An adenosine derivative promotes mitochondrial supercomplexes reorganization and restoration of mitochondria structure and bioenergetics in a diethylnitrosamine-induced hepatocellular carcinoma model.

Hepatocellular carcinoma (HCC) progression is associated with dysfunctional mitochondria and bioenergetics impairment. However, no data about the relationship between mitochondrial supercomplexes (hmwSC) formation and ATP production rates in HCC are available. Our group has developed an adenosine derivative, IFC-305, which improves mitochondrial function, and it has been proposed as a therapeutic candidate for HCC. We aimed to determine the role of IFC-305 on both mitochondrial structure and bioenergetics in a sequential cirrhosis-HCC model in rats. Our results showed that IFC-305 administration decreased the number and size of liver tumors, reduced the expression of tumoral markers, and reestablished the typical architecture of the hepatic parenchyma. The livers of treated rats showed a reduction of mitochondria number, recovery of the mtDNA/nDNA ratio, and mitochondrial length. Also, IFC-305 increased cardiolipin and phosphatidylcholine levels and promoted hmwSC reorganization with changes in the expression levels of hmwSC assembly-related genes. IFC-305 in HCC modified the expression of several genes encoding elements of electron transport chain complexes and increased the ATP levels by recovering the complex I, III, and V activity. We propose that IFC-305 restores the mitochondrial bioenergetics in HCC by normalizing the quantity, morphology, and function of mitochondria, possibly as part of its hepatic restorative effect.

Systematic review and bioinformatics analysis of plasma and serum extracellular vesicles proteome in type 2 diabetes.

Background: Type 2 diabetes (T2D) is a complex metabolic ailment marked by a global high prevalence and significant attention in primary healthcare settings due to its elevated morbidity and mortality rates. The pathophysiological mechanisms underlying the onset and progression of this disease remain subjects of ongoing investigation. Recent evidence underscores the pivotal role of the intricate intercellular communication network, wherein cell-derived vesicles, commonly referred to as extracellular vesicles (EVs), emerge as dynamic regulators of diabetes-related complications. Given that the protein cargo carried by EVs is contingent upon the metabolic conditions of the originating cells, particular proteins may serve as informative indicators for the risk of activating or inhibiting signaling pathways crucial to the progression of T2D complications. Methods: In this study, we conducted a systematic review to analyze the published evidence on the proteome of EVs from the plasma or serum of patients with T2D, both with and without complications (PROSPERO: CRD42023431464). Results: Nine eligible articles were systematically identified from the databases, and the proteins featured in these articles underwent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. We identified changes in the level of 426 proteins, with CST6, CD55, HBA1, S100A8, and S100A9 reported to have high levels, while FGL1 exhibited low levels. Conclusion: These proteins are implicated in pathophysiological mechanisms such as inflammation, complement, and platelet activation, suggesting their potential as risk markers for T2D development and progression. Further studies are required to explore this topic in greater detail.

Combining aperiodic 1/f slopes and brain simulation: An EEG/MEG proxy marker of excitation/inhibition imbalance in Alzheimer's disease.

INTRODUCTION: Accumulation and interaction of amyloid-beta (Aß) and tau proteins during progression of Alzheimer's disease (AD) are shown to tilt neuronal circuits away from balanced excitation/inhibition (E/I). Current available techniques for noninvasive interrogation of E/I in the intact human brain, for example, magnetic resonance spectroscopy (MRS), are highly restrictive (i.e., limited spatial extent), have low temporal and spatial resolution and suffer from the limited ability to distinguish accurately between different neurotransmitters complicating its interpretation. As such, these methods alone offer an incomplete explanation of E/I. Recently, the aperiodic component of neural power spectrum, often referred to in the literature as the '1/f slope', has been described as a promising and scalable biomarker that can track disruptions in E/I potentially underlying a spectrum of clinical conditions, such as autism, schizophrenia, or epilepsy, as well as developmental E/I changes as seen in aging. METHODS: Using 1/f slopes from resting-state spectral data and computational modeling, we developed a new method for inferring E/I alterations in AD. RESULTS: We tested our method on recent freely and publicly available electroencephalography (EEG) and magnetoencephalography (MEG) datasets of patients with AD or prodromal disease and demonstrated the method's potential for uncovering regional patterns of abnormal excitatory and inhibitory parameters. DISCUSSION: Our results provide a general framework for investigating circuit-level disorders in AD and developing therapeutic interventions that aim to restore the balance between excitation and inhibition.

A Review of Automated Techniques for Assisting the Early Detection of Alzheimer's Disease with a Focus on EEG.

