siRNA against presenilin 1 (PS1) down regulates amyloid β42 production in IMR-32 cells

Background  

One of the pathological hallmarks of Alzheimer's disease (AD) is the deposition of the ~4 kDa amyloid β protein (Aβ) within lesions known as senile plaques. Aβ is also deposited in the walls of cerebral blood vessels in many cases of AD. A substantial proportion of the Aβ that accumulates in the AD brain is deposited as Amyloid, which is highly insoluble, proteinaceous material with a β-pleated-sheet conformation and deposited extracellularly in the form of 5-10 nm wide straight fibrils. As γ-secretase catalyzes the final cleavage that releases the Aβ42 or 40 from amyloid β -protein precursor (APP), therefore, it is a potential therapeutic target for the treatment of AD. γ-Secretase cleavage is performed by a high molecular weight protein complex containing presenilins (PSs), nicastrin, Aph-1 and Pen-2. Previous studies have demonstrated that the presenilins (PS1 and PS2) are critical components of a large enzyme complex that performs γ-secretase cleavage.     

Comparison of techniques for the measurement of skin temperature during exercise in a hot,humid environment

Exercising or working in a hot, humid environment can results in the onset of heat-related illness when an individual''s temperature is not carefully monitored. The purpose of the present study was to compare three techniques (data loggers, thermal imaging, and wired electrodes) for the measurement of peripheral (bicep) and central (abdominal) skin temperature. Young men and women (N = 30) were recruited to complete the present study. The three skin temperature measurements were made at 0 and every 10-min during 40-min (60% VO₂max) of cycling in a hot (39±2°C), humid (45±5% RH) environment. Data was statistically analyzed using the Bland-Altman method and correlation analysis. For abdominal skin temperature, the Bland-Altman limits of agreement indicated that data loggers (1.5) were a better index of wired than was thermal imaging (3.5), For the bicep skin temperature the limits of agreement was similar between data loggers (1.9) and thermal (1.9), suggesting the both were suitable measurements. We also found that when skin temperature exceeded 35°C, we observed progressively better prediction between data loggers, thermal imaging, and wired skin sensors. This report describes the potential for the use of data loggers and thermal imaging to be used as alternative measures of skin temperature in exercising, human subjects.     

Antiangiogenic properties of Koetjapic acid, a natural triterpene isolated from Sandoricum koetjaoe Merr

Background

Angiogenesis, the formation of new blood vessels, has become an important target in cancer therapy. Angiogenesis plays an important role in tumor growth and metastasis. Koetjapic acid (KA) is a seco-A-ring oleanene triterpene isolated from S. koetjape. The solvent extract of this plant species was shown previously to have strong antiangiogenic activity; however the active ingredient(s) that conferred the biological activity and the mode of action was not established. Given the high concentration of KA in S. koetjape, an attempt has been made in this study to investigate the antiangiogenic properties of KA.

Results

Treatment with 10-50 μg/ml KA resulted in dose dependent inhibition of new blood vessels growth in ex vivo rat aortic ring assay. KA was found to be non-cytotoxic against HUVECs with IC₅₀ 40.97 ± 0.37 μg/ml. KA inhibited major angiogenesis process steps, endothelial cell migration and differentiation as well as VEGF expression.

Conclusions

The non-cytotoxic compound, KA, may be a potent antiangiogenic agent; its activity may be attributed to inhibition of endothelial cells migration and differentiation as well VEGF suppression.     

PAHs,OCPs and PCBs in sediments from three catchments in Durban,South Africa

Polycyclic aromatic hydrocarbons (PAHs), organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) were analysed from sediment samples collected in 2012 from rivers, surface runoff canals and estuaries in three highly urbanised catchments in durban, KwaZulu-Natal, South Africa. PAHs were ubiquitous, at concentrations between 36–6 800 ng g^?1 dry mass (dm). Congener ratio diagnosis suggests the PAHs were derived predominantly from pyrogenic sources. Four OCPs and/or their metabolites were detected at varying frequencies and concentrations. Of these, dichlorodiphenyltrichloroethane (ddT) and metabolites were most frequently detected and were at a high concentration in sediment in some systems. Toxaphene was detected at a high concentration at some sites. The total PCB concentration varied widely, from below the method detection limit to 110 ng g^?1 (dm). Based on the comparison of chemical concentrations to international sediment quality guidelines, PAH, OCP and PCB concentrations in most sediment samples posed a low risk to sediment-dwelling organisms. However, in some instances the risk was moderate or high. It is recommended that these compounds be monitored more frequently and comprehensively in aquatic ecosystems to better understand the ecological and human health implications.     

