Rosario González-Férez, a researcher at the UGR’s Department of Atomic, Molecular and Nuclear Physics and at the “Carlos I” Institute of Theoretical and Computational Physics, has produced this work in collaboration with a research group from Harvard University

Dr. Rosario González-Férez, a researcher at the Department of Atomic, Molecular and Nuclear Physics and the “Carlos I” Institute of Theoretical and Computational Physics of the University of Granada, has published the article “Ultralong-Range Rydberg Bi-molecules” in the prestigious scientific journal Physical Review Letters. The results of the study show a new type of bi-molecule formed from two nitric oxide (NO) molecules, both in their ground state and in the Rydberg electronic state.    

The work was made possible thanks to the scientific collaboration between the researcher and the Institute for Theoretical Atomic, Molecular and Optical Physics (ITAMP) at Harvard University. The study began during her stay at Harvard between March and July 2020, meaning that the entire process, from data-gathering and analysis to final written conclusions, was conducted during the Covid-19 pandemic. The stay, which was funded by the Fulbright Foundation and the Salvador de Madariaga programme of the Spanish Ministry of Science, Innovation and Universities, enjoyed the scientific collaboration of ITAMP’s Hossein R. Sadeghpour and Janine Shertzer.

This new type of bi-molecule is the result of the union of two molecules of nitric oxide (NO) whose structure is arranged in such a way that the NO is located in one of the poles, while, in the other, is the NO + ion. The electron orbits around both, acting like a “glue” that binds this bi-molecule. In addition, its size corresponds to between 200 and 1,000 times that of NO, and its lifetime is long enough to enable its observation and experimental control, as these fragile systems are easily manipulated by means of very weak electric fields.

This type of bi-molecule enables researchers to implement and study chemical reactions at low temperatures from a quantum perspective and facilitates the investigation of intermolecular interactions at large distances, since they coexist at low temperatures.

Dr. González-Férez observes that the use of these bi-molecules in quantum technologies would be interesting both for the processing of information by entanglement and for the development of quantum sensors, with multiple technological applications in quantum optics and quantum computing.

González-Férez continues her work with two research groups, from the University of British Columbia in Canada and the University of Stuttgart in Germany, which aims to create this bi-molecule experimentally and confirm the theoretical predictions made over the last year.

In the image, Rosario González- Férez, researcher at the Department of Atomic, Molecular and Nuclear Physics and the “Carlos I” Institute of Theoretical and Computational Physics of the UGR 

Bibliography:

Rosario González-Férez, Janine Shertzer, and H.R. Sadeghpour (2021) ‘Ultralong-Range Rydberg Bi-molecules’ Phys. Rev. Lett. 126, 043401. https://journals.aps.org/prl/abstract/10.1103/PhysRevLett.126.043401

Media enquiries:

Dr. Rosario González-Férez

Department of Atomic, Molecular and Nuclear Physics of the University of Granada

Email: rogonzal@ugr.es 

A team of researchers has studied the molecular profile of small “messenger” vesicles called exosomes, produced by cancer stem cells (CSCs), which play a key role in the process of carcinogenesis and metastasis in the blood of patients with malignant melanoma.

Their study has shown that these malignant melanoma vesicles produced by CSCs have a different molecular composition from that of differentiated tumour cells. These molecules were also found to be detectable in exosomes present in the blood, and they presented differences in patients with malignant melanoma compared to healthy individuals. This makes them potentially suitable as biomarkers for the diagnosis and prognosis of this disease.

The results have been published in the prestigious scientific journal Molecular Oncology.

Malignant melanoma is one of the most aggressive types of skin cancer and its prevalence has been increasing worldwide in recent years. Among the factors that contribute to the life-threatening nature and severity of this disease are the late appearance of the first symptoms, the lack of effective treatments, its high metastasis capacity, and also the difficulty of detecting this particular cancer. Unfortunately, the diagnosis of malignant melanoma therefore continues to be problematic due to the lack of indicators—known as biomarkers—to accurately signal the early stages of this disease and predict how it might evolve in a given patient, once detected.

