Humic Acid Derived from Agricultural Biomass Mitigates Alveolar Bone Loss and Modulates Systemic Inflammatory Cytokines in Rats with Periodontitis.

BACKGROUND: Humic acid (HA) is a bioproduct that can be extracted from different sources and has anti-inflammatory properties that have been little explored in the treatment and prevention of Periodontal Disease (PD). Thus, we aimed to investigate the effects of oral administration of HA on the progression of PD in rats. METHODS: Twenty-four male Wistar rats were distributed into three experimental groups (Control/ Sham, PD, and PD + HA). HA was administered by gavage (80 mg/kg/day) for 28 days, and PD was induced 14 days after the beginning of treatment. Bone loss, bone topography, and surface elemental composition were analyzed. Circulating IL1-beta, TNF-alpha, and IL-10 levels were evaluated through Enzyme-Linked Immunosorbent Assay (ELISA). RESULTS: The animals treated with HA showed lower bone loss (p < 0.05). Calcium and phosphorus levels on the alveolar bone surface were lower in the PD group (p < 0.05) compared to the control group, whereas the animals treated with HA exhibited attenuation in this loss (p < 0.05). The animals treated with HA showed reduced TNF-alpha, IL1-beta, IL-10, and the TNF-alpha/IL-10 ratio compared to those with PD (p < 0.05). CONCLUSION: Treatment with HA attenuated the parameters of alveolar bone loss and modulated systemic inflammatory parameters in rats with ligature-induced PD.

Epigenetic inheritance is unfaithful at intermediately methylated CpG sites.

DNA methylation at the CpG dinucleotide is considered a stable epigenetic mark due to its presumed long-term inheritance through clonal expansion. Here, we perform high-throughput bisulfite sequencing on clonally derived somatic cell lines to quantitatively measure methylation inheritance at the nucleotide level. We find that although DNA methylation is generally faithfully maintained at hypo- and hypermethylated sites, this is not the case at intermediately methylated CpGs. Low fidelity intermediate methylation is interspersed throughout the genome and within genes with no or low transcriptional activity, and is not coordinately maintained between neighbouring sites. We determine that the probabilistic changes that occur at intermediately methylated sites are likely due to DNMT1 rather than DNMT3A/3B activity. The observed lack of clonal inheritance at intermediately methylated sites challenges the current epigenetic inheritance model and has direct implications for both the functional relevance and general interpretability of DNA methylation as a stable epigenetic mark.

Intentional creation of carbon-rich dark earth soils in the Amazon.

Fertile soil known as Amazonian dark earth is central to the debate over the size and ecological impact of ancient human populations in the Amazon. Dark earth is typically associated with human occupation, but it is uncertain whether it was created intentionally. Dark earth may also be a substantial carbon sink, but its spatial extent and carbon inventory are unknown. We demonstrate spatial and compositional similarities between ancient and modern dark earth and document modern Indigenous practices that enrich soil, which we use to propose a model for the formation of ancient dark earth. This comparison suggests that ancient Amazonians managed soil to improve fertility and increase crop productivity. These practices also sequestered and stored carbon in the soil for centuries, and we show that some ancient sites contain as much carbon as the above-ground rainforest biomass. Our results demonstrate the intentional creation of dark earth and highlight the value of Indigenous knowledge for sustainable rainforest management.

Artificial selection reveals complex genetic architecture of shoot branching and its response to nitrate supply in Arabidopsis.

Quantitative traits may be controlled by many loci, many alleles at each locus, and subject to genotype-by-environment interactions, making them difficult to map. One example of such a complex trait is shoot branching in the model plant Arabidopsis, and its plasticity in response to nitrate. Here, we use artificial selection under contrasting nitrate supplies to dissect the genetic architecture of this complex trait, where loci identified by association mapping failed to explain heritability estimates. We found a consistent response to selection for high branching, with correlated responses in other traits such as plasticity and flowering time. Genome-wide scans for selection and simulations suggest that at least tens of loci control this trait, with a distinct genetic architecture between low and high nitrate treatments. While signals of selection could be detected in the populations selected for high branching on low nitrate, there was very little overlap in the regions selected in three independent populations. Thus the regulatory network controlling shoot branching can be tuned in different ways to give similar phenotypes.

