Establishing the tolerability and performance of tamarind seed polysaccharide (TSP) in treating dry eye syndrome: results of a clinical study

BACKGROUND: One of the problems arising from available preparations for dry eye syndrome is the limited residence time of products on the ocular surface. In this paper, we look at an innovative new treatment for dry eye, tamarind seed polysaccharide (TSP). TSP possesses mucomimetic, mucoadhesive and pseudoplastic properties. The 'mucin-like' molecular structure of TSP is similar to corneal and conjunctival mucin 1 (MUC1), a transmembrane glycoprotein thought to play an essential role in protecting and wetting the corneal surface and may explain its increased retention on the eye surface. METHODS: The activity of TSP and hyaluronic acid (HA) in the treatment of dry eye syndrome was compared in an open-label, randomised, single-centre clinical study. Thirty patients were randomised to receive three or more applications per day of either TSP 0.5%, TSP 1% or HA 0.2% (Hyalistil™) over a period of 90 days. The primary objective of tolerability was assessed by visual analogue scale (VAS), scoring of specific symptoms and the incidence of adverse events. Secondary objectives included improvement in stability of the precorneal tear film, subjective symptoms and corneal and conjunctival staining. RESULTS: TSP 0.5% and 1% were comparable to HA 0.2% with regard to both primary and secondary objective parameters. TSP 1% showed benefits over HA 0.2% for the subjective symptoms; trouble blinking, ocular burning and foreign body sensation. CONCLUSION: This study suggests that TSP 0.5% and 1% offer at least equivalent relief to HA 0.2% for dry eye syndrome. All treatments demonstrated optimal tolerability and are suitable for frequent use in the therapy of dry eye. TSP 1% produced promising results in terms of improvements in certain patient symptoms and suggests benefits of the TSP formulation. This study paves the way for a larger study to further establish the performance and safety of TSP compared with HA and highlights the need to expand this therapeutic agent to a wider dry eye population

Circadian Organization in Hemimetabolous Insects

The circadian system of hemimetabolous insects is reviewed in respect to the locus of the circadian clock and multioscillatory organization. Because of relatively easy access to the nervous system, the neuronal organization of the clock system in hemimetabolous insects has been studied, yielding identification of the compound eye as the major photoreceptor for entrainment and the optic lobe for the circadian clock locus. The clock site within the optic lobe is inconsistent among reported species; in cockroaches the lobula was previously thought to be a most likely clock locus but accessory medulla is recently stressed to be a clock center, while more distal part of the optic lobe including the lamina and the outer medulla area for the cricket. Identification of the clock cells needs further critical studies. Although each optic lobe clock seems functionally identical, in respect to photic entrainment and generation of the rhythm, the bilaterally paired clocks form a functional unit. They interact to produce a stable time structure within individual insects by exchanging photic and temporal information through neural pathways, in which serotonin and pigment-dispersing factor (PDF) are involved as chemical messengers. The mutual interaction also plays an important role in seasonal adaptation of the rhythm

Smooth Loops and Fiber Bundles: Theory of Principal Q-bundles

A nonassociative generalization of the principal fiber bundles with a smooth loop mapping on the fiber is presented. Our approach allows us to construct a new kind of gauge theories that involve higher ''nonassociative'' symmetries.Comment: 20 page

Tear fluid biomarkers in ocular and systemic disease: potential use for predictive, preventive and personalised medicine

In the field of predictive, preventive and personalised medicine, researchers are keen to identify novel and reliable ways to predict and diagnose disease, as well as to monitor patient response to therapeutic agents. In the last decade alone, the sensitivity of profiling technologies has undergone huge improvements in detection sensitivity, thus allowing quantification of minute samples, for example body fluids that were previously difficult to assay. As a consequence, there has been a huge increase in tear fluid investigation, predominantly in the field of ocular surface disease. As tears are a more accessible and less complex body fluid (than serum or plasma) and sampling is much less invasive, research is starting to focus on how disease processes affect the proteomic, lipidomic and metabolomic composition of the tear film. By determining compositional changes to tear profiles, crucial pathways in disease progression may be identified, allowing for more predictive and personalised therapy of the individual. This article will provide an overview of the various putative tear fluid biomarkers that have been identified to date, ranging from ocular surface disease and retinopathies to cancer and multiple sclerosis. Putative tear fluid biomarkers of ocular disorders, as well as the more recent field of systemic disease biomarkers, will be shown

