Striking reduction of amyloid plaque burden in an Alzheimer's mouse model after chronic administration of carmustine

BACKGROUND: Currently available therapies for Alzheimer's disease (AD) do not treat the underlying cause of AD. Anecdotal observations in nursing homes from multiple studies strongly suggest an inverse relationship between cancer and AD. Therefore, we reasoned that oncology drugs may be effective against AD. METHODS: We screened a library of all the FDA-approved oncology drugs and identified bis-chloroethylnitrosourea (BCNU or carmustine) as an effective amyloid beta (Aβ) reducing compound. To quantify Aβ levels, Chinese hamster ovary (CHO) cells stably expressing amyloid precursor protein 751WT (APP751WT) called 7WD10 cells were exposed to different concentrations of BCNU for 48 hours and the conditioned media were collected. To detect Aβ the conditioned media were immunoprecipitated with Ab9 antibody and subjected to immunoblot detection. Amyloid plaques were quantified in the brains of a mouse model of AD after chronic exposure to BCNU by thoflavin S staining. RESULTS: BCNU decreased normalized levels of Aβ starting from 5 μM by 39% (P < 0.05), 10 μM by 51% (P < 0.01) and 20 μM by 63% (P < 0.01) in CHO cells compared to a control group treated with butyl amine, a structural derivative of BCNU. Interestingly, soluble amyloid precursor protein α (sAPPα) levels were increased to 167% (P < 0.01) at 0.5 μM, 186% (P < 0.05) at 1 μM, 204% (P < 0.01) at 5 μM and 152% (P < 0.05) at 10 μM compared to untreated cells. We also tested the effects of 12 structural derivatives of BCNU on Aβ levels, but none of them were as potent as BCNU. BCNU treatment at 5 μM led to an accumulation of immature APP at the cell surface resulting in an increased ratio of surface to total APP by 184% for immature APP, but no change in mature APP. It is also remarkable that BCNU reduced Aβ generation independent of secretases which were not altered up to 40 μM. Interestingly, levels of transforming growth factor beta (TGFβ) were increased at 5 μM (43%, P < 0.05), 10 μM (73%, P < 0.01) and 20 μM (92%, P < 0.001). Most significantly, cell culture results were confirmed in vivo after chronic administration of BCNU at 0.5 mg/kg which led to the reduction of Aβ40 by 75% and amyloid plaque burden by 81%. Conversely, the levels of sAPPα were increased by 45%. CONCLUSIONS: BCNU reduces Aβ generation and plaque burden at non-toxic concentrations possibly through altered intracellular trafficking and processing of APP. Taken together these data provided unequivocal evidence that BCNU is a potent secretase-sparing anti-Aβ drug. See related commentary article here http://www.biomedcentral.com/1741-7015/11/8

An Access Protection Solution for Heavy Load Unfairness in DQDB

This paper discusses the unfairness issue arising in a 802.6 DQDB network at high loads-- when the traffic demand to a bus exceeds the capacity of that bus. As per the 802.6 protocol, at heavy loads, the end nodes along a bus experience longer delays than the other nodes. The origin and remedy of this heavy load unfairness is discussed. An access control scheme is proposed as a solution. The comparison of the proposed scheme with 802.6 protocol is presented. The simulation results and performance characteristics are discussed under several types of loads. With symmetric load conditions under the proposed scheme, all active nodes along a bus experience almost the same access delay and packet loss characteristics. Performance under several other load condition are also found to be satisfactory

A Protocol for Dynamic Assessment of Network Topology in DQDB MANs

The 802.6 protocol of DQDB MANs aims to maintain a distributed queue for network access and yet inherits access unfairness. In this paper, the DANT protocol is proposed to provide head-end nodes as well as each active node in a DQDB network with real time information about the active node population, the intermodal distance, the position of each node along what bus and the length of a node\u27s downstream bus segment. DANT\u27s current implementation introduces an overhead of 5 bits per slot but alternative implementations which retain the current slot structure of 802.6 and implement the DANT protocol through the use of periodically issued control slots are possible. Results presented in {3,4,5} show that DANT holds much promise for its use in the context of new load balancing and access protection schemes for DQDB MANs

