A novel neuron-enriched protein SDIM1 is down regulated in Alzheimer's brains and attenuates cell death induced by DNAJB4 over-expression in neuro-progenitor cells

<p>Abstract</p> <p>Background</p> <p>Molecular changes in multiple biological processes contribute to the development of chronic neurodegeneration such as late onset Alzheimer's disease (LOAD). To discover how these changes are reflected at the level of gene expression, we used a subtractive transcription-based amplification of mRNA procedure to identify novel genes that have altered expression levels in the brains of Alzheimer's disease (AD) patients. Among the genes altered in expression level in AD brains was a transcript encoding a novel protein, SDIM1, that contains 146 amino acids, including a typical signal peptide and two transmembrane domains. Here we examined its biochemical properties and putative roles in neuroprotection/neurodegeneration.</p> <p>Results</p> <p>QRT-PCR analysis of additional AD and control post-mortem human brains showed that the SDIM1 transcript was indeed significantly down regulated in all AD brains. SDIM1 is more abundant in NT2 neurons than astrocytes and present throughout the cytoplasm and neural processes, but not in the nuclei. In NT2 neurons, it is highly responsive to stress conditions mimicking insults that may cause neurodegeneration in AD brains. For example, SDIM1 was significantly down regulated 2 h after oxygen-glucose deprivation (OGD), though had recovered 16 h later, and also appeared significantly up regulated compared to untreated NT2 neurons. Overexpression of SDIM1 in neuro-progenitor cells improved cells' ability to survive after injurious insults and its downregulation accelerated cell death induced by OGD. Yeast two-hybrid screening and co-immunoprecipitation approaches revealed, both <it>in vitro </it>and <it>in vivo</it>, an interaction between SDIM1 and DNAJB4, a heat shock protein hsp40 homolog, recently known as an enhancer of apoptosis that also interacts with the mu opioid receptor in human brain. Overexpression of DNAJB4 alone significantly reduced cell viability and SDIM1 co-overexpression was capable of attenuating the cell death caused DNAJB4, suggesting that the binding of SDIM1 to DNAJB4 might sequester DNAJB4, thus increasing cell viability.</p> <p>Conclusion</p> <p>Taken together, we have identified a small membrane protein, which is down regulated in AD brains and neuronal cells exposed to injurious insults. Its ability to promote survival and its interaction with DNAJB4 suggest that it may play a very specific role in brain cell survival and/or receptor trafficking.</p

Building consensus: shifting strategies in the territorial targeting of Turkey's public transport investment

© 2019, © 2019 Regional Studies Association. A growing amount of research explores how the allocation of regional development monies follows electoral reasons. Yet, the existing literature on distributive politics provides different and contrasting expectations on which geographical areas will be targeted. The paper focuses on proportional representation (PR) systems. While in such settings governments have incentives to target core districts and punish foes, it is suggested that when incumbents attempt to build a state–party image they may broaden the territorial allocation of benefits and even target opposition out-groups. The paper exploits data on Turkey's public transport investment for the period 2003–14 and in-depth interviews to provide results in support of the hypothesis.Harvard Emirates Leadership Initiative Fellowshi

Getting the Grip on Nonspecific Treatment Effects: Emesis in Patients Randomized to Acupuncture or Sham Compared to Patients Receiving Standard Care

Background: It is not known whether or not delivering acupuncture triggers mechanisms cited as placebo and if acupuncture or sham reduces radiotherapy-induced emesis more than standard care. Methodology/Principal Findings: Cancer patients receiving radiotherapy over abdominal/pelvic regions were randomized to verum (penetrating) acupuncture (n = 109; 99 provided data) in the alleged antiemetic acupuncture point PC6 or sham acupuncture (n = 106; 101 provided data) performed with a telescopic non-penetrating needle at a sham point 2-3 times/week during the whole radiotherapy period. The acupuncture cohort was compared to a reference cohort receiving standard care (n = 62; 62 provided data). The occurrence of emesis in each group was compared after a mean dose of 27 Gray. Nausea and vomiting were experienced during the preceding week by 37 and 8% in the verum acupuncture group, 38 and 7% in the sham acupuncture group and 63 and 15% in the standard care group, respectively. The lower occurrence of nausea in the acupuncture cohort (verum and sham) compared to patients receiving standard care (37% versus 63%, relative risk (RR) 0.6, 95 % confidence interval (CI) 0.5-0.8) was also true after adjustment for potential confounding factors for nausea (RR 0.8, CI 0.6 to 0.9). Nausea intensity was lower in the acupuncture cohort (78% no nausea, 13% a little, 8% moderate, 1% much) compared to the standard care cohort (52% no nausea, 32% a little, 15% moderate, 2% much) (p = 0.002). The acupuncture cohort expected antiemetic effects from their treatment (95%). Patients who expected nausea had increased risk for nausea compared to patients who expected low risk for nausea (RR 1.6; Cl 1.2-2.4). Conclusions/Significance: Patients treated with verum or sham acupuncture experienced less nausea and vomiting compared to patients receiving standard care, possibly through a general care effect or due to the high level of patient expectancy.Original Publication:Anna Enblom, Mats Lekander, Mats Hammar, Anna Johnsson, Erik Onelov, Martin Ingvar, Gunnar Steineck and Sussanne Börjeson, Getting the Grip on Nonspecific Treatment Effects: Emesis in Patients Randomized to Acupuncture or Sham Compared to Patients Receiving Standard Care, 2011, PLOS ONE, (6), 3, .http://dx.doi.org/10.1371/journal.pone.0014766Licensee: Public Library of Science (PLoS)http://www.plos.org

Percutaneous Epidural Hydrogel Sealant for the Treatment of Spontaneous Intracranial Hypotension: A Case Report of Chronic Thoracic Neuralgia and Technical Lessons Learned

We report a case in which a 34-year-old female with refractory intracranial hypotension headaches due to a spontaneous dural tear was ultimately treated with CT-guided transforaminal epidural placement of a synthetic absorbable sealant (DuraSeal®). The procedure successfully resolved her headaches; however she subsequently developed thoracic neuralgia presumably due to mass effect of the sealant material on the lower thoracic spinal cord and nerve roots. This case report describes the potential for significant spinal cord and nerve root compression as well as the development of chronic neuralgia with the placement of epidural hydrogel and fibrin glue sealants. Careful consideration should be taken into the needle gauge, needle position, injectate volumes, and injection velocity when delivering the sealant to the epidural space. Use of an 18-gauge Tuohy needle with a slow but steady injection pressure, constant patient feedback, and a conservative injectate volume (less than 2 ml per level) may best optimize sealant delivery to minimize the risk of spinal cord compression and neurologic injury

La motivation du chirurgien-dentiste (approche psychologique et sociologique)

L'interrogation sur la motivation du chirurgien-dentiste, en tant qu'acteur de santé publique et garant de son propre équilibre physique et psychique, est posée. Dans une première partie, le concept de motivation professionnelle est abordé sous diverses approches : physiologique, psychologique ou sociologique. Puis dans une deuxième partie, les nombreux et potentiels facteurs de motivation concernant la profession de chirurgien-dentiste sont décrits. La troisième partie est consacrée aux risques de la " démotivation ". Des propositions pour éviter ou surmonter cette situation sont présentées. Enfin, la quatrième partie illustre les propos précédents par une enquête de motivation sur une promotion de jeunes praticiens.TOULOUSE3-BU Santé-Centrale (315552105) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF