Researchers from the University of Granada have used computerized microtomography techniques to perform the first complete reconstruction of the Asian citrus psyllid, Diaphorina citri, a tiny insect measuring approximately 3 mm that causes significant damage to citrus fruit crops worldwide 

Scientists from the University of Granada (UGR) have made the first anatomical atlas of a tiny insect measuring just 3 mm called Diaphorina citri, the Asian citrus psyllid (ACP), which responsible for the greatest economic losses in citrus crops worldwide. 

As a pest, Diaphorina citri is very harmful to citrus trees (lemons, limes, oranges, grapefruits, tangerines, and kumquats ) due to the bacteria it spreads (Candidatus Liberibacter spp.). These bacteria cause Huanglongbing (HLB) disease (also known as citrus greening disease), considered the most serious bacterial disease affecting citrus fruits, as the bacterial infection causes yield losses, small, bitter, and foul-tasting fruits, and, finally the death of the tree. This translates into annual losses of millions of dollars.  

To date, this species has not been detected in the Iberian Peninsula, although another related species (Trioza erytreae) capable of transmitting the bacteria that cause Huanglongbing has already spread. Diaphorina citri could potentially cause devastating damage to the economy of those Spanish regions with large-scale citrus production, and the relevant authorities must make every effort to avoid the introduction of this insect (or diseased plants) when importing citrus fruits from countries where the disease and this vector species are present. 

The research group, led by Professor Susan J. Brown from Kansas State University, conducted a multidisciplinary macro-project to study the insect, the bacteria it transmits, its effects, and means of control (www.citrusgreening.org).

The US research team approached Javier Alba-Tercedor of the UGR’s Department of Zoology to lead the study of the functional anatomy of the insect using microtomographic techniques. Alba-Tercedor has an extensive track-record in the microtomographic study of insects, and his work (including photos and videos) has received various international awards. Given their spectacular aesthetic qualities, these have also been widely disseminated by the media.

Following a formal agreement between the UGR and Kansas State University, including collaboration with Dr. Wayne Hunter (from the Department of Agriculture in Fort Pierce, Florida), the insects were obtained for the study.

This study forms part of the doctoral thesis of Ignacio Alba-Alejandre (supervised by Alba-Tercedor). A recent article published in the prestigious journal Scientific Reports (by Nature) closes the series of articles providing a highly detailed vision of both the external and the internal structures of this insect.    

This study offers the first complete micro-CT reconstruction of this pest and constitutes a ground-breaking detailed anatomical study of a psyllid as the first anatomical micro-CT study of a hemipteran to be studied in its entirety. And, together with other papers already published by this team from the UGR on the coffee borer beetle, these studies represent the anatomical reconstructions of the smallest insects carried out to date using micro-CT.

Based on the descriptive aspects of the study, the team was able to elucidate the operation of different structures. Among the most noteworthy examples are the male sperm pump—an impellent suction pump that serves to expel sperm—and, similarly, the spermatheca (sac) in which females store sperm. This, too, acts as an impellent suction pump, performing an inward sucking motion, retaining the sperm after copulation, storing and nourishing them, and later, at the point of laying, contracting the walls of the sac to expel the sperm and fertilize the eggs. This mechanism requires a complex series of special valves and muscles.

An articulated reproductive organ

The complexity of the articulated reproductive organ of males is particularly striking, as is the fact that females have a more voluminous nervous system than males. The latter phenomenon undoubtedly occurs because they have to perform more complex vital functions, such as selecting the ideal location for subsequent egg-laying.

Curiously, the hindgut of the female is posteriorly differentiated into a rectum that forms a small rectal ampulla, into which it deposits small amounts of excrement. By contracting the walls of the ampulla, the faeces are violently propelled away from the body, thereby avoiding contact that could contaminate the eggs.

Another interesting discovery to emerge from the analysis carried out at the UGR was that these insects have glands at the base of the legs (coxal glands) and others at the base of the antennae (antennal glands) that produce sex pheromones. Thus, when the insect settles on the leaves, it impregnates them with the secretions of the coxal glands, which also attracts the opposite sex. Once males and females are close to one another, they begin a kind of “dance” in which they touch antennae and, thanks to the secretions of the antennal glands, recognize each other’s sexes.

