DNA mismatch repair （MMR） is a highly conserved biological pathway that plays a key role in maintaining genomic stability. The specificity of MMR is primarily for base-base mismatches and ...insertion/deletion mispairs generated during DNA replication and recombination. MMR also suppresses homeologous recombination and was recently shown to play a role in DNA damage signaling in eukaryotic cells. Escherichia coli MutS and MutL and their eukaryotic homologs, MutSα and MutLα, respectively, are key players in MMR-associated genome maintenance. Many other protein components that participate in various DNA metabolic pathways, such as PCNA and RPA, are also essential for MMR. Defects in MMR are associated with genome-wide instability, predisposition to certain types of cancer including hereditary non-polyposis colorectal cancer, resistance to certain chemotherapeutic agents, and abnormalities in meiosis and sterility in mammalian systems.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Eight-hydroxy-2′-deoxyguanosine (8-OHdG) is increased in the brain in late-stage Alzheimer's disease (LAD) and mild cognitive impairment (MCI). To determine if decreased base-excision repair ...contributes to these elevations, we measured oxoguanine glycosylase 1 (OGG1) protein and incision activities in nuclear and mitochondrial fractions from frontal (FL), temporal (TL), and parietal (PL) lobes from 8 MCI and 7 LAD patients, and 6 age-matched normal control (NC) subjects. OGG1 activity was significantly (
P
<
0.05) decreased in nuclear specimens of FL, TL, and PL in MCI and LAD and in mitochondria from LAD FL and TL and MCI TL. Nuclear OGG1 protein was significantly decreased in LAD FL and MCI and LAD PL. No differences in mitochondrial OGG1 protein levels were found. Overall, our results suggest that decreased OGG1 activity occurs early in the progression of AD, possibly mediated by 4-hydroxynonenal inactivation and may contribute to elevated 8-OHdG in the brain in MCI and LAD.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The ongoing new coronavirus pneumonia (Corona Virus Disease 2019, COVID-19) outbreak is spreading in China, but it has not yet reached its peak. Five million people emigrated from Wuhan before ...lockdown, potentially representing a source of virus infection. Determining case distribution and its correlation with population emigration from Wuhan in the early stage of the epidemic is of great importance for early warning and for the prevention of future outbreaks.
The official case report on the COVID-19 epidemic was collected as of January 30, 2020. Time and location information on COVID-19 cases was extracted and analyzed using ArcGIS and WinBUGS software. Data on population migration from Wuhan city and Hubei province were extracted from Baidu Qianxi, and their correlation with the number of cases was analyzed.
The COVID-19 confirmed and death cases in Hubei province accounted for 59.91% (5806/9692) and 95.77% (204/213) of the total cases in China, respectively. Hot spot provinces included Sichuan and Yunnan, which are adjacent to Hubei. The time risk of Hubei province on the following day was 1.960 times that on the previous day. The number of cases in some cities was relatively low, but the time risk appeared to be continuously rising. The correlation coefficient between the provincial number of cases and emigration from Wuhan was up to 0.943. The lockdown of 17 cities in Hubei province and the implementation of nationwide control measures efficiently prevented an exponential growth in the number of cases.
The population that emigrated from Wuhan was the main infection source in other cities and provinces. Some cities with a low number of cases showed a rapid increase in case load. Owing to the upcoming Spring Festival return wave, understanding the risk trends in different regions is crucial to ensure preparedness at both the individual and organization levels and to prevent new outbreaks.
C(sp2)−H functionalization offers an efficient strategy for the synthesis of various elaborated N‐containing heteroarenes. Along these lines, oxazino pyridines that can be readily prepared from ...pyridines, have been introduced as powerful substrates in radical‐ and ionic‐mediated meta‐C−H functionalization. However, the regioselective meta‐C−H arylation of pyridines remains a great challenge. Herein, a copper‐catalyzed meta‐selective C−H arylation of pyridines and isoquinolines through bench‐stable dearomatized intermediates is reported. Electrophilic aryl‐Cu(III) species, generated from readily accessible aryl I(III) reagents, enable the efficient meta‐arylation of a broad range of pyridines and isoquinolines. The method also allows the meta‐selective alkenylation of these heteroarenes using the corresponding alkenyl I(III)‐reagents. Late‐stage arylation of drug‐derived pyridines and larger‐scale experiments demonstrate the potential of this synthetic methodology.
Meta‐arylated pyridines are prepared via bench stable oxazino pyridine intermediates with unsymmetrical iodonium salts using Cu‐catalysis. The strategy can be applied for meta‐alkenylation upon simply switching to the corresponding alkenyl I(III) reagents and both C‐H‐functionalizations also work on isoquinolines.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
A radial uniform circular array (UCA) is proposed for orbital angular momentum (OAM) generation and dual-mode communication based on a multilayer design. Theoretical derivation is presented for the ...demonstration of the OAM generation from radial UCAs. The UCA of single mode is realized by cascading an eight-dividing feeding network with equal magnitude and specific phases for each of two neighbor ports and eight microstrip antenna elements. Both the full-wave simulations and measurements of a final fabricated antenna array are carried out. From 5.72 to 5.95 GHz, the proposed antenna possesses good -15-dB bandwidths at the ±1 modes, and a very weak cross coupling (less than -24 dB) exists in this frequency band. The helical phase wavefronts are obtained, and the radiation patterns are presented. Moreover, the dual-mode multiplexing is achieved with isolations of different channels more than 19 dB in measurements.
