α

Amyotrophic lateral sclerosis (ALS) is a progressively paralytic neurodegenerative disease that can be caused by mutations in Cu/Zn-superoxide dismutase 1 (SOD1). Transgenic mice that overexpress mutant SOD1 develop paralysis and accumulate aggregates of mutant protein in the brainstem and spinal cord. Bee venom (BV), which is also known as apitoxin, is extracted from honeybees and is commonly used in oriental medicine for the treatment of chronic rheumatoid arthritis and osteoarthritis. The purpose of the present study was to determine whether BV affects misfolded protein aggregates such as alpha-synuclein, which is a known pathological marker in Parkinson disease, and ubiquitin-proteasomal activity in hSOD1G93A mutant mice. BV was bilaterally administered into a 98-day-old hSOD1G93A animal model. We found that BV-treated hSOD1G93A transgenic mice showed reduced detergent-insoluble polymerization and phosphorylation of α-synuclein. Furthermore, phosphorylated or nitrated α-synuclein was significantly reduced in the spinal cords and brainstems of BV-treated hSOD1G93A mice and reduced proteasomal activity was revealed in the brainstems of BV-treated symptomatic hSOD1G93A. From these findings, we suggest that BV treatment attenuates the dysfunction of the ubiquitin-proteasomal system in a symptomatic hSOD1G93A ALS model and may help to slow motor neuron loss caused by misfolded protein aggregates in ALS models

Potassium chloride elicits enhancement of bilobalide and Ginkgolides production by Ginkgo biloba cell cultures

This study investigated the ability of potassium chloride (KCl) to elicit the production of bilobalide (BB), ginkgolide A (GA) and ginkgolide B (GB) by Ginkgo biloba cell suspension cultures. The salt stress by KCl treatments increased production of BB, GA and GB in both suspended cells and cultured medium. Especially, treatment of KCl 800 mM of highest concentration was stimulated emission into cultured medium BB, GA and GB compounds accumulated in cells. Although KCl 800 mM severely inhibited cells growth, the maximum content of GA and GB in cells was obtained in the treatment of KCl 800 mM, which was 1.9 and 4.0 times higher than the control. These results thus suggest that salt stress can afford enhanced production of secondary metabolites by plant cell cultures

Melittin restores proteasome function in an animal model of ALS

Amyotrophic lateral sclerosis (ALS) is a paralyzing disorder characterized by the progressive degeneration and death of motor neurons and occurs both as a sporadic and familial disease. Mutant SOD1 (mtSOD1) in motor neurons induces vulnerability to the disease through protein misfolding, mitochondrial dysfunction, oxidative damage, cytoskeletal abnormalities, defective axonal transport- and growth factor signaling, excitotoxicity, and neuro-inflammation

5-Fluoro­isophthalic acid

In the crystal structure of the title compound, C8H5FO4, the complete molecule is generated by crystallographic twofold symmetry with two C atoms and the F atom lying on the axis. The mol­ecule is almost planar with the carboxyl group twisted with respect to the mean plane of the benzene ring by a dihedral angle of 2.01 (1)°. In the crystal, inter­molecular O—H⋯O hydrogen bonds and C—H⋯F inter­actions connect the mol­ecules into a two-dimensional supra­molecular array

Selection of high berberine yielding phellodendron insulare nak. lines and the antimicrobial activity of their extracts

High berberine yielding Phellodendron insulare Nak. lines were selected by aggregate cloning method and the antimicrobial activity of their extracts was assessed. The berberine producing cork tree lines were selected by adopting a colorimetric method. In all 300 high berberine producing lines were selected with a colorimetric reagent containing 5M HCl and H2O2 and established from dissociated cell aggregates. The crude extracts from these lines showed antibacterial activities against tested Escherichia coli, Staphylococcus aureus, Salmonella typhimulium, and Listeria monocytogenes. The cork tree extracts were found to be inhibitory to these test organisms. Further the antimicrobial activity of plant extracts was on par with the berberine isolated from the extracts from native cork trees. These results have potential for developing alternative plant products as antimicrobial substances for application in agriculture and food industry

