Exploring the flavour structure of the MSSM with rare K decays

We present an extensive analysis of rare K decays, in particular of the two neutrino modes K+->pi+ nu nu-bar and KL->pi0 nu nu-bar, in the Minimal Supersymmetric extension of the Standard Model. We analyse the expectations for the branching ratios of these modes, both within the restrictive framework of the minimal flavour violation hypothesis and within a more general framework with new sources of flavour-symmetry breaking. In both scenarios, the information that can be extracted from precise measurements of the two neutrino modes turn out to be very useful in restricting the parameter space of the model, even after taking into account the possible information on the mass spectrum derived from high-energy colliders, and the constraints from B-physics experiments. In the presence of new sources of flavour-symmetry breaking, additional significant constraints on the model can be derived also from the two KL->pi0 l+l- modes.Comment: 22 pages, 10 figures (high quality figures available on request

Supersymmetric models with minimal flavour violation and their running

We revisit the formulation of the principle of minimal flavor violation (MFV) in the minimal supersymmetric extension of the standard model, both at moderate and large tan(beta), and with or without new CP-violating phases. We introduce a counting rule which keeps track of the highly hierarchical structure of the Yukawa matrices. In this manner, we are able to control systematically which terms can be discarded in the soft SUSY breaking part of the Lagrangian. We argue that for the implementation of this counting rule, it is convenient to introduce a new basis of matrices in which both the squark (and slepton) mass terms as well as the trilinear couplings can be expanded. We derive the RGE for the MFV parameters and show that the beta functions also respect the counting rule. For moderate tan(beta), we provide explicit analytic solutions of these RGE and illustrate their behaviour by analyzing the neighbourhood (also switching on new phases) of the SPS-1a benchmark point. We then show that even in the case of large tan(beta), the RGE remain valid and that the analytic solutions obtained for moderate tan(beta) still allow us to understand the most important features of the running of the parameters, as illustrated with the help of the SPS-4 benchmark point.Comment: plain latex, 38 pages and 5 figures Eq. (12) corrected and one reference added, conclusions unchanged. Published versio

Threonine 149 Phosphorylation Enhances ΔFosB Transcriptional Activity to Control Psychomotor Responses to Cocaine

Stable changes in neuronal gene expression have been studied as mediators of addicted states. Of particular interest is the transcription factor ΔFosB, a truncated and stable FosB gene product whose expression in nucleus accumbens (NAc), a key reward region, is induced by chronic exposure to virtually all drugs of abuse and regulates their psychomotor and rewarding effects. Phosphorylation at Ser[superscript 27] contributes to ΔFosB's stability and accumulation following repeated exposure to drugs, and our recent work demonstrates that the protein kinase CaMKIIα phosphorylates ΔFosB at Ser[superscript 27] and regulates its stability in vivo. Here, we identify two additional sites on ΔFosB that are phosphorylated in vitro by CaMKIIα, Thr[superscript 149] and Thr[superscript 180], and demonstrate their regulation in vivo by chronic cocaine. We show that phosphomimetic mutation of Thr[superscript 149] (T149D) dramatically increases AP-1 transcriptional activity while alanine mutation does not affect transcriptional activity when compared with wild-type (WT) ΔFosB. Using in vivo viral-mediated gene transfer of ΔFosB-T149D or ΔFosB-T149A in mouse NAc, we determined that overexpression of ΔFosB-T149D in NAc leads to greater locomotor activity in response to an initial low dose of cocaine than does WT ΔFosB, while overexpression of ΔFosB-T149A does not produce the psychomotor sensitization to chronic low-dose cocaine seen after overexpression of WT ΔFosB and abrogates the sensitization seen in control animals at higher cocaine doses. We further demonstrate that mutation of Thr[superscript 149] does not affect the stability of ΔFosB overexpressed in mouse NAc, suggesting that the behavioral effects of these mutations are driven by their altered transcriptional properties

Functional Genomic and Proteomic Analysis Reveals Disruption of Myelin-Related Genes and Translation in a Mouse Model of Early Life Neglect