In this paper, we review state-of-the-art approaches that apply signal processing (SP) and machine learning (ML) to automate the detection of Alzheimer's disease (AD) and its prodromal stages. In the first part of the document, we describe the economic and social implications of the disease, traditional diagnosis techniques, and the fundaments of automated AD detection. Then, we present electroencephalography (EEG) as an appropriate alternative for the early detection of AD, owing to its reduced cost, portability, and non-invasiveness. We also describe the main time and frequency domain EEG features that are employed in AD detection. Subsequently, we examine some of the main studies of the last decade that aim to provide an automatic detection of AD and its previous stages by means of SP and ML. In these studies, brain data was acquired using multiple medical techniques such as magnetic resonance imaging, positron emission tomography, and EEG. The main aspects of each approach, namely feature extraction, classification model, validation approach, and performance metrics, are compiled and discussed. Lastly, a set of conclusions and recommendations for future research on AD automatic detection are drawn in the final section of the paper.

Ciencia en el Madrid del "no pasarán". La protección de las colecciones de Historia Natural y el Instituto Nacional de Ciencias Naturales durante la Guerra Civil / Science in No Pasarán Madrid. The protection of the collections of Natural History and the Instituto Nacional de Ciencias Naturales during the Civil War (1936-1939)

Los edificios culturales y científicos de Madrid se vieron muy perjudicados por la guerra civil española (1936-1939). Madrid fue una ciudad asediada y bombardeada por los sublevados. En la capital se encontraban los más importantes museos, la Biblioteca Nacional y las principales instituciones científicas y de humanidades, en donde trabajaban los más relevantes investigadores de la época. A comienzos de la guerra tuvo lugar la incautación de bibliotecas y colecciones de ciencias naturales en palacios y edificios pertenecientes a aristócratas, financieros, personas contrarias a la República y colegios de religiosos. Los naturalistas del Instituto Nacional de Ciencias Naturales organizaron la conservación y protección de las colecciones biológicas, mientras que bombas y obuses impactaban en las instituciones científicas de la zona republicana

The cultural and scientific buildings of Madrid were severely damaged by the Spanish Civil War (1936-1939). Madrid was a city besieged and bombed by the rebels. In the capital were the most important museums, the National Library and the main scientific and humanities institutions, where the most important researchers of the time worked. At the beginning of the war the confiscation of libraries and collections of natural sciences took place in palaces and buildings belonging to aristocrats, financiers, people opposed to the Republic and religious schools. The naturalists of the National Institute of Natural Sciences organized the conservation and protection of the biological collections, while bombs and howitzers fell on the scientific institutions of the republican zone

A Neuronal Network Model of the Primate Visual System: Color Mechanisms in the Retina, LGN and V1.

Color plays a key role in human vision but the neural machinery that underlies the transformation from stimulus to perception is not well understood. Here, we implemented a two-dimensional network model of the first stages in the primate parvocellular pathway (retina, lateral geniculate nucleus and layer 4C ß in V1) consisting of conductance-based point neurons. Model parameters were tuned based on physiological and anatomical data from the primate foveal and parafoveal vision, the most relevant visual field areas for color vision. We exhaustively benchmarked the model against well-established chromatic and achromatic visual stimuli, showing spatial and temporal responses of the model to disk- and ring-shaped light flashes, spatially uniform squares and sine-wave gratings of varying spatial frequency. The spatiotemporal patterns of parvocellular cells and cortical cells are consistent with their classification into chromatically single-opponent and double-opponent groups, and nonopponent cells selective for luminance stimuli. The model was implemented in the widely used neural simulation tool NEST and released as open source software. The aim of our modeling is to provide a biologically realistic framework within which a broad range of neuronal interactions can be examined at several different levels, with a focus on understanding how color information is processed.

Portable System for Real-Time Detection of Stress Level.

Currently, mental stress is a major problem in our society. It is related to a wide variety of diseases and is mainly caused by daily-life factors. The use of mobile technology for healthcare purposes has dramatically increased during the last few years. In particular, for out-of-lab stress detection, a considerable number of biosignal-based methods and systems have been proposed. However, these approaches have not matured yet into applications that are reliable and useful enough to significantly improve people's quality of life. Further research is needed. In this paper, we propose a portable system for real-time detection of stress based on multiple biosignals such as electroencephalography, electrocardiography, electromyography, and galvanic skin response. In order to validate our system, we conducted a study using a previously published and well-established methodology. In our study, ten subjects were stressed and then relaxed while their biosignals were simultaneously recorded with the portable system. The results show that our system can classify three levels of stress (stress, relax, and neutral) with a resolution of a few seconds and 86% accuracy. This suggests that the proposed system could have a relevant impact on people's lives. It can be used to prevent stress episodes in many situations of everyday life such as work, school, and home.

