Clinical and Molecular Study of the NOG Gene in Families with Mandibular Micrognathism

Q1Pacientes con Micrognatismo mandibularObjectives: Previous studies showed that noggin gene (NOG) sequence alterations, as well as epigenetic factors, could influence mandibular development. The aim of this study was to analyze clinical characteristics, NOG gene sequences, and promoter methylation sites in patients with mandibular micrognathism. Materials and Methods: A total of 35 individuals of five Colombian families were subject to clinical and cephalometric analysis for mandibular micrognathism. One nonaffected individual of each family was included as a control. DNA was isolated from whole blood sample from all individuals by salting out method. Nine NOG gene fragments were amplified by polymerase chain reaction (PCR) and sequenced. Identification of CpG islands for methylation analysis at the NOG gene promoter was performed by MSP-PCR kit (Qiagen R). Statistical Analysis: A descriptive statistical analysis was carried out evaluating the presence or absence of genetics variants and the methylation sites in the NOG gene. Results: NOG sequence results of affected individuals with mandibular micrognathism for one of the families studied demonstrated that they were heterozygous for 672 C/A (new mutation). For a second family, individuals were heterozygous for 567 G/C (single nucleotide polymorphism [SNP] RS116716909). For DNA analyzed from all patients studied, no methylations were observed at the NOG gene promoter region. Conclusion: Our results suggested that 672 C/A and 567 G/C variants could be involved in the presence of mandibular micrognathism. Moreover, lack of methylation sites at the NOG gene promoter region of all individuals studied suggests possibly other epigenetic factors could modulate mandibular growth. The search of genetic variants related with mandibular micrognathism will allow to predict in an integral way the development patterns of the patients and therefore establish a better clinical treatment.https://orcid.org/0000-0002-2112-2563https://orcid.org/0000-0002-9879-9775https://orcid.org/0000-0003-0770-9138https://orcid.org/0000-0003-2527-3593Revista Internacional - IndexadaA2N

Fauna de escarabajos melolóntidos (coleoptera: scarabaeoidea) en el municipio de Villaflores, Chiapas, México

A first approach to the knowledge of the Melolonthid beetles of the region Frailesca in the State of Chiapas, Mexico, is presented. Most part of the original tropical deciduous forest today is replaced by great extensions with agricultural and cattle production. Studied localities were Francisco Villa, Cuauhtémoc, El Jardín and the surrounds of Villaflores city, all from the municipality of Villaflores. Diurnal and nocturnal systematic collections of adult beetles were made in agricultural parcels during May to September, 2006, by mean of light traps, transects, and fruit traps We obtained 6,780 specimens that represent four subfamilies, eight tribes, 17 genera and 46 species. The genera with greatest number of species and individuals were Phyllophaga, Diplotaxis and Ligyrus; along with the species of the genera Cyclocephala, Anomala and Strigoderma cover 88,7% of the total abundance. An updated list of the 368 species of Melolonthidae recorded in the state of Chiapas is included.Como un primer acercamiento al conocimiento de los escarabajos melolóntidos de la región Frailesca de Chiapas, México, caracterizada por un ambiente original de bosque tropical caducifolio, en su mayor parte ahora reemplazado por grandes extensiones con producción agrícola y ganadera, se realizó la presente investigación en los ejidos de Francisco Villa, Cuauhtémoc, El Jardín y la ciudad de Villaflores, pertenecientes al municipio de Villaflores. En parcelas agrícolas se hicieron recolectas sistemáticas, diurnas y nocturnas, de escarabajos adultos durante los meses de mayo a septiembre de 2006. Se obtuvieron 6,780 ejemplares, que representan a cuatro subfamilias, ocho tribus, 17 géneros y 46 especies. Los géneros con mayor número de especies e individuos fueron Phyllophaga, Diplotaxis y Ligyrus; junto con los escarabajos de los géneros Cyclocephala, Anomala y Strigoderma cubren el 88.7 % de la abundancia total. Se incluye una lista actualizada de las 368 especies de Melolonthidae registradas en el estado de Chiapas

Il6 gene promoter polymorphism (-174G/C) influences the association between fat mass and cardiovascular risk factors

During the last decades, the prevalence of obesity has increased rapidly among young people. A polymorphism in the promoter region of the IL6 gene (-174G/C), has been previously reported to be involved in obesity and metabolic syndrome development. Therefore, the aim of the study was to examine whether the IL6 -174G/C polymorphism influence the association of body fat with low-grade inflammatory markers and blood lipids and lipoproteins in Spanish adolescents. 504 Spanish adolescents participating in the AVENA study were genotyped for the -174G/C polymorphism of the IL6 gene. Anthropometric and body composition measurements were taken and blood samples were collected for plasma molecules determinations. No differences between genotypes were observed in anthropometric values, body composition measurements and plasma markers concentration. Physical activity level differ between genotypes with subjects carrying the C allele of the polymorphism being significantly (p<0.05) more active than GG subjects. The association between body fat mass and plasma glucose was influenced by the -174G/C polymorphism of the IL6 gene. Subjects carrying the C allele of the mutation seem to have higher values of lipoprotein (a) and C-reactive protein as their percentage of body fat mass increase. Our results suggest that this promoter polymorphism influences the association between adiposity and some plasma markers