These are just a few examples of the many discoveries made during the course of the UGR study. In the words of the researchers, “we often feel like true explorers discovering new territories, contemplating structures from never-before-seen perspectives, uncovering previously unknown structures, and deducing the how and why of their function.”

Scientific and aesthetic value

The work has produced numerous plates of figures that, as well as being of great scientific interest, have undoubted aesthetic value. Furthermore, the research team has been able to reconstruct in 3D—for the first time—an adult feeding on the leaf of a citrus fruit, showing how its stylets pierce the walls of the leaf to reach the vessels of the phloem and feed by sucking the sap. They have also produced a 3D model version for mobile devices (tablets and smartphones).

All of this work combined, together with numerous animated videos that enable viewers to see the structures in detail from multiple perspectives, renders this research a unique and extremely useful anatomical atlas not only for the study of this particular species but also for the investigation of insects in general. In addition, its impressive aesthetics make this material ideal for teaching and scientific dissemination purposes.

Bibliography:

ALBA-TERCEDOR, J., HUNTER, W.B. & ALBA-ALEJANDRE, I. (2021) ‘Using micro-computed tomography to reveal the anatomy of adult Diaphorina citri uwayama (Insecta: Hemiptera, Liviidae) and how it pierces and feeds within a citrus leaf’, Sci Rep 11, 1358. https://www.nature.com/articles/s41598-020-80404-z

The UGR researchers Javier Alba-Tercedor and Ignacio Alba-Alejandre in the laboratory, showing some of the results of the study. Behind, the Skyscan 1172 microtomograph and, on the screens, some microtomographic reconstructions of the anatomy of the Asian citrus psyllid under study

Microtomographic reconstructions showing anatomical details of an adult Asian citrus psyllid. The arrows indicating the structures and the corresponding names have been removed to better appreciate the aesthetic beauty of the images

The insect Diaphorina citri, whose common name is the Asian citrus psyllid (image credit: Wikipedia)

Videos:

Adult digestive and nervous system

An adult feeding on an orange tree leaf

Media enquiries:

Javier Alba-Tercedor

Department of Zoology, Faculty of Science, University of GranadaEmail: jalba@ugr.es

Scientists from the University of Granada and the Salamanca-based company Tebrio have used the insect Tenebrio molitor, more commonly known as the mealworm, as a source of antidiabetic peptides

Scientists from the Bioreactors Research Group (BIO-110) of the University of Granada (UGR) have demonstrated that a natural treatment based on flour made from the insect Tenebrio molitor (more commonly known as the mealworm) can help prevent Type II diabetes mellitus.

The researchers successfully obtained and identified peptides (molecules comprising one or more amino acids linked by chemical bonds) that can exert a preventive effect against diabetes from the protein fraction of the insect Tenebrio molitor.

The substrate used was flour from the insect which was donated by the Salamanca-based company Tebrio, a pioneering company in the breeding of insects on an industrial scale in Europe. Insect production is more sustainable and economical than other means of obtaining protein sources and the nutritional value of this source is of interest for its use in human foodstuffs.

Type II diabetes mellitus is one of the most prevalent diseases in the world today, with more than 400 million people affected. The World Health Organization estimates that it was the seventh most-prevalent cause of death in 2016 and that 700 million people may affected by this disease by 2045. The solutions currently applied in its treatment are insulin injections or the oral administration of various drugs that act by inhibiting enzymes such as DPP-IV or glucosidase, or hormone analogues involved in the restoration of insulin activity—a defining characteristic of this disease. However, these options often produce unwanted side-effects in humans.

Antidiabetic effect

The potential use of peptides derived from dietary proteins with the ability to inhibit these enzymes, thereby generating an antidiabetic effect in the patient, is now being actively investigated. Its advantage over current treatments is the absence of side-effects and the relative ease with which these peptides can be obtained using natural protein resources. There are in vivo studies with milk and marine proteins, for example, that show them to be a feasible alternative for use as active ingredients in functional food.

