Summary
Hox genes encode transcription factors that play an important role in establishing the basic body plan of animals. In Drosophila, Antennapedia is one of the five genes that make up the ...Antennapedia complex (ANT‐C). Antennapedia determines the identity of the second thoracic segment, known as the mesothorax. Misexpression of Antennapedia at different developmental stages changes the identity of the mesothorax, including the muscles, nervous system, and cuticle. In Drosophila, Antennapedia has two distinct promoters highly regulated throughout development by several transcription factors. Antennapedia proteins are found with other transcription factors in different ANTENNAPEDIA transcriptional complexes to regulate multiple subsets of target genes. In this review, we describe the different mechanisms that regulate the expression and function of Antennapedia and the role of this Hox gene in the development of Drosophila.
Discrepancies between the measurement of body mass index (BMI) and metabolic health status have been described for the onset of metabolic diseases. Studying novel biomarkers, some of which are ...associated with metabolic syndrome, can help us to understand the differences between metabolic health (MetH) and BMI. A group of 1469 young adults with pre-specified anthropometric and blood biochemical parameters were selected. Of these, 80 subjects were included in the downstream analysis that considered their BMI and MetH parameters for selection as follows: norm weight metabolically healthy (MHNW) or metabolically unhealthy (MUNW); overweight/obese metabolically healthy (MHOW) or metabolically unhealthy (MUOW). Our results showed for the first time the differences when the MetH status and the BMI are considered as global MetH statures. First, all the evaluated miRNAs presented a higher expression in the metabolically unhealthy group than the metabolically healthy group. The higher levels of leptin, IL-1b, IL-8, IL-17A, miR-221, miR-21, and miR-29 are directly associated with metabolic unhealthy and OW/OB phenotypes (MUOW group). In contrast, high levels of miR34 were detected only in the MUNW group. We found differences in the SIRT1-PGC1α pathway with increased levels of SIRT1+ cells and diminished mRNA levels of PGCa in the metabolically unhealthy compared to metabolically healthy subjects. Our results demonstrate that even when metabolic diseases are not apparent in young adult populations, MetH and BMI have a distinguishable phenotype print that signals the potential to develop major metabolic diseases.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
OBJECTIVETo report a case of a patient infected with severe acute respiratory syndrome coronavirus 2 (SARS–CoV-2) who acutely developed a hypokinetic-rigid syndrome.
METHODSPatient data were obtained ...from medical records from the Hospital Universitario 12 de Octubre in Madrid, Spain. I-ioflupane dopamine transporter (DaT) SPECT images were acquired 4 hours after a single dose of 185 MBq of I-FP-CIT. Quantitative analysis was performed with DaTQUANT software providing the specific binding ratio and z score values of the striatum.
RESULTSWe report a previously healthy 58-year-old man who developed hyposmia, generalized myoclonus, fluctuating and transient changes in level of consciousness, opsoclonus, and an asymmetric hypokinetic-rigid syndrome with ocular abnormalities after a severe SARS–CoV-2 infection. DaT-SPECT confirmed a bilateral decrease in presynaptic dopamine uptake asymmetrically involving both putamina. Significant improvement in the parkinsonian symptoms was observed without any specific treatment.
CONCLUSIONThis case study provides clinical and functional neuroimaging evidence to support that SARS–CoV-2 can gain access to the CNS, affecting midbrain structures and leading to neurologic signs and symptoms.
wingless expression is exquisitely regulated by different factors and enhancers in the imaginal wing discs of Drosophila melanogaster in four domains: the dorsal band, the dorso-ventral boundary, and ...the inner and outer ring domains. tonalli is a trithorax group gene that encodes a putative SUMO E3 ligase that binds to chromatin to regulate the expression of its targets, including the Hox genes. However, its role in modulating gene expression is barely known. Here, we show that TnaA modulates the wingless expression at two domains of the wing disc, the dorso-ventral boundary and the inner ring. At first, tonalli interacts genetically with Notch to form the wing margin. In the inner ring domain, TnaA modulates wingless transcription. When the dosage of TnaA increases in or near the inner ring since early larval stages, this domain expands with a rapid increase in wingless expression. TnaA occupies the wingless Inner Ring Enhancer at the wing disc, meanwhile it does not affect wingless expression directed by the Ventral Disc Enhancer in leg discs, suggesting that TnaA acts as a wingless enhancer-specific factor. We describe for the first time the presence of TnaA at the Inner Ring Enhancer as a specific regulator of wingless in the development of wing boundaries.
