Evidence for intrinsic DNA dynamics and deformability in damage sensing by the Rad4/XPC nucleotide excision repair complex.

Altered DNA dynamics at lesion sites are implicated in how DNA repair proteins sense damage within genomic DNA. Using laser temperature-jump (T-jump) spectroscopy combined with cytosine-analog Förster Resonance Energy Transfer (FRET) probes that sense local DNA conformations, we measured the intrinsic dynamics of DNA containing 3 base-pair mismatches recognized in vitro by Rad4 (yeast ortholog of XPC). Rad4/XPC recognizes diverse lesions from environmental mutagens and initiates nucleotide excision repair.

Detection and phylogenetic analysis of blood-associated pathogens from spleen samples of wild raccoons (Procyon lotor) in Germany.

Raccoons (Procyon lotor) originated in North America and have been introduced to Europe. Due to their close contact with human settlements, they are important reservoirs for zoonotic pathogens, such as Baylisascaris procyonis. The relevance and prevalence of vector-borne pathogens have not yet been fully elucidated.

Concanavalin A Delivers a Photoactive Protein to the Bacterial Wall.

Modular supramolecular complexes, where different proteins are assembled to gather targeting capability and photofunctional properties within the same structures, are of special interest for bacterial photodynamic inactivation, given their inherent biocompatibility and flexibility. We have recently proposed one such structure, exploiting the tetrameric bacterial protein streptavidin as the main building block, to target protein A. To expand the palette of targets, we have linked biotinylated Concanavalin A, a sugar-binding protein, to a methylene blue-labelled streptavidin.

Combining low-cost electronic structure theory and low-cost parallel computing architecture.

The computational efficiency of low-cost electronic structure methods can be further improved by leveraging heterogenous computing architectures. The software package TeraChem has been developed since 2008 to make use of graphical processing units (GPUs), particularly their strong single-precision performance, for the acceleration of quantum chemical calculations. Here, we present the implementation of three low-cost methods, namely HF-3c, PBEh-3c, and the recently introduced ωB97X-3c.

Prevalence of Antibodies and Risk Factors in Two Sympatric Invasive Carnivores ( and ) from Zgorzelec County, Poland.

The intracellular protozoan is distributed worldwide and infects many species of warm-blooded animals. Most mammals, including humans, can serve as intermediate hosts. This pathogen, with its zoonotic potential, causes toxoplasmosis, a condition that can range from subclinical to fatal in humans.

CREST-A program for the exploration of low-energy molecular chemical space.

Conformer-rotamer sampling tool (CREST) is an open-source program for the efficient and automated exploration of molecular chemical space. Originally developed in Pracht et al. [Phys.

Prevalence of in Wild American Mink (): The First Serological Study in Germany and Poland.

is an obligate intracellular protozoan that causes toxoplasmosis in warm-blooded animals. Although most infections in humans and animals are subclinical, an infection can nevertheless be fatal. One of the important characteristics in the epidemiology of this parasite is waterborne transmission.

Diaryltriazolium Photoswitch: Reaching a Millisecond Cycloreversion with High Stability and NIR Absorption.

The exceptional thermal stability of diarylethene closed isomers enabled many applications but also prevented utilization in photochromic systems that require rapid thermal reversibility. Herein, we report the diaryltriazolium (DAT ) photoswitch undergoing thermal cycloreversion within a few milliseconds and absorption of the closed form in the near-infrared region above 900 nm. Click chemistry followed by alkylation offers modular and fast access to the electron-deficient DAT scaffold.

Providing AI expertise as an infrastructure in academia.

Artificial intelligence (AI) is proliferating and developing faster than any domain scientist can adapt. To support the scientific enterprise in the Helmholtz association, a network of AI specialists has been set up to disseminate AI expertise as an infrastructure among domain scientists. As this effort exposes an evolutionary step in science organization in Germany, this article aspires to describe our setup, goals, and motivations.

Bi-allelic SNAPC4 variants dysregulate global alternative splicing and lead to neuroregression and progressive spastic paraparesis.

The vast majority of human genes encode multiple isoforms through alternative splicing, and the temporal and spatial regulation of those isoforms is critical for organismal development and function. The spliceosome, which regulates and executes splicing reactions, is primarily composed of small nuclear ribonucleoproteins (snRNPs) that consist of small nuclear RNAs (snRNAs) and protein subunits. snRNA gene transcription is initiated by the snRNA-activating protein complex (SNAPc).

CD47 restricts antiviral function of alveolar macrophages during influenza virus infection.

