Summary
Sugarcane is the world's most efficient feedstock for commercial production of bioethanol due to its superior biomass production and accumulation of sucrose in stems. Integrating first‐ and ...second‐generation ethanol conversion processes will enhance the biofuel yield per unit area by utilizing both sucrose and cell wall‐bound sugars for fermentation. RNAi suppression of the lignin biosynthetic gene caffeic acid O‐methyltransferase (COMT) has been demonstrated to improve bioethanol production from lignocellulosic biomass. Genome editing has been used in a number of crops for creation of loss of function phenotypes but is very challenging in sugarcane due to its highly polyploid genome. In this study, a conserved region of COMT was targeted with a single‐transcription activator‐like effector nuclease (TALEN) pair for multi‐allelic mutagenesis to modify lignin biosynthesis in sugarcane. Field‐grown TALEN‐mediated COMT mutants showed up to 19.7% lignin reduction and significantly decreased syringyl to guaiacyl (S/G) ratio resulting in an up to 43.8% improved saccharification efficiency. Biomass production of COMT mutant lines with superior saccharification efficiency did not differ significantly from the original cultivar under replicated field conditions. Sanger sequencing of cloned COMT amplicons (1351–1657 bp) revealed co‐editing of 107 of the 109 unique COMT copies/alleles in vegetative progeny of line CB6 using a single TALEN pair. Line CB6 combined altered cell wall composition and drastically improved saccharification efficiency with good agronomic performance. These findings confirm the feasibility of co‐mutagenesis of a very large number of target alleles/copies for improvement in crops with complex genomes.
Wearable contact lenses which can monitor physiological parameters have attracted substantial interests due to the capability of direct detection of biomarkers contained in body fluids. However, ...previously reported contact lens sensors can only monitor a single analyte at a time. Furthermore, such ocular contact lenses generally obstruct the field of vision of the subject. Here, we developed a multifunctional contact lens sensor that alleviates some of these limitations since it was developed on an actual ocular contact lens. It was also designed to monitor glucose within tears, as well as intraocular pressure using the resistance and capacitance of the electronic device. Furthermore, in-vivo and in-vitro tests using a live rabbit and bovine eyeball demonstrated its reliable operation. Our developed contact lens sensor can measure the glucose level in tear fluid and intraocular pressure simultaneously but yet independently based on different electrical responses.
We aimed to examine the association between Obstructive Sleep Apnea (OSA) risk, health behaviors, and depressive symptoms in a representative Korean sample.
Cross-sectional data from the 2020 Korea ...National Health and Nutrition Examination Survey (KNHANES) were analyzed. The sample included 4,352 adults aged 40 years and older. Multiple linear regression analysis was performed to examine the association between OSA risk, health behaviors, and depressive symptoms.
In total, 23.1% of the participants reported a high risk of OSA. Of the respondents, 39.8%, 19.0%, 27.2%, and 8.7% reported hypertension, snoring, tiredness, and observed apnea, respectively. The prevalence of moderate-severe depressive symptoms among adults with high-risk OSA was 7.5%. The significant associations between OSA risk and sex with PHQ-9 were shown in univariate linear regression. In the multiple linear regression analysis, the association between high risk of OSA and PHQ-9 showed in total (B = 1.58; P < 0.001), male (B = 1.21; P < 0.001), and female (B = 1.93; P < 0.001).
A high risk of OSA was associated with an increased prevalence of depressive symptoms. Monitoring the risk factors of depressive symptoms, including OSA, or unhealthy behaviors may decrease the mental health issues of middle-aged and older adults.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Transparent electrodes that can remain electrically conductive and stable under large mechanical deformations are highly desirable for applications in flexible and wearable electronics. This paper ...describes a comprehensive study of the electrical, optical, and mechanical properties of hybrid nanostructures based on two-dimensional graphene and networks of one-dimensional metal nanowires, and their use as transparent and stretchable electrodes. Low sheet resistance (33 Ω/sq) with high transmittance (94% in visible range), robust stability against electric breakdown and oxidation, and superb flexibility (27% in bending strain) and stretchability (100% in tensile strain) are observed, and these multiple functionalities of the hybrid structures suggest a future promise for next generation electronics. The use of hybrid electrodes to fabricate oxide semiconductor transistors and single-pixel displays integrated on wearable soft contact lenses with in vivo tests are demonstrated.
Replication-Factor-C (RFC) and RFC-like complexes (RLCs) mediate chromatin engagement of the proliferating cell nuclear antigen (PCNA). It remains controversial how RFC and RLCs cooperate to regulate ...PCNA loading and unloading. Here, we show the distinct PCNA loading or unloading activity of each clamp loader. ATAD5-RLC possesses the potent PCNA unloading activity. ATPase motif and collar domain of ATAD5 are crucial for the unloading activity. DNA structures did not affect PCNA unloading activity of ATAD5-RLC. ATAD5-RLC could unload ubiquitinated PCNA. Through single molecule measurements, we reveal that ATAD5-RLC unloaded PCNA through one intermediate state before ATP hydrolysis. RFC loaded PCNA through two intermediate states on DNA, separated by ATP hydrolysis. Replication proteins such as Fen1 could inhibit the PCNA unloading activity of Elg1-RLC, a yeast homolog of ATAD5-RLC in vitro. Our findings provide molecular insights into how PCNA is released from chromatin to finalize DNA replication/repair.
Transparent and stretchable electronics with remarkable bendability, conformability, and lightness are the key attributes for sensing or wearable devices. Transparent and stretchable field‐effect ...transistor sensors using graphene–metal nanowire hybrid nanostructures have high mobility (≈3000 cm2 V−1 s−1) with low contact resistance, and they are transferrable onto a variety of substrates. The integration of these sensors for RLC circuits enables wireless monitoring.
