Hydrogen Gas Inhalation Treatment for Coronary Artery Lesions in a Kawasaki Disease Mouse Model.

BACKGROUND: Kawasaki disease (KD) is a syndrome primarily affecting young children, typically under the age of five, and is characterized by the development of acute vasculitis. Through extensive research conducted on both murine and human subjects, it has been demonstrated that heightened levels of reactive oxygen species (ROS) play a pivotal role in the development of KD, especial coronary artery lesions (CALs). Hydrogen gas exhibits potent antioxidant properties that effectively regulate ROS production and the inflammatory response. METHODS: We used Lactobacillus casei cell wall extract (LCWE)-induced vasculitis in mice as an animal model of KD and treated the mice with hydrogen gas inhalation. RESULTS: We observed significant dilatation and higher Z scores in the left coronary artery (LCA) in D21 and D28 in mice after LCWE treatment compared to the control group (p < 0.001) and a significant resolution of LCA diameters (p < 0.01) and Z scores (p < 0.01) after treatment with inhaled hydrogen gas. We further demonstrated that serum IL-6 expression was higher in mice after LCWE treatment (p < 0.01) and IL-6 significantly decreased after inhaled hydrogen gas therapy (p < 0.001). CONCLUSION: According to our literature review, this is the first report where hydrogen gas inhalation has been demonstrated to be effective for the treatment of coronary artery dilatation in a KD murine model.

Evaluating artificial intelligence-enhanced digital urine cytology for bladder cancer diagnosis.

BACKGROUND: This study evaluated the diagnostic effectiveness of the AIxURO platform, an artificial intelligence-based tool, to support urine cytology for bladder cancer management, which typically requires experienced cytopathologists and substantial diagnosis time. METHODS: One cytopathologist and two cytotechnologists reviewed 116 urine cytology slides and corresponding whole-slide images (WSIs) from urology patients. They used three diagnostic modalities: microscopy, WSI review, and AIxURO, per The Paris System for Reporting Urinary Cytology (TPS) criteria. Performance metrics, including TPS-guided and binary diagnosis, inter- and intraobserver agreement, and screening time, were compared across all methods and reviewers. RESULTS: AIxURO improved diagnostic accuracy by increasing sensitivity (from 25.0%-30.6% to 63.9%), positive predictive value (PPV; from 21.6%-24.3% to 31.1%), and negative predictive value (NPV; from 91.3%-91.6% to 95.3%) for atypical urothelial cell (AUC) cases. For suspicious for high-grade urothelial carcinoma (SHGUC) cases, it improved sensitivity (from 15.2%-27.3% to 33.3%), PPV (from 31.3%-47.4% to 61.1%), and NPV (from 91.6%-92.7% to 93.3%). Binary diagnoses exhibited an improvement in sensitivity (from 77.8%-82.2% to 90.0%) and NPV (from 91.7%-93.4% to 95.8%). Interobserver agreement across all methods showed moderate consistency (κ = 0.57-0.61), with the cytopathologist demonstrating higher intraobserver agreement than the two cytotechnologists across the methods (κ = 0.75-0.88). AIxURO significantly reduced screening time by 52.3%-83.2% from microscopy and 43.6%-86.7% from WSI review across all reviewers. Screening-positive (AUC+) cases required more time than negative cases across all methods and reviewers. CONCLUSIONS: AIxURO demonstrates the potential to improve both sensitivity and efficiency in bladder cancer diagnostics via urine cytology. Its integration into the cytopathological screening workflow could markedly decrease screening times, which would improve overall diagnostic processes.

Nitrogen Configuration Effects on Charge Carrier Dynamics in CsPbBr3/Carbon Dots S-Scheme Heterojunction for Photocatalytic CO2 Reduction.