The 3-Tier Structured Access Protocol to Control Unfairness in DQDB MANs

This paper addresses the unfairness problem appearing in 802.6-based DQDB MANs. Traffic load demand is characterized as low (below 0.4 of the channel capacity), normal (from 0.4 to 0.9 of the channel capacity) or heavy (greater than 0.9 of the channel capacity). At low loads the 802.6 protocol is acceptably fair. At normal loads, however, the protocol performance is markedly unfair. The unfairness is related to the latency in transporting a request. At heavy loads the unfairness is both latency-related and flooding-related. In this paper, both types of unfairness are carefully analyzed. As a control measure, a 3-Tier Structured Access protocol is proposed. At low loads the 802.6 performance is retained. For normal loads, extra slots are allowed based on predicted demand. At heavy loads access protection is applied. A Dynamic Assessment of Network Topology (DANT) protocol is also presented. The DANT dynamically maintains the additional information required for the implementation of the 3-tier structure. The proposed fair access protocol is studied under different load types and traffic demand. A tuning scheme is proposed to optimized the performance for a particular load environment in real time. The proposed protocol has the potential for dynamic bandwidth allocation and yields satisfactory performance

An experimental investigation of flow fields near a liquid-liquid moving contact line

A moving contact line occurs at the intersection of an interface formed between two immiscible liquids and a solid. According to viscous theory, the flow is entirely governed by just two parameters, the viscosity ratio, $\lambda$, and the dynamic contact angle, $\theta_d$. While a majority of experimental studies on moving contact lines involve determining the relationship between the dynamic contact angle and capillary number, a few studies have focused on measuring the flow field in the vicinity of the contact line involving liquid-gas interfaces. However, none of the studies have considered liquid-liquid moving contact lines and the present study fills this vital gap. Using particle image velocimetry, we simultaneously measure the velocity field in both the liquid phases using refractive index matching techniques. The flow field obtained from experiments in both phases is directly compared against theoretical models. Measurement of interface speed reveals that material points rapidly slow down as the contact line is approached. Further, the experiments also reveal the presence of slip along the moving wall in the vicinity of the contact line suggesting a clear mechanism for how the singularity is arrested at the contact line.Comment: 15 pages, 13 figures, based on work presented at the 11th Conference of the International Marangoni Association, Bordeaux, France, June 202

Genetic variability studies in amaranthus (Amaranthus spp.)

An investigation was carried out to estimate the nature and extent of genetic variability​ ​among twenty Amaranthus genotypes (Amaranthus spp.) under a randomized block designduring the year 2019-20. The phenotypic coefficient of variation was higher than the genotypic​ ​coefficient of variation for all the traits. High genotypic coefficient of variation (GCV) and​ ​phenotypic coefficient variation (PCV) was observed for leaf area, leaf area index, leaf area​ ​duration, AGR, dry weight of leaf per plant, specific leaf weight, speed of germination,​ ​chlorophyll content and ascorbic acid (vitamin C). Moderate GCV and PCV were observed​ ​for leaf length, leaf width, petiole length, dry weight of stem per plant, leaf: stem ratio and​ ​foliage yield per plant. The high estimates of heritability coupled with higher values of genetic​ ​advance as per cent mean (GAM) were observed for the parameters like test weight, speed of​ ​germination, germination percentage, seedling dry matter, seedling vigour index-1, seedling​ ​vigour index-2, plant height, leaf length, leaf width, leaf area, leaf area index, leaf area​ ​duration, AGR, specific leaf weight, stem weight per plot, dry weight of leaf, dry weight of​ ​stem, leaf: stem ratio, foliage yield per plant, chlorophyll, ascorbic acid and beta- carotene​ ​content which indicates the predominance of additive gene action. Arka Arunima,​ ​Chikmagalur local, IC-551486, IC-551494 and IC-551466 recorded high foliage yield per​ ​plot and these can be utilized in further breeding programmes

Characterization and evaluation of morphological and yield traits of tamarind genotypes