A root phloem pole cell atlas reveals common transcriptional states in protophloem-adjacent cells.

Single-cell sequencing has recently allowed the generation of exhaustive root cell atlases. However, some cell types are elusive and remain underrepresented. Here we use a second-generation single-cell approach, where we zoom in on the root transcriptome sorting with specific markers to profile the phloem poles at an unprecedented resolution. Our data highlight the similarities among the developmental trajectories and gene regulatory networks common to protophloem sieve element (PSE)-adjacent lineages in relation to PSE enucleation, a key event in phloem biology. As a signature for early PSE-adjacent lineages, we have identified a set of DNA-binding with one finger (DOF) transcription factors, the PINEAPPLEs (PAPL), that act downstream of PHLOEM EARLY DOF (PEAR) genes and are important to guarantee a proper root nutrition in the transition to autotrophy. Our data provide a holistic view of the phloem poles that act as a functional unit in root development.

Cell-by-cell dissection of phloem development links a maturation gradient to cell specialization.

In the plant meristem, tissue-wide maturation gradients are coordinated with specialized cell networks to establish various developmental phases required for indeterminate growth. Here, we used single-cell transcriptomics to reconstruct the protophloem developmental trajectory from the birth of cell progenitors to terminal differentiation in the Arabidopsis thaliana root. PHLOEM EARLY DNA-BINDING-WITH-ONE-FINGER (PEAR) transcription factors mediate lineage bifurcation by activating guanosine triphosphatase signaling and prime a transcriptional differentiation program. This program is initially repressed by a meristem-wide gradient of PLETHORA transcription factors. Only the dissipation of PLETHORA gradient permits activation of the differentiation program that involves mutual inhibition of early versus late meristem regulators. Thus, for phloem development, broad maturation gradients interface with cell-type-specific transcriptional regulators to stage cellular differentiation.

An ABA-GA bistable switch can account for natural variation in the variability of Arabidopsis seed germination time.

Genetically identical plants growing in the same conditions can display heterogeneous phenotypes. Here we use Arabidopsis seed germination time as a model system to examine phenotypic variability and its underlying mechanisms. We show extensive variation in seed germination time variability between Arabidopsis accessions and use a multiparent recombinant inbred population to identify two genetic loci involved in this trait. Both loci include genes implicated in modulating abscisic acid (ABA) sensitivity. Mutually antagonistic regulation between ABA, which represses germination, and gibberellic acid (GA), which promotes germination, underlies the decision to germinate and can act as a bistable switch. A simple stochastic model of the ABA-GA network shows that modulating ABA sensitivity can generate the range of germination time distributions we observe experimentally. We validate the model by testing its predictions on the effects of exogenous hormone addition. Our work provides a foundation for understanding the mechanism and functional role of phenotypic variability in germination time.

Natural variation in Arabidopsis shoot branching plasticity in response to nitrate supply affects fitness.

The capacity of organisms to tune their development in response to environmental cues is pervasive in nature. This phenotypic plasticity is particularly striking in plants, enabled by their modular and continuous development. A good example is the activation of lateral shoot branches in Arabidopsis, which develop from axillary meristems at the base of leaves. The activity and elongation of lateral shoots depends on the integration of many signals both external (e.g. light, nutrient supply) and internal (e.g. the phytohormones auxin, strigolactone and cytokinin). Here, we characterise natural variation in plasticity of shoot branching in response to nitrate supply using two diverse panels of Arabidopsis lines. We find extensive variation in nitrate sensitivity across these lines, suggesting a genetic basis for variation in branching plasticity. High plasticity is associated with extreme branching phenotypes such that lines with the most branches on high nitrate have the fewest under nitrate deficient conditions. Conversely, low plasticity is associated with a constitutively moderate level of branching. Furthermore, variation in plasticity is associated with alternative life histories with the low plasticity lines flowering significantly earlier than high plasticity lines. In Arabidopsis, branching is highly correlated with fruit yield, and thus low plasticity lines produce more fruit than high plasticity lines under nitrate deficient conditions, whereas highly plastic lines produce more fruit under high nitrate conditions. Low and high plasticity, associated with early and late flowering respectively, can therefore be interpreted alternative escape vs mitigate strategies to low N environments. The genetic architecture of these traits appears to be highly complex, with only a small proportion of the estimated genetic variance detected in association mapping.

