Interplay between Alternative Splicing and Alternative Polyadenylation Defines the Expression Outcome of the Plant Unique OXIDATIVE TOLERANT-6 Gene.

Pre-mRNA alternative splicing and alternative polyadenylation have been implicated to play important roles during eukaryotic gene expression. However, much remains unknown regarding the regulatory mechanisms and the interactions of these two processes in plants. Here we focus on an Arabidopsis gene OXT6 (Oxidative Tolerant-6) that has been demonstrated to encode two proteins through alternative splicing and alternative polyadenylation.

The anti-asthmatic drug pranlukast suppresses the delayed-phase vomiting and reverses intracellular indices of emesis evoked by cisplatin in the least shrew (Cryptotis parva).

The introduction of second generation serotonin 5-HT receptor (5-HT) antagonist palonosetron combined with long-acting substance P neurokinin NK receptor (NK) antagonists (e.g. netupitant) has substantially improved antiemetic therapy against early- and delayed-phases of emesis caused by highly emetogenic chemotherapeutics such as cisplatin.

"Liquid Crystalline Nanoparticles": Rationally Designed Vehicle To Improve Stability and Therapeutic Efficacy of Insulin Following Oral Administration.

In the present article we investigate the feasibility of liquid crystalline nanoparticles (LCNPs) to improve the stability and therapeutic efficacy of insulin following oral administration. Compatibility studies of different formulation ingredients with insulin and extensive optimization of different process variables resulted into the formation of LCNPs with particle size of 245.50 ± 6.

Outcomes Following Traumatic Grain Elevator Injuries.

Objectives: The absence of a comprehensive database of grain elevator-associated injuries hinders accurate evaluation of injury prevalence and may lead to discordant information about injury frequencies. The main purpose of this study was to identify the most common mechanisms of injury related to grain elevator events. Comparisons of hospital outcomes between patients who sustained traumatic injuries associated with grain elevators at Occupational Safety and Health Administration (OSHA)-regulated industrial sites versus those on OSHA-exempt farming operations were also made.

Restoring Cytokine Balance in HIV-Positive Individuals with Low CD4 T Cell Counts.

HIV infects and destroys CD4+ T cells leading to a compromised immune system. In a double-blinded study, a group of HIV-infected individuals with CD4+ T cell counts below 350 cells/mm were given either an empty liposomal supplement or a liposomal glutathione (L-GSH) supplement to take over a 3-month period. Baseline measurements in HIV-positive subjects show a significant decrease in levels of interleukin (IL)-12, IL-2, and interferon (IFN)-γ, along with a substantial increase in the levels of IL-6, IL-10, transforming growth factor (TGF)-β, and free radicals, compared to healthy individuals.

Targeting Signaling Pathways in Cancer Stem Cells for Cancer Treatment.

The Wnt, Hedgehog, and Notch pathways are inherent signaling pathways in normal embryogenesis, development, and hemostasis. However, dysfunctions of these pathways are evident in multiple tumor types and malignancies. Specifically, aberrant activation of these pathways is implicated in modulation of cancer stem cells (CSCs), a small subset of cancer cells capable of self-renewal and differentiation into heterogeneous tumor cells.

Development of anticancer agents targeting the Hedgehog signaling.

Hedgehog signaling is an evolutionarily conserved pathway which is essential in embryonic and postnatal development as well as adult organ homeostasis. Abnormal regulation of Hedgehog signaling is implicated in many diseases including cancer. Consequently, substantial efforts have made in the past to develop potential therapeutic agents that specifically target the Hedgehog signaling for cancer treatment.

Protection of the Queuosine Biosynthesis Enzyme QueF from Irreversible Oxidation by a Conserved Intramolecular Disulfide.

QueF enzymes catalyze the nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reduction of the nitrile group of 7-cyano-7-deazaguanine (preQ₀) to 7-aminomethyl-7-deazaguanine (preQ₁) in the biosynthetic pathway to the tRNA modified nucleoside queuosine. The QueF-catalyzed reaction includes formation of a covalent thioimide intermediate with a conserved active site cysteine that is prone to oxidation in vivo. Here, we report the crystal structure of a mutant of QueF, which reveals an unanticipated intramolecular disulfide formed between the catalytic Cys55 and a conserved Cys99 located near the active site.

Does Bone Grafting Improve Outcomes in Coronectomy Surgery? Long-Term (5- to 9-Year) Clinical and Radiographic Follow-Up of 78 Adult Patients.