Small-Scale Extrusion of Corn Masa By-Products

Corn masa by-product streams are high in fiber and are amenable for utilization in livestock feed rations. This approach is a potentially viable alternative to landfilling, the traditional disposal method for these processing residues. Suspended solids were separated from a masa processing waste stream, blended with soybean meal at four levels (0, 10, 20, and 30% wb), and extruded in a laboratory-scale extruder at speeds of 50 rpm (5.24 rad/sec) and 100 rpm (10.47 rad/sec) with temperature profiles of 80-90-100°C and 100-110-120°C. Processing conditions, including dough and die temperatures, drive torque, specific mechanical energy consumption, product and feed material throughput rates, dough apparent viscosity, and dough density, were monitored during extrusion. The resulting products were subjected to physical and nutritional characterization to determine the effects of processing conditions for these blends. Extrudate analysis included moisture content, water activity, crude protein, in vitro protein digestibility, crude fat, ash, product diameter, expansion ratios, unit and true density, color, water absorption and solubility, and durability. All blends were suitable for extrusion at the processing conditions used. Blend ratio had little effect on either processing parameters or extrudate properties; extrusion temperature and screw speed, on the other hand, significantly affected both processing and product properties

Quantitative 3D Analysis of Plant Roots Growing in Soil Using Magnetic Resonance Imaging

Precise measurements of root system architecture traits are an important requirement for plant phenotyping. Most of the current methods for analyzing root growth require either artificial growing conditions (e.g. hydroponics), are severely restricted in the fraction of roots detectable (e.g. rhizotrons), or are destructive (e.g. soil coring). On the other hand, modalities such as magnetic resonance imaging (MRI) are noninvasive and allow high-quality three-dimensional imaging of roots in soil. Here, we present a plant root imaging and analysis pipeline using MRI together with an advanced image visualization and analysis software toolbox named NMRooting. Pots up to 117 mm in diameter and 800 mm in height can be measured with the 4.7 T MRI instrument used here. For 1.5 l pots (81 mm diameter, 300 mm high), a fully automated system was developed enabling measurement of up to 18 pots per day. The most important root traits that can be nondestructively monitored over time are root mass, length, diameter, tip number, and growth angles (in two-dimensional polar coordinates) and spatial distribution. Various validation measurements for these traits were performed, showing that roots down to a diameter range between 200 μm and 300 μm can be quantitatively measured. Root fresh weight correlates linearly with root mass determined by MRI. We demonstrate the capabilities of MRI and the dedicated imaging pipeline in experimental series performed on soil-grown maize (Zea mays) and barley (Hordeum vulgare) plants

Expression of Distal-less, dachshund, and optomotor blind in Neanthes arenaceodentata (Annelida, Nereididae) does not support homology of appendage-forming mechanisms across the Bilateria