Nitrogen-doped carbon dots (NCDs) featuring primary pyrrolic N and pyridinic N dominated configurations were prepared using hydrothermal (H-NCDs) and microwave (M-NCDs) methods, respectively. These H-NCDs and M-NCDs were subsequently applied to decorate CsPbBr3 nanocrystals (CPB NCs) individually, using a ligand-assisted reprecipitation process. Both CPB/M-NCDs and CPB/H-NCDs nanoheterostructures (NHSs) exhibited S-scheme charge transfer behavior, which enhanced their performance in photocatalytic CO2 reduction and selectivity of CO2-to-CH4 conversion, compared to pristine CPB NCs. The presence of pyrrolic N configuration at the heterojunction of CPB/H-NCDs facilitated efficient S-scheme charge transfer, leading to a remarkable 43-fold increase in photoactivity. In contrast, CPB/M-NCDs showed only a modest 3-fold enhancement in photoactivity, which was attributed to electron trapping by pyridinic N at the heterojunction. The study offers crucial insights into charge carrier dynamics within perovskite/carbon NHSs at the molecular level to advance the understanding of solar fuel generation.

Cost-effectiveness analysis of mosunetuzumab for treatment of relapsed or refractory follicular lymphoma after two or more lines of systemic therapy in the United States.

AIMS: Mosunetuzumab has received accelerated approval by the US Food and Drug Administration for adult patients with relapsed or refractory (R/R) follicular lymphoma (FL) after two or more lines of systemic therapy. We evaluated the cost-effectiveness of mosunetuzumab for the treatment of R/R FL from a US private payer perspective. MATERIALS AND METHODS: A partitioned survival model simulated lifetime costs and outcomes of mosunetuzumab against seven comparators: axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), tazemetostat (taz, EZH2 wild-type only), rituximab plus lenalidomide (R-Len) or bendamustine (R-Benda), obinutuzumab plus bendamustine (O-Benda), and a retrospective real-world cohort (RW) based on current patterns of care derived from US electronic health records (Flatiron Health). Efficacy data for mosunetuzumab were from the pivotal Phase II GO29781 trial (NCT02500407). Relative treatment efficacy was estimated from indirect treatment comparisons (ITCs). Costs included were related to treatment, adverse events, routine care, and terminal care. Except for drug costs (March 2023), all costs were inflated to 2022 US dollars. Costs and quality-adjusted life-years (QALYs) were used to calculate incremental cost-effectiveness ratios (ICERs). Net monetary benefit (NMB) was calculated using a willingness-to-pay (WTP) threshold of $150,000/QALY. RESULTS: Mosunetuzumab dominated taz, tisa-cel, and axi-cel with greater QALYs and lower costs. Mosunetuzumab was projected to be cost-effective against R-Benda, O-Benda, and RW with ICERs of $78,607, $42,731, and $21,434, respectively. Mosunetuzumab incurred lower costs but lower QALYs vs. R-Len. NMBs showed that mosunetuzumab was cost-effective against comparators except R-Len. LIMITATIONS: Without head-to-head comparative data, the model had to rely on ITCs, some of which were affected by residual bias. Model inputs were obtained from multiple sources. Extensive sensitivity analyses assessed the importance of these uncertainties. CONCLUSION: Mosunetuzumab is estimated to be cost-effective compared with approved regimens except R-Len for the treatment of adults with R/R FL.

Budget Impact of Introducing Fixed-Duration Mosunetuzumab for the Treatment of Relapsed or Refractory Follicular Lymphoma After Two or More Lines of Systemic Therapy in the USA.

