Human Regulatory Protein Ki-1/57 Is a Target of SUMOylation and Affects PML Nuclear Body Formation.

Ki-1/57 is a nuclear and cytoplasmic regulatory protein first identified in malignant cells from Hodgkin's lymphoma. It is involved in gene expression regulation on both transcriptional and mRNA metabolism levels. Ki-1/57 belongs to the family of intrinsically unstructured proteins and undergoes phosphorylation by PKC and methylation by PRMT1.

Next Generation Sequencing Reveals Potentially Actionable Alterations in the Majority of Patients with Lymphoid Malignancies.

Next generation sequencing (NGS) identifies alterations that may be potentially targetable by Food and Drug Administration (FDA) approved drugs and/or by available experimental agents that may not have otherwise been contemplated. Many targeted drugs have been developed for diverse solid cancers; a smaller number of genomically targeted drugs have been approved for lymphoid malignancies. We analyzed NGS results from 60 patients with various lymphoid malignancies and found a total of 224 alterations (median per patient = 3).

To what extent can ecosystem services motivate protecting biodiversity?

Society increasingly focuses on managing nature for the services it provides people rather than for the existence of particular species. How much biodiversity protection would result from this modified focus? Although biodiversity contributes to ecosystem services, the details of which species are critical, and whether they will go functionally extinct in the future, are fraught with uncertainty. Explicitly considering this uncertainty, we develop an analytical framework to determine how much biodiversity protection would arise solely from optimising net value from an ecosystem service.

Two rheumatoid arthritis-specific autoantigens correlate microbial immunity with autoimmune responses in joints.

In rheumatoid arthritis (RA), immunological triggers at mucosal sites, such as the gut microbiota, may promote autoimmunity that affects joints. Here, we used discovery-based proteomics to detect HLA-DR-presented peptides in synovia or peripheral blood mononuclear cells and identified 2 autoantigens, N-acetylglucosamine-6-sulfatase (GNS) and filamin A (FLNA), as targets of T and B cell responses in 52% and 56% of RA patients, respectively. Both GNS and FLNA were highly expressed in synovia.

Microfluidic Capillary Electrophoresis-Mass Spectrometry for Analysis of Monosaccharides, Oligosaccharides, and Glycopeptides.

Glycomics and glycoproteomics analyses by mass spectrometry require efficient front-end separation methods to enable deep characterization of heterogeneous glycoform populations. Chromatography methods are generally limited in their ability to resolve glycoforms using mobile phases that are compatible with online liquid chromatography-mass spectrometry (LC-MS). The adoption of capillary electrophoresis-mass spectrometry methods (CE-MS) for glycomics and glycoproteomics is limited by the lack of convenient interfaces for coupling the CE devices to mass spectrometers.

Modified Low-Dose Triiodo-L-thyronine Therapy Safely Improves Function Following Myocardial Ischemia-Reperfusion Injury.

We have shown that thyroid hormones (THs) are cardioprotective and can be potentially used as safe therapeutic agents for diabetic cardiomyopathy and permanent infarction. However, no reliable, clinically translatable protocol exists for TH treatment of myocardial ischemia-reperfusion (IR) injury. We hypothesized that modified low-dose triiodo-L-thyronine (T3) therapy would confer safe therapeutic benefits against IR injury.

The Use of a Fresh-Tissue Cadaver Model for the Instruction of Dermatological Procedures: A Laboratory Study for Training Medical Students.

Background: A realistic model for the instruction of basic dermatologic procedural skills was developed, while simultaneously increasing medical student exposure to the field of dermatology.

Objective: The primary purpose of the authors' study was to evaluate the utilization of a fresh-tissue cadaver model (FTCM) as a method for the instruction of common dermatologic procedures. The authors' secondary aim was to assess students' perceived clinical skills and overall perception of the field of dermatology after the lab.

Range contraction enables harvesting to extinction.

Economic incentives to harvest a species usually diminish as its abundance declines, because harvest costs increase. This prevents harvesting to extinction. A known exception can occur if consumer demand causes a declining species' harvest price to rise faster than costs.

Construction of a Database of Collision Cross Section Values for Glycopeptides, Glycans, and Peptides Determined by IM-MS.

An ion mobility quadrupole time-of-flight mass spectrometer was used to examine the gas-phase structures of a set of glycopeptides resulting from proteolytic digestion of the well-characterized glycoproteins bovine ribonuclease B, human transferrin, bovine fetuin and human α-acid glycoprotein, the corresponding deglycosylated peptides, and the glycans released by the endoglycosidase PNGase F. When closely related glycoforms did not occur naturally, exoglycosidases were used to achieve stepwise removal of individual saccharide units from the nonreducing termini of the multiantennary structures. Collision cross sections (CCS) were calculated and plotted as a function of mass-to-charge ratio.

Minimum standards for ultrasound equipment in intensive care. Recommendations from CICM Ultrasound Special Interest Group.

Critical care ultrasonography allows rapid bedside assessment and monitoring of severely ill patients. It provides important information on a real-time basis for patients' management and clinical decision-making, leading to improvements in delivered quality of care. Provision of this service is not possible without appropriate equipment.

Multiple Myeloma, Version 3.2017, NCCN Clinical Practice Guidelines in Oncology.

