The High-Resolution Structure of a Variable Lymphocyte Receptor From Petromyzon marinus Capable of Binding to the Brain Extracellular Matrix.

Variable lymphocyte receptors (VLRs) are antigen receptors derived from the adaptive immune system of jawless vertebrates such as lamprey (Petromyzon marinus). First discovered in 2004, VLRs have been the subject of numerous biochemical and structural investigations. Due to their unique antigen binding properties, VLRs have been leveraged as possible drug delivery agents.

The effects of L-DOPA on gait abnormalities in a unilateral 6-OHDA rat model of Parkinson's disease.

Parkinson's Disease (PD) is a neurodegenerative movement disorder characterized by dopamine (DA) cell loss in the substantia nigra pars compacta (SNc). As PD progresses, patients display disruptions in gait such as changes in posture, bradykinesia, and shortened stride. DA replacement via L-DOPA alleviates many PD symptoms, though its effects on gait are not well demonstrated.

Biosynthesis of Cytidine Diphosphate-6-d-Glucitol for the Capsular Polysaccharides of .

is a Gram-negative pathogenic bacterium commonly found in chickens and is the leading cause of human diarrheal disease worldwide. The various serotypes of produce structurally distinct capsular polysaccharides (CPSs) on the exterior surfaces of the cell wall. The capsular polysaccharide from serotype HS:5 is composed of a repeating sequence of d--d--heptose and d-glucitol-6-phosphate.

Structural analysis of a bacterial UDP-sugar 2-epimerase reveals the active site architecture before and after catalysis.

The sugar, 2,3-diacetamido-2,3-dideoxy-d-mannuronic acid, was first identified ∼40 years ago in the O-antigen of Pseudomonas aeruginosa O:3,a,d. Since then, it has been observed on the O-antigens of various pathogenic Gram-negative bacteria including Bordetella pertussis, Escherichia albertii, and Pseudomonas mediterranea. Previous studies have established that five enzymes are required for its biosynthesis beginning with uridine dinucleotide (UDP)-N-acetyl-d-glucosamine (UDP-GlcNAc).

Characterization of a novel inhibitor for the New Delhi metallo-β-lactamase-4: Implications for drug design and combating bacterial drug resistance.

The bacterial metallo-β-lactamases (MBLs) catalyze the inactivation of β-lactam antibiotics. Identifying novel pharmacophores remains crucial for the clinical development of additional MBL inhibitors. Previously, 1-hydroxypyridine-2(1H)-thione-6-carboxylic acid, hereafter referred to as 1,2-HPT-6-COOH, was reported as a low cytotoxic nanomolar β-lactamase inhibitor of Verona-integron-encoded metallo-β-lactamase 2, capable of rescuing β-lactam antibiotic activity.

Bifunctional Epimerase/Reductase Enzymes Facilitate the Modulation of 6-Deoxy-Heptoses Found in the Capsular Polysaccharides of .

is a human pathogen and the leading cause of food poisoning in the United States and Europe. Surrounding the exterior surface of this bacterium is a capsular polysaccharide (CPS) that consists of a repeating sequence of common and unusual carbohydrate segments. At least 10 different heptose sugars have thus far been identified in the various strains of .

Investigation of the enzymes required for the biosynthesis of 2,3-diacetamido-2,3-dideoxy-d-glucuronic acid in Psychrobacter cryohalolentis K5.

Psychrobacter cryohalolentis K5 is a Gram-negative bacterium first isolated from Siberian permafrost in 2006. It has a complex O-antigen containing l-rhamnose, d-galactose, two diacetamido-sugars, and one triacetamido-sugar. The biosynthetic pathway for one of the diacetamido-sugars, namely 2,3-diacetamido-2,3-dideoxy-d-glucuronic acid, is presently unknown.

Noise-driven bifurcations in a neural field system modelling networks of grid cells.

The activity generated by an ensemble of neurons is affected by various noise sources. It is a well-recognised challenge to understand the effects of noise on the stability of such networks. We demonstrate that the patterns of activity generated by networks of grid cells emerge from the instability of homogeneous activity for small levels of noise.

C3- and C3/C5-Epimerases Required for the Biosynthesis of the Capsular Polysaccharides from .

is a human pathogen and one of the leading causes of food poisoning in Europe and the United States. The outside of the bacterium is coated with a capsular polysaccharide that assists in the evasion of the host immune system. Many of the serotyped strains of contain a 6-deoxy-heptose moiety that is biosynthesized from GDP-d--d--heptose by the successive actions of a 4,6-dehydratase, a C3/C5-epimerase, and a C4-reductase.

Reaction Mechanism and Three-Dimensional Structure of GDP-d-glycero-α-d-manno-heptose 4,6-Dehydratase from .

is a human pathogen and a leading cause of food poisoning in the United States and Europe. Surrounding the outside of the bacterium is a carbohydrate coat known as the capsular polysaccharide. Various strains of have different sequences of unusual sugars and an assortment of decorations.

Structure and function of an N-acetyltransferase from the human pathogen Acinetobacter baumannii isolate BAL_212.

Acinetobacter baumannii is a Gram-negative bacterium commonly found in soil and water that can cause human infections of the blood, lungs, and urinary tract. Of particular concern is its prevalence in health-care settings where it can survive on surfaces and shared equipment for extended periods of time. The capsular polysaccharide surrounding the organism is known to be the major contributor to virulence.

[Intramural gastric abscess].

Background: Fever and abdominal pain are common symptoms with many possible differential diagnoses.

Case Presentation: An otherwise healthy man in his twenties was admitted to hospital with fever and epigastric pain. On admission he was febrile.