OBJECTIVE: This study aimed to assess the budget impact of introducing fixed-duration mosunetuzumab as a treatment option for adult patients with relapsed or refractory follicular lymphoma after at least two prior systemic therapies and to estimate the total cumulative costs per patient in the USA. METHODS: A 3-year budget impact model was developed for a hypothetical 1-million-member cohort enrolled in a mixed commercial/Medicare health plan. Comparators were: axicabtagene ciloleucel, tisagenlecleucel, tazemetostat, rituximab plus lenalidomide, copanlisib, and older therapies (rituximab or obinutuzumab ± chemotherapy). Costs per patient comprised treatment-associated costs including the drug, its administration, adverse events, and routine care. Dosing and safety data were ascertained from respective package inserts and clinical trial data. Drug costs (March 2023) were estimated based on the average wholesale acquisition cost reported in AnalySource®, and all other costs were based on published sources and inflated to 2022 US dollars. Market shares were obtained from Genentech internal projections and expert opinion. Budget impact outcomes were presented on a per-member per-month basis. RESULTS: Compared with a scenario without mosunetuzumab, its introduction over 3 years resulted in a budget increase of $69,812 (1% increase) and an average per-member per-month budget impact of $0.0019. Among the newer therapies, mosunetuzumab had the second-lowest cumulative per patient cost (mosunetuzumab = $202,039; axicabtagene ciloleucel = $505,845; tisagenlecleucel = $476,293; rituximab plus lenalidomide = $263,520; tazemetostat = $250,665; copanlisib = $127,293) and drug costs, and its introduction only increased total drug costs by 0.1%. By year 3, the cumulative difference in the per patient cost with mosunetuzumab was -$303,805 versus axicabtagene ciloleucel, -$274,254 versus tisagenlecleucel, -$61,481 versus rituximab plus lenalidomide, -$48,625 versus tazemetostat, and $74,747 versus copanlisib. Older therapies were less costly with 3-year cumulative costs that ranged from $36,512 to $147,885. CONCLUSIONS: Over 3 years, the estimated cumulative per patient cost of mosunetuzumab is lower than most available newer therapies, resulting in a small increase in the budget after its formulary adoption for the treatment of relapsed or refractory follicular lymphoma.

Ptychographic Nanoscale Imaging of the Magnetoelectric Coupling in Freestanding BiFeO3.

Understanding the magnetic and ferroelectric ordering of magnetoelectric multiferroic materials at the nanoscale necessitates a versatile imaging method with high spatial resolution. Here, soft X-ray ptychography is employed to simultaneously image the ferroelectric and antiferromagnetic domains in an 80 nm thin freestanding film of the room-temperature multiferroic BiFeO3 (BFO). The antiferromagnetic spin cycloid of period 64 nm is resolved by reconstructing the corresponding resonant elastic X-ray scattering in real space and visualized together with mosaic-like ferroelectric domains in a linear dichroic contrast image at the Fe L3 edge. The measurements reveal a near perfect coupling between the antiferromagnetic and ferroelectric ordering by which the propagation direction of the spin cycloid is locked orthogonally to the ferroelectric polarization. In addition, the study evinces both a preference for in-plane propagation of the spin cycloid and changes of the ferroelectric polarization by 71° between multiferroic domains in the epitaxial strain-free, freestanding BFO film. The results provide a direct visualization of the strong magnetoelectric coupling in BFO and of its fine multiferroic domain structure, emphasizing the potential of ptychographic imaging for the study of multiferroics and non-collinear magnetic materials with soft X-rays.

Resonant x-ray diffraction measurements in charge ordered kagome superconductors KV3Sb5and RbV3Sb5.

We report on (resonant) x-ray diffraction experiments on the normal state properties of kagome-lattice superconductors KV3Sb5and RbV3Sb5. We have confirmed previous reports indicating that the charge density wave (CDW) phase is characterized by a doubling of the unit cell in all three crystallographic directions. By monitoring the temperature dependence of Bragg peaks associated with the CDW phase, we ascertained that it develops gradually over several degrees, as opposed to CsV3Sb5, where the CDW peak intensity saturates promptly just below the CDW transition temperature. Analysis of symmetry modes indicates that this behavior arises due to lattice distortions linked to the formation of CDWs. These distortions occur abruptly in CsV3Sb5, while they progress more gradually in RbV3Sb5and KV3Sb5. In contrast, the amplitude of the mode leading to the crystallographic symmetry breaking fromP6/mmmtoFmmmappears to develop more gradually in CsV3Sb5as well. Diffraction measurements close to the V K edge and the Sb L1edge show no sensitivity to inversion- or time-symmetry breaking, which are claimed to be associated with the onset of the CDW phase. The azimuthal angle dependence of the resonant diffraction intensity observed at the Sb L1edge is associated with the difference in the population of unoccupied states and the anisotropy of the electron density of certain Sb ions.

