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Marco Armando, Corrado Sandini, Maelle Chambaz, Marie Schaer, Maude Schneider, Stephan Eliez
Converging evidence suggests that psychosis emerges from the complex interaction of genetic and environmental factors. Stressful life events (SLEs) play a prominent role in combination with coping strategies and with a dysfunctional hypothalamus-pituitary-adrenal axis (HPAA). It has been proposed that the framework of schizotypy might help disentangle the interaction between genetic and environmental factors in the pathogenesis of psychosis. Similarly, 22q11.2 deletion syndrome (22q11DS) is considered as a genetic model of psychosis vulnerability...
March 14, 2018: Schizophrenia Bulletin
Tales Rocha de Moura, Sina Mozaffari-Jovin, Csaba Zoltán Kibédi Szabó, Jana Schmitzová, Olexandr Dybkov, Constantin Cretu, Michael Kachala, Dmitri Svergun, Henning Urlaub, Reinhard Lührmann, Vladimir Pena
Human nineteen complex (NTC) acts as a multimeric E3 ubiquitin ligase in DNA repair and splicing. The transfer of ubiquitin is mediated by Prp19-a homotetrameric component of NTC whose elongated coiled coils serve as an assembly axis for two other proteins called SPF27 and CDC5L. We find that Prp19 is inactive on its own and have elucidated the structural basis of its autoinhibition by crystallography and mutational analysis. Formation of the NTC core by stepwise assembly of SPF27, CDC5L, and PLRG1 onto the Prp19 tetramer enables ubiquitin ligation...
March 15, 2018: Molecular Cell
Joshua M Peterson, Carolyn Chlebek, Ashley M Clough, Alexandra K Wells, Eric H Ledet
STUDY DESIGN: In vitro biomechanical testing of human cadaveric cervical and goat cervical motion segments. OBJECTIVE: To measure the effects of plate stiffness on load-sharing, instantaneous axis of rotation (IAR), and posterior element loading after anterior cervical discectomy and fusion (ACDF). SUMMARY OF BACKGROUND DATA: ACDF is intended to create an environment which facilitates sufficient stability and biomechanical conditions to promote bone formation...
March 15, 2018: Spine
Carolyn H Tuohy
As the National Health Service (NHS) turns 70, it bears comparison with another universal system celebrating an anniversary this year: Canada's 50-year-old medicare model. Each system is iconically popular, and each revolves around a profession-state accommodation. Both the popularity and the central axis of each system have been tested by external shocks in the form of periodic fiscal cycles of investment and austerity, and internal stresses generating organizational cycles of centralization and decentralization...
March 16, 2018: Health Economics, Policy, and Law
Joyce Pham, Gordon J Miller
Using density functional theory, the crystal structure variation of AAuAl (A = Ca, Sc, and Ti) from orthorhombic Co2 Si-type to distorted hexagonal Fe2 P-type and then Ni2 In-type structures is shown to correlate with their electronic structures and valence electron counts, sizes of the active metals A, and site preferences for Au and Al atoms, which are arranged to maximize Au-Al nearest neighbor contacts. An evaluation of chemical pressure imposed by the varying A metals using total energy vs volume calculations indicates that larger unit cell volumes favor the orthorhombic structure, whereas smaller volumes favor the hexagonal structures...
March 16, 2018: Inorganic Chemistry
Muralidhar Pai K, R Chandrasekhar Naidu, A Raja, Y S Rai, Niranjan Kumar, Anand Kini, Santhosh Joseph, Vinod Hegde, H S Ballal, Ramoorthi Rao, Saroja V Sharma, Vinay Kumar Valakatte
Craniopagus twins are conjoined twins fused at the cranium. This is the rarest anomaly seen in conjoined twins and craniopagus twins account for 2- 6% of conjoined twins. Conjoined twins are also extremely rare, with the anomaly seen in about 10-20 subjects per billion births. A female preponderance has been noted. Craniopagus twins can be classified into complete or partial, depending on whether or not they have shared dural venous sinuses. They can be further classified into angular or total depending on the alignment of the inter-twin longitudinal axis...
March 2018: Neurology India
James Hope, Frederique Vanholsbeeck, A J McDaid
In neural interfaces for peripheral nerve a trade-off exists between the level of invasiveness and the selectivity of neural recordings. In this study, we implement electrical impedance tomography (EIT) in a nerve cuff with the aim to investigate the achievable level of selectivity.
 Approach: Established modelling approaches in neural-EIT are expanded on to be used, for the first time, on myelinated fibres which are abundant in mammalian peripheral nerves and transmit motor commands. The model is then used to evaluate the viability of using EIT with a nerve cuff to record neural activity in peripheral nerves...
