Nanomaterials are frontier technological products used in different manufactured goods. Because of their unique physicochemical, electrical, mechanical, and thermal properties, single-walled carbon ...nanotubes (SWCNT) are finding numerous applications in electronics, aerospace devices, computers, and chemical, polymer, and pharmaceutical industries. SWCNT are relatively recently discovered members of the carbon allotropes that are similar in structure to fullerenes and graphite. Previously, we (47) have reported that pharyngeal aspiration of purified SWCNT by C57BL/6 mice caused dose-dependent granulomatous pneumonia, oxidative stress, acute inflammatory/cytokine responses, fibrosis, and decrease in pulmonary function. To avoid potential artifactual effects due to instillation/agglomeration associated with SWCNT, we conducted inhalation exposures using stable and uniform SWCNT dispersions obtained by a newly developed aerosolization technique (2). The inhalation of nonpurified SWCNT (iron content of 17.7% by weight) at 5 mg/m(3), 5 h/day for 4 days was compared with pharyngeal aspiration of varying doses (5-20 microg per mouse) of the same SWCNT. The chain of pathological events in both exposure routes was realized through synergized interactions of early inflammatory response and oxidative stress culminating in the development of multifocal granulomatous pneumonia and interstitial fibrosis. SWCNT inhalation was more effective than aspiration in causing inflammatory response, oxidative stress, collagen deposition, and fibrosis as well as mutations of K-ras gene locus in the lung of C57BL/6 mice.
Background and purpose
Autosomal recessive cerebellar ataxia (ARCA) comprises a large and heterogeneous group of neurodegenerative disorders. We studied three families diagnosed with ARCA.
Methods
To ...determine the gene lesions responsible for their disorders, we performed high‐density single‐nucleotide polymorphism genotyping and exome sequencing.
Results
We identified a new mutation in the SACS gene and a known mutation in SPG11. Notably, we also identified a homozygous variant in APOB, a gene previously associated with ataxia.
Conclusions
These findings demonstrate that exome sequencing is an efficient and direct diagnostic tool for identifying the causes of complex and genetically heterogeneous neurodegenerative diseases, early‐stage disease or cases with limited clinical data.
Several quinazoline derivatives have been found to possess a broad spectrum of biological activities. Previously our research group has synthesized and studied the anti-proliferative effects of ...N-Decyl-N-(2-Methyl-4-Quinazolinyl) Amine (DMQA). The current study evaluated the cytotoxic and apoptotic properties of DMQA in THP-1 cells. The cytotoxic potential of DMQA was assessed using MTT assay on a panel of cancer cell lines which include HeLa, Mia PaCa-2, A 375, B16-F10, A 549,A 431, U937, THP-1, HL-60 and peripheral blood mononuclear cells (PBMC's). Preliminary data revealed that the highest cytotoxic activity was against THP-1 leukemia cell line (IC50=0.66 μg/ml). The apoptotic properties of DMQA on THP-1 cells were characterized by change in nuclear morphology, DNA fragmentation, reduction of pro-caspases-3, 9, Bax/Bcl-2 levels, cleavage of poly (ADP-ribose) polymerase and cytosolic release of cytochrome c. Further investigation revealed a sub-G1 peak, phosphatidyl serine exposure and loss of mitochondrial membrane potential (MMP) in THP-1 cells. The role of caspases was crucial and was demonstrated by the inhibitors Z-VAD-FMK and Z-DEVD-FMK. Moreover DMQA was markedly less effective in inhibiting the growth of normal cells (PBMC's, IC50 =62.17 μg/ml). Based on the results we suggest that DMQA induced apoptosis via intrinsic pathway and could be a promising anticancer agent.
•DMQA induced apoptosis via intrinsic pathway in THP-1 leukemia cells.•DMQA was markedly less effective in inhibiting the growth of normal cells.•The role of caspases was demonstrated by the inhibitors Z-VAD-FMK and Z-DEVD-FMK.
Mechanisms proposed in the literature are compared with a current scenario for the formation of single-wall carbon nanotubes in the laser-ablation process that is based on our spectral emission and ...laser-induced fluorescence measurements. It is suggested that the carbon which serves as feedstock for nanotube formation not only comes from the direct ablation of the target, but also from carbon particles suspended in the reaction zone. Fullerenes formed in the reaction zone may be photo-dissociated into C2 and other low molecular weight species, and also may serve as feedstock for nanotube growth. Confinement of the nanotubes in the reaction zone within the laser beam allows the nanotubes to be 'purified' and annealed during the formation process by laser heating.
Bioassay directed fractionation and purification led to the successful isolation of a furano sesquiterpene, Methyl 5-(1E,5E)-2,6-Dimethyl octa-1,5,7-trienyl furan-3-carboxylate (MDTFC), a bioactive ...component from a soft coral, Sinularia kavarittiensis. Its structure was determined by analyzing ¹H, ¹³C NMR and FAB-MS. The results show that MDTFC could efficiently and selectively inhibit the proliferation of several human cancer cell lines. Among all the cell lines, THP-1 was found to be most sensitive (IC₅₀ 29.59 μM), whereas the peripheral blood mononuclear cells were least effected (IC₅₀ 464.16 μM). The molecular mechanism of MDTFC mediated apoptosis was investigated for the first time. Induction of apoptosis in THP-1 cells was characterized by cell membrane blebbing, chromatin condensation, DNA fragmentation, and decrease in level of pro-caspases 3, 9 and increase in Bax/Bcl-2 ratio. Our results were further strengthened through cleavage of poly (ADP-ribose) polymerase, reduction of mitochondrial membrane potential (Ψm) and cytosolic release of cytochrome c, which are key events during apoptosis. Moreover, phosphatidyl serine exposure and appearance of sub-G1 peak also demonstrated cell death, when analyzed by flow cytometry. DNA fragmentation was prevented moderately when pretreated with caspase-9 inhibitor (Z-LEHD-FMK) and largely with caspase-3 inhibitor (Z-DEVD-FMK). In summary, MDTFC mediated apoptosis involves mitochondria-dependent pathway and the present compound of marine origin might have a therapeutic value against human cancer cell lines and especially on leukemia cells.
Background
Scottish Terriers have a high incidence of juvenile onset hereditary ataxia primarily affecting the Purkinje neuron of the cerebellar cortex and causing slowly progressive cerebellar ...dysfunction.
Objective
To identify chromosomal regions associated with hereditary ataxia in Scottish Terriers.
Animals
One hundred and fifty‐three Scottish Terriers were recruited through the Scottish Terrier Club of America.
Materials and Methods
Prospective study. Dogs were classified as affected if they had slowly progressive cerebellar signs. When possible, magnetic resonance imaging and histopathological evaluation of the brain were completed as diagnostic aids. To identify genomic regions connected with the disease, genome‐wide mapping was performed using both linkage‐ and association‐based approaches. Pedigree evaluation and homozygosity mapping were also performed to examine mode of inheritance and to investigate the region of interest, respectively.
Results
Linkage and genome‐wide association studies in a cohort of Scottish Terriers both identified a region on CFA X strongly associated with the disease trait. Homozygosity mapping revealed a 4 Mb region of interest. Pedigree evaluