ABSTRACT
Obesity is a major public health issue that is associated with metabolic diseases including diabetes mellitus type 2 and metabolic syndrome. This pathology leads to detrimental cardiovascular health and secondary effects, such as lipotoxicity, inflammation, and oxidative stress. Recently, extracellular vesicles (EVs) have been highlighted as novel players participating in human physiology and pathophysiology. In obesity, adipose tissue is related to the active shedding of adipocyte-derived extracellular vesicles (AdEVs). The current review explores and highlights the role of AdEVs and their cargo in obesity and metabolic syndrome. AdEVs are proposed to play an important role in obesity and its comorbidities. AdEVs are biological nanoparticles mainly shed by visceral and subcutaneous adipose tissue, acting in physiological and pathophysiological conditions, and also carrying different cargo biomolecules, such as RNA, microRNA (miRNA), proteins, and lipids, among others. RNA and miRNA have local and systemic effects affecting gene expression in target cell types via paracrine and endocrine actions. State of the art analyses identified some miRNAs, such as miR-222, miR-23b, miR-4429, miR-148b, and miR-4269, that could potentially affect cell pathways involved in obesity-related comorbidities, such as chronic inflammation and fibrosis. Similarly, AdEVs-proteins (RBP4, perilipin-A, FABP, mimecan, TGFBI) and AdEVs-lipids (sphingolipids) have been linked to the obesity pathophysiology. The current knowledge about AdEVs along with further research would support and reveal novel pathways, potential biomarkers, and therapeutic options in obesity.
ABSTRACT
Mutualistic symbioses between cnidarians and photosynthetic algae are modulated by complex interactions between host immunity and environmental conditions. Here, we investigate how symbiosis interacts with food limitation to influence gene expression and stress response programming in the sea anemone Exaiptasia pallida (Aiptasia). Transcriptomic responses to starvation were similar between symbiotic and aposymbiotic Aiptasia; however, aposymbiotic anemone responses were stronger. Starved Aiptasia of both symbiotic states exhibited increased protein levels of immune-related transcription factor NF-κB, its associated gene pathways, and putative target genes. However, this starvation-induced increase in NF-κB correlated with increased immunity only in symbiotic anemones. Furthermore, starvation had opposite effects on Aiptasia susceptibility to pathogen and oxidative stress challenges, suggesting distinct energetic priorities under food scarce conditions. Finally, when we compared starvation responses in Aiptasia to those of a facultative coral and non-symbiotic anemone, 'defence' responses were similarly regulated in Aiptasia and the facultative coral, but not in the non-symbiotic anemone. This pattern suggests that capacity for symbiosis influences immune responses in cnidarians. In summary, expression of certain immune pathways-including NF-κB-does not necessarily predict susceptibility to pathogens, highlighting the complexities of cnidarian immunity and the influence of symbiosis under varying energetic demands.
Subject(s)
Dinoflagellida , Sea Anemones , Animals , Symbiosis/physiology , NF-kappa B/genetics , NF-kappa B/metabolism , NF-kappa B/pharmacology , Sea Anemones/physiology , Photosynthesis , Transcriptome , Dinoflagellida/physiologyABSTRACT
The rise and fall of the Roman Empire was a socio-political process with enormous ramifications for human history. The Middle Danube was a crucial frontier and a crossroads for population and cultural movement. Here, we present genome-wide data from 136 Balkan individuals dated to the 1st millennium CE. Despite extensive militarization and cultural influence, we find little ancestry contribution from peoples of Italic descent. However, we trace a large-scale influx of people of Anatolian ancestry during the Imperial period. Between â¼250 and 550 CE, we detect migrants with ancestry from Central/Northern Europe and the Steppe, confirming that "barbarian" migrations were propelled by ethnically diverse confederations. Following the end of Roman control, we detect the large-scale arrival of individuals who were genetically similar to modern Eastern European Slavic-speaking populations, who contributed 30%-60% of the ancestry of Balkan people, representing one of the largest permanent demographic changes anywhere in Europe during the Migration Period.
