Beyond the Standard Model B-parameters with improved staggered fermions in Nf=2+1N_f=2+1 QCD

We calculate the kaon mixing B-parameters for operators arising generically in theories of physics beyond the standard model. We use HYP-smeared improved staggered fermions on the $N_f = 2+1$ MILC asqtad lattices. Operator matching is done perturbatively at one-loop order. Chiral extrapolations are done using "golden combinations" in which one-loop chiral logarithms are absent. For the combined sea-quark mass and continuum extrapolation, we use three lattice spacings: $a \approx 0.045, 0.06$ and $0.09 \text{fm}$. Our results have a total error of 5-6%, which is dominated by the systematic error from matching and continuum extrapolation. For two of the BSM $B$-parameters, we agree with results obtained using domain-wall and twisted-mass dynamical fermions, but we disagree by $(4-5)\sigma$ for the other two.Comment: 7 pages, 5 figures, Lattice 2013 Proceedin

Calculation of BSM Kaon B-parameters using Staggered Quarks

We present updated results for kaon B-parameters for operators arising in models of new physics. We use HYP-smeared staggered quarks on the $N_f = 2+1$ MILC asqtad lattices. During the last year we have added new ensembles, which has necessitated chiral-continuum fitting with more elaborate fitting functions. We have also corrected an error in a two-loop anomalous dimension used to evolve results between different scales. Our results for the beyond-the-Standard-Model B-parameters have total errors of $5-10$\%. We find that the discrepancy observed last year between our results and those of the RBC/UKQCD and ETM collaborations for some of the B-parameters has been reduced from $4\!-\!5\,\sigma$ to $2\!-\!3\,\sigma$.Comment: 7 pages, 8 figures, Lattice 2014 proceedin

A roadmap for research in octoploid strawberry

The cultivated strawberry (Fragaria × ananassa) is an allo-octoploid species, originating nearly 300 years ago from wild progenitors from the Americas. Since that time the strawberry has become the most widely cultivated fruit crop in the world, universally appealing due to its sensory qualities and health benefits. The recent publication of the first high-quality chromosome-scale octoploid strawberry genome (cv. Camarosa) is enabling rapid advances in genetics, stimulating scientific debate and provoking new research questions. In this forward-looking review we propose avenues of research toward new biological insights and applications to agriculture. Among these are the origins of the genome, characterization of genetic variants, and big data approaches to breeding. Key areas of research in molecular biology will include the control of flowering, fruit development, fruit quality, and plant–pathogen interactions. In order to realize this potential as a global community, investments in genome resources must be continually augmented.Peer reviewe

Valosin-containing protein is a key mediator between autophagic cell death and apoptosis in adult hippocampal neural stem cells following insulin withdrawal

Background: Programmed cell death (PCD) plays essential roles in the regulation of survival and function of neural stem cells (NSCs). Abnormal regulation of this process is associated with developmental and degenerative neuronal disorders. However, the mechanisms underlying the PCD of NSCs remain largely unknown. Understanding the mechanisms of PCD in NSCs is crucial for exploring therapeutic strategies for the treatment of neurodegenerative diseases. Result: We have previously reported that adult rat hippocampal neural stem (HCN) cells undergo autophagic cell death (ACD) following insulin withdrawal without apoptotic signs despite their normal apoptotic capabilities. It is unknown how interconnection between ACD and apoptosis is mediated in HCN cells. Valosin-containing protein (VCP) is known to be essential for autophagosome maturation in mammalian cells. VCP is abundantly expressed in HCN cells compared to hippocampal tissue and neurons. Pharmacological and genetic inhibition of VCP at basal state in the presence of insulin modestly impaired autophagic flux, consistent with its known role in autophagosome maturation. Of note, VCP inaction in insulin-deprived HCN cells significantly decreased ACD and down-regulated autophagy initiation signals with robust induction of apoptosis. Overall autophagy level was also substantially reduced, suggesting the novel roles of VCP at initial step of autophagy. Conclusion: Taken together, these data demonstrate that VCP may play an essential role in the initiation of autophagy and mediation of crosstalk between ACD and apoptosis in HCN cells when autophagy level is high upon insulin withdrawal. This is the first report on the role of VCP in regulation of NSC cell death. Elucidating the mechanism by which VCP regulates the crosstalk of ACD and apoptosis will contribute to understanding the molecular mechanism of PCD in NSCs. © 2016 Yeo et al.1

GSK3B induces autophagy by phosphorylating ULK1

Unc-51-like autophagy activating kinase 1 (ULK1), a mammalian homolog of the yeast kinase Atg1, has an essential role in autophagy induction. In nutrient and growth factor signaling, ULK1 activity is regulated by various posttranslational modifications, including phosphorylation, acetylation, and ubiquitination. We previously identified glycogen synthase kinase 3 beta (GSK3B) as an upstream regulator of insulin withdrawal-induced autophagy in adult hippocampal neural stem cells. Here, we report that following insulin withdrawal, GSK3B directly interacted with and activated ULK1 via phosphorylation of S405 and S415 within the GABARAP-interacting region. Phosphorylation of these residues facilitated the interaction of ULK1 with MAP1LC3B and GABARAPL1, while phosphorylation-defective mutants of ULK1 failed to do so and could not induce autophagy flux. Furthermore, high phosphorylation levels of ULK1 at S405 and S415 were observed in human pancreatic cancer cell lines, all of which are known to exhibit high levels of autophagy. Our results reveal the importance of GSK3B-mediated phosphorylation for ULK1 regulation and autophagy induction and potentially for tumorigenesis. © 2021, The Author(s).1