The evaluation of morphological and yield traits of tamarind genotypes was carried out during 2017-18 at Forest Research Station, Govinkovi, Honnali taluk, Davangere district. The experiment was laid out in randomized complete block design with 16 genotypes and three replications. Trees were 14-years-old and of grafted origin. All the morphological and yield traits showed significant difference among the selected genotypes indicating the presence of adequate variations. The genotypes recorded morphological variation in terms of tree shape (semi-circle to irregular shape), foliage arrangement (dense to sparse), flowering time (early, mid and late), stem colour (dark brown, brown and light brown), bud colour (greenish white, pink, dark pink), petal colour (yellow and pale yellow), pod colour (greyish brown, brown, light brown and dark brown), pulp colour (light brown, brown and reddish brown), pod shape (straight, slightly curved, curved and deeply curved) and pod size (very big, big, medium and small). The analysis of variance revealed significant difference with respect to tree height, stem girth, pod traits, pod yield per tree (K-9 : 12.80 kg), number of pods per tree (NTI-52 : 989.07) and pulp per cent (K-9 : 48.87). Among the 16 genotypes, the genotype K-9 was found superior with respect to pod size, pod weight, pulp weight and pod yield per tree. Genotype K-9 was found promising and due to perennial in nature further evaluation is required for stability

Phenotypic trait association studies in brinjal upon drought stress

Eggplant is popularly known as poor man’s vegetable. With respect to present situation of climatic challenges, fruit yield of eggplant is reduced due to drought or moisture stresses. In view of this condition, an experiment was aimed to study character association between yield and yield components in eggplant. The resultant outcome from correlation analysis computed among nine eggplant characters indicated that traits like plant height and total plant length at harvesting, fruit length and number of fruits per plant significantly correlated with fruit yield per plant. Whereas, traits like plant height and total plant length observed at harvesting stage, number of days for flower initiation, number of primary branches, fruit length and average fruit weight were significantly associated with fruit yield per plant under moisture stressed condition

Dissection of genetic diversity present in eggplant populations using simple sequence repeat markers

Eggplant (Solanum melongena L.) is the third most important solanaceous vegetable and most diversified within species spread across the world-geographical area. A study was conducted to assess the genetic diversity among the selected fifty-four eggplant genotypes (sub-categorized into five sub-population) using twenty-three SSR markers. The Analysis of Molecular Variance among the five sub-population of eggplant revealed the existence of 90.67% variation within populations and 9.34% variation among populations. The SSR markers analysis revealed important locus-wise information like mean Observed-Heterozygosity (0.216), mean Expected-Heterozygosity (0.496), Shannon’s Information Index (0.879), mean number of different alleles (3.209), mean number of effective alleles (2.535), Fixation-Index (0.649). Further, Phylogenetic-analysis clearly categorize genetically distinct individuals in which the most diversified clusters was cluster-1 (C1) out of total of five clusters and especially, wild cultivars were grouped into cluster-5 (C5). The obtained results can be used in eggplant breeding and germplasm conservation in a resourceful manner

Genetic Diversity Analysis and Barcoding in Tuberose (Polianthes tuberosa L.) Cultivars Using RAPD and ISSR Markers

Tuberose is one of the most important bulbous ornamentals grown commercially for loose as well as cut flowers. RAPD and ISSR markers used in the study revealed 53% and 73% polymorphism, respectively, among ten tuberose varieties. Polymorphic Information Content (PIC) and Resolving Power (RP) for RAPD varied from 0.35 - 0.46 and 0.8 - 3.6, respectively, and that for ISSR was 0.36 - 0.49 and 0.91 - 4.55, respectively. The dendrogram (UPGMA), based on Jaccards co-efficient as similarity index for RAPD and ISSR, grouped ten varieties into two major clusters, and, combined RAPD-ISSR cluster analysis formed three major clusters based on their genetic relatedness/variation. PCA revealed that the spatial arrangement of these 10 cultivars was congruent with dendrogram analysis. Mantel's test indicated very good correlation, with r = 0.86 for combination of ISSR and RAPD-ISSR. To facilitate identification of tuberose cultivars, a cultivar identification diagram (CID) was developed in which seven ISSR loci could differentiate all the ten cultivars used in the study. Barcodes were developed for five cultivars released by IIHR using 57 polymorphic loci generated by 11 ISSR primers. The size of these loci ranged from 252bp to 2.2kb. These barcodes can be used as a standard reference source for quick identification of cultivars