These characteristics, which make this type of cancer such a serious disease, may be partly attributable to so-called cancer stem cells (CSCs), a sub-population of cells that exist in tumours and that present the typical characteristics of stem cells. They are responsible for tumour initiation, maintenance, and progression, as well as metastasis and recurrence—even years after a tumour has been eradicated.

Now, a team of scientists led by Professor Juan Antonio Marchal Corrales of the Department of Human Anatomy and Embryology at the University of Granada (UGR) and Director of the “Doctores Galera y Requena” Chair in Research on Cancer Stem Cells, pertaining to the Biohealth Research Institute in Granada (ibs.GRANADA) and the MNat Scientific Unit of Excellence (ModelingNature), has studied these CSCs—specifically, the microvesicles that act as “messengers” for these cells. Known as exosomes, these cells produce and send other cells and tissues to communicate via the transfer of certain biomolecules, thereby promoting the emergence of metastases.

These exosomes have been shown to be involved in many tumour processes. As cells release them and circulate via the bloodstream, they offer a very interesting source of biomarkers as they can be easily isolated from a blood sample. This study focused on the molecular characterization of exosomes produced by CSCs and isolated in the blood from patients with malignant melanoma. Metabolomic techniques were used to analyse the molecular profile of biological systems in order to identify possible biomarkers for the diagnosis of this disease.

This study is the result of extensive multidisciplinary work in which translational researchers, bioinformaticians, and clinical researchers have joined forces to take another step in the field of Personalized Medicine or Precision Medicine in Oncology. The team comprises members from the UGR; Fundación MEDINA (led by Francisca Vicente and José Pérez del Palacio, Area Head and Principal Investigator of the Screening Department, respectively); and the “Virgen de las Nieves” and “San Cecilio” Teaching Hospitals in Granada (all members of ibs.GRANADA ); the University of Vigo; and the Spanish National Cancer Research Centre (CNIO).

Among its findings, the study showed that the molecular composition of exosomes produced by CSCs is different from those released by differentiated tumour cells. To investigate this, using a primary patient-derived malignant melanoma cell line enriched in CSCs, both types of cells were cultivated in large quantities and the exosomes that they produced and released into the culture were isolated. Once the properties and characteristics of both the cells and the exosomes they produced had been tested, a metabolomic analysis was carried out. This enabled the molecules (metabolites) present in the biological sample to be studied. After the molecules had been detected and extracted using a mass spectrometer, which quantifies them with great precision, a series of statistical analyses were carried out to determine which molecules were found in the highest concentration in the exosomes of each cell type. Thus, the researchers tentatively identified some lipidic metabolites differentially present in exosomes of CSCs and differentiated tumour cells.

Metabolomic profile

Subsequently, and following the same scientific approach, a similar study was carried out comparing the metabolomic profile of exosomes isolated from the blood of patients with malignant melanoma in different stages and healthy individuals who acted as controls. The study concluded that certain metabolites, including some of those previously identified in CSCs, were also present in exosomes isolated from blood in different concentrations among melanoma patients and healthy individuals. By means of the corresponding statistical models, these molecules and their different concentrations in blood made it possible to distinguish individuals with malignant melanoma from those without the disease. This makes them suitable candidates for acting as potential biomarkers for its diagnosis.

However, the authors emphasise that this study is only a first step. The identification of some of these molecules, the complete characterization of those already tentatively identified, and the replication of the study with a greater number of samples to validate and verify their clinical application as biomarkers all remain pending.

Studies such as this constitute a new avenue for the discovery of cancer biomarkers aimed at improving early diagnosis, prognosis, and treatment-response prediction. And, of course, these results can be extrapolated to many other tumours, in the quest to identify biomarkers that help us better understand the pathogenesis of these diseases and achieve personalized precision medicine.

