Hepatic Notch1 deletion predisposes to diabetes and steatosis via glucose-6-phosphatase and perilipin-5 upregulation

Notch signaling pathways have recently been implicated in the pathogenesis of metabolic diseases. However, the role of hepatic Notch signaling in glucose and lipid metabolism remains unclear and needs further investigation as it might be a candidate therapeutic target in metabolic diseases such as nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD). We used hepatocyte-specific Notch1 knockout (KO) mice and liver biopsies from NASH and NAFLD patients to analyze the role of Notch1 in glucose and lipid metabolism. Hepatocyte-specific Notch1 KO mice were fed with a high fat diet (HFD) or a regular diet (RD). We assessed the metabolic phenotype, glucose and insulin tolerance tests, and liver histology. Hepatic mRNA expression was profiled by Affymetrix Mouse Gene arrays and validated by quantitative reverse transcription PCR (qPCR). Akt phosphorylation was visualized by immunoblotting. Gene expression was analyzed in liver biopsies from NASH, NAFLD, and control patients by qPCR. We found that Notch1 KO mice had elevated fasting glucose. Gene expression analysis showed an upregulation of glucose-6-phosphatase, involved in the final step of gluconeogenesis and glucose release from glycogenolysis, and perilipin-5, a regulator of hepatic lipid accumulation. When fed with an HFD KO mice developed overt diabetes and hepatic steatosis. Akt was highly phosphorylated in KO animals and the Foxo1 target gene expression was altered. Accordingly, a reduction in Notch1 and increase in glucose-6-phosphatase and perilipin-5 expression was observed in liver biopsies from NAFLD/NASH compared with controls. Notch1 is a regulator of hepatic glucose and lipid homeostasis. Hepatic impairment of Notch1 expression may be involved in the pathogenesis of human NAFLD/NASH

Lower Bound on the Pseudoscalar Mass in the Minimal Supersymmetric Standard Model

In the Higgs sector of the Minimal Supersymmetric Standard Model, the mass of the pseudoscalar $A$ is an independent parameter together with $\tan \beta \equiv v_2/v_1$. If $m_A$ is small, then the process $e^+ e^- \to h + A$ is kinematically allowed and is suppressed only if $\tan \beta$ is small. On the other hand, the mass of the charged Higgs boson is now near $M_W$, and the decay $t \to b + h^+$ is enhanced if $\tan \beta$ is small. Since the former has not been observed, and the branching fraction of $t \to b + W$ cannot be too small (by comparing the experimentally derived $t \bar t$ cross section from the leptonic channels with the theoretical prediction), we can infer a phenomenological lower bound on $m_A$ of at least 60 GeV for all values of $\tan \beta$.Comment: 11 pages including 2 figs, reference adde

Vectorial Control of Magnetization by Light

Coherent light-matter interactions have recently extended their applications to the ultrafast control of magnetization in solids. An important but unrealized technique is the manipulation of magnetization vector motion to make it follow an arbitrarily designed multi-dimensional trajectory. Furthermore, for its realization, the phase and amplitude of degenerate modes need to be steered independently. A promising method is to employ Raman-type nonlinear optical processes induced by femtosecond laser pulses, where magnetic oscillations are induced impulsively with a controlled initial phase and an azimuthal angle that follows well defined selection rules determined by the materials' symmetries. Here, we emphasize the fact that temporal variation of the polarization angle of the laser pulses enables us to distinguish between the two degenerate modes. A full manipulation of two-dimensional magnetic oscillations is demonstrated in antiferromagnetic NiO by employing a pair of polarization-twisted optical pulses. These results have lead to a new concept of vectorial control of magnetization by light

Two-Higgs doublet models from TeV-scale supersymmetric extra U(1) models

We investigate the reduction of a general TeV-scale supersymmetric extra U(1) model to a 2HDM below the TeV- scale through the tree level non-decoupling. Portions of the parameter space of the extra U(1) model appropriate for obtaining a 2HDM are identified. Various properties of the resulting 2HDM are connected to the parameter space of the underlying model. PACS: 12.60.Jv, 12.60.Cn, 12.60.FrComment: 12 pages, 4 postscript figures, to appear in Phys. Rev.

