Hierarchical Protofilament Intertwining Rules the Formation of Mixed-Curvature Amyloid Polymorphs.

Amyloid polymorphism is a hallmark of almost all amyloid species, yet the mechanisms underlying the formation of amyloid polymorphs and their complex architectures remain elusive. Commonly, two main mesoscopic topologies are found in amyloid polymorphs characterized by non-zero Gaussian and mean curvatures: twisted ribbons and helical fibrils, respectively. Here, a rich heterogeneity of configurations is demonstrated on insulin amyloid fibrils, where protofilament packing can occur, besides the common polymorphs, also in a combined mode forming mixed-curvature polymorphs.

Fully co-factor-free ClearTau platform produces seeding-competent Tau fibrils for reconstructing pathological Tau aggregates.

Tau protein fibrillization is implicated in the pathogenesis of several neurodegenerative diseases collectively known as Tauopathies. For decades, investigating Tau fibrillization in vitro has required the addition of polyanions or other co-factors to induce its misfolding and aggregation, with heparin being the most commonly used. However, heparin-induced Tau fibrils exhibit high morphological heterogeneity and a striking structural divergence from Tau fibrils isolated from Tauopathies patients' brains at ultra- and macro-structural levels.

Role of p38 MAPK, Akt and NFκB in renoprotective effects of nebivolol on renal ischemia-reperfusion injury in rats.

Renal ischemia-reperfusion (I-R) injury is a complex pathophysiologic condition characterized by oxidative stress, inflammation and apoptosis. We investigated the potential renoprotective effect of nebivolol, a β adrenergic receptor blocker, against renal I-R injury. We focused on the role of nebivolol in activating p38 mitogen-activated protein kinase (MAPK) signaling, Akt (protein kinase B) and nuclear factor-κB (NFκB) transcription factors, which contribute to oxidative stress, inflammation and apoptosis during renal I-R.

Systematic Analysis of Metabolic Bottlenecks in the Methylerythritol 4-Phosphate (MEP) Pathway of Zymomonas mobilis.

Zymomonas mobilis is an industrially relevant aerotolerant anaerobic bacterium that can convert up to 96% of consumed glucose to ethanol. This highly catabolic metabolism could be leveraged to produce isoprenoid-based bioproducts via the methylerythritol 4-phosphate (MEP) pathway, but we currently have limited knowledge concerning the metabolic constraints of this pathway in Z. mobilis.

Nanoscale resolution of microbial fiber degradation in action.

The lives of microbes unfold at the micron scale, and their molecular machineries operate at the nanoscale. Their study at these resolutions is key toward achieving a better understanding of their ecology. We focus on cellulose degradation of the canonical system to comprehend how microbes build and use their cellulosomal machinery at these nanometer scales.

Rapid Targeted Quantitation of Protein Overexpression with Direct Infusion Shotgun Proteome Analysis (DISPA-PRM).

While much effort has been placed on comprehensive quantitative proteome analysis, certain applications demand the measurement of only a few target proteins from complex systems. Traditional approaches to targeted proteomics rely on nanoliquid chromatography (nLC) and targeted mass spectrometry (MS) methods, e.g.

The cellular environment shapes the nuclear pore complex architecture.

Nuclear pore complexes (NPCs) create large conduits for cargo transport between the nucleus and cytoplasm across the nuclear envelope (NE). These multi-megadalton structures are composed of about thirty different nucleoporins that are distributed in three main substructures (the inner, cytoplasmic and nucleoplasmic rings) around the central transport channel. Here we use cryo-electron tomography on DLD-1 cells that were prepared using cryo-focused-ion-beam milling to generate a structural model for the human NPC in its native environment.

Computational analyses reveal spatial relationships between nuclear pore complexes and specific lamins.

Nuclear lamin isoforms form fibrous meshworks associated with nuclear pore complexes (NPCs). Using datasets prepared from subpixel and segmentation analyses of 3D-structured illumination microscopy images of WT and lamin isoform knockout mouse embryo fibroblasts, we determined with high precision the spatial association of NPCs with specific lamin isoform fibers. These relationships are retained in the enlarged lamin meshworks of Lmna-/- and Lmnb1-/- fibroblast nuclei.

A lamin A/C variant causing striated muscle disease provides insights into filament organization.

The gene encodes the A-type lamins, which polymerize into ∼3.5-nm-thick filaments and, together with B-type lamins and associated proteins, form the nuclear lamina. Mutations in cause a wide variety of pathologies.

Unveiling the polarity of actin filaments by cryo-electron tomography.

The actin cytoskeleton plays a fundamental role in numerous cellular processes, such as cell motility, cytokinesis, and adhesion to the extracellular matrix. Revealing the polarity of individual actin filaments in intact cells would foster an unprecedented understanding of cytoskeletal processes and their associated mechanical forces. Cryo-electron tomography provides the means for high-resolution structural imaging of cells.

