Using scanning tunneling microscopy and spectroscopy, we demonstrate that the adsorption of a minute amount of Cs on a Pb mesa grown in the quantum regime can induce dramatic morphological changes of ...the mesa, characterized by the appearance of populous monatomic-layer-high Pb nano-islands on top of the mesa. The edges of the Pb nano-islands are decorated with Cs adatoms, and the nano-islands preferentially nucleate and grow on the quantum mechanically unstable regions of the mesa. Furthermore, first-principles calculations within density functional theory show that the Pb atoms forming these nano-islands were expelled by the adsorbed Cs atoms via a kinetically accessible place exchange process when the Cs atoms alloyed into the top layer of the Pb mesa.
Oncogenic H-Ras G12V and its variants have been shown to inhibit muscle differentiation. However, the role of proto-oncogenic Ras (c-Ras) in muscle differentiation remains unclear. The active ...GTP-bound form of Ras has been known to associate with diverse effectors including Raf, phosphatidylinositol 3-kinase (PI3K), Ral-GDS, and other molecules to transmit downstream signals. We hypothesize that c-Ras may stimulate muscle differentiation by selectively activating PI3K, an important mediator for muscle differentiation. In our experiments, inhibition of c-Ras by farnesyltransferase inhibitors and a dominant negative form of H-Ras (Ras S17N) suppressed muscle differentiation. Consistently, individual knockdown of H-Ras, K-Ras, and N-Ras by siRNAs all blocked muscle differentiation. Interestingly, we found that c-Ras preferentially interacts with PI3K rather than its major binding partner c-Raf, during myogenic differentiation, with total c-Ras activity remaining unchanged. PI3K and its downstream myogenic pathway, the Nox2/NF-kappaB/inducible nitric oxide synthase (iNOS) pathway, were found to be suppressed by inhibition of c-Ras activity during differentiation. Furthermore, expression of a constitutively active form of PI3K completely rescued the differentiation block and reactivated the Nox2/NF-kappaB/iNOS pathway in c-Ras-inhibited cells. On the basis of our results, we conclude that contrary to oncogenic Ras, proto-oncogenic H-Ras, K-Ras, and N-Ras are directly involved in the promotion of muscle differentiation via PI3K and its downstream signaling pathways. In addition, PI3K pathway activation is associated with a concurrent suppression of the otherwise predominantly activated Raf/Mek/Erk pathway.
Key message
Calli protoplasts isolated from three soybean cultivars are useful tools to evaluate guide RNAs for clustered regularly interspaced short palindromic repeats (CRISPR)-based precise gene ...editing.
A type V CRISPR effector, LbCpf1(Cas12a) from
Lachnospiraceae bacterium
ND 2006, has been used for precision editing of the plant genome. We report that callus-derived protoplasts from three soybeans, including
Glycine Max
var. Williams 82 and two Korean cultivars (Kwangan and Daewon) represent efficient systems for the screening of active crRNA for CRISPR/LbCpf1. CRISPR/LbCpf1 ribonucleoproteins (RNPs) were delivered as complexes of purified endonucleases mixed with designed crRNA to simultaneously edit target genes of
GlymaFAD2-1A
and
GlymaFAD2-1B
transfected into three soybean protoplasts including genome-sequenced Williams 82 with cultivars, Kwangan and Daewon. Previously, we reported that nine crRNAs designed for LbCpf1 exhibited varying degrees of editing efficacy for two
FAD2
genes. Among the nine crRNAs, the LbCpf1-crRNA3 complexes showed the highest efficiency in soybean cotyledon protoplasts. The new screening systems of callus protoplasts from three soybeans have been successfully used to transfect GFP-tagged markers and CRISPR/LbCpf1 RNPs. The callus protoplasts confirm that the LbCpf1-crRNA3 complex is an active crRNA for LbCpf1 to edit two
FAD2
genes similar to cotyledon protoplasts. These results demonstrate that soybean callus protoplast-based CRISPR/crRNA selection is a new and practical tool to screen the efficacy of crRNAs and a prerequisite for progressive regeneration of the edited soybean.
