OST Catalytic Subunit Redundancy Enables Therapeutic Targeting of N-Glycosylation.

Protein asparagine (N)-glycosylation, which promotes folding and trafficking of cell surface receptors such as the EGFR, has not been considered a viable target in oncology due to the essential and non-redundant enzymatic activities required for glycan synthesis and transfer. In mammals an exception to this rule is the presence of the oligosaccharyltransferase (OST) catalytic subunit paralogs, STT3A and STT3B. Here we delineate the chemical biology of OST inhibitors and develop an approach for limited inhibition of N-glycosylation optimized for downstream effects on EGFR.

Haemoglobinopathies and other rare anemias in Spain: ten years of a nationwide registry (REHem-AR).

REHem-AR was created in 2013. The progressive implementation of neonatal screening for haemoglobinopathies in Spanish autonomous communities where the registry had not been implemented, as well as the addition of new centres during this period, has considerably increased the sample of patients covered. In this study, we update our previous publication in this area, after a follow-up of more than 5 years.

Signal recognition particle receptor-β (SR-β) coordinates cotranslational N-glycosylation.

Proteins destined for the secretory compartment of the cell are cotranslationally translocated into the endoplasmic reticulum. The majority of these proteins are N-glycosylated, a co- and posttranslational modification that ensures proper protein folding, stability, solubility, and cellular localization. Here, we show that the [Formula: see text] subunit of the signal recognition particle receptor (SR) is required for assembly of the N-glycosylation-competent translocon.

Exploring the anti-inflammatory potential of Colocasia esculenta root extract in in-vitro and in-vivo models of inflammation.

Ethnopharmacological Relevance: Colocasia esculenta (CE) (L.) Schott is an annual herbaceous tropical plant from the family of Araceae which has been traditionally used for the healing of various ailments such as asthma, arthritis, internal hemorrhage, diarrhea, and neurological disorders. The plant is reported to have potential anti-microbial, anti-fungal, antimetastatic, anti-hepatotoxic, and anti-lipid peroxidative activities.

The role of Wnt pathway in obesity induced inflammation and diabetes: a review.

Diabetes has become a major killer worldwide and at present, millions are affected by it. Being a chronic disease it increases the risk of other diseases ranging from pulmonary disorders to soft tissue infections. The loss of insulin-producing capacity of the pancreatic β-cells is the main reason for the development of the disease.

Exploring the role of Aquaporins (AQPs) in LPS induced systemic inflammation and the ameliorative effect of Garcinia in male Wistar rat.

The Aquaporins (AQPs) could prove to be striking targets of inflammation. The aim of this study was to study the involvement of AQPs and explore the anti-inflammatory activity of Garcinia extract in LPS induced acute systemic inflammation in Wistar rats. Adult male Wistar rats (n = 6) were pretreated with Garcinia orally twice for 7 days, followed by a single intraperitoneal dose (5.

Upper arm length along with mid-upper arm circumference to enhance wasting prevalence estimation and diagnosis: sensitivity and specificity in 6-59-months-old children.

Objective: To evaluate the added value of the use of upper arm length (UAL) along with mid-upper arm circumference (MUAC) to diagnose and estimate the prevalence of wasting in comparison to current WHO standard and other MUAC-based methods.

Design: UAL and usual anthropometric measurements were collected during a national cross-sectional nutritional survey. Children were classified into three upper arm length groups (UALGs): UALG1, UALG2 and UALG3 according to the following UAL limits: ≤150, 151-180 and ≥181 mm, respectively.

STING enhances cell death through regulation of reactive oxygen species and DNA damage.

Resistance to DNA-damaging agents is a significant cause of treatment failure and poor outcomes in oncology. To identify unrecognized regulators of cell survival we performed a whole-genome CRISPR-Cas9 screen using treatment with ionizing radiation as a selective pressure, and identified STING (stimulator of interferon genes) as an intrinsic regulator of tumor cell survival. We show that STING regulates a transcriptional program that controls the generation of reactive oxygen species (ROS), and that STING loss alters ROS homeostasis to reduce DNA damage and to cause therapeutic resistance.

Acute pancreatitis in Chile: A multicenter study on epidemiology, etiology and clinical outcome. Retrospective analysis of clinical files.

