Heterogeneity in Lowe Syndrome: Mutations Affecting the Phosphatase Domain of OCRL1 Differ in Impact on Enzymatic Activity and Severity of Cellular Phenotypes.

Lowe Syndrome (LS) is a condition due to mutations in the gene, characterized by congenital cataracts, intellectual disability, and kidney malfunction. Unfortunately, patients succumb to renal failure after adolescence. This study is centered in investigating the biochemical and phenotypic impact of patient's OCRL1 variants (OCRL1).

Worldwide Assessment of the Mandibular First Molar Second Distal Root and Root Canal: A Cross-sectional Study with Meta-analysis.

Introduction: This study assessed the prevalence of radix entomolaris and 2 canals at the distal aspect of mandibular first molars among different geographic regions by means of cone-beam computed tomographic imaging.

Methods: Precalibrated observers from 23 worldwide geographic locations followed a standardized screening protocol to assess 5750 cone-beam computed tomographic images of mandibular first molars (250 per region), gathering demographic data and recording the presence of radix entomolaris and a second canal at the distal aspect of teeth. Intra- and interrater reliability tests were conducted and comparisons among groups were performed using proportions and odds ratio forest plots.

Worldwide Prevalence of a Lingual Canal in Mandibular Premolars: A Multicenter Cross-sectional Study with Meta-analysis.

Introduction: The presence of multiple root canals is an important morphologic aspect of mandibular premolars. This study aimed to perform a worldwide analysis on the prevalence of a lingual canal in mandibular premolars and to evaluate its influence on patients' demographics in 23 countries using cone-beam computed tomographic images.

Methods: Observers from 23 countries were instructed to evaluate cone-beam computed tomographic images of 300 first and 300 second premolars (13,800 teeth) regarding the presence of a lingual canal, canal configuration, and data related to patients' ethnicity, age, and sex following a standardized screening methodology.

Worldwide Analyses of Maxillary First Molar Second Mesiobuccal Prevalence: A Multicenter Cone-beam Computed Tomographic Study.

Introduction: Maxillary first molar second mesiobuccal (MB2) root canal prevalence may change among different populations. The aim of this study was to analyze the worldwide prevalence of the MB2 root canal and understand its possible relation with sex, age, side, and root configuration using in vivo cone-beam computed tomographic (CBCT) assessment.

Methods: Observers from 21 regions were calibrated to achieve a similar CBCT assessment methodology and instructed to collect data from 250 maxillary first molars in previously existing examinations.

Disaggregation of gold nanoparticles by .

The use of manufactured nanomaterials is rapidly increasing, while our understanding of the consequences of releasing these materials into the environment is still limited and many questions remain, for example, how do nanoparticles affect living organisms in the wild? How do organisms adapt and protect themselves from exposure to foreign materials? How does the environment affect the performance of nanoparticles, including their surface properties? In an effort to address these crucial questions, our main aim has been to probe the effects of aquatic organisms on nanoparticle aggregation. We have, therefore, carried out a systematic study with the purpose to disentangle the effects of the freshwater zooplankter, , on the surface properties, stability, and aggregation properties of gold (Au) nanoparticles under different aqueous conditions as well as identified the proteins bound to the nanoparticle surface. We show that Au nanoparticles aggregate in pure tap water, but to a lesser extent in water that either contains or has been pre-conditioned with .

Kidney-differentiated cells derived from Lowe Syndrome patient's iPSCs show ciliogenesis defects and Six2 retention at the Golgi complex.

Lowe syndrome is an X-linked condition characterized by congenital cataracts, neurological abnormalities and kidney malfunction. This lethal disease is caused by mutations in the OCRL1 gene, which encodes for the phosphatidylinositol 5-phosphatase Ocrl1. While in the past decade we witnessed substantial progress in the identification and characterization of LS patient cellular phenotypes, many of these studies have been performed in knocked-down cell lines or patient's cells from accessible cell types such as skin fibroblasts, and not from the organs affected.

Intracanal Cryotherapy Reduces Postoperative Pain in Teeth with Symptomatic Apical Periodontitis: A Randomized Multicenter Clinical Trial.

Introduction: A prospective, multicentered, randomized clinical trial was designed to assess if controlled irrigation with cold saline could result in less incidence and intensity of postoperative pain in patients presenting with pulp necrosis and symptomatic apical periodontitis.

Methods: A total of 210 patients (presenting with necrotic uniradicular teeth with a diagnosis of symptomatic apical periodontitis and a preoperative visual analog scale (VAS) score higher than 7) were randomly allocated in the control or experimental group after the completion of shaping and cleaning procedures. The experimental group received a final irrigation with 20 mL sterile cold (2.