The similarity in the genetic regulation of arthropod and vertebrate appendage formation has been interpreted as the product of a plesiomorphic gene network that was primitively involved in bilaterian appendage development and co-opted to build appendages (in modern phyla) that are not historically related as structures. Data from lophotrochozoans are needed to clarify the pervasiveness of plesiomorphic appendage forming mechanisms. We assayed the expression of three arthropod and vertebrate limb gene orthologs, Distal-less (Dll), dachshund (dac), and optomotor blind (omb), in direct-developing juveniles of the polychaete Neanthes arenaceodentata. Parapodial Dll expression marks premorphogenetic notopodia and neuropodia, becoming restricted to the bases of notopodial cirri and to ventral portions of neuropodia. In outgrowing cephalic appendages, Dll activity is primarily restricted to proximal domains. Dll expression is also prominent in the brain. dac expression occurs in the brain, nerve cord ganglia, a pair of pharyngeal ganglia, presumed interneurons linking a pair of segmental nerves, and in newly differentiating mesoderm. Domains of omb expression include the brain, nerve cord ganglia, one pair of anterior cirri, presumed precursors of dorsal musculature, and the same pharyngeal ganglia and presumed interneurons that express dac. Contrary to their roles in outgrowing arthropod and vertebrate appendages, Dll, dac, and omb lack comparable expression in Neanthes appendages, implying independent evolution of annelid appendage development. We infer that parapodia and arthropodia are not structurally or mechanistically homologous (but their primordia might be), that Dll’s ancestral bilaterian function was in sensory and central nervous system differentiation, and that locomotory appendages possibly evolved from sensory outgrowths

The Dynamics and Evolutionary Potential of Domain Loss and Emergence

The wealth of available genomic data presents an unrivaled opportunity to study the molecular basis of evolution. Studies on gene family expansions and site-dependent analyses have already helped establish important insights into how proteins facilitate adaptation. However, efforts to conduct full-scale cross-genomic comparisons between species are challenged by both growing amounts of data and the inherent difficulty in accurately inferring homology between deeply rooted species. Proteins, in comparison, evolve by means of domain rearrangements, a process more amenable to study given the strength of profile-based homology inference and the lower rates with which rearrangements occur. However, adapting to a constantly changing environment can require molecular modulations beyond reach of rearrangement alone. Here, we explore rates and functional implications of novel domain emergence in contrast to domain gain and loss in 20 arthropod species of the pancrustacean clade. Emerging domains are more likely disordered in structure and spread more rapidly within their genomes than established domains. Furthermore, although domain turnover occurs at lower rates than gene family turnover, we find strong evidence that the emergence of novel domains is foremost associated with environmental adaptation such as abiotic stress response. The results presented here illustrate the simplicity with which domain-based analyses can unravel key players of nature's adaptational machinery, complementing the classical site-based analyses of adaptation

Disruption of TGF-β Signaling Improves Ocular Surface Epithelial Disease in Experimental Autoimmune Keratoconjunctivitis Sicca

TGF-β is a pleiotropic cytokine that can have pro- or anti-inflammatory effects depending on the context. Elevated levels of bioactive TGF-β1 in tears and elevated TGF-β1mRNA transcripts in conjunctiva and minor salivary glands of human Sjögren's Syndrome patients has also been reported. The purpose of this study was to evaluate the response to desiccating stress (DS), an experimental model of dry eye, in dominant-negative TGF-β type II receptor (CD4-DNTGFβRII) mice. These mice have a truncated TGF-β receptor in CD4(+) T cells, rendering them unresponsive to TGF-β.DS was induced by subcutaneous injection of scopolamine and exposure to a drafty low humidity environment in CD4-DNTGFβRII and wild-type (WT) mice, aged 14 weeks, for 5 days. Nonstressed (NS) mice served as controls. Parameters of ocular surface disease included corneal smoothness, corneal barrier function and conjunctival goblet cell density. NS CD4-DNTGFβRII at 14 weeks of age mice exhibited a spontaneous dry eye phenotype; however, DS improved their corneal barrier function and corneal surface irregularity, increased their number of PAS+ GC, and lowered CD4(+) T cell infiltration in conjunctiva. In contrast to WT, CD4-DNTGFβRII mice did not generate a Th-17 and Th-1 response, and they failed to upregulate MMP-9, IL-23, IL-17A, RORγT, IFN-γ and T-bet mRNA transcripts in conjunctiva. RAG1KO recipients of adoptively transferred CD4+T cells isolated from DS5 CD4-DNTGFβRII showed milder dry eye phenotype and less conjunctival inflammation than recipients of WT control.Our results showed that disruption of TGF-β signaling in CD4(+) T cells causes paradoxical improvement of dry eye disease in mice subjected to desiccating stress