The study was funded by: the Spanish Ministry of Science, Innovation and Universities (project RTI2018-101309 -B-C2) and the Training Programme for University Teaching Staff (FPU) awarded to José Luis Palacios Ferrer (ref: FPU15/03682); the “Carlos III” Health Institute (project PIE16- 00045); the Ministry of Economy, Knowledge, Business and University of the Junta de Andalucía; the European Regional Development Fund (project SOMM17/6109/UGR, UCE-PP2017-3), the UGR’s “Doctores Galera y Requena” Chair in Research on Cancer Stem Cells; and Fundación MEDINA.

Bibliography:

Palacios-Ferrer JL, García-Ortega MB, Gallardo-Gómez M, García MÁ, Díaz C, Boulaiz H, Valdivia J, Jurado JM, Almazán-Fernández FM, Arias-Santiago S, Amezcua V, Peinado H, Vicente F, Pérez Del Palacio J, and Marchal JA. (2021) ‘Metabolomic profile of cancer stem cell-derived exosomes from patients with malignant melanoma’, Mol Oncol, 15(2), 407–28. doi: 10.1002/1878-0261.12823

Graphic showing the research project on the metabolomic profile of exosomes isolated from CSCs and blood from patients with malignant melanoma. From cell cultures of CSCs and differentiated tumour cells, and from the blood of patients with malignant melanoma vs. healthy controls, the exosomes were extracted and characterized, and their molecular composition was analysed to identify characteristic molecules of CSCs differentially present in the blood of malignant melanoma patients, with the potential to act as diagnostic biomarkers of the disease

Images of isolated exosomes from patients with malignant melanoma

Media enquiries:

Juan Antonio Marchal Corrales

Department of Human Anatomy and Embryology, Faculty of Medicine, University of Granada

Tel.: +34 958 241000 Ext. 20080 / 958 249321

Email: jmarchal@ugr.es

Scientists from the University of Granada also found that, if the exercise is performed in the afternoon, the effects of the caffeine are more marked than in the morning

Scientists from the Department of Physiology of the University of Granada (UGR) have shown that caffeine (about 3 mg/kg, the equivalent of a strong coffee) ingested half an hour before aerobic exercise significantly increases the rate of fat-burning. They also found that if the exercise is performed in the afternoon, the effects of the caffeine are more marked than in the morning.

In their study, published in the Journal of the International Society of Sports Nutrition, the researchers aimed to determine whether caffeine—one of the most commonly-consumed ergogenic substances in the world to improve sports performance—actually does increase oxidation or “burning” of fat during exercise. Despite the fact that its consumption in the form of supplements is very common, the scientific evidence for its beneficial claims is scarce.

“The recommendation to exercise on an empty stomach in the morning to increase fat oxidation is commonplace. However, this recommendation may be lacking a scientific basis, as it is unknown whether this increase is due to exercising in the morning or due to going without food for a longer period of time,” explains the lead author of this research, Francisco José Amaro-Gahete of the UGR’s Department of Physiology.

A total of 15 men (mean age, 32) participated in the research, completing an exercise test four times at seven-day intervals. Subjects ingested 3 mg/kg of caffeine or a placebo at 8am and 5pm (each subject completed the tests in all four conditions in a random order). The conditions prior to each exercise test (hours elapsed since last meal, physical exercise, or consumption of stimulant substances) were strictly standardized, and fat oxidation during exercise was calculated accordingly.

Maximum fat oxidation

“The results of our study showed that acute caffeine ingestion 30 minutes before performing an aerobic exercise test increased maximum fat oxidation during exercise regardless of the time of day,” explains Francisco J. Amaro. The existence of a diurnal variation in fat oxidation during exercise was confirmed, the values ​​being higher in the afternoon than in the morning for equal hours of fasting.

These results also show that caffeine increases fat oxidation during morning exercise in a similar way to that observed without caffeine intake in the afternoon.

