Ludwig-Maximilians-Universität München
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On the Further Development of Silver Nitrotetrazolate for Practical Use as a Primary Explosive
Get PDFSilver nitrotetrazolate (AgNT) is a less-known but very powerful primary explosive with fast deflagration-to-detonation transition (DDT). Unfortunately, the compound never found any practical application due to its undesirable powder properties paired with a very high sensitivity toward mechanical stimuli. The adaption of conditions similar to those used in the Costain process resulted in precipitation of a new compound AgNT·¼NH3, incorporating 0.25 eq. ammonia, proven by single crystal x-ray diffraction and elemental analysis. This compound has been characterized and optimized for use as a primary explosive and shows greatly enhanced properties over common silver nitrotetrazolate
Single-cell transcriptome-wide Mendelian randomization and colocalization analyses uncover cell-specific mechanisms in atherosclerotic cardiovascular disease
Get PDFGenome-wide association studies (GWASs) have identified numerous genetic loci influencing human disease risk; however, linking these to causal genes remains challenging, limiting opportunities for drug target discovery. Transcriptome-wide association studies (TWASs) address this by linking variants to gene expression but typically rely on bulk RNA sequencing, limiting cell-specific resolution. Here, we present a single-cell TWAS pipeline combining cis-Mendelian randomization (MR) with colocalization analyses at the single-cell level. As a case study, we examined how genetically proxied gene expression in immune cells influences atherosclerotic cardiovascular disease (ASCVD) risk. We integrated single-cell expression quantitative trait loci (sc-eQTLs) for 14 immune cell types with GWASs for coronary artery disease, large artery atherosclerotic stroke, and peripheral artery disease. sc-cis-MR revealed 440 gene-outcome associations across cell types, 88% of which were missed by bulk TWASs, despite the considerably smaller sample size of the sc-eQTL dataset. Of these associations, 21 were replicated with external cis-eQTLs and colocalized with ASCVD GWAS signals. Expanding on previous evidence linking genetically proxied LIPA expression in whole blood to coronary artery disease, we found genetic variants influencing LIPA expression, particularly in monocytes, to drive associations with coronary artery disease, large artery atherosclerotic stroke, and subclinical atherosclerosis traits. A phenome-wide association study confirmed these findings without evidence of associations with unexpected clinical outcomes. scRNA sequencing and immunohistochemistry of human carotid plaques revealed high LIPA expression in plaque macrophages. Our pipeline enables the discovery of cell-specific expression patterns that drive genetic predisposition to human disease, potentially impacting target selection for cell-tailored therapeutics
Evaluation of spinal deformity and its progression in pyogenic spondylodiscitis: A retrospective MRI study of 59 cases
Get PDFIntroduction
Pyogenic spondylodiscitis management often remains conservative without surgical intervention, yet the risk of spinal deformity under such therapy is unclear.
Research question
This study explores spinal deformity progression in conservatively treated patients and identifies predictive factors for deformity advancement.
Material and methods
Retrospective cohort design with radiological data analysis from 59 patients with conservatively treated pyogenic spondylodiscitis. Deformities were categorized into four progression types reflecting severity: Type 1 (progressive vertebral body edema/endplate erosion), Type 2 (Type 1 plus disc space collapse), Type 3 (vertebral body destruction/mild translation), and Type 4 (significant segmental kyphosis >20°/severe translation).
Results
Among 59 patients, 66% exhibited progressive deformity over a mean follow-up of 10.75 months. The distribution of deformity progression was: Type 1 in two cases (3%), Type 2 in seven cases (12%), Type 3 in 13 cases (22%), and Type 4 in 17 cases (29%). Progression of deformity included a 92% increase in cases with segmental kyphosis >20°; and a 167% increase in cases with segmental translation. Risk factors for significant kyphosis included >50% vertebral body erosive destruction (p < 0.01) and the presence of an epidural abscess (p < 0.05). Lumbar region involvement significantly reduced the likelihood of spinal fusion at follow-up (p < 0.05). A paravertebral abscess was significantly associated with the presence of a fractured vertebrae at follow-up (p < 0.05).
