Development of a prime editor with improved editing efficiency in Arabidopsis.

Prime editing is widely used in many organisms to introduce site-specific sequence modifications, such as base substitutions, insertions, and deletions, in genomic DNA without generating double-strand breaks. Despite their wide-ranging applications, prime editors (PEs) have low editing efficiency, especially in dicot plants, and are therefore barely used for genome engineering in these plant species. Here, based on the previous approaches used to improve prime editing efficiency, we generated multiple different combinations of PE components and prime editing guide RNAs (pegRNAs) and examined their prime editing efficiency in Arabidopsis thaliana protoplasts as the dicot model system.

Efficient inverse design of optical multilayer nano-thin films using neural network principles: backpropagation and gradient descent.

Optical multilayer thin films have a wide range of applications due to their ability to manipulate transmissive or reflective wavelengths by adjusting the thickness of composed layers, enabling diverse uses. Although their light weight, flexible nature and ease of fabrication position them as promising components for future devices, determining their optimal layer thickness for the desired functionality demands extensive simulations, leading to inefficient utilization of computational resources and time. To overcome these challenges, inverse design methods, leveraging machine learning and deep learning, are being explored.

Gulf war illness: a tale of two genomes.

Introduction: Gulf War illness (GWI) is an environmentally-triggered chronic multisymptom illness typified by protean symptoms, in which mitochondrial impairment is evident. It has been likened to accelerated aging. Nuclear genetics of detoxification have been linked to GWI.

Quantum-Dot Light-Emitting Fiber Toward All-In-One Clothing-Type Health Monitoring.

In the Fourth Industrial Revolution, as the connection between objects and people becomes increasingly important, interest in wearable optoelectronic device-based medical diagnosis is on the rise. Pulse oximetry sensors based on a fiber platform, which is the smallest unit of clothing, could be considered an attractive candidate for this application. In this study, red and green quantum-dot light-emitting fibers (QDLEFs) based on a 250 μm-diameter 1-dimensional fiber were successfully implemented, achieving high current efficiencies of approximately 22.

Bioenergetic impairment in Gulf War illness assessed via P-MRS.

Time for post-exercise phosphocreatine-recovery (PCr-R), deemed a robust index of mitochondrial function in vivo, was previously reported to be elevated (signifying impaired ATP production) in veterans with Gulf War illness (GWI). Here we sought to replicate the finding and assess the impact of contravening previous eligibility requirements. The replication sample comprised white males.

Susceptibility to radiation adverse effects in veterans with Gulf War illness and healthy civilians.

We evaluated whether veterans with Gulf War illness (VGWI) report greater ionizing radiation adverse effects (RadAEs) than controls; whether radiation-sensitivity is tied to reported chemical-sensitivity; and whether environmental exposures are apparent risk factors for reported RadAEs (rRadAEs). 81 participants (41 VGWI, 40 controls) rated exposure to, and rRadAEs from, four radiation types. The relations of RadAE-propensity (defined as the ratio of rRadAEs to summed radiation exposures) to Gulf War illness (GWI) presence and severity, and to reported chemical-sensitivity were assessed.

Genome-wide in-locus epitope tagging of Arabidopsis proteins using prime editors.

Prime editors (PEs), which are CRISPR-Cas9 nickase (H840A)-reverse transcriptase fusion proteins programmed with prime editing guide RNAs (pegRNAs), can not only edit bases but also install transversions, insertions, or deletions without both donor DNA and double-strand breaks at the target DNA. As the demand for in-locus tagging is increasing, to reflect gene expression dynamics influenced by endogenous genomic contexts, we demonstrated that PEs can be used to introduce the hemagglutinin (HA) epitope tag to a target gene locus, enabling molecular and biochemical studies using in-locus tagged plants. To promote genome-wide in-locus tagging, we also implemented a publicly available database that designs pegRNAs for in-locus tagging of all the Arabidopsis genes.

Effect of a Mismatched Vaccine against the Outbreak of a Novel FMD Strain in a Pig Population.