Rheumatoid arthritis (RA) is a systemic inflammatory disease that mainly affects the synovial joints. Although involvement of the fibroblast growth factor (FGF) signaling pathway has been suggested ...as an important modulator in RA development, no clear evidence has been provided. In this study, we found that synovial fluid basic FGF (bFGF) concentration was significantly higher in RA than in osteoarthritis (OA) patients. bFGF stimulates proliferation and migration of human fibroblast-like synoviocytes (FLSs) by activation of the bFGF-FGF receptor 3 (FGFR3)-ribosomal S6 kinase 2 (RSK2) signaling axis. Moreover, a molecular docking study revealed that kaempferol inhibited FGFR3 activity by binding to the active pocket of the FGFR3 kinase domain. Kaempferol forms hydrogen bonds with the FGFR3 backbone oxygen of Glu555 and Ala558 and the side chain of Lys508. Notably, the inhibition of bFGF-FGFR3-RSK2 signaling by kaempferol suppresses the proliferation and migration of RA FLSs and the release of activated T-cell-mediated inflammatory cytokines, such as IL-17, IL-21, and TNF-α. We further found that activated phospho-FGFR3 and -RSK2 were more highly observed in RA than in OA synovium. The hyperplastic lining and sublining lymphoid aggregate layers of RA synovium showed p-RSK2-expressing CD68
macrophages with high frequency, while pRSK2-expressing CD4
T-cells was observed at a lower frequency. Notably, kaempferol administration in collagen-induced arthritis mice relieved the frequency and severity of arthritis. Kaempferol reduced osteoclast differentiation in vitro and in vivo relative to the controls and was associated with the inhibition of osteoclast markers, such as tartrate-resistant acid phosphatase, integrin β3, and MMP9. Conclusively, our data suggest that bFGF-induced FGFR3-RSK2 signaling may play a critical role during the initiation and progression of RA in terms of FLS proliferation and enhanced osteoclastogenesis, and that kaempferol may be effective as a new treatment for RA.
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•Metabolic engineering improves microbial production of cellulosic fuels.•We highlight a paradigm shift in engineering of ethanol producer, S. cerevisiae.•Strain engineering focuses ...on improving carbon utilization and stress tolerance.•An oleaginous yeast, Y. lipolytica, is an emerging cellulosic biodiesel producer.
Cellulosic fuels are expected to have great potential industrial applications in the near future, but they still face technical challenges to become cost-competitive fuels, thus presenting many opportunities for improvement. The economical production of viable biofuels requires metabolic engineering of microbial platforms to convert cellulosic biomass into biofuels with high titers and yields. Fortunately, integrating traditional and novel engineering strategies with advanced engineering toolboxes has allowed the development of more robust microbial platforms, thus expanding substrate ranges. This review highlights recent trends in the metabolic engineering of microbial platforms, such as the industrial yeasts Saccharomyces cerevisiae and Yarrowia lipolytica, for the production of renewable fuels.
The petrochemical industry has grown to meet the need for massive production of energy and commodities along with an explosive population growth; however, serious side effects such as greenhouse gas ...emissions and global warming have negatively impacted the environment. Lignocellulosic biomass with myriad quantities on Earth is an attractive resource for the production of carbon-neutral fuels and chemicals through environmentally friendly processes of microbial fermentation. This review discusses metabolic engineering efforts to achieve economically feasible industrial production of fuels and chemicals from microbial cell factories using the carbohydrate portion of lignocellulosic biomass as substrates. The combined knowledge of systems biology and metabolic engineering has been applied to construct robust platform microorganisms with maximum conversion of monomeric sugars, such as glucose and xylose, derived from lignocellulosic biomass. By comprehensively revisiting carbon conversion pathways, we provide a rationale for engineering strategies, as well as their features, feasibility, and recent representative studies. In addition, we briefly discuss how tools in systems biology can be applied in the field of metabolic engineering to accelerate the development of microbial cell factories that convert lignocellulosic biomass into carbon-neutral fuels and chemicals with economic feasibility.
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•Lignocellulosic carbohydrates are carbon-neutral substrates for producing fuels and chemicals.•Natural carbon catabolic pathways have been rewired in bacteria and yeasts.•The aim was to improve the efficiency of lignocellulosic carbohydrate utilization.•Strain developments by metabolic engineering has improved carbon conversion and energy balance.•Recent progress and perspectives in the use of lignocellulosic carbohydrates are discussed.
Neuronal degeneration in the zebrafish retina stimulates Müller glia (MG) to proliferate and generate multipotent progenitors for retinal repair. Controlling this proliferation is critical to ...successful regeneration. Previous studies reported that retinal injury stimulates pSmad3 signaling in injury-responsive MG. Contrary to these findings, we report pSmad3 expression is restricted to quiescent MG and suppressed in injury-responsive MG. Our data indicates that Tgfb3 is the ligand responsible for regulating pSmad3 expression. Remarkably, although overexpression of either Tgfb1b or Tgfb3 can stimulate pSmad3 expression in the injured retina, only Tgfb3 inhibits injury-dependent MG proliferation; suggesting the involvement of a non-canonical Tgfb signaling pathway. Furthermore, inhibition of Alk5, PP2A or Notch signaling rescues MG proliferation in Tgfb3 overexpressing zebrafish. Finally, we report that this Tgfb3 signaling pathway is active in zebrafish MG, but not those in mice, which may contribute to the different regenerative capabilities of MG from fish and mammals.
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