Dynamic Chromatin Organization during Foregut Development Mediated by the Organ Selector Gene PHA-4/FoxA

Central regulators of cell fate, or selector genes, establish the identity of cells by direct regulation of large cohorts of genes. In Caenorhabditis elegans, foregut (or pharynx) identity relies on the FoxA transcription factor PHA-4, which activates different sets of target genes at various times and in diverse cellular environments. An outstanding question is how PHA-4 distinguishes between target genes for appropriate transcriptional control. We have used the Nuclear Spot Assay and GFP reporters to examine PHA-4 interactions with target promoters in living embryos and with single cell resolution. While PHA-4 was found throughout the digestive tract, binding and activation of pharyngeally expressed promoters was restricted to a subset of pharyngeal cells and excluded from the intestine. An RNAi screen of candidate nuclear factors identified emerin (emr-1) as a negative regulator of PHA-4 binding within the pharynx, but emr-1 did not modulate PHA-4 binding in the intestine. Upon promoter association, PHA-4 induced large-scale chromatin de-compaction, which, we hypothesize, may facilitate promoter access and productive transcription. Our results reveal two tiers of PHA-4 regulation. PHA-4 binding is prohibited in intestinal cells, preventing target gene expression in that organ. PHA-4 binding within the pharynx is limited by the nuclear lamina component EMR-1/emerin. The data suggest that association of PHA-4 with its targets is a regulated step that contributes to promoter selectivity during organ formation. We speculate that global re-organization of chromatin architecture upon PHA-4 binding promotes competence of pharyngeal gene transcription and, by extension, foregut development

The study of Priapulus caudatus reveals conserved molecular patterning underlying different gut morphogenesis in the Ecdysozoa

Background The digestive systems of animals can become highly specialized in response to their exploration and occupation of new ecological niches. Although studies on different animals have revealed commonalities in gut formation, the model systems Caenorhabditis elegans and Drosophila melanogaster, which belong to the invertebrate group Ecdysozoa, exhibit remarkable deviations in how their intestines develop. Their morphological and developmental idiosyncrasies have hindered reconstructions of ancestral gut characters for the Ecdysozoa, and limit comparisons with vertebrate models. In this respect, the phylogenetic position, and slow evolving morphological and molecular characters of marine priapulid worms advance them as a key group to decipher evolutionary events that occurred in the lineages leading to C. elegans and D. melanogaster. Results In the priapulid Priapulus caudatus, the gut consists of an ectodermal foregut and anus, and a mid region of at least partial endodermal origin. The inner gut develops into a 16-cell primordium devoid of visceral musculature, arranged in three mid tetrads and two posterior duplets. The mouth invaginates ventrally and shifts to a terminal anterior position as the ventral anterior ectoderm differentially proliferates. Contraction of the musculature occurs as the head region retracts into the trunk and resolves the definitive larval body plan. Despite obvious developmental differences with C. elegans and D. melanogaster, the expression in P. caudatus of the gut-related candidate genes NK2.1, foxQ2, FGF8/17/18, GATA456, HNF4, wnt1, and evx demonstrate three distinct evolutionarily conserved molecular profiles that correlate with morphologically identified sub-regions of the gut. Conclusions The comparative analysis of priapulid development suggests that a midgut formed by a single endodermal population of vegetal cells, a ventral mouth, and the blastoporal origin of the anus are ancestral features in the Ecdysozoa. Our molecular data on P. caudatus reveal a conserved ecdysozoan gut-patterning program and demonstrates that extreme morphological divergence has not been accompanied by major molecular innovations in transcriptional regulators during digestive system evolution in the Ecdysozoa. Our data help us understand the origins of the ecdysozoan body plan, including those of C. elegans and D. melanogaster, and this is critical for comparisons between these two prominent model systems and their vertebrate counterparts

