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Zero-valent iron (ZVI) applied to the remediation of contaminated groundwater (GW) in situ, especially using engineered permeable reactive barriers (PRBs), has been proven to be an effective reactive material. However, many of ZVI brands do not represent tailored reagents specifically regarding destroying pollutants in GW. Thus, their reactivity towards certain contaminants in GW may vary significantly in a wide range even with different production batches of the same ZVI brand. This issue has rarely been known and consequently not addressed to a higher extend so far. Therefore, this study implemented extensive, long-term column experiments followed by short-term batch experiments for chlorinated volatile organic compounds (cVOCs) degradation for developing a semi-empirical test methodology to thoroughly resolve this pivotal issue by achieving an improved quality assurance guidance regarding proper field-scale emplacement of different ZVI brands and their production batches. The results showed that during column experiments perchloroethylene (PCE) led to a significant degradation up to a certain period but sulfate-reducing microorganisms enhanced the dehalogenation and led approximately to 100 % PCE removal. However, the efficacy varied for different ZVI brands, i.e., Gotthart Maier (GM) and Sponge Iron (Responge®). Furthermore, it could be shown that it might even vary among different production batches of the same ZVI brand. It was also observed that evolution of sulfate-reducing microorganisms may improve the efficacy of PCE degradation vastly that occur at different intensities with different ZVI brands and their respective production batches over time. Further, comparing comprehensive long-term column (k obs  = 0.0488 1/h) and short-term batch experiments (k obs = 0.07794 1/h) as well as refined kinetic analyses (k obs  = 0.0424 1/h) clearly prove that an appropriate guidance protocol for successful full-scale in situ remediation is required for properly select the right ZVI brand and production batch before it is loaded to a PRB in the field., Competing Interests: Declaration of competing interest The authors declared that they have no known competing financial interests or personal relationships, which seem to affect the work reported in this article. We declare that we have no human participants, human data, or human issues. We do not have any individual person's data in any form. The authors declare no competing interests., (Copyright © 2024. Published by Elsevier Ltd.)

Rare diseases (RDs) are a challenge for medicine due to their heterogeneous clinical manifestations and low prevalence. There is a lack of specific treatments and only a few hundred of the approximately 7,000 RDs have an approved regime. Rapid technological development in genome sequencing enables the mass identification of potential candidates that in their mutated form could trigger diseases but are often not confirmed to be causal. Knockout (KO) mouse models are essential to understand the causality of genes by allowing highly standardized research into the pathogenesis of diseases. The German Mouse Clinic (GMC) is one of the pioneers in mouse research and successfully uses (preclinical) data obtained from single-gene KO mutants for research into monogenic RDs. As part of the International Mouse Phenotyping Consortium (IMPC) and INFRAFRONTIER, the pan-European consortium for modeling human diseases, the GMC expands these preclinical data toward global collaborative approaches with researchers, clinicians, and patient groups.Here, we highlight proprietary genes that when deleted mimic clinical phenotypes associated with known RD targets (Nacc1, Bach2, Klotho alpha). We focus on recognized RD genes with no pre-existing KO mouse models (Kansl1l, Acsf3, Pcdhgb2, Rabgap1, Cox7a2) which highlight novel phenotypes capable of optimizing clinical diagnosis. In addition, we present genes with intriguing phenotypic data (Zdhhc5, Wsb2) that are not presently associated with known human RDs.This report provides comprehensive evidence for genes that when deleted cause differences in the KO mouse across multiple organs, providing a huge translational potential for further understanding monogenic RDs and their clinical spectrum. Genetic KO studies in mice are valuable to further explore the underlying physiological mechanisms and their overall therapeutic potential., (© 2023. The Author(s).)

We study a long standing open problem by Ulam, which is whether the Euclidean ball is the unique body of uniform density which will float in equilibrium in any direction. We answer this problem in the class of origin symmetric n-dimensional convex bodies whose relative density to water is \frac {1}{2}. For n=3, this result is due to Falconer. [ABSTRACT FROM AUTHOR]

The genetic landscape of diseases associated with changes in bone mineral density (BMD), such as osteoporosis, is only partially understood. Here, we explored data from 3,823 mutant mouse strains for BMD, a measure that is frequently altered in a range of bone pathologies, including osteoporosis. A total of 200 genes were found to significantly affect BMD. This pool of BMD genes comprised 141 genes with previously unknown functions in bone biology and was complementary to pools derived from recent human studies. Nineteen of the 141 genes also caused skeletal abnormalities. Examination of the BMD genes in osteoclasts and osteoblasts underscored BMD pathways, including vesicle transport, in these cells and together with in silico bone turnover studies resulted in the prioritization of candidate genes for further investigation. Overall, the results add novel pathophysiological and molecular insight into bone health and disease., Competing Interests: The authors have declared that no competing interests exist.

