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- 2020 (42) (remove)
Keywords
- Inborn error of metabolism (3)
- Organic aciduria (3)
- Crystallinity (2)
- Ketone body (2)
- Metabolic acidosis (2)
- cytokine-induced killer cells (2)
- ACAT1 (1)
- ADP release (1)
- ASIC (1)
- Abies nordmanniana (1)
Multiwalled carbon nanotubes (MWCNTs) were easily and efficiently functionalised with highly cross-linked polyamines. The radical polymerisation of two bis-vinylimidazolium salts in the presence of pristine MWCNTs and azobisisobutyronitrile (AIBN) as a radical initiator led to the formation of materials with a high functionalisation degree. The subsequent treatment with sodium borohydride gave rise to the reduction of imidazolium moieties with the concomitant formation of secondary and tertiary amino groups. The obtained materials were characterised by thermogravimetric analysis (TGA), elemental analysis, solid state 13C-NMR, Fourier-transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), potentiometric titration, and temperature programmed desorption of carbon dioxide (CO2-TPD). One of the prepared materials was tested as a heterogeneous base catalyst in C–C bond forming reactions such as the Knoevenagel condensation and Henry reaction. Furthermore, two examples concerning a sequential one-pot approach involving two consecutive reactions, namely Knoevenagel and Michael reactions, were reported.
The development of metals tailored to the metallurgical conditions of laser-based additive manufacturing is crucial to advance the maturity of these materials for their use in structural applications. While efforts in this regard are being carried out around the globe, the use of high strength eutectic alloys have, so far, received minor attention, although previous works showed that rapid solidification techniques can result in ultrafine microstructures with excellent mechanical performance, albeit for small sample sizes. In the present work, a eutectic Ti-32.5Fe alloy has been produced by laser powder bed fusion aiming at exploiting rapid solidification and the capability to produce bulk ultrafine microstructures provided by this processing technique.
Process energy densities between 160 J/mm³ and 180 J/mm³ resulted in a dense and crack-free material with an oxygen content of ~ 0.45 wt.% in which a hierarchical microstructure is formed by µm-sized η-Ti4Fe2Ox dendrites embedded in an ultrafine eutectic β-Ti/TiFe matrix. The microstructure was studied three-dimensionally using near-field synchrotron ptychographic X-ray computed tomography with an actual spatial resolution down to 39 nm to analyse the morphology of the eutectic and dendritic structures as well as to quantify their mass density, size and distribution. Inter-lamellar spacings down to ~ 30–50 nm were achieved, revealing the potential of laser-based additive manufacturing to generate microstructures smaller than those obtained by classical rapid solidification techniques for bulk materials. The alloy was deformed at 600 °C under compressive loading up to a strain of ~ 30% without damage formation, resulting in a compressive yield stress of ~ 800 MPa.
This study provides a first demonstration of the feasibility to produce eutectic Ti-Fe alloys with ultrafine microstructures by laser powder bed fusion that are suitable for structural applications at elevated temperature.
Background: 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (HMGCLD) is an autosomal recessive disorder of ketogenesis and leucine degradation due to mutations in HMGCL.
Method: We performed a systematic literature search to identify all published cases. Two hundred eleven patients of whom relevant clinical data were available were included in this analysis. Clinical course, biochemical findings and mutation data are highlighted and discussed. An overview on all published HMGCL variants is provided.
Results: More than 95% of patients presented with acute metabolic decompensation. Most patients manifested within the first year of life, 42.4% already neonatally. Very few individuals remained asymptomatic. The neurologic long-term outcome was favorable with 62.6% of patients showing normal development.
Conclusion: This comprehensive data analysis provides a systematic overview on all published cases with HMGCLD including a list of all known HMGCL mutations.
2-methylacetoacetyl-coenzyme A thiolase (beta-ketothiolase) deficiency: one disease - two pathways
(2020)
Background: 2-methylacetoacetyl-coenzyme A thiolase deficiency (MATD; deficiency of mitochondrial acetoacetyl-coenzyme A thiolase T2/ “beta-ketothiolase”) is an autosomal recessive disorder of ketone body utilization and isoleucine degradation due to mutations in ACAT1.
Methods: We performed a systematic literature search for all available clinical descriptions of patients with MATD. Two hundred forty-four patients were identified and included in this analysis. Clinical course and biochemical data are presented and discussed.
Results: For 89.6% of patients at least one acute metabolic decompensation was reported. Age at first symptoms ranged from 2 days to 8 years (median 12 months). More than 82% of patients presented in the first 2 years of life, while manifestation in the neonatal period was the exception (3.4%). 77.0% (157 of 204 patients) of patients showed normal psychomotor development without neurologic abnormalities. Conclusion: This comprehensive data analysis provides a systematic overview on all cases with MATD identified in the literature. It demonstrates that MATD is a rather benign disorder with often favourable outcome, when compared with many other organic acidurias.
