New Drugs from Marine Organisms in Alzheimer’s Disease

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder. Current approved drugs may only ameliorate symptoms in a restricted number of patients and for a restricted period of time. Currently, there is a translational research challenge into identifying the new effective drugs and their respective new therapeutic targets in AD and other neurodegenerative disorders. In this review, selected examples of marine-derived compounds in neurodegeneration, specifically in AD field are reported. The emphasis has been done on compounds and their possible relevant biological activities. The proposed drug development paradigm and current hypotheses should be accurately investigated in the future of AD therapy directions although taking into account successful examples of such approach represented by Cytarabine, Trabectedin, Eribulin and Ziconotide. We review a complexity of the translational research for such a development of new therapies for AD. Bryostatin is a prominent candidate for the therapy of AD and other types of dementia in humans.     

Neuroprotective Effects of the Cultivated Chondrus crispus in a C. elegans Model of Parkinson’s Disease

Parkinson’s disease (PD) is the second most common neurodegenerative disorder in the elderly people, currently with no cure. Its mechanisms are not well understood, thus studies targeting cause-directed therapy or prevention are needed. This study uses the transgenic Caenorhabditis elegans PD model. We demonstrated that dietary supplementation of the worms with an extract from the cultivated red seaweed Chondrus crispus decreased the accumulation of α-synulein and protected the worms from the neuronal toxin-, 6-OHDA, induced dopaminergic neurodegeneration. These effects were associated with a corrected slowness of movement. We also showed that the enhancement of oxidative stress tolerance and an up-regulation of the stress response genes, sod-3 and skn-1, may have served as the molecular mechanism for the C. crispus-extract-mediated protection against PD pathology. Altogether, apart from its potential as a functional food, the tested red seaweed, C. crispus, might find promising pharmaceutical applications for the development of potential novel anti-neurodegenerative drugs for humans.     

Synthesis and Neuroprotective Action of Xyloketal Derivatives in Parkinson’s Disease Models

Parkinson’s disease (PD) is the second most common neurodegenerative disease affecting people over age 55. Oxidative stress actively participates in the dopaminergic (DA) neuron degeneration of PD. Xyloketals are a series of natural compounds from marine mangrove fungus strain No. 2508 that have been reported to protect against neurotoxicity through their antioxidant properties. However, their protection versus 1-methyl-4-phenylpyridinium (MPP+)-induced neurotoxicity is only modest, and appropriate structural modifications are necessary to discover better candidates for treating PD. In this work, we designed and synthesized 39 novel xyloketal derivatives (1–39) in addition to the previously reported compound, xyloketal B. The neuroprotective activities of all 40 compounds were evaluated in vivo via respiratory burst assays and longevity-extending assays. During the zebrafish respiratory burst assay, compounds 1, 9, 23, 24, 36 and 39 strongly attenuated reactive oxygen species (ROS) generation at 50 μM. In the Caenorhabditis elegans longevity-extending assay, compounds 1, 8, 15, 16 and 36 significantly extended the survival rates (p < 0.005 vs. dimethyl sulfoxide (DMSO)). A total of 15 compounds were tested for the treatment of Parkinson’s disease using the MPP+-induced C. elegans model, and compounds 1 and 8 exhibited the highest activities (p < 0.005 vs. MPP⁺). In the MPP+-induced C57BL/6 mouse PD model, 40 mg/kg of 1 and 8 protected against MPP+-induced dopaminergic neurodegeneration and increased the number of DA neurons from 53% for the MPP+ group to 78% and 74%, respectively (p < 0.001 vs. MPP+ group). Thus, these derivatives are novel candidates for the treatment of PD.     

Bioactive Compounds Offered in Microcapsules to Determine the Nutritional Value of Copepods’ Natural Diet

Experiments were performed, feeding Calanus pacificus seston and a food consisting of seston and microcapsules (μ-caps), i.e., protein and lipid μ-caps to test for potential biochemical limitation. Seston was collected off Scripps Pier (La Jolla, CA, USA). Whereas protein μ-caps were too small to be efficiently ingested, lipid μ-caps rich in ω3-highly-unsaturated fatty acids (ω3-HUFA) were ingested similarly to natural seston and lipids were assimilated. However, egg production experiments exhibited that animals fed with lipid μ-caps didn’t produce significantly more eggs than with seston of equal carbon concentration and egg production even declined when the diet consisted of 50% lipid μ-caps. Thus, the content of certain ω3-HUFA seemed to have been sufficiently high in seston to prevent limitation. Algal counts revealed that seston consisted mainly of plankton rich in those fatty acids, such as cryptophytes, dinoflagellates, diatoms, and ciliates in the edible size range. This might be characteristic for upwelling systems like the area off Southern California which are known for high trophic transfer efficiency.     

