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Abstract Argonaute proteins are the central effectors of RNA-guided RNA silencing pathways in eukaryotes, playing crucial roles in gene repression and defense against viruses and transposons. Eukaryotic Argonautes are subdivided into two clades: AGOs generally facilitate miRNA- or siRNA-mediated silencing, while PIWIs generally facilitate piRNA-mediated silencing. It is currently unclear when and how Argonaute-based RNA silencing mechanisms arose and diverged during the emergence and early evolution of eukaryotes. Here, we show that in Asgard archaea, the closest prokaryotic relatives of eukaryotes, an evolutionary expansion of Argonaute proteins took place. In particular, a deep-branching PIWI protein (HrAgo1) encoded by the genome of the Lokiarchaeon ‘Candidatus Harpocratesius repetitus’ shares a common origin with eukaryotic PIWI proteins. Contrasting known prokaryotic Argonautes that use single-stranded DNA as guides and/or targets, HrAgo1 mediates RNA-guided RNA cleavage, and facilitates gene silencing when expressed in human cells and supplied with miRNA precursors. A cryo-EM structure of HrAgo1, combined with quantitative single-molecule experiments, reveals that the protein displays structural features and target-binding modes that are a mix of those of eukaryotic AGO and PIWI proteins. Thus, this deep-branching archaeal PIWI may have retained an ancestral molecular architecture that preceded the functional and mechanistic divergence of eukaryotic AGOs and PIWIs.

La lucha contra el olvido después de la Guerra Civil en El Salvador (1980-1992) resalta la urgencia de apoyar el trabajo de los archivos de memoria histórica. Este artículo examina el papel fundamental desempeñado por la Mediateca del Centro Arte para la Paz (CAP), ubicado en Suchitoto, El Salvador, como un espacio abierto de consulta de información digital, dedicado a la preservación y accesibilidad de archivos relacionados con la Memoria Histórica. Este centro se presenta como custodio de valiosos documentos, propios y donados, los cuales abarcan desde el patrimonio cultural e histórico institucional hasta contribuciones de terceros con derechos de autor. Posicionamos el trabajo del CAP dentro de un marco de archivos comunitarios, prácticas informadas sobre el trauma y justicia transicional.

Introduction: Approximately 20%-45% of familial melanoma (FM) cases are associated with genetic predisposition. Objectives: This single-center retrospective study aimed to assess the frequency of pathogenic variants (PV) in the main melanoma-predisposing genes in patients with cutaneous melanoma and investigate the clinical predictors of genetic predisposition. Methods: Patients included were those diagnosed with cutaneous melanoma at the Dermatology Unit of the University Hospital, Verona, Italy, from 2000 to 2022, presenting at least one of the following: multiple melanomas (≥3); personal/family history of pancreatic cancer (PC) (up to second-degree relatives); ≥2 first-degree relatives with melanoma; ≥1 first-degree relatives with early onset (

Abstract Suspect screening and untargeted analysis using UHPLC-qToF are two advanced analytical approaches now used to achieve an extensive chemical profile of samples, which are then typically confirmed through targeted analysis. These techniques can detect a large number of chemical features simultaneously and are currently being introduced into the study of contaminants of emerging concern (CECs) and into the study of the extent of human chemical exposure (the exposome). Here is described the use of these techniques to characterize chemical mixtures derived from the OECD 301F ready biodegradability test (RBT) of a chemical and natural formulation currently used to treat reflux disease and functional dyspepsia. Untargeted analysis clearly evidenced a different behavior between formulations containing only natural products with respect to that containing synthetic and non-naturally occurring substances. Suspect screening analysis improved the untargeted analysis of the omeprazole-based medicine, leading to the tentative identification of a number of omeprazole-derived transformation products, thereby enabling their preliminary quali-quantitative evaluation. Targeted analysis was then performed to confirm the preliminary data gained from the suspect screening approach. The validation of the analytical method for the quantitative determination of omeprazole and its major metabolite, omeprazole sulphide, has provided robust data to evaluate the behavior of omeprazole during the OECD 301F test. Using advanced analytical approaches, the RBT performed on the two products under investigation confirmed that omeprazole is not readily biodegradable, while the medical device made of natural substances has proven to be readily biodegradable.