Subject(s)
Human Migration , White People , Humans , Balkan Peninsula , Europe , White People/geneticsABSTRACT
Lack of proper nutrition has important consequences for the physiology of all organisms, and nutritional status can affect immunity, based on many studies in terrestrial animals. Here we show a positive correlation between nutrition and immunity in the sea anemone Nematostella vectensis. Gene expression profiling of adult anemones shows downregulation of genes involved in nutrient metabolism, cellular respiration, and immunity in starved animals. Starved adult anemones also have reduced protein levels and activity of immunity transcription factor NF-κB. Starved juvenile anemones have increased sensitivity to bacterial infection and also have lower NF-κB protein levels, as compared to fed controls. Weighted Gene Correlation Network Analysis (WGCNA) is used to identify significantly correlated gene networks that were downregulated with starvation. These experiments demonstrate a correlation between nutrition and immunity in an early diverged marine metazoan, and the results have implications for the survival of marine organisms as they encounter changing environments.
Subject(s)
NF-kappa B , Sea Anemones , Animals , NF-kappa B/genetics , NF-kappa B/metabolism , Sea Anemones/genetics , Sea Anemones/metabolism , Gene Expression Regulation , Gene Expression ProfilingABSTRACT
The human face is one of the most visible features of our unique identity as individuals. Interestingly, monozygotic twins share almost identical facial traits and the same DNA sequence but could exhibit differences in other biometrical parameters. The expansion of the world wide web and the possibility to exchange pictures of humans across the planet has increased the number of people identified online as virtual twins or doubles that are not family related. Herein, we have characterized in detail a set of "look-alike" humans, defined by facial recognition algorithms, for their multiomics landscape. We report that these individuals share similar genotypes and differ in their DNA methylation and microbiome landscape. These results not only provide insights about the genetics that determine our face but also might have implications for the establishment of other human anthropometric properties and even personality characteristics.
Subject(s)
Facial Recognition , Algorithms , DNA Methylation/genetics , Epigenesis, Genetic , Humans , Twins, Monozygotic/geneticsABSTRACT
Background: The Patient Health Questionnaire-9 (PHQ-9) is the most well-known self-report measure to screen for depressive symptomatology, although discerning which is the factor structure that represents the best fit remains a challenge. Objective: The aim of this study was to analyze the psychometric properties and factorial structure of the Spanish version of the PHQ-9 in a large sample of Ecuadorian college students. Methods: A total of 5,394 students (M = 22.03 years; SD = 3.05; 54.8% female) from three Ecuadorian universities were surveyed using a computerized questionnaire within a 4-week assessment period. The PHQ-9 was tested for factorial structure, reliability, and correlations with other mental health-related measures. Results: The hierarchical model that included a general factor and three nested factors had a better fit, and such a hierarchical structure remained invariant across sex and age. Total omega value (ω) was 0.90 for the total scale and hierarchical omega values (ωh) were 0.68 for the general factor, as well as 0.34, 0.38, and 0.44 for the respective nested factors (somatic, cognitive/affective, concentration/motor). Moreover, PHQ-9 scores were significantly higher among women, although effect sizes of comparison of those sex differences were very small. Finally, the PHQ-9 scores correlated with multiple mental health indicators (psychological inflexibility, loneliness, stress, and satisfaction with life). Discussion: The Spanish version of the PHQ-9 showed good psychometric properties among Ecuadorian college students. The hierarchical structure showed the best fit for the data, including not only a dominant general factor, but also the somatic, cognitive/affective and concentration/motor subcomponents. In conclusion, the PHQ-9 tool seems to represent an easy-to-implement screening questionnaire to design preventive programs for those Ecuadorian college students at risk of developing depressive disorders.
ABSTRACT
The Asian Central Steppe, consisting of current-day Kazakhstan and Russia, has acted as a highway for major migrations throughout history. Therefore, describing the genetic composition of past populations in Central Asia holds value to understanding human mobility in this pivotal region. In this study, we analyse paleogenomic data generated from five humans from Kuygenzhar, Kazakhstan. These individuals date to the early to mid-18th century, shortly after the Kazakh Khanate was founded, a union of nomadic tribes of Mongol Golden Horde and Turkic origins. Genomic analysis identifies that these individuals are admixed with varying proportions of East Asian ancestry, indicating a recent admixture event from East Asia. The high amounts of DNA from the anaerobic Gram-negative bacteria Tannerella forsythia, a periodontal pathogen, recovered from their teeth suggest they may have suffered from periodontitis disease. Genomic analysis of this bacterium identified recently evolved virulence and glycosylation genes including the presence of antibiotic resistance genes predating the antibiotic era. This study provides an integrated analysis of individuals with a diet mostly based on meat (mainly horse and lamb), milk, and dairy products and their oral microbiome.
