A shortcut to identifying small molecule signals that regulate behavior and development in Caenorhabditis elegans

Small molecule metabolites play important roles in Caenorhabditis elegans biology, but effective approaches for identifying their chemical structures are lacking. Recent studies revealed that a family of glycosides, the ascarosides, differentially regulate C. elegans development and behavior. Low concentrations of ascarosides attract males and thus appear to be part of the C. elegans sex pheromone, whereas higher concentrations induce developmental arrest at the dauer stage, an alternative, nonaging larval stage. The ascarosides act synergistically, which presented challenges for their identification via traditional activity-guided fractionation. As a result the chemical characterization of the dauer and male attracting pheromones remained incomplete. Here, we describe the identification of several additional pheromone components by using a recently developed NMR-spectroscopic approach, differential analysis by 2D NMR spectroscopy (DANS), which simplifies linking small molecule metabolites with their biological function. DANS-based comparison of wild-type C. elegans and a signaling-deficient mutant, daf-22, enabled identification of 3 known and 4 previously undescribed ascarosides, including a compound that features a p-aminobenzoic acid subunit. Biological testing of synthetic samples of these compounds revealed additional evidence for synergy and provided insights into structure–activity relationships. Using a combination of the three most active ascarosides allowed full reconstitution of the male-attracting activity of wild-type pheromone extract. Our results highlight the efficacy of DANS as a method for identifying small-molecule metabolites and placing them within a specific genetic context. This study further supports the hypothesis that ascarosides represent a structurally diverse set of nematode signaling molecules regulating major life history traits

The Manufacture of Eastern Sigillata C and Late Roman C at Çandarlı, Ancient Pitane: Results of the Intensive Survey (2019–2021)

Dieser Artikel stellt die Ergebnisse eines intensiven archäologischen Surveys im modernen Çandarlı (antikes Pitane) vor, das seit 1911 als Herstellungsort für Terra Sigillata in den ersten drei Jahrhunderten n. Chr. bekannt ist. Im Rahmen des TransPergMikro-Projekts wurde die archäologische Zone im Zentrum der Çandarlı-Halbinsel in den Jahren 2019 und 2020 systematisch begangen, um die lokale Keramikherstellung als Teil einer breiteren handwerklichen und wirtschaftlichen Entwicklung innerhalb der Mikroregion Pergamon während der hellenistischen und römischen Kaiserzeit zu untersuchen  zu dokumentieren. Der Survey erbrachte eine umfangreiche und reichhaltige Sammlung von Artefakten, die 2021 vollständig untersucht wurde und ein klareres Bild des typologischen Repertoires sowie der technologischen Aspekte der eigentlichen Herstellung und des Brennens vermittelt. Eines der interessantesten Ergebnisse war die Entdeckung archäologischer Beweise für die lokale Produktion von Late Roman C-Ware, was bedeutet, dass die Geschirrherstellung in Pitane bis in die Spätantike hinein andauerte.This article presents the results of an intensive archaeological survey at modern Çandarlı (ancient Pitane), which since 1911 is well-known as a place of manufacture for terra sigillata during the first three centuries A.D. Within the framework of the TransPergMicro Project, the archaeological zone in the centre of the Çandarlı Peninsula was systematically fieldwalked in 2019 and 2020 in order to investigate and document local pottery manufacture as part of broader artisanal and economic developments within the Pergamon micro-region during the Hellenistic and Roman Imperial periods. The survey yielded an abundant and rich collection of artefacts – fully studied in 2021 – which provides a clearer picture of the typological repertoire as well as technological aspects of the actual manufacture and firing. One of the more interesting results was finding archaeological evidence for the local production of Late Roman C, which signifies that tableware manufacture at Pitane continued into Late Antiquity.Bu makalede, MS 1.–3. yüzyılda terra sigillata üretimiyle bilinen Çandarlı\u27daki arkeolojik yüzey araştırmalarının sonuçları tanıtılmaktadır. Buradaki üretimin varlığı 1911\u27de saptanmıştır. 2019 ile 2020 yılında, Çandarlı Yarımadası\u27nın merkezindeki arkeolojik alan, »Pergamon Mikrocoğrafyasının Dönüşümü« (TransPergMikro) adlı proje çerçevesinde sistemli olarak taranmıştır. Yüzey araştırmasının amacı, Pergamon\u27un Hellenistik ve Roma dönemi mikrocoğrafyasındaki zanaat ve ekonomiye dayalı daha büyük bir gelişimin bir parçası olan yerel keramik üretimini araştırmak ve belgelemektir. Bu sayede son derece zengin bir buluntu topluluğu elde edilmiştir. Değerlendirmelerin 2021 yılında tamamlanmasıyla form repertuarı, keramik yapımı ve fırınlamaya yönelik teknik konular açıklığa kavuşmuştur. Arkeolojik kanıtlar sayesinde ulaşılan en ilginç sonuçlardan biri, Late Roman C grubunun yerel üretildiğidir. Bu durum, Pitane\u27deki keramik üretiminin Geç Antik Dönem\u27e kadar devam ettiğini göstermektedir

