Identification and treatment of the visual processing asymmetry in MS patients with optic neuritis: The Pulfrich phenomenon

BACKGROUND: The Pulfrich phenomenon (PF) is the illusory perception that an object moving linearly along a 2-D plane appears to instead follow an elliptical 3-D trajectory, a consequence of inter-eye asymmetry in the timing of visual object identification in the visual cortex; with optic neuritis as a common etiology. OBJECTIVE: We have designed an objective method to identify the presence and magnitude of the PF, in conjunction with a cooresponding strategy by which to abolish the effect; with monocular application of neutral density filters to the less affected fellow eye, in patients with MS and a history of optic neuropathy (e.g. related to acute optic neuritis or subclinical optic neuropathy). METHODS: Twenty-three MS patients with a history of acute unilateral or bilateral optic neuritis, and ten healthy control subjects (HC) were recruited to participate in a pilot study to assess our strategy. Subjects were asked to indicate whether a linearly moving pendulum ball followed a linear 2-D path versus an illusory 3-D elliptical object-motion trajectory, by reporting the ball's approximation to one of nine horizontally-oriented colored wires that were positioned parallel to one another and horizontal to the linear pendulum path. Perceived motion of the bob that moved along wires behind or in front (along the 'Z' plane) of the middle reference wire indicated an illusory elliptical trajectory of ball motion consistent with the PF. RESULTS: When the neutral density filter titration was applied to the fellow eye the severity of the PF decreased, eventually being fully abolished in all but one patient. The magnitude of neutral density filtering required correlated to the severity of the patient's initial PF magnitude (p < 0.001). CONCLUSIONS: We ascertained the magnitude of the visual illusion associated with the PF, and the corresponding magnitude of neutral density filtering necessary to abolish it

Functional characterization of a class III acid endochitinase from the traps of the carnivorous pitcher plant genus, Nepenthes

Carnivory in plants is an adaptation strategy to nutrient-poor environments and soils. Carnivorous plants obtain some additional mineral nutrients by trapping and digesting prey; the genus Nepenthes is helped by its specialized pitcher traps. To make the nutrients available, the caught prey needs to be digested, a process that requires the concerted activity of several hydrolytic enzymes. To identify and investigate the various enzymes involved in this process, fluid from Nepenthes traps has been analysed in detail. In this study, a novel type of Nepenthes endochitinase was identified in the digestion fluid of closed pitchers. The encoding endochitinase genes have been cloned from eight different Nepenthes species. Among these, the deduced amino acid sequence similarity was at least 94.9%. The corresponding cDNA from N. rafflesiana was heterologously expressed, and the purified protein, NrChit1, was biochemically characterized. The enzyme, classified as a class III acid endochitinase belonging to family 18 of the glycoside hydrolases, is secreted into the pitcher fluid very probably due to the presence of an N-terminal signal peptide. Transcriptome analyses using real-time PCR indicated that the presence of prey in the pitcher up-regulates the endochitinase gene not only in the glands, which are responsible for enzyme secretion, but at an even higher level, in the glands’ surrounding tissue. These results suggest that in the pitchers’ tissues, the endochitinase as well as other proteins from the pitcher fluid might fulfil a different, primary function as pathogenesis-related proteins

Interferon-γ Activates Nuclear Factor-κ B in Oligodendrocytes through a Process Mediated by the Unfolded Protein Response

Our previous studies have demonstrated that the effects of the immune cytokine interferon-γ (IFN-γ) in immune-mediated demyelinating diseases are mediated, at least in part, by the unfolded protein response (UPR) in oligodendrocytes. Data indicate that some biological effects of IFN-γ are elicited through activation of the transcription factor nuclear factor-κB (NF-κB). Interestingly, it has been shown that activation of the pancreatic endoplasmic reticulum kinase (PERK) branch of the UPR triggers NF-κB activation. In this study, we showed that IFN-γ-induced NF-κB activation was associated with activation of PERK signaling in the oligodendroglial cell line Oli-neu. We further demonstrated that blockage of PERK signaling diminished IFN-γ-induced NF-κB activation in Oli-neu cells. Importantly, we showed that NF-κB activation in oligodendrocytes correlated with activation of PERK signaling in transgenic mice that ectopically express IFN-γ in the central nervous system (CNS), and that enhancing IFN-γ-induced activation of PERK signaling further increased NF-κB activation in oligodendrocytes. Additionally, we showed that suppression of the NF-κB pathway rendered Oli-neu cells susceptible to the cytotoxicity of IFN-γ, reactive oxygen species, and reactive nitrogen species. Our results indicate that the UPR is involved in IFN-γ-induced NF-κB activation in oligodendrocytes and suggest that NF-κB activation by IFN-γ represents one mechanism by which IFN-γ exerts its effects on oligodendrocytes in immune-mediated demyelinating diseases

Multiple sclerosis: Executive dysfunction, task switching and the role of attention.