In December 2014, a novel foot and mouth disease (FMD) virus was introduced to a pig farm in South Korea, despite the animals being vaccinated. A marginal antigenic matching between the novel and vaccine strains potentially led to the infection of the vaccinated animals. To understand the impact of using an FMD vaccine on the transmission dynamics of an unmatched field strain, simulation models were employed using daily reported data on clinical cases from the farm.

Adverse effect propensity: A new feature of Gulf War illness predicted by environmental exposures.

A third of 1990-1 Gulf-deployed personnel developed drug/chemical-induced multisymptom illness, "Gulf War illness" (). Veterans with GWI () report increased drug/exposure adverse effects (). Using previously collected data from a case-control study, we evaluated whether the fraction of exposures that engendered AEs ("AE Propensity") is increased in VGWI (it was); whether AE Propensity is related to self-rated "chemical sensitivity" (it did); and whether specific exposures "predicted" AE Propensity (they did).

Statin Use in Relation to COVID-19 and Other Respiratory Infections: Muscle and Other Considerations.

Statins have been widely advocated for use in COVID-19 based on large favorable observational associations buttressed by theoretical expected benefits. However, past favorable associations of statins to pre-COVID-19 infection outcomes (also buttressed by theoretical benefits) were unsupported in meta-analysis of RCTs, RR = 1.00.

MutSα and MutSβ as size-dependent cellular determinants for prime editing in human embryonic stem cells.

Precise genome editing in human pluripotent stem cells (hPSCs) has potential applications in isogenic disease modeling and stem cell therapy, necessitating diverse genome editing tools. However, unlike differentiated somatic cells, hPSCs have unique cellular properties that maintain genome integrity, which largely determine the overall efficiency of an editing tool. Considering the high demand for prime editors (PEs), it is imperative to characterize the key molecular determinants of PE outcomes in hPSCs.

Visual function restoration in a mouse model of Leber congenital amaurosis via therapeutic base editing.

Leber congenital amaurosis (LCA), an inherited retinal degeneration, causes severe visual dysfunction in children and adolescents. In patients with LCA, pathogenic variants, such as , are evident in specific genes, related to the functions of retinal pigment epithelium and photoreceptors. In contrast to the original Cas9, base editing tools can correct pathogenic substitutions without generation of DNA double-stranded breaks (DSBs).

Changes in Long-Term Functional Independence in Patients with Moderate and Severe Ischemic Stroke: Comparison of the Responsiveness of the Modified Barthel Index and the Functional Independence Measure.

This study investigated the long-term functional changes in patients with moderate-to-severe ischemic stroke. In addition, we investigated whether there was a difference between the modified Barthel Index (MBI) and Functional Independence Measure (FIM) according to severity. To evaluate the changes in the long-term functional independence of the subjects, six evaluations were conducted over 2 years, and the evaluation was performed using MBI and FIM.

High expression of uracil DNA glycosylase determines C to T substitution in human pluripotent stem cells.

Precise genome editing of human pluripotent stem cells (hPSCs) is crucial not only for basic science but also for biomedical applications such as stem cell therapy and genetic disease modeling. However, hPSCs have unique cellular properties compared to somatic cells. For instance, hPSCs are extremely susceptible to DNA damage, and therefore Cas9-mediated DNA double-strand breaks (DSB) induce p53-dependent cell death, resulting in low Cas9 editing efficiency.

Understanding the transmission of African swine fever in wild boars of South Korea: A simulation study for parameter estimation.

Since the introduction of African swine fever (ASF) to Georgia in 2007, the disease has spread to many other countries including South Korea. Initial detection of ASF from wild boars (WB) in South Korea was reported in early October 2019. Since then, more than a thousand WB samples collected from the northern part of the country have been confirmed as ASF positive (2.

Arabidopsis ATXR2 represses de novo shoot organogenesis in the transition from callus to shoot formation.

Plants exhibit high regenerative capacity, which is controlled by various genetic factors. Here, we report that ARABIDOPSIS TRITHORAX-RELATED 2 (ATXR2) controls de novo shoot organogenesis by regulating auxin-cytokinin interaction. The auxin-inducible ATXR2 Trithorax Group (TrxG) protein temporally interacts with the cytokinin-responsive type-B ARABIDOPSIS RESPONSE REGULATOR 1 (ARR1) at early stages of shoot regeneration.