Positive Echocardiographic Association between Carotid Artery and Coronary Artery Diameter and Z-Score in a Mouse Model of Kawasaki Disease.

Kawasaki disease (KD) occurs in young children, has an unknown etiology, and can cause such life-threatening complications as coronary artery aneurysm. A mouse model using Lactobacillus casei cell wall extract (LCWE) with intraperitoneal injection was established for KD years ago. Histological examination of coronary artery lesions indicated features similar to those of vascular lesions of patients with KD. Since animals must be sacrificed during histological examination, the longitudinal survey of coronary artery lesions (CALs) is difficult. The aim of this study was to survey the vasculitis status of the coronary artery and the carotid artery in a KD mouse model. METHOD: LCWE was intraperitoneally injected into 5-week-old male C57BL/6 mice to induce CALs. We studied the longitudinal status of the carotid and coronary arteries and analyzed the Z-score of coronary artery diameter. RESULTS: Carotid artery wall thickness (day 7) and diameter (day 14) significantly increased in the LCWE group with a dose-dependent effect (p < 0.05). Aortic diameter and wall thickness demonstrated significant increases on day 28 and day 7, respectively (p < 0.05). Carotid artery outer diameter and wall thickness were positively associated with coronary artery diameter on day 28 (p < 0.01). Coronary artery diameter significantly increased in the LCWE group after day 7 (p < 0.05). The percentage of Z > 3.0 indicated was more than 80% in the high-dose LCWE group and 0% in the control group. CONCLUSIONS: This report is the first to use coronary artery Z-score in a mouse model of KD by echocardiography and to find a positive association between carotid artery and coronary artery diameter.

Deep learning based decision tree ensembles for incomplete medical datasets.

BACKGROUND: In practice, the collected datasets for data analysis are usually incomplete as some data contain missing attribute values. Many related works focus on constructing specific models to produce estimations to replace the missing values, to make the original incomplete datasets become complete. Another type of solution is to directly handle the incomplete datasets without missing value imputation, with decision trees being the major technique for this purpose. OBJECTIVE: To introduce a novel approach, namely Deep Learning-based Decision Tree Ensembles (DLDTE), which borrows the bounding box and sliding window strategies used in deep learning techniques to divide an incomplete dataset into a number of subsets and learning from each subset by a decision tree, resulting in decision tree ensembles. METHOD: Two medical domain problem datasets contain several hundred feature dimensions with the missing rates of 10% to 50% are used for performance comparison. RESULTS: The proposed DLDTE provides the highest rate of classification accuracy when compared with the baseline decision tree method, as well as two missing value imputation methods (mean and k-nearest neighbor), and the case deletion method. CONCLUSION: The results demonstrate the effectiveness of DLDTE for handling incomplete medical datasets with different missing rates.

Antibacterial and antibiofilm effects of Camellia oleifera seed dreg extract and its application in cosmetics.