Purpose: To report the long-term outcomes of 78 adult patients who underwent coronectomy with bone grafting (CWG) of the bony crypt.

Materials And Methods: Seventy-eight patients with follow-up of at least 5 to 9 years underwent CWG. Preoperative imaging and probing depths were recorded, as were yearly follow-up radiographs or cone-beam computed tomograms and yearly postoperative probing depths.

Calpain-1 deletion impairs mGluR-dependent LTD and fear memory extinction.

Recent studies indicate that calpain-1 is required for the induction of long-term potentiation (LTP) elicited by theta-burst stimulation in field CA1 of hippocampus. Here we determined the contribution of calpain-1 in another type of synaptic plasticity, the long-term depression (LTD) elicited by activation of type-I metabotropic glutamate receptors (mGluR-LTD). mGluR-LTD was associated with calpain-1 activation following T-type calcium channel opening, and resulted in the truncation of a regulatory subunit of PP2A, B56α.

Effector Mechanisms of Neutrophils within the Innate Immune System in Response to Mycobacterium tuberculosis Infection.

Neutrophils have a significant yet controversial role in the innate immune response to () infection, which is not yet fully understood. In addition to neutrophils' well-known effector mechanisms, they may also help control infection of through the formation of neutrophil extracellular traps (NETs), which are thought to further promote the killing of by resident alveolar macrophages. Cytokines such as IFN-γ have now been shown to serve an immunomodulatory role in neutrophil functioning in conjunction to its pro-inflammatory function.

Mechanism and catalytic strategy of the prokaryotic-specific GTP cyclohydrolase-IB.

Guanosine 5'-triphosphate (GTP) cyclohydrolase-I (GCYH-I) catalyzes the first step in folic acid biosynthesis in bacteria and plants, biopterin biosynthesis in mammals, and the biosynthesis of 7-deazaguanosine-modified tRNA nucleosides in bacteria and archaea. The type IB GCYH (GCYH-IB) is a prokaryotic-specific enzyme found in many pathogens. GCYH-IB is structurally distinct from the canonical type IA GCYH involved in biopterin biosynthesis in humans and animals, and thus is of interest as a potential antibacterial drug target.

A Novel Method for the Generation of Region-Specific Neurons and Neural Networks from Human Pluripotent Stem Cells.

Stem cell-based neuronal differentiation has provided a unique opportunity for disease modeling and regenerative medicine. We have reported a novel culture condition and method for generating neuronal progenitors and neural networks from human embryonic and induced pluripotent stem cells without any genetic manipulation. Neurospheres generated under 10% CO with Supplemented Knockout Serum Replacement Medium (SKSRM) had doubled the expression of NESTIN, PAX6 and FOXG1 genes compared to the neurospheres generated under 5% CO.

Bioinformatics Analysis of Chicken miRNAs Associated with Monocyte to Macrophage Differentiation and Subsequent IFNγ Stimulated Activation.

Background: The goal of this project was to characterize the molecular and cellular roles of various gene targets regulated by miRNAs identified in differentiating and stimulating avian macrophages. Once a monocyte arrives to a site of infection, local signals induce a redistribution of resources into a macrophage phenotype. This may involve upregulating pathogen pattern recognizing receptors and increasing the efficiency of lysosomal biogenesis, while simultaneously recycling components involved in circulatory migration and leukocyte extravasation.

Alternative Destination Transport? The Role of Paramedics in Optimal Use of the Emergency Department.

Introduction: Alternative destination transportation by emergency medical services (EMS) is a subject of hot debate between those favoring all patients being evaluated by an emergency physician (EP) and those recognizing the need to reduce emergency department (ED) crowding. This study aimed to determine whether paramedics could accurately assess a patient's acuity level to determine the need to transport to an ED.

Methods: We performed a prospective double-blinded analysis of responses recorded by paramedics and EPs of arriving patients' acuity level in a large Level II trauma center between April 2015 and November 2015.

Silver nanoparticles exhibit coating and dose-dependent neurotoxicity in glutamatergic neurons derived from human embryonic stem cells.

Silver nanoparticles (AgNPs) are used extensively as anti-microbial agents in various products, but little is known about their potential neurotoxic effects. In this study, we used glutamatergic neurons derived from human embryonic stem cells as a cellular model to study 20nm citrate-coated AgNPs (AgSCs) and Polyvinylpyrrolidone-coated AgNPs (AgSPs) induced neurotoxicity. AgSCs significantly damaged neurite outgrowths; increased the production of reactive oxygen species and Ca influxes; reduced the expression of MAP2, PSD95, vGlut1 and NMDA receptor proteins at concentrations as low as 0.

