Locomotor hyperactivity in 14-3-3Zeta KO mice is associated with dopamine transporter dysfunction

Dopamine (DA) neurotransmission requires a complex series of enzymatic reactions that are tightly linked to catecholamine exocytosis and receptor interactions on pre- and postsynaptic neurons. Regulation of dopaminergic signalling is primarily achieved through reuptake of extracellular DA by the DA transporter (DAT) on presynaptic neurons. Aberrant regulation of DA signalling, and in particular hyperactivation, has been proposed as a key insult in the presentation of schizophrenia and related neuropsychiatric disorders. We recently identified 14-3-3ζ as an essential component of neurodevelopment and a central risk factor in the schizophrenia protein interaction network. Our analysis of 14-3-3ζ-deficient mice now shows that baseline hyperactivity of knockout (KO) mice is rescued by the antipsychotic drug clozapine. 14-3-3ζ KO mice displayed enhanced locomotor hyperactivity induced by the DA releaser amphetamine. Consistent with 14-3-3ζ having a role in DA signalling, we found increased levels of DA in the striatum of 14-3-3ζ KO mice. Although 14-3-3ζ is proposed to modulate activity of the rate-limiting DA biosynthesis enzyme, tyrosine hydroxylase (TH), we were unable to identify any differences in total TH levels, TH localization or TH activation in 14-3-3ζ KO mice. Rather, our analysis identified significantly reduced levels of DAT in the absence of notable differences in RNA or protein levels of DA receptors D1–D5. Providing insight into the mechanisms by which 14-3-3ζ controls DAT stability, we found a physical association between 14-3-3ζ and DAT by co-immunoprecipitation. Taken together, our results identify a novel role for 14-3-3ζ in DA neurotransmission and provide support to the hyperdopaminergic basis of pathologies associated with schizophrenia and related disorders.H Ramshaw, X Xu, EJ Jaehne, P McCarthy, Z Greenberg, E Saleh, B McClure, J Woodcock, S Kabbara, S Wiszniak, Ting-Yi Wang, C Parish, M van den Buuse, BT Baune, A Lopez and Q Schwar

Strong interface-induced spin-orbit coupling in graphene on WS2

Interfacial interactions allow the electronic properties of graphene to be modified, as recently demonstrated by the appearance of satellite Dirac cones in the band structure of graphene on hexagonal boron nitride (hBN) substrates. Ongoing research strives to explore interfacial interactions in a broader class of materials in order to engineer targeted electronic properties. Here we show that at an interface with a tungsten disulfide (WS2) substrate, the strength of the spin-orbit interaction (SOI) in graphene is very strongly enhanced. The induced SOI leads to a pronounced low-temperature weak anti-localization (WAL) effect, from which we determine the spin-relaxation time. We find that spin-relaxation time in graphene is two-to-three orders of magnitude smaller on WS2 than on SiO2 or hBN, and that it is comparable to the intervalley scattering time. To interpret our findings we have performed first-principle electronic structure calculations, which both confirm that carriers in graphene-on-WS2 experience a strong SOI and allow us to extract a spin-dependent low-energy effective Hamiltonian. Our analysis further shows that the use of WS2 substrates opens a possible new route to access topological states of matter in graphene-based systems.Comment: Originally submitted version in compliance with editorial guidelines. Final version with expanded discussion of the relation between theory and experiments to be published in Nature Communication

Breast cancer in neurofibromatosis type 1 : overrepresentation of unfavourable prognostic factors

Background: An increased breast cancer incidence and poor survival have been reported for women with neurofibromatosis 1 (NF1). To explain the poor survival, we aimed to link the histopathology and clinical characteristics of NF1-associated breast cancers. Methods: The Finnish Cancer Registry and the Finnish NF Registry were cross-referenced to identify the NF1 patients with breast cancer. Archival NF1 breast cancer specimens were retrieved for histopathological typing and compared with matched controls. Results: A total of 32 breast cancers were diagnosed in 1404 NF1 patients during the follow-up. Women with NF1 had an estimated lifetime risk of 18.0% for breast cancer, and this is nearly two-fold compared with that of the general Finnish female population (9.74%). The 26 successfully retrieved archival NF1 breast tumours were more often associated with unfavourable prognostic factors, such as oestrogen and progesterone receptor negativity and HER2 amplification. However, survival was worse in the NF1 group (P = 0.053) even when compared with the control group matched for age, diagnosis year, gender and oestrogen receptor status. Scrutiny of The Cancer Genome Atlas data set showed that NF1 mutations and deletions were associated with similar characteristics in the breast cancers of the general population. Conclusions: These results emphasise the role of the NF1 gene in the pathogenesis of breast cancer and a need for active follow-up for breast cancer in women with NF1.Peer reviewe

