetes. A symposium was held by UPNA in Pamplona on Thursday 9 May to discuss exercise prescription as a way to improve health in all ages. Organised by the School of Medical Sciences and the Department of Medical Sciences, the event drew some 130 sports, health and biomedical experts.

Two UPNA researchers, who are also members of Navarrabiomed (the joint biomedical research centre of the Government of Navarra and the Public University of Navarra) and the Navarra Medical Research Institute (IdiSNA), delivered speeches: Mikel Izquierdo Redín, organiser the event, and Robinson Ramírez-Vélez. Mikel Izquierdo talked about strength training and the functions of the muscular system, ‘which a number of health professionals consider important for improving health and recovering from diseases linked with a sedentary lifestyle and population ageing, as well as for optimising sport performance after muscle injury.’ He debunked some of the myths created by pseudo-therapies in connection with strength training and improved muscle function. He said that muscle loss is not an inevitable outcome of ageing, as it can be prevented with proper training. He also observed that it is not true that children cannot do strength training exercises; on the contrary, they can, as long as they engage in controlled movements that are suitable for their age. He insisted that fitness ‘always’ offers benefits to patients who suffer from diseases such as type 2 diabetes and denied that the best muscle training is the one associated with extreme fatigue.

Finally, Izquierdo questioned the effectiveness and validity of the Kinesio Taping Method (which consists in applying elastic strips on muscles to treat pain), hypopressive techniques, electro stimulation suits and muscle roller sticks.

Health and pregnancy

Robinson Ramírez-Vélez said that, despite the efforts made to prevent non-communicable chronic disease, such as promoting healthy habits like physical exercise, a balanced diet, a good night’s sleep, quitting smoking and drinking, and so on, ‘we have failed to obtain the desired results.’ Studies reveal, he added, that ‘the mother’s state of health during pregnancy conditions to some extent the developing baby’s health later in life.’ He highlighted the importance of physical activity in children and adolescents – both aerobic exercise and resistance/strength training. Also, he insisted that health professionals should prescribe physical activity in all stages of life, even pregnancy.

The closing lecture was delivered by Antonio García-Hermoso, of Navarrabiomed and IdiSNA. He showed his disappointment in the fact that ‘Physical Education in school is not considered to be as important as subjects.’ He cited important international studies concluding that ‘exercise in youth is good for both physical and mental wellbeing.’ Finally, García-Hermoso recommended that ‘sports should be given the importance they deserve in primary, secondary and higher education.’

The Microbial Pathogenesis Unit of Navarrabiomed-Public University of Navarra (UPNA) has found a new genetic organisation in bacteria that helps better understand bacterial biology. The study of this genetic architecture was published in Proceedings of the National Academy of Sciences of the United States of America (PNAS).

Research background

In 1961, François Jacob and Jacques Monod discovered that bacteria group the genes that encode the proteins for a certain metabolic pathway in a single transcription unit (which they called ‘operon’). They won the Nobel Prize in Physiology or Medicine in 1965 for their discovery.

The bacteria they chose for their study was Escherichia coli, which normally lives in the intestines of healthy people; specifically, they studied the set of genes E. coli bacteria need to transport lactose (milk sugar) and break it down. E. coli only produces the three proteins it needs to digest lactose when the sugar is available. To simplify transcription regulation, the three genes involved are adjacent in the genome and under a single regulation system. Similar transcriptional regulation systems are found in other metabolic pathways in all bacteria.

Research at Navarrabiomed

In 2018, the team of researchers at Navarrabiomed coordinated by Iñigo Lasa Uzcudun, Head of the Microbial Pathogenesis Unit and Director of the biomedical research centre, described a new way genes are organised in bacteria. This regulation system has a higher level of regulation in operon structure, which the authors of the study named ‘non-contiguous operon’.

The bacterial model analysed has a group of four genes that are transcribed as a transcription unit despite the existence of a separate gene between the second and third genes that is transcribed in the opposite direction.

