The youth movement Nashi: contentious politics, civil society, and party politics

The youth movement Nashi was established in Russia with the support of the Putin regime in 2005. The success of anti-regime demonstrators in Ukraine's ‘Orange Revolution’ in 2004 had been noted in Moscow, and Nashi's role was to serve as a pro-regime force to be mobilised against the opposition. Its focus was the contentious politics of the street. Nashi represents an interesting theoretical case from the perspective of contentious politics and its relationship with civil society and formal party politics. Nashi's role has developed to include facilitating young people's engagement with party politics and business. Its early centralised control has been ameliorated somewhat by a reorganisation focused on local action. Nonetheless, Nashi exists with state support. Its continued role in contentious politics in support of the Putin regime, for example, countering opposition demonstrations in Moscow in December 2011, makes its identification as a component of democratic civil society problematic

Efficacy of Esophageal Protector in Treating Gastroesophageal Reflux Disease with Extraesophageal Symptoms: a Multicenter, Open-Label, Observational Study

Aim: to assess effects of esophageal protector Alfasoxx on extraesophageal symptoms in patients with GERD.Materials and methods. A prospective open multicenter post-registration observational study was conducted. The study included 546 patients aged 6 to 85 years (the average age of patients is 42.4 ± 16.9 years) with a verified diagnosis of GERD (endoscopically and/or pH-metrically), the presence of extraesophageal symptoms of the disease (according to the results of an objective examination and consultations of specialists), to whom the attending physician prescribed a course of treatment with a medical device Alfasoxx in accordance with the instructions for medical use. The patients were recruited by 51 researchers in 26 cities of Russia. The study in chronological order consisted of a screening visit and two recorded visits (the observation period within the framework of the use of the Alfasoxx esophagoprotector). The screening visit was conducted on the day of the patient's admission. Visit 1 could be conducted on the same day as the screening visit, whereas visit 2 was conducted 4–5 weeks after visit 1 at the end of the course of treatment.Results. According to the results obtained, at the end of the study, 42.7 % (95 % CI: 38.5–46.9) had complete disappearance of extraesophageal GERD symptoms (questionnaire RSI = 0 points). When comparing the average values of the total RSI score before and after treatment, there was also a statistically significant regression from 13.8 points (95 % CI: 13.2–14.4) at visit 1 to 2.0 points (95 % CI: 1.8–2.2) at visit 2. Thus, the decrease in the total score was significant and exceeded 80 % of the initial value. When analyzing the dynamics of individual indicators of the RSI scale before and after treatment, a significant regression in the severity of all symptoms of the disease was noted. In addition, the results showed that the proportion of patients taking antacid-containing drugs at visit 1 significantly decreased from 58.2 % (95 % CI: 54.0–62.4) to 15.2 % (95 % CI: 12.1–18.3) by visit 2. The average score on the Likert scale of satisfaction with treatment was 4.8 (95 % CI: 4.8–4.9), whereas the convenience of using Alfasoxx is 4.7.Conclusion. This prospective observational multicenter study demonstrated that the addition of Alfasoxx to standard GERD therapy contributes to a significant regression of both esophageal and extraesophageal symptoms, as well as a decrease in the need for antacid medications

Identification and Characterization of the Lamprey High-Mobility Group Box 1 Gene

High-mobility group box 1 (HMGB1), a highly conserved DNA-binding protein, plays an important role in maintaining nucleosome structures, transcription, and inflammation. We identified a homolog of HMGB1 in the Japanese lamprey (Lampetra japonica). The Lampetra japonica HMGB1 gene (Lj-HMGB1) has over 70% sequence identity with its homologs in jawed vertebrates. Despite the reasonably high sequence identity with other HMGB1 proteins, Lj-HMGB1 did not group together with these proteins in a phylogenetic analysis. We examined Lj-HMGB1 expression in lymphocyte-like cells, and the kidneys, heart, gills, and intestines of lampreys before and after the animals were challenged with lipopolysaccharide (LPS) and concanavalin A (ConA). Lj-HMGB1 was initially expressed at a higher level in the heart, but after treatment with LPS and ConA only the gills demonstrated a significant up-regulation of expression. The recombinant Lj-HMGB1 (rLj-HMGB1) protein bound double-stranded DNA and induced the proliferation of human adenocarcinoma cells to a similar extent as human HMGB1. We further revealed that Lj-HMGB1 was able to induce the production of tumor necrosis factor-α (TNF-α), a pro-inflammatory mediator, in activated human acute monocytic leukemia cells. These results suggest that lampreys use HMGB1 to activate their innate immunity for the purpose of pathogen defense

Laforin, a Dual Specificity Phosphatase Involved in Lafora Disease, Is Present Mainly as Monomeric Form with Full Phosphatase Activity

Lafora Disease (LD) is a fatal neurodegenerative epileptic disorder that presents as a neurological deterioration with the accumulation of insoluble, intracellular, hyperphosphorylated carbohydrates called Lafora bodies (LBs). LD is caused by mutations in either the gene encoding laforin or malin. Laforin contains a dual specificity phosphatase domain and a carbohydrate-binding module, and is a member of the recently described family of glucan phosphatases. In the current study, we investigated the functional and physiological relevance of laforin dimerization. We purified recombinant human laforin and subjected the monomer and dimer fractions to denaturing gel electrophoresis, mass spectrometry, phosphatase assays, protein-protein interaction assays, and glucan binding assays. Our results demonstrate that laforin prevalently exists as a monomer with a small dimer fraction both in vitro and in vivo. Of mechanistic importance, laforin monomer and dimer possess equal phosphatase activity, and they both associate with malin and bind glucans to a similar extent. However, we found differences between the two states' ability to interact simultaneously with malin and carbohydrates. Furthermore, we tested other members of the glucan phosphatase family. Cumulatively, our data suggest that laforin monomer is the dominant form of the protein and that it contains phosphatase activity