Electron spin plays a critical role in chemical processes, particularly in reactions involving metal complexes with unpaired electrons. However, more definitive state-to-state experiments are needed to better elucidate the role of electronic spin. Herein, we chose nickel (II) 5,10,15,20-tetrakis(pentafluorophenyl) porphyrin 1 as a catalyst, which allows switching from a low spin to a high spin state of Ni (II) center through an axial pyridine coordination, for electrocatalytic hydrogen evolution reaction (HER). When pyridine is present, we observed β-hydrogenation of porphyrin through electron transfer followed by proton transfer. In contrast, hydrogen evolution mainly occurs via the concerted proton-coupling electron transfer without pyridine coordination. Similar distinct spin-dependent selectivity was also observed in chemical reduction of 1 by CoCp 2 with subsequent addition of pyridinium p-toluenesulfonate. Computational calculations using density functional theory demonstrated that the transition from low spin to high spin state enriches the ligand's electron density after one-electron reduction, leading to preferential protonation of β-periphery rather than meso-position or metal center., (© 2024 Wiley-VCH GmbH.)

Extensive use of quantum chemical calculations has been made to rationally design a molecule whose spin state can be switched reversibly using light of two different wavelengths at room temperature in solution. Spin change is induced by changing the coordination number of a nickel complex. The coordination number in turn is switched using a photochromic ligand that binds in one configuration and dissociates in the other. We demonstrate that successful design relies on a precise geometry fit and delicate electronic tuning. Our designer complex exhibits an extremely high long-term switching stability (more than 20000 cycles) and a high switching efficiency. The high-spin state is extraordinarily stable with a half-life of 400 days at room temperature. Switching between the dia- and paramagnetic state is achieved with visible light (500 and 430 nm). The compound can also be used as a molecular logic gate with light and pH as input and the magnetic state as non-destructive read-out. [ABSTRACT FROM AUTHOR]

Antibiotic resistance has emerged as a global public health crisis in the 21 st century, leading to treatment failures. To address this issue, the medical and pharmaceutical sectors are confronted with two challenges: i) finding potent new antimicrobial agents that would work against resistant-pathogens, and ii) developing conceptually new or unconventional strategies by which a particular antibiotic would remain effective persistently. Photopharmacology with the aid of reversibly controllable light-active antibiotics that we call "photoantibiotics" shows great promise to meet the second challenge, which has inspired many research laboratories worldwide to align their research in inventing or developing such antibiotics. In this review, we have given an overview of the progress made over the last ten years or so towards developing such photoantibiotics. Although making such antibiotics that hold high antimicrobial potency like the native drugs and subsequently maintain a significant activity difference between light-irradiated and non-irradiated states is very challenging, the progress being reported here demonstrates the feasibility of various approaches to engineer photoantibiotics. This review provides a future perspective on the use of such antibiotics in clinical practice with the identification of potential problems and their solutions., (© 2024 Wiley-VCH GmbH.)

Metabolic diseases are a worldwide problem but the underlying genetic factors and their relevance to metabolic disease remain incompletely understood. Genome-wide research is needed to characterize so-far unannotated mammalian metabolic genes. Here, we generate and analyze metabolic phenotypic data of 2016 knockout mouse strains under the aegis of the International Mouse Phenotyping Consortium (IMPC) and find 974 gene knockouts with strong metabolic phenotypes. 429 of those had no previous link to metabolism and 51 genes remain functionally completely unannotated. We compared human orthologues of these uncharacterized genes in five GWAS consortia and indeed 23 candidate genes are associated with metabolic disease. We further identify common regulatory elements in promoters of candidate genes. As each regulatory element is composed of several transcription factor binding sites, our data reveal an extensive metabolic phenotype-associated network of co-regulated genes. Our systematic mouse phenotype analysis thus paves the way for full functional annotation of the genome.

An invading pathogen must be held in check by the innate immune system until a specific immune response can be mounted. In the case of Gram-negative bacteria, the principal stimulator is LPS, a component of the outer membrane of the bacteria. In vitro LPS is bound by LBP and transferred to the LPS receptor CD14 on the macrophage surface. Binding to CD14 triggers an inflammatory response which is crucial for keeping an infection under control. In vitro, LBP mediates a response not only to LPS but also to intact Gram-negative bacteria. We show that whole Escherichia coli bacteria are recognised by CD14 on human monocytes, and subsequently may become phagocytosed. Although neither LBP nor CD14 interact with the heat inactivated, intact Gram-positive bacterium Bacillus subtilis both proteins form stable complexes with lipoteichoic acid derived from the bacterial cell wall. A brief exposure of B. subtilis to serum or antibiotics converts them into a form which can be recognised by CD14 in an LBP-dependent manner followed by phagocytosis. In preliminary experiments, it is shown that LBP is essential in vitro for the oxidative burst response of mouse macrophages induced by living Salmonella typhimurium as well as Staphylococcus epidermidis. Our results indicate that, in addition to CD14, LBP is also a pattern recognition element and is required to induce a rapid inflammatory response to Gram-negative as well as to Gram-positive bacteria and to initiate their phagocytosis. [ABSTRACT FROM PUBLISHER]