This transcriptional architecture results in an antisense transcript that acts as a mutual regulation system for the expression of the genes in the operon and the gene that produces this antisense transcript. Therefore, the concept of non-contiguous operon includes not only the genes transcribed from the same transcription unit but also overlapping genes whose expression is coordinated with that of the genes in the operon.

This finding deepens the understanding of bacterial biology and may trigger novel developments in the fields of synthetic biology and bacterial biotechnology.
The study was carried out as part of the scientific activity done at the Navarra Medical Research Institute (IdiSNA).

• Paper published in PNAS.

• El estudio, financiado por el Ministerio de Economía, ha sido publicado por la prestigiosa revista Nature Communication.

Un equipo científico del centro de investigación biomédica Navarrabiomed -centro mixto del Gobierno de Navarra y la Universidad Pública de Navarra (UPNA)- ha conseguido caracterizar el sistema sensorial que las bacterias utilizan entre otras cosas para multiplicarse en el cuerpo humano y causar infección.

El avance, que ha sido publicado por la revista científica Nature Communications y cuenta con financiación del Ministerio de Economía, Industria y Competitividad, permite comprender mejor cómo las bacterias se adaptan a las diferentes condiciones ambientales y posibilitará el desarrollo de antibióticos más específicos y eficaces.
El estudio ha contado con el liderazgo del doctor Iñigo Lasa, director de Navarrabiomed e investigador responsable del Grupo de Patogénesis Microbiana del centro. Asimismo, han colaborado investigadores del Instituto de Agrobiotecnología (UPNA-CSIC-Gobierno de Navarra), del Instituto de Biomedicina de Valencia (CSIC) y del Institute of Infection, Immunity and Inflammation, University of Glasgow.

Bacterias superresistentes

Actualmente, la aparición de bacterias farmacorresistentes, que no responden a tratamientos con antibióticos, constituye uno de los problemas sanitarios a escala mundial priorizados por la Organización Mundial de la Salud (OMS).

Las bacterias detectan, responden y se adaptan a los cambios en su entorno utilizando unos elementos sensoriales denominados sistemas de dos componentes. Este tipo de sistemas sensoriales están presentes en bacterias, hongos y plantas, pero no se encuentran en células animales. En el caso de las bacterias, regulan procesos celulares tan importantes como la virulencia o su propio crecimiento, lo que los convierte en dianas para el diseño de nuevas terapias antimicrobianas.

El objetivo del trabajo ha consistido en eliminar todos los sistemas de dos componentes, es decir el sistema sensorial completo, en Staphylococcus aureus, uno de los principales patógenos humanos según la OMS y, posteriormente, en la generación de una colección de bacterias cada una de las cuales contiene un único sistema de dos-componentes. Esta estrategia ha permitido simplificar una compleja red sensorial en cada uno de sus elementos para comprender cuál es la función individual de cada uno de los sistemas y la relación existente entre ellos. 

Aplicación clínica de la investigación

En relación a la aplicación clínica, Iñigo Lasa apunta al desarrollo de nuevos antibióticos más específicos. “El hecho de que los sistemas de dos componentes estén presentes en todas las bacterias patógenas y no en las células de nuestro organismo nos puede permitir desarrollar fármacos que bloqueen estos sistemas, evitando así el desarrollo de la bacteria durante la infección, sin causar ningún efecto secundario sobre nuestras células”.

En este sentido, las bacterias generadas en este estudio han sido patentadas y actualmente el equipo analiza diversos compuestos marinos que puedan incorporarse en el tratamiento y control de infecciones en la práctica clínica.

La investigación forma parte de la actividad científica del Instituto de Investigación Sanitaria de Navarra (IdiSNA), agrupación público-privada para el fomento de la investigación biomédica en la Comunidad Foral y de la que son miembros Navarrabiomed y la UPNA.

• Información adicional sobre el paper: Behind the paper - Nature Microbiology: "Life without sensing. Can Staphylococcus aureus live without two-component sensorial system?"