March 16, 2018: Physiological Measurement
Eric M Hill, Christian P Petersen
Most animals undergo homeostatic tissue maintenance, yet those capable of robust regeneration in adulthood use mechanisms significantly overlapping with homeostasis. Here we show in planarians that modulations to body-wide patterning systems shift the target site for eye regeneration while still enabling homeostasis of eyes outside this region. The uncoupling of homeostasis and regeneration, which can occur during normal positional rescaling after axis truncation, is not due to altered injury signaling or stem cell activity, nor specific to eye tissue...
March 16, 2018: ELife
Clémence Granier, Alain Gey, Charles Dariane, Arnaud Mejean, Marc-Olivier Timsit, Charlotte Blanc, Virginie Verkarre, Camélia Radulescu, Elisabeth Fabre, Yann Vano, Stéphane Oudard, Cécile Badoual, Éric Tartour
T cells harboring multiple co-inhibitory molecules lose their anti-tumoral functionality. PD-1 is a clinically approved target in cancer therapy, but its expression alone does not mean dysfunctionality. The expression of Tim-3 on numerous cell types (T cell, Treg, dendritic cell, myeloid cells) favors tumor escape to immune cells. Within many tumors, PD-1/Tim-3 coexpressing CD8-T cells lose their ability to secrete cytokines (IFNγ, IL-2, TNFα) and their intratumoral infiltration correlates with a bad prognosis...
March 2018: Médecine Sciences: M/S
Naomi Weintrob, Anita Schachter Davidov, Anat Segev Becker, Galit Israeli, Asaf Oren, Ori Eyal
OBJECTIVE: The total cortisol (TC) response may be measured during the glucagon stimulation test (GST) for growth hormone (GH) reserve in order to assess the integrity of the hypothalamic-pituitary-adrenal (HPA) axis. Measurements of TC are unreliable in conditions of albumin and cortisol-binding globulin (CBG) alterations (e.g., hypoproteinemia or CBG deficiency). We aimed to measure the serum free cortisol (sFC) response to the GST in children and adolescents and determine whether it could predict the GH response to glucagon stimulation...
March 2018: Endocrine Practice
Michael B Ranke, Jan M Wit
Growth hormone (GH) research and its clinical application for the treatment of growth disorders span more than a century. During the first half of the 20th century, clinical observations and anatomical and biochemical studies formed the basis of the understanding of the structure of GH and its various metabolic effects in animals. The following period (1958-1985), during which pituitary-derived human GH was used, generated a wealth of information on the regulation and physiological role of GH - in conjunction with insulin-like growth factors (IGFs) - and its use in children with GH deficiency (GHD)...
March 16, 2018: Nature Reviews. Endocrinology
Stephan Petersenn
Secondary adrenal insufficiency may pose specific challenges during pregnancy. The interpretation of diagnostic tests is hindered by physiological adaptations of the HPA axis. Due the relevant increases in CBG, measurement of salivary cortisol may be preferable, but lacks sufficiently established cut-offs both for early-morning evaluation and during dynamic testing. Hydrocortisone should be used for replacement to avoid overexposure of the fetus, with dose adjustments according to clinical judgement. To account for increased free cortisol levels during the course of pregnancy, hydrocortisone may be increased by 5-7...
March 15, 2018: Minerva Endocrinologica
Naoya Ishibashi, Tatsuaki Watanabe, Masahiko Kanehira, Yui Watanabe, Yasushi Hoshikawa, Hirotsugu Notsuda, Masafumi Noda, Akira Sakurada, Shinya Ohkouchi, Takashi Kondo, Yoshinori Okada
PURPOSE: Using a rat model of allograft lung transplantation, we investigated the effectiveness of mesenchymal stromal cells (MSCs) as prophylactic and therapeutic agents against the acute rejection of lung grafts. METHODS: Lung grafts were harvested from donor rats and transplanted orthotopically into major histocompatibility complex-mismatched rats. MSCs were administered to the recipients once (on day 0) or twice (on days 0 and 3) after transplantation. The grade of acute rejection was evaluated both macroscopically and microscopically 6 days after transplantation...
March 15, 2018: Surgery Today
Ahmad Alobeid, Tarek El-Bialy, Susanne Reimann, Ludger Keilig, Dirk Cornelius, Andreas Jäger, Christoph Bourauel
Background/objective: The aim of this study was to evaluate the efficacy of tooth alignment with conventional and self-ligating labial and lingual orthodontic bracket systems. Materials/methods: We tested labial brackets (0.022″ slot size) and lingual brackets (0.018″ slot size). The labial brackets were: (i) regular twin brackets (GAC-Twin [Dentsply]), (ii) passive self-ligating brackets including (Damon-Q® [ORMCO]; Ortho classic H4™ [Orthoclassic]; FLI®SL [RMO]), and (iii) active self-ligating brackets (GAC In-Ovation®C [DENTSPLY] and SPEED™[Strite])...