Associations between Organochlorine Pesticides and Vitamin D Deficiency in the U.S. Population

Background: Recently low dose organochlorine (OC) pesticides have been strongly linked to various chronic diseases including diabetes and cardiovascular diseases. Both field and animal studies have suggested a possibility that persistent lipophilic chemicals like OC pesticides can cause vitamin D deficiency, but there have been no human studies of exposure to any chemical as a possible cause of vitamin D deficiency. This study was performed to examine if serum concentrations of OC pesticides were associated with serum concentrations of 25-hydroxyvitamin D (25(OH)D) in the U.S. general population. Methodology/Principal Findings: Cross-sectional associations of serum OC pesticides with serum 25(OH)D were investigated in 1,275 subjects aged $20 in the National Health and Nutrition Examination Survey(NHANES), 2003–2004. We selected 7 OC pesticides detectable in$80 % of participants. Among the 7 OC pesticides, p,p9-DDT (b = 20.022, P,0.01), p,p9-DDE (b = 20.018, P = 0.04), and b-hexachlorocyclohexane (b = 20.022, P = 0.02) showed significant inverse associations with serum 25(OH)D levels. When study subjects were stratified by age, race, and the presence of various chronic diseases, p,p9-DDT showed consistent inverse associations in all subgroups, although stronger associations tended to be observed among subjects with old age, white race, or chronic diseases. Conclusion/Significance: The current study suggests that the background exposure to some OC pesticides leads to vitamin D deficiency in human. Considering the importance of vitamin D deficiency in the development of chronic diseases

Bee venom attenuates neuroinflammatory events and extends survival in amyotrophic lateral sclerosis models

<p>Abstract</p> <p>Background</p> <p>Amyotrophic lateral sclerosis (ALS) is a disease affecting the central nervous system that is either sporadic or familial origin and causing the death of motor neurons. One of the genetic factors contributing to the etiology of ALS is mutant SOD1 (mtSOD1), which induces vulnerability of motor neurons through protein misfolding, mitochondrial dysfunction, oxidative damage, cytoskeletal abnormalities, defective axonal transport, glutamate excitotoxicity, inadequate growth factor signaling, and neuroinflammation. Bee venom has been used in the practice of Oriental medicine and evidence from the literature indicates that BV plays an anti-inflammatory or anti-nociceptive role against inflammatory reactions associated with arthritis and other inflammatory diseases. The purpose of the present study was to determine whether bee venom suppresses motor neuron loss and microglial cell activation in hSOD1^G93Amutant mice.</p> <p>Methods</p> <p>Bee venom (BV) was bilaterally injected (subcutaneously) into a 14-week-old (98 day old) male hSOD1^G93Aanimal model at the Zusanli (ST36) acupoint, which is known to mediate an anti-inflammatory effect. For measurement of motor activity, rotarod test was performed and survival statistics were analyzed by Kaplan-Meier survival curves. The effects of BV treatment on anti-neuroinflammation of hSOD1^G93Amice were assessed via immunoreactions using Iba 1 as a microglia marker and TNF-α antibody. Activation of ERK, Akt, p38 MAP Kinase (MAPK), and caspase 3 proteins was evaluated by western blotting.</p> <p>Results</p> <p>BV-treated mutant hSOD1 transgenic mice showed a decrease in the expression levels of microglia marker and phospho-p38 MAPK in the spinal cord and brainstem. Interestingly, treatment of BV in symptomatic ALS animals improved motor activity and the median survival of the BV-treated group (139 ± 3.5 days) was 18% greater than control group (117 ± 3.1 days). Furthermore, we found that BV suppressed caspase-3 activity and blocked the defects of mitochondrial structure and cristae morphology in the lumbar spinal cord of hSOD1^G93Amice at the symptomatic stage.</p> <p>Conclusion</p> <p>From these findings, our research suggests BV could be a potential therapeutic agent for anti-neuroinflammatory effects in an animal model of ALS.</p