Discussion and conclusion
This study underscores the importance of closely monitoring patients with conservatively managed pyogenic spondylodiscitis for progressive spinal deformity, and suggests considering early surgical intervention in cases with a high risk of progression
Late Neo-Elamite Kingdoms, the Rise of Cyrus the Great, the Fall of Babylon and the End of the Babylonian Captivity
Get PDFDefect Imide Double Antiperovskites AE5AsPn(NH)2 (AE=Ca, Sr; Pn=Sb, Bi) as Potential Solar Cell Absorber Materials
Get PDFAn abundance of oxide, halide and chalcogenide perovskites have been explored, demonstrating outstanding properties, while the emerging nitride perovskites are extremely rare due to their challenging synthesis requirements. By inverting the ion type in the perovskite structure, the corresponding antiperovskite structure is obtained. Among them, ternary antiperovskite nitrides X3AN (X=Ba, Sr, Ca, Mg; A=As, Sb) have recently been identified as exhibiting excellent optoelectronic properties. To explore the unrealized composition space of nitride perovskites, the ammonothermal method was applied, yielding three new layered quaternary imide-based defect-antiperovskites, namely AE5AsPn(NH)2 (AE=Ca, Sr; Pn=Sb, Bi). These new compounds feature distorted square-pyramidal coordination around the imide-group (Ca5NH). Layers with Ca2+ vacancies are found with an alternating As3− and Pn3− (Pn3−=Sb3−, Bi3−) coordination along the A-site, forming a two-dimensional (2D) structure. All three AE5AsPn(NH)2 compounds show suitable direct band gaps within the visible light spectrum. Density functional theory calculations reveal favorable band dispersion, as well as transport and optical properties, especially along the out-of-plane direction, demonstrating their 3D character of electronic transport. The narrow tunable direct band gaps and favorable charge carrier properties make AE5AsPn(NH)2 promising candidates for solar cell absorber materials
Histological evidence of myxomatous tissue in a Labrador puppy with pulmonic stenosis and tricuspid valve dysplasia
Get PDFA six-week-old Labrador retriever was presented for lethargy and anorexia, revealing a systolic heart murmur. Tricuspid valve dysplasia involving the whole tricuspid valve apparatus and the right ventricular wall was found, and an additional pulmonic stenosis was present. Histopathological examination of the tricuspid and pulmonary leaflets highlighted an unusual myxomatous mesenchymal component, interpreted as being of ontogenetic origin
Recovery from Pediatric Inflammatory Multisystem Syndrome Temporally-Associated with SARS-CoV-2: Follow-Up from a Nationwide German Cohort
No full textObjective
To investigate the intermediate-term health impacts of pediatric inflammatory multisystem syndrome temporally-associated with SARS-CoV-2 (PIMS-TS).
Study design
Using a standardized questionnaire in a multicenter study, follow-up data from acute PIMS-TS patients were collected, including detailed information on patient characteristics, clinical progression, laboratory findings, imaging results, and outcomes. These follow-up data were then linked to data from the patients' acute-phase PIMS disease, as recorded in the German (and Innsbruck, Austria) PIMS-TS registry.
Results
Of the 920 cases originally documented in the acute-phase PIMS-TS registry, follow-up data were collected from 6 pediatric centers on 127 patients; 81 patients were male. Mean age during the acute phase was 8 years (SD: 4.4 years). Median follow-up time was 125 days (IQR: 50.5 to 290.5 days). Overall, a majority of patients achieved full recovery, with 81/127 doing so even before their first follow-up visit. However, abnormal echocardiographic findings continued in 18/67 patients. Coronary dilatation persisted in 14/33 (42%) and resolved in all but 3. Residual cardiovascular and general symptoms were more frequent in older children, as well as among those who had required intensive care unit treatment during the acute phase.
Conclusion
Our findings confirm the generally favorable intermediate-term outcome in patients with PIMS-TS. However, a subset of patients in our cohort, particularly older children and those requiring intensive care unit care during the acute phase, experienced prolonged symptoms, especially cardiovascular complications. Close follow-up and multidisciplinary care are recommended in order to monitor these patients' recovery
Quantification of Propargylated RNA Nucleosides After Metabolic Labeling Via the Methylation Pathway
No full textRNA modifications are involved in numerous biological processes and vary in different cell types. Methylation is the most widespread type of RNA modification and occurs via S-adenosyl-L-methionine (SAM). We recently developed a metabolic labeling approach based on intracellular formation of a clickable SAM analog (SeAdoYn) and demonstrated its use in mapping methyltransferase (MTase) target sites in mRNA from HeLa cells. Here we investigate how metabolic labeling via the clickable SAM analog modifies four different nucleosides in RNA of HEK293T in comparison to HeLa cells. We find that HEK293T cells retain higher cell viability upon feeding the clickable metabolic SAM precursor. In poly(A)+ RNA we find high Aprop/A levels (0.04 %) and in total RNA (but not poly(A)+ RNA) we detect prop3C, which had not been detected previously in HeLa cells. We discuss the findings in the context of data from the literature with respect to mRNA half-lives in cancer and non-cancer cell lines and suggest that CMTr2 is most likely responsible for the high Aprop level in poly(A)+ RNA