Exogenous phospholipids specifically affect transmembrane potential of brain mitochondria and cytochrome C release.

Release of cytochrome c, a decrease of membrane potential (Deltapsi(m)), and a reduction of cardiolipin (CL) of rat brain mitochondria occurred upon incubation in the absence of respiratory substrates. Since CL is critical for mitochondrial functioning, CL enrichment of mitochondria was achieved by fusion with CL liposomes. Fusion was triggered by potassium phosphate at concentrations producing mitochondrial permeability transition pore opening but not cytochrome c release, which was observed only at10 mm. Cyclosporin A inhibited phosphate-induced CL fusion, whereas Pronase pretreatment of mitochondria abolished it, suggesting that mitochondrial permeability transition pore and protein(s) are involved in the fusion process. Phosphate-dependent fusion was enhanced in respiratory state 3 and influenced by phospholipid classes in the order CLphosphatidylglycerol (PG)phosphatidylserine. The probe 10-nonylacridine orange indicated that fused CL had migrated to the inner mitochondrial membrane. In state 3, CL enrichment of mitochondria resulted in a pH decrease in the intermembrane space. Cytofluorimetric analysis of mitochondria stained with 3,3'-diexyloxacarbocyanine iodide and 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzymidazolylcarbocyanine iodide showed Deltapsi(m) increase upon fusion with CL or PG. In contrast, phosphatidylserine fusion required Deltapsi(m) consumption, suggesting that Deltapsi(m) is the driving force in mitochondrial phospholipid importation. Moreover, enrichment with CL and PG brought the low energy mitochondrial population to high Deltapsi(m) values and prevented phosphate-dependent cytochrome c release

Munc18b is an essential gene in mice whose expression is limiting for secretion by airway epithelial and mast cells

Airway mucin secretion and MC (mast cell) degranulation must be tightly controlled for homoeostasis of the lungs and immune system respectively. We found the exocytic protein Munc18b to be highly expressed in mouse airway epithelial cells and MCs, and localized to the apical pole of airway secretory cells. To address its functions, we created a mouse with a severely hypomorphic Munc18b allele such that protein expression in heterozygotes was reduced by∼50%. Homozygous mutant mice were not viable, but heterozygotes showed a ∼50% reduction in stimulated release of mucin from epithelial cells and granule contents from MCs. The defect in MCs affected only regulated secretion and not constitutive or transporter-mediated secretion. The severity of passive cutaneous anaphylaxiswas also reduced by ∼50%, showing that reduction of Munc18b expression results in an attenuation of physiological responses dependent on MC degranulation. The Munc18b promoter is controlled by INR (initiator), Sp1 (specificity protein 1), Ets, CRE (cAMP-response element), GRE (glucocorticoid-response element), GATA and E-box elements in airway epithelial cells; however, protein levels did not change during mucous metaplasia induced by allergic inflammation. Taken together, the results of the present study identifyMunc18b as an essential gene that is a limiting component of the exocytic machinery of epithelial cells and MCs

Glaucoma, Pseudoexfoliation and Hearing Loss: A Systematic Literature Review

Purpose: To investigate the relationship between glaucoma, pseudoexfoliation and hearing loss (HL). Methods: A systematic literature search following PRISMA guidelines was conducted using the PubMed, Embase, Scopus and Cochrane databases from 1995 up to 28 August 2023. Results: Thirty studies out of the 520 records screened met the inclusion criteria and were included. Most articles (n = 20) analysed the association between pseudoexfoliation syndrome (XFS) and HL, showing XFS patients to have higher prevalence of sensorineural hearing loss (SNHL) at both speech frequencies (0.25, 0.5, 1 and 2 kHz), and higher frequencies (4 and 8 kHz) compared to controls in most cases. No significant differences in prevalence or level of HL between XFS and pseudoexfoliative glaucoma (XFG) were detected in most studies. Eight articles analysed the relationship between primary open-angle glaucoma (POAG) and HL. Overall, a positive association between the two conditions was highlighted across all studies except for two cases. Similarly, articles focusing on NTG and HL (n = 4) showed a positive association in most cases. The role of autoimmunity and, in particular, the presence of antiphosphatidylserine antibodies (APSA) in patients with NTG and HL suggested an underlying autoimmune or vascular mechanism contributing to their pathogenesis. Only one study analysed the relationship between angle-closure glaucoma (ACG) and HL, showing higher incidence of ACG in patients with SNHL compared to normal hearing controls. Conclusions: Most studies detected an association between XFS and HL as well as POAG/NTG/ACG and HL, suggesting the presence of a similar pathophysiology of neurodegeneration. However, given the strength of the association of XFS with HL, it remains unclear whether the presence of XFG is further associated with SNHL. Further research specifically targeted to assess the correlation between glaucoma, XFS and HL is warranted to provide a more comprehensive understanding of this association

Underlying Event measurements in pp collisions at s=0.9 \sqrt {s} = 0.9 and 7 TeV with the ALICE experiment at the LHC

We present measurements of Underlying Event observables in pp collisions at s√=0.9 and 7TeV. The analysis is performed as a function of the highest charged-particle transverse momentum p T,LT in the event. Different regions are defined with respect to the azimuthal direction of the leading (highest transverse momentum) track: Toward, Transverse and Away. The Toward and Away regions collect the fragmentation products of the hardest partonic interaction. The Transverse region is expected to be most sensitive to the Underlying Event activity. The study is performed with charged particles above three different p T thresholds: 0.15, 0.5 and 1.0 GeV/c. In the Transverse region we observe an increase in the multiplicity of a factor 2–3 between the lower and higher collision energies, depending on the track p T threshold considered. Data are compared to Pythia 6.4, Pythia 8.1 and Phojet. On average, all models considered underestimate the multiplicity and summed p T in the Transverse region by about 10–30%

Centrality dependence of the charged-particle multiplicity density at mid-rapidity in Pb-Pb collisions at sNN\sqrt{s_{NN}} = 2.76 TeV

The centrality dependence of the charged-particle multiplicity density at mid-rapidity in Pb-Pb collisions at $\sqrt{s_{NN}}$ = 2.76 TeV is presented. The charged-particle density normalized per participating nucleon pair increases by about a factor 2 from peripheral (70-80%) to central (0-5%) collisions. The centrality dependence is found to be similar to that observed at lower collision energies. The data are compared with models based on different mechanisms for particle production in nuclear collisions.The centrality dependence of the charged-particle multiplicity density at mid-rapidity in Pb-Pb collisions at $\sqrt{s_{\rm NN}}$ = 2.76 TeV is presented. The charged-particle density normalized per participating nucleon pair increases by about a factor 2 from peripheral (70-80%) to central (0-5%) collisions. The centrality dependence is found to be similar to that observed at lower collision energies. The data are compared with models based on different mechanisms for particle production in nuclear collisions