A PDEM-COM framework for uncertainty quantification of backward issues involving both aleatory and epistemic uncertainties

Uncertainties that exist in nature or due to lack of knowledge have been widely recognized by researchers and engineering practitioners throughout engineering design and analysis for decades. Though great efforts have been devoted to the issues of uncertainty quantification (UQ) in various aspects, the methodologies on the quantification of aleatory uncertainty and epistemic uncertainty are usually logically inconsistent. For instance, the aleatory uncertainty is usually quantified in the framework of probability theory, whereas the epistemic uncertainty is quantified mostly by non-probabilistic methods. In the present paper, a probabilistically consistent framework for the quantification of both aleatory and epistemic uncertainty by synthesizing the probability density evolution method (PDEM) and the change of probability measure (COM) is outlined. The framework is then applied to the backward issues of uncertainty quantification. In particular, the uncertainty model updating issue is discussed in this paper. A numerical example is presented, and the results indicate the flexibility and efficiency of the proposed PDEM-COM framework

Effects of Bee Venom on Glutamate-Induced Toxicity in Neuronal and Glial Cells

Bee venom (BV), which is extracted from honeybees, is used in traditional Korean medical therapy. Several groups have demonstrated the anti-inflammatory effects of BV in osteoarthritis both in vivo and in vitro. Glutamate is the predominant excitatory neurotransmitter in the central nervous system (CNS). Changes in glutamate release and uptake due to alterations in the activity of glutamate transporters have been reported in many neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis. To assess if BV can prevent glutamate-mediated neurotoxicity, we examined cell viability and signal transduction in glutamate-treated neuronal and microglial cells in the presence and absence of BV. We induced glutamatergic toxicity in neuronal cells and microglial cells and found that BV protected against cell death. Furthermore, BV significantly inhibited the cellular toxicity of glutamate, and pretreatment with BV altered MAP kinase activation (e.g., JNK, ERK, and p38) following exposure to glutamate. These findings suggest that treatment with BV may be helpful in reducing glutamatergic cell toxicity in neurodegenerative diseases

Effect of cultivar and fertilization on functional value of sweet potato (Ipomoea batatas L.)