The study carried out at the UGR focused on obtaining peptides with an antidiabetic capacity and involved optimizing the release of peptides contained in the protein of Tenebrio molitor by means of enzymatic processes. The scientists successfully obtained insect protein hydrolysates with bioactivity values comparable to traditional sources, pointing to the possibility of encouraging the production of this type of product from this sustainable protein source. Seven inhibitor peptides of the DPP-IV enzyme were identified, with a mean length of 5 amino acids, and six inhibitor peptides of the glucosidase enzyme, with a mean length of between 2 and 4 amino acids.

The use of insects in functional food is—and will continue to be—a highly-relevant research topic as it offers a potential solution to various challenges that we currently face in society, conclude the UGR researchers.

Images of the insect Tenebrio molitor (commonly known as the mealworm) used in this study

Bibliography:

Rivero-Pino, F., Espejo-Carpio, F.J., & Guadix, E.M. (2020) ‘Antidiabetic Food-Derived Peptides for Functional Feeding: Production, Functionality and In Vivo Evidences’,  Foods 9, 983. https://doi.org/10.3390/foods9080983

Rivero-Pino, F., Espejo-Carpio, F. J., Pérez-Gálvez, R., Guadix, A., & Guadix, E. M. (2020) ‘Effect of ultrasound pretreatment and sequential hydrolysis on the production of Tenebrio molitor antidiabetic peptides’, Food and Bioproducts Processing 123, 217–224. https://doi.org/10.1016/j.fbp.2020.07.003

Rivero-Pino, F., Pérez-Gálvez, A. R., Espejo-Carpio, F. J., & Guadix, E. M. (2020) ‘Evaluation of Tenebrio Molitor protein as source of peptides modulating physiological processes’, Food & Function 11, 4376–4386. https://doi.org/10.1039/D0FO00734J

Rivero-Pino, F., Guadix, A. & Guadix, E. M. (2021) ‘Identification of novel dipeptidyl peptidase IV and α-glucosidase inhibitory peptides from Tenebrio molitor’, Food & Function 12, 873–880 https://doi.org/10.1039/D0FO02696D

More information can be found at: https://tebrio.com

Media enquiries: 

Fernando Rivero Pino 

Department of Chemical Engineering, University of Granada, PhD candidate in the Bioreactors Research Group (BIO-110)

Email: frivero@ugr.es

Emilia M. Guadix 

Department of Chemical Engineering, University of Granada, Director of the Bioreactors Research Group (BIO-110)

Email: eguadix@ugr.es

A study carried out by the University of Granada indicates that smoking cannabis significantly alters key visual functions, such as visual acuity, contrast sensitivity, three-dimensional vision (stereopsis), the ability to focus, and glare sensitivity

Yet, more than 90% of users believe that using cannabis has no effect on their vision, or only a slight effect

A group of researchers from the Department of Optics of the University of Granada (UGR) has studied the effects of smoking cannabis on various visual parameters compared to the effect that the users themselves perceive the drug to have on their vision.

This study, led by Carolina Ortiz Herrera and Rosario González Anera, has been published in the journal Scientific Reports. Its main author, Sonia Ortiz Peregrina, explains that cannabis use is on the rise despite being an illegal drug. According to the national Survey on Alcohol, Drugs and Other Addictions in Spain 2019–2020, cannabis use nationally has increased since 2011, with 37% of Spanish adults having used this drug at some time. Approximately 10% consumed it in the last year.    

In this study, which had the approval of the Human Research Ethics Committee of the UGR (ref. 921/CCEIH/2019), an exhaustive visual trial was conducted on 31 cannabis users, both when they had not consumed any substance in advance and also when they were under the effect of the drug. The researchers also studied the participants’ perception of the visual effects of having consumed this drug.

The results showed that, following consumption, visual aspects such as visual acuity, contrast sensitivity, three-dimensional vision (stereopsis), the ability to focus, and glare sensitivity significantly worsened. Despite this, not all subjects reported a worsening of their vision after smoking cannabis. Indeed, 30% reported that their vision had not suffered at all, while 65% responded that it had worsened only slightly. The authors note that the visual parameter that could be most strongly linked to users’ perception of the visual effect is contrast sensitivity.

