Insulin-like growth factor 1 and growth seasonality in reindeer (Rangifer tarandus) - comparisons with temperate and tropical cervids

Growth in temperate and arctic deer is seasonal, with higher growth rates in spring and summer while growth rates are low or negative in autumn and winter. We have measured IGF1 concentrations in the plasma of reindeer calves exposed to a manipulated photoperiod, indoors, of either 16 hours light followed by 8 hours dark each day (16L:8D) (n = 3) or 8L:16D (n = 3) from about the autumnal to the vernal equinox, to determine whether the seasonal growth spurt normally seen in spring is associated with changes in the circulating level of IGF1. A high quality concentrate diet was available ad libitum. The animals were weighed, and bled every 2 weeks and plasma samples assayed for IGF1 by radioimmunoassay. 6-8 weeks after the start of the study those calves exposed to 16L.-8D showed a significant increase in plasma IGF1 concentration which was maintained until the close of the experiment, 24 weeks after the start. In contrast IGF1 plasma concentrations in those calves exposed to a daylength of 8L:16D did not significantly alter during the study. The elevated IFG1 in the 16L:8D group was associated with rapid weight gain compared with the 8L:16D group. We have shown that the seasonal growth spurt is preceded by an elevation in plasma IFG1 concentration. Further, this elevation in IGF1 is daylength dependent. For comparison IGF1 and growth rate seasonal profiles from temperate and tropical deer are included. This comparison reveals that seasonal increases in IGF1 take place only in animals with a seasonal growth spurt. Thus IGF1 plasma level elevations seem most closely associated with the resumption of rapid growth in spring following the winter

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

The Large Enriched Germanium Experiment for Neutrinoless Double Beta Decay (LEGEND)

The observation of neutrinoless double-beta decay (0${\nu}{\beta}{\beta}$) would show that lepton number is violated, reveal that neutrinos are Majorana particles, and provide information on neutrino mass. A discovery-capable experiment covering the inverted ordering region, with effective Majorana neutrino masses of 15 - 50 meV, will require a tonne-scale experiment with excellent energy resolution and extremely low backgrounds, at the level of $\sim$0.1 count /(FWHM$\cdot$t$\cdot$yr) in the region of the signal. The current generation $^{76}$Ge experiments GERDA and the MAJORANA DEMONSTRATOR utilizing high purity Germanium detectors with an intrinsic energy resolution of 0.12%, have achieved the lowest backgrounds by over an order of magnitude in the 0${\nu}{\beta}{\beta}$ signal region of all 0${\nu}{\beta}{\beta}$ experiments. Building on this success, the LEGEND collaboration has been formed to pursue a tonne-scale $^{76}$Ge experiment. The collaboration aims to develop a phased 0${\nu}{\beta}{\beta}$ experimental program with discovery potential at a half-life approaching or at $10^{28}$ years, using existing resources as appropriate to expedite physics results.Comment: Proceedings of the MEDEX'17 meeting (Prague, May 29 - June 2, 2017

Longitudinal study on birthweight and the incidence of endometrial cancer

From 1976 to 2004, we followed 71 751 participants of the Nurses' Health Study and identified 676 invasive endometrial cancer cases. Birthweight, assessed in 1992, was not associated with the incidence of endometrial cancer. No effect modification by menopausal status was observed, but statistical power to detect an interaction was limited

Primary mucinous carcinoma of the skin: a case of metastasis after 10 years of disease-free interval

Primary mucinous carcinoma of the skin (MCS) is a rare neoplasm. Clinically, it has a high local recurrence rate, but it is known to be a slow-growing benign tumor with a rare incidence of distant metastases. We present a case of primary MCS on the jaw that underwent tumor resection twice and was disease-free for 10 years after the second surgery. The patient had no evidence of local recurrence and distant metastasis until his 11th year follow-up. At that time, he was diagnosed with lung and bone metastasis and died 3 years after this. To our knowledge, this is the first case of MCS that presented with metastasis with more than 10-year disease-free interval. Since MCS is a slow-growing asymptomatic tumor, distant metastasis is difficult to diagnose without detailed radiological examination. We believe that computed tomography and resonance imaging should be performed for early diagnosis of metastasis even for cases with long-term disease-free interval, especially cases of local recurrence

Pinning down electron correlations in RaF via spectroscopy of excited states

We report the spectroscopy of 11 electronic states in the radioactive molecule radium monofluoride (RaF). The observed excitation energies are compared with state-of-the-art relativistic Fock-space coupled cluster (FS-RCC) calculations, which achieve an agreement of >99.71% (within ~8 meV) for all states. High-order electron correlation and quantum electrodynamics corrections are found to be important at all energies. Establishing the accuracy of calculations is an important step towards high-precision studies of these molecules, which are proposed for sensitive searches of physics beyond the Standard Model.Comment: Submitted for publicatio

The Serotonin 5-HT7Dro Receptor Is Expressed in the Brain of Drosophila, and Is Essential for Normal Courtship and Mating

The 5-HT7 receptor remains one of the less well characterized serotonin receptors. Although it has been demonstrated to be involved in the regulation of mood, sleep, and circadian rhythms, as well as relaxation of vascular smooth muscles in mammals, the precise mechanisms underlying these functions remain largely unknown. The fruit fly, Drosophila melanogaster, is an attractive model organism to study neuropharmacological, molecular, and behavioral processes that are largely conserved with mammals. Drosophila express a homolog of the mammalian 5-HT7 receptor, as well as homologs for the mammalian 5-HT1A, and 5-HT2, receptors. Each fly receptor couples to the same effector pathway as their mammalian counterpart and have been demonstrated to mediate similar behavioral responses. Here, we report on the expression and function of the 5-HT7Dro receptor in Drosophila. In the larval central nervous system, expression is detected postsynaptically in discreet cells and neuronal circuits. In the adult brain there is strong expression in all large-field R neurons that innervate the ellipsoid body, as well as in a small group of cells that cluster with the PDF-positive LNvs neurons that mediate circadian activity. Following both pharmacological and genetic approaches, we have found that 5-HT7Dro activity is essential for normal courtship and mating behaviors in the fly, where it appears to mediate levels of interest in both males and females. This is the first reported evidence of direct involvement of a particular serotonin receptor subtype in courtship and mating in the fly

Endothelial Stomatal and Fenestral Diaphragms in Normal Vessels and Angiogenesis

Vascular endothelium lines the entire cardiovascular system where performs a series of vital functions including the control of microvascular permeability, coagulation inflammation, vascular tone as well as the formation of new vessels via vasculogenesis and angiogenesis in normal and disease states. Normal endothelium consists of heterogeneous populations of cells differentiated according to the vascular bed and segment of the vascular tree where they occur. One of the cardinal features is the expression of specific subcellular structures such as plasmalemmal vesicles or caveolae, transendothelial channels, vesiculo-vacuolar organelles, endothelial pockets and fenestrae, whose presence define several endothelial morphological types. A less explored observation is the differential expression of such structures in diverse settings of angiogenesis. This review will focus on the latest developments on the components, structure and function of these specific endothelial structures in normal endothelium as well as in diverse settings of angiogenesis