PACAP-PAC1R modulates fear extinction via the ventromedial hypothalamus

Exposure to traumatic stress can lead to fear dysregulation, which has been associated with posttraumatic stress disorder (PTSD). Previous work showed that a polymorphism in the PACAP-PAC1R (pituitary adenylate cyclase-activating polypeptide) system is associated with PTSD risk in women, and PACAP (ADCYAP1)-PAC1R (ADCYAP1R1) are highly expressed in the hypothalamus. Here, we show that female mice subjected to acute stress immobilization (IMO) have fear extinction impairments related to Adcyap1 and Adcyap1r1 mRNA upregulation in the hypothalamus, PACAP-c-Fos downregulation in the Medial Amygdala (MeA), and PACAP-FosB/ΔFosB upregulation in the Ventromedial Hypothalamus dorsomedial part (VMHdm). DREADD-mediated inhibition of MeA neurons projecting to the VMHdm during IMO rescues both PACAP upregulation in VMHdm and the fear extinction impairment. We also found that women with the risk genotype of ADCYAP1R1 rs2267735 polymorphism have impaired fear extinction

Design of the nutritional therapy for overweight and obese Spanish adolescents conducted by registered dieticians: the EVASYON study

Background: Dietary treatment for obese adolescents should aim to ensure adequate growth and development, by reducing excessive fat mass accumulation, avoiding loss of lean body mass, improving well-being and selfesteem and preventing cyclical weight regain. The aim of this article is to describe the dietary intervention design and the methods used to evaluate nutritional knowledge and behavior in the EVASYON study (Development, implementation and evaluation of the efficacy of a therapeutic programme for overweight/obese adolescents). Methods/design: EVASYON is a multi-centre study conducted in 5 Spanish hospital settings (Granada, Madrid, Pamplona, Santander and Zaragoza), where 204 overweight/obese Spanish adolescents were treated in groups of 9 to 11 subjects over 20 visits. The study was implemented in two stages: an intensive, calorie-restricted period for the first 9 weeks, and an extensive body-weight follow-up period for the last 11 months. A moderate energy intake restriction was applied in the intensive period according to the degree of obesity, on the basis of a balanced diet supplying 50-55% of daily energy as carbohydrates; 30-35% as fats and 10-15% as proteins. In the intensive period, adolescents were prescribed both a fixed full-day meal plan for the first three weeks and a full day meal plan with different food-choices for 6 weeks. Later, adolescents received a flexible meal plan based on food exchanges for the follow-up period until the end of the trial. Data on food intake, dietary and meal-related habits and behavior were collected by means of dietary questionnaires. To analyse nutritional knowledge, adolescents were examined regarding nutrient concepts and food items for a healthy diet with the appropriate tools. Participants were given nutritional information with complementary teaching material, which was available on the EVASYON website (www.estudioevasyon.com). Discussion: The dietary intervention of the EVASYON programme with a moderate calorie restriction for a limi - ted period of time could be a good strategy in treating overweight and obese adolescents and that will be tested further. Moreover, combining fixed plan with free-choice menus may help adolescents and their families to make right decisions for every day meals

Treating horse chronic laminitis with allogeneic bone marrow mesenchymal stem cells