Batat (Ipomoea batatas L.) je višegodišnja tropska vrsta iznimno velike nutritivne vrijednosti korijena i lista. Pripada u skupinu funkcionalne hrane zbog značajne količine specijaliziranih biljnih metabolita, antioksidativnih spojeva (vitamina, polifenola, karotenoida) i sadržaja esencijalnih minerala, dijetalnih vlakana, uz niski glikemijski indeks korijena. Sastav i koncentracija specijaliziranih biljnih metabolita su promjenjivi, zbog utjecaja genotipa, ekoloških uvjeta uzgoja i gnojidbe, što predstavlja problem u proizvodnji povrća kao funkcionalne hrane, od koje se očekuje ujednačena hranidbena i zdravstvena vrijednost. S obzirom na povećan interes za proizvodnjom batata stabilne antioksidacijske aktivnosti te malobrojne rezultate o toj problematici, uočena je potreba istraživanja utjecaja sorte i rastuće gnojidbe posebice kalijem na komponente prinosa, udio polifenola i antioksidacijsku aktivnost korijena i lista batata, u cilju dobivanja smjernica tehnologije uzgoja batata povećanih nutritivnih vrijednosti i ujednačene kvalitete. S tim ciljem je u SZ Hrvatskoj na Pokusno-pokaznom polju u Varaždinu, provedeno dvogodišnje istraživanje, radi utvrđivanja smjernica tehnologije uzgoja batata veće funkcionalne vrijednosti. Tijekom 2008. i 2009. godine postavljeni su istovjetni dvofaktorijalni poljski pokusi po metodi slučajnog bloknog rasporeda u četiri ponavljanja. Prvi faktor je sorta u dvije razine (ʹBatʹ i ʹBoniatoʹ), i drugi gnojidba dušikom i kalijem u tri razine (kontrolna gnojidba odnos N i K 1:1, druga razina odnos N i K 1:2,5 i treća odnos N i K 1:5). Tijekom istraživanja s obzirom na sortu i rastuću gnojidbu dušikom i kalijem ostvareni su u obje godine veći prinosi korijena m-2 (ʹBatʹ 2,78 do 4,67 kg i ʹBoniatoʹ 2,70 do 4,92 kg) i lista (ʹBatʹ 1,82 do 3,73 kg i ʹBoniatoʹ 3,68 do 5,33 kg) veći postotak K u korijenu (ʹBatʹ 1,49 do 2,34 % i ʹBoniatoʹ 1,20 do 1,81%) i listu (ʹBatʹ 2,22 do 3,20 % i ʹBoniatoʹ 2,72 do 3,68 %), veći postotak N u korijenu (ʹBatʹ 1,49 do 1,80 % i ʹBoniatoʹ 1,55 do 1,83 %) i listu (ʹBatʹ 3,16 do 3,73 % i ʹBoniatoʹ 3,04 do 3,38 %),veći udio krupnije frakcije korijena (ʹBatʹ 17,29 do 19,86% i ʹBoniatoʹ 9,61 do 17,79 %), veći udio ukupnih polifenola korijena sorte ʹBatʹ (3,75 do 16,08 mg GAE g-1 st) i ORAC vrijednosti korijena (ʹBatʹ 15,10 do 73,03 µmol TE g-1 st) i veći udio flavonoida u listu (ʹBatʹ 8,27 do 11,58 mg g-1 ST i ʹBoniatoʹ 9,59 do 20,61 mg g-1 ST), dok je udio ukupnih polifenola u listu (ʹBatʹ 49,68 do 50,25 i ʹBoniatoʹ 51,77 do 53,31 mg g-1 ST) i ORAC vrijednosti (ʹBatʹ 402,50 do 422,17 µmol TE g-1 ST i ʹBoniatoʹ 439,90 do 474,96 µmol TE g-1 ST) bio veći u drugoj godini istraživanja. Obje sorte su uz veću razinu gnojidbe dale veće prinose korijena i lista, veći udio N, sirovih proteina, K, dok je udio ukupnih polifenola i antioksidacijska aktivnost bila značajno veća u listu u odnosu na korijen kod obje razine gnojidbe.Sweet potato (lat. Ipomoea batatas) is a vegetable species of extremely high nutritional value of roots and leaves. It belongs to a group of functional foods because of the significant amount of specialized herbal metabolites, antioxidants (vitamins, polyphenols, carotenoids) and the content of essential minerals, dietary fibres, with low glycaemic root index. Polyphenol compounds include a large group of specialized plant metabolites that contribute to better organoleptic and nutritional components of vegetables and fruits. Specialized secondary herbal metabolites are compounds synthesized in plants as secondary metabolic products in the interaction of plants with agro-environmental conditions. Specialized metabolites differ according to the chemical structure and their function in the organism. In food, specialized metabolites are most often defined as natural non-nutritional food ingredients, which have health-beneficial effects if consumed in adequate quantities. Moreover, antioxidants play an important role in human nutrition due to the strong function of protecting the body and boosting the immune system. By consuming foods rich in antioxidants, we help the body