Metabolism of Vertebrate Amino Sugars with N-Glycolyl Groups: RESISTANCE OF α2-8-LINKED N-GLYCOLYLNEURAMINIC ACID TO ENZYMATIC CLEAVAGE

The sialic acid (Sia) N-acetylneuraminic acid (Neu5Ac) and its hydroxylated derivative N-glycolylneuraminic acid (Neu5Gc) differ by one oxygen atom. CMP-Neu5Gc is synthesized from CMP-Neu5Ac, with Neu5Gc representing a highly variable fraction of total Sias in various tissues and among different species. The exception may be the brain, where Neu5Ac is abundant and Neu5Gc is reported to be rare. Here, we confirm this unusual pattern and its evolutionary conservation in additional samples from various species, concluding that brain Neu5Gc expression has been maintained at extremely low levels over hundreds of millions of years of vertebrate evolution. Most explanations for this pattern do not require maintaining neural Neu5Gc at such low levels. We hypothesized that resistance of α2-8-linked Neu5Gc to vertebrate sialidases is the detrimental effect requiring the relative absence of Neu5Gc from brain. This linkage is prominent in polysialic acid (polySia), a molecule with critical roles in vertebrate neural development. We show that Neu5Gc is incorporated into neural polySia and does not cause in vitro toxicity. Synthetic polymers of Neu5Ac and Neu5Gc showed that mammalian and bacterial sialidases are much less able to hydrolyze α2-8-linked Neu5Gc at the nonreducing terminus. Notably, this difference was not seen with acid-catalyzed hydrolysis of polySias. Molecular dynamics modeling indicates that differences in the three-dimensional conformation of terminal saccharides may partly explain reduced enzymatic activity. In keeping with this, polymers of N-propionylneuraminic acid are sensitive to sialidases. Resistance of Neu5Gc-containing polySia to sialidases provides a potential explanation for the rarity of Neu5Gc in the vertebrate brain.     

The effects of carbenoxolone, a semisynthetic derivative of glycyrrhizinic acid, on peripheral and central ischemia-reperfusion injuries in the skeletal muscle and hippocampus of rats

As carbenoxolone, a semisynthetic derivative of glycyrrhizinic acid, has a free radical scavenging property, thus the effects of carbenoxolone during ischemia-reperfusion was evaluated on an animal model of ischemia-reperfusion injury in the rat hind limb and hippocampus. Peripheral and central ischemia were induced by free-flap surgery in skeletal muscle and four-vessel-occulation (4VO) of rat, respectively. Carbenoxolone (50-200 mg/kg) and normal saline (10 ml/ kg) were administered intraperitoneally. In peripherlal ischemia, during preischemia, ischemia and reperfusion conditions the electromyographic (EMG) potentials in the muscles were recorded. The malondialdehyde (MDA) was measured by the thiobarbituric acid (TBA) test after reperfusion in peripheral and central ischemia. In peripheral ischemia, the average peak-to-peak amplitude during ischemic-reperfusion was found to be significantly larger in carbenoxolone group (100-200mg/kg) in comparison to control group. The MDA levels were recovered significantly upon carbenoxolone (100-200 mg/kg) therapy in the skeletal muscle and hippocampus of ischemic rats. These results suggest that carbenoxolone can salvage the skeletal muscle and hippocampus from acute ischemia-reperfusion injury.     

Improved Intraoperative Visualization of Nerves through a Myelin-Binding Fluorophore and Dual-Mode Laparoscopic Imaging

The ability to visualize and spare nerves during surgery is critical for avoiding chronic morbidity, pain, and loss of function. Visualization of such critical anatomic structures is even more challenging during minimal access procedures because the small incisions limit visibility. In this study, we focus on improving imaging of nerves through the use of a new small molecule fluorophore, GE3126, used in conjunction with our dual-mode (color and fluorescence) laparoscopic imaging instrument. GE3126 has higher aqueous solubility, improved pharmacokinetics, and reduced non-specific adipose tissue fluorescence compared to previous myelin-binding fluorophores. Dosing and kinetics were initially optimized in mice. A non-clinical modified Irwin study in rats, performed to assess the potential of GE3126 to induce nervous system injuries, showed the absence of major adverse reactions. Real-time intraoperative imaging was performed in a porcine model. Compared to white light imaging, nerve visibility was enhanced under fluorescence guidance, especially for small diameter nerves obscured by fascia, blood vessels, or adipose tissue. In the porcine model, nerve visualization was observed rapidly, within 5 to 10 minutes post-intravenous injection and the nerve fluorescence signal was maintained for up to 80 minutes. The use of GE3126, coupled with practical implementation of an imaging instrument may be an important step forward in preventing nerve damage in the operating room.     

Modulation of the NOD-like receptors NOD1 and NOD2: A chemist’s perspective

The innate immune system is the body’s first defense against invading microorganisms, relying on the recognition of bacterial-derived small molecules by host protein receptors. This recognition event and downstream immune response rely heavily on the specific chemical features of both the innate immune receptors and their bacterial derived ligands. This review presents a chemist’s perspective on some of the most crucial and complex components of two receptors (NOD1 and NOD2): starting from the structural and chemical characteristics of bacterial-derived small molecules, to the specific proposed models of molecular recognition of these molecules by immune receptors, to the subsequent post-translational modifications that ultimately dictate downstream immune signaling. Recent advances in the field are discussed, as well as the potential for the development of targeted therapeutics.     

Arbuscular Mycorrhizal Fungi and Rhizobacteria Promote Growth of Russian Knapweed (Acroptilon repens L.) in a Cd-Contaminated Soil

Journal of Plant Growth Regulation - Improving soil microbial activity and using microbial synergistic relations, such as arbuscular mycorrhizal fungi (AMF) and plant growth-promoting rhizobacteria...     

ASTRAL-Pro: Quartet-Based Species-Tree Inference despite Paralogy

Phylogenetic inference from genome-wide data (phylogenomics) has revolutionized the study of evolution because it enables accounting for discordance among evolutionary histories across the genome. To this end, summary methods have been developed to allow accurate and scalable inference of species trees from gene trees. However, most of these methods, including the widely used ASTRAL, can only handle single-copy gene trees and do not attempt to model gene duplication and gene loss. As a result, most phylogenomic studies have focused on single-copy genes and have discarded large parts of the data. Here, we first propose a measure of quartet similarity between single-copy and multicopy trees that accounts for orthology and paralogy. We then introduce a method called ASTRAL-Pro (ASTRAL for PaRalogs and Orthologs) to find the species tree that optimizes our quartet similarity measure using dynamic programing. By studying its performance on an extensive collection of simulated data sets and on real data sets, we show that ASTRAL-Pro is more accurate than alternative methods.     

Promoter-Enhancer Communication Occurs Primarily within Insulated Neighborhoods

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Cockroach wings-promoted safe and greener synthesis of silver nanoparticles and their insecticidal activity

Bioprocess and Biosystems Engineering - Simpler and biocompatible greener approaches for the assembly of nanoparticles (NPs) have been the focus lately which have minimum environmental damage and...