Planta MedDOI: 10.1055/a-1146-8369 Hericium erinaceus is a very popular edible and medicinal mushroom used for the treatment of enervation and gastrointestinal diseases in Eastern Asia. Chemical investigation on the fruiting body of Hericium erinaceus led to the isolation of 4 new (1 – 4) and 10 known meroterpenoids (5 – 14). The structures of new compounds were determined via analysis of NMR and MS data in combination with chemical derivatization. The inhibitory activities of 1 – 14 against...
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Enoyl-acyl carrier protein reductase (FabI) catalyzes a rate-controlling step in bacterial fatty-acid synthesis and is a target for antibacterial drug development. A phylogenetic analysis shows that FabIs fall into four divergent clades. Members of clades 1–3 have been structurally and biochemically characterized, but the fourth clade found in members of phylum Bacteroidetes is uncharacterized. Here, we identified the unique structure and conformational changes that distinguish clade 4 FabIs. Alistipes...
Mutations in the genes encoding the highly conserved Ca2+-sensing protein calmodulin (CaM) cause severe cardiac arrhythmias, including catecholaminergic polymorphic ventricular tachycardia (CPVT) or long QT syndrome, and sudden cardiac death. Most of the identified arrhythmogenic mutations reside in the C-terminal domain of CaM, and mostly affect Ca2+-coordinating residues. One exception is the CPVT-causing N53I substitution, which resides in the N-terminal domain (N-domain). It does not affect Ca2+-coordination...
Most malaria deaths are caused by the protozoan parasite Plasmodium falciparum. Its life cycle is regulated by a cGMP-dependent protein kinase (PfPKG), whose inhibition is a promising antimalaria strategy. Allosteric kinase inhibitors, such as cGMP analogs, offer enhanced selectivity unlike competitive kinase inhibitors. However, the mechanisms underlying allosteric PfPKG inhibition are incompletely understood. Here, we show that 8-NBD-cGMP is an effective PfPKG antagonist. Using comparative NMR...
Activation of the T cell receptor (TCR) results in binding of the adapter protein Nck (non-catalytic region of tyrosine kinase) to the CD3 subunit of the TCR. The interaction was suggested to be important for the amplification of TCR signals and is governed by a proline-rich sequence (PRS) in CD3 that binds to the first SH3 domain of Nck (Nck-SH3.1). Inhibition of this protein/protein interaction ameliorated inflammatory symptoms in mouse models of multiple sclerosis, psoriasis, and asthma. A small...
S-Acylation of the SNARE protein synaptosome-associated protein of 25kDa (SNAP25) is mediated by a subset of Golgi zinc finger DHHC-type palmitoyltransferase (zDHHC) enzymes, particularly zDHHC17. The ankyrin repeat (ANK) domain of zDHHC17 interacts with a short linear motif known as the zDHHC ANK-binding motif (zDABM) in SNAP25 (112-VVASQP-117), which is downstream of its S-acylated, cysteine-rich domain (85-CGLCVCPC-92). Here, we investigated the importance of a flexible linker region (amino acids...
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British Journal of Cancer, Published online: 22 April 2020; doi:10.1038/s41416-020-0840-8Alternative macrophage polarisation associated with resistance to anti-PD1 blockade is possibly supported by the splicing of FKBP51 immunophilin in melanoma patients
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Abstract Primary human hepatocytes (PHHs) are considered the “gold standard” for evaluating hepatic metabolism and toxicity of xenobiotics. In the present study, we evaluated the genotoxic potential of four indirect-acting (requiring metabolic activation) and six direct-acting genotoxic carcinogens, one aneugen, and five non-carcinogens that are negative or equivocal for genotoxicity in vivo in cryopreserved PHHs derived from three individual donors. DNA damage was determined...
Abstract Polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTR) are related to cognitive dysfunction and mental disability. These genes, along with folate and vitamin B12 levels, are regulators of one-carbon metabolism, which synthesizes S-adenosylmethionine (SAM) as a methyl donor for arsenic methylation. The aim of this study was to explore whether polymorphisms of MTHFR and MTR influence arsenic methylation capacity and plasma folate and...
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Abstract Brassica napus is an allopolyploid plant, derived from spontaneous hybridization between Brassica rapa and Brassica oleracea. Intensive breeding has led to a significant reduction in genetic and phenotypic diversity within this species. Newly resynthesized hybrids from progenitor species may restore some diversity in B. napus, but they often are chromosomally and phenotypically unstable. Using fluorescence in situ hybridization, we tested chromosome constitutions in a...