BACKGROUND: Cosmetic care products contain a high proportion of water and nutrients. Therefore, preventing bacterial growth is an important issue to ensure product quality and safety. The application of antibacterial natural ingredients derived from plants is considered to have the potential to maintain product quality and reduce the use of chemicals in formulations. Additionally, chemically synthesized antiseptic and antibacterial agents are widely used in the industry at present. However, some preservative ingredients have been reported that may cause skin irritation, redness, allergies, and even dermatitis. AIMS: This study aimed to prepare extract from Camellia oleifera tea seed dregs (CTSD), investigate the antibacterial effects on two pathogenic bacteria and evaluate the product preservative ability. METHODS: Ethanol extraction was prepared and subjected to characterize their triterpenoid contents. The minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and minimum biofilm eradication concentration (MBEC) were determined for Pseudomonas aeruginosa and Staphylococcus aureus. The product's stability and preservative qualities, along with its ability to scavenge free radicals through antioxidant activity, were also assessed. RESULTS: The gram-positive S. aureus showed greater susceptibility to the treatment. In additional, CTSD possessed significant free radical scavenging activity in vitro and cultured normal human skin fibroblast CCD-966SK cells under nontoxic concentration. The challenge test and accelerated storage test confirmed the CTSD containing formulated emulsion is eligible for commercialization. CONCLUSIONS: CTSD has the potential to be developed as an alternative agent to control microbial biofilm formation, or can be used as an adjuvant compound for infectious disease control.

PREVALENCE AND CLINICAL FEATURES OF RADIAL FUNDUS AUTOFLUORESCENCE IN HIGH MYOPIC WOMEN.

PURPOSE: To determine the prevalence and characteristics of radial fundus autofluorescence (FAF) in highly myopic women. METHODS: This was a retrospective, observational case study to determine the prevalence of radial FAF in the ultra-widefield FAF images in women. The clinical characteristics of these patients were evaluated. RESULTS: Fifteen of 1,935 (0.78%) highly myopic women were found to have radial FAF. Their mean age was 36.6 ± 25.6 years, and their mean best-corrected visual acuity was 0.3 ± 0.42 logMAR units. The mean axial length (AL) was 28.8 ± 2.8 mm. Among the 15 cases, eight did not have pigmentary changes and seven had pigmentary changes in the ultra-widefield FAF images. The women with the pigmentary changes were significantly older ( P = 0.021), had poorer BCVA ( P = 0.001), and had longer ALs ( P = 0.002). The visual fields and electroretinograms were worse in the eyes with pigmentary changes. CONCLUSION: The prevalence of radial FAF was 0.78% in women with high myopia. These patients might have mutations in the RPGR or RP2 genes and can develop high myopia and retinitis pigmentosa. Ultra-widefield FAF images should be examined in all highly myopic patients for early detection of radial FAF, and myopia prevention and genetic counseling for possible genetic therapy are recommended.

Anethole mitigates H2 O2 -induced inflammation in HIG-82 synoviocytes by suppressing the aquaporin 1 expression and activating the protein kinase A pathway.

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease affecting approximately 1% of the global population, with a higher prevalence in women than in men. Chronic inflammation and oxidative stress play pivotal roles in the pathogenesis of RA. Anethole, a prominent compound derived from fennel (Foeniculum vulgare), possesses a spectrum of therapeutic properties, including anti-arthritic, anti-inflammatory, antioxidant, and tumor-suppressive effects. However, its specific impact on RA remains underexplored. This study sought to uncover the potential therapeutic value of anethole in treating RA by employing an H2 O2 -induced inflammation model with HIG-82 synovial cells. Our results demonstrated that exposure to H2 O2 induced the inflammation and apoptosis in these cells. Remarkably, anethole treatment effectively countered these inflammatory and apoptotic processes triggered by H2 O2 . Moreover, we identified the aquaporin 1 (AQP1) and protein kinase A (PKA) pathway as critical regulators of inflammation and apoptosis. H2 O2 stimulation led to an increase in the AQP1 expression and a decrease in p-PKA-C, contributing to cartilage degradation. Conversely, anethole not only downregulated the AQP1 expression but also activated the PKA pathway, effectively suppressing cell inflammation and apoptosis. Furthermore, anethole also inhibited the enzymes responsible for cartilage degradation. In summary, our findings highlight the potential of anethole as a therapeutic agent for mitigating H2 O2 -induced inflammation and apoptosis in synovial cells, offering promising prospects for future RA treatments.