Background: Epidemiology of acute pancreatitis (AP) is variable in different geographical regions.

Objectives: To compare etiology and severity of AP to published data from South America and the rest of world, study impact of demographical factors and treatment on its outcome in Chilean hospitals.

Methods: Multicenter observational study.

Neuregulin Signaling Is a Mechanism of Therapeutic Resistance in Head and Neck Squamous Cell Carcinoma.

EGFR signaling confers resistance to radiotherapy and is a validated target in head and neck squamous cell carcinoma (HNSCC). The inhibition of EGFR in combination with radiotherapy improves local control and overall survival in these patients; however, therapeutic resistance limits the efficacy of this approach. We therefore sought to identify cellular mechanisms that cause resistance to EGFR inhibition and radiotherapy in HNSCC.

Maternal views on facilitators of and barriers to breastfeeding preterm infants.

Background: The supply of breast milk to preterm infants tends to occur at a lower rate than that recorded among term infants. We aimed to investigate the facilitators of and barriers to breastfeeding during hospital stay according to the experiences of mothers that gave birth to premature infants requiring admission to neonatal intensive care unit.

Methods: A cross-sectional questionnaire survey was conducted.

Oligosaccharyltransferase Inhibition Overcomes Therapeutic Resistance to EGFR Tyrosine Kinase Inhibitors.

Asparagine (N)-linked glycosylation is a posttranslational modification essential for the function of complex transmembrane proteins. However, targeting glycosylation for cancer therapy has not been feasible due to generalized effects on all glycoproteins. Here, we perform sensitivity screening of 94 lung cancer cell lines using NGI-1, a small-molecule inhibitor of the oligosaccharyltransferase (OST) that partially disrupts N-linked glycosylation, and demonstrate a selective loss of tumor cell viability.

Oligosaccharyltransferase Inhibition Reduces Receptor Tyrosine Kinase Activation and Enhances Glioma Radiosensitivity.

Purpose: Parallel signaling reduces the effects of receptor tyrosine kinase (RTK)-targeted therapies in glioma. We hypothesized that inhibition of protein N-linked glycosylation, an endoplasmic reticulum co- and posttranslational modification crucial for RTK maturation and activation, could provide a new therapeutic approach for glioma radiosensitization. We investigated the effects of a small-molecule inhibitor of the oligosaccharyltransferase (NGI-1) on EGFR family receptors, MET, PDGFR, and FGFR1.

Atypical Autoimmune Hematologic Disorders in a Patient With Kabuki Syndrome.

Kabuki syndrome is a rare genetic disorder characterized by congenital anomalies and developmental delay. It is often associated with impaired immune response and autoimmune abnormalities. We report the clinical case of a girl with Kabuki syndrome who developed autoimmune neutropenia, not previously reported, followed by hemolytic anemia and autoimmune thrombocytopenia.

Tunable Magnetism in Nanoporous CuNi Alloys by Reversible Voltage-Driven Element-Selective Redox Processes.

Voltage-driven manipulation of magnetism in electrodeposited 200 nm thick nanoporous single-phase solid solution Cu Ni (at%) alloy films (with sub 10 nm pore size) is accomplished by controlled reduction-oxidation (i.e., redox) processes in a protic solvent, namely 1 m NaOH aqueous solution.

Unravelling the Elusive Antiferromagnetic Order in Wurtzite and Zinc Blende CoO Polymorph Nanoparticles.

Although cubic rock salt-CoO has been extensively studied, the magnetic properties of the main nanoscale CoO polymorphs (hexagonal wurtzite and cubic zinc blende structures) are rather poorly understood. Here, a detailed magnetic and neutron diffraction study on zinc blende and wurtzite CoO nanoparticles is presented. The zinc blende-CoO phase is antiferromagnetic with a 3rd type structure in a face-centered cubic lattice and a Néel temperature of T (zinc-blende) ≈225 K.

Clustering analysis strategies for electron energy loss spectroscopy (EELS).

In this work, the use of cluster analysis algorithms, widely applied in the field of big data, is proposed to explore and analyze electron energy loss spectroscopy (EELS) data sets. Three different data clustering approaches have been tested both with simulated and experimental data from FeO/MnO core/shell nanoparticles. The first method consists on applying data clustering directly to the acquired spectra.