Autoregulation of Nisin Biosynthesis in Lactococcus lactis by Signal Transduction

The post-translationally modified, antimicrobial peptide nisin is secreted by strains of Lactococcus lactis that contain the chromosomally located nisin biosynthetic gene cluster nisABTCIPRKFEG. When a 4-base pair deletion is introduced into the structural nisA gene (ΔnisA), transcription of ΔnisA is abolished. Transcription of the ΔnisA gene is restored by adding subinhibitory amounts of nisin, nisin mutants, or nisin analogs to the culture medium, but not by the unmodified precursor peptide or by several other antimicrobial peptides. Upon disruption of the nisK gene, which encodes a putative sensor protein that belongs to the class of two-component regulators, transcription of ΔnisA was no longer inducible by nisin. Fusion of a nisA promoter fragment to the promoterless reporter gene gusA resulted in expression of gusA in L. lactis NZ9800 (ΔnisA) only upon induction with nisin species. The expression level of gusA was directly related to the amount of inducer that was added extracellularly. These results provide insight into a new mechanism of autoregulation through signal transduction in prokaryotes and demonstrate that antimicrobial peptides can exert a second function as signaling molecules.

Fate specification and tissue-specific cell cycle control of the <i>Caenorhabditis elegans</i> intestine

Coordination between cell fate specification and cell cycle control in multicellular organisms is essential to regulate cell numbers in tissues and organs during development, and its failure may lead to oncogenesis. In mammalian cells, as part of a general cell cycle checkpoint mechanism, the F-box protein β-transducin repeat-containing protein (β-TrCP) and the Skp1/Cul1/F-box complex control the periodic cell cycle fluctuations in abundance of the CDC25A and B phosphatases. Here, we find that the Caenorhabditis elegans β-TrCP orthologue LIN-23 regulates a progressive decline of CDC-25.1 abundance over several embryonic cell cycles and specifies cell number of one tissue, the embryonic intestine. The negative regulation of CDC-25.1 abundance by LIN-23 may be developmentally controlled because CDC-25.1 accumulates over time within the developing germline, where LIN-23 is also present. Concurrent with the destabilization of CDC-25.1, LIN-23 displays a spatially dynamic behavior in the embryo, periodically entering a nuclear compartment where CDC-25.1 is abundant

Model for the formation of a microscopic Turing structure: The facetting of Pt(110) during catalytic oxidation of CO

A Monte Carlo simulation of the formation of regular facet patterns during catalytic CO oxidation on Pt(110) has been conducted. The simulation was based on the elementary steps of the surface reaction, the CO-induced 1×1⇄1×2 phase transition, and the enhancement of O2 adsorption at step sites. The model can reproduce the formation of sawtoothlike facet patterns with a spacing of ∼100 to 200 Å. The facets represent a Turing structure caused by the coupling of kinetic instabilities with the mass transport of Pt atoms

Formation of Turing structures in catalytic surface reactions: The facetting of Pt(110) in CO+O₂

The Pt(110) surface facets during the catalytic oxidation of CO, if reaction conditions are adjusted such that the CO‐induced 1×1⇄1×2 phase transition can take place simultaneously. A detailed low‐energy electron diffraction beam profile analysis revealed that regularly spaced (430) and (340) facets are formed with a lateral periodicity of ∼70 lattice units along the [11̄0] direction. This result, together with the observation that the facetted surface is only stable under reaction conditions, indicates a dissipative structure of the Turing type. Such structures, which are stationary but exhibit a periodic variation of the concentration variables in space, have so far almost exclusively been discussed theoretically. The interpretation of the facetted surface as a Turing structure could be confirmed by a Monte Carlo simulation based on the Langmuir Hinshelwood mechanism of catalytic CO oxidation and the CO‐induced 1×1⇄1×2 phase transition