659 research outputs found
Link between allosteric signal transduction and functional dynamics in a multi-subunit enzyme: S-adenosylhomocysteine hydrolase
S-adenosylhomocysteine hydrolase (SAHH), a cellular enzyme that plays a key
role in methylation reactions including those required for maturation of viral
mRNA, is an important drug target in the discovery of antiviral agents. While
targeting the active site is a straightforward strategy of enzyme inhibition,
evidences of allosteric modulation of active site in many enzymes underscore
the molecular origin of signal transduction. Information of co-evolving
sequences in SAHH family and the key residues for functional dynamics that can
be identified using native topology of the enzyme provide glimpses into how the
allosteric signaling network, dispersed over the molecular structure,
coordinates intra- and inter-subunit conformational dynamics. To study the link
between the allosteric communication and functional dynamics of SAHHs, we
performed Brownian dynamics simulations by building a coarse-grained model
based on the holo and ligand-bound structures. The simulations of
ligand-induced transition revealed that the signal of intra-subunit closure
dynamics is transmitted to form inter-subunit contacts, which in turn invoke a
precise alignment of active site, followed by the dimer-dimer rotation that
compacts the whole tetrameric structure. Further analyses of SAHH dynamics
associated with ligand binding provided evidence of both induced fit and
population shift mechanisms, and also showed that the transition state ensemble
is akin to the ligand-bound state. Besides the formation of enzyme-ligand
contacts at the active site, the allosteric couplings from the residues distal
to the active site is vital to the enzymatic function.Comment: 35 pages, 14 figures, 3 Table
Influence of the molecular structure of metal-phthalocyanine on electrocatalytic reactions
The demand for new catalysts for renewable energy production has become crucial. As an alternative to metal catalysts for electrocatalysis to produce energy sources, metal-phthalocyanine (MPc) electrocatalysts have shown potential. Their physicochemical and electrochemical properties depend on the chemical structure of the MPc and the central metal atom. Recent reviews of MPcs focused on their electrochemical performance in specific catalytic reactions, such as oxygen reduction reaction and CO2 reduction reaction. However, understanding the structure of MPcs in depth is important, since their electrochemical catalytic activity is affected by structural modifications of MPcs. Therefore, this minireview focuses on how the molecular structure of MPcs affects electrochemical catalysis
Therapeutic effects of phlorotannins in the treatment of neurodegenerative disorders
Phlorotannins are natural polyphenolic compounds produced by brown marine algae and are currently found in nutritional supplements. Although they are known to cross the blood–brain barrier, their neuropharmacological actions remain unclear. Here we review the potential therapeutic benefits of phlorotannins in the treatment of neurodegenerative diseases. In mouse models of Alzheimer’s disease, ethanol intoxication and fear stress, the phlorotannin monomer phloroglucinol and the compounds eckol, dieckol and phlorofucofuroeckol A have been shown to improve cognitive function. In a mouse model of Parkinson’s disease, phloroglucinol treatment led to improved motor performance. Additional neurological benefits associated with phlorotannin intake have been demonstrated in stroke, sleep disorders, and pain response. These effects may stem from the inhibition of disease-inducing plaque synthesis and aggregation, suppression of microglial activation, modulation of pro-inflammatory signaling, reduction of glutamate-induced excitotoxicity, and scavenging of reactive oxygen species. Clinical trials of phlorotannins have not reported significant adverse effects, suggesting these compounds to be promising bioactive agents in the treatment of neurological diseases. We therefore propose a putative biophysical mechanism of phlorotannin action in addition to future directions for phlorotannin research
First report of Septoria centellae associated with leaf spot of Centella asiatica in Korea
Septoria centellae associated with leaf spot of Centella asiatica is reported for the first time in Korea. The fungus is described and illustrated in detail. It is also compared with related species of Septoria present on Centella and Hydrocotyle spp. with taxonomic comments. Two monoconidial isolates from Jeju and Wando were successfully cultured and have been deposited in the Korean Agricultural Culture Collection.Facultad de Ciencias Agrarias y Forestale
Using Individualized Brain Network for Analyzing Structural Covariance of the Cerebral Cortex in Alzheimer's Patients
Deleted copy number variation of Hanwoo and Holstein using next generation sequencing at the population level
This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Abstract
Background
Copy number variation (CNV), a source of genetic diversity in mammals, has been shown to underlie biological functions related to production traits. Notwithstanding, there have been few studies conducted on CNVs using next generation sequencing at the population level.
Results
Illumina NGS data was obtained for ten Holsteins, a dairy cattle, and 22 Hanwoo, a beef cattle. The sequence data for each of the 32 animals varied from 13.58-fold to almost 20-fold coverage. We detected a total of 6,811 deleted CNVs across the analyzed individuals (average length = 2732.2 bp) corresponding to 0.74% of the cattle genome (18.6 Mbp of variable sequence). By examining the overlap between CNV deletion regions and genes, we selected 30 genes with the highest deletion scores. These genes were found to be related to the nervous system, more specifically with nervous transmission, neuron motion, and neurogenesis. We regarded these genes as having been effected by the domestication process. Further analysis of the CNV genotyping information revealed 94 putative selected CNVs and 954 breed-specific CNVs.
Conclusions
This study provides useful information for assessing the impact of CNVs on cattle traits using NGS at the population level
Effect of chitinase- 3- like protein 1 on glucose metabolism: In vitro skeletal muscle and human genetic association study
We investigated the effect of chitinase- 3- like protein 1 (CHI3L1) on glucose metabolism and its underlying mechanisms in skeletal muscle cells, and evaluated whether the observed effects are relevant in humans. CHI3L1 was associated with increased glucose uptake in skeletal muscles in an AMP- activated protein kinase (AMPK)- dependent manner, and with increased intracellular calcium levels via PAR2. The improvement in glucose metabolism observed in an intraperitoneal glucose tolerance test on male C57BL/6J mice supported this association. Inhibition of the CaMKK was associated with suppression of CHI3L1- mediated glucose uptake. Additionally, CHI3L1 was found to influence glucose uptake through the PI3K/AKT pathway. Results suggested that CHI3L1 stimulated the phosphorylation of AS160 and p38 MAPK downstream of AMPK and AKT, and the resultant GLUT4 translocation. In primary myoblast cells, stimulation of AMPK and AKT was observed in response to CHI3L1, underscoring the biological relevance of CHI3L1. CHI3L1 levels were elevated in cells under conditions that mimic exercise in vitro and in exercised mice in vivo, indicating that CHI3L1 is secreted during muscle contraction. Finally, similar associations between CHI3L1 and metabolic parameters were observed in humans alongside genotype associations between CHI3L1 and diabetes at the population level. CHI3L1 may be a potential therapeutic target for the treatment of diabetes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162777/2/fsb220907.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162777/1/fsb220907_am.pd
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