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1.
Electrical stimuli applied to the olfactory tract for one minute caused partial depletion, but for two to five minutes resulted in complete depletion of the neurosecretory material (NSM) from the Dahlgren cells as well as from the urophysis. However, if similar stimuli were directly applied to the caudal spinal cord for one minute, the NSM was completely depleted. The neurosecretory granules were reaccumulated in the neurons within fifteen minutes after the stimuli were cut of A rapid depletion of the NSM from the caudal neurons was correlated with their electrical properties and rapid transduction of nervous information into the hormonal message. The immediate response of the caudal neurons to the olfactory tract stimulation suggested that the former are synaptically controlled by a center in the brain. 相似文献
2.
The cell cycle of neurons remains suppressed to maintain the state of differentiation and aberrant cell cycle reentry results in loss of neurons, which is a feature in neurodegenerative disorders like Alzheimer''s disease (AD). Present studies revealed that the expression of microRNA 34a (miR-34a) needs to be optimal in neurons, as an aberrant increase or decrease in its expression causes apoptosis. miR-34a keeps the neuronal cell cycle under check by preventing the expression of cyclin D1 and promotes cell cycle arrest. Neurotoxic amyloid β1–42 peptide (Aβ42) treatment of cortical neurons suppressed miR-34a, resulting in unscheduled cell cycle reentry, which resulted in apoptosis. The repression of miR-34a was a result of degradation of TAp73, which was mediated by aberrant activation of the MEK extracellular signal-regulated kinase (ERK) pathway by Aβ42. A significant decrease in miR-34a and TAp73 was observed in the cortex of a transgenic (Tg) mouse model of AD, which correlated well with cell cycle reentry observed in the neurons of these animals. Importantly, the overexpression of TAp73α and miR-34a reversed cell cycle-related neuronal apoptosis (CRNA). These studies provide novel insights into how modulation of neuronal cell cycle machinery may lead to neurodegeneration and may contribute to the understanding of disorders like AD. 相似文献
3.
Nepali K Agarwal A Sapra S Mittal V Kumar R Banerjee UC Gupta MK Satti NK Suri OP Dhar KL 《Bioorganic & medicinal chemistry》2011,19(18):5569-5576
A series of forty two N-(1,3-diaryl-3-oxopropyl)amides were synthesized via an efficient, modified Dakin-West reaction and were evaluated for in vitro xanthine oxidase inhibitory activity for the first time. Structure-activity relationship analyses have been presented. Selected active xanthine oxidase inhibitors (3r, 3s, and 3zh) were assessed in vivo to study their anti-hyperuricemic effect in potassium oxonate induced hyperuricemic mice model. Compound 3s emerged as the most potent xanthine oxidase inhibitor (IC(50)=2.45 μM) as well as the most potent anti-hyperuricemic agent. The basis of significant inhibition of xanthine oxidase by 3s was rationalized by its molecular docking into catalytic site of xanthine oxidase. 相似文献
4.
Kathryn Davidson Paul Grevitt Maria F. Contreras-Gerenas Katherine S. Bridge Miguel Hermida Kunal M. Shah Faraz K. Mardakheh Mark Stubbs Rosemary Burke Pedro Casado Pedro R. Cutillas Sarah A. Martin Tyson V. Sharp 《Cell death & disease》2021,12(11)
An early event in lung oncogenesis is loss of the tumour suppressor gene LIMD1 (LIM domains containing 1); this encodes a scaffold protein, which suppresses tumorigenesis via a number of different mechanisms. Approximately 45% of non-small cell lung cancers (NSCLC) are deficient in LIMD1, yet this subtype of NSCLC has been overlooked in preclinical and clinical investigations. Defining therapeutic targets in these LIMD1 loss-of-function patients is difficult due to a lack of ‘druggable’ targets, thus alternative approaches are required. To this end, we performed the first drug repurposing screen to identify compounds that confer synthetic lethality with LIMD1 loss in NSCLC cells. PF-477736 was shown to selectively target LIMD1-deficient cells in vitro through inhibition of multiple kinases, inducing cell death via apoptosis. Furthermore, PF-477736 was effective in treating LIMD1−/− tumours in subcutaneous xenograft models, with no significant effect in LIMD1+/+ cells. We have identified a novel drug tool with significant preclinical characterisation that serves as an excellent candidate to explore and define LIMD1-deficient cancers as a new therapeutic subgroup of critical unmet need.Subject terms: Targeted therapies, Non-small-cell lung cancer 相似文献
5.
