Holomorphic selection rules, the origin of the mu term, and thermal inflation

When an abelian gauge theory with integer charges is spontaneously broken by the expectation value of a charge Q field, there remains a Z_Q discrete symmetry. In a supersymmetric theory, holomorphy adds additional constraints on the operators that can appear in the effective superpotential. As a result, operators with the same mass dimension but opposite sign charges can have very different coupling strengths. In the present work we characterize the operator hierarchies in the effective theory due to holomorphy, and show that there exist simple relationships between the size of an operator and its mass dimension and charge. Using such holomorphy-induced operator hierarchies, we construct a simple model with a naturally small supersymmetric mu term. This model also provides a concrete realization of late-time thermal inflation, which has the ability to solve the gravitino and moduli problems of weak-scale supersymmetry.Comment: 18 pages, 1 figur

A microporous metal-organic framework constructed from a 1D column made of linear trinuclear manganese secondary building units

A metal-organic framework (MOF) was prepared based on a 1D column made of a linear trinuclear manganese cluster as a secondary building unit (SBU), where the SBU is connected to two adjacent SBUs by carboxylates to form a 1D column and the column is further connected to four adjacent 1D columns via the SBUs to form a microporous MOF of pcu network topology.close7

Chronic Infection Depletes Hematopoietic Stem Cells through Stress-Induced Terminal Differentiation

Chronic infections affect a third of the world’s population and can cause bone marrow suppression, a severe condition that increases mortality from infection. To uncover the basis for infection-associated bone marrow suppression, we conducted repeated infection of WT mice with Mycobacterium avium. After 4–6 months, mice became pancytopenic. Their hematopoietic stem and progenitor cells (HSPCs) were severely depleted and displayed interferon gamma (IFN-γ) signaling-dependent defects in self-renewal. There was no evidence of increased HSPC mobilization or apoptosis. However, consistent with known effects of IFN-γ, transcriptome analysis pointed toward increased myeloid differentiation of HSPCs and revealed the transcription factor Batf2 as a potential mediator of IFN-γ-induced HSPC differentiation. Gain- and loss-of-function studies uncovered a role for Batf2 in myeloid differentiation in both murine and human systems. We thus demonstrate that chronic infection can deplete HSPCs and identify BATF2 as a mediator of infection-induced HSPC terminal differentiation

Spatial rank-based multifactor dimensionality reduction to detect gene–gene interactions for multivariate phenotypes

Background Identifying interaction effects between genes is one of the main tasks of genome-wide association studies aiming to shed light on the biological mechanisms underlying complex diseases. Multifactor dimensionality reduction (MDR) is a popular approach for detecting gene–gene interactions that has been extended in various forms to handle binary and continuous phenotypes. However, only few multivariate MDR methods are available for multiple related phenotypes. Current approaches use Hotellings T2 statistic to evaluate interaction models, but it is well known that Hotellings T2 statistic is highly sensitive to heavily skewed distributions and outliers. Results We propose a robust approach based on nonparametric statistics such as spatial signs and ranks. The new multivariate rank-based MDR (MR-MDR) is mainly suitable for analyzing multiple continuous phenotypes and is less sensitive to skewed distributions and outliers. MR-MDR utilizes fuzzy k-means clustering and classifies multi-locus genotypes into two groups. Then, MR-MDR calculates a spatial rank-sum statistic as an evaluation measure and selects the best interaction model with the largest statistic. Our novel idea lies in adopting nonparametric statistics as an evaluation measure for robust inference. We adopt tenfold cross-validation to avoid overfitting. Intensive simulation studies were conducted to compare the performance of MR-MDR with current methods. Application of MR-MDR to a real dataset from a Korean genome-wide association study demonstrated that it successfully identified genetic interactions associated with four phenotypes related to kidney function. The R code for conducting MR-MDR is available at https://github.com/statpark/MR-MDR Conclusions Intensive simulation studies comparing MR-MDR with several current methods showed that the performance of MR-MDR was outstanding for skewed distributions. Additionally, for symmetric distributions, MR-MDR showed comparable power. Therefore, we conclude that MR-MDR is a useful multivariate non-parametric approach that can be used regardless of the phenotype distribution, the correlations between phenotypes, and sample size.This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government(MSIT) (2013M3A9C4078158, NRF-2021R1A2C1007788)

Antioxidant and Hepatoprotective Effects of Procyanidins fromWild Grape (Vitis amurensis) Seeds in Ethanol-Induced Cells and Rats

In the present study, we characterized the antioxidant and hepatoprotective mechanisms underlying of wild grape seed procyanidins (WGP) against oxidative stress damage in ethanol-treated HepG2 cell and Sprague-Dawley (SD)-rat models. In HepG2 cells, WGP not only diminished the ethanol (EtOH, 100 mM)-induced reactive oxygen species (ROS) formation and cytochrome P450 2E1 (CYP2E1) expression, but also renovated both the activity and expression of antioxidant enzymes including catalase, superoxide dismutase, and glutathione peroxidase. Additionally, to investigate the hepatoprotective effect of WGP, rats were orally administered 10 or 50 mg/kg WGP once daily for seven days prior to the single oral administration of EtOH (6 g/kg). The results show that WGP administration decreased the EtOH-induced augment of the levels of serum aspartate transaminase and alanine transaminase as well as serum alcohol and acetaldehyde. WGP treatment upregulated the activities and protein levels of hepatic alcohol dehydrogenase, aldehyde dehydrogenase, and antioxidant enzymes but downregulated the protein expression level of liver CYP2E1 in EtOH-treated rats. Moreover, the decreased phosphorylation levels of mitogen activated protein kinases (MAPKs) by ethanol were induced in both HepG2 cell and rat models. Overall, pretreatment of WGP displayed the protective activity against EtOH-mediated toxicity through the regulation of antioxidant enzymes and alcohol metabolism systems via MAPKs pathways