•A higher frequency of CD4+IL-17A + T cells, RORC2 expression and miR-326 in adipose tissue from individuals with obesity.•Altered levels of proinflammatory cytokines in adipose tissue mononuclear ...cells from individuals with obesity in vitro.•High degree of FOXP3 methylation and low level of FOXP3 expression in adipose tissue mononuclear cells from individuals with obesity.
miRNAs are important immune regulators in the control of the CD4 + T cells phenotype. miR-326 regulates the differentiation towards Th17 cells and the inhibition of miR-155 is associated with low levels of Treg cells. However, miRNAs expression and transcription factors associated with these lymphocyte subsets in obesity-induced adipose tissue inflammation is still unknown. The aim of this work was to identify Th17 cells in subcutaneous adipose tissue (SAT), proinflammatory cytokine production and their association with the miRNAs and transcription factors involved. We collected SAT samples obtained by lipoaspiration from individuals with normal weight, overweight and obesity. We obtained the stromal vascular fractions and then a Ficoll gradient was performed to obtain adipose tissue mononuclear cells (ATMC). Th17 cells were evaluated by flow cytometry and the expression of miR-326, miR-155, RORC2 and FOXP3 by qRT-PCR. We also analyzed cytokines from the supernatants of the ATMC culture and measured the FOXP3 methylation percentage by bisulfite conversion by PCR. According to the results, the frequency of Th17 cells and RORC2 expression was higher in individuals with obesity and associated with miR-326 expression. The ATMC from this group secreted a proinflammatory cytokine profile by in vitro assay. In contrast, lower levels of mRNA FOXP3 expression was detected in ATMC from individuals with obesity that correlated with methylation percentage of FOXP3 gene but no association with miR-155 was detected. Our results suggested that miR-326 participates in the polarization towards Th17 promoting the inflammatory state in the obesity-induced adipose tissue.
Sirtuins regulate energy metabolism and insulin sensitivity through their ability to act as energy sensors and regulators in several metabolic tissues.
To evaluate the expression levels of sirtuin ...genes SIRT1, SIRT2, SIRT3 and SIRT6 and their target genes (PPAR-α, PGC1-α, NRF1, DGAT1, PPAR-γ and FOXO3a) in subcutaneous adipose tissue collected from individuals with normoweight, overweight and obesity.
Adipose tissue samples, obtained by lipoaspiration during liposuction surgery, were processed to obtain RNA, which was reverse-transcribed to cDNA. Then, we measured the expression levels of each gene by qPCR.
We found differences in the mRNA expression of SIRT1, SIRT2, SIRT3 and SIRT6 and their target genes (PPAR-α, PGC1-α, NRF1, DGAT1, PPAR-γ and FOXO3a) in adipose tissue from overweight or obese subjects when compared to normoweight subjects. All genes analyzed, except SIRT2, showed correlation with BMI.
Our findings in human subcutaneous adipose tissue show that increased body mass index modifies the expression of genes encoding sirtuins and their target genes, which are metabolic regulators of adipose tissue. Therefore, these could be used as biomarkers to predict the ability of adipose tissue to gain mass of adipose tissue.
This study aimed to characterize the molecular immune networks and microglia reactivity in the nucleus accumbens (NAc) shell affected by fetal nutritional programming leading to addiction-like ...behavior in the offspring of Wistar rats. Fetal nutritional programming by energy-dense foods leads to addiction-like behavior in the offspring. Exposure to energy-dense foods also activates systemic and central inflammation in the offspring.
Females Wistar rats were exposed to cafeteria (CAF) diet or control diet for 9 weeks (prepregnancy, pregnancy and lactation), and male offspring at 2 months of age were diagnosed with food addiction-like behavior using operant conditioning. Global microarray analysis, RTqPCR, proinflammatory plasma profile and microglia immunostaining were performed in the NAc shell of male rats. SIM-A9 microglia cells were stimulated with IFN-α and palmitic acid, and microglia activation and phagocytosis were determined by RTqPCR and incubation of green-fluorescent latex beads, respectively.