Biophysical network modeling of the dLGN circuit: Effects of cortical feedback on spatial response properties of relay cells.

Despite half-a-century of research since the seminal work of Hubel and Wiesel, the role of the dorsal lateral geniculate nucleus (dLGN) in shaping the visual signals is not properly understood. Placed on route from retina to primary visual cortex in the early visual pathway, a striking feature of the dLGN circuit is that both the relay cells (RCs) and interneurons (INs) not only receive feedforward input from retinal ganglion cells, but also a prominent feedback from cells in layer 6 of visual cortex. This feedback has been proposed to affect synchronicity and other temporal properties of the RC firing. It has also been seen to affect spatial properties such as the center-surround antagonism of thalamic receptive fields, i.e., the suppression of the response to very large stimuli compared to smaller, more optimal stimuli. Here we explore the spatial effects of cortical feedback on the RC response by means of a a comprehensive network model with biophysically detailed, single-compartment and multicompartment neuron models of RCs, INs and a population of orientation-selective layer 6 simple cells, consisting of pyramidal cells (PY). We have considered two different arrangements of synaptic feedback from the ON and OFF zones in the visual cortex to the dLGN: phase-reversed ('push-pull') and phase-matched ('push-push'), as well as different spatial extents of the corticothalamic projection pattern. Our simulation results support that a phase-reversed arrangement provides a more effective way for cortical feedback to provide the increased center-surround antagonism seen in experiments both for flashing spots and, even more prominently, for patch gratings. This implies that ON-center RCs receive direct excitation from OFF-dominated cortical cells and indirect inhibitory feedback from ON-dominated cortical cells. The increased center-surround antagonism in the model is accompanied by spatial focusing, i.e., the maximum RC response occurs for smaller stimuli when feedback is present.

The evolutionist debate in Spain during the nineteenth century: a re-examination. / La polémica evolucionista en España durante el siglo XIX: una revisión.

This article re-examines the research on evolutionism in Spain and updates knowledge on this topic in light of the work of Thomas Glick, the more philosophical work of Diego Núñez and contributions in recent years from the Latin American network of historians of biology and evolution, who have dealt with the more polemical aspects of the reception of evolution theory. It includes new arguments, such as identification of the drawings in El Museo Universal, whose Lamarckian or Darwinian nature has been a subject of ongoing debate. It also covers the crucial role of the acceptance of Haeckel's work in Spain in comparison to the weaker support for a strictly Darwinian perspective, the role of the Spanish histology school, and the impact of evolutionism on literature.

Resumen Este artículo realiza una revisión de los estudios sobre el evolucionismo en España y actualiza los conocimientos sobre el mismo tras los trabajos de Thomas Glick, la obra más filosófica de Diego Núñez y las aportaciones en los últimos años de la red latinoamericana de historia de la biología y la evolución, incidiendo en los aspectos más polémicos de la recepción de esta teoría. Incluye novedades como la identificación de los dibujos de El Museo Universal, siempre en discusión sobre su naturaleza lamarckiana o darwinista, el papel fundamental de la recepción de la obra de Haeckel en España frente a una recepción estrictamente darwiniana más débil, el papel jugado en la escuela histológica española y el impacto en la literatura.

Blue lighting accelerates post-stress relaxation: Results of a preliminary study.

Several authors have studied the influence of light on both human physiology and emotions. Blue light has been proved to reduce sleepiness by suppression of melatonin secretion and it is also present in many emotion-related studies. Most of these have a common lack of objective methodology since results and conclusions are based on subjective perception of emotions. The aim of this work was the objective assessment of the effect of blue lighting in post-stress relaxation, in comparison with white lighting, by means of bio-signals and standardized procedures. We conducted a study in which twelve healthy volunteers were stressed and then performed a relaxation session within a chromotherapy room with blue (test group) or white (control group) lighting. We conclude that the blue lighting accelerates the relaxation process after stress in comparison with conventional white lighting. The relaxation time decreased by approximately three-fold (1.1 vs. 3.5 minutes). We also observed a convergence time (3.5-5 minutes) after which the advantage of blue lighting disappeared. This supports the relationship between color of light and stress, and the observations reported in previous works. These findings could be useful in clinical and educational environments, as well as in daily-life context and emerging technologies such as neuromarketing. However, our study must be extended to draw reliable conclusions and solid scientific evidence.