fight against various diseases caused by free radicals. The composition and concentration of specialized plant metabolites are variable due to the influence of genotypes, ecological conditions of cultivation and fertilization, which presents a problem in the production of vegetables as a functional food, which is expected to have a consistent nutritional and health value. The functional value of food is found in products that, besides basic nutritional value, have a positive effect on human health, preventing and reducing the risk of developing certain diseases. Due to the content of specialized metabolites, sweet potato is classified into functional foods because besides being a good source of minerals and vitamins, it supplies the body with important antioxidants. Antioxidants are produced in the cells or are introduced into our body through food intake, and function in several ways: they prevent the formation of new free radicals in the body, they destroy the radicals created in the body, or repair damage in the cells created by the action of free radicals. Oxidative stress implies a shift of balance in cellular oxidationreduction reactions in the direction of oxidation. Oxidative stress causes excessive formation of free radicals of oxygen, resulting in the loss of balance in creating free radicals and the inability of a cell to disintegrate them, and causing changes related to cell damage. The root and leaf consumption of sweet potatoes is associated with various positive physiological effects on health, such as antioxidant activity, ant mutagenicity, anti cancerogenicity, antimicrobial activity, and antidiabetic effect. Functional values of the sweet potato prompted producers to commercially breed sweet potato, as a new vegetable crop in Croatia. Due to the increased interest in the production of sweet potato with stable antioxidant activity and a small number of results on this problem, the need to investigate cultivar influence and growing fertilization, especially potassium on yield components, polyphenol concentrations and antioxidant activity of its root and leaf, has been recognized. With this aim, a two-year research was conducted in the Experimental-demonstration field in Varazdin to determine the guidelines for the breeding technology of equally balanced but nutritional and functional values of the sweet potato. During 2008 and 2009, identical twofactor polymorphisms were set up according to the method of randomized complete block design with four repetitions. The first factor is the variety in two steps, and the second fertilization with nitrogen and potassium in three steps. Two types of fertilization (ʹBatʹ and ʹBoniatoʹ) and two increased fertilization levels (500 and 1000 kg ha-1 NPK 7:14:21) were carried out with the addition of potassium salt K2SO4 to achieve a ratio of N:K 1:2.5 and 1: 5t. As a control variant, a lower fertilization level was used with the ratio N:K 1:1 with 250 kg ha-1 NPK 15:15:15. Transplant production with a lump of substrate in polystyrene containers was organized in the protected area of the Department of Vegetable Crops of the Faculty of Agriculture. Planting was carried out in mid-May, with 2 plants per m2 on raised bed covered with PE film, or 40 plants per basic parcel of 20 m2. Sweet potato transplants were planted manually on a 1.2 m spacing distance and a 0.4 m line spacing, enabling 2 plants per square meter. Fertilization was performed prior to machine shaping and setting of PE film. Temperatures and rainfall were monitored daily on CDA devices. Thirty-sixty days after planting, leaves and stems were counted on each plot, and the length of the stem and leaf area index was measured, while the total yield of leaf mass and root was weighed at the end of the vegetation. After the roots’ transport and storage, individual weighing of each root was performed, in order to calculate the share of individual root fractions and the influence of variety and fertilization on root size and marketable yield. The reference root and leaf sample were analyzed on the content of dry weigh, nitrogen, phosphorus