Impact of Mild Cognitive Impairment on Quality of Life in Young and Typical Onset Parkinson's Disease.

Introduction: Younger age of onset and mild cognitive impairment (MCI) are both independently associated with poorer quality of life (QOL) in Parkinson's disease (PD).

Objectives: The primary objective was to determine whether MCI differentially impacts QOL in young-onset PD (YOPD) and typical-onset PD (TOPD).

Methods: YOPD patients (n = 77) were diagnosed at age 50 or younger, TOPD (n = 77) were diagnosed after age 50, and the groups were matched for cognitive status, education, and disease duration.

4-Deoxy-4-fluoro-GalNAz (4FGalNAz) Is a Metabolic Chemical Reporter of O-GlcNAc Modifications, Highlighting the Notable Substrate Flexibility of O-GlcNAc Transferase.

Bio-orthogonal chemistries have revolutionized many fields. For example, metabolic chemical reporters (MCRs) of glycosylation are analogues of monosaccharides that contain a bio-orthogonal functionality, such as azides or alkynes. MCRs are metabolically incorporated into glycoproteins by living systems, and bio-orthogonal reactions can be subsequently employed to install visualization and enrichment tags.

Biochemical investigation of an N-acetyltransferase from Helicobacter pullorum.

N-acetylated sugars are often found, for example, on the lipopolysaccharides of Gram-negative bacteria, on the S-layers of Gram-positive bacteria, and on the capsular polysaccharides. Key enzymes involved in their biosynthesis are the sugar N-acetyltransferases. Here, we describe a structural and functional analysis of one such enzyme from Helicobacter pullorum, an emerging pathogen that may be associated with gastroenteritis and gallbladder and liver diseases.

Investigation of the enzymes required for the biosynthesis of an unusual formylated sugar in the emerging human pathogen Helicobacter canadensis.

It is now well established that the Gram-negative bacterium, Helicobacter pylori, causes gastritis in humans. In recent years, it has become apparent that the so-called non-pylori Helicobacters, normally infecting pigs, cats, and dogs, may also be involved in human pathology via zoonotic transmission. Indeed, more than 30 species of non-pylori Helicobacters have been identified thus far.

Characterization of an aminotransferase from Acanthamoeba polyphaga Mimivirus.

Acanthamoeba polyphaga Mimivirus, a complex virus that infects amoeba, was first reported in 2003. It is now known that its DNA genome encodes for nearly 1,000 proteins including enzymes that are required for the biosynthesis of the unusual sugar 4-amino-4,6-dideoxy-d-glucose, also known as d-viosamine. As observed in some bacteria, the pathway for the production of this sugar initiates with a nucleotide-linked sugar, which in the Mimivirus is thought to be UDP-d-glucose.

Biosynthesis of d--l--Heptose in the Capsular Polysaccharides of .

is the leading cause of food poisoning in the United States and Europe. The exterior cell surface of is coated with a capsular polysaccharide (CPS) that is essential for the maintenance and integrity of the bacterial cell wall and evasion of the host immune response. The identity and sequences of the monosaccharide components of the CPS are quite variable and dependent on the specific strain of .

Age-related differences in memory for "who," "when," and "where" are detectable in middle-aged adults.

Our study examined age-related differences across the adult lifespan using a recently developed test assessing memory for "who, when, and where" in addition to associations among these elements. Young (ages 18-25), middle-aged (ages 40-55), and older adults (ages 60+) were asked to remember a sequence of pictures of different faces paired with different places and place the pairs in the correct sequence. Young adults remembered significantly mores face-place pairs in the correct sequence than middle-aged ( < .

Characterization of two enzymes from Psychrobacter cryohalolentis that are required for the biosynthesis of an unusual diacetamido-d-sugar.

Psychrobacter cryohalolentis strain K5 is a Gram-negative organism first isolated in 2006. It has a complex O-antigen that contains, in addition to l-rhamnose and d-galactose, two diacetamido- and a triacetamido-sugar. The biochemical pathways for the production of these unusual sugars are presently unknown.

Evolutionarily stable strategies in stable and periodically fluctuating populations: The Rosenzweig-MacArthur predator-prey model.

An evolutionarily stable strategy (ESS) is an evolutionary strategy that, if adapted by a population, cannot be invaded by any deviating (mutant) strategy. The concept of ESS has been extensively studied and widely applied in ecology and evolutionary biology [M. Smith, (1972)] but typically on the assumption that the system is ecologically stable.

The high-resolution structure of a UDP-L-rhamnose synthase from Acanthamoeba polyphaga Mimivirus.

For the field of virology, perhaps one of the most paradigm-shifting events so far in the 21st century was the identification of the giant double-stranded DNA virus that infects amoebae. Remarkably, this virus, known as Mimivirus, has a genome that encodes for nearly 1,000 proteins, some of which are involved in the biosynthesis of unusual sugars. Indeed, the virus is coated by a layer of glycosylated fibers that contain d-glucose, N-acetyl-d-glucosamine, l-rhamnose, and 4-amino-4,6-dideoxy-d-glucose.

Structural Analysis of Cj1427, an Essential NAD-Dependent Dehydrogenase for the Biosynthesis of the Heptose Residues in the Capsular Polysaccharides of .

Many strains of display modified heptose residues in their capsular polysaccharides (CPS). The precursor heptose was previously shown to be GDP-d--α-d--heptose, from which a variety of modifications of the sugar moiety have been observed. These modifications include the generation of 6-deoxy derivatives and alterations of the stereochemistry at C3-C6.