Triple-transgenic model of Alzheimer's disease with plaques and tangles: intracellular Abeta and synaptic dysfunction

The neuropathological correlates of Alzheimer's disease (AD) include amyloid-beta (Abeta) plaques and neurofibrillary tangles. To study the interaction between Abeta and tau and their effect on synaptic function, we derived a triple-transgenic model (3xTg-AD) harboring PS1(M146V), APP(Swe), and tau(P301L) transgenes. Rather than crossing independent lines, we microinjected two transgenes into single-cell embryos from homozygous PS1(M146V) knockin mice, generating mice with the same genetic background. 3xTg-AD mice progressively develop plaques and tangles. Synaptic dysfunction, including LTP deficits, manifests in an age-related manner, but before plaque and tangle pathology. Deficits in long-term synaptic plasticity correlate with the accumulation of intraneuronal Abeta. These studies suggest a novel pathogenic role for intraneuronal Abeta with regards to synaptic plasticity. The recapitulation of salient features of AD in these mice clarifies the relationships between Abeta, synaptic dysfunction, and tangles and provides a valuable model for evaluating potential AD therapeutics as the impact on both lesions can be assessed.     

A novel strategy of oxygen restriction by some diazotrophic enteric bacteria

Protection of nitrogenase against oxygen inactivation in diazotrophs involves numerous strategies. Glutathione is known to play an important role in scavenging oxyradicals in many living systems. The involvement of glutathione (reduced) (GSH), glutathione peroxidase (GPX) and glutathione reductase (GR) in the protection of nitrogenase in free living diazotrophs is reported here for the first time. Reduced glutathione content and the activity of glutathione peroxidase and glutathione reductase increased with increase in oxygen concentration under nitrogen fixing conditions but decreased under anaerobic and nitrogenase repressed conditions. This correlation is used to postulate a protecting role for GSH-GPX-GR system against oxygen inactivation of nitrogenase.     

Two flavonoids from tephrosia purpurea

Purpurenone, a new β-hydroxychalcone; (+)-purpurin, a diastereoisomer of(?)purpurin; dehydroisoderricin, and (?)-maackiain have been isolated from the roots of Tephrosio purpurea in addition to the earlier reported flavonoids [1, 2]. Pseudosemiglabrin was obtained in admixture with (?)-semiglabrin     

Cytogenetic behavior of spore killer genes in neurospora

Crosses heterozygous and homozygous for Sk-1, Sk-2 and Sk-3 were examined by light microscopy. All three Spore killers behave similarly. In heterozygous killer x sensitive crosses, meiosis and ascospore development are normal until after the second postmeiotic mitosis when four of the eight ascospores in each ascus stop developing and degenerate. The four surviving ascospores carry the killer. Death of sensitives thus occurs only after killer and sensitive alleles, Sk^K and Sk^S, have segregated into separate ascospores. Homozygous killer x killer crosses do not show such a pattern of degeneration. Either all ascospores are normal or, if some fail to mature, they do not resemble the degenerating sensitive ascospores in heterozygous asci.——With Sk-2, it was shown that Sk^S nuclei do not abort when both Sk^K and Sk^S are present in the same ascospore. Mutants affecting ascus development were used to obtain large ascospores enclosing both Sk^K and Sk^S meiotic products in a common cytoplasm. Sk^S nuclei do not then undergo the degeneration that would be seen if they were sequestered into separate ascospores, and viable Sk^S progeny are recovered in undiminished numbers when the mixed multinucleate large ascospores are germinated. In a four-spored mutant, where each ascospore encloses a single nucleus following meiosis, degeneration of Sk^S ascospores nevertheless occurs, even though the third nuclear division is omitted. Cycloheximide and temperature treatments do not affect the expression of Sk^K.     

Heavy meromyosin labeling of intermediate filaments in cultured connective tissue cells

Mild treatment with trypsin causes a radical change in the heavy meromyosin (HMM) binding properties of intermediate filaments in glycerinated, myosin-extracted cultured chick embryo connective tissue cells. In non-trypsin-treated cells, HMM labeling of filaments was often indistinct and variable in its distribution. By contrast, in cells treated with trypsin (under conditions which allowed most intermediate filaments to survive), virtually all filaments, including those of intermediate size, decorated with HMM to give distinct arrowhead patterns. We suggest that most intermediate filaments in such cells contain a core of F-actin masked by trypsin-labile accessory proteins.     