Selection and gene flow shape genomic islands that control floral guides.

Genomes of closely-related species or populations often display localized regions of enhanced relative sequence divergence, termed genomic islands. It has been proposed that these islands arise through selective sweeps and/or barriers to gene flow. Here, we genetically dissect a genomic island that controls flower color pattern differences between two subspecies of Antirrhinum majus, A.m.striatum and A.m.pseudomajus, and relate it to clinal variation across a natural hybrid zone. We show that selective sweeps likely raised relative divergence at two tightly-linked MYB-like transcription factors, leading to distinct flower patterns in the two subspecies. The two patterns provide alternate floral guides and create a strong barrier to gene flow where populations come into contact. This barrier affects the selected flower color genes and tightly-linked loci, but does not extend outside of this domain, allowing gene flow to lower relative divergence for the rest of the chromosome. Thus, both selective sweeps and barriers to gene flow play a role in shaping genomic islands: sweeps cause elevation in relative divergence, while heterogeneous gene flow flattens the surrounding "sea," making the island of divergence stand out. By showing how selective sweeps establish alternative adaptive phenotypes that lead to barriers to gene flow, our study sheds light on possible mechanisms leading to reproductive isolation and speciation.

Evolution of flower color pattern through selection on regulatory small RNAs.

Small RNAs (sRNAs) regulate genes in plants and animals. Here, we show that population-wide differences in color patterns in snapdragon flowers are caused by an inverted duplication that generates sRNAs. The complexity and size of the transcripts indicate that the duplication represents an intermediate on the pathway to microRNA evolution. The sRNAs repress a pigment biosynthesis gene, creating a yellow highlight at the site of pollinator entry. The inverted duplication exhibits steep clines in allele frequency in a natural hybrid zone, showing that the allele is under selection. Thus, regulatory interactions of evolutionarily recent sRNAs can be acted upon by selection and contribute to the evolution of phenotypic diversity.

Prevalence of metabolic syndrome in a Portuguese obese adolescent population according to three different definitions.

In order to determine the prevalence of metabolic syndrome (MS) in a Portuguese pediatric overweight population according to three different sets of criteria, 237 overweight and obese adolescents were evaluated at engagement in a specific multidisciplinary program. Two of the used definitions were based on the National Cholesterol Education Program (ATPIII) guidelines modified for pediatric age and were proposed by Cook et al. (Arch Pediatr Adolesc Med 157(8):821-827, 2003) and de Ferranti et al. (Circulation 110(16):2494-2497, 2004). The third definition used resulted from a consensus of the International Diabetes Federation (IDF 2005). All of them include five components: waist circumference, blood pressure, high-density lipoprotein cholesterol, triglycerides, and fasting glucose values, with different cut-off points. Of the studied sample, 53% were girls, median age 13.4 years, 89% classified as obese, and the remaining as overweight. MS prevalence was 15.6%, 34.9%, and 8.9% according to Cook's, de Ferranti's, and IDF definitions, respectively. No adolescent fulfilled the five MS criteria, and only three (1.2%), 15 (6%), and 13 (5.1%) had no criteria at all, according to the three definitions used. Waist circumference was the most prevalent component (89.5%, 98.7%, and 93.2%), and high fasting glucose the least (1.3% for the two first and 2.5% according to the IDF definition). A significant correlation between increased body mass index and MS was found, using the two first definitions (Cook et al. p < 0.05; de Ferranti et al. p < 0.01), but not when using the third one. Considerable prevalence differences were found using three different MS criteria. It is urgent to establish a consensus on MS definition to allow early identification of adolescents at risk and the development of prospective studies to define what cut-offs are the best indicators of future morbidity.

[Eosinophilic esophagitis: increasing incidence in paediatric population]. / Esofagite eosinofílica: uma patologia emergente em pediatría.

