Effect of conjugated linoleic acid, μ-calpain inhibitor,on pathogenesis of Alzheimer's disease

μ-Calpain is a calcium-dependent cysteine protease, which is activated by μM concentration of calcium in vitro. Disrupted intracellular calcium homeostasis leads to hyper-activation of μ-calpain. Hyper-activated μ-calpain enhances the accumulation of β-amyloid peptide by increasing the expression level of β-secretase (BACE1) and induces hyper-phosphorylation of tau along with the formation of neurofibrillary tangle by mediating p35 cleavage into p25, both of which are the major mechanisms of neurodegeneration in Alzheimer's disease (AD). Hence, inhibition of μ-calpain activity is very important in the treatment and prevention of AD. In this study, conjugated linoleic acid (CLA), an eighteen-carbon unsaturated fatty acid, was discovered as a μ-calpain-specific inhibitor. CLA showed neuroprotective effects against neurotoxins such as H₂O₂ and Aβ_1–42 in SH-SY5Y cells, and inhibited Aβ oligomerization/fibrillation and Aβ-induced Zona Occludens-1 degradation. In addition, CLA decreased the levels of proapoptotic proteins, p35 conversion to p25 and tau phosphorylation. These findings implicate CLA as a new core structure for selective μ-calpain inhibitors with neuroprotective effects. CLA should be further evaluated for its potential use as an AD therapeutic agent.     

Effect of the association of IGF-I, IGF-II, bFGF, TGF-β1, GM-CSF, and LIF on the development of bovine embryos produced in vitro

This study examined the influence of the following growth factors and cytokines on early embryonic development: insulin-like growth factors I and II (IGF-I, IGF-II), basic fibroblast growth factor (bFGF), transforming growth factor (TGF-β), granulocyte-macrophage colony-stimulating factor (GM-CSF), and leukemia inhibitory factor (LIF). Synthetic oviduct fluid (SOF) was used as the culture medium. We studied the development of bovine embryos produced in vitro and cultured until Day 9 after fertilization. TGF-β1, bFGF, GM-CSF, and LIF used on their own significantly improved the yield of hatched blastocysts. IGF-I, bFGF, TGF-β1, GM-CSF, and LIF significantly accelerated embryonic development, especially the change from the expanded blastocyst to hatched blastocyst stages. Use of a combination of these growth factors and cytokines (GF-CYK) in SOF medium produced higher percentages of blastocysts and hatched blastocysts than did use of SOF alone (45% and 22% vs. 24% and 12%; P < 0.05) on Day 8 after in vitro fertilization and similar results to use of SOF + 10% fetal calf serum (38% and 16%, at the same stages, respectively). The averages of total cells, inner cell mass cells, and trophectoderm cells of exclusively in vitro Day-8 blastocysts for pooled GF-CYK treatments were higher than those for SOF and similar to those for fetal calf serum. The presence of these growth factors and cytokines in the embryo culture medium therefore has a combined stimulatory action on embryonic development; in particular through an increase in hatching rate and in the number of cells of both the inner cell mass and trophoblast. These results are the first to demonstrate that use of a combination of recombinant growth factors and cytokine, as IGF-I, IGF-II, bFGF, TGF-β1, LIF, and GM-CSF, produces similar results to 10% fetal calf serum for the development of in vitro-produced bovine embryos. This entirely synthetic method of embryo culture has undeniable advantages for the biosecurity of embryo transfer.     

Effect of thymopentin on the production of cytokines, heat shock proteins, and NF-κB signaling proteins

In vivo effects of thymopentin, an active fragment of the naturally occurring thymic hormone thymopoietin, on the production of cytokines, nitric oxide, heat shock proteins, and signaling proteins NF-κB, phNF-κB, and IκB-α in lymphoid cells of male NMRI mice was studied. Activation of production of several cytokines (IL-1α, IL-2, IL-6, IL-10, and IFN-γ), nitric oxide, and heat shock proteins (HSP70 and HSP90) was observed in peritoneal macrophages and spleen lymphocytes of mice that received intraperitoneal injections of thymopentin (15μg per 100 g body weight). Thymopentin apparently produces stress-like rather than damaging effects. A probable action mechanism of this hormone is activation of the NF-κB signaling pathway, which is most pronounced at the NF-κB phosphorylation stage.     