Corrigendum: Molecular markers associated to two non-allelic genic male sterility genes in peppers (Capsicum annuum L.).

[This corrects the article DOI: 10.3389/fpls.2018.01343.].

Single-sized N-functionality graphene quantum dot in tunable dual-modality near infrared-I/II illumination detection and photodynamic therapy under multiphoton nonlinear excitation.

Doping sorted graphene quantum dots (GQDs) with heteroatoms and functionalizing them with amino acid could improve their radiative recombination and two-photon properties-including their excitation-wavelength-independent photoluminescence from the ultraviolet to the near-infrared-I (NIR-I) region, absorption, quantum yield, absolute cross section, lifetime, and radiative-to-nonradiative decay ratio-under two-photon excitation (TPE) at a low excitation energy and short photoexcitation duration, as determined using a self-made optical microscopy system with a femtosecond Ti-sapphire laser. Four types of sorted GQDs were investigated: undoped GQDs, nitrogen-doped GQDs (N-GQDs), amino-functionalized GQDs (amino-GQDs), and N-doped and amino-functionalized GQDs (amino-N-GQDs). Among them, the sorted amino-N-GQDs are effective as a two-photon photosensitizer and generate the highest quantity of reactive oxygen species for the elimination of multidrug-resistant cancer cells through two-photon photodynamic therapy (PDT). Larger amino-N-GQDs result in a greater number of C-N and N-functionalities, leading to a superior photochemical effect and more favorable intrinsic luminescence properties, making the dots effective contrast agents for tracking and localizing cancer cells during in-depth bioimaging in a three-dimensional biological environment under TPE in the NIR-II region. Overall, this study highlights the potential of large amino-N-GQDs as a material for future application to dual-modality two-photon PDT and biomedical imaging.

Soluble CD4 effectively prevents excessive TLR activation of resident macrophages in the onset of sepsis.

T lymphopenia, occurring in the early phase of sepsis in response to systemic inflammation, is commonly associated with morbidity and mortality of septic infections. We have previously shown that a sufficient number of T cells is required to constrain Toll-like receptors (TLRs) mediated hyperinflammation. However, the underlying mechanisms remains unsolved. Herein, we unveil that CD4+ T cells engage with MHC II of macrophages to downregulate TLR pro-inflammatory signaling. We show further that the direct contact between CD4 molecule of CD4+ T cells or the ectodomain of CD4 (soluble CD4, sCD4), and MHC II of resident macrophages is necessary and sufficient to prevent TLR4 overactivation in LPS and cecal ligation puncture (CLP) sepsis. sCD4 serum concentrations increase after the onset of LPS sepsis, suggesting its compensatory inhibitive effects on hyperinflammation. sCD4 engagement enables the cytoplasmic domain of MHC II to recruit and activate STING and SHP2, which inhibits IRAK1/Erk and TRAF6/NF-κB activation required for TLR4 inflammation. Furthermore, sCD4 subverts pro-inflammatory plasma membrane anchorage of TLR4 by disruption of MHC II-TLR4 raft domains that promotes MHC II endocytosis. Finally, sCD4/MHCII reversal signaling specifically interferes with TLR4 but not TNFR hyperinflammation, and independent of the inhibitive signaling of CD40 ligand of CD4+ cells on macrophages. Therefore, a sufficient amount of soluble CD4 protein can prevent excessive inflammatory activation of macrophages via alternation of MHC II-TLR signaling complex, that might benefit for a new paradigm of preventive treatment of sepsis.

SENP2 restrains the generation of pathogenic Th17 cells in mouse models of colitis.