The study found a negative effect on all of the visual parameters evaluated, with the effect of cannabis on some of the parameters being analysed for the first time in this research. These results, together with the lack of awareness that the participants presented about the visual impairment caused by smoking cannabis, indicate the need to carry out awareness-raising campaigns, as this visual deterioration can pose a danger when performing everyday tasks.

Bibliography:

Ortiz-Peregrina, S., Ortiz, C., Casares-López, M. Jiménez, J. R. & Anera, R. G. (2021) ‘Effects of cannabis on visual function and self-perceived visual quality’, Scientific Reports, 11, 1655. https://doi.org/10.1038/s41598-021-81070-5

The UGR researchers who conducted this study

According to the national Survey on Alcohol, Drugs and Other Addictions in Spain 2019–2020, cannabis use has increased since 2011 in Spain

Media enquiries:

Sonia Ortiz Peregrina

UGR Optics Department

Tel.: +34 958 241925Email: soniaortiz@ugr.es

Researchers from the University of Granada and the “San Cecilio de Granada” Teaching Hospital confirm that endocrine disruptors—chemical substances that may mimic or block the action of hormones—are present in some cosmetic products

The use of some cosmetic and beauty products (such as facemasks, lipsticks, face creams, nail polish, hair dyes, creams, hairspray, and hair mousse) could be related to an increased likelihood of developing endometriosis, due to certain chemical ingredients that  mimic or block the action of hormones (known as endocrine disruptors).

This is one of the conclusions of a study conducted by researchers from the University of Granada (UGR) and the “San Cecilio de Granada” Teaching Hospital, published in the journal Environmental Research. The work forms part of a wider research project called EndEA.   

Endometriosis is a very common gynaecological disease: it is estimated that one in 10 women of reproductive age could suffer from it. It is characterized by abnormal growth of endometrial tissue (which normally lines the inside of the uterus). This tissue extends into various areas of the abdomen and pelvis, causing a wide range of symptoms including intense chronic pain in the pelvic region, intestinal problems, and infertility, notably decreasing the quality of life of these women.

This disease is also notoriously difficult to diagnose (it requires a surgical intervention to definitively confirm it), which can cause a significant delay in diagnosis—estimated at 10 years, on average, from the onset of symptoms. In addition, the lack of a definitive treatment to cure endometriosis makes it a chronic disease that can render daily life a challenge.

The role of hormones

The researchers responsible for this project, the gynaecologist Olga Ocón from the “San Cecilio de Granada” Teaching Hospital and UGR lecturer Francisco Artacho, explain: “Although the exact causes of its appearance are not known, a diverse range of factors are suspected of being involved, including genetic, epigenetic, and environmental causes , with hormones appearing to play a key role.”   

For this reason, the presence of chemical substances, known as endocrine disruptors, in many everyday products is of particular concern. These substances are capable of mimicking or blocking the natural action of hormones and could therefore be contributing to the increase in the number of women diagnosed with endometriosis in recent years, as has been shown for other pathologies such as breast cancer, obesity, or diabetes.

These endocrine disruptors include parabens and benzophenones, both of which are widely used in the cosmetics and beauty products industry and which are part of the so-called “exposome”. This relatively new term encompasses all the non-genetic environmental factors to which human beings are exposed from birth onward that contribute to the risk of illness and disease.

Against this backdrop, these researchers are now studying the role that endocrine disruptors may play in the development of endometriosis. Their work is part of the EndEA research project funded by the “Carlos III Health Institute” (pertaining to the Spanish Ministry of Science and Innovation) and the “Antonio Chamorro-Alejandro Otero” Research Chair.

As part of their investigations, the scientists quantified internal levels of parabens and benzophenones among 124 women (with and without endometriosis), from public hospitals in Granada. They also gathered detailed information on each woman’s use of cosmetics and beauty products.

The results obtained, which are part of the doctoral thesis being developed by researcher Francisco M. Peinado, showed a clear link between greater use of various types of cosmetics (facemasks, lipsticks, face creams, footcare products, hair dyes, creams, hairspray, and hair mousse) and higher internal levels of parabens and benzophenones. Ocón and Artacho note that they also found that “the internal levels of some of these endocrine disruptors were related to the risk of endometriosis.”