A Modular BAM Complex in the Outer Membrane of the α-Proteobacterium Caulobacter crescentus

Mitochondria are organelles derived from an intracellular α-proteobacterium. The biogenesis of mitochondria relies on the assembly of β-barrel proteins into the mitochondrial outer membrane, a process inherited from the bacterial ancestor. Caulobacter crescentus is an α-proteobacterium, and the BAM (β-barrel assembly machinery) complex was purified and characterized from this model organism. Like the mitochondrial sorting and assembly machinery complex, we find the BAM complex to be modular in nature. A ∼150 kDa core BAM complex containing BamA, BamB, BamD, and BamE associates with additional modules in the outer membrane. One of these modules, Pal, is a lipoprotein that provides a means for anchorage to the peptidoglycan layer of the cell wall. We suggest the modular design of the BAM complex facilitates access to substrates from the protein translocase in the inner membrane

Lateral opening in the intact β-barrel assembly machinery captured by cryo-EM

The β-barrel assembly machinery (BAM) is a ~203 kDa complex of five proteins (BamA-E) which is essential for viability in E. coli. BAM promotes the folding and insertion of β-barrel proteins into the outer membrane via a poorly understood mechanism. Several current models suggest that BAM functions through a ‘lateral gating’ motion of the β-barrel of BamA. Here we present a cryo-EM structure of the BamABCDE complex, at 4.9 Å resolution. The structure is in a laterally open conformation showing that gating is independent of BamB binding. We describe conformational changes throughout the complex, and interactions between BamA, B, D, and E and the detergent micelle that suggest communication between BAM and the lipid bilayer. Finally, using an enhanced reconstitution protocol and functional assays, we show that for the outer membrane protein OmpT, efficient folding in vitro requires lateral gating in BAM

Outer membrane protein folding from an energy landscape perspective

The cell envelope is essential for the survival of Gram-negative bacteria. This specialised membrane is densely packed with outer membrane proteins (OMPs), which perform a variety of functions. How OMPs fold into this crowded environment remains an open question. Here, we review current knowledge about OFMP folding mechanisms in vitro and discuss how the need to fold to a stable native state has shaped their folding energy landscapes. We also highlight the role of chaperones and the β-barrel assembly machinery (BAM) in assisting OMP folding in vivo and discuss proposed mechanisms by which this fascinating machinery may catalyse OMP folding

A unified model for BAM function that takes into account type Vc secretion and species differences in BAM composition

Transmembrane proteins in the outer membrane of Gram-negative bacteria are almost exclusively β-barrels. They are inserted into the outer membrane by a conserved and essential protein complex called the BAM (for β-barrel assembly machinery). In this commentary, we summarize current research into the mechanism of this protein complex and how it relates to type V secretion. Type V secretion systems are autotransporters that all contain a β-barrel transmembrane domain inserted by BAM. In type Vc systems, this domain is a homotrimer. We argue that none of the current models are sufficient to explain BAM function particularly regarding type Vc secretion. We also find that current models based on the well-studied model system Escherichia coli mostly ignore the pronounced differences in BAM composition between different bacterial species. We propose a more holistic view on how all OMPs, including autotransporters, are incorporated into the lipid bilayer

Carotid body tumors – diagnostis and treatment. Case report

Introduction: Glomus tumors are tumors of the paraganglia in the skull base and neck. These paraganglia are named according to their specific location – glomus caroticum, glomus jugular, tympanicum or vagal, thus the tumors are referred to as tumor of glomus caroticum of glomus jugular etc. Carotid body tumors are rare, benign neoplasms, originating from chemoreceptor cells located in the vessel adventitium of the carotid bifurcation. Considering the high risk during the surgical procedure, accurate preoperative diagnosis is of a great importance.Materials and Methods: We present a clinical case of a 54 y.o. patient Y. G. The patient is diagnosed with a glomus caroticum tumor in the left, found intraoperatively, followed by multidisciplinary treatment approach.Results: The patient Y. G. 54 y.o. is hospitalized in Ear, Nose and Throat department, "St. George" University Hospital – Plovdiv. With complaints as follows: painless swelling in the left region of the neck, with soft-elastic consistency. After a CT examination, the patient undergoes a surgical procedure, during which, together with a team of vascular surgeons, a glomus caroticus tumor is found. Tumor resection is not done. MRT-angiography is made and a decision for placing a coil implant is taken. After placing the coil implant in the region of the internal carotid artery, the patient is followed; for a period of 6 months the tumor is with reduced size, no postoperative complications are observed.Conclusion: Diagnostic and treatment a of carotid body tumors acquires multidisciplinary approach and assessment of the risks and benefits of surgical intervention. The use of Shamblin classification has its important clinical meaning regarding the decision for undeertaking surgical intervention. There are contradictory opinions regarding the embolization of glomus caroticus tumor, never the less in Shamblin III the risk of resectiong and reconstructing the carotid artery is much more considerable