BackgroundMembers of the HMGN protein family modulate chromatin structure and influence epigenetic modifications. HMGN1 and HMGN2 are highly expressed during early development and in the neural stem/progenitor cells of the developing and adult brain. Here, we investigate whether HMGN proteins contribute to the chromatin plasticity and epigenetic regulation that is essential for maintaining pluripotency in stem cells.ResultsWe show that loss of Hmgn1 or Hmgn2 in pluripotent embryonal carcinoma cells leads to increased levels of spontaneous neuronal differentiation. This is accompanied by the loss of pluripotency markers Nanog and Ssea1, and increased expression of the pro-neural transcription factors Neurog1 and Ascl1. Neural stem cells derived from these Hmgn-knockout lines also show increased spontaneous neuronal differentiation and Neurog1 expression. The loss of HMGN2 leads to a global reduction in H3K9 acetylation, and disrupts the profile of H3K4me3, H3K9ac, H3K27ac and H3K122ac at the Nanog and Oct4 loci. At endodermal/mesodermal genes, Hmgn2-knockout cells show a switch from a bivalent to a repressive chromatin configuration. However, at neuronal lineage genes whose expression is increased, no epigenetic changes are observed and their bivalent states are retained following the loss of HMGN2.ConclusionsWe conclude that HMGN1 and HMGN2 maintain the identity of pluripotent embryonal carcinoma cells by optimising the pluripotency transcription factor network and protecting the cells from precocious differentiation. Our evidence suggests that HMGN2 regulates active and bivalent genes by promoting an epigenetic landscape of active histone modifications at promoters and enhancers.

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Alzheimer's disease (AD) is a neurodegenerative disorder characterized clinically by the progressive decline of memory and cognition. Histopathologically, two main hallmarks have been identified in AD: amyloid-β peptide extracellular neuritic plaques and neurofibrillary tangles formed by posttranslational modified tau protein. A definitive diagnosis can only be achieved after the post mortem verification of the histological mentioned alterations. Therefore, the development of biomarkers that allow an early diagnosis and/or predict disease progression is imperative. The prospect of a blood-based biomarker is possible with the finding of circulating microRNAs (miRNAs), a class of small non-coding RNAs of 22–25 nucleotides length that regulate mRNA translation rate. miRNAs travel through blood and recent studies performed in potential AD cases suggest the possibility of finding pathology-associated differences in circulating miRNA levels that may serve to assist in early diagnosis of the disease. However, these studies analyzed samples at a single time-point, limiting the use of miRNAs as biomarkers in AD progression. In this study we evaluated miRNA levels in plasma samples at different time-points of the evolution of an AD-like pathology in a transgenic mouse model of the disease (3xTg-AD). We performed multiplex qRT-PCR and compared the plasmatic levels of 84 miRNAs previously associated to central nervous system development and disease. No significant differences were detected between WT and transgenic young mice. However, age-related significant changes in miRNA abundance were observed for both WT and transgenic mice, and some of these were specific for the 3xTg-AD. In agreement, variations in the levels of particular miRNAs were identified between WT and transgenic old mice thus suggesting that the age-dependent evolution of the AD-like pathology, rather than the presence and expression of the transgenes, modifies the circulating miRNA levels in the 3xTg-AD mice.

<p><strong>Resumen</strong></p><p>La microbiota intestinal desempeña relevantes funciones mediante las cuales contribuye directa o indirectamente a la estabilidad del organismo humano; actualmente su papel es incuestionable en la modulación del sistema inmune, la regulación del sistema nervioso, la síntesis de vitaminas, la defensa del intestino y el movimiento peristáltico.</p><p>Las nuevas herramientas de la biología molecular han sido determinantes para la revelación de los sorprendentes hallazgos publicados en los últimos lustros, los cuales han dado origen a términos y frases tales como “psicobióticos”, “un órgano adicional del humano”, “el segundo cerebro” y “el eje microbiota-intestino-cerebro”.</p><p>Por otra parte, el desequilibrio de la microbiota intestinal se traduce en la generación o agravamiento de diversas enfermedades crónicas, entre las que destacan la obesidad, diabetes tipo 2, enfermedad inflamatoria del intestino, síndrome metabólico, depresión, ansiedad.</p><p>De aquí que la comunidad científica se encuentre trabajando intensamente en el conocimiento de su composición y en el impacto de la proporción o ausencia de las principales especies en el funcionamiento global de la microbiota intestinal y, consecuentemente, del organismo humano.</p><p>La presente revisión contribuye a la actualización del tema “Microbiota Habitual” que se imparte en las carreras de Química Farmacéutico Biólogo, Química de Alimentos y carreras afines.</p><p><strong>Abstract</strong></p><p>The gut microbiota plays relevant functions in the human organism, contributing directly or indirectly to its homeostasis. To name a few, it participates in the immune and the nervous system modulation, the vitamins synthesis, the gut defence and the peristaltic movement.</p><p>Novel molecular biology techniques have been determinant to reveal amazing findings in recent years, and now the authors use terms and phrases such as “psychobiotics”, “an additional human tissue”, “the second brain”, and “the microbiota-gut-brain axis”, when referring to the gut microbiota functions.</p><p>In contrast, misregulation of gut microbiota is involved in the pathogenicity of chronical diseases, such as obesity, type II diabetes, metabolic syndrome, gut inflammatory disease, depression and anxiety, among others. Therefore, it is important to investigate the gut microbiota composition and the individual contribution of each specie to the gut microbiota function, and subsequently, to the human organism physiology.</p><p>This review article summarizes recent contributions in the field, suitable when teaching the theme of “Habitual Microbiota” in the Biological Pharmaceutical Chemistry, Food Chemistry, and related bachelor degrees.</p>

Massive testing is a cornerstone in efforts to effectively track infections and stop COVID-19 transmission, including places with good vaccination coverage. However, SARS-CoV-2 testing by RT-qPCR requires specialized personnel, protection equipment, commercial kits, and dedicated facilities, which represent significant challenges for massive testing in resource-limited settings. It is therefore important to develop testing protocols that are inexpensive, fast, and sufficiently sensitive. Here, we optimized the composition of a buffer (PKTP), containing a protease, a detergent, and an RNase inhibitor, which is compatible with the RT-qPCR chemistry, allowing for direct SARS-CoV-2 detection from saliva without extracting RNA. PKTP is compatible with heat inactivation, reducing the biohazard risk of handling samples. We assessed the PKTP buffer performance in comparison to the RNA-extraction-based protocol of the US Centers for Disease Control and Prevention in saliva samples from 70 COVID-19 patients finding a good sensitivity (85.7% for the N1 and 87.1% for the N2 target) and correlations (R = 0.77, p < 0.001 for N1, and R = 0.78, p < 0.001 for N2). We also propose an auto-collection protocol for saliva samples and a multiplex reaction to minimize the PCR reaction number per patient and further reduce costs and processing time of several samples, while maintaining diagnostic standards in favor of massive testing.