Mechanistic Insights Into Post-translational α-Keto-β-Amino Acid Formation by a Radical S-Adenosyl Methionine Peptide Splicease.

Radical S-adenosyl methionine enzymes catalyze a diverse repertoire of post-translational modifications in protein and peptide substrates. Among these, an exceptional and mechanistically obscure example is the installation of α-keto-β-amino acid residues by formal excision of a tyrosine-derived tyramine unit. The responsible spliceases are key maturases in a widespread family of natural products termed spliceotides that comprise potent protease inhibitors, with the installed β-residues being crucial for bioactivity.

Transportome remodeling of a symbiotic microalga inside a planktonic host.

Metabolic exchange is one of the foundations of symbiotic associations between organisms and is a driving force in evolution. In the ocean, photosymbiosis between heterotrophic hosts and microalgae is powered by photosynthesis and relies on the transfer of organic carbon to the host (e.g.

Reconstructing the last common ancestor of all eukaryotes.

Understanding the origin of eukaryotic cells is one of the most difficult problems in all of biology. A key challenge relevant to the question of eukaryogenesis is reconstructing the gene repertoire of the last eukaryotic common ancestor (LECA). As data sets grow, sketching an accurate genomics-informed picture of early eukaryotic cellular complexity requires provision of analytical resources and a commitment to data sharing.

[Self-help offers for people with severe mental illness: who uses which format?].

Background: Self-help can play an important supplementary role in the treatment of people with severe mental illness; however, little is known about the utilization of the various approaches.

Objective: This study describes the use of various self-help options by patients with severe mental illness and examines potential predictors.

Material And Methods: As part of the observational cross-sectional study on patients with severe mental illness (IMPPETUS, N = 397), trained staff collected sociodemographic, illness-associated and treatment-associated data between March 2019 and September 2019.

A structurally conserved helix enables leader-independent tyramine splicing of proteins.

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are natural products that feature diverse modifications. They show a wide range of biological activities and are therefore of great interest for drug discovery and protein engineering. An unusual modification found in spliceotide RiPPs is the installation of β-amino acid residues with diverse side chains, generated by backbone excision of a tyramine moiety derived from tyrosine.

Targeting CDC42 reduces skeletal degeneration after hematopoietic stem cell transplantation.

Osteopenia and osteoporosis are common long-term complications of the cytotoxic conditioning regimen for hematopoietic stem cell transplantation (HSCT). We examined mesenchymal stem and progenitor cells (MSPCs), which include skeletal progenitors, from mice undergoing HSCT. Such MSPCs showed reduced fibroblastic colony-forming units frequency, increased DNA damage, and enhanced occurrence of cellular senescence, whereas there was a reduced bone volume in animals that underwent HSCT.

[Thyroid nodules as an incidental finding : Value of sonography and scintigraphy in primary diagnostics].

Due to the widespread use of high-resolution sonography, numerous thyroid nodules are diagnosed, often as incidental findings. The challenge lies in evaluating various criteria such as size, shape, and echogenicity to assess the nodules' malignancy risk. Risk stratification systems have been developed to enable systematic assessment as well as to avoid unnecessary medical interventions and malignant findings being overlooked.

Mid-infrared tunable filter based on a femtosecond-written silica volume Bragg grating.

A silica volume Bragg grating (VBG) is used to filter the light of a mid-infrared (mid-IR) supercontinuum laser. The VBG with a 7 µm period was inscribed with 800 nm pulses with a 100 fs duration and the phase-mask technique over a glass thickness of 3 mm. Despite silica's absorption, the VBG allows obtaining a narrowband light source tunable from 2.

Brainstem raphe hypoechogenicity is an independent predictor of post-stroke depression.

Purpose: Post-stroke depression (PSD) is a common complication after stroke and has a substantial effect on the quality of life of patients. Nevertheless, reliable individual prediction of PSD is not possible. As depressive symptoms have been associated with brainstem raphe (BR) hypoechogenicity on transcranial sonography (TCS), we aimed to explore the association of BR hypoechogenicity and the occurrence of PSD.

Diverse patterns of correspondence between protist metabarcodes and protist metagenome-assembled genomes.

Two common approaches to study the composition of environmental protist communities are metabarcoding and metagenomics. Raw metabarcoding data are usually processed into Operational Taxonomic Units (OTUs) or amplicon sequence variants (ASVs) through clustering or denoising approaches, respectively. Analogous approaches are used to assemble metagenomic reads into metagenome-assembled genomes (MAGs).

Novel types of RiPP-modifying enzymes.

Novel discoveries in natural product biosynthesis reveal hidden bioactive compounds and expand our knowledge in enzymology. Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a rapidly growing class of natural products featuring diverse non-canonical amino acids introduced by maturation enzymes as a class-defining characteristic. Underexplored RiPP sources, such as the human microbiome, the oceans, uncultured microorganisms, and plants are rich hunting grounds for novel enzymology.