In hypothyroid patients needing large doses of levothyroxine (L-T4) (>1.7–2 μg/kg/day) to reach euthyroidism, lactose intolerance (LI) needs to be excluded, owing to the high prevalence in the population. If LI is present, a lactose-free diet decreases the rate of L-T4 malabsorption. However, an increased requirement of L-T4 is described in patients with LI, which can be beneficially treated using lactose-free L-T4 formulation. The lactose-free liquid L-T4 formulation is able to circumvent LI malabsorption leading to the normalization of thyroid-stimulating hormone (TSH) in patients with subclinical hypothyroidism and long-term stable TSH levels.

Intentionally preserved biological material in natural history collections represents a vast repository of biodiversity. Advances in laboratory and sequencing technologies have made these specimens increasingly accessible for genomic analyses, offering a window into the genetic past of species and often permitting access to information that can no longer be sampled in the wild. Due to their age, preparation and storage conditions, DNA retrieved from museum and herbarium specimens is often poor in yield, heavily fragmented and biochemically modified. This not only poses methodological challenges in recovering nucleotide sequences, but also makes such investigations susceptible to environmental and laboratory contamination. In this paper, we review the practical challenges associated with making the recovery of DNA sequence data from museum collections more routine. We first review key operational principles and issues to address, to guide the decision-making process and dialogue between researchers and curators about when and how to sample museum specimens for genomic analyses. We then outline the range of steps that can be taken to reduce the likelihood of contamination including laboratory set-ups, workflows and working practices. We finish by presenting a series of case studies, each focusing on protocol practicalities for the application of different mainstream methodologies to museum specimens including: (i) shotgun sequencing of insect mitogenomes, (ii) whole genome sequencing of insects, (iii) genome skimming to recover plant plastid genomes from herbarium specimens, (iv) target capture of multi-locus nuclear sequences from herbarium specimens, (v) RAD-sequencing of bird specimens and (vi) shotgun sequencing of ancient bovid bone samples.

The approach to ensure food safety (FS) has evolved, including the concept of FS culture, which has been shaped by both the legislation and the scientific literature. In this study, two companies that produce foods associated with potential risks of cross-contamination (gluten-free foods and frozen pastry, respectively) and are certified according to international voluntary FS standards, such as the British Retail Council Global Standard (BRC) and the International Featured Standards Food Version (IFS), were investigated to assess: (a) if the assessment of FS culture’s pillars can uncover unexpected critical areas; (b) if the scores of the FS culture’s pillars are related to personal traits, namely, age, seniority in the company and locus of control orientation, i.e., the beliefs that an event is the result of external factors (luck, destiny or superior beings), or the result of internal factors (human behavior). Questionnaires for the survey and the scoring system applied were selected from the literature. Results showed that all food handlers had an optimistic bias, which paradoxically could be the consequence of the rigorous application of hygienic procedures. The younger food handlers had significantly (p < 0.05) lower commitment than the older ones. Moreover, the segment of food handlers having an external locus orientation demonstrated weaker normative beliefs than those having an internal locus of control orientation. Results showed that the FS culture survey, which is related to the shared FS culture, could disclose unknown weakness in third-party certified companies, even if the well implemented principles of voluntary FS standards are aligned with the FS-culture pillars. Moreover, the segmentation of food handlers according to their age and the locus of control assessment could provide additional information on the individual orientation toward FS behavior. Hence these tools could assist the leaders in the management of the dynamic nature of human capital.

Fiber-reinforced elastomeric isolators (FREIs) are composite devices consisting of an alternation of elastomer layers and fiber reinforcement layers. They have mechanical properties comparable to those of conventional Steel-Reinforced Elastomeric Isolators (SREIs). The mechanical and construction characteristics of FREIs, together with their lower cost, make them potentially usable on a large scale. However, for their actual use, it is necessary to take into account the current regulations regarding seismic isolation. The application of FREIs provides the absence of anchoring to the structure, but the European Technical Standard UNI EN 15129 requires that the isolators are attached to the structure by mechanical fastening only. In this research work, a constraint device that fulfills this requirement but, at the same time, does not significantly alter the mechanical behavior of FREIs is investigated. The properties of the selected device and its installation method are presented. The results of both a simple compression test and a combined compression and shear test performed on two isolators reinforced by quadri-directional carbon fiber fabrics and two isolators reinforced by bi-directional fabrics are presented. The tests were performed in the absence and presence of the constraint device in order to investigate the modifications produced by the device.

