208 research outputs found
Table_1_De novo LAMP2 insertion mutation causes cardiac-only Danon disease: A case report.xlsx
Danon disease is a rare disease caused by glycogen storage lysosomal disorder. It is related to the pathogenic mutation of the LAMP2 gene. In this case report, we present a patient with a novel pathogenic mutation (c.764_765insGA) with cardiac-only symptoms. Her family members do not carry the same mutation she does, suggesting this is a de novo mutation. Further tests revealed vacuoles and glycogen disposition in the patient's heart tissue and a significant decrease in LAMP2 protein expression. Protein structure remodeling of LAMP2 predicted that the mutant protein has conformational change lacking an important transmembrane domain, subsequently causing protein destabilization.</p
Reconstructing Biosynthetic Pathway of the Plant-Derived Cancer Chemopreventive-Precursor Glucoraphanin in <i>Escherichia coli</i>
Epidemiological
data confirmed a strong correlation between regular
consumption of cruciferous vegetables and lower cancer risk. This
cancer preventive property is mainly attributed to the glucosinolate
products, such as glucoraphanin found in broccoli that is derived
from methionine. Here we report the first successful reconstruction
of the complete biosynthetic pathway of glucoraphanin from methionine
in <i>Escherichia coli</i> <i>via</i> gene selection,
pathway design, and protein engineering. We used branched-chain amino
transferase 3 to catalyze two transamination steps to ensure the purity
of precursor molecules and used cysteine as a sulfur donor to simplify
the synthesis pathway. Two chimeric cytochrome P450 enzymes were engineered
and expressed in <i>E. coli</i> functionally. The original
plant C–S lyase was replaced by the <i>Neurospora crassa</i> hercynylcysteine sulfoxide lyase. Other pathway enzymes were successfully
mined from <i>Arabidopsis thaliana</i>, <i>Brassica
rapa</i>, and <i>Brassica oleracea</i>. Biosynthesis
of glucoraphanin upon coexpression of the optimized enzymes <i>in vivo</i> was confirmed by liquid chromatography–tandem
mass spectrometry analysis. No other glucosinolate analogues (except
for glucoiberin) were identified that could facilitate the downstream
purification processes. Production of glucoraphanin in this study
laid the foundation for microbial production of such health-beneficial
glucosinolates in a large-scale
Image_1_De novo LAMP2 insertion mutation causes cardiac-only Danon disease: A case report.pdf
Danon disease is a rare disease caused by glycogen storage lysosomal disorder. It is related to the pathogenic mutation of the LAMP2 gene. In this case report, we present a patient with a novel pathogenic mutation (c.764_765insGA) with cardiac-only symptoms. Her family members do not carry the same mutation she does, suggesting this is a de novo mutation. Further tests revealed vacuoles and glycogen disposition in the patient's heart tissue and a significant decrease in LAMP2 protein expression. Protein structure remodeling of LAMP2 predicted that the mutant protein has conformational change lacking an important transmembrane domain, subsequently causing protein destabilization.</p
Biosynthesis of the High-Value Plant Secondary Product Benzyl Isothiocyanate via Functional Expression of Multiple Heterologous Enzymes in <i>Escherichia coli</i>
Plants produce a
wide variety of secondary metabolites that are
highly nutraceutically and pharmaceutically important. Isothiocyanates,
which are found abundantly in cruciferous vegetables, are believed
to reduce the risk of several types of cancers and cardiovascular
diseases. The challenges arising from the structural diversity and
complex chemistry of these compounds have spurred great interest in
producing them in large amounts in microbes. In this study, we aimed
to synthesize benzyl isothiocyanate in <i>Escherichia coli</i> via gene mining, pathway engineering, and protein modification.
Two chimeric cytochrome P450 enzymes were constructed and functionally
expressed in <i>E. coli</i>. The <i>E. coli</i> cystathionine β-lyase was used to replace the plant-derived
C-S lyase; its active form cannot be expressed in <i>E. coli</i>. Suitable desulfoglucosinolate:PAPS sulfotransferase from <i>Arabidopsis thaliana</i> ecotype Col-0 and myrosinase from <i>Brevicoryne brassicae</i> were successfully mined from the database.