Making Atomic-Level Magnetism Tunable with Light at Room Temperature

The capacity to manipulate magnetization in two-dimensional dilute magnetic semiconductors (2D-DMSs) using light, specifically in magnetically doped transition metal dichalcogenide (TMD) monolayers (M-doped TX2, where M = V, Fe, Cr; T = W, Mo; X = S, Se, Te), may lead to innovative applications in spintronics, spin-caloritronics, valleytronics, and quantum computation. This Perspective paper explores the mediation of magnetization by light under ambient conditions in 2D-TMD DMSs and heterostructures. By combining magneto-LC resonance (MLCR) experiments with density functional theory (DFT) calculations, we show that the magnetization can be enhanced using light in V-doped TMD monolayers (e.g., V-WS2, V-WSe2, V-MoS2). This phenomenon is attributed to excess holes in the conduction and valence bands, as well as carriers trapped in magnetic doping states, which together mediate the magnetization of the semiconducting layer. In 2D-TMD heterostructures such as VSe2/WS2 and VSe2/MoS2, we demonstrate the significance of proximity, charge-transfer, and confinement effects in amplifying light-mediated magnetism. This effect is attributed to photon absorption at the TMD layer (e.g., WS2, MoS2) that generates electron-hole pairs mediating the magnetization of the heterostructure. These findings will encourage further research in the field of 2D magnetism and establish a novel direction for designing 2D-TMDs and heterostructures with optically tunable magnetic functionalities, paving the way for next-generation magneto-optic nanodevices

Supersymmetric One-family Model without Higgsinos

The Higgs potential and the mass spectrum of the N=1 supersymmetric extension of a recently proposed one-family model based on the local gauge group $SU(3)_c \otimes SU(3)_L \otimes U(1)_X$, which is a subgroup of the electroweak-strong unification group $E_6$, is analyzed. In this model the slepton multiplets play the role of the Higgs scalars and no Higgsinos are needed, with the consequence that the sneutrino, the selectron and six other sleptons play the role of the Goldstone bosons. We show how the $\mu$ problem is successfully addressed in the context of this model which also predicts the existence of a light CP-odd scalar.Comment: REVTeX 4, 10 pages. Included discussions about constraints coming from the rho-parameter and from Muon (g-2). References added. Version to appear in Phys. Rev.

Decoration of T-independent antigen with ligands for CD22 and Siglec-G can suppress immunity and induce B cell tolerance in vivo

Autoreactive B lymphocytes first encountering self-antigens in peripheral tissues are normally regulated by induction of anergy or apoptosis. According to the "two-signal" model, antigen recognition alone should render B cells tolerant unless T cell help or inflammatory signals such as lipopolysaccharide are provided. However, no such signals seem necessary for responses to T-independent type 2 (TI-2) antigens, which are multimeric antigens lacking T cell epitopes and Toll-like receptor ligands. How then do mature B cells avoid making a TI-2-like response to multimeric self-antigens? We present evidence that TI-2 antigens decorated with ligands of inhibitory sialic acid-binding Ig-like lectins (siglecs) are poorly immunogenic and can induce tolerance to subsequent challenge with immunogenic antigen. Two siglecs, CD22 and Siglec-G, contributed to tolerance induction, preventing plasma cell differentiation or survival. Although mutations in CD22 and its signaling machinery have been associated with dysregulated B cell development and autoantibody production, previous analyses failed to identify a tolerance defect in antigen-specific mutant B cells. Our results support a role for siglecs in B cell self-/nonself-discrimination, namely suppressing responses to self-associated antigens while permitting rapid "missing self"-responses to unsialylated multimeric antigens. The results suggest use of siglec ligand antigen constructs as an approach for inducing tolerance

\mbox{SU}(3)_L \otimes \mbox{U}(1)_N and \mbox{SU}(4)_L \otimes \mbox{U}(1)_N gauge models with right-handed neutrinos

Pisano and Pleitez have introduced an interesting \mbox{SU}(3)_C \otimes \mbox{SU}(3)_L \otimes \mbox{U}(1)_N gauge model which has the property that gauge anomaly cancellation requires the number of generations to be a multiple of 3. We consider generalizing that model to incorporate right-handed neutrinos. We find that there exists a non-trivial generalization of the Pisano-Pleitez model with right-handed neutrinos which is actually simpler than the original model in that symmetry breaking can be achieved with just three \mbox{SU}(3)_L triplets (rather than 3 \mbox{SU}(3)_L triplets and a sextet). We also consider a gauge model based on \mbox{SU}(3)_C\otimes \mbox{SU}(4)_L \otimes \mbox{U}(1)_N symmetry. Both of these new models also have the feature that the anomalies cancel only when the number of generations is divisible by 3.Comment: 8, McGill/94-1