As Francisco Peinado observes, given its difficult diagnosis and the fact that there is still no treatment that definitively cures endometriosis, it is important to establish preventive measures aimed at reducing exposure to these compounds, by switching to products free from endocrine disruptors or using them less frequently.

These results build on the previous findings published in another recent study by the same researchers, which showed that one specific endocrine disruptor, bisphenol A, could also be involved in the development of this disease.

Bibliography:

F.M. Peinado, O. Ocón-Hernández, L.M. Iribarne-Durán, F. Vela-Soria, A. Ubiña, C. Padilla, J.C. Mora, J. Cardona, J. León, M.F. Fernández, N. Olea, and F. Artacho-Cordón (2020) ‘Cosmetic and personal care product use, urinary levels of parabens and benzophenones, and risk of endometriosis: Results from the EndEA study’, Environmental Research 110342.

Some of the cosmetic products analysed by the scientists in this study

Researchers Francisco M. Peinado (first author of the study, whose doctoral thesis underpins this research) and Luz M. Iribarne, collaborating author

Media enquiries:

Francisco Artacho Cordón

Department of Radiology and Physical Medicine, University of Granada

Tel.: +34 958 249983Email: fartacho@ugr.es

Scientists from the University of Granada have analysed the levels of cortisol (a steroid hormone that is released in response to stress) in the hair of pregnant women in the period spanning from before conception to week 9 of their pregnancy, to determine whether there was any link to the sex of the baby  

A total of 108 women participated in the research from the first weeks of pregnancy to delivery, having recorded their stress levels before, during, and after conception (via the concentration of cortisol in hair) and performed different psychological tests

A study carried out by scientists from the University of Granada (UGR) has revealed that women who experience stress both before becoming pregnant and during conception are almost twice as likely to have a girl as a boy.

Researchers from the Mind, Brain and Behaviour Research Centre (CIMCYC), the Department of Pharmacology (Faculty of Pharmacy), and the Faculty of Psychology have analysed the levels of cortisol (a steroid hormone that is released in response to stress) in the hair of pregnant women in the period spanning from before conception to week 9 of pregnancy, to determine whether there was any link with the sex of the baby.

A total of 108 women were monitored from the first weeks of pregnancy through to delivery, to record their stress levels before, during, and after conception via the concentration of cortisol in their hair and various psychological tests. The measurement of cortisol in hair samples taken approximately in week 8–10 of pregnancy showed the concentration of cortisol in the pregnant woman for the previous three months (one month per centimetre of hair growth), meaning that it covered the period preceding and after conception. Subsequently, the UGR scientists recorded different variables relating to the birth and the sex of the baby.

María Isabel Peralta Ramírez, the main author of this work and researcher at the UGR’s Department of Personality, Evaluation and Psychological Treatment explains: “The results we found were surprising, as they showed that the women who had given birth to girls presented higher concentrations of hair cortisol in the weeks before, during, and after the point of conception than those who had boys.” In fact, these cortisol concentrations in the hair of mothers who subsequently had girls were almost double those who had boys.  

Consequences of stress

There is ample scientific evidence demonstrating the impact of stress on the mother in the processes of pregnancy, birth, and even infant neurodevelopment. “Specifically, our research group has shown in numerous publications how psychological stress in the mother generates a greater number of psychopathological symptoms during pregnancy, postpartum depression, a greater likelihood of assisted delivery, an increase in the time taken for lactation to commence (lactogenesis), or inferior neurodevelopment of the baby six months after birth,” says Peralta.

All of the existing research tells us about the effect of stress when pregnancy has already occurred. However, few studies have shown the link between stress and the mother-to-be before or during the conception of the baby, the present study being a rare exception. Its findings were recently published in the prestigious Journal of Developmental Origins of Health and Disease. 

One possible explanation for the results would be that the activation of the “stress system”—the hypothalamus-pituitary-adrenal gland system—which involves an increase in cortisol secretion, modifies the concentrations of sex hormones at the time of conception. However, the mechanisms underlying this modification are not clear, because, on the one hand, there is evidence that testosterone could influence the determination of the baby’s sex, since the higher the levels of prenatal stress, the higher the levels of female testosterone. 