Biosynthesis of benzyl isothiocyanate by the combined expression of
the optimized enzymes <i>in vitro</i> was confirmed by gas
chromatography–mass spectrometry analysis. This study provided
a proof of concept for the production of benzyl isothiocyanate by
microbially produced enzymes and, importantly, laid the groundwork
for further metabolic engineering of microbial cells for the production
of isothiocyanates
Additional file 1: of Single-cell genome-wide bisulfite sequencing uncovers extensive heterogeneity in the mouse liver methylome
Supplementary materials. The supplementary materials include Figures S1–S3, Tables S1–S3, and Supplementary Experimental Procedures. (PDF 473 kb
Table_1_Fulvic acid alleviates cadmium-induced root growth inhibition by regulating antioxidant enzyme activity and carbon–nitrogen metabolism in apple seedlings.docx
IntroductionSubstantial previous studies have reported that fulvic acid (FA) application plays an important role in Chinese agricultural production. However, little is known about the mechanisms for using FA to increase apple trees resistance to Cd toxicity. In order to clarify the mechanism underlying FA alleviation in Cd-induced growth inhibition in apple seedlings.MethodsHerein, we treated M9T337 seedlings to either 0 or 30 µM/L Cd together with 0 or 0.2 g/L FA and analyzed the root growth, antioxidant enzyme activities, carbon (C) assimilation, nitrogen (N) metabolism, and C and N transport.ResultsThe results presented that, compared with CK (without Cd addition or FA spraying application), Cd poisoning significantly inhibited the root growth of apple seedlings. However, this Cd-induced root growth inhibition was significantly alleviated by FA spraying relative to the Cd treatment (Cd addition alone). On the one hand, the mitigation of inhibition effects was due to the reduced oxidative damage by enhancing antioxdiant enzyme (SOD, POD, and CAT) activities in leaves and roots. On the other hand, this growth advantage demonstrated compared to the Cd treatment was found to be associated with the strengthen of photosynthetic performance and the elevation of C and N metabolism enzymes activities. Meanwhile, we also found that under Cd stress condition, the distribution of C and N nutrients in apple seedlings was optimised by FA spraying application relative to the Cd treatment, according to the results of 13C and 15N tracing.ConclusionConclusively, our results suggested that the inhibitory effect of Cd on apple seedlings root growth was alleviated by FA through regulating antioxdiant capacities and C and N metabolism.</p
Optimization of Alkyl Side Chain Length in Polyimide for Gate Dielectrics to Achieve High Mobility and Outstanding Operational Stability in Organic Transistors
Alkyl chain modification strategies in both organic semiconductors
and inorganic dielectrics play a crucial role in improving the performance
of organic thin-film transistors (OTFTs). Polyimide (PI) and its derivatives
have received extensive attention as dielectrics for application in
OTFTs because of flexibility, high-temperature resistance, and low
cost. However, low-temperature solution processing PI-based gate dielectric
for flexible OTFTs with high mobility, low operating voltage, and
high operational stability remains an enormous challenge. Furthermore,
even though di-n-decyldinaphtho[2,3-b:2′,3′-f]thieno[3,2-b]thiophene (C10-DNTT) is known to have very
high mobility as an air-stable and high-performance organic semiconductor,
the C10-DNTT-based TFTs on the PI gate dielectrics still
showed relatively low mobility. Here, inspired by alkyl side chain
engineering, we design and synthesize a series of PI materials with
different alkyl side chain lengths and systematically investigate
the PI surface properties and the evolution of organic semiconductor
morphology deposited on PI surfaces during the variation of alkyl
side chain lengths. It is found that the alkyl side chain length has
a critical influence on the PI surface properties, as well as the
grain size and molecular orientation of semiconductors. Good field-effect
characteristics are obtained with high mobilities (up to 1.05 and
5.22 cm2/Vs, which are some of the best values reported
to date), relatively low operating voltage, hysteresis-free behavior,
and high operational stability in OTFTs. These results suggest that
the strategy of optimizing alkyl side-chain lengths opens up a new
research avenue for tuning semiconductor growth to enable high mobility
and outstanding operational stability of PI-based OTFTs
Self-Healing Surface Hydrophobicity by Consecutive Release of Hydrophobic Molecules from Mesoporous Silica
The paper reports a novel approach to achieve self-healing
surface
hydrophobicity. Mesoporous silica is used as the reservoir for hydrophobic
molecules, i.e., octadecylamine (ODA), that can release and refresh
the surface hydrophobicity consecutively. A polymdopamine layer is
used to further encapsulate silica–ODA, providing a reactive
layer, governing release of the underlying ODA, and improving the
dispersivity of silica nanoparticles in bulk resin. The approach arrives
at self-healing (super)Âhydrophobicity without using any fluoro-containing
compounds
Durable, Transparent, and Hot Liquid Repelling Superamphiphobic Coatings from Polysiloxane-Modified Multiwalled Carbon Nanotubes
Although encouraging
progress in the field of superamphiphobic
coatings has been obtained, the superamphiphobic coatings with high
durability, transparency, and repellency to hot liquids are very rare.
Here, durable, transparent, and hot liquid-repelling superamphiphobic
coatings were successfully prepared using polysiloxane-modified multiwalled
carbon nanotubes (MWCNTs@POS) as the templates. The hydrolytic condensation
of <i>n</i>-hexadecyltrimethoxysilane (HDTMS) and tetraethoxysilane
on the surface of MWCNTs formed MWCNTs@POS, which are highly dispersible
in toluene. The superamphiphobic coatings were prepared by spray-coating
the homogeneous suspension of MWCNTs@POS in toluene onto glass slides,
calcination in air to form the silica nanotubes (SNTs), and then modification
with 1<i>H</i>,1<i>H</i>,2<i>H</i>,2<i>H</i>-perfluorodecyltrichlorosilane in dry toluene. The changes
in the surface microstructure, surface chemical composition, and wettability
were characterized by various techniques such as scanning electron
microscopy, transmission electron microscopy, and X-ray photoelectron
spectroscopy. It was found that the microstructures of the SNTs have
great influences on superamphiphobicity and transparency of the coatings
and can be regulated by the concentration of HDTMS and the diameter
of MWCNTs. The SNTs with tunable wall thickness and diameter could
be obtained using the method. The superamphiphobic coatings showed
high contact angles and low sliding angles for various cool and hot
liquids of different surface tensions. The superamphiphobic coatings
also exhibited high transparency and comprehensive durability
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