Blood groups and ABH saliva secretion in Koya Dora and Konda Kammara tribes of Andhra Pradesh

The present paper reports the distribution of blood groups and ABH saliva secretion in two Andhra tribal populations: the Koya Dora and the Konda Kammara. 100 Koya Dora and nearly 110 Konda Kammara adults of both sexes were tested for A1A2BO, MN, Rh (CcDEe) blood groups and ABH saliva secretion. The gene frequencies for A1A2BO, MN and ABH and the gene as well as chromosome frequencies for Rh (CcDEe) systems were calculated. Koya Doras show a higher incidence of A gene than B gene, while the reverse trend is seen in Konda Kammaras. Both the tribes show a high M gene frequency. No Rh(D) negative individual was found in Koya Doras, while 4.59% of Konda Kammaras are Rh(D) negative. The chromosomes CDE, CdE, cDe, cdE, Cde and cde are absent in Koya Doras, while only the four chromosomes CDE, CdE, cDe and cdE are absent in Konda Kammaras. The chromosome CDe shows the highest frequency in both the tribes. The frequency of secretors is, as usual, higher than that of nonsecretors in both the tribes. The intergroup variation between the two tribes is not statistically significant for MN, Rh (CcDEe) and ABH systems, while the difference is significant for the A1A2BO blood groups. Suitable comparisons have also been made with all the other available data from Andhra Pradesh tribal populations with respect to different systems studied. Finally Fi estimates have been calculated after Harpending et al. (1973) and Workman et al. (1974) for Koya Doras and Konda Kammaras to assess their degree of endogamy, considering the codominant systems studied, which suggest that Koya Doras are relatively more isolated than Konda Kammaras.     

From LC-MS/MS metabolomics profiling of Kanchanara Guggulu to molecular docking and dynamics simulation of quercetin pentaacetate with aldose reductase

Kanchanara Guggulu (KG) is an important traditional medicine that is prescribed by the Ayurveda physicians for the treatment of swellings in various organs such as the thyroid, and lymph nodes. High-resolution mass-spectrometry-based metabolomics found metabolites in KG. LC-MS/MS-based metabolomics analysis of KG identified 2,579 compounds including quercetin and kaempferol derivatives. The molecular docking and dynamics analysis of quercetin pentaacetate with aldose reductase is documented for further consideration in drug discovery.     

Optical analysis of RE3+ (RE = Eu,Tb):MgLa2V2O9 nano-phosphors

Red and green rare-earth ion (RE³⁺) (RE = Eu, Tb):MgLa₂V₂O₉ micro-powder phosphors were produced utilizing a standard solid-state chemical process. The X-ray diffraction examination performed on the phosphors showed that they were crystalline and had a monoclinic structure. The particles grouped together, as shown in the scanning electron microscopy (SEM) images. Powder phosphors were examined using a variety of spectroscopic techniques, including photoluminescence (PL), Fourier-transform infrared, and energy dispersive X-ray spectroscopy. Brilliant red emission at 615 nm (⁵D₀ → ⁷F₂) having an excitation wavelength (λ_exci) of 396 nm (⁷F₀ → ⁵L₆) and green emission at 545 nm (⁵D₄ → ⁷F₅) having an λ_exci = 316 nm (⁵D₄ → ⁷F₂) have both been seen in the emission spectra of Tb³⁺:MgLa₂V₂O₉ nano-phosphors. The emission mechanism that is raised in Eu³⁺:MgLa₂V₂O₉ and Tb³⁺:MgLa₂V₂O₉ powder phosphors has been explained in an energy level diagram.     

Synthesis and biological evaluation of thiophene [3,2-b] pyrrole derivatives as potential anti-inflammatory agents

A series of thiophene [3,2-b] pyrrole derivatives were synthesized and evaluated their abilities to inhibit anti-inflammatory activity. In this series, substituent effects at the N-1, 2 and 5 positions of thiophene [3,2-b] pyrrole were examined. The results obtained are compared to those previously reported anti-inflammatory drugs like Tenidap sodium, Diclofenac sodium and Piroxicam. The results indicated the critical role of the group linked in the N-1 position and 2, 5 positions of thiophene [3,2-b] pyrrole with different functional groups.     

Tracking the 'general': tagging skin-derived dendritic cells

Dendritic cells (DCs) are the sentinels of the immune system; their migration, maturation and mobilization are fundamental to immunity and tolerance. The recent tracking of DCs from the skin to lymph node (LN) and their enumeration using a Cre/loxP system demonstrate the recruitment of a higher than expected number of DCs to the draining LN after cutaneous administration of DNA-coated gold particles. The longevity of the migrated DCs was also longer than previously reported.