La polémica evolucionista en España durante el siglo XIX: una revisión / The evolutionist debate in Spain during the nineteenth century: a re-examination

Resumen Este artículo realiza una revisión de los estudios sobre el evolucionismo en España y actualiza los conocimientos sobre el mismo tras los trabajos de Thomas Glick, la obra más filosófica de Diego Núñez y las aportaciones en los últimos años de la red latinoamericana de historia de la biología y la evolución, incidiendo en los aspectos más polémicos de la recepción de esta teoría. Incluye novedades como la identificación de los dibujos de El Museo Universal, siempre en discusión sobre su naturaleza lamarckiana o darwinista, el papel fundamental de la recepción de la obra de Haeckel en España frente a una recepción estrictamente darwiniana más débil, el papel jugado en la escuela histológica española y el impacto en la literatura.

Abstract This article re-examines the research on evolutionism in Spain and updates knowledge on this topic in light of the work of Thomas Glick, the more philosophical work of Diego Núñez and contributions in recent years from the Latin American network of historians of biology and evolution, who have dealt with the more polemical aspects of the reception of evolution theory. It includes new arguments, such as identification of the drawings in El Museo Universal, whose Lamarckian or Darwinian nature has been a subject of ongoing debate. It also covers the crucial role of the acceptance of Haeckel's work in Spain in comparison to the weaker support for a strictly Darwinian perspective, the role of the Spanish histology school, and the impact of evolutionism on literature.

Stress Assessment by Prefrontal Relative Gamma.

Stress assessment has been under study in the last years. Both biochemical and physiological markers have been used to measure stress level. In neuroscience, several studies have related modification of stress level to brain activity changes in limbic system and frontal regions, by using non-invasive techniques such as functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). In particular, previous studies suggested that the exhibition or inhibition of certain brain rhythms in frontal cortical areas indicates stress. However, there is no established marker to measure stress level by EEG. In this work, we aimed to prove the usefulness of the prefrontal relative gamma power (RG) for stress assessment. We conducted a study based on stress and relaxation periods. Six healthy subjects performed the Montreal Imaging Stress Task (MIST) followed by a stay within a relaxation room while EEG and electrocardiographic signals were recorded. Our results showed that the prefrontal RG correlated with the expected stress level and with the heart rate (HR; 0.8). In addition, the difference in prefrontal RG between time periods of different stress level was statistically significant (p < 0.01). Moreover, the RG was more discriminative between stress levels than alpha asymmetry, theta, alpha, beta, and gamma power in prefrontal cortex. We propose the prefrontal RG as a marker for stress assessment. Compared with other established markers such as the HR or the cortisol, it has higher temporal resolution. Additionally, it needs few electrodes located at non-hairy head positions, thus facilitating the use of non-invasive dry wearable real-time devices for ubiquitous assessment of stress.

A Computational Framework for Realistic Retina Modeling.

Computational simulations of the retina have led to valuable insights about the biophysics of its neuronal activity and processing principles. A great number of retina models have been proposed to reproduce the behavioral diversity of the different visual processing pathways. While many of these models share common computational stages, previous efforts have been more focused on fitting specific retina functions rather than generalizing them beyond a particular model. Here, we define a set of computational retinal microcircuits that can be used as basic building blocks for the modeling of different retina mechanisms. To validate the hypothesis that similar processing structures may be repeatedly found in different retina functions, we implemented a series of retina models simply by combining these computational retinal microcircuits. Accuracy of the retina models for capturing neural behavior was assessed by fitting published electrophysiological recordings that characterize some of the best-known phenomena observed in the retina: adaptation to the mean light intensity and temporal contrast, and differential motion sensitivity. The retinal microcircuits are part of a new software platform for efficient computational retina modeling from single-cell to large-scale levels. It includes an interface with spiking neural networks that allows simulation of the spiking response of ganglion cells and integration with models of higher visual areas.

The post-humanist embryo: genetic manipulation, assited reproductive technologies and the principle of procreative beneficence / El embrión post-humano: manipulación genética, reproducción asistida y el principio de beneficencia procreativa

Drawing from Julian Savulescu's argument for the obligation to use technological interventions for the enhancement human life, the Principle of Procreative Beneficence (PPB) states that parents have a moral obligation to use available reproductive technologies, including techniques of genetic manipulation, to create children who have the best chance of enjoying the best possible life. The aim of this study is to analyse the extent to which the possibility of using genetic manipulation to promote specific personality traits and thereby enhance human life is actually supported by current scientific knowledge and to determine whether the techniques employed in embryo selection comply with the PPB. In light of this analysis, the importance of involving the scientific community in the enhancement debate will be made clear. Moreover, when current knowledge of genetic and epigenetic processes and evidence of the risks of assisted reproductive technologies are taken into account, we find sufficient reason-even when guided by the PPB-to abstain from the use of current techniques of genetic manipulation and embryonic selection

