Diacylglycerol is required for the formation of COPI vesicles in the Golgi-to-ER transport pathway

Diacylglycerol is necessary for trans-Golgi network (TGN) to cell surface transport, but its functional relevance in the early secretory pathway is unclear. Although depletion of diacylglycerol did not affect ER-to-Golgi transport, it led to a redistribution of the KDEL receptor to the Golgi, indicating that Golgi-to-ER transport was perturbed. Electron microscopy revealed an accumulation of COPI-coated membrane profiles close to the Golgi cisternae. Electron tomography showed that the majority of these membrane profiles originate from coated buds, indicating a block in membrane fission. Under these conditions the Golgi-associated pool of ARFGAP1 was reduced, but there was no effect on the binding of coatomer or the membrane fission protein CtBP3/BARS to the Golgi. The addition of 1,2-dioctanoyl-sn-glycerol or the diacylglycerol analogue phorbol 12,13-dibutyrate reversed the effects of endogenous diacylglycerol depletion. Our findings implicate diacylglycerol in the retrograde transport of proteins from Golgi to the ER and suggest that it plays a critical role at a late stage of COPI vesicle formation.

Er-Coupled Si Nanocluster Waveguide

Rib-loaded waveguides containing Er3+-coupled Si nanoclusters (Si-nc) have been produced to observe optical gain at 1535 nm. The presence ofSi-nc strongly improves the efficiency ofEr 3+ excitation but may introduce optical loss mechanisms, such as Mie scattering and confined carrier absorption. Losses strongly affect the possibility of obtaining positive optical gain. Si-nc-related losses have been minimized to 1 dB/cm by lowering the annealing time ofthe Er3+-doped silicon-rich oxide deposited by reactive magnetron cosputtering. Photoluminescence (PL) and lifetime measurements show that all Er3+ ions are optically active while those that can be excited at high pump rates via Si-nc are only a small percentage. Er3+ absorption cross section is found comparable to that ofEr 3+ in SiO 2.However, dependence on the effective refractive index has been found. In pump-probe measurements, it is shown how the detrimental role ofconfined carrier absorption can be attenuated by reducing the annealing time. A maximum signal enhancement ofabout 1.34 at 1535 nm was measured.

HDLs protect pancreatic β-cells against ER stress by restoring protein folding and trafficking.

Endoplasmic reticulum (ER) homeostasis alteration contributes to pancreatic β-cell dysfunction and death and favors the development of diabetes. In this study, we demonstrate that HDLs protect β-cells against ER stress induced by thapsigargin, cyclopiazonic acid, palmitate, insulin overexpression, and high glucose concentrations. ER stress marker induction and ER morphology disruption mediated by these stimuli were inhibited by HDLs. Using a temperature-sensitive viral glycoprotein folding mutant, we show that HDLs correct impaired protein trafficking and folding induced by thapsigargin and palmitate. The ability of HDLs to protect β-cells against ER stress was inhibited by brefeldin A, an ER to Golgi trafficking blocker. These results indicate that HDLs restore ER homeostasis in response to ER stress, which is required for their ability to promote β-cell survival. This study identifies a cellular mechanism mediating the beneficial effect of HDLs on β-cells against ER stress-inducing factors.

ER stress activates the NLRP3 inflammasome via an UPR-independent pathway.

Uncontrolled endoplasmic reticulum (ER) stress responses are proposed to contribute to the pathology of chronic inflammatory diseases such as type 2 diabetes or atherosclerosis. However, the connection between ER stress and inflammation remains largely unexplored. Here, we show that ER stress causes activation of the NLRP3 inflammasome, with subsequent release of the pro-inflammatory cytokine interleukin-1β. This ER-triggered proinflammatory signal shares the same requirement for reactive oxygen species production and potassium efflux compared with other known NLRP3 inflammasome activators, but is independent of the classical unfolded protein response (UPR). We thus propose that the NLRP3 inflammasome senses and responds to ER stress downstream of a previously uncharacterized ER stress response signaling pathway distinct from the UPR, thus providing mechanistic insight to the link between ER stress and chronic inflammatory diseases.