ARID1A (the AT-rich interaction domain 1A, also known as BAF250a) is one of the most commonly mutated genes in cancer
. The majority of ARID1A mutations are inactivating mutations and lead to loss of ...ARID1A expression
, which makes ARID1A a poor therapeutic target. Therefore, it is of clinical importance to identify molecular consequences of ARID1A deficiency that create therapeutic vulnerabilities in ARID1A-mutant tumors. In a proteomic screen, we found that ARID1A interacts with mismatch repair (MMR) protein MSH2. ARID1A recruited MSH2 to chromatin during DNA replication and promoted MMR. Conversely, ARID1A inactivation compromised MMR and increased mutagenesis. ARID1A deficiency correlated with microsatellite instability genomic signature and a predominant C>T mutation pattern and increased mutation load across multiple human cancer types. Tumors formed by an ARID1A-deficient ovarian cancer cell line in syngeneic mice displayed increased mutation load, elevated numbers of tumor-infiltrating lymphocytes, and PD-L1 expression. Notably, treatment with anti-PD-L1 antibody reduced tumor burden and prolonged survival of mice bearing ARID1A-deficient but not ARID1A-wild-type ovarian tumors. Together, these results suggest ARID1A deficiency contributes to impaired MMR and mutator phenotype in cancer, and may cooperate with immune checkpoint blockade therapy.
A novel frequency-selective rasorber (FSR) is proposed in this paper which has a nearly transparent window between two absorption bands. The FSR consists of a resistive sheet and a bandpass ...frequency-selective surface (FSS). The impedance conditions of absorption/transmission for both the resistive sheet and the bandpass FSS are theoretically derived based on equivalent circuit analysis. The insertion loss of FSR at the resonant frequency of lossless bandpass FSS is proven to be only related to the equivalent impedance of the resistive sheet. When the resistive sheet is in parallel resonance at the passband, a nearly transparent window can be achieved regardless of lossy properties. An interdigital resonator (IR) is designed to realize parallel resonance in the resistive element by extending one finger of a strip-type interdigital capacitor to connect the two separate parts of the capacitor. The IR is equivalent to a parallel LC circuit. Lumped resistors are loaded around the IR to absorb the incident wave at lower and upper absorption bands. With the bandpass FSS as the ground plane, the absorption performances at both the lower and upper bands around the resonant frequency are improved compared to a metal-plane-backed absorber structure. The FSR passband is designed at 10 GHz with an insertion loss of 0.2 dB. The band with a reflection coefficient below -10 dB extends from 4.8 to 15.5 GHz. A further extension to dual-polarized FSR is designed, fabricated, and measured to validate the proposed design.
Histone H3 trimethylation at lysine 36 (H3K36me3) is an important histone mark involved in both transcription elongation and DNA mismatch repair (MMR). It is known that H3K36me3 recruits the ...mismatch-recognition protein MutSα to replicating chromatin via its physical interaction with MutSα's PWWP domain, but the exact role of H3K36me3 in transcription is undefined. Using ChIP combined with whole-genome DNA sequencing analysis, we demonstrate here that H3K36me3, together with MutSα, is involved in protecting against mutation, preferentially in actively transcribed genomic regions. We found that H3K36me3 and MutSα are much more co-enriched in exons and actively transcribed regions than in introns and nontranscribed regions. The H3K36me3–MutSα co-enrichment correlated with a much lower mutation frequency in exons and actively transcribed regions than in introns and nontranscribed regions. Correspondingly, depleting H3K36me3 or disrupting the H3K36me3–MutSα interaction elevated the spontaneous mutation frequency in actively transcribed genes, but it had little influence on the mutation frequency in nontranscribed or transcriptionally inactive regions. Similarly, H2O2-induced mutations, which mainly cause base oxidations, preferentially occurred in actively transcribed genes in MMR-deficient cells. The data presented here suggest that H3K36me3-mediated MMR preferentially safeguards actively transcribed genes not only during replication by efficiently correcting mispairs in early replicating chromatin but also during transcription by directly or indirectly removing DNA lesions associated with a persistently open chromatin structure.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Intelligent metasurfaces have gained significant importance in recent years due to their ability to dynamically manipulate electromagnetic (EM) waves. Their multifunctional characteristics, realized ...by incorporating active elements into the metasurface designs, have huge potential in numerous novel devices and exciting applications. In this article, recent progress in the field of intelligent metasurfaces are reviewed, focusing particularly on tuning mechanisms, hardware designs, and applications. Reconfigurable and programmable metasurfaces, classified as space gradient, time modulated, and space–time modulated metasurfaces, are discussed. Then, reconfigurable intelligent surfaces (RISs) that can alter their wireless environments, and are considered as a promising technology for sixth‐generation communication networks, are explored. Next, the recent progress made in simultaneously transmitting and reflecting reconfigurable intelligent surfaces (STAR‐RISs) that can achieve full‐space EM wave control are summarized. Finally, the perspective on the challenges and future directions of intelligent metasurfaces are presented.
This review presents the recent progress of intelligent metasurfaces, focusing on tuning mechanisms, hardware designs, and applications. The authors discuss the reconfigurable and programmable metasurfaces, classified as space‐gradient, time‐modulated, and space–time modulated metasurfaces. Furthermore, the emerging research direction of reconfigurable intelligent surfaces are demonstrated. Finally, the challenges and future directions of intelligent metasurfaces are presented.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
We report on a theoretical study of spin-dependent electron transport through single-helical molecules connected by two nonmagnetic electrodes, and explain the experiment of significant ...spin-selective phenomenon observed in α-helical protein and the contradictory results between the protein and single-stranded DNA. Our results reveal that the α-helical protein is an efficient spin filter and the spin polarization is robust against the disorder. These results are in excellent agreement with recent experiments Mishra D, et al. (2013) Proc Natl Acad Sci USA 110(37):14872–14876; Göhler B, et al. (2011) Science 331(6019):894–897 and may facilitate engineering of chiral-based spintronic devices.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
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