Neuroprotective Effect of the Marine-Derived Compound 11-Dehydrosinulariolide through DJ-1-Related Pathway in In Vitro and In Vivo Models of Parkinson’s Disease

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by tremor, rigidity, bradykinesia, and gait impairment. In a previous study, we found that the marine-derived compound 11-dehydrosinulariolide (11-de) upregulates the Akt/PI3K pathway to protect cells against 6-hydroxydopamine (6-OHDA)-mediated damage. In the present study, SH-SY5Y, zebrafish and rats were used to examine the therapeutic effect of 11-de. The results revealed the mechanism by which 11-de exerts its therapeutic effect: the compound increases cytosolic or mitochondrial DJ-1 expression, and then activates the downstream Akt/PI3K, p-CREB, and Nrf2/HO-1 pathways. Additionally, we found that 11-de could reverse the 6-OHDA-induced downregulation of total swimming distance in a zebrafish model of PD. Using a rat model of PD, we showed that a 6-OHDA-induced increase in the number of turns, and increased time spent by rats on the beam, could be reversed by 11-de treatment. Lastly, we showed that 6-OHDA-induced attenuation in tyrosine hydroxylase (TH), a dopaminergic neuronal marker, in zebrafish and rat models of PD could also be reversed by treatment with 11-de. Moreover, the patterns of DJ-1 expression observed in this study in the zebrafish and rat models of PD corroborated the trend noted in previous in vitro studies.     

Marine Derived Hamacanthins as Lead for the Development of Novel PDGFRβ Protein Kinase Inhibitors

In this study, we report on pyrazin-2(1H)-ones as lead for the development of potent adenosine triphosphate (ATP) competitive protein kinase inhibitors with implications as anti-cancer drugs. Initially, we identified the pyrazin-2(1H)-one scaffold from hamacanthins (deep sea marine sponge alkaloids) by Molecular Modeling studies as core binding motif in the ATP pocket of receptor tyrosine kinases (RTK), which are validated drug targets for the treatment of various neoplastic diseases. Structure-based design studies on a human RTK member PDGFR (platelet-derived growth factor receptor) suggested a straight forward lead optimization strategy. Accordingly, we focused on a Medicinal Chemistry project to develop pyrazin-2(1H)-ones as optimized PDGFR binders. In order to reveal Structure-Activity-Relationships (SAR), we established a flexible synthetic route via microwave mediated ring closure to asymmetric 3,5-substituted pyrazin-2(1H)-ones and produced a set of novel compounds. Herein, we identified highly potent PDGFR binders with IC₅₀ values in an enzymatic assay below µM range, and possessing significant activity against PDGFR dependent cancer cells. Thus, marine hamacanthin-derived pyrazin-2(1H)-ones showing interesting properties as lead for their further development towards potent PDGFR-inhibitors.     

Gluten and non-gluten proteins of wheat as target antigens in autism,Crohn’s and celiac disease

Studies show that patients with celiac disease react not only with gluten wheat proteins but also with non-gluten wheat components. Our goal was to measure IgG or IgA antibodies against wheat proteins or peptides that would provide the most sensitive method for the detection of wheat immune reaction in children with autism spectrum disorder, and patients with Crohn’s and celiac disease (CD). Using ELISA, we measured these antibodies against various gluten and non-gluten wheat proteins. Compared to controls in all three conditions, the strongest reaction was against CXCR3-binding gliadin peptide, followed by a wheat protein mixture, and α-gliadin 33-mer peptide. We determined that a sample that strongly reacted against non-gluten proteins also reacted strongly against gluten proteins. We also found that IgA antibodies against CXCR3-binding gliadin peptide were strongly reactive in a subgroup of 33% in the autism group, 42% in the Crohn’s group, and all tested samples with CD. The results indicate that measuring IgG and IgA antibodies against non-gluten proteins adds nothing to the pathologic relevance of these antibodies. Further research is needed on CXCR3-binding gliadin peptide antibodies as a possible biomarker and as a guide for dietary elimination in CD, Crohn’s disease and a subgroup of children with ASD.     