Micelle-Assisted Electrodeposition of Mesoporous Fe-Pt Smooth Thin Films and their Electrocatalytic Activity towards the Hydrogen Evolution Reaction.

Mesoporous Fe-Pt thin films are obtained by micelle-assisted electrodeposition onto metallic substrates with dissimilar activity (namely, gold, copper, and aluminum seed layers evaporated on Si/Ti) under constant applied potential (E=-1.1 V vs. Ag/AgCl) and deposition time (600 s).

Micelle-assisted electrodeposition of highly mesoporous Fe-Pt nodular films with soft magnetic and electrocatalytic properties.

Mesoporous Fe-Pt nodular films (with a regular spatial arrangement of sub-15 nm pores) are grown onto evaporated Au, Cu and Al conductive layers by micelle-assisted electrodeposition from metal chloride salts in the presence of Pluronic P123 tri-block copolymer dissolved in the aqueous electrolytic bath. This synthetic approach constitutes a simple, one-step, versatile procedure to grow multifunctional mesoporous layers appealing for diverse applications that take advantage of materials with an ultra-high surface area-to-volume ratio. The films exhibit tuneable composition with relative Fe/Pt weight ratios, disregarding oxygen, varying from 4/96 to 52/48.

Biodegradable FeMnSi Sputter-Coated Macroporous Polypropylene Membranes for the Sustained Release of Drugs.

Pure Fe and FeMnSi thin films were sputtered on macroporous polypropylene (PP) membranes with the aim to obtain biocompatible, biodegradable and, eventually, magnetically-steerable platforms. Room-temperature ferromagnetic response was observed in both Fe- and FeMnSi-coated membranes. Good cell viability was observed in both cases by means of cytotoxicity studies, though the FeMnSi-coated membranes showed higher biodegradability than the Fe-coated ones.

Nanoporous Fe-Based Alloy Prepared by Selective Dissolution: An Effective Fenton Catalyst for Water Remediation.

A fully nanoporous Fe-rich alloy, prepared by selective dissolution of melt-spun FeCu ribbons, exhibits outstanding properties as a heterogeneous Fenton catalyst toward the degradation of methyl orange (MO) in aqueous solution. In addition, the ferromagnetic characteristics of this material enable its wireless manipulation toward specific locations within polluted wastewater. The influence of selective dissolution on the microstructure, sample morphology (surface and cross-section), elemental composition, and magnetic properties of the resulting nanoporous alloy is investigated.

Room-temperature synthesis of three-dimensional porous ZnO@CuNi hybrid magnetic layers with photoluminescent and photocatalytic properties.

A facile synthetic approach to prepare porous ZnO@CuNi hybrid films is presented. Initially, magnetic CuNi porous layers (consisting of phase separated CuNi alloys) are successfully grown by electrodeposition at different current densities using H bubbles as a dynamic template to generate the porosity. The porous CuNi alloys serve as parent scaffolds to be subsequently filled with a solution containing ZnO nanoparticles previously synthesized by sol-gel.

Novel Fe-Mn-Si-Pd alloys: insights into mechanical, magnetic, corrosion resistance and biocompatibility performances.

Two new Fe-based alloys, Fe-10Mn6Si1Pd and Fe-30Mn6Si1Pd, have been fabricated by arc-melting followed by copper mold suction casting. The Fe-30Mn6Si1Pd alloy mainly consists of ε-martensite and γ-austenite Fe-rich phases whereas the Fe-10Mn6Si1Pd alloy primarily contains the α-Fe(Mn)-ferrite phase. Additionally, Pd-rich precipitates were detected in both alloys.

Spontaneous formation of spiral-like patterns with distinct periodic physical properties by confined electrodeposition of Co-In disks.

Spatio-temporal patterns are ubiquitous in different areas of materials science and biological systems. However, typically the motifs in these types of systems present a random distribution with many possible different structures. Herein, we demonstrate that controlled spatio-temporal patterns, with reproducible spiral-like shapes, can be obtained by electrodeposition of Co-In alloys inside a confined circular geometry (i.