스트레스에 의한 성체해마신경줄기세포의 자가포식사멸 규명 및 관련 분자기전 연구

adult hippocampal neural stem cells, chronic stress, autophagic cell death, p53prohibitionⅠ. General Introduction 1 1.1 Adult Neural Stem Cells 1 1.2 Programmed Cell Death 4 1.2.1 Apoptosis 4 1.2.2 Necroptosis 4 1.2.1 Autophagic Cell Death 5 1.3 Autophagy 5 1.3.1 Autophagy dependent cell death 6 1.3.2 Autophagic cell death in hippocampal neural stem cells 7 1.4 Stress 8 1.4.1 Stress and Neurogenesis 9 ⅠI. General Materials and Methods 12 2.1 Animals and CRS procedures 12 2.2 CORT injection 12 2.3 BrdU injection 12 2.4 CORT measurement 13 2.5 Constructs and virus production 13 2.6 Neurosphere assay 13 2.7 Generation of KO or stable knockdown HCN cells 14 2.8 Electron microscopy 14 2.9 Sucrose preference test 15 2.10 Stereotaxic injection 15 2.11 Cell culture 15 2.12 Cell Death Assay 16 2.13 Western Blotting Analysis 16 2.14 Immunofluorescence staining 16 2.15 Stereological cell counting 17 2.16 Elevated Plus Maze Test 17 2.17 Open Field Test 17 2.18 Y-Maze Test 17 2.19 Morris Water Maze Test 18 2.20 Hippocampus tissue lysis 18 2.21 Plasmids and transfection 18 2.22 In situ hybridization 19 2.23 LABORAS test (automated 24-h movement analysis) 19 2.24 Nest building test 19 2.25 Quantitative Real-Time PCR (qRT-PCR) 20 2.26 Co-immunoprecipitation 20 2.27 Statistical analysis 20 ⅠII. Autophagic death of neural stem cells mediates chronic stress-induced decline of adult hippocampal neurogenesis and cognitive deficits 21 3.1 Introduction 21 3.2 Results 22 3.2.1 Adult hippocampal NSCs are protected from chronic restraint stress (CRS) in Atg7-NSC cKO mice 22 3.2.2 CRS-induced autophagy is blocked in Atg7-NSC cKO mice 25 3.2.3 Suppression of neurogenesis and cognitive deficits induced by CRS are prevented in Atg7-NSC cKO mice 29 3.2.4 Loss of NSCs activity after CRS is blocked by autophagy deficiency 32 3.2.5 Chronic CORT injection-induced autophagy is blocked in Atg7-NSC cKO mice 34 3.2.6 CORT induces ACD, but not apoptosis or necroptosis 38 3.2.7 SGK3 is a critical mediator of CORT-induced ACD in HCN cells 44 3.2.8 Deletion of SGK3, but not SGK1, blocks CRS-induced HCN cell death in vivo 48 ⅠV. Cytosolic p53 protects hippocampal neural stem cells and cognitive functions from chronic stress by blocking autophagic cell death. 50 4.1 Introduction 50 4.2 Results 51 4.2.1 High Expression Level of Endogenous p53 in hippocampal NSCs. 51 4.2.2 p53 KO mice is sensitive to stress and induces anxiety like behavior and cognitive deficits. 53 4.2.3 Degradation of p53 by Autophagy 55 4.2.4 Cytosolic p53 protects HCN cells from CORT-induced ACD 57 4.2.5 Specific p53 activator, RITA prevents CORT-induced cell death and stress in-duced cognitive and mood deficits 59 V. Pro-survival roles of cytosolic p53 in adult hippocampal neural stem cells 62 5.1 Introduction 62 5.2 Results 62 5.2.1 Degradation of p53 by Autophagy Following Insulin Withdrawal 62 5.2.2 Endogenous p53 is Transcriptionally Inactive and is Located in the Cytosol of HCN Cells 65 5.2.3 Different Localization of p53 Depending on Cell Type and Change in p53 Locali-zation during Differentiation of HCN Cells 68 5.2.4 Cytosolic p53 Protects HCN Cells from Insulin Withdrawal and Apoptotic Stress. 70 5.2.5 Interaction of p53 with GSK-3β 72 VI. General Discussion 76 Reference Summary (국문요약)DoctordCollectio

Autophagy as a decisive process for cell death

Cell death: cell component recycling in health and disease A natural cellular recycling process could be harnessed or targeted for the treatment of multiple diseases including cancer and psychological disorders. Autophagy is a process that occurs within cells, whereby damaged, toxic, or obsolete cellular components are degraded and recycled to release energy and maintain balance. However, scientists now recognize that autophagy can trigger cell death under certain conditions. Seong-Woon Yu and co-workers at the Daegu Gyeongbuk Institute of Science and Technology, South Korea, reviewed recent research into the mechanisms and role of autophagy in health and disease. Autophagic cell death is implicated in the suppression of tumor development; for example, inducing autophagy led to the death of precancerous cells in mice. Autophagy may also regulate immune cell populations, and play a role in the death of brain cells during chronic stress-related disorders

Parental control and college students' depressive symptoms: A latent class analysis.

We examined how maternal and paternal parental control (helicopter parenting, behavioral control, and psychological control) among college students are related to their depressive symptoms. We collected data from college students who attended a private university in Upstate New York (n = 455) and analyzed it using three-step latent class analysis. Latent class analysis identified four parental control latent classes: weak parental control, strong psychological control, strong helicopter parenting, and strong parental control. College students in the weak parental control class reported lower depressive symptoms than those in strong psychological control and strong parental control classes. In addition, college students in the strong helicopter parenting class reported lower depressive symptoms than those in strong psychological control and strong parental control classes. College students' depressive symptoms were not significantly different between weak parental control and strong helicopter parenting classes. Future researchers are encouraged to continue to acknowledge the characteristics of different forms of parental control and their influence on college students' quality of life in the transition to adulthood, considering the unique approaches of both parents