Prediction of the fabric’s crease recovery property with Taguchi design of experiment

The creasing characteristic of fabrics is affected by many factors like yarn twist, fabric density, fabric constructions, fabric thickness apart from the fiber type. In the first part of this study, the effect of yarn fineness, yarn twist, fabric tightness and weave construction factors on crease recovery was studied. In the second part of the study, in order to improve the creasing recovery of the fabrics, shape memory alloy (SMA) wires were used and the effect of shape memory alloy (SMA) wire on the crease recovery of cotton fabrics produced with different types of weave constructions were determined. Due to the high cost of SMA wire and the weaving operation adversity the two experimental plans were designed according to Taguchi design of experiment (TDOE). From the analysis of the first part, it was found that the yarn linear density had the greatest effect on fabric crease recovery compare to others. Twist coefficient was the second, weft density was third and the weave construction had the least significant effect on the crease recovery. The fabrics produced with coarser and low twisted yarns with high tightness and longer floats in the weave construction have higher crease recovery property. In the second part of the study, the application of the SMA wire significantly increased the crease recovery angle of the fabrics. The thickness of the SMA wire is very important and the effect depends on the wire thickness. The increase of the SMA wire thickness increases the crease recovery significantly. However it must be appropriate with the yarn and fabric properties. The distance between the SMA wire distances was expected to increase the crease recovery however the effect was found not significant. The fabrics produced with coarser yarns with longer floats in the weave construction have higher crease recovery property. However, statistically the effects of these parameters were found not significant due to the dominant effect of the wire thickness.     

The change of the cationic peroxidase in the leaves at the fertile transformation period in Nongken 58s

Nongken 58s is a type of photoperiod sensitivegenic male sterile rice which gives rice to malesterility when illuminated time is longer than13.75 h/d. The photoperiod sensitive stagesare from the differentiation of primary branchprimordum (Ⅱ) in young ears to fullness ofcontents of the pollen (Ⅶ). The changes ofactivity and isoenzymes in cation peroxidase atphotoperiod sensitive stages and the relation-     

Potato growers 1961 yearbook acclaimed one of the nation’s finest

American Journal of Potato Research -     

Natural Marine and Synthetic Xenobiotics Get on Nematode’s Nerves: Neuro-Stimulating and Neurotoxic Findings in Caenorhabditis elegans

Marine algae release a plethora of organic halogenated compounds, many of them with unknown ecological impact if environmentally realistic concentrations are applied. One major compound is dibromoacetic acid (DBAA) which was tested for neurotoxicity in the invertebrate model organism Caenorhabditis elegans (C. elegans). This natural compound was compared with the widespread synthetic xenobiotic tetrabromobisphenol-A (TBBP-A) found in marine sediments and mussels. We found a neuro-stimulating effect for DBAA; this is contradictory to existing toxicological reports of mammals that applied comparatively high dosages. For TBBP-A, we found a hormetic concentration-effect relationship. As chemicals rarely occur isolated in the environment, a combination of both organobromines was also examined. Surprisingly, the presence of DBAA increased the toxicity of TBBP-A. Our results demonstrated that organohalogens have the potential to affect single organisms especially by altering the neurological processes, even with promoting effects on exposed organisms.     

Effect of intermittent irrigation following the system of rice intensification (SRI) on rice yield in a farmer’s paddy fields in Indonesia

System of rice intensification (SRI) has been disseminated in many countries because of its high yield, although the mechanism of yield increase has yet to be fully understood. The aims of this study were to clarify the actual water management of a skilled SRI farmer in irrigated paddy field of Indonesia and to examine the effect of intermittent water management on rice growth and yield. Yield and yield components were compared in the field experiments in the farmer’s fields under intermittent (SRI) or flooded (FL) irrigation for 4 years from 2013 to 2016. The daily mean water depth of SRI plots during 0–40 days after transplanting showed very shallow (ca. 2 cm) or little lower than soil surface and continued to be lower than soil surface during reproductive stage when panicles were formed. The yield of SRI significantly exceeded that of FL for 4 years by 13% (P?=?0.0004), so did the panicle numbers per area (P?=?0.036). The yield increase in SRI was associated with the increased number of panicles, which should have resulted from enhanced tiller development under shallow water level during the vegetative stage. The increased number of panicles was, however, counteracted by the reduced number of spikelets per panicle and resulted in nonsignificant increase in the spikelet density, defined as number of spikelets per unit area of crop. This dampening change in spikelet number per panicle could have been caused by limited supply of either nitrogen or carbohydrate during the panicle development stage under the intermittent water supply. A greater yield increase by SRI could be expected by improving nutrient or water management during the reproductive stage.     