Ecological factors affect the level and scaling of avian BMR

The basal rate of metabolism (BMR) in 533 species of birds, when examined with ANCOVA, principally correlates with body mass, most of the residual variation correlating with food habits, climate, habitat, a volant or flightless condition, use or not of torpor, and a highland or lowland distribution. Avian BMR also correlates with migratory habits, if climate and a montane distribution is excluded from the analysis, and with an occurrence on small islands if a flightless condition and migration are excluded. Residual variation correlates with membership in avian orders and families principally because these groups are behaviorally and ecologically distinctive. However, the distinction between passerines and other birds remains a significant correlate of avian BMR, even after six ecological factors are included, with other birds having BMRs that averaged 74% of the passerine mean. This combination of factors accounts for 97.7% of the variation in avian BMR. Yet, migratory species that belong to Anseriformes, Charadriiformes, Pelecaniformes, and Procellariiformes and breed in temperate or polar environments have mass-independent basal rates equal to those found in passerines. In contrast, penguins belong to an order of polar, aquatic birds that have basal rates lower than passerines because their flightless condition depresses basal rate. Passerines dominate temperate, terrestrial environments and the four orders of aquatic birds dominate temperate and polar aquatic environments because their high BMRs facilitate reproduction and migration. The low BMRs of tropical passerines may reflect a sedentary lifestyle as much as a life in a tropical climate. Birds have BMRs that are 30-40% greater than mammals because of the commitment of birds to an expensive and expansive form of flight.     

Nest desertion by a cowbird host: an antiparasite behavior or a response to egg loss?

Natural selection can favor songbirds that desert nests containingeggs of the parasitic brown-headed cowbird (Molothrus ater).However, the high variability in desertion of parasitized nestswithin species is perplexing in light of the typically highcosts of parasitism. Because nest desertion can also be a responseto partial clutch predation, we first asked if Bell's vireos(Vireo bellii) deserted nests in response to the presence ofcowbird eggs (antiparasite response hypothesis) or to egg removalby predators and female cowbirds (egg predation hypothesis).Second, we asked whether variation in nest desertion was dueto intrinsic differences among individuals or to variation innest contents. We monitored a large number of nests (n = 494)and performed a clutch manipulation experiment to test thesehypotheses. The number of vireo eggs that remained in a nestwas a strong predictor of desertion both within and among pairs.Neither the presence of a single cowbird egg, which leads tonest failure for this host, nor the number of cowbird eggs receivedin a vireo nest influenced nest desertion. Furthermore, vireosdid not desert experimental nests when we immediately exchangedcowbird eggs for vireo eggs but deserted if we removed vireoeggs and replaced them with cowbird eggs the following morning.Desertion of parasitized nests by Bell's vireos can be almostentirely explained as a response to partial or complete clutchloss and does not appear to have been altered by selection frombrood parasitism.     

An investigation of genome-wide studies reported susceptibility loci for ulcerative colitis shows limited replication in north Indians

Genome-Wide Association studies (GWAS) of both Crohn's Disease (CD) and Ulcerative Colitis (UC) have unearthed over 40 risk conferring variants. Recently, a meta-analysis on UC revealed several loci, most of which were either previously associated with UC or CD susceptibility in populations of European origin. In this study, we attempted to replicate these findings in an ethnically distinct north Indian UC cohort. 648 UC cases and 850 controls were genotyped using Infinium Human 660W-quad. Out of 59 meta-analysis index SNPs, six were not in the SNP array used in the study. Of the remaining 53 SNPs, four were found monomorphic. Association (p<0.05) at 25 SNPs was observed, of which 15 were CD specific. Only five SNPs namely rs2395185 (HLA-DRA), rs3024505 (IL10), rs6426833 (RNF186), rs3763313 (BTNL2) and rs2066843 (NOD2) retained significance after Bonferroni correction. These results (i) reveal limited replication of Caucasian based meta-analysis results; (ii) reiterate overlapping molecular mechanism(s) in UC and CD; (iii) indicate differences in genetic architecture between populations; and (iv) suggest that resources such as HapMap need to be extended to cover diverse ethnic populations. They also suggest a systematic GWAS in this terrain may be insightful for identifying population specific IBD risk conferring loci and thus enable cross-ethnicity fine mapping of disease loci.     