Granulocyte colony-stimulating factor (G-CSF) upregulates β1 integrin and increases migration of human trophoblast Swan 71 cells via PI3K and MAPK activation.

Multiple cytokines and growth factors expressed at the fetal-maternal interface are involved in the regulation of trophoblast functions and placental growth, but the role of G-CSF has not been completely established. Based on our previous study showing that G-CSF increases the activity of matrix metalloproteinase-2 and the release of vascular endothelial growth factor in Swan 71 human trophoblast cells, in this work we explore the possible contribution of G-CSF to cell migration and the G-CSF-triggered signaling pathway. We found that G-CSF induced morphological changes on actin cytoskeleton consistent with a migratory cell phenotype.

Ciliopathies: the trafficking connection.

The primary cilium (PC) is a very dynamic hair-like membrane structure that assembles/disassembles in a cell-cycle-dependent manner and is present in almost every cell type. Despite being continuous with the plasma membrane, a diffusion barrier located at the ciliary base confers the PC properties of a separate organelle with very specific characteristics and membrane composition. Therefore, vesicle trafficking is the major process by which components are acquired for cilium formation and maintenance.

Rationale for gastrectomy with D2 lymphadenectomy in the treatment of gastric cancer.

Background: In the surgical management of gastric cancer, D2 lymphadenectomy aims to reduce the incidence of locoregional relapse, and to increase patient survival.

Methods: A prospective study was made of 126 consecutive patients operated upon for gastric cancer, with gastrectomy and D2 lymphadenectomy. Hospital morbidity and mortality, relapses, and patient survival after 5 years were studied.

Surgical treatment of recurrent gastric cancer.

Background: The value of programs to detect recurrence of a previously operated gastric cancer is a controversial subject. D2 lymphadenectomy achieves better local control and a lower local recurrence rate than D1 lymphadenectomy.

Methods: The results achieved with surgical treatment of recurrent gastric cancer in a series of 126 consecutive patients who had been treated with gastrectomy with D2 lymphadenectomy are reported.

[Morbidity and mortality in gastrectomy with D2 lymphadenectomy in a specialised unit].

Introduction: The combination of gastrectomy and D2 lymphadenectomy is still not a widely accepted therapeutic option by Western surgeons, due to its high post-operative morbidity and mortality.

Objective: To evaluate the morbidity and mortality in a series of patients with gastric cancer treated by gastrectomy and D2 lymphadenectomy, and compare these results with those published by centres with notable experience.

Patients And Method: A descriptive and prospective study on a series of 126 consecutive patients with gastric cancer treated by gastrectomy and D2 lymphadenectomy.

Epsin N-terminal homology domains perform an essential function regulating Cdc42 through binding Cdc42 GTPase-activating proteins.

Epsins are endocytic proteins with a structured epsin N-terminal homology (ENTH) domain that binds phosphoinositides and a poorly structured C-terminal region that interacts with ubiquitin and endocytic machinery, including clathrin and endocytic scaffolding proteins. Yeast has two redundant genes encoding epsins, ENT1 and ENT2; deleting both genes is lethal. We demonstrate that the ENTH domain is both necessary and sufficient for viability of ent1Deltaent2Delta cells.

Role of the mammalian retromer in sorting of the cation-independent mannose 6-phosphate receptor.

The cation-independent mannose 6-phosphate receptor (CI-MPR) mediates sorting of lysosomal hydrolase precursors from the TGN to endosomes. After releasing the hydrolase precursors into the endosomal lumen, the unoccupied receptor returns to the TGN for further rounds of sorting. Here, we show that the mammalian retromer complex participates in this retrieval pathway.

Ubiquitin: not just for proteasomes anymore.

Ubiquitin is a small protein that can be covalently linked to itself or other proteins, either as single ubiquitin molecules or as chains of polyubiquitin. Addition of ubiquitin to a target protein requires a series of enzymatic activities (by ubiquitin-activating, -conjugating and -ligating enzymes). The first function attributed to ubiquitin was the covalent modification of misfolded cytoplasmic proteins, thereby directing proteasome-dependent proteolysis.

The yeast Epsin Ent1 is recruited to membranes through multiple independent interactions.

In addition to its well known role in targeting proteins for proteasomal degradation, ubiquitin (Ub) is also involved in promoting internalization of cell surface proteins into the endocytic pathway. Moreover, putative Ub interaction motifs (UIMs) as well as Ub-associated (UBA) domains have been identified in key yeast endocytic proteins (the epsins Ent1 and Ent2, and the Eps15 homolog Ede1). In this study, we characterized the interaction of Ub with the Ede1 UBA domain and with the UIMs of Ent1.