Early life neglect is an important public health problem which can lead to lasting psychological dysfunction. Good animal models are necessary to understand the mechanisms responsible for the behavioral and anatomical pathology that results. We recently described a novel model of early life neglect, maternal separation with early weaning (MSEW), that produces behavioral changes in the mouse that persist into adulthood. To begin to understand the mechanism by which MSEW leads to these changes we applied cDNA microarray, next-generation RNA-sequencing (RNA-seq), label-free proteomics, multiple reaction monitoring (MRM) proteomics, and methylation analysis to tissue samples obtained from medial prefrontal cortex to determine the molecular changes induced by MSEW that persist into adulthood. The results show that MSEW leads to dysregulation of markers of mature oligodendrocytes and genes involved in protein translation and other categories, an apparent downward biasing of translation, and methylation changes in the promoter regions of selected dysregulated genes. These findings are likely to prove useful in understanding the mechanism by which early life neglect affects brain structure, cognition, and behavior

ABRF Proteome Informatics Research Group (iPRG) 2016 Study: Inferring Proteoforms from Bottom-up Proteomics Data.

This report presents the results from the 2016 Association of Biomolecular Resource Facilities Proteome Informatics Research Group (iPRG) study on proteoform inference and false discovery rate (FDR) estimation from bottom-up proteomics data. For this study, 3 replicate Q Exactive Orbitrap liquid chromatography-tandom mass spectrometry datasets were generated from each of

A Rare Case of Wilson Disease in a 72-Year-Old Patient.

Wilson disease is an autosomal recessive disorder of abnormal copper metabolism that is prevalent in the younger population, rarely presenting in patients older than 40 years. Clinical presentation may be variable, and diagnosis is often aided by clinical and biochemical tests. We report the case of a 72-year-old woman who presented with acute liver failure initially of unclear etiology. Our patient was initially managed for presumed drug-induced liver injury but ultimately diagnosed with Wilson disease on the basis of clinical presentation, laboratory testing, liver biopsy, quantitative hepatic copper, and abnormal genetic testing

The s ---> d gamma decay in and beyond the Standard Model

The New Physics sensitivity of the s ---> d gamma transition and its accessibility through hadronic processes are thoroughly investigated. Firstly, the Standard Model predictions for the direct CP-violating observables in radiative K decays are systematically improved. Besides, the magnetic contribution to epsilon prime is estimated and found subleading, even in the presence of New Physics, and a new strategy to resolve its electroweak versus QCD penguin fraction is identified. Secondly, the signatures of a series of New Physics scenarios, characterized as model-independently as possible in terms of their underlying dynamics, are investigated by combining the information from all the FCNC transitions in the s ---> d sector.Comment: 54 pages, 14 eps figure

current evidence and programmatic considerations

Funding Information: We are thankful to Ann Prentice for her critical review of the section ?Concerns in populations with low calcium intake.? The convenings of the Calcium Task Force and the development of this paper and its open access were supported by funding from The Children's Investment Fund Foundation to the Nutrition Science Program of the New York Academy of Sciences. Publisher Copyright: © 2022 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals LLC on behalf of New York Academy of Sciences.Most low- and middle-income countries present suboptimal intakes of calcium during pregnancy and high rates of mortality due to maternal hypertensive disorders. Calcium supplementation during pregnancy is known to reduce the risk of these disorders and associated complications, including preeclampsia, maternal morbidity, and preterm birth, and is, therefore, a recommended intervention for pregnant women in populations with low dietary calcium intake (e.g., where ≥25% of individuals in the population have intakes less than 800 mg calcium/day). However, this intervention is not widely implemented in part due to cost and logistical issues related to the large dose and burdensome dosing schedule (three to four 500-mg doses/day). WHO recommends 1.5–2 g/day but limited evidence suggests that less than 1 g/day may be sufficient and ongoing trials with low-dose calcium supplementation (500 mg/day) may point a path toward simplifying supplementation regimens. Calcium carbonate is likely to be the most cost-effective choice, and it is not necessary to counsel women to take calcium supplements separately from iron-containing supplements. In populations at highest risk for preeclampsia, a combination of calcium supplementation and food-based approaches, such as food fortification with calcium, may be required to improve calcium intakes before pregnancy and in early gestation.publishersversionpublishe