The molecular mechanisms contributing to the regulation of Th17-mediated inflammation remain underexplored. We here report a SUMO-specific protease (SENP)2-mediated pathway induced in pathogenic Th17 cells that restricts the pathogenesis of inflammatory colitis. SENP2 regulates the maturation of small ubiquitin-like modifiers (SUMO) and recycles SUMO from the substrate proteins. We find higher levels of SENP2 in pathogenic Th17 cells. By deleting Senp2 in T-cell lineages in mice, we demonstrate that the lack of Senp2 exacerbates the severity of experimental colitis, which is linked to elevated levels of GM-CSF+IL-17A+ pathogenic Th17 cells and more severe dysbiosis of the intestinal microbiome. Adoptive transfer experiments demonstrate the cell-autonomous effect of Senp2 in restraining Th17 differentiation and colitis. The enzymatic activity of SENP2 is important for deSUMOylation of Smad4, which reduces Smad4 nuclear entry and Rorc expression. Our findings reveal a SENP2-mediated regulatory axis in the pathogenicity of Th17 cells.

Use of the dTAG system in vivo to degrade CDK2 and CDK5 in adult mice and explore potential safety liabilities.

The degradation tag (dTAG) system for target protein degradation can remove proteins from biological systems without the drawbacks of some genetic methods, such as slow kinetics, lack of reversibility, low specificity, and the inability to titrate dosage. These drawbacks can make it difficult to compare toxicity resulting from genetic and pharmacological interventions, especially in vivo. Because the dTAG system has not been studied extensively in vivo, we explored the use of this system to study the physiological sequalae resulting from CDK2 or CDK5 degradation in adult mice. Mice with homozygous knock-in of the dTAG sequence onto CDK2 and CDK5 were born at Mendelian ratios despite decreased CDK2 or CDK5 protein levels in comparison with wild-type mice. In bone marrow cells and duodenum organoids derived from these mice, treatment with the dTAG degrader dTAG-13 resulted in rapid and robust protein degradation but caused no appreciable change in viability or the transcriptome. Repeated delivery of dTAG-13 in vivo for toxicity studies proved challenging; we explored multiple formulations in an effort to maximize degradation while minimizing formulation-related toxicity. Degradation of CDK2 or CDK5 in all organs except the brain, where dTAG-13 likely did not cross the blood brain barrier, only caused microscopic changes in the testis of CDK2dTAG mice. These findings were corroborated with conditional CDK2 knockout in adult mice. Our results suggest that the dTAG system can provide robust protein degradation in vivo and that loss of CDK2 or CDK5 in adult mice causes no previously unknown phenotypes.

Rating System for Phytophthora Root Rot Influences Quantitative Trait Locus Detection and Reveals Incomplete Dominance and Duplicative Recessive Epistatic Gene Action in Capsicum annuum.

Phytophthora capsici is one of the most devastating pathogens facing pepper (Capsicum annuum) producers worldwide. Numerous factors, such as the race of the pathogen, the growing environment, and the source of resistance, have resulted in an overall lack of widely applicable molecular markers associated with resistance. Our objective was to determine the effect of the rating system on quantitative trait locus (QTL) detection and understand inheritance patterns of host resistance that can influence selection and molecular marker accuracy. We evaluated an F2:11 recombinant inbred line population screened against the highly virulent strain (Pc134) and scored using two widely used methods, developed by Bosland and Lindsey and by Black. The rating system developed by Bosland and Lindsey resulted in slightly higher logarithm of odds for the QTL on chromosome 5, and we detected a QTL on chromosome 12 uniquely using this rating system. A QTL on chromosome 10 was detected using both rating systems, but Black resulted in considerably higher logarithm of odds for this QTL compared with the Bosland and Lindsey system. Molecular markers developed were nominally better at accurately predicting the phenotype than previously published molecular markers but did not completely explain resistance in our validation populations. The inheritance pattern of resistance in one of our F2 populations did not significantly deviate from a 7:9 segregation ratio, indicating duplicative recessive epistasis. However, these results could be confounded by the presence of incomplete gene action, which was found through the improved selection accuracy when the phenotypes of heterozygous individuals were grouped with those with susceptible alleles.