Multiple myeloma (MM) is caused by the neoplastic proliferation of plasma cells. These neoplastic plasma cells proliferate and produce monoclonal immunoglobulin in the bone marrow causing skeletal damage, a hallmark of multiple myeloma. Other MM-related complications include hypercalcemia, renal insufficiency, anemia, and infections.

Asparagine-Linked Glycans of Contain a Single Long Arm, Are Barely Processed in the Endoplasmic Reticulum (ER) or Golgi, and Show a Strong Bias for Sites with Threonine.

causes severe diarrhea in infants in developing countries and in immunosuppressed persons, including those with AIDS. We are interested in the Asn-linked glycans (-glycans) of , because (1) the -glycan precursor is predicted to contain five mannose and two glucose residues on a single long arm nine mannose and three glucose residues on the three-armed structure common in host -glycans, (2) is a rare eukaryote that lacks the machinery for -glycan-dependent quality control of protein folding in the lumen of the Endoplasmic Reticulum (ER), and (3) ER and Golgi mannosidases, as well as glycosyltransferases that build complex -glycans, are absent from the predicted proteome. The -glycans reported here, which were determined using a combination of collision-induced dissociation and electronic excitation dissociation, contain a single, unprocessed mannose arm ± terminal glucose on the trimannosyl chitobiose core.

An update on the role of daratumumab in the treatment of multiple myeloma.

Monoclonal antibodies (mAbs) have emerged as a promising new drug class for the treatment of multiple myeloma (MM). Daratumumab (DARA), a CD38 mAb, has demonstrated safety, tolerability and activity in a range of clinical trials, both as monotherapy and in combination strategies for MM. The favorable efficacy results in heavily pretreated patients with advanced MM have provided the rationale for the investigation of DARA in a number of ongoing and future phase II and III trials.

High fishery catches through trophic cascades in China.

Indiscriminate and intense fishing has occurred in many marine ecosystems around the world. Although this practice may have negative effects on biodiversity and populations of individual species, it may also increase total fishery productivity by removing predatory fish. We examine the potential for this phenomenon to explain the high reported wild catches in the East China Sea-one of the most productive ecosystems in the world that has also had its catch reporting accuracy and fishery management questioned.

The minimum information required for a glycomics experiment (MIRAGE) project: improving the standards for reporting glycan microarray-based data.

MIRAGE (Minimum Information Required for A Glycomics Experiment) is an initiative that was created by experts in the fields of glycobiology, glycoanalytics and glycoinformatics to produce guidelines for reporting results from the diverse types of experiments and analyses used in structural and functional studies of glycans in the scientific literature. As a sequel to the guidelines for sample preparation (Struwe et al. 2016, Glycobiology, 26:907-910) and mass spectrometry  data (Kolarich et al.

Site-Specific N-Glycosylation of Endothelial Cell Receptor Tyrosine Kinase VEGFR-2.

Vascular endothelial growth factor receptor-2 (VEGFR-2) is an important receptor tyrosine kinase (RTK) that plays critical roles in both physiologic and pathologic angiogenesis. The extracellular domain of VEGFR-2 is composed of seven immunoglobulin-like domains, each with multiple potential N-glycosylation sites (sequons). N-glycosylation plays a central role in RTK ligand binding, trafficking, and stability.

Evidence of the Immune Relevance of Prevotella copri, a Gut Microbe, in Patients With Rheumatoid Arthritis.

Objective: Prevotella copri, an intestinal microbe, may overexpand in stool samples from patients with new-onset rheumatoid arthritis (RA), but it is not yet clear whether the organism has immune relevance in RA pathogenesis.

Methods: HLA-DR-presented peptides (T cell epitopes) from P copri were sought directly in the patients' synovial tissue or peripheral blood mononuclear cell (PBMC) samples using tandem mass spectrometry. The antigenicity of peptides or their source proteins was examined in samples from the RA patients or comparison groups.

Implementation of the American Society of Anesthesiology's guidelines to reduce prolonged fasting times in pediatric preoperative patients: a best practice implementation project.

Background: The American Society of Anesthesiology (ASA) guidelines for pediatric preoperative fasting have been a standard for well over a decade. However, use of protocols involving an excessive fasting duration exposes patients to the physiological impacts of fluid volume loss.

Objectives: The current project aimed to improve fluid supplementation during presurgical fasting in pediatric patients at an academic medical center.

IGPR-1 Is Required for Endothelial Cell-Cell Adhesion and Barrier Function.

Endothelial cell (EC) barrier function plays a prevalent regulatory mechanism for the integrity and homeostasis of blood vessels and modulates angiogenesis and immune responses. Cell adhesion molecules (CAMs) play a central role in the barrier function of ECs. Although Ig-containing and proline-rich receptor-1(IGPR-1) was recently identified as a novel CAM expressed in ECs, the molecular mechanisms underlying the function of IGPR-1 in ECs remain uncharacterized.

Depression: Loss of Reinforcers or Loss of Reinforcer Effectiveness? - Republished Article.

A number of behavior therapists have proposed that depression results when a discriminative stimulus or reinforcer for behavior is removed. It is proposed here that the depressed person's general loss of interest in his environment suggests that there is a loss of reinforcer effectiveness. The manner in which environmental events, including the loss of a reinforcer, may result in this general loss of reinforcer effectiveness is discussed.