Microarray analysis in the NAc shell of the male offspring exposed to CAF during development and diagnosed with addiction-like behavior showed increasing in the type I interferon-inducible gene, Ift1 , gene network. Genomic and cellular characterization also confirmed microglia hyperreactivity and upregulation of the Ifit1 in the NAc shell of animals with addiction-like behavior. In-vitro models demonstrated that microglia do respond to IFN-α promoting a time-dependent genomic expression of Ift1, IL-1β and IL-6 followed by increased phagocytosis.
Prenatal exposure to energy-dense foods primes the IFN type I signaling and microglia complexity in the NAc shell of rats diagnosed with food addiction-like behavior.
•P2X4 receptor on CD4 + T cells from PB and AT was increased in individuals with BMI ≥ 25 Kg/m2.•CD4 + T cells expressing P2X4 and P2X7 from PB and AT were augmented in individuals with BMI ≥ 25 ...Kg/m2.•CD4 + T cells with P2X4 and P2X7 showed a higher percentage in cells isolated from AT compared to PB.•ATP-induced shedding of CD62 L was higher in PBMC than in ATMC.•Influx of Ca2+ dependent of ATP-induced P2X4 activation in PBMC was higher than in ATMC.
Obesity is characterized by immune cell infiltration and inflammation. Purinergic receptors such as P2X1, 4 and 7 are expressed on immune cells and their activation contributes with an inflammatory response. However, the simultaneous expression of P2X1, 4 and 7 during overweight or obesity have not been described. Therefore, the aim of this study was to determine single and simultaneously expression and function of the P2X1, 4 and 7 receptors in lymphocytes and CD4 + T cells from peripheral blood (PB) and adipose tissue (AT). Our results showed a higher expression of the P2X4 receptor on CD4 + T cells from PB regarding P2X7 and P2X1 receptor expression. In addition, P2X4 receptor expression on CD4 + T cells from PB and AT was increased in individuals with BMI ≥ 25 Kg/m2. Moreover, a higher simultaneous expression of the P2X4 and P2X7 receptors on CD4 + T cells from AT compared to CD4 + T cells expressing P2X1 and P2X7 receptors simultaneously. Besides, CD4 + T cells expressing P2X4 and P2X7 receptors from PB and AT were augmented in individuals with BMI ≥ 25 Kg/m2. In addition, the percentage of lymphocytes and also CD4 + T cells expressing P2X4 receptor were elevated both in PB and AT compared to cells expressing P2X7 or P2X1. However, CD4 + T cells expressing P2X4 and P2X7 were augmented in AT compared to PB. The function of the receptors showed a lower shedding of CD62 L in adipose tissue mononuclear cells (ATMC) compared with peripheral blood mononuclear cells (PBMC) and a greater participation of P2X4 in the mobilization of intracellular calcium. We concluded that it was possible to determine for the first time the simultaneous expression of purinergic receptors in ATMC, where the P2X4 receptor has a greater participation in the activation of CD4 + T cells possibly modulating the function of the other two receptors.
Overweight and obesity are important risk factors for chronic disorders. Fat accumulation is one of the central manifestations; it occurs via a complex mechanism where multiple metabolic signals ...converge. Sirtuins are an enzyme family with deacetylase functions that are implicated in the regulation of several genes. Sirt1 and its upstream regulator (miR-34a) are elements of a converging mechanism that integrates the dynamic metabolic state. In this work, we hypothesized that elevated levels of miR-34a in overweight/obese group inhibits Sirt1 activity. Therefore, we studied the miR-34a/Sirt1 axis in mononuclear cells obtained from adipose tissue.
Adipose tissue samples were collected from 36 subjects, and they were categorized according to body mass index (BMI) as overweight/obesity and normoweight. Subcutaneous adipose tissue samples were enzymatically dissociated, and mononuclear cells from adipose tissue were isolated by Ficoll Hypaque. Sirt1-positive cells and relative Sirt1 expression were determined by flow cytometry and real-time polymerase chain reaction (qPCR), respectively. Finally, Sirt1 activity was measured with a luminescence assay.