Balasubramanian Radhakrishnan Radha Prasanna Pranita Jaiswal Saswati Nayak Prem Dureja 《Biologia》2009,64(5):881-889
An investigation was undertaken to evaluate a set of cyanobacterial strains in terms of production of biocidal compounds exhibiting
allelochemical and fungicidal properties. Two cyanobacterial strains — Anabaena sp. and Calothrix sp. were selected for further investigation, on the basis of their larger inhibition zones on the lawn of Synechocystis and Synechococcus sp. and two phytopathogenic fungi — Rhizoctonia bataticola and Pythium debaryanum. The diameter of the inhibition zone was largest when extracellular filtrates of the two cultures incubated at high light
intensity (90–100 μmol photons m−2 s−1) and temperature (40 ± 2 °C) or grown in medium containing two-folds higher P (1.4 mg/L, as compared to 0.7 mg/L in BG 11
medium) were taken. A pH of 8 was the most optimal for both strains, in terms of growth and biocidal activity. Partial purification
of ethyl acetate extract using TLC, followed by GLC revealed a single peak. This study highlights the importance of environmental
factors in aggravating or reducing the toxic effects of these harmful cyanobacteria and their potential as a biocontrol agent. 相似文献
6.
Amelia A. Langston Cathryn S. Mellersh Cassandra L. Neal Kunal Ray Gregory M. Acland Mark Gibbs Gustavo D. Aguirre R.E.K. Fournier Elaine A. Ostrander 《Genomics》1997,46(3):317
We have constructed a collection of canine–rodent microcell hybrid cell lines by fusion of canine fibroblast microcell donors with immortalized rodent recipient cells. Characterization of the hybrid cell lines using a combination of fluorescencein situhybridization and PCR analysis of canine microsatellite repeat sequences allowed selection of a panel of hybrids in which most canine chromosomes are represented. Approximately 90% of genetic markers and genes that were tested could be assigned to 1 of 31 anonymous canine chromosome groups, based on common patterns of retention in the hybrid set. Many of these putative chromosome groups have now been validated by linkage analysis. This panel of cell lines provides a tool for development of genetic, physical, and comparative maps of the canine genome. 相似文献
7.
Christina Bergonzo Kunal Dharmadhikari Emily Samuels Makenzie Christensen Jennifer Tullman 《Proteins》2020,88(9):1189-1196
ClpS2 is a small protein under development as a probe for selectively recognizing N-terminal amino acids of N-degron peptide fragments. To understand the structural basis of ClpS2 specificity for an N-terminal amino acid, all atom molecular dynamics (MD) simulations were conducted using the sequence of a bench-stable mutant of ClpS2, called PROSS. We predicted that a single amino acid leucine to asparagine substitution would switch the specificity of PROSS ClpS2 to an N-terminal tyrosine over the preferred phenylalanine. Experimental validation of the mutant using a fluorescent yeast-display assay showed an increase in tyrosine binding over phenylalanine, in support of the proposed hypothesis. 相似文献
8.
The maternally inherited obligate bacteria Wolbachia is known to infect various lepidopteran insects. However, so far only a few butterfly species harbouring this bacterium have
been thoroughly studied. The current study aims to identify the infection status of these bacteria in some of the commonly
found butterfly species in India. A total of nine butterfly species belonging to four different families were screened using
PCR with Wolbachia-specific wsp and ftsZ primers. The presence of the Wolbachia super group ‘B’ in the butterflies Red Pierrot, Talicada nyseus (Guerin) (Lepidoptera: Lycaenidae) and Blue Mormon, Papilio polymnestor Cramer (Papilionidae), is documented for the first time in India. The study also gives an account on the lifetime fecundity
and female-biased sex ratio in T. nyseus, suggesting a putative role for Wolbachia in the observed female-biased sex ratio distortion. 相似文献
9.
10.
Shrey Kohli Aastha Chhabra Astha Jaiswal Yashika Rustagi Manish Sharma Vibha Rani 《PloS one》2013,8(10)