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A Complicated Pulmonary Cystic Echinococcosis in Pregnancy
Published in Wickii T. Vigneswaran, Thoracic Surgery, 2019
Yulia N. Matveeva, Kalpaj R. Parekh
E. granulosus forms a cyst containing protoscolices filled with a clear “hydatid” fluid. The cyst is made of an inner germinative (endocyst) and a distinct, white, outer acellular-laminated layer (exocyst). It is surrounded by the host inflammatory layer (pericyst). Unlike extrapulmonary cysts, pulmonary HCs do not undergo calcifications, while mediastinal, pleural, and pericardial cysts may calcify. “Daughter” vesicles of variable size may be present inside or outside the “mother” cyst, but they are rare in the lung. Over 70% of patients present with a single organ involvement by a solitary cyst. The liver-to-lung involvement ratio is approximately 5:1. In lungs, lower lobes are more frequently affected. In addition to hematogenous spread to lungs via portal circulation, parasites can bypass the liver entering the chest via the thoracic duct or the lymphatics of the diaphragm. Transdiaphragmatic rupture of liver HCs may account for some simultaneous hepatopulmonary cases. A direct route from inhalation of eggs has been described as well. Involvement of other organs is rare. Cysts of CE are unilocular and expansile, causing mass effect. Pulmonary HC doubling time is 16–20 weeks. HCs achieve 1–2 cm in diameter by the end of six months, up to 6 cm in one year, and they grow further; they may persist for years without changes. HC growth and variation in morphology depends on geographic regions, intraspecies parasite genotype variations, and host differences.
Exocytosis of Nonclassical Neurotransmitters
Published in Tian-Le Xu, Long-Jun Wu, Nonclassical Ion Channels in the Nervous System, 2021
Xiao Su, Vincent R. Mirabella, Kenneth G. Paradiso, Zhiping P. Pang
Neuropeptide Y (NPY), the most abundant peptide in the hypothalamus of the mammalian central nervous system, plays a key role in regulating energy homeostasis including food intake, storage of energy, and stimulating insulin secretion (Billington et al., 1991; Stanley et al., 1986, 1992). NPY contributes a large degree to inhibiting neurotransmitter release from excitatory CA3 neurons in the hippocampus and inhibits excitatory neurotransmission presynaptically at the striatum radiatum-CA1 synapse by reducing calcium influx into the axon terminal (Colmers et al., 1988). NPY shares the same SNARE complex-mediated vesicular exocytosis as oxytocin. However, it can be packaged into dense core vesicles with a smaller volume than LDCV in magnocellular neurons (van den Pol, 2012). Using an optical imaging reporter (i.e. NPY-pHluorin), Dr. Matthijs Verhage’s laboratory conducted a series of interesting studies that revealed that NPY release from the DCV requires active zone proteins such as Munc13, as well as the RAB3-Rim pathway. Their study proposed that RIMs and Munc13 work as mammalian alternatives to the yeast exocyst complex RAB3/SEC4 and regulates DCV fusion sites by positioning Munc13 and recruiting NPY-DCVs via RAB3. By applying genetic techniques to knockout different components of active zone proteins, they verified the essential function of each component. For example, NPY-DCV fusion was reduced by over 90% in RAB3 quadruple knockout neurons. In RIM-conditional knockout neurons, DCV release was completely lost and fully restored by expressing the N-terminal RAB3- and Munc13-interacting domains of RIM in a RAB3-dependent manner. Overexpression of Munc13-2 and N-terminal truncated Munc13-2 also rescued the DCV fusion in RIM-deficient neurons (Persoon et al., 2019). In the Munc13-1 and -2 double deletion model, synaptic DCV fusion was reduced but not abolished with loss of synaptic preference, and the remaining fusion required prolonged stimulation, similar to extrasynaptic fusion in WT neurons. However, the overexpression of Munc13-1 promoted extrasynaptic DCV release without prolonged stimulation. Munc13-1/2 facilitated DCV fusion in a different way for synaptic vesicles, which is not essential for DCV release, and overexpression of Munc13 can promote efficient DCV release extrasynaptically (van de Bospoort et al., 2012).
Small GTPases in platelet membrane trafficking
Published in Platelets, 2019
Tony G. Walsh, Yong Li, Andreas Wersäll, Alastair W. Poole
Of particular relevance to this review are the Ras-like (Ral) GTPases, RalA and RalB. Like most Ras GTPases, Rals have been implicated in numerous cellular processes including oncogenic transformations, but have also been implicated as regulators of vesicle trafficking [80]. They are ubiquitously expressed, with high abundance in brain, testes and platelets sharing 82% sequence identity, with ~ 55% identity to other Ras GTPases [81]. A well-characterised effector of Rals is the exocyst complex, comprising of 8 proteins (EXOC1-8) that facilitate the tethering of exocytic vesicles to the plasma membrane [82]. Notably, all components of this octameric complex are present in human (and mouse) platelets and GTP-loaded Rals have been shown to bind EXOC2 and EXOC8 in a mutually exclusive manner [83]. Similarly, other established effectors of Rals include Ral binding protein (RalBP1) and phospholipase D, but their relevance to platelet function and/or vesicle trafficking remains to be determined. Of relevance, RalBP1 has been shown to play a role in receptor-mediated endocytosis by interacting with epsin homology domain proteins Reps1 and Reps2, aswell as clathrin adaptor protein complex AP2, all of which are present in platelets and are supportive of an endocytic function for platelet Rals (Figure 1) [84].
Targeting TANK-binding kinase 1 (TBK1) in cancer
Published in Expert Opinion on Therapeutic Targets, 2020
Or-Yam Revach, Shuming Liu, Russell W. Jenkins
Tumor cells maintain rapid growth by switching to glycolysis for a needed supply of energy. In this process, glucose uptake is elevated in the cancer cells and this appears to be controlled by increased expression of glucose transporters [111]. It was reported that upon activation of RalA, downstream of RAS, TBK1 phosphorylates the exocyst protein Exo84, which leads to translocation of the GLUT4 glucose transporter to the cell membrane [112]. TBK1 also phosphorylates the insulin receptor (thereby blocking its activity) potentially contributing to insulin-resistance [113]. Alterations in tumor cell glycolysis have also been described following epidermal growth factor (EGF) stimulation of cancer cells [28].