ABSTRACT
We provide a functional characterization of transcription factor NF-κB in protists and provide information about the evolution and diversification of this biologically important protein. We characterized NF-κB in two protists using phylogenetic, cellular, and biochemical techniques. NF-κB of the holozoan Capsaspora owczarzaki (Co) has an N-terminal DNA-binding domain and a C-terminal Ankyrin repeat (ANK) domain, and its DNA-binding specificity is more similar to metazoan NF-κB proteins than to Rel proteins. Removal of the ANK domain allows Co-NF-κB to enter the nucleus, bind DNA, and activate transcription. However, C-terminal processing of Co-NF-κB is not induced by IκB kinases in human cells. Overexpressed Co-NF-κB localizes to the cytoplasm in Co cells. Co-NF-κB mRNA and DNA-binding levels differ across three Capsaspora life stages. RNA-sequencing and GO analyses identify possible gene targets of Co-NF-κB. Three NF-κB-like proteins from the choanoflagellate Acanthoeca spectabilis (As) contain conserved Rel Homology domain sequences, but lack C-terminal ANK repeats. All three As-NF-κB proteins constitutively enter the nucleus of cells, but differ in their DNA-binding abilities, transcriptional activation activities, and dimerization properties. These results provide a basis for understanding the evolutionary origins of this key transcription factor and could have implications for the origins of regulated immunity in higher taxa.
Subject(s)
Choanoflagellata/genetics , Evolution, Molecular , NF-kappa B/genetics , Protozoan Proteins/genetics , Transcription Factors/genetics , Choanoflagellata/metabolism , NF-kappa B/metabolism , Protozoan Proteins/metabolism , Species Specificity , Transcription Factors/metabolismABSTRACT
Ancient pathogen genomics is an emerging field allowing reconstruction of past epidemics. The demise of post-contact American populations may, at least in part, have been caused by paratyphoid fever brought by Europeans. We retrieved genome-wide data from two Spanish soldiers who were besieging the city of Barcelona in 1652, during the Reapers' War. Their ancestry derived from the Basque region and Sardinia, respectively, (at that time, this island belonged to the Spanish kingdom). Despite the proposed plague epidemic, we could not find solid evidence for the presence of the causative plague agent in these individuals. However, we retrieved from one individual a substantial fraction of the Salmonella enterica serovar Paratyphi C lineage linked to paratyphoid fever in colonial period Mexico. Our results support a growing body of evidence that Paratyphi C enteric fever was more prevalent in Europe and the Americas in the past than it is today.
ABSTRACT
Extensive genomic and transcriptomic sequencing over the past decade has revealed NF-κB signaling pathway homologs in organisms basal to insects, for example, in members of the phyla Cnidaria (e.g., sea anemones, corals, hydra, jellyfish) and Porifera (sponges), and in several single-celled protists (e.g., Capsaspora owczarzaki, some choanoflagellates). Therefore, methods are required to study the function of NF-κB and its pathway members in early branching organisms, many of which do not have histories as model organisms. Here, we describe a combination of cellular, molecular, and biochemical techniques that have been used for studying NF-κB, and related pathway proteins, in some of these basal organisms. These methods are useful for studying the evolution of NF-κB signaling, and may be adaptable to the study of NF-κB in other non-model organisms.
Subject(s)
Signal Transduction , Animals , Evolution, Molecular , Genomics , Hydra/metabolism , NF-kappa B/genetics , NF-kappa B/metabolism , Phylogeny , Sea AnemonesABSTRACT
Bacillus thuringiensis (Bt) toxins constitute effective, environmentally safe biopesticides. Nevertheless, insects' tolerance to Bt is influenced by environmental factors affecting immunity. To understand larval immune response in the devastating coleopteran insect pest Colorado potato beetle (CPB), we undertook a proteomic analysis of hemolymph of non-treated control larvae and larvae consuming non-lethal doses of spore-crystal mixtures containing the coleopteran-active Cry3Aa toxin. Results revealed lower amount of proteins involved in insect growth and higher amount of immune response-related proteins in challenged insects, sustaining the larval weight loss observed. Additionally, we found a potential regulatory role of the evolutionary conserved miR-8 in the insect's immune response relying on antimicrobial peptides (AMPs) production. Upon toxin challenge, different patterns of hemolymph AMPs expression and phenoloxidase activity were observed in CPB larvae reared on different Solanaceae plants. This suggests that diet and diet-associated insect midgut microbiota might modulate this insects' tolerance to non-lethal doses of Bt.