In summary, the findings of this study suggest that the combination of acute caffeine intake and aerobic exercise performed at moderate intensity in the afternoon provides the optimal scenario for people seeking to increase fat-burning during physical exercise.

Bibliography:

Mauricio Ramírez-Maldonado, Lucas Jurado-Fasoli, Juan del Coso, Jonatan R. Ruiz,  and Francisco J. Amaro-Gahete (2021) ‘Caffeine increases maximal fat oxidation during a graded exercise test: Is there a diurnal variation?’ Journal of the International Society of Sports Nutrition 18, 5 https://doi.org/10.1186/s12970-020-00400-6

Image captions: 

The UGR researchers who conducted this study, in the Sport and Health University Research Institute (iMUDS) 

The scientists have demonstrated that consuming caffeine (about 3 mg/kg or the equivalent of a strong coffee) half an hour before aerobic exercise significantly increases fat-burning

Media enquiries:

Francisco José Amaro-Gahete

Department of Physiology, University of Granada

Email: amarof@ugr.es 

Researchers from the University of Granada are leading the ActiveBrains project, in which more than 100 overweight or obese children have participated

Their work shows that children who are in better physical shape have higher total brain volumes than children who are less fit

Children with a higher level of physical fitness have larger brains, and both aerobic capacity and strength/speed are related to the amount of grey and white matter in the brain, meaning that overweight or obese children are adversely affected. Furthermore, a greater amount of white matter in the brain is linked to superior cognitive performance.

These are the findings derived by a team of researchers from the University of Granada (UGR)—the Department of Physical Education and Sports (Faculty of Sport Sciences), the Sport and Health University Research Institute (iMUDS), and the Mind, Brain and Behaviour Research Centre (CIMCYC). The team is leading the ActiveBrains project, in which more than 100 overweight or obese children have participated to date.

This study, published in the Scandinavian Journal of Medicine & Science in Sports, revealed that children who were classified as ‘physically fit’ had more grey matter and white matter, and, in general, larger brains than those children who were deemed to be ‘in poor shape’. Having more white matter was also found to be related to higher cognitive performance—specifically, greater cognitive flexibility and executive function.

“Our research shows the importance of being in good physical shape at an early age for better brain development in such a critical stage as childhood,” explains Cristina Cadenas-Sánchez , postdoctoral researcher from the UGR’s PROFITH research group and the main author of the work.

The principal investigator of the project, Francisco B. Ortega, continues: “Previous studies had shown that, during the ageing process, the brain shrinks and physical exercise and keeping fit can help mitigate this physiological process. Our study shows, for the first time, that in childhood, when the brain is growing and developing, maintaining good levels of physical fitness is linked to greater overall brain development. These findings have important implications: 1) assessing children’s fitness levels at school not only provides information about their level of physical health, as previous studies have already shown, but also about brain health; and 2) the results open the pathway to further research into how increasing children’s level of physical fitness via exercise programmes can benefit brain development and cognition.”

Bibliography

Cadenas-Sanchez Cristina, Migueles JH, Erickson KI, Esteban-Cornejo I, Catena A, and Ortega FB (2020) ‘Do fitter kids have bigger brains?’ Scand J Med Sci Sports 30(12): 2498–502. doi: 10.1111/sms.13824. 

https://onlinelibrary.wiley.com/doi/full/10.1111/sms.13824

ActiveBrains project website: http://profith.ugr.es/activebrains

Image captions:

Example of an original MRI image from which the researchers determined the amount of grey matter, white matter, and total matter

UGR researchers Cristina Cadenas-Sánchez and Francisco Ortega, authors of this work

Informative illustration of this research

Media enquiries:

Cristina Cadenas-Sánchez

PROFITH (“PROmotingFITness and Health through physical activity”) research group, University of GranadaEmail: cristina.cadenas.sanchez@gmail.com