Background: It has been suggested that switching ability might not be affected in multiple sclerosis (MS) as previously thought; however, whether this is true under more 'real-world' conditions when asymmetry in task difficulty is present has not been ascertained. Objective: The objective of this paper is to examine the impact of task difficulty asymmetry on task switching ability in MS. Method: An ocular motor (OM) paradigm that interleaves the simple task of looking towards a target (prosaccade, PS) with the cognitively more difficult task of looking away from a target (antisaccade, PS) was used. Two switching conditions: (1) PS switch cost, switching to a simple task from a difficult task (PS switch), relative to performing two simple tasks concurrently (PS repeat); (2) AS switch cost, switching to a difficult task from a simple task (AS switch) relative to performing two difficult tasks concurrently (AS repeat). Forty-five relapsing-remitting MS patients and 30 control individuals were compared. Results: Controls and patients produced a similar magnitude PS switch cost, suggesting that task difficulty asymmetry does not detrimentally impact MS patients when transitioning from a more difficult task to a simpler task. However, MS patients alone found switching from the simpler PS trial to the more difficult AS trial easier (shorter latency and reduced error) than performing two AS trials consecutively (AS switch benefit). Further, MS patients performed significantly more errors than controls when required to repeat the same trial consecutively. Conclusion: MS patients appear to find the maintenance of task-relevant processes difficult not switching per se, with deficits exacerbated under increased attentional demands

Application of an evidence-based, out-patient treatment strategy for COVID-19: Multidisciplinary medical practice principles to prevent severe disease

The COVID-19 pandemic has devastated individuals, families, and institutions throughout the world. Despite the breakneck speed of vaccine development, the human population remains at risk of further devastation. The decision to not become vaccinated, the protracted rollout of available vaccine, vaccine failure, mutational forms of the SARS virus, which may exhibit mounting resistance to our molecular strike at only one form of the viral family, and the rapid ability of the virus(es) to hitch a ride on our global transportation systems, means that we are will likely continue to confront an invisible, yet devastating foe. The enemy targets one of our human physiology’s most important and vulnerable life-preserving body tissues, our broncho-alveolar gas exchange apparatus. Notwithstanding the fear and the fury of this microbe's potential to raise existential questions across the entire spectrum of human endeavor, the application of an early treatment intervention initiative may represent a crucial tool in our defensive strategy. This strategy is driven by evidence-based medical practice principles, those not likely to become antiquated, given the molecular diversity and mutational evolution of this very clever “world traveler”

A role for phosphatidic acid in COPI vesicle fission yields insights into Golgi maintenance

Proteins essential for vesicle formation by the Coat Protein I (COPI) complex are being identified, but less is known about the role of specific lipids. Brefeldin-A ADP-ribosylated substrate (BARS) functions in the fission step of COPI vesicle formation. Here, we show that BARS induces membrane curvature in cooperation with phosphatidic acid. This finding has allowed us to further delineate COPI vesicle fission into two sub-stages: 1) an earlier stage of bud-neck constriction, in which BARS and other COPI components are required, and 2) a later stage of bud-neck scission, in which phosphatidic acid generated by phospholipase D2 (PLD2) is also required. Moreover, in contrast to the disruption of the Golgi seen on perturbing the core COPI components (such as coatomer), inhibition of PLD2 causes milder disruptions, suggesting that such COPI components have additional roles in maintaining Golgi structure other than through COPI vesicle formation

A pectin glucuronyltransferase gene is essential for intercellular attachment in the plant meristem

Intercellular attachment is an essential process in the morphogenesis of multicellular organisms. A unique mutant, nolac-H18 (nonorganogenic callus with loosely attached cells), generated by T-DNA transformation using leaf-disk cultures of haploid Nicotiana plumbaginifolia, lost the ability to form tight intercellular attachments and adventitious shoots. The gene tagged with T-DNA, named NpGUT1 (glucuronyltransferase 1), was similar to the gene for the catalytic domains of animal glucuronyltransferases and was expressed predominantly in shoot and root apical meristems. The transformation of NpGUT1 complemented the nolac-H18 mutation, and the expression of antisense NpGUT1 RNA produced crumbled shoots. The mutation caused defects in the glucuronic acid of rhamnogalacturonan II of pectin, which drastically reduced the formation of borate cross-linking of rhamnogalacturonan II. NpGUT1, which encodes a unique glucuronyltransferase, is a glycosyltransferase gene identified in pectin biosynthesis and is essential for intercellular attachment in plant meristems and tissues

Characterization of the Ustilago maydis sid2 Gene, Encoding a Multidomain Peptide Synthetase in the Ferrichrome Biosynthetic Gene Cluster

Ustilago maydis, the causal agent of corn smut disease, acquires and transports ferric ion by producing the extracellular, cyclic peptide, hydroxamate siderophores ferrichrome and ferrichrome A. Ferrichrome biosynthesis likely proceeds by hydroxylation and acetylation of l-ornithine, and later steps likely involve covalently bound thioester intermediates on a multimodular, nonribosomal peptide synthetase. sid1 encodes l-ornithine N(5)-oxygenase, which catalyzes hydroxylation of l-ornithine, the first committed step of ferrichrome and ferrichrome A biosynthesis in U. maydis. In this report we characterize sid2, another biosynthetic gene in the pathway, by gene complementation, gene replacement, DNA sequence, and Northern hybridization analysis. Nucleotide sequencing has revealed that sid2 is located 3.7 kb upstream of sid1 and encodes an intronless polypeptide of 3,947 amino acids with three iterated modules of an approximate length of 1,000 amino acids each. Multiple motifs characteristic of the nonribosomal peptide synthetase protein family were identified in each module. A corresponding iron-regulated sid2 transcript of 11 kb was detected by Northern hybridization analysis. By contrast, constitutive accumulation of this large transcript was observed in a mutant carrying a disruption of urbs1, a zinc finger, GATA family transcription factor previously shown to regulate siderophore biosynthesis in Ustilago. Multiple GATA motifs are present in the intergenic region between sid1 and sid2, suggesting bidirectional transcription regulation by urbs1 of this pathway. Indeed, mutation of two of these motifs, known to be important to regulation of sid1, altered the differential regulation of sid2 by iron