March 13, 2018: European Journal of Orthodontics
Andrzej T Slominski, Michal A Zmijewski, Przemyslaw M Plonka, Jerzy P Szaflarski, Ralf Paus
The skin, a self-regulating protective barrier organ, is empowered with sensory and computing capabilities to counteract the environmental stressors to maintain/restore disrupted cutaneous homeostasis. These complex functions are coordinated by a cutaneous neuro-endocrine system that also communicates in a bidirectional fashion with the central nervous, endocrine and immune systems, all acting in concert to control body homeostasis. While ultraviolet energy (UV) has played an important role in the origin and evolution of life, UV absorption by the skin not only triggers mechanisms that defend skin integrity and regulate global homeostasis, but also induces skin pathology (e...
March 12, 2018: Endocrinology
Min Huang, Li Zhu, Jacqueline S Garcia, Michael X Li, Andrew J Gentles, Beverly S Mitchell
We have recently reported that activation of Brd4 is associated with the presence of autophagy in NPMc+ and MLL AML cells. In order to determine the mechanisms underlying this relationship, we have examined the role of Brd4 in regulating the expression of several genes that are central to the process of autophagy. We found that Brd4 binds to the promoters of ATG 3, 7 and CEBPβ, and expression of these genes is markedly reduced by inhibitors of Brd4, as well as by Brd4-shRNA and depletion of CEBPβ. Inhibitors of Brd4 also dramatically suppress the transcription of Keap1, thereby increasing the expression of anti-oxidant genes through the Nrf2 pathway and reducing the cytotoxicity induced by Brd4 inhibitors...
February 20, 2018: Oncotarget
Julia Fernandez Puñal de Araújo, Priscila Lang Podratz, Eduardo Merlo, Isabela Valim Sarmento, Charles Santos da Costa, Oscar Mauricio Santamaria Niño, Rodrigo Alves Faria, Leandro Ceotto Freitas Lima, Jones Bernardes Graceli
Organotin (OTs) compounds are organometallic compounds that are widely used in industry, such as in the manufacture of plastics, pesticides, paints, and others. OTs are released into the environment by anthropogenic actions, leading to contact with aquatic and terrestrial organisms that occur in animal feeding. Although OTs are degraded environmentally, reports have shown the effects of this contamination over the years because it can affect organisms of different trophic levels. OTs act as endocrine-disrupting chemicals (EDCs), which can lead to several abnormalities in organisms...
2018: Frontiers in Endocrinology
Mariana Fortunata Donadon, Rocio Martin-Santos, Flávia de Lima Osório
Studies have shown that traumatic experiences may affect hormonal systems mediated by the hypothalamic-pituitary-adrenal (HPA) axis and the oxytocinergic system. This effect is the result of long-term impairments in hypothalamic structures and negative feedback mechanisms within the HPA axis, structures that mediate the response to stress. This deregulation reduces the production and release of cortisol and oxytocin (OXT), which may alter stress responses and lead to increased vulnerability to impairments from stressful experiences...
2018: Frontiers in Pharmacology
Ji-Hye Do, Won-Gyu Yoo
[Purpose] The purpose of this study was to investigate the effectiveness of using a visual feedback-equipped reacher when performing reach-to-grasp tasks. [Subjects and Methods] Seventeen healthy participants with no illnesses or physical disabilities were selected for this study. Activation of the flexor digitorum superficialis and extensor digitorum muscles was assessed using electromyography. Wrist and shoulder momentums were calculated using a three-axis acceleration sensor. Participants were instructed to move 10 ears of plastic corn from right to left using a reacher with and without visual feedback...
February 2018: Journal of Physical Therapy Science
Zsofia Miskolczi, Michael P Smith, Emily J Rowling, Jennifer Ferguson, Jorge Barriuso, Claudia Wellbrock
Despite the general focus on an invasive and de-differentiated phenotype as main driver of cancer metastasis, in melanoma patients many metastatic lesions display a high degree of pigmentation, indicative for a differentiated phenotype. Indeed, studies in mice and fish show that melanoma cells switch to a differentiated phenotype at secondary sites, possibly because in melanoma differentiation is closely linked to proliferation through the lineage-specific transcriptional master regulator MITF. Importantly, while a lot of effort has gone into identifying factors that induce the de-differentiated/invasive phenotype, it is not well understood how the switch to the differentiated/proliferative phenotype is controlled...
March 16, 2018: Oncogene
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