Current understanding of the human microbiome

Author Posting. © The Author(s), 2018. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature Medicine 24 (2018): 392–400, doi:10.1038/nm.4517.Our understanding of the link between the human microbiome and disease, including obesity, inflammatory bowel disease, arthritis and autism, is rapidly expanding. Improvements in the throughput and accuracy of DNA sequencing of the genomes of microbial communities associated with human samples, complemented by analysis of transcriptomes, proteomes, metabolomes and immunomes, and mechanistic experiments in model systems, have vastly improved our ability to understand the structure and function of the microbiome in both diseased and healthy states. However, many challenges remain. In this Review, we focus on studies in humans to describe these challenges, and propose strategies that leverage existing knowledge to move rapidly from correlation to causation, and ultimately to translation.Many of the studies described here in our laboratories were supported by the NIH, NSF, DOE, and the Alfred P. Sloan Foundation.2018-10-1

Neutrinos

Report of the Community Summer Study 2013 (Snowmass) Intensity Frontier Neutrino Working GroupReport of the Community Summer Study 2013 (Snowmass) Intensity Frontier Neutrino Working GroupThis document represents the response of the Intensity Frontier Neutrino Working Group to the Snowmass charge. We summarize the current status of neutrino physics and identify many exciting future opportunities for studying the properties of neutrinos and for addressing important physics and astrophysics questions with neutrinos

Genome Analysis of Planctomycetes Inhabiting Blades of the Red Alga

Porphyra is a macrophytic red alga of the Bangiales that is important ecologically and economically. We describe the genomes of three bacteria in the phylum Planctomycetes (designated P1, P2 and P3) that were isolated from blades of Porphyra umbilicalis (P.um.1). These three Operational Taxonomic Units (OTUs) belong to distinct genera; P2 belongs to the genus Rhodopirellula, while P1 and P3 represent undescribed genera within the Planctomycetes. Comparative analyses of the P1, P2 and P3 genomes show large expansions of distinct gene families, which can be widespread throughout the Planctomycetes (e.g., protein kinases, sensors/response regulators) and may relate to specific habitat (e.g., sulfatase gene expansions in marine Planctomycetes) or phylogenetic position. Notably, there are major differences among the Planctomycetes in the numbers and sub-functional diversity of enzymes (e.g., sulfatases, glycoside hydrolases, polysaccharide lyases) that allow these bacteria to access a range of sulfated polysaccharides in macroalgal cell walls. These differences suggest that the microbes have varied capacities for feeding on fixed carbon in the cell walls of P.um.1 and other macrophytic algae, although the activities among the various bacteria might be functionally complementary in situ. Additionally, phylogenetic analyses indicate augmentation of gene functions through expansions arising from gene duplications and horizontal gene transfers; examples include genes involved in cell wall degradation (e.g., κ-carrageenase, alginate lyase, fucosidase) and stress responses (e.g., efflux pump, amino acid transporter). Finally P1 and P2 contain various genes encoding selenoproteins, many of which are enzymes that ameliorate the impact of environmental stresses that occur in the intertidal habitat

Measurement of the WW and WZ production cross section using final states with a charged lepton and heavy-flavor jets in the full CDF Run II data set

Citation: Aaltonen, T., Amerio, S., Amidei, D., Anastassov, A., Annovi, A., Antos, J., . . . Zucchelli, S. (2016). Measurement of the WW and WZ production cross section using final states with a charged lepton and heavy-flavor jets in the full CDF Run II data set. Physical Review D - Particles, Fields, Gravitation and Cosmology, 94(3). doi:10.1103/PhysRevD.94.032008We present a measurement of the total WW and WZ production cross sections in pp collision at s=1.96 TeV, in a final state consistent with leptonic W boson decay and jets originating from heavy-flavor quarks from either a W or a Z boson decay. This analysis uses the full data set collected with the CDF II detector during Run II of the Tevatron collider, corresponding to an integrated luminosity of 9.4 fb-1. An analysis of the dijet mass spectrum provides 3.7? evidence of the summed production processes of either WW or WZ bosons with a measured total cross section of ?WW+WZ=13.7±3.9 pb. Independent measurements of the WW and WZ production cross sections are allowed by the different heavy-flavor decay patterns of the W and Z bosons and by the analysis of secondary-decay vertices reconstructed within heavy-flavor jets. The productions of WW and of WZ dibosons are independently seen with significances of 2.9? and 2.1?, respectively, with total cross sections of ?WW=9.4±4.2 pb and ?WZ=3.7-2.2+2.5 pb. The measurements are consistent with standard-model predictions. © 2016 American Physical Society

ass and lifetime measurements of bottom and charm baryons in ppˉp\bar p collisions at $\sqrt{s}= 1.96 TeV