On the other hand, there is scientific evidence that sperm carrying the X chromosome (which determines that the baby will be female) perform better at passing through the cervical mucus in circumstances of adversity. Therefore, due to the hormonal changes associated with stress in the mother, these sperm are more likely to be successful in reaching the egg than sperm carrying the Y chromosome (which determines that the baby will be male).

“There are other possible hypotheses that attempt to explain this phenomenon. Among the strongest theories is the idea that there are more terminations of male foetuses on medical grounds during the first weeks of gestation in situations of severe maternal stress. That said, in light of the design of these studies, it is recommended that the results are corroborated in greater depth,” observes Peralta.

The effect of stress on the foetus

What does appear to be clear— and this has been shown in several studies—is that foetuses are vulnerable to the effect of stress, since it plays a key role in their development. An example of this is the proven fact that male (XY) foetuses mature more slowly than female (XX) foetuses; they tend to be associated with more complications in pregnancy and premature delivery; and, at birth, they are more likely to have shorter telomeres. This renders XY foetuses more vulnerable to adverse prenatal environments, suggesting that women who experience high levels of stress around the time of conception may be less likely to give birth to a boy.

This study was conducted by members of the research group Neuropsychology and Psychoneuroimmunology Applied to Children, Adults and the Elderly. It operates under the auspices of the Framework for R&D Projects granted by the Spanish Ministry of Science, Innovation and Universities (ABORSTRESS AND CHILDSTRESS).

Bibliography:

Romero-González, B., Puertas-González, J.A., González-Pérez, R., Dávila, M., & Peralta-Ramirez, M.I. (2021) ‘Hair cortisol levels in pregnancy as a possible determinant of fetal sex: A longitudinal study, Journal of Developmental Origins of Health and Disease 7, 1–6.

https://doi.org/10.1017/S2040174420001300

The UGR research team that conducted this study

Media enquiries:

Maria Isabel Peralta Ramírez

Department of Personality, Evaluation and Psychological Treatment, University of Granada  / Mind, Brain and Behaviour Research Centre (CIMCYC)

Tel.: +34 655 987 812Email: mperalta@ugr.es

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

This study, published recently in the international journal Insects, was conducted by researchers from the University of Granada, the Doñana Biological Station, and the Biomedical Research Networking Centre for Epidemiology and Public Health (CIBERESP) 

Researchers from the University of Granada (UGR), the Doñana Biological Station (EBD-CSIC), and the Biomedical Research Networking Centre for Epidemiology and Public Health (CIBERESP) have carried out the most comprehensive study to date of the eating patterns of the tiger mosquito (Aedes albopictus) and other invasive species of the same genus in Europe. The results of the study were recently published in the international journal Insects.

This research, which reviews all previously published studies on this topic, shows that these species of mosquitoes feed off different groups of vertebrates, especially mammals, and humans are also common hosts. Not surprisingly, human blood represents 93% of the blood meals of Aedes aegypti, the mosquito responsible for yellow fever. 

Mosquitoes are one of the main groups of vector insects—that is, insects involved in the transmission of major pathogens that adversely affect people, livestock, and wildlife. As with other groups of animals, different species of invasive mosquitoes have become established in areas outside their original range. This is the case with different species of mosquitoes of the Aedes genus, which are of particular importance from the public health perspective, due to their capacity to transmit pathogens that cause serious diseases. 

“Thus, the appearance of these species can modify the local epidemiology of many pathogens in invaded areas, including pathogens that circulate naturally in the environment, or imported pathogens,” explains one of the authors of the work, Josué Martínez de la Puente, a researcher at the UGR’s Department of Parasitology.

So far, four invasive species of the Aedes genus have established populations in Europe, which include such relevant vector species as the tiger mosquito, Aedes albopictus.

Blood meals

To complete their life cycle and the development of their eggs, female mosquitoes require blood meals taken from different vertebrate hosts. In addition to causing discomfort, the bites they cause can transmit different pathogens. “Therefore, this blood-feeding behaviour represents a fundamental factor, the relevance of which needs to be studied to understand the epidemiology of different diseases. In this review article, we study the feeding patterns of those four invasive mosquitoes of the Aedes genus in Europe,” explains Martínez de la Puente.