Impact of risk-based partial vaccination on clinical incidence and seroprevalence of foot and mouth disease in Lao PDR.

Foot and mouth disease (FMD) is endemic in the Lao People's Democratic Republic (PDR) and it causes economic loss to smallholder husbandry systems. An intervention programme based on a risk-based partial vaccination strategy was implemented in three provinces of Lao PDR (Champasak, Savannakhet and Xiangkhouang) to immunise domestic cattle and buffalo during 2016-2020. Two cross-sectional surveys were conducted in 2016/17 and 2020 to evaluate the impact of the vaccination programme on the prevalence of FMD virus exposure and clinical incidence of the disease.

Lower blood malondialdehyde is associated with past pesticide exposure: findings in Gulf War illness and healthy controls.

Background: Malondialdehyde (MDA) is a candidate general marker of oxidative stress (OS). We sought to assess the relation of MDA to Gulf War illness (GWI) and to a variety of exposures.

Methods: This is an observational study involving subjects from Southern California recruited from October 2011 to May 2014.

genome editing in single mammalian brain neurons through CRISPR-Cas9 and cytosine base editors.

Gene manipulation is a useful approach for understanding functions of genes and is important for investigating basic mechanisms of brain function on the level of single neurons and circuits. Despite the development and the wide range of applications of CRISPR-Cas9 and base editors (BEs), their implementation for an analysis of individual neurons remained limited. In fact, conventional gene manipulations are generally achieved only on the population level.

Efficient Human Cell Coexpression System and Its Application to the Production of Multiple Coronavirus Antigens.

Coproduction of multiple proteins at high levels in a single human cell line would be extremely useful for basic research and medical applications. Here, a novel strategy for the stable expression of multiple proteins by integrating the genes into defined transcriptional hotspots in the human genome is presented. As a proof-of-concept, it is shown that EYFP is expressed at similar levels from hotspots and that the EYFP expression increases proportionally with the copy number.

A Pilot Study of Bioenergetic Marker Relationships in Gulf War Illness: Phosphocreatine Recovery vs. Citric Acid Cycle Intermediates.

Impaired bioenergetics have been reported in veterans with Gulf War illness (VGWIs), including prolonged post-exercise recovery of phosphocreatine (PCr-R) assessed with Phosphorus magnetic resonance spectroscopy. The citric acid cycle (CAC) is considered the most important metabolic pathway for supplying energy, with relationships among CAC markers reported to shift in some but not all impaired bioenergetic settings. We sought to assess relations of CAC markers to one another and to PCr-R.

Parallel-Stacked Flexible Organic Light-Emitting Diodes for Wearable Photodynamic Therapeutics and Color-Tunable Optoelectronics.

Deformable organic light-emitting diode (OLED) based optoelectronic devices hold promise for various wearable applications including biomedical systems and displays, but current OLED technologies require high voltage and lack the power needed for wearable photodynamic therapy (PDT) applications and wearable displays. This paper presents a parallel-stacked OLED (PAOLED) with high power, more than 100 mW/cm, at low voltage (<8 V). The current dispersion ratio can be tuned by optimizing the structure of the individual OLEDs stacked to create the PAOLED, allowing control of the PAOLED's wavelength shapes, current efficiency, and power.

Differences in antibiotic usage patterns for acute pyelonephritis according to hospital type and region in the Republic of Korea: A population-based study.

This study aimed to determine the differences in antibiotic usage patterns in the treatment of acute pyelonephritis according to hospital type and region in Korea.The claims database of the Health Insurance Review and Assessment Service in Korea was used to select patients with the International Classification of Diseases, Tenth Revision code N10 (acute tubulo-interstitial nephritis) or N12 (tubulo-interstitial nephritis, neither acute nor chronic) as the primary discharge diagnosis in 2010-2014. Usage of each class of antibiotics was expressed as the defined daily dose (DDD)/event.