Effect of γ-Irradiation on Development of Lachrymator of Onion

A thermosensitive uracil requiring mutant of Bacillus subtilis Marburg 168 thy trp₂ ts42 was examined as to the colony forming ability at the permissive and nonpermissive temperatures. The viability of the mutant cells decreased rapidly at the restrictive temperature in the modified Woese’s (MW) medium. However, the cells retained viability when sodium succinate or potassium chloride was added to the medium at that temperature although uracil deficiency was unchanged. A little but significant incorporation of adenine-8-¹⁴C into RNA still continued even after the incorporation of N-acetyl-³H-d-glucosamine into acid insoluble fraction of the cells terminated in the MW medium at 48°C. Both incorporations as well as increase of absorbance were slowed down in the presence of sodium succinate at 48°C. This mutant, ts42, was more sensitive to deoxycholate (DOC) than the parent strain. The restoration of colony forming ability after the temperature shift back from 48 to 37°C was suppressed by the addition of DOC to the medium. However, the cell became resistant to DOC when uracil was added to the medium prior to the temperature shift.     

Effect of p,p′ DDT on nitrogen fixation of white clover in volcanic soils of Chile

Summary The effect of increasing concentrations of p,p DDT on dry matter production and nitrogen fixation of white clover (Trifolium repens L.) growing in pots with volcanic soils of the southern region of Chile was studied. The chlorinated insecticides content of the soils ranged from low to very high (>20 mg/kg), being associated with the amount of insecticide applied. A detrimental effect of medium and high levels of DDT on growth, dry matter production and N-accumulation of clover was observed. The effects on nodulation and nitrogenase activity were smaller. These effects were higher when nutrient solutions were used instead of soil, because of the protective effects of soil colloids.

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Resumen Se estudió el efecto de concentraciones crecientes de p,p DDT sobre la producción y parámetros de fijación de N del trébol blanco (Trifolium repens L.) en condiciones de invernadero en suelos volcánicos de la zona sur de Chile. Los contenidos de insecticidas clorados de los suelos de la región son desde bajos hasta muy altos (>20 mg/kg), dependiendo de las aplicaciones. Se apreció un efecto depresivo del DDT a dosis medias y altas sobre el crecimiento, producción de materia seca y N-acumulado del trébol y un efecto menor sobre nodulación y actividad nitrogenásica. Estos efectos fueron más acentuados cuando se trabajó con soluciones nutritivas que con suelo, debido a la protección ejercida por los coloides del suelo.

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Résumé On a étudié l'effet de concentrations croissantes de p,p-DDT sur la production de matière sèche et sur la fixation de l'azote par le trèfle blanc (Trifolium repens L.) cultivé en serre sur des échantillons de sols volcaniques du sud du Chili. Dans les sols de cette région, la teneur en résidus d'insecticides chlorés varie entre <1 et >20 mg/kg suivant le niveau des prelévements. Le DDT inhibe la croissance, la production de matière sèche et l'accumulation d'azote par le trèfle. De plus, nous avons constaté un effet secondaire sur la nodulation et l'activité nitrogénasique. Ces effets sont plus marqués lorsqu'on utilise des solutions nutritives au lieu de terre, ce qui est dû à une protection éxercée par les colloides du sol.