La laminitis crónica es una condición incapacitante que afecta el corion laminar de los cascos del caballo. Por lo general, se desarrolla como una lesión colateral de numerosas enfermedades sistémicas primarias. Se cree que el evento fisiopatológico crítico que hace que un casco sea vuelva laminítico es la pérdida de células madre mesenquimales. Esta pérdida perjudica en gran medida la capacidad del corion laminar para regenerarse. Aunque el trabajo previo proporciona credibilidad a esta noción, quedan cuestiones sin resolver que deben abordarse antes de aceptarla como un hecho bien fundado. Aquí, se reexaminó el principio central del modelo fisiopatológico de la laminitis mediante la infusión de células madre mesenquimales alogénicas derivadas de la médula ósea (CMM-AMO), a través de la vena palmar digital, en los cascos de los caballos afectados por laminitis crónica. Los caballos fueron monitoreados clínicamente durante 6 meses, evaluándolos mensualmente utilizando la escala de Obel-Glasgow de cojera modificada y la termografía de cascos. Se tomaron venogramas y biopsias laminares al principio y al final del período de estudio para reunir evidencia sobre la remodelación vascular y la regeneración del corion laminar. Los resultados mostraron que la infusión de CMM-AMO promueve la remodelación vascular y la regeneración del corion laminar, lo que respalda aún más que la pérdida de células madre es el evento crítico que conduce a la laminitis crónica. Este trabajo también demostró que la infusión de CMM-AMO es segura ya que los caballos tratados no desarrollaron manifestaciones clínicas negativas locales o sistémicas en sintonía con reacciones de rechazo, al menos durante el período de 6 meses en que se les dio seguimiento y bajo el esquema terapéutico propuesto.Chronic laminitis is a disabling condition that affects the laminar corium of the horse’s hooves. Commonly, it develops as a collateral injury of numerous primary systemic diseases. It is believed that the critical physiopathological event that renders a hoof laminitic is the loss of mesenchymal stem cells. This loss greatly impairs the ability of the laminar corium to regenerate. Although previous work provides credibility to this notion, there remain unsettled issues that must be addressed before accepting it as a well-founded fact. Here, it was reexamined the central tenet of the physiopathological model of laminitis by infusing allogeneic bone marrow-derived mesenchymal stem cells (ABM-MSCs), through the digital palmar vein, into the hooves of horses afflicted by chronic laminitis. Horses were clinically monitored during 6 mo by evaluating them monthly using the lameness-modified Obel-Glasgow’s scale and hooves thermography. Venograms and lamellar biopsies were taken at the beginning and at the end of the study period to gathered evidence on vascular remodeling and laminar corium regeneration. The results showed that ABM-MSCs infusion promotes vascular remodeling and laminar corium regeneration, further supporting that the loss of stem cells is the critical event leading to chronic laminitis. This work also demonstrated that the infusion of ABM-MSCs is safe since the treated horses did not develop local or systemic, negative clinical manifestations attuned with rejection reactions, at least during the 6-mo period they were follow up and under the therapeutic scheme proposed

INHIBITING CSF1R ALLEVIATES CEREBROVASCULAR WHITE MATTER DISEASE AND COGNITIVE IMPAIRMENT

White matter abnormalities, related to poor cerebral perfusion, are a core feature of small vessel cerebrovascular disease, and critical determinants of vascular cognitive impairment and dementia. Despite this importance there is a lack of treatment options. Proliferation of microglia producing an expanded, reactive population and associated neuroinflammatory alterations have been implicated in the onset and progression of cerebrovascular white matter disease, in patients and in animal models, suggesting that targeting microglial proliferation may exert protection. Colony-stimulating factor-1 receptor (CSF1R) is a key regulator of microglial proliferation. We found that the expression of CSF1R/Csf1r and other markers indicative of increased microglial abundance are significantly elevated in damaged white matter in human cerebrovascular disease and in a clinically relevant mouse model of chronic cerebral hypoperfusion and vascular cognitive impairment. Using the mouse model, we investigated long-term pharmacological CSF1R inhibition, via GW2580, and demonstrated that the expansion of microglial numbers in chronic hypoperfused white matter is prevented. Transcriptomic analysis of hypoperfused white matter tissue showed enrichment of microglial and inflammatory gene sets, including phagocytic genes that were the predominant expression modules modified by CSF1R inhibition. Further, CSF1R inhibition attenuated hypoperfusion-induced white matter pathology and rescued spatial learning impairments and to a lesser extent cognitive flexibility. Overall, this work suggests that inhibition of CSF1R and microglial proliferation mediates protection against chronic cerebrovascular white matter pathology and cognitive deficits. Our study nominates CSF1R as a target for the treatment of vascular cognitive disorders with broader implications for treatment of other chronic white matter diseases.<br/

Differential DNA methylation patterns between high and low responders to a weight loss intervention in overweight or obese adolescents: the EVASYON study

In recent years, epigenetic markers emerged as a new tool to understand the influence of lifestyle factors on obesity phenotypes. Adolescence is considered an important epigenetic window over a human's lifetime. The objective of this work was to explore baseline changes in DNA methylation that could be associated with a better weight loss response after a multidisciplinary intervention program in Spanish obese or overweight adolescents. Overweight or obese adolescents (n=107) undergoing 10 wk of a multidisciplinary intervention for weight loss were assigned as high or low responders to the treatment. A methylation microarray was performed to search for baseline epigenetic differences between the 2 groups (12 subjects/group), and MALDI-TOF mass spectrometry was used to validate (n=107) relevant CpG sites and surrounding regions. After validation, 5 regions located in or near AQP9, DUSP22, HIPK3, TNNT1, and TNNI3 genes showed differential methylation levels between high and low responders to the multidisciplinary weight loss intervention. Moreover, a calculated methylation score was significantly associated with changes in weight, BMI-SDS, and body fat mass loss after the treatment. In summary, we have identified 5 DNA regions that are differentially methylated depending on weight loss response. These methylation changes may help to better understand the weight loss response in obese adolescents