Spinal cord injury (SCI) is a complex cause of rapid low bone mass that easily predisposes the affected individuals to osteoporosis-induced fractures. Several studies have investigated osteoporosis ...pathophysiology in SCI; however, those associated with its diagnosis in SCI are limited. Additionally, errors in osteoporosis diagnosis and its prevalence vary based on the bone mineral density (BMD) reference values (BMDRV), and no studies have reported BMDRV application for osteoporosis diagnosis in individuals with SCI. Therefore, this study aimed to compare the prevalence of osteoporosis among Korean adults aged ≥ 50 years with SCI according to BMDRV for diagnosing osteoporosis.
Overall, 855 patients with SCI who underwent BMD tests of the lumbar spine, femoral neck, and total hip at the National Rehabilitation Center (NRC) in Korea between 2010 and 2020 were included in this retrospective cross-sectional study. Osteoporosis was diagnosed in patients with SCI by comparing the differences in prevalence, diagnostic consistency, and risk factors according to the region-based BMDRV of the dual-energy x-ray absorptiometry (DXA) manufacturer and international BMDRV based on the Third National Health and Nutrition Examination Survey (NHANES III) data of females aged 20-29 years.
The prevalence of osteoporosis according to the T-score provided by a single reference population of the NHANES III (TNHA) (PONHA) (males: 26.69%; females: 69.35%) was significantly higher in females and males than that according to the T-scores provided by the DXA manufacturer (TDXA) (PODXA) (males: 15.32%; females: 43.15%). The lumbar spine and femoral neck were major osteoporosis diagnosis sites for the PODXA and PONHA, respectively. Risk factors for osteoporosis differed based on the probability of osteoporosis (also known as the OZ ratio) according to the BMD criteria; however, the risk factors were similar according to old age, female sex, low body mass index (BMI), and long SCI period. No significant relationship was noted between the different SCI-related clinical factors (p > 0.05).
The osteoporosis diagnostic site and prevalence in SCI differed according to the regional-based TDXA and international standards of the TNHA. Therefore, further studies on BMDRV are warranted to establish accurate diagnostic criteria for osteoporosis prevention in patients with SCI.
Abstract
The outbreak of novel COVID-19 disease elicited a wide range of anti-contagion and economic policies like school closure, income support, contact tracing, and so forth, in the mitigation and ...suppression of the spread of the SARS-CoV-2 virus. However, a systematic evaluation of these policies has not been made. Here, 17 implemented policies from the Oxford COVID-19 Government Response Tracker dataset employed in 90 countries from December 31, 2019, to August 31, 2020, were analyzed. A Poisson regression model was applied to analyze the relationship between policies and daily confirmed cases using a generalized estimating equations approach. A lag is a fixed time displacement in time series data. With that, lagging (0, 3, 7, 10, and 14 days) was also considered during the analysis since the effects of policies implemented on a given day may affect the number of confirmed cases several days after implementation. The countries were divided into three groups depending on the number of waves of the pandemic observed in each country. Through subgroup analysis, we showed that with and without lagging, contact tracing and containment policies were significant for countries with two waves, while closing, economic, and health policies were significant for countries with three waves. Wave-specific analysis for each wave showed that significant health, economic, and containment policies varied across waves of the pandemic. Emergency investment in healthcare was consistently significant among the three groups of countries, while the Stringency index was significant among all waves of the pandemic. These findings may help in making informed decisions regarding whether, which, or when these policies should be intensified or lifted.
Although the incidence of inflammatory bowel disease IBD is increasing in Asia, data on long-term epidemiological trends are limited. We performed a 30-year longitudinal study to investigate temporal ...trends in the epidemiology of Crohn's disease CD and ulcerative colitis UC in Seoul, Korea.
This population-based study included 1431 IBD patients 418 CD, 1013 UC diagnosed between 1986 and 2015 in the Songpa-Kangdong district of Seoul, Korea. Temporal trends in incidence, prevalence, and disease phenotype at diagnosis were analysed.