The taste of polycose in hamsters

Hamsters show a preference for Polycose, a mixture of starch-derived glucose polymers, that is as strong as their preference for sucrose. However, in the hamster, taste aversions to Polycose may be less easily acquired than taste aversions to sucrose and the qualitative aspects of Polycose are unknown in this species. In order to examine the taste of Polycose in the hamster, we utilized a taste-aversion protocol with two conditioning trials. Animals were trained to avoid one of three different conditioning stimuli: 50 mM sucrose, 100 mM Polycose and a mixture of 50 mM sucrose with 100 mM Polycose. Control animals were conditioned with deionized water. After the second conditioning trial, generalization testing began for the three conditioning stimuli plus 3 mM citric acid, 300 mM KCI and 30 mM NaCl. The results showed that aversions to Polycose, sucrose or the Polycose/sucrose mixture cross- generalized, demonstrating that Polycose and sucrose share a common taste percept in the hamster. None of the aversions generalized to NaCl, citric acid or KCI. In addition, comparisons among the patterns of taste generalizations indicated that the tastes of Polycose and sucrose also had distinct qualitative components. Finally, although the taste of 100 mM Polycose was more salient than the taste of 50 mM sucrose, the taste of sucrose could still be detected in a mixture with Polycose.      

Palatability and efficacy to possums and rats of pest control baits containing bird repellents

Repellents used to reduce by-kill of birds during pest control must not compromise acceptance by target species. Two repellents combined, anthraquinone (AQ; 0.4 g kg^?1) and d-pulegone (DP; 1.0) did not reduce the palatability of blue-coloured carrot baits to laboratory rats (Rattus norvegicus); nor did DP (2.0). Green-coloured carrot baits coated with AQ, DP or AQ + DP were taken from bait stations by wild possums (Trichosurus vulpecula) and rats. Toxic (1080) bait coated with AQ (0.4) and peanut oil (0.1) had reduced palatability but was accepted by laboratory rats. However, laboratory rats did not consume enough baits coated with AQ and bacon, peanut butter, cinnamon or DP to be killed. Anthraquinone (0.4 or 0.8) plus cinnamon and DP (0.5) did not affect palatability or lethality to captive ship rats (R. rattus) or possums. Anthraquinone and DP as surface coatings on baits are therefore acceptable to possums and possibly rats, at concentrations that deter some bird species.     

Isolation of zoosporogenous actinomycetes from desert soils

We have undertaken a study to estimate the species diversity of zoosporogenous actinomycetes that can be isolated from an arid environment. The study site encompassed an area of approximately 22 000 square kilometers of the Mojave Desert along the California-Nevada border. A series of 29 soil samples was collected along two intersecting transects of approximately 190 and 240 km which traversed a number of distinct ecosystems. A₀ horizon soils were collected from the rhizosphere of the predominant vegetation at each sampling site and screened for the target genera using selective isolation techniques: chemoattraction (xylose and -collidine) and baiting with hair. Following incubation of primary isolation plates for 28 days at 28°C, all colonies that exhibited filamentous growth, presence of sporangia and/or motile spores upon direct microscopic observation (450 and 1000×) were further characterized by fatty acid analysis (FAME). Most of the isolates fell into three broad clusters that roughly correlated with presumptive genus assignments. Individual isolates could be assigned to 226 FAME biotypes based on chromatographic similarity (85%). The dominant species (514/826 isolates) belong to a previously undescribed taxon that morphologically resemblesGeodermatophilus but possesses unique FAME profiles that include at least three novel lipids. The remainder of the isolates were species ofActinoplanes, indeterminate species or vagrant isolates ofStreptomyces.