El principio de beneficencia procreativa (PPB), propuesto por Julian Savulescu, establece que los padres tienen la obligación moral de utilizar las técnicas de manipulación genética y reproducción humana asistida disponibles para crear niños que tengan la mejor oportunidad de disfrutar de la mejor vida posible . El objetivo de este trabajo es analizar, por un lado, hasta qué punto la manipulación genética para la obtención de rasgos concretos tienen en consideración el paradigma actual de la ciencia y, por otro lado, si las técnicas implicadas en la selección embrionaria propuestas cumplen con el objetivo perseguido por el PPB. Además, esta exposición pretende mostrar la importancia de implicar en la discusión sobre el enhancement a la comunidad científica. Teniendo en cuenta el conocimiento científico sobre los procesos genéticos y epigenéticos del desarrollo y los riesgos asociados a las técnicas de reproducción asistida, nos encontramos con razones suficientes para tomar la decisión de no someter a los niños a las técnicas actuales de manipulación y selección embrionaria

El mito de Atapuerca. Orígenes, ciencia, divulgación / No disponible

No disponible

The post-humanist embryo: genetic manipulation, assisted reproductive technologies and the Principle of Procreative Beneficence.

Drawing from Julian Savulescu's argument for the obligation to use technological interventions for the enhancement human life, the Principle of Procreative Beneficence (PPB) states that parents have a moral obligation to use available reproductive technologies, including techniques of genetic manipulation, to create children who have the best chance of enjoying the best possible life. The aim of this study is to analyse the extent to which the possibility of using genetic manipulation to promote specific personality traits and thereby enhance human life is actually supported by current scientific knowledge and to determine whether the techniques employed in embryo selection comply with the PPB. In light of this analysis, the importance of involving the scientific community in the enhancement debate will be made clear. Moreover, when current knowledge of genetic and epigenetic processes and evidence of the risks of assisted reproductive technologies are taken into account, we find sufficient reason - even when guided by the PPB - to abstain from the use of current techniques of genetic manipulation and embryonic selection.

Visual training and emotional state of people with retinitis pigmentosa.

The purpose of the study was to improve the visual functioning of people with restriction in contrast sensitivity (CS), such as retinitis pigmentosa (RP), by means of a visual training program. Twenty-six volunteers with RP participated, distributed in two groups: 15 who made up the experimental group (who received the training program) and 11 who participated as a control group (without training). Participants were evaluated before beginning training, on completion, and 3 mo following completion for CS with the Pelli-Robson Contrast Sensitivity (P&R) test, visual functioning with the Visual Function Questionnaire (VFQ), and in emotional state with the Beck Depression Inventory (BDI). The training program is based on software that generates luminous stimuli of varying duration and intensity and registers the stimuli perceived by the subject. The outcomes showed significant differences posttraining in the experimental group in depression (F1,14 = 5.42; p < 0.04), VFQ (Z = -2.27; p < 0.02), and P&R in the right eye (Z = -1.99; p < 0.046) and left eye (Z = -2.30; p < 0.02) but not in binocular (Z = -0.96; p < 0.34). The outcomes showed that the experimental group made significant progress in all variables and these effects remained after 3 mo, which suggests that the program could be a helpful addition to RP rehabilitation and help mitigate the damage.

[Massive transfusion and trauma patient management: pathophysiological approach to treatment].

Bleeding that requires massive blood transfusion is one of the main causes of cardiac arrest and death in the operating room. Its mortality varies widely between 15 and 54%, and it is strongly related to multiple factors such as acidosis, hypothermia and hypocoagulation. We undertook this study to describe the mechanisms that perpetuate bleeding during massive hemorrhage and the particular issues under the different clinical conditions of controlled and uncontrolled tissue damage. Laboratory tests for coagulation status diagnosis as well as treatment guidelines for usage of different fluid replacement solutions and hemoderivatives are described. A well-established response plan is needed by the surgical team and the blood bank in order to quickly facilitate blood products to the patient. Measures to avoid hypothermia and availability of rapid infusion systems are also necessary.

Toward the development of a cortically based visual neuroprosthesis.

Motivated by the success of cochlear implants for deaf patients, we are now facing the goal of creating a visual neuroprosthesis designed to interface with the occipital cortex as a means through which a limited but useful sense of vision could be restored in profoundly blind patients. We review the most important challenges regarding this neuroprosthetic approach and emphasize the need for basic human psychophysical research on the best way of presenting complex stimulating patterns through multiple microelectrodes. Continued research will hopefully lead to the development of and design specifications for the first generation of a cortically based visual prosthesis system.