The evolution of acute stroke care in Germany from 2019 to 2021: analysis of nation-wide administrative datasets.

Background: The treatment of ischemic stroke (IS) has changed considerably in recent years. Particularly the advent of mechanical thrombectomy (MTE) has revolutionized the available treatment options. Most patients in developed countries have access to intravenous thrombolysis (IVT).

Risk stratification of thyroid nodules: Assessing the suitability of ChatGPT for text-based analysis.

Purpose: Accurate risk stratification of thyroid nodules is essential for optimal patient management. This study aimed to assess the suitability of ChatGPT for risk stratification of thyroid nodules using a text-based evaluation.

Methods: A dataset was compiled comprising 50 anonymized clinical reports and associated risk assessments for thyroid nodules.

The protist cultural renaissance.

Protists are key players in the biosphere. Here, we provide a perspective on integrating protist culturing with omics approaches, imaging, and high-throughput single-cell manipulation strategies, concluding with actions required for a successful return of the golden age of protist culturing.

The primacy of temporal dynamics in driving spatial self-organization of soil iron redox patterns.

This study investigates mechanisms that generate regularly spaced iron-rich bands in upland soils. These striking features appear in soils worldwide, but beyond a generalized association with changing redox, their genesis is yet to be explained. Upland soils exhibit significant redox fluctuations driven by rainfall, groundwater changes, or irrigation.

Legacies of Pre-1960s Municipal Waste Incineration in the Pb of City Soils.

A 1937 street map of Durham, North Carolina, located four city-run waste incinerators that we recognized to be sites of contemporary city parks. We obtained city permission to sample three park's soils, developed a sampling design for geospatial mapping of hypothetical incinerator-ash contamination of park soils, and queried online Durham newspapers to understand histories of incinerator operations, ash disposal, and incinerator-to-park conversions. In 2021-2022, seven decades after parks were created, two parks had soil-Pb > 400 mgPb/kg, EPA's threshold for safe soil in play areas.

Software- and TDM-Guided Dosing of Meropenem Promises High Rates of Target Attainment in Critically Ill Patients.

Various studies have reported insufficient beta-lactam concentrations in critically ill patients. The optimal dosing strategy for beta-lactams in critically ill patients, particularly in septic patients, is an ongoing matter of discussion. This retrospective study aimed to evaluate the success of software-guided empiric meropenem dosing (CADDy, Calculator to Approximate Drug-Dosing in Dialysis) with subsequent routine meropenem measurements and expert clinical pharmacological interpretations.

Site-specific bioorthogonal protein labelling by tetrazine ligation using endogenous β-amino acid dienophiles.

The tetrazine ligation is an inverse electron-demand Diels-Alder reaction widely used for bioorthogonal modifications due to its versatility, site specificity and fast reaction kinetics. A major limitation has been the incorporation of dienophiles in biomolecules and organisms, which relies on externally added reagents. Available methods require the incorporation of tetrazine-reactive groups by enzyme-mediated ligations or unnatural amino acid incorporation.

First steps in the development of next-generation chirped volume Bragg gratings by means of fs laser inscription in fused silica.

The first steps towards the development and characterization of next-generation chirped volume Bragg gratings (CVBGs) by means of fs laser inscription were made. Based on the phase mask inscription technique we realized CVBGs in fused silica with a 3 × 3 mm aperture and a length of almost 12 mm with a chirp rate of ∼190 ps/nm around a central wavelength of 1030.5 nm.

Cortical blindness as a sign of delayed post-hypoxic encephalopathy: a case report.

We present a case of a 67-year-old female patient, who presented with acute cortical blindness five days after a successful resuscitation from cardiac arrest. The magnetic resonance tomography revealed a mild FLAIR signal increase of the bilateral occipital cortex. A lumbar puncture revealed considerably elevated tau protein levels, in the presence of normal phospho-tau, as a marker of brain injury, whilst neuron-specific enolase levels were normal.

Regulatory and coding sequences of TRNP1 co-evolve with brain size and cortical folding in mammals.

Brain size and cortical folding have increased and decreased recurrently during mammalian evolution. Identifying genetic elements whose sequence or functional properties co-evolve with these traits can provide unique information on evolutionary and developmental mechanisms. A good candidate for such a comparative approach is , as it controls proliferation of neural progenitors in mice and ferrets.

Taxonomic composition, community structure and molecular novelty of microeukaryotes in a temperate oligomesotrophic lake as revealed by metabarcoding.

Microbial eukaryotes are diverse and ecologically important organisms, yet sampling constraints have hindered the understanding of their distribution and diversity in freshwater ecosystems. Metabarcoding has provided a powerful complement to traditional limnological studies, revealing an unprecedented diversity of protists in freshwater environments. Here, we aim to expand our knowledge of the ecology and diversity of protists in lacustrine ecosystems by targeting the V4 hypervariable region of the 18S rRNA gene in water column, sediment and biofilm samples collected from Sanabria Lake (Spain) and surrounding freshwater ecosystems.