Aplicaciones de los láseres de Er:YAG y de Er,Cr:YSGG en odontologia

Los láseres de Er:YAG y de Er,Cr:YSGG por su longitud de onda son bien absorbidos, tanto por el agua que contienen los tejidos blandos como por los cristales de hidroxiapatita presentes en los tejidos duros. Estas características hacen posible que estos láseres puedan ser absorbidos por los tejidos duros. Se presentan los múltiples usos y aplicaciones que tiene esta tecnología en Odontología, tanto en cirugía de tejidos blandos, como sus aplicaciones sobre tejidos duros, como por ejemplo los tratamientos de la caries o la cirugía ósea reemplazando en ambos casos al instrumental rotatorio. Desde la incorporación de estos láseres en los tratamientos odontológicos, se ha abierto una nueva perspectiva en relación con el uso de la anestesia local. Con la utilización de esta tecnología se pueden realizar tratamientos quirúrgicos poco extensos sin necesidad de aplicar anestesia locorregional, si bien su uso más común es para diversos procedimientos de terapéutica dental.

HDLs protect the MIN6 insulinoma cell line against tunicamycin-induced apoptosis without inhibiting ER stress and without restoring ER functionality.

HDLs protect pancreatic beta cells against apoptosis induced by several endoplasmic reticulum (ER) stressors, including thapsigargin, cyclopiazonic acid, palmitate and insulin over-expression. This protection is mediated by the capacity of HDLs to maintain proper ER morphology and ER functions such as protein folding and trafficking. Here, we identified a distinct mode of protection exerted by HDLs in beta cells challenged with tunicamycin (TM), a protein glycosylation inhibitor inducing ER stress. HDLs were found to inhibit apoptosis induced by TM in the MIN6 insulinoma cell line and this correlated with the maintenance of a normal ER morphology. Surprisingly however, this protective response was neither associated with a significant ER stress reduction, nor with restoration of protein folding and trafficking in the ER. These data indicate that HDLs can use at least two mechanisms to protect beta cells against ER stressors. One that relies on the maintenance of ER function and one that operates independently of ER function modulation. The capacity of HDLs to activate several anti-apoptotic pathways in beta cells may explain their ability to efficiently protect these cells against a variety of insults.

Comparative study of upper lip frenectomy with the CO2 laser versus the Er, Cr: YSGG laser

Objectives: To compare upper lip frenulum reinsertion, bleeding, surgical time and surgical wound healing in frenectomies performed with the CO2 laser versus the Er, Cr:YSGG laser. Study design: A prospective study was carried out on 50 randomized pediatric patients who underwent rhomboidal resection of the upper lip frenulum with either the CO2 laser or the Er,Cr:YSGG laser. Twenty-five patients were assigned to each laser system. All patients were examined at 7, 14, 21 days and 4 months after the operation in order to assess the surgical wound healing. Results: Insertion of the frenulum, which was preoperatively located between the upper central incisors, migrated to the mucogingival junction as a result of using both laser systems in all patients. Only two patients required a single dose of 650 mg of paracetamol, one of either study group. CO2 laser registered improved intraoperative bleeding control results and shorter surgical times. On the other hand, the Er,Cr:YSGG laser achieved faster healing. Conclusions: Upper lip laser frenectomy is a simple technique that results in minimum or no postoperative swelling or pain, and which involves upper lip frenulum reinsertion at the mucogingival junction. The CO2 laser offers a bloodless field and shorter surgical times compared with the Er,Cr:YSGG laser. On the other hand, the Er,Cr:YSGG laser achieved faster wound healing.

Phosphorylation of CARMA1: the link(er) to NF-kappaB activation.

Antigen receptor-induced NF-kappaB activation depends on receptor-proximal and -distal signaling events. Two papers in this issue of Immunity demonstrate that PKC-dependent phosphorylation of CARMA1 is the critical molecular link that controls the activation of the IKK signalosome and NF-kappaB.