The results show that these species of mosquitoes feed off different groups of vertebrates, especially mammals. Humans are common hosts for these mosquitoes, representing 93% of the blood meals of the Aedes aegypti species. In addition, mosquitoes are capable of feeding on the blood of other groups of vertebrates, including birds and even ectothermic animals (those whose body temperature changes in line with the temperature of the environment). 

Given their capacity to transmit different pathogens and their feeding rates among humans, invasive mosquito species of the Aedes genus may have a significant impact on the transmission of these pathogens in urban and periurban areas, the authors conclude. 

Bibliography:

Sonia Cebrián-Camisón, Josué Martínez-de la Puente, & Jordi Figuerola (2020) ‘A literature review of host feeding patterns of invasive Aedes mosquitoes in Europe’, Insects 11(12), 848. https://doi.org/10.3390/insects11120848

Image captions:

Images of the tiger mosquito (Aedes albopictus). Photo credit: Martina Ferraguti

The tiger mosquito (Aedes albopictus). Photo credit: Julia López

The researcher Sonia Cebrián-Camisón

The UGR researcher Josué Martínez-de la Puente

Media enquiries:

Josué Martínez de la Puente

Department of Parasitology, University of Granada

Email: jmp@ugr.es

Unlike the Higgs boson, discovered at CERN’s Large Hadron Collider in 2012 after a 40-year quest, the new particle proposed by these researchers is so heavy that it could not be produced directly even in this collider

The University of Granada is among the participants in this major scientific advancement in Theoretical Physics, which could help unravel the mysteries of dark matter

Scientists from the University of Granada (UGR) and the Johannes Gutenberg University Mainz (Germany) have recently published a study in which they endeavour to extend the Standard Model of particle physics (the equivalent of ‘the periodic table’ for particle physics) and answer some of the questions that this model is unable to answer. Such puzzles include: What is dark matter made of? Why do the various constituents of fermionic dark matter have such different masses? Or, why is the force of gravity much weaker than electromagnetic interaction?

This work, published in the European Physical Journal C, is based on the existence of a dimension in spacetime that is “so small that we can only detect evidence of it through its indirect effects,” explains one of the authors of the article, Adrián Carmona, Athenea3i Fellow at the UGR and a member of the Department of Theoretical Physics and the Cosmos.   

As early as the 1920s, in an attempt to unify the forces of gravity and electromagnetism, Theodor Kaluza and Oskar Klein speculated on the existence of an extra dimension beyond the familiar three space dimensions and time (which, in physics, are combined into a 4-dimensional spacetime).

Such models became popular in the 1990s, when theoretical physicists realized that theories with curved extra dimensions could explain some of the major mysteries in this field. However, despite their many strengths, such models generally lacked a viable dark-matter candidate.

Now, more than 20 years later, Adrián Carmona and collaborators from the University of Mainz, Professor Matthias Neubert and doctoral student Javier Castellano, have predicted the existence of a new heavy particle in these models with properties similar to those of the famous Higgs boson.

A new dimension

“This particle could play a fundamental role in the generation of masses of all the particles sensitive to this extra dimension, and at the same time be the only relevant window to a possible dark sector responsible for the existence of dark matter, which would simultaneously solve two of the biggest problems of these theories that, a priori, appear disconnected,” explains the UGR researcher.

However, unlike the Higgs boson, which was discovered at CERN’s Large Hadron Collider in 2012 after a 40-year quest, the new particle proposed by these researchers is so heavy that it could not be produced directly even in this, the highest-energy particle collider in the world.

In the article, the researchers explore other possible ways of discovering this particle by looking for clues about the physics surrounding a very early stage in the history of our universe, when dark matter was produced.