The adjusted mean annual incidence rates of CD and UC per 100 000 inhabitants increased from 0.06 (95% confidence interval CI, 0.05-0.07) and 0.29 95% CI, 0.27-0.31, respectively, in 1986-1990 to 2.44 95% CI, 2.38-2.50 and 5.82 95% CI, 5.73-5.92, respectively, in 2011-2015. Average annual percentage change in IBD incidence was 12.3% in 1986-1995, 12.3% in 1996-2005, and 3.3% in 2006-2015. The male-to-female ratio of the adjusted incidence rate was 3.3:1 for CD and 1.2:1 for UC. Perianal fistula/abscess was present in 43.3% of patients before or at CD diagnosis. At diagnosis, 54.3% of UC patients presented only with proctitis. The adjusted prevalence rate in 2015 was 31.59/100 000 95% CI, 31.10-32.07 for CD and 76.66/100 000 95% CI, 75.91-77.42 for UC.
The incidence and prevalence of IBD in Korea have continued to increase over the past three decades. Korean patients have distinct demographic and phenotypic characteristics, including a male predominance and high frequency of perianal fistula/abscess in CD and high proportion of proctitis in UC.
Since the discovery of messenger RNA (mRNA), there have been tremendous efforts to wield them in the development of therapeutics and vaccines. During the COVID-19 pandemic, two mRNA vaccines were ...developed and approved in record-breaking time, revolutionizing the vaccine development landscape. Although first-generation COVID-19 mRNA vaccines have demonstrated over 90% efficacy, alongside strong immunogenicity in humoral and cell-mediated immune responses, their durability has lagged compared to long-lived vaccines, such as the yellow fever vaccine. Although worldwide vaccination campaigns have saved lives estimated in the tens of millions, side effects, ranging from mild reactogenicity to rare severe diseases, have been reported. This review provides an overview and mechanistic insights into immune responses and adverse effects documented primarily for COVID-19 mRNA vaccines. Furthermore, we discuss the perspectives of this promising vaccine platform and the challenges in balancing immunogenicity and adverse effects.
The viscosity and thermal conductivity of ZnO nanofluids with nanoparticle shapes of nearly rectangular and of sphere, were experimentally investigated under various volume concentrations of the ...nanoparticles, ranging from 0.05 to 5.0 vol.%. The viscosity of the nanofluids increased with increases in the volume concentration by up to 69%. In addition, the enhancement of the viscosity of the nearly rectangular shape nanoparticles was found to be greater by 7.7%, than that of the spherical nanoparticles. The thermal conductivity of the ZnO nanofluids increased by up to 12% and 18% at 5.0 vol.% for the spherical and the nearly rectangular shape nanoparticles, respectively, compared to that of the base fluid (water). The shape of the particles is found to have a significant effect on the viscosity and thermal conductivity enhancements.
•Viscosity and conductivity of ZnO nanofluids increased with increase of ZnO concentration.•Viscosity and conductivity of rectangular shape ZnO nanofluid were higher than sphere's.•The Chen et al. model and the Prasher model showed minimum prediction error.
DNA-free, clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein (Cas) ribonucleoprotein (RNP)-based genome editing is a simple, convincing, and promising tool for ...precision crop breeding. The efficacy of designed CRISPR-based genome editing tools is a critical prerequisite for successful precision gene editing in crops.
This study demonstrates that soil-grown leaf- or callus-derived pepper protoplasts are a useful system for screening of efficient guide RNAs for CRISPR/Cas9 or CRISPR/Cas12a (Cpf1). CRISPR/Cas9 or Cpf1 were delivered as CRISPR/RNP complexes of purified endonucleases mixed with the designed single guide RNA, which can edit the target gene, CaMLO2 in two pepper cultivars with whole genome sequenced, Capsicum annuum 'CM334' and C. annuum 'Dempsey'. The designed guide RNAs (sgRNAs for Cas9 or crRNAs for Cpf1) are conserved for CaMLO2 in both CM334 and Dempsey and cleave CaMLO2 in vitro. CRISPR/Cas9- or /Cpf1-RNP complexes were transfected into purely isolated protoplasts of the hot pepper CM334 and sweet pepper Dempsey by PEG-mediated delivery. Targeted deep sequencing analysis indicated that the targeted CaMLO2 gene was differentially edited in both cultivars, depending on the applied CRISPR/RNPs.
Pepper protoplast-based CRISPR guide-RNA selection is a robust method to check the efficacy of designed CRISPR tools and is a prerequisite for regenerating edited plants, which is a critical time-limiting procedure. The rapid and convincing selection of guide RNA against a target genome reduces the laborious efforts for tissue culture and facilitates effective gene editing for pepper improvement.
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