     

Effect of Heavy Metals （Cd, Cu） on the Gametophytes of Laminaria japonica Aresch

Effects of various concentrations of two heavy metals, namely Cd and Cu, on gametophytes of Laminariajaponica Aresch were determined by recording morphological changes of gametophytes, determining pH values and the heavy metal content of the culture solution, calculating the germination rate of sporophytes, and observing heavy metal （Cd） distribution using a fluorescence microscope. The results showed that heavy metals damaged the gametophytes, and were even lethal, and that the higher the concentration of heavy metal ions, the greater the injury to gametophytes. Gametophytes could not survive in culture solutions containing more than 100 mg/L Cd and 50 mg/L Cu and were only able to survive in culture solution containing a mixture of Cd and Cu up to a concentration of 10 mg/L, which indicates that gametophytes have a higher tolerance to Cd than Cu and that multiple heavy metal ions in solution markedly aggravate the damage to gametophytes compared with individual heavy metal ions. With increases in the concentration of the heavy metal, the burgeoning rate of sporophytes decreased acutely, and solutions containing multiple heavy metal ions caused even more marked harm to sporophytes than solutions containing a single heavy metal ion, because most sporophytes died in mixed solutions. The pH value of the culture medium dropped immediately at the beginning （the first day） of treatment, increased over the following days, and then decreased again. The pH of culture media containing multiple heavy metal ions showed greater variation than media containing a single heavy metal ion, with the extent of the decrease in pH of culture media containing multiple ions being greatest during the last period of the experiment. With increases in the concentration of heavy metals, the capacity of gametophytes to accumulate these ions increased. The blue fluorescent light emitted by the Cd-and Cd-binding protein complex existing in gametophytes in media containing different concentrations of Cd showed clearly the distribution of the ion in gametophytes and the results obtained were consistent with distribution determined using other methods. All results of the present study showed that gametophytes of L. japonica play a remarkable role as heavy metal decontaminators, especially with regard to Cd.     

Effect of Methylglyoxal Modification of Human α-Crystallin on the Structure,Stability and Chaperone Function

α-Crystallin functions as a molecular chaperone and maintains transparency of eye lens by protecting other lens-proteins. Non-enzymatic glycation of α-crystallin by methylglyoxal, plays a crucial role on its chaperone function and structural stability. Our studies showed that methylglyoxal modification even in lower concentration caused significant decrease in chaperone function of α-crystallin as reflected both in thermal aggregation assay and enzyme refolding assay. Thermal denaturation studies showed drastic reduction of denaturation temperature with increase in the degree of modification. Thermodynamic stability studies by urea denaturation assay reflected a decrease of transition midpoint. Quantitatively we found that ΔG° of native α-crystallin decreased from 21.6 kJ/mol to 10.4 kJ/mol due to 72 h modification by 10 mM methylglyoxal. The surface hydrophobicity of α-crystallin after MG modification, was found to be decreased. Circular dichroism spectroscopy revealed conversion of β-sheet structure to random coil structure. Significant cross-linking was also observed due to methylglyoxal modification of human α-crystallin.     

Effect of protein-surfactant interactions on aggregation of β-lactoglobulin

The milk protein β-lactoglobulin (βLG) dominates the properties of whey aggregates in food products. Here we use spectroscopic and calorimetric techniques to elucidate how anionic, cationic and non-ionic surfactants interact with bovine βLG and modulate its heat-induced aggregation. Alkyl trimethyl ammonium chlorides (xTAC) strongly promote aggregation, while sodium alkyl sulfates (SxS) and alkyl maltopyranosides (xM) reduce aggregation. Sodium dodecyl sulfate (SDS) binds to non-aggregated βLG in several steps, but reduction of aggregation was associated with the first binding step, which occurs far below the critical micelle concentration. In contrast, micellar concentrations of xMs are required to reduce aggregation. The ranking order for reduction of aggregation (normalized to their tendency to self-associate) was C10-C12>C8>C14 for SxS and C8>C10>C12>C14>C16 for xM. xTAC promote aggregation in the same ranking order as xM reduce it. We conclude that SxS reduce aggregation by stabilizing the protein's ligand-bound state (the melting temperature t(m) increases by up to 10°C) and altering its charge potential. xM monomers also stabilize the protein's ligand-bound state (increasing t(m) up to 6°C) but in the absence of charged head groups this is not sufficient by itself to prevent aggregation. Although micelles of both anionic and non-ionic surfactants destabilize βLG, they also solubilize unfolded protein monomers, leaving them unavailable for protein-protein association and thus inhibiting aggregation. Cationic surfactants promote aggregation by a combination of destabilization and charge neutralization. The food compatible surfactant sodium dodecanoate also inhibited aggregation well below the cmc, suggesting that surfactants may be a practical way to modulate whey protein properties.     