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ACS NanoDOI: 10.1021/acsnano.0c00309
ACS NanoDOI: 10.1021/acsnano.0c00628
ACS NanoDOI: 10.1021/acsnano.0c02026
ACS NanoDOI: 10.1021/acsnano.9b10081
ACS NanoDOI: 10.1021/acsnano.0c02325
ACS NanoDOI: 10.1021/acsnano.0c01000
ACS NanoDOI: 10.1021/acsnano.9b09873
ACS NanoDOI: 10.1021/acsnano.0c00326
ACS NanoDOI: 10.1021/acsnano.0c01427
ACS NanoDOI: 10.1021/acsnano.0c00076
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Abstract Purpose The current trend for continuous drug product manufacturing requires new, affordable process analytical techniques (PAT) to ensure control of processing. This work evaluates whether property models based on spectral data from recent Fabry–Pérot Interferometer based NIR sensors can generate a high-resolution moisture signal suitable for process control. ...
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Abstract Deep brain neurostimulators (DBS) have enabled thousands of individuals to overcome movement disorders, thus offering them a new chance for social integration while enhancing their self-esteem. A classic DBS consists of a central implantable pulse generator (IPG) and its respective wires and leads that extend to the scalp to reach the brain. The classic positioning of the generator is currently subcutaneous, usually just below the clavicle or in the abdominal wall. As...
Abstract Background Breast reconstruction (BR) has revealed significant benefits on physical and psychological well-being. Satisfaction is currently a key outcome on BR. This study aimed to assess the impact of timing and reconstructive technique on satisfaction, monitoring the influence of patient’s characteristics and complications. Methods A single-center...
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Abstract To investigate the spatial and temporal variations of sulfur (S) in plant-soil systems of Phragmites australis (PA, native invasive species) and Cyperus malaccensis (CM, common native species) marshes, in situ filed sampling was conducted in the two marshes at different seasons. Results showed that the variations of total sulfur (TS) contents in soils differed among seasons or marshes. Higher levels of TS in soils of PA marsh generally occurred in winter and summer, while...
Abstract Paddy fields play an important role as alternative habitats for various wetland-dependent species. Agricultural intensification in paddy fields, however, presents serious threats to these species. Here, we examined the environmental factors, including those related to modern farming practices, affecting the distribution of the Sado wrinkled frog (Glandirana susurra) in paddy fields on Sado Island, Japan. We recorded the abundance of frogs at 42 sites in early and late...
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Extolling the many virtues of the Perron-Frobenius theorem and linear algebra -- Read more on ScientificAmerican.com
The administration’s preference for economic interests over environmental interests is reflected in its attitude toward both climate change and COVID-19 -- Read more on ScientificAmerican.com
The Trump Administration wants to scale back on Clean Air Act enforcement—even as we learn that places with more pollution have more coronavirus deaths -- Read more on ScientificAmerican.com
Poor access to health insurance will afflict patients, health systems and states -- Read more on ScientificAmerican.com
A nation’s prior experience with similar disasters can make a big difference -- Read more on ScientificAmerican.com
Leaders from hospital administrators to the president have failed them and betrayed their trust -- Read more on ScientificAmerican.com
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Abstract Pentoxifylline (PTX), an anti-hemorrhage drug used in the treatment of intermittent claudication, is extensively metabolized by the liver resulting in a reduction of the therapeutic levels within a short duration of time. Self-nano-emulsifying drug delivery system (SNEDDS) is well reported to enhance the bio-absorption of drugs by forming nano-sized globules upon contact with the biological fluids after oral administration. The present study aimed to formulate, characterize,...
Abstract In the presented study, insight into the development and optimisation of the dry emulsion formulation and spray drying process is provided. The aim was to facilitate the dissolution of the poorly soluble, highly lipophilic drug, simvastatin, by forming spray-dried dry emulsion particles having adequate powder flow properties, while assuring sufficient drug content. Simvastatin and a mixture of caprylic, capric triglyceride and 1-oleoyl-rac-glycerol were employed as...
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Abstract Fate determination in self-renewal and differentiation of hematopoietic stem and progenitor cells (HSCs and HPCs) is ultimately controlled by gene expression, which is profoundly influenced by the global and local chromatin state. Cellular metabolism directly influences the chromatin state through the dynamic regulation of the enzymatic activities that modify DNA and histones, but also generates genotoxic metabolites that can damage DNA and thus pose threat to the genome...
Abstract Faithful chromosome segregation during mitosis requires the correct assembly of kinetochore on the centromere. CENP-A is a variant of histone H3, which specializes the centromere region on chromatin and mediates the kinetochore assembly. The Mis18 complex plays a critical role in initiating the centromere loading of the newly-synthesized CENP-A. However, it remains unclear how Mis18 complex (spMis18, spMis16 and spMis19) is located to the centromere to license the recruitment...
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