and potassium at the Faculty of Agriculture, while total and individual polyphenols and antioxidant activity were analyzed at the Faculty of Food Technology at the Department of Biochemical Engineering. During the study, the validity of varieties was affirmed, along with fertilizers and their interaction on the amount of dry weigh in the leaf in both research years (ʹBatʹ 5.97 to 7.34 %, ʹBoniatoʹ 5.81 to 7.29 %), on raw protein in the leaf (ʹBatʹ 18.43 to 23.34 %, ʹBoniatoʹ 18.81 to 21.13 %), the total amount of N in the leaf (ʹBatʹ 2.95 to 3.74 %, ʹBoniatoʹ 3.04 to 3.38 %), (ʹBatʹ 0.22 to 0.33 %, ʹBoniatoʹ 0.21 to 0.34 %), quantity of K in the leaf (ʹBatʹ 2.22 to 3.20 %, ʹBoniatoʹ 2.23 to 3.68 %). The values of the antioxidant activity of the leaf and total polyphenols of the ʹBatʹ variety were growing (80.07 to 121.27 μmol Trolox g-1 DW, that is 14.38 to 23.17 mg GAE g-1 DW in 2008 and 396.87 to 422 , 2 μmol TE g-1 DW, or 48.52 to 50.25 mg GAE g-1 DW in 2009) and the ʹBoniatoʹ variety values were falling (in 2008, 126 to 104 μmol TE g-1 DW, ie 22,03 to 20,58 mg GAE g-1 DW and increased in 2009 to 396.38 to 474.96 μmol TE g-1 DW, that is 50.02 to 53.31 mg GAE g-1 DW). There were higher values of individual and total flavonoids in the leaf (ʹBatʹ 8.27 to 11.58 mg g-1 DW and ʹBoniatoʹ 9.56 to 20.61 mg g-1 DW). In the roots, bigger amounts of dry weigh were found in both research years (ʹBatʹ 14.50 to 25.28 %, ʹBoniatoʹ 16.15 to 23.64 %), as well as raw protein in the root (ʹBatʹ 9.18 to 11.25 %, ʹBoniatoʹ 8.56 to 11.44 %), the total amount of N in the root (ʹBatʹ 1.47 to 1.80 %, ʹBoniatoʹ 1.37 to 1.83 %), the amount of P in the root (ʹBatʹ 0.15 to 0.28 %, ʹBoniatoʹ 0.19 to 0.27 %), the amount of K in the root (ʹBatʹ 1.49 to 2.34 %, ʹBoniatoʹ 1.18 to 1.81 %). The values of the antioxidant activity of root and total polyphenols of the Bat variety were growing (9.26 to 17.40 μmol TE g-1 fw, that is 2.30 to 4.32 mg GAE g-1 fw in 2008 and 48.73 to 61,56 μmol TE g-1 fw, or 13.03 to 16.08 mg GAE g-1 fw in 2009). The values of the ʹBoniatoʹ variety were falling (30.69 to 20.34 μmol TE g-1 fw, or 7.62 to 5.05 mg GAE g-1 fw in 2008, and in 2009 51.00 to 48.08 μmol TE g-1 fw, while polyphenols were growing 11.88 to 13.02 mg GAE g-1 fw). During the study, varying impact of variety and fertilization and their interaction with morphological properties (length of stem, number of stems, leaf counts and leaf area index) was determined, with ʹBoniatoʹ variety having significantly higher values compared to the ʹBatʹ variety. The length of stem thirty days after planting (ʹBatʹ 27.68 to 29.90 cm, ʹBoniatoʹ 30.00 to 31.88 cm), number of stems (ʹBatʹ 1.57 to 1.80, ʹBoniatoʹ 1.63 to 1.80 ), number of leaves (ʹBatʹ 21.93 to 25.78, ʹBoniatoʹ 28.88 to 40.45), leaf area index (ʹBatʹ 200.40 to 235.63 cm2, ʹBoniato ʹ263.93 to 369.73 cm2). The length of stem sixty days after planting was (ʹBatʹ 50.93 to 61.45 cm, ʹBoniatoʹ 59.83 to 63.78 cm), number of stems (ʹBatʹ 12.80 to 15.38, ʹBoniatoʹ 15.40 to 18.28), number of leaves (ʹBatʹ 219.30 to 255.25, ʹBoniatoʹ 313.93 to 369.00), leaf area index (ʹBatʹ 2004.40 to 2330.70 cm2, ʹBoniatoʹ 2869.25 to 3305.95 cm2). In both years, variety and fertilization interactions provided higher root yields per m2 (ʹBatʹ 2,78 to 4,67 kg and ʹBoniatoʹ 2,70 to 4,92 kg) and leaves (ʹBatʹ 1,82 to 3,73 kg and ʹBoniatoʹ 3,68 to 5,33 kg), a higher share of a larger root fraction (ʹBatʹ 17.29 to 19.86 % and ʹBoniatoʹ 9.61 to 17.79 %) and a higher share of the total marketable root (ʹBatʹ 89.78 to 91,12 % and ʹBoniatoʹ 83.77 to 87.68 % in 2008 and in 2009 ʹBatʹ 78.1 to 86.57 % and ʹBoniatoʹ 87.80 to 90.95 %). Higher level of fertilization in both varieties gave higher roots and leaf yields, higher percentage of dry weigh and crude protein, higher amounts of N, P and K, and bigger quantities of larger roots fractions. Total and individual polyphenols and antioxidant activity were variable (higher in ʹBatʹ variety and slightly lower in ʹBoniatoʹ variety), but significantly higher in the leaf of both varieties compared to the root