CD47 is an ubiquitously expressed surface molecule with significant impact on immune responses. However, its role for antiviral immunity is not fully understood. Here, we revealed that the expression of CD47 on immune cells seemed to disturb the antiviral immune response as CD47-deficient mice (CD47) showed an augmented clearance of influenza A virus (IAV).

First detection and low prevalence of spp. in wild raccoons () from Central Europe.

The urinary bladder and lower urinary tract of domestic and wild carnivores can be parasitised by filamentous nematodes from the genus (syn. ). Infestations are often asymptomatic, but severe courses in dogs and cats have been described.

Molecular analysis of blood-associated pathogens in European wildcats () from Germany.

European wildcats () have not been investigated in large numbers for blood-associated pathogens in Germany, because wildcats, being a protected species, may not be hunted, and the collection of samples is therefore difficult. Thus, spleen tissue and whole blood from 96 wildcats from Germany found as roadkill or dead from other causes in the years 1998-2020 were examined for the prevalence of blood associated pathogens using molecular genetic tools. PCR was used to screen for haemotrophic spp.

Recommendations on compiling test datasets for evaluating artificial intelligence solutions in pathology.

Artificial intelligence (AI) solutions that automatically extract information from digital histology images have shown great promise for improving pathological diagnosis. Prior to routine use, it is important to evaluate their predictive performance and obtain regulatory approval. This assessment requires appropriate test datasets.

Newly identified disorder of copper metabolism caused by variants in CTR1, a high-affinity copper transporter.

The high-affinity copper transporter CTR1 is encoded by CTR1 (SLC31A1), a gene locus for which no detailed genotype-phenotype correlations have previously been reported. We describe identical twin male infants homozygous for a novel missense variant NM_001859.4:c.

Interactions of cranial helminths in the European polecat (): Implications for host body condition.

Multiple helminth species commonly co-occur within mammals and their interactions may negatively affect the survival and breeding success of their hosts. However, it has been difficult to prove competition or mutualism between co-infesting helminths in field studies of wild mammals. The sinus cavities of European polecats () can be parasitised by the trematode and the nematode and both helminths can co-occur within hosts.

Photochemical Deracemization of Chiral Alkenes via Triplet Energy Transfer.

A visible-light-mediated, enantioselective approach to axially chiral alkenes is described. Starting from a racemic mixture, a major alkene enantiomer is formed due to selective triplet energy transfer from a catalytically active chiral sensitizer. A catalyst loading of 2 mol % was sufficient to guarantee consistently high enantioselectivities and yields (16 examples, 51%-quant.

Modulation of free energy landscapes as a strategy for the design of antimicrobial peptides.

Computational design of antimicrobial peptides (AMPs) is a promising area of research for developing novel agents against drug-resistant bacteria. AMPs are present naturally in many organisms, from bacteria to humans, a time-tested mechanism that makes them attractive as effective antibiotics. Depending on the environment, AMPs can exhibit α-helical or β-sheet conformations, a mix of both, or lack secondary structure; they can be linear or cyclic.

Cycloadditions of Donor-Acceptor Cyclopropanes and -butanes using S=N-Containing Reagents: Access to Cyclic Sulfinamides, Sulfonamides, and Sulfinamidines.

We present (3+2)- and (4+2)-cycloadditions of donor-acceptor (D-A) cyclopropanes and cyclobutanes with N-sulfinylamines and a sulfur diimide, along with a one-pot, two-step strategy for the formal insertion of HNSO into D-A cyclopropanes. These are rare examples of cycloadditions with D-A cyclopropanes and cyclobutanes whereby the 2π component consists of two different heteroatoms, thus leading to five- and six-membered rings containing adjacent heteroatoms.

First record of Troglotrema acutum (Trematoda, Troglotrematidae) in European polecats Mustela putorius from Luxembourg.

We report the first record of the trematode Troglotrema acutum in skulls of European polecats (Mustela putorius) from Luxembourg. Thirty-one road-killed polecats from the northern and eastern parts of the country were examined. We found the trematode in three polecats from the administrative districts of Clervaux and Vianden in the northeast of the country.

A Combination of Anti-PD-L1 Treatment and Therapeutic Vaccination Facilitates Improved Retroviral Clearance via Reactivation of Highly Exhausted T Cells.

PD-1-targeted therapies have shown modest antiviral effects in preclinical models of chronic viral infection. Thus, novel therapy protocols are necessary to enhance T cell immunity and viral control to overcome T cell dysfunction and immunosuppression. Here, we demonstrate that nanoparticle-based therapeutic vaccination improved PD-1-targeted therapy during chronic infection with Friend retrovirus (FV).