A new direction in international cooperation, utilizing Japan’s experience and expertise in the field of agricultural and rural development

There is an urgent need for the international community to address not only the issues of preserving the global environment and reducing poverty in developing countries, but to also face up to new challenges, such as providing assistance to the reconstruction in Afghanistan. Furthermore, it is necessary to address these issues and challenges by means of mutual collaboration. This latter point has been the subject of lively discussion.In this paper, we describe a new direction in international cooperation taken by the Rural Development Bureau of the Ministry of Agriculture, Forestry and Fisheries, Japan in response to the trend of international discussions. This shoulb be achieved by utilizing Japans experience and expertise gained in the development of its own paddy rice agriculture.Specifically, based on the philosophy that sustainable agricultural and rural development can conserve a regional environment, the Bureau intends to undertake: (1) extension of the results from a cooperation project to other regions, by modifying it and converting it to multi-purpose use; (2) collaboration with aid-related entities in Japan and abroad, and dissemination of related information to them; and (3) promotion of cooperation focused on a specific topic.Furthermore, the Bureau will promote the following matters as the basis for international cooperation in each major task. (1) Contribution towards sustainable water use. (2) Extension of the participatory integrated rural development, and its modification for reconstruction assistance. (3) Extension of desertification control, and its modification and conversion for multi-purpose use. (4) Conversion of the technology for soil erosion control into multi-purpose use.     

Switchable Wettability of the Honeybee’s Tongue Surface Regulated by Erectable Glossal Hairs

Various nectarivorous animals apply bushy-hair-equipped tongues to lap nectar from nectaries of flowers. A typical example is provided by the Italian honeybee (Apis mellifera ligustica), who protracts and retracts its tongue (glossa) through a temporary tube, and actively controls the erectable glossal hairs to load nectar. We first examined the microstructure of the honeybee’s glossal surface, recorded the kinematics of its glossal hairs during nectar feeding process and observed the rhythmical hair erection pattern clearly. Then we measured the wettability of the glossal surface under different erection angles (EA) in sugar water of the mass concentration from 25 to 45%, mimicked by elongating the glossa specimens. The results show that the EA in retraction approximately remains stable under different nectar concentrations. In a specific concentration (35, 45, or 55%), the contact angle decreases and glossal surface area increases while the EA of glossal hairs rises, the glossa therefore could dynamically alter the glossal surface and wettability in foraging activities, not only reducing the energy consumption for impelling the nectar during tongue protraction, but also improving the nectar-trapping volume for feeding during glossa retraction. The dynamic glossal surface with switchable wettability regulated by erectable hairs may reveal the effective adaptation of the honeybee to nectar intake activities.     

Evaluation of the structural properties of plain fabrics woven from various fibers using Peirce’s model

Peirce’s fabric model has been widely used to predict the structural behavior of various plain woven fabrics. The structure of plain woven fabric can be defined in terms of the warp yarn number, weft yarn number, warp fabric density, weft fabric density, warp crimp, and weft crimp. The warp and weft yarn diameters are calculated from the warp and weft yarn numbers, and the effective coefficient of the yarn diameter is defined by using this model. We have investigated structural properties, such as the effective coefficient of the yarn diameter, yarn crimp, and fabric thickness for two different fabrics in which the constituent yarns are assumed to be either incompressible or compressible. This model is also applied to various plain fabrics woven from cotton, rayon, wool, linen, nylon, acetate, polyester, and silk yarns.     

Ultrasound-Assisted Extraction for the Recovery of Carotenoids from Guava’s Pulp and Waste Powders

Plant Foods for Human Nutrition - In this work, lycopene- and β-carotene-rich extracts were obtained from guava’s pulp and waste powders using maceration (ME), ultrasonic bath (BUAE,...