Abstract Hematite is a common iron oxide found in nature, and the α‐Fe2O3(0001) plane is prevalent on the nanomaterial utilized in photo‐ and electrocatalytic applications. The atomic‐scale structure of the surface remains controversial despite decades of study, partly because it depends on sample history as well as the preparation conditions. Here, a comprehensive study is performed using an arsenal of surface techniques (non‐contact atomic force microscopy, scanning tunneling microscopy, low‐energy electron diffraction, and X‐ray photoemission spectroscopy) complemented by analyses of the near surface region by high‐resolution transmission electron microscopy and electron energy loss spectroscopy. The results show that the so‐called “bi‐phase” termination forms even under highly oxidizing conditions; a (1 × 1) surface is only observed in the presence of impurities. Furthermore, it is shown that the biphase is actually a continuous layer distorted due to a mismatch with the subsurface layers, and thus not the proposed mixture of FeO(111) and α‐Fe2O3(0001) phases. Overall, the results show how combining surface and cross‐sectional imaging provides a full view that can be essential for understanding the role of the near‐surface region on oxide surface properties.

Mica is a naturally occurring 2D mineral that has been heavily studied in many diverse areas. Here authors present atomic force microscopy images to study the mica surface in ultra-high vacuum conditions; they unveil the distribution of its surface K+ ions and give insights into the distribution of subsurface Al3+ ions.

Summary: Proton-dependent oligopeptide transporters (POTs) are promiscuous transporters of the major facilitator superfamily that constitute the main route of entry for a wide range of dietary peptides and orally administrated peptidomimetic drugs. Given their clinical and pathophysiological relevance, several POT homologs have been studied extensively at the structural and molecular level. However, the molecular basis of recognition and transport of diverse peptide substrates has remained elusive. We present 14 X-ray structures of the bacterial POT DtpB in complex with chemically diverse di- and tripeptides, providing novel insights into the plasticity of the conserved central binding cavity. We analyzed binding affinities for more than 80 peptides and monitored uptake by a fluorescence-based transport assay. To probe whether all 8400 natural di- and tripeptides can bind to DtpB, we employed state-of-the-art molecular docking and machine learning and conclude that peptides with compact hydrophobic residues are the best DtpB binders.

Abstract Recent technological advances in long‐read high‐throughput sequencing and assembly methods have facilitated the generation of annotated chromosome‐scale whole‐genome sequence data for evolutionary studies; however, generating such data can still be difficult for many plant species. For example, obtaining high‐molecular‐weight DNA is typically impossible for samples in historical herbarium collections, which often have degraded DNA. The need to fast‐freeze newly collected living samples to conserve high‐quality DNA can be complicated when plants are only found in remote areas. Therefore, short‐read reduced‐genome representations, such as target capture and genome skimming, remain important for evolutionary studies. Here, we review the pros and cons of each technique for non‐model plant taxa. We provide guidance related to logistics, budget, the genomic resources previously available for the target clade, and the nature of the study. Furthermore, we assess the available bioinformatic analyses, detailing best practices and pitfalls, and suggest pathways to combine newly generated data with legacy data. Finally, we explore the possible downstream analyses allowed by the type of data generated using each technique. We provide a practical guide to help researchers make the best‐informed choice regarding reduced genome representation for evolutionary studies of non‐model plants in cases where whole‐genome sequencing remains impractical.

IntroductionIn the study of therapeutic strategies for the treatment of cancer, eco-evolutionary dynamics are of particular interest, since characteristics of the tumor population, interaction with the environment and effects of the treatment, influence the geometric and epigenetic characterization of the tumor with direct consequences on the efficacy of the therapy and possible relapses. In particular, when considering radiotherapy, oxygen concentration plays a central role both in determining the effectiveness of the treatment and the selective pressure due to hypoxia.MethodsWe propose a mathematical model, settled in the framework of epigenetically structured population dynamics and formulated in terms of systems of coupled non-linear integro-differential equations that aims to catch these phenomena and to provide a predictive tool for the tumor mass evolution and therapeutic effects.ResultsThe outcomes of the simulations show how the model is able to explain the impact of environmental selection and therapies on the evolution of the mass, motivating observed dynamics such as relapses and therapeutic failures.DiscussionThis novel modeling framework, together with the experimental results obtained so far, offers a first hint for the development of therapies which can be adapted to overcome problems of resistance and relapses. Further studies, based on a quantification of medical data, could include the development of a mathematical tool for medical support in optimizing therapeutic protocols.