We report on mass and lifetime measurements of several ground state charmed and bottom baryons, using a data sample corresponding to 9.6 $\textrm{fb}^{-1}$ from $p\bar p$ collisions at $\sqrt{s}=1.96$ TeV, and recorded with the Collider Detector at Fermilab. Baryon candidates are reconstructed from data collected with an online event selection designed for the collection of long-lifetime heavy-flavor decay products and a second event selection designed to collect $J/\psi \rightarrow \mu^+ \, \mu^-$ candidates. First evidence for the process $\Omega_b^- \rightarrow \Omega_c^0 \, \pi^-$ is presented with a significance of $3.3\sigma$. We measure the following baryon masses: \begin{eqnarray} M(\Xi_c^{0}) = 2470.85\pm0.24(stat)\pm0.55(syst) \, MeV/c^2, \nonumber M(\Xi_c^{+}) = 2468.00\pm0.18(stat)\pm0.51(syst) \, MeV/c^2, \nonumber \\ M(\Lambda_b) = 5620.15\pm0.31(stat)\pm0.47(syst) \, MeV/c^2, \nonumber \\ M(\Xi_b^-) = 5793.4\pm1.8(stat)\pm0.7(syst) \, MeV/c^2, \nonumber \\ M(\Xi_b^0) = 5788.7\pm4.3(stat)\pm1.4(syst) \, MeV/c^2, \, and \nonumber \\ M(\Omega_b^-) = 6047.5\pm3.8(stat)\pm0.6(syst) \, MeV/c^2. \nonumber \end{eqnarray} The isospin splitting of the $\Xi_b^{-,0}$ states is found to be $M(\Xi_b^-)-M(\Xi_b^0)=4.7\pm4.7(stat)\pm0.7(syst)$ MeV/$c^2$. The isospin splitting of the $\Xi_c^{0,+}$ states is found to be $M(\Xi_c^0)-M(\Xi_c^+)$ = $2.85\pm0.30(stat)\pm0.04(syst)$ MeV/$c^2$. The following lifetime measurements are made: \begin{eqnarray} \tau(\Lambda_b) = 1.565\pm0.035(stat)\pm0.020(syst) \, ps, \nonumber \\ \tau(\Xi_b^-) = 1.32\pm0.14(stat)\pm0.02(syst) \, ps, \nonumber \\ \tau(\Omega_b^-) = 1.66^{+0.53}_{-0.40}(stat)\pm0.02(syst) \, ps. \nonumber \end{eqnarray

Neutrinos

229 pages229 pages229 pagesThe Proceedings of the 2011 workshop on Fundamental Physics at the Intensity Frontier. Science opportunities at the intensity frontier are identified and described in the areas of heavy quarks, charged leptons, neutrinos, proton decay, new light weakly-coupled particles, and nucleons, nuclei, and atoms

Measurement of sin2 θlept eff using eþe− pairs from γ=Z bosons produced in pp collisions at a center-of-momentum energy of 1.96 TeV

At the Fermilab Tevatron proton-antiproton (pp¯) collider, Drell-Yan lepton pairs are produced in the process pp¯→e+e−+X through an intermediate γ∗/Z boson. The forward-backward asymmetry in the polar-angle distribution of the e− as a function of the e+e−-pair mass is used to obtain sin2θlepteff, the effective leptonic determination of the electroweak-mixing parameter sin2θW. The measurement sample, recorded by the Collider Detector at Fermilab (CDF), corresponds to 9.4  fb−1 of integrated luminosity from pp¯ collisions at a center-of-momentum energy of 1.96 TeV, and is the full CDF Run II data set. The value of sin2θlepteff is found to be 0.23248±0.00053. The combination with the previous CDF measurement based on μ+μ− pairs yields sin2θlepteff=0.23221±0.00046. This result, when interpreted within the specified context of the standard model assuming sin2θW=1−M2W/M2Z and that the W- and Z-boson masses are on-shell, yields sin2θW=0.22400±0.00045, or equivalently a W-boson mass of 80.328±0.024  GeV/c2