The motor protein myosin drives a wide range of cellular and muscular functions by generating directed movement and force, fueled through adenosine triphosphate (ATP) hydrolysis. Release of the hydrolysis product adenosine diphosphate (ADP) is a fundamental and regulatory process during force production. However, details about the molecular mechanism accompanying ADP release are scarce due to the lack of representative structures. Here we solved a novel blebbistatin-bound myosin conformation with critical structural elements in positions between the myosin pre-power stroke and rigor states. ADP in this structure is repositioned towards the surface by the phosphate-sensing P-loop, and stabilized in a partially unbound conformation via a salt-bridge between Arg131 and Glu187. A 5 Å rotation separates the mechanical converter in this conformation from the rigor position. The crystallized myosin structure thus resembles a conformation towards the end of the two-step power stroke, associated with ADP release. Computationally reconstructing ADP release from myosin by means of molecular dynamics simulations further supported the existence of an equivalent conformation along the power stroke that shows the same major characteristics in the myosin motor domain as the resolved blebbistatin-bound myosin-II·ADP crystal structure, and identified a communication hub centered on Arg232 that mediates chemomechanical energy transduction.
Toshiyuki Fukao
(2020)
Coumarin as a structural component of substrates and probes for serine and cysteine proteases
(2020)
Surface-enhanced Raman spectroscopy (SERS) with subsequent chemometric evaluation was performed for the rapid and non-destructive differentiation of seven important meat-associated microorganisms, namely Brochothrix thermosphacta DSM 20171, Pseudomonas fluorescens DSM 4358, Salmonella enterica subsp. enterica sv. Enteritidis DSM 14221, Listeria monocytogenes DSM 19094, Micrococcus luteus DSM 20030, Escherichia coli HB101 and Bacillus thuringiensis sv. israelensis DSM 5724. A simple method for collecting spectra from commercial paper-based SERS substrates without any laborious pre-treatments was used. In order to prepare the spectroscopic data for classification at genera level with a subsequent chemometric evaluation consisting of principal component analysis and discriminant analysis, a pre-processing method with spike correction and sum normalisation was performed. Because of the spike correction rather than exclusion, and therefore the use of a balanced data set, the multivariate analysis of the data is significantly resilient and meaningful. The analysis showed that the differentiation of meat-associated microorganisms and thereby the detection of important meat-related pathogenic bacteria was successful on genera level and a cross-validation as well as a classification of ungrouped data showed promising results, with 99.5 % and 97.5 %, respectively.
Cytokine-induced killer (CIK) cells are heterogeneous, major histocompatibility complex (MHC)-unrestricted T lymphocytes that have acquired the expression of several natural killer (NK) cell surface markers following the addition of interferon gamma (IFN-γ), OKT3 and interleukin-2 (IL-2). Treatment with CIK cells demonstrates a practical approach in cancer immunotherapy with limited, if any, graft versus host disease (GvHD) toxicity. CIK cells have been proposed and tested in many clinical trials in cancer patients by autologous, allogeneic or haploidentical administration. The possibility of combining them with specific monoclonal antibodies nivolumab and ipilimumab will further expand the possibility of their clinical utilization. Initially, phenotypic analysis was performed to explore CD3, CD4, CD56, PD-1 and CTLA-4 expression on CIK cells and PD-L1/PD-L2 expression on tumor cells. We further treated CIK cells with nivolumab and ipilimumab and measured the cytotoxicity of CIK cells cocultured to renal carcinoma cell lines, A-498 and Caki-2. We observed a significant decrease in viability of renal cell lines after treating with CIK cells (p < 0.0001) in comparison to untreated renal cell lines and anti-PD-1 or anti-CTLA-4 treatment had no remarkable effect on the viability of tumor cells. Using CCK-8, Precision Count Beads™ and Cell Trace™ violet proliferation assays, we proved significant increased proliferation of CIK cells in the presence of a combination of anti-PD-1 and anti-CTLA-4 antibodies compared to untreated CIK cells. The IFN-γ secretion increased significantly in the presence of A-498 and combinatorial blockade of PD-1 and CTLA-4 compared to nivolumab or ipilimumab monotreatment (p < 0.001). In conclusion, a combination of immune checkpoint inhibition with CIK cells augments cytotoxicity of CIK cells against renal cancer cells.
Carbachol dimers with primary carbamate groups as homobivalent modulators of muscarinic receptors
(2020)
Apple replant disease (ARD) is a soil-borne disease, which is of particular importance for fruit tree nurseries and fruit growers. The disease manifests by a poor vegetative development, stunted growth, and reduced yield in terms of quantity and quality, if apple plants (usually rootstocks) are replanted several times at the same site. Genotype-specific differences in the reaction of apple plants to ARD are documented, but less is known about the genetic mechanisms behind this symptomatology. Recent transcriptome analyses resulted in a number of candidate genes possibly involved in the plant response. In the present study, the expression of 108 selected candidate genes was investigated in root and leaf tissue of four different apple genotypes grown in untreated ARD soil and ARD soil disinfected by γ-irradiation originating from two different sites in Germany. Thirty-nine out of the 108 candidate genes were differentially expressed in roots by taking a p-value of < 0.05 and a fold change of > 1.5 as cutoff. Sixteen genes were more than 4.5-fold upregulated in roots of plants grown in ARD soil. The four genes MNL2 (putative mannosidase); ALF5 (multi antimicrobial extrusion protein); UGT73B4 (uridine diphosphate (UDP)-glycosyltransferase 73B4), and ECHI (chitin-binding) were significantly upregulated in roots. These genes seem to be related to the host plant response to ARD, although they have never been described in this context before. Six of the highly upregulated genes belong to the phytoalexin biosynthesis pathway. Their genotype-specific gene expression pattern was consistent with the phytoalexin content measured in roots. The biphenyl synthase (BIS) genes were found to be useful as early biomarkers for ARD, because their expression pattern correlated well with the phenotypic reaction of the Malus genotypes investigated.