INTRODUCTION: Eosinophilic Esophagitis has been increasingly diagnosed and results from a chronic esophagic inflammation with eosinophilic infiltrate. MATERIAL AND METHODS: Evaluation of the diagnosed paediatric cases in our centre between 2004 and 2008 and revision of current literature on this subject. RESULTS: Four caucasian boys, aged eight to fifteen years old, were diagnosed with Eosinophilic Esophagitis. They presented with disphagia and food impaction and endoscopic findings included multiple concentric rings (pseudo-trachea pattern) and friable mucosa. All of them had mucosal eosinophil counts higher than 20 eosinophils/high-powered field and were given corticosteroids, either topic or systemic (one case) with therapeutic success. DISCUSSION: The diagnosis of Eosinophilic Esophagitis must be considered in presence of disphagia, food impaction or gastroesophageal reflux symptoms refractory to treatment. Endoscopic evaluation may be normal and the diagnosis is based on histological findings, making biopsy mandatory whenever clinically suspected. The increasing incidence of the last years associated with the high recurrence rate will lead to future prevalence increased both in child and adulthood.

Induction of a hyperanxious state by antenatal dexamethasone: a case for less detrimental natural corticosteroids.

BACKGROUND: Synthetic glucocorticoids are commonly prescribed during pregnancy, despite a lack of systematic investigations of their potential impact on the developing brain and neurological and behavioral performance. METHODS: Neuroendocrine parameters and behavior in the adult offspring of pregnant Wistar rats treated antenatally with either dexamethasone (DEX) or corticosterone (CORT) were monitored; DEX (.1 mg/kg and 1 mg/kg) and CORT (25 mg/kg) were given to pregnant rat dams on gestation days 18 and 19. RESULTS: Despite normal basal levels of corticosterone, the adult offspring of mothers given DEX or CORT displayed abnormal responses in the dexamethasone-suppression test. Neither treatment influenced spatial memory performance, but both DEX and CORT facilitated development of depression-like behavior following chronic stress. The latter finding demonstrates that high-dose antenatal corticotherapy can impair the organism's resilience to stress in adulthood. Interestingly, comparison of the progeny of CORT-treated and DEX-treated mothers revealed that the latter were more anxious. CONCLUSIONS: Since DEX and CORT differ in their affinity for glucocorticoid and mineralocorticoid receptors and corticosteroid-binding globulin, our findings emphasize the need to consider the pharmacologic properties of antenatal corticotherapies and demonstrate the potential long-term benefits of ligands that can bind to both receptors.

A felicidade no mal-estar

Sem resumo

40 anos de fenomenologia da percepcao

O objetivo do presente artigo e celebrar os quarenta anos da Fenomenologia da Percepcao (publicada em 1945), procurando situar o pensamento de Merleau-Ponty - ao nivel de seu livro fundamental - no panorama da filosofia moderna e contemporanea.

Perdas dentárias precoces na população da Unidade Básica de Saúde São Geraldo, Pirapora/MG: proposta de intervenção

O levantamento de necessidades realizado na área de abrangência da unidade Básica de Saúde (UBS)-São Geraldo, em Pirapora, MG, detectou um elevado índice de perdas dentárias precoces. No intuito de minimizar estas perdas, foi elaborado um plano de intervenção, que contemplou a elaboração de estratégias com o objetivo de estruturar/organizar os serviços de saúde para enfrentar as principais causas das perdas dentarias que são respectivamente; cárie e doença periodontal. Um levantamento de necessidades foi realizado em uma amostra não probabilística, intencional e envolveu 300 pessoas da comunidade do São Geraldo, sendo avaliadas 60 pessoas de cada faixa etária (5, 12, 15 a 19, 35 a 44 e 65 a 74 anos). Nas faixas etárias de 5, 12, 15 a 19, 35 a 44 e 65 a 74 anos avaliou-se a prevalência e a gravidade da cárie dentária e na população de 12, 15 a 19, 35 a 44 e 65 a 74 anos, avaliou-se também a extensão e gravidade da doença periodontal. As perdas dentárias se associam e mantém relação com diversos fatores à exemplo: hábitos de vida inadequados, baixa acessibilidade aos serviços de saúde, deficiências no processo de trabalho da equipe e baixo grau de informação/conscientização da população à respeito de questões de saúde bucal. O plano de intervenção proporcionará dessa forma, a médio prazo, melhorias nas condições de saúde bucal e qualidade de vida da população adscrita, na medida em que, proporcionará uma redução no número de perdas dentárias que acabam por comprometer a capacidade funcional e estética dos pacientes.