Subject(s)
Bacillus thuringiensis Toxins/metabolism , Bacillus thuringiensis/physiology , Coleoptera/immunology , Endotoxins/metabolism , Gram-Positive Bacterial Infections/immunology , Hemolysin Proteins/metabolism , Insect Proteins/genetics , Animals , Bacillus thuringiensis Toxins/genetics , Diet , Endotoxins/genetics , Hemolysin Proteins/genetics , Immunity , Insect Proteins/metabolism , Larva , MicroRNAs/genetics , Monophenol Monooxygenase/metabolism , Pore Forming Cytotoxic Proteins/genetics , Proteomics , SolanaceaeABSTRACT
Down syndrome causes a reduction in cognitive abilities, with visual-motor skills being particularly affected. In this work, we have focused on this skill in order to stimulate better learning. The proposal relies on stimulating the cognitive visual-motor skills of individuals with Down Syndrome (DS) using exercises with a gestural interaction platform based on the KINECT sensor named TANGO:H, the goal being to improve them. To validate the proposal, an experimental single-case study method was designed using two groups: a control group and an experimental one, with similar cognitive ages. Didactic exercises were provided to the experimental group using visual cognitive stimulation. These exercises were created on the TANGO:H Designer, a platform that was designed for gestural interaction using the KINECT sensor. As a result, TANGO:H allows for visual-motor cognitive stimulation through the movement of hands, arms, feet and head. The "Illinois Test of Psycholinguistic Abilities (ITPA)" was applied to both groups as a pre-test and post-test in its four reference sections: visual comprehension, visual-motor sequential memory, visual association, and visual integration. Two checks were made, one using the longitudinal comparison of the pre-test/post-test of the experimental group, and another that relied on comparing the difference of the means of the pre-test/post-test. We also used an observational methodology for the working sessions from the experimental group. Although the statistical results do not show significant differences between the two groups, the results of the observations exhibited an improvement in visual-motor cognitive skills.
Subject(s)
Cognition/physiology , Down Syndrome/physiopathology , Motor Skills/physiology , Visual Perception/physiology , Adolescent , Adult , Case-Control Studies , Child , Female , Humans , Male , Video Games , Young AdultABSTRACT
One of the principal problems of rehabilitation is that therapy sessions can be boring due the repetition of exercises. Serious games, and in particular exergames in rehabilitation, can motivate, engage and increase patients' adherence to their treatment. Also, the automatic personalization of exercises to each patient can help therapists. Thus, the main objective of this work is to build an intelligent exergame-based rehabilitation system consisting of a platform with an exergame player and a designer tool. The intelligent platform includes a recommender system which analyzes user interactions, along with the user's history, to select new gamified exercises for the user. The main contributions of this paper focus, first, on defining a recommender system based on different difficulty levels and user skills. The recommender system offers the ability to provide the user with a personalized game mode based on his own history and preferences. The results of a triple validation with experts, users and rehabilitation center professionals reveal a positive impact on gestural interaction and rehabilitation uses. Also, different methods are presented for testing the rehabilitation recommender system.
Subject(s)
Exercise Therapy/methods , Games, Recreational , Rehabilitation/methods , Computational Biology , Exercise Therapy/statistics & numerical data , Gestures , Humans , Motivation , Rehabilitation/statistics & numerical data , User-Computer Interface , Virtual RealityABSTRACT
El presente trabajo de investigación está dividido en dos componentes: el primer componente hace referencia a la elaboración del Plan Hospitalario para Desastres del Hospital Eugenio Espejo, y el segundo componente consiste en la realización de un Seminario-Taller sobre desastres. Componente I: Elaboración del Plan Hospitalario para Desastres Internos y Externos. Se realizó una evaluación de la vulnerabilidad estructural y no estructural del Hospital lo que le permitió tomar las medidas de prevención y mitigación necesarias. Se evaluó el actual funcionamiento de los servicios básicos con los que cuenta el Hospital (agua potable, luz eléctrica, alcantarillado, comunicaciones) y se tomó los correctivos necesarios; igualmente se estableció formas alternas de funcionamiento que suelen ser esenciales ante las situaciones críticas que suelen presentarse en situaciones de desastres...