Bibliography:

Carmona, A., Castellano Ruiz, J. & Neubert, M. (2021) ‘A warped scalar portal to fermionic dark matter’, Eur. Phys. J. C 81, 58. https://doi.org/10.1140/epjc/s10052-021-08851-0

https://link.springer.com/article/10.1140%2Fepjc%2Fs10052-021-08851-0

Simulation of a collision in the Large Hadron Collider, producing the Higgs boson. © 1997–2021 CERN (License: CC-BY-SA-4.0)

The UGR researcher Adrián Carmona Bermúdez, from the Department of Theoretical Physics and the Cosmos of the UGR

Media enquiries:

Adrián Carmona Bermúdez

Department of Theoretical Physics and the Cosmos,

University of Granada

Email: adrian@ugr.es

The results, recently published in the journal Communications Biology, have important applications in the field of coevolutionary biology 

The physical movement of species determines their potential scope to leave their primary ecosystem behind in the quest for new niches in which to survive or reproduce—a decisive factor for the processes that determine their genomic characteristics.

Researchers from the University of Granada (UGR) and the University of Illinois (UI) have, for the first time, analysed the relationship between this potential for movement in different species of parasites—their dispersal capacity—and their levels of genetic introgression. Introgression—the gradual movement of genes from one species into the gene pool of another—affects the proportion of regions of the genome of a given species that comes from different species via hybridisation.

This new study on this phenomenon was led by Jorge Doña Reguera, a Marie Curie postdoctoral researcher from the Department of Zoology at the University of Granada and a member of the University of Illinois at Urbana-Champaign. Its results were recently published in the journal Communications Biology. 

The team of scientists demonstrated that differences in the dispersal capacities of different species can modulate levels of genomic introgression—that is, the parasite species with the greatest ability to reach different host species presented higher levels of introgression.

Doña Reguera, together with Drs Andrew Sweet and Kevin Johnson, began this study in 2018, focusing on the relationship between dispersal capabilities and genomic introgression levels in the case of bird lice. Currently, the research is expanding its focus within the Marie Curie “INTROSYM” project in which, together with Drs Juan Gabriel Martínez Suarez from the UGR and Kevin Johnson, introgression processes in symbionts is being investigated. This project will analyse the incidence of this phenomenon and its impact on the ecology, evolution, and conservation of symbiont species (for more information, visit https://cordis.europa.eu/project/id/886532/en). 

Returning to the bird lice study, the ecological replicate system of wing and body lice of pigeons and doves was used. That is, this replicate system (which is ecologically similar, but phylogenetically independent), was used to study both the louse group with the highest dispersal capacities (wing lice) and the group with the lowest dispersal capacity (body lice).

First, the authors found a higher proportion of introgressed regions and, subsequently, a greater number of reticulated phylogenetic networks in the genus of wing lice. Therefore, the results indicated that species with higher dispersal abilities present increased genomic signatures of introgression (due to hybridisation events).

“The fact that dispersal capacities are linked to introgression rates could enable us to get closer to predicting the introgression rate of a given species of parasite, which could have very important implications for understanding parasite–host dynamics,” explains the UGR researcher.

For example, this knowledge could be of great value in the case of co-adaptation processes between species (that is, the adaptation of a species in response to interaction with another) or modulating the speciation processes of parasites by modifying the opportunities for colonisation of new hosts, “something that may be important for understanding the emergence of infectious diseases.”

Doña notes the warm reception the publication has received in the scientific community, although much remains to be done, due to the novelty of the subject. Matter. “One very important aspect of this work is that the study system that we used, bird lice, was the same as that of numerous foundational studies in coevolutionary biology and reference books such as Coevolution of Life on Hosts,” he says. “The fact that we have found evidence of introgression in this system opens up many questions, such as how does this new process/result fit into everything we knew before?” As the INTROSYM project continues to evolve, he expects new answers to be uncovered.        

Bibliography:

Doña, J., Sweet, A.D. & Johnson, K.P. (2020) ‘Comparing rates of introgression in parasitic feather lice with differing dispersal capabilities’, Communications Biology 3, 610.  https://doi.org/10.1038/s42003-020-01345-x

The authors of this research

In this study, the ecological replicate system—ecologically similar, but phylogenetically independent—of wing lice (the louse group with the highest dispersal capacities) and body lice (the group with the lowest dispersal capacity) of pigeons was used

Media enquiries:

Jorge Doña Reguera

Department of Zoology, University of Granada

Email: jorged@ugr.es