Effect of uniconazole and limited water on growth,water relations,and mineral nutrition of “Lalandei” Pyracantha

Pyracantha (Pyracantha coccinea M. J. Roem. Lalandei) plants were treated with uniconazole at 0.5 mg ai container^–1 as a medium drench, 150 mg ai L^–1 as a foliar spray, or left untreated. Plants from all treatments were placed under three water regimes: drought acclimated, nonacclimated and later exposed to drought, or nonstressed. Acclimated plants were conditioned by seven 4-day stress cycles (water withheld), while nonacclimated were well watered prior to a single 4-day stress cycle at the same time as the seventh drought cycle of acclimated plants. Nonstressed plants were well watered throughout the study. Nonstressed plants had higher leaf water potentials and leaf conductances than acclimated and nonacclimated plants, and transpiration rates were higher in nonacclimated than acclimated plants. Uniconazole did not affect leaf water potential, leaf conductance, or transpiration rate. Acclimated plants had smaller leaf areas and leaf, stem, and root dry weights than nonacclimated or nonstressed plants. Plants drenched with uniconazole had the lowest stem and root dry weights. Acclimated plants also contained higher N concentrations than nonacclimated or nonstressed plants, and higher P concentrations than nonacclimated plants. Uniconazole medium drench treatments increased levels of Mn and P. Calcium concentration was increased in plants receiving either medium drench or foliar applications.     

Effect of 2-deoxyglucose, α-methylglucoside,and glucosamine on aflatoxin production by Aspergillus parasiticus

The effects of 2-deoxyglucose (2-DOG), -methylglucoside (-MG), and glucosamine (GA) on aflatoxin production by Aspergillus parasiticus were studied using conidia-initiated and replacement cultures. In conidia-initiated, 2-DOG, -MG, and GA supported varying amounts of growth when employed as sole carbon sources. In both conidia-initiated and replacement cultures, 2-DOG, but not -MG nor GA, as sole carbon sources support toxin formation. None of the compounds inhibited aflatoxin production when used in combination with glucose. It appears that neither 2-DOG, -MG, nor GA can be considered nonmetabolizable analogs of glucose in A. parasiticus.Abbreviations YES yeast extract sucrose - PMS peptone-mineral salts - 2-DOG L-deoxyglucose - -MG -methylglucoside - GA glucosamine     

Effect of weight and storage time of broiler breeders’ eggs on morphology and biochemical features of eggs,embryogenesis, hatchability,and chick quality