A novel hemostatic scaffold material and the importance of scaffold formation on ending hemorrhage: An experimental rat study.

Background: Different pharmacological agents are developed to control bleeding. However, it is critical for these agents to induce thrombin formation and have an effect on vasoconstriction, coagulation, and scaffold. In this study, we aimed to demonstrate the agents' ability to stop bleeding properties on minor and major open bleedings after skin clefts, extracorporal injuries, traumatic cuts, spontaneous or surgical intervention besides scaffold properties.

Genome Wide Phosphoproteome Analysis of Under Anaerobic, Aerobic, and N-Fixing Conditions.

Protein phosphorylation is a post-translational modification with widespread regulatory roles in both eukaryotes and prokaryotes. Using mass spectrometry, we performed a genome wide investigation of protein phosphorylation in the non-model organism and biofuel producer under anaerobic, aerobic, and N-fixing conditions. Our phosphoproteome analysis revealed 125 unique phosphorylated proteins, belonging to major pathways such as glycolysis, TCA cycle, electron transport, nitrogen metabolism, and protein synthesis.

Factors that influence the decision for hyperbaric oxygen therapy (HBOT) in cases of carbon monoxide poisoning: a retrospective study.

Carbon monoxide poisoning (COP) is one of the most common types of potentially fatal poisoning throughout the world. Hyperbaric oxygen therapy (HBOT) is an effective and quick response modality that clears symptoms and prevents sequelae. HBOT should be administered within 4-6 hours after poisoning.

Methemoglobinemia treated with hyperbaric oxygen therapy: A case report.

Methemoglobinemia is a rare but clinically important condition that should be considered among differential diagnosis' in cyanosis. The conventional treatments of methemoglobinemia are high flow oxygen and methylene blue therapies. We present a 52-year-old male patient who admitted to emergency room with severe cyanosis and dyspnea after he was exposed to paint thinner and zinc phosphate solution.

Physical abuse of the elderly: a 4-year retrospective evaluation in the emergency department.

Aim: Elderly physical abuse (EPA) is defined as injury or assault to or the restriction of an elderly person. Although EPA is an important social problem, its diagnosis is difficult because of tendency to cover up the event. In this study, patients aged 65 years and over who presented at the emergency department (ED) for forensic reasons and in whom physical abuse was suspected were examined.

A novel homozygous W99G mutation in CLDN-16 gene causing familial hypomagnesemic hypercalciuric nephrocalcinosis in Turkish siblings.

Alparslan C, Öncel EP, Akbay S, Alaygut D, Mutlubaş F, Tatlı M, Konrad M, Yavaşcan Ö, Kasap-Demir B. A novel homozygous W99G mutation in CLDN-16 gene causing familial hypomagnesemic hypercalciuric nephrocalcinosis in Turkish siblings. Turk J Pediatr 2018; 60: 76-80.

Insight into the functional organization of nuclear lamins in health and disease.

Lamins are the main component of the nuclear lamina, a protein meshwork at the inner nuclear membrane which primarily provide mechanical stability to the nucleus. Lamins, type V intermediate filament proteins, are also involved in many nuclear activities. Structural analysis of nuclei revealed that lamins form 3.

Evaluation of Relationship between Obsessive-compulsive Disorder and Dissociative Experiences.

Objective: The aim of the study is to evaluate the relationship between obsessive-compulsive disorder (OCD) symptoms and dissociative experiences and the effect of childhood traumatic experiences on this relationship in OCD patients.

Methods: Fifty consecutive OCD patients and 50 healthy controls are enrolled for this study. Sociodemographic and Clinical Data Form, Dissociative Experiences Scale (DES), Padua Inventory (PI) and Childhood Trauma Questionnaire (CTQ) are applied to participants.

Diagnostic value of urine soluble triggering receptor expressed on myeloid cells (sTREM-1) for late-onset neonatal sepsis in infected preterm neonates.

Objective Sepsis is a complex clinical condition caused by a dysregulated immune response to an infection resulting in a fatal outcome. This study aimed to investigate the value of urine soluble triggering receptor expressed on myeloid cells (sTREM-1) for diagnosing culture-proven sepsis in preterm infants. Methods Preterm neonates were evaluated for late-onset sepsis (LOS).

High-throughput droplet microfluidics screening platform for selecting fast-growing and high lipid-producing microalgae from a mutant library.

Biofuels derived from microalgal lipids have demonstrated a promising potential as future renewable bioenergy. However, the production costs for microalgae-based biofuels are not economically competitive, and one strategy to overcome this limitation is to develop better-performing microalgal strains that have faster growth and higher lipid content through genetic screening and metabolic engineering. In this work, we present a high-throughput droplet microfluidics-based screening platform capable of analyzing growth and lipid content in populations derived from single cells of a randomly mutated microalgal library to identify and sort variants that exhibit the desired traits such as higher growth rate and increased lipid content.