Replicative genetic association study between functional polymorphisms in AVPR1A and social behavior scales of autism spectrum disorder in the Korean population

Abbreviations ADI-A1: Failure to use nonverbal behaviors to regulate social interaction; ADIA2: Failure to develop peer relationship; ADI-A3: Lack of shared enjoyment; ADI-A4: Lack of socioemotional reciprocity; ANOVA: Analysis of variance; ASD: Autism spectrum disorder; ASDS: Asperger Syndrome Diagnostic Scale; AVP: Arginine vasopressin; AVPR1A: Arginine vasopressin receptor 1A; Df: Degree of freedom; EMSA: Electrophoretic mobility-shift assay; FBAT: Family-based association test; HBAT: Haplotype family-based association test; IRB: Institutional Review Board; K-ADI-R: Korean version of the Autism Diagnostic Interview-Revised; K-ADOS: Korean version of the Autism Diagnostic Observation Schedule; K-CBCL: Korean Child Behavior Checklist; KEDI-WISC-R: Korean Educational Development Institute-Wechsler Intelligence Scale for Children-Revised; K-SMS: Korean version of the Social Maturity Scale; MAF: Minor allele frequency; PDD-NOS: Pervasive developmental disorder that were not otherwise specified; RLUs: Relative luciferase units; SCQ: Social Communication Questionnaires; SNPs: Single nucleotide polymorphisms; SRS: Social Responsiveness Scale; TDT: Transmission disequilibrium test; VABS: Vineland Adaptive BehaviorAbstract Background Arginine vasopressin has been shown to affect social and emotional behaviors, which is mediated by the arginine vasopressin receptor (AVPR1A). Genetic polymorphisms in the AVPR1A promoter region have been identified to be associated with susceptibility to social deficits in autism spectrum disorder (ASD). We hypothesize that alleles of polymorphisms in the promoter region of AVPR1A may differentially interact with certain transcriptional factors, which in turn affect quantitative traits, such as sociality, in children with autism. Methods We performed an association study between ASD and polymorphisms in the AVPR1A promoter region in the Korean population using a family-based association test (FBAT). We evaluated the correlation between genotypes and the quantitative traits that are related to sociality in children with autism. We also performed a promoter assay in T98G cells and evaluated the binding affinities of transcription factors to alleles of rs7294536. Results The polymorphisms—RS1, RS3, rs7294536, and rs10877969—were analyzed. Under the dominant model, RS1–310, the shorter allele, was preferentially transmitted. The FBAT showed that the rs7294536 A allele was also preferentially transmitted in an additive and dominant model under the bi-allelic mode. When quantitative traits were used in the FBAT, rs7294536 and rs10877969 were statistically significant in all genotype models and modes. Luciferase and electrophoretic mobility-shift assays suggest that the rs7294536 A/G allele results in a Nf-κB binding site that exhibits differential binding affinities depending on the allele. Conclusion These results demonstrate that polymorphisms in the AVPR1A promoter region might be involved in pathophysiology of ASD and in functional regulation of the expression of AVPR1A.This work has been supported by the Healthcare Technology R&D project (no. HI12C0021) by the Ministry of Health and Welfare, Republic of Korea; the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (NRF-2014R1A2A1A110 53289 and NRF-2017M3C7A1027467

Procyanidins from Wild Grape (Vitis amurensis) Seeds Regulate ARE-Mediated Enzyme Expression via Nrf2 Coupled with p38 and PI3K/Akt Pathway in HepG2 Cells

Procyanidins, polymers of flavan-3-ol units, have been reported to exhibit many beneficial health effects such as antioxidant and anti-carcinogenic effects. In this study, we investigated the cancer chemopreventive properties of procyanidins from wild grape (Vitis amurensis) seeds in particular their roles in inducing phase II detoxifying/antioxidant enzymes as well as in modulating the upstream kinases. Ethanolic extract of V. amurensis seeds was fractionated with a series of organic solvents and finally separated into six fractions, F1–F6. Chemical properties of the procyanidins were analyzed by vanillin assay, BuOH-HCl test, and depolymerization with phloroglucinol followed by LC/MS analysis. The F5 had the highest procyanidin content among all the fractions and strongly induced the reporter activity of antioxidant response element as well as the protein expression of nuclear factor E2-related factor (Nrf2) in HepG2 human hepatocarcinoma cells. The procyanidin-rich F5 also strongly induced the expression of the phase II detoxifying and antioxidant enzymes such as NAD(P)H:quinone oxidoreductase1 and hemeoxygenase1. Phosphorylations of the upstream kinases such as MAPKs and PI3K/Akt were significantly increased by treatment with procyanidin fraction. In addition, the procyanidin-mediated Nrf2 expression was partly attenuated by PI3K inhibitor LY294002, and almost completely by p38 inhibitor SB202190, but neither by JNK inhibitor SP600125 nor by MEK1/2 inhibitor U0126. Taken together, the procyanidins from wild grape seeds could be used as a potential natural chemopreventive agent through Nrf2/ARE-mediated phase II detoxifying/antioxidant enzymes induction via p38 and PI3K/Akt pathway