Mercury in the Canadian Environment: Current Research Challenges

Elevated methyl mercury concentrations are common in fish and other wildlife in ecosystems remote from any industrial point sources. Concern about chronic exposure to methyl mercury for people who depend on fish as a dietary staple has focused attention on mercury sources and cycling processes in rural and remote areas, and on the potential for airborne mercury to travel hundreds to thousands of kilometres. A number of other studies have demonstrated that elevated concentrations of mercury in fish may be attributable to local geological sources. Compared to the large body of literature that is emerging on anthropogenic sources, however, there is a relative lack of research aimed at quantifying the contribution of mercury from natural sources. This has resulted in a debate over the relative significance of anthropogenic and natural mercury inputs to rural and remote lakes. Geoscience research is needed to improve our understanding of the biogeochemical cycling of mercury species released from common sulphide minerals and other crustal sources into soil, sediments, air, water, vegetation and ultimately into the human food chain. Résumé Les niveaux de mercure méthylé sont souvent élevés dans les tissus des poissons et ceux d'autres animaux de la faune des écosystèmes éloignés des sources industrielles. Découlant des préoccupations concernant les risques d'une exposition régulière au mercure méthylé pour les populations dont la diète est basée sur le poisson, les recherches ont porté sur les sources possibles du mercure, ses cycles de transport ainsi que sur la possibilité que le mercure atmosphérique puisse être transporté sur des milliers de kilomètres. D'autres études ont démontré que des sources géologiques pourraient être à l'origine de concentrations élevées en mercure dans les poissons. Si la documentation sur les sources anthropogéniques de mercure est abondante, on constate en contrepartie qu'il n'y a pas assez de recherches scientifiques visant à chiffrer l'apport des sources naturelles. En conséquence, la question de l'apport relatif en mercure des sources anthropogéniques et naturelles en milieu rural et dans les lacs éloignés demeure-t-elle encore matière à discussion. Des études géoscientifiques devront être réalisées afin d'améliorer nos connaissances sur le cycle biochimique des composés du mercure provenant des minéraux de sulfures usuels et d'autres sources crustales, dans le sol, les sédiments, l'air, l'eau, la végétation, et en bout de piste, dans la chaîne alimentaire des humains

Systematic Literature Review: Potensi Aktivitas Anti-Apoptosis Tanaman Herbal Panax notoginseng pada Sel Otot Jantung

Apoptosis dapat terjadi pada semua sel normal, termasuk sel otot jantung yaitu kardiomiosit. Apoptosis yang tidak tepat merupakan faktor dalam timbulnya banyak penyakit, salah satunya penyakit jantung. Jantung merupakan organ dengan kemampuan regenerasi yang sangat rendah, sehingga sulit untuk meregenerasi kardiomiosit apabila mengalami kerusakan. Panax notoginseng dapat digunakan sebagai alternatif pengobatan karena memiliki senyawa saponin yang dapat menekan terjadinya apoptosis pada kardiomiosit yang telah mengalami kerusakan. Penelitian ini bertujuan untuk mengetahui potensi aktivitas anti-apoptosis dan mekanisme yang terlibat dari Panax notoginseng, serta metabolit sekunder spesifik yang berperan sebagai anti-apoptosis. Metode yang digunakan pada penelitian ini adalah Systematic Literature Review. Pencarian artikel yang komprehensif dilakukan menggunakan aplikasi Harzing’s Publish or Perish pada beberapa database yaitu Google Scholar, Pubmed, dan Scopus dengan menggunakan kata kunci “Panax notoginseng” AND “apoptosis” AND “cardiomyocyte” AND “mechanism” OR “secondary metabolites”. Alur penyeleksian pada artikel yaitu menggunakan protokol PRISMA. Total hasil pencarian artikel yang didapatkan sebanyak 1026 artikel, dan terdapat 34 artikel yang memenuhi kriteria inklusi dan eksklusi yang telah ditetapkan. Hasil penelitian ini menyimpulkan bahwa efektivitas Panax notoginseng sebagai anti-apoptosis ditunjukkan dengan cara meningkatkan viabilitas sel, mengurangi fragmentasi DNA dan jumlah kaskade caspase, antara lain, cleaved-caspase-3,9; caspase-3,8,9; caspase 12, serta dengan meningkatkan ekspresi protein anti-apoptosis Bcl-2 dan Bcl-xL dan menekan ekspresi protein pro-apoptosis Bax, tBid, Bim. Metabolit sekunder yang berperan sebagai anti-apoptosis antara lain PNS dengan konsentrasi 50 mg/ml dan 200 μM, ginsenoside Rb1 konsentrasi 10 mg/kg, Rg1 konsentrasi 15 mg/kg, Rh3 konsentrasi 0,5 mg/kg, dan NGR1 konsentrasi 20 μM, 25 μg/mL dan 5 mg/kg