Crystal structure of the archaeosine synthase QueF-like-Insights into amidino transfer and tRNA recognition by the tunnel fold.

The tunneling-fold (T-fold) structural superfamily has emerged as a versatile protein scaffold of diverse catalytic activities. This is especially evident in the pathways to the 7-deazaguanosine modified nucleosides of tRNA queuosine and archaeosine. Four members of the T-fold superfamily have been confirmed in these pathways and here we report the crystal structure of a fifth enzyme; the recently discovered amidinotransferase QueF-Like (QueF-L), responsible for the final step in the biosynthesis of archaeosine in the D-loop of tRNA in a subset of Crenarchaeota.

Genome-wide dynamics of alternative polyadenylation in rice.

Alternative polyadenylation (APA), in which a transcript uses one of the poly(A) sites to define its 3'-end, is a common regulatory mechanism in eukaryotic gene expression. However, the potential of APA in determining crop agronomic traits remains elusive. This study systematically tallied poly(A) sites of 14 different rice tissues and developmental stages using the poly(A) tag sequencing (PAT-seq) approach.

Analysis of Gene Expression Network Components Underlying Pigmentation Phenotypes in the Python Identified Evolutionarily Conserved Clusters of Transcription Factor Binding Sites.

Color variation provides the opportunity to investigate the genetic basis of evolution and selection. Reptiles are less studied than mammals. Comparative genomics approaches allow for knowledge gained in one species to be leveraged for use in another species.

Differential Activation of Calpain-1 and Calpain-2 following Kainate-Induced Seizure Activity in Rats and Mice.

Systemic injection of kainate produces repetitive seizure activity in both rats and mice. It also results in short-term synaptic modifications as well as delayed neurodegeneration. The signaling cascades involved in both short-term and delayed responses are not clearly defined.

Triptonide Effectively Inhibits Wnt/β-Catenin Signaling via C-terminal Transactivation Domain of β-catenin.

Abnormal activation of canonical Wnt/β-catenin signaling is implicated in many diseases including cancer. As a result, therapeutic agents that disrupt this signaling pathway have been highly sought after. Triptonide is a key bioactive small molecule identified in a traditional Chinese medicine named Tripterygium wilfordii Hook F.

In Vitro Biomechanical Testing of the Tube Knot.

Objective: To compare in vitro biomechanical properties of the tube knot (TB) to a crimp clamp (CC) system, and square knot (SQ) using 3 monofilament materials.

Study Design: In vitro biomechanical study.

Sample Population: Suture loops (n=20 per material/knot construct).

Data on pro-inflammatory cytokines IL-1β, IL-17, and IL-6 in the peripheral blood of HIV-infected individuals.

Our most recent data indicate differences in the levels of pro-inflammatory cytokines (IL-1β, IL-17, and IL-6) and malondialdehyde (MDA), a stable end-product of lipid peroxidation in the plasma samples between HIV positive individuals with low CD4 T cell counts <200 mm(3) and HIV positive individuals with CD4 T cell counts between 200 and 300 mm(3) (ee). The data lend support and provide valuable correlation between CD4 T cell counts and the levels of inflammatory cytokines in HIV positive individuals.

PlantAPA: A Portal for Visualization and Analysis of Alternative Polyadenylation in Plants.

Alternative polyadenylation (APA) is an important layer of gene regulation that produces mRNAs that have different 3' ends and/or encode diverse protein isoforms. Up to 70% of annotated genes in plants undergo APA. Increasing numbers of poly(A) sites collected in various plant species demand new methods and tools to access and mine these data.

Deleting both PHLPP1 and CANP1 rescues impairments in long-term potentiation and learning in both single knockout mice.

Calpain-1 (CANP1) has been shown to play a critical role in synaptic plasticity and learning and memory, as its deletion in mice results in impairment in theta-burst stimulation- (TBS) induced LTP and various forms of learning and memory. Likewise, PHLPP1 (aka SCOP) has also been found to participate in learning and memory, as PHLPP1 overexpression impairs hippocampus-dependent learning. We previously showed that TBS-induced LTP was associated with calpain-1 mediated truncation of PHLPP1.