The percentage of Sirt1-positive mononuclear cells from adipose tissue decreased along with Sirt1 enzymatic activity in overweight/obese participants. miR-34a expression increased in the overweight/obese group compared to normoweight individuals. There was a negative association between the relative miR-34a expression and Sirt1-positive cells and a synergistic effect on Sirt1-positive cells mediated by the miR-34a inhibitor and Sirt1 agonist.
Our results describe for the first time the presence of miR-34a and Sirt1 in mononuclear cells isolated from subcutaneous adipose tissue. Additionally, these results suggest altered sirtuin function in overweight/obese patients and open the possibility for new therapies that involve these metabolic targets.
•Sirt1 is downregulated and miR-34 levels are increased in subcutaneous adipose tissue mononuclear cells from obese subjects.•A negative correlation between miR-34 and Sirt1 expression in obese subjects was found.•Sirt1 function could be a target for new therapies to molecules involved in the metabolism of obese subjects.
To develop and validate equations to estimate the percentage of body fat of children and adolescents from Mexico using anthropometric measurements.
A cross-sectional study was carried out with 601 ...children and adolescents from Mexico aged 5–19 years. The participants were randomly divided into the following two groups: the development sample (n=398) and the validation sample (n=203). The validity of previously published equations (e.g., Slaughter) was also assessed. The percentage of body fat was estimated by dual-energy X-ray absorptiometry. The anthropometric measurements included height, sitting height, weight, waist and arm circumferences, skinfolds (triceps, biceps, subscapular, supra-iliac, and calf), and elbow and bitrochanteric breadth. Linear regression models were estimated with the percentage of body fat as the dependent variable and the anthropometric measurements as the independent variables.
Equations were created based on combinations of six to nine anthropometric variables and had coefficients of determination (r2) equal to or higher than 92.4% for boys and 85.8% for girls. In the validation sample, the developed equations had high r2 values (≥85.6% in boys and ≥78.1% in girls) in all age groups, low standard errors (SE≤3.05% in boys and ≤3.52% in girls), and the intercepts were not different from the origin (p>0.050). Using the previously published equations, the coefficients of determination were lower, and/or the intercepts were different from the origin.
The equations developed in this study can be used to assess the percentage of body fat of Mexican schoolchildren and adolescents, as they demonstrate greater validity and lower error compared with previously published equations.
Desenvolver e validar equações para estimar o percentual de gordura corporal (%GC) de crianças e adolescentes do México utilizando medidas antropométricas.
Foi realizado um estudo transversal com 601 crianças e adolescentes do México com idades entre 5 e 19 anos. Os participantes foram divididos aleatoriamente nos seguintes dois grupos: a amostra de desenvolvimento (n=398) e a amostra de validação (n=203). A validade das equações publicadas anteriormente (por exemplo, Slaughter) também foi avaliada. O %GC foi estimado por absorciometria de dupla energia de raios-X (raio-X de dupla energia (DXA)). As medidas antropométricas incluíram estatura, altura sentado, peso, circunferências da cintura e do braço, dobras cutâneas (tríceps, bíceps, subescapular, suprailíaca e panturrilha) e larguras do cotovelo e bitrocantérica. Os modelos de regressão linear foram estimados com o %GC sendo a variável dependente e as medidas antropométricas como as variáveis independentes.
As equações foram criadas com base nas combinações de seus a nove variáveis antropométricas e apresentaram coeficientes de determinação (r2) iguais ou superiores a 92,4% para meninos e 85,8% para meninas. Na amostra de validação, as equações desenvolvidas apresentaram altos valores de r2 (≥ 85,6% em meninos e≥78,1% em meninas) em todos os grupos, baixo nível de erros padrão (EP≤3,05% em meninos e≤3,52% em meninas) e os interceptos não foram diferentes da origem (p>0,050). Utilizando as equações publicadas anteriormente, os coeficientes de determinação foram menores e/ou os interceptos foram diferentes da origem.
As equações desenvolvidas neste estudo podem ser utilizadas para avaliar o %GC das crianças em idade escolar e adolescentes mexicanos, pois elas possuem uma maior validade e menor erro em comparação às equações publicadas anteriormente.
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