The transfer of hatchability results obtained under experimental conditions to the commercial ground with a positive financial effect proves the value and usefulness of these data. On the other hand, finding results on commercial processes of broiler breeders’ egg incubation in the literature is challenging. The presented study aimed to determine the effects of egg weight and storage time on the physical, biochemical characteristics of hatching eggs, embryogenesis and hatchability in Ross 308 broiler breeders. On the laying day, the eggs were divided into four weight groups: S – small eggs (57–61 g), M – medium eggs (62–66 g), L – large eggs (67–71 g), and XL – extra-large eggs (72–76 g). The eggs were then stored for 3, 7, 14, and 21 days under controlled conditions. As the egg storage time increased, a decrease in the yolk quality (lower index) was observed. The highest Haugh units were found in eggs from the S and M groups. The cholesterol content of the M, L, and XL groups was lower on days 7, 14, and 21 as compared to that of eggs only stored for 3 days. Egg weight loss during incubation decreased with an increase in the egg weight. An extension of the egg storage time caused an increase in the loss of egg weight. On the 14th and 18th days of hatching, an increase in the eggshell temperature was noted with an increase in the weight of the egg. The eggs stored for 7 days were characterised by the highest shell temperature on each day. The highest hatchability percentage was recorded for the M group. The hatchability rate decreased with the prolongation of the storage time, while the number of crippled chicks after hatching increased. The results confirmed that the increased weight of the eggs and prolonged storage time (14 and 21 days) increased the weight and decreased the length of the newly hatched chicks, respectively. Chicks from the heaviest eggs and those stored for 14 and 21 days showed poor results on the Pasgar score® test. The observations indicate the need to adopt various (of those available) methods to assess the quality of newly hatched chicks in hatcheries in order to produce high-quality broiler chickens. The results also indicate that prolonged egg storing beyond 14 days may affect the thyroid hormone economy during the hatching of chicks, especially in the XL group.     

Effect of Several Environmental Conditions on the “Thermal Death Rate” of Endospores of Aerobic, Thermophilic Bacteria

The composition of the recovery medium affected the apparent heat resistance of Bacillus stearothermophilus when the pH of the medium was 7.0 but not when the pH was 6.5. The rate of thermal death at 110 C was exponential. Deviations from exponential rates of thermal death during the initial phases of heating at 96 C were observed with endospores of B. coagulans under different conditions of sporulation. Additionally, the apparent heat resistance was influenced by the composition of the media used for sporulation and recovery and by the composition of the suspending menstruum. The presence of 0.001 m sorbic acid in the suspending menstruum at pH 7.0 and the temperature of incubation of the cultures after heating did not affect the apparent heat resistance of B. coagulans. Several explanations are discussed for the observed deviations from exponential thermal death rates and the effect of the environment on the apparent heat resistance of B. coagulans.     

Is the Effect of Aerobic Exercise on Cognition a Placebo Effect?

A number of studies and meta-analyses conclude that aerobic fitness (walking) interventions improve cognition. Such interventions typically compare improvements from these interventions to an active control group in which participants engage in non-aerobic activities (typically stretching and toning) for an equivalent amount of time. However, in the absence of a double-blind design, the presence of an active control group does not necessarily control for placebo effects; participants might expect different amounts of improvement for the treatment and control interventions [1]. We conducted a large survey to explore whether people expect greater cognitive benefits from an aerobic exercise intervention compared to a control intervention. If participants expect greater improvement following aerobic exercise, then the benefits of such interventions might be due in part to a placebo effect. In general, expectations did not differ between aerobic and non-aerobic interventions. If anything, some of the results suggest the opposite (e.g., respondents expected the control, non-aerobic intervention to yield bigger memory gains). These results provide the first evidence that cognitive improvements following aerobic fitness training are not due to differential expectations.     

Effect of changing mortality on the working life of American men and women, 1970–1990

Abstract

The mortality patterns of men and women of working age, in terms of the major causes of death, have changed over the past three decades. This study assesses the extent to which mortality among persons of working age represents an economic loss to society. This economic loss is measured by the per capita loss of productive working life, defined as the number of years, on the average, a person can expect to be an active member of the labor force. Causes of death affecting primarily older Americans (heart disease, cancer, stroke) had a relatively small and declining impact on the working lives of men and women. Major causes of death affecting the young (motor vehicle accidents, homicide, AIDS), although accounting for fewer deaths, were responsible for many more years of lost productivity. Gender and socioeconomic differentials in mortality suggest that different strategies are necessary for future reductions in lost work‐years.     

Effect of α-actinin on actin viscosity

As determined by analytical ultracentrifugation, purified α-actinin does not form stable complexes with G-actin, myosin, tropomyosin, or the tropomyosintroponin complex. However, α-actinin forms a stable complex with F-actin polymerized either in 100 mM KC1 or in 2mM MgCl₂ without KCl. Viscosity studies confirm that α-actinin interacts as strongly with Mg²⁺-polymerized actin as it does with KCl-polymerized actin.     

Synergistic Effect of α-Hexachlorocy-clohexane with Pyrethrins

The more potent inhibitory activity against angiotensin-converting enzyme (ACE) was excised from a glyceraldehyde-3-phosphate dehydrogenase (GAPDH) preparation of Bacillus stearothermophilus by heating at 120°C in 1 m AcOH–20mm HCI, as compared with GAPDH preparations of yeast and pig. Sufficient excision of B. stearothermophilus ACE inhibitors required a longer proteolysis time of 60 min. Two inhibitors were then purified by gel-permeation and reverse-phase chromatog-raphies. One of the B. stearothermophilus ACE inhibitors, BG-1, was the GAPDH peptide 68–77 (Gly-Lys-Glu-Ile-Ile-Val-Lys-Ala-Glu-Arg, IC₅₀: 32 μm). Another inhibitor, BG-2 (Gly-Lys-Met-Val-Lys-Val-Val-Ser-Trp-Tyr, IC₅₀: 6 μM), corresponded to GAPDH peptide 304–313. These sequences were quite different from those of vertebrate GAPDH peptides and the venom peptide family with ACE inhibitory activity. BG-2 was found to be a non-competitive type inhibitor, differing from many natural peptide inhibitors. Thus, B. stearothermophilus GAPDH seemed to be a good source of new type ACE inhibitors, in addition to the advantages due to its thermophilic property.     

Effect of humidity on the disintegrant property of α-cellulose,Part II: A technical note

Conclusion  The summary is that the high humidity impaired the disintegrant property of α-cellulose in all 3 tablets tested. Tablets of aspirin, which is the more hygroscopic drug, were also more sensitive to the humidity effect, while tablets of chloroquine phosphate, which is a water-soluble drug, were the least sensitive to the humidity effect. The results permit the conclusion that moisture uptake with subsequent gelling of the α-cellulose is the mechanism of impairment of its disintegrant property. The tablets would not normally be stored under an RH as high as 100%, nevertheless, the results of the accelerated stability study have underscored the need to protect tablets containing α-cellulose as disintegrant from moisture. Published: August 10, 2005     

Effect of Oxidation of αA- and αB-Crystallins on their Structure, Oligomerization and Chaperone Function

The purpose of this study was to investigate the effect of metal-catalyzed oxidation by H₂O₂ on the structure, oligomerization, and chaperone function of αA- and αB-crystallins. Recombinant αA-and αB-crystallins were prepared by expressing them in E. coli and purifying by size-exclusion chromatography. They were incubated with 1.5 mM H₂O₂ and 0.1 mM FeCl₃ at 37 ^∘C for 24 hrs and the reaction was stopped by adding catalase. Structural changes due to oxidation were ascertained by circular dichroism (CD) measurements and chaperone activity was assayed with alcohol dehydrogenase (ADH) and insulin as target proteins. The oligomeric nature of the oxidized proteins was assessed by molecular sieve HPLC. The secondary structure of the oxidized αA- and αB-crystallins has been substantially altered due to significant increase in random coils, in addition to decrease in β-sheet or α-helix contents. The tertiary structure also showed significant changes indicative of different mode of folding of the secondary structural elements. Chaperone function was significantly compromised as supported by nearly 50% loss in chaperone activity. Oxidation also resulted in the formation of higher molecular weight (HMW) proteins as well as lower molecular weight (LMW) proteins. Thus, oxidation leads to disintegration of the oligomeric structure of αA- and αB-crystallins. Chaperone activity of the HMW fraction is normal whereas the LMW fraction lacks any chaperone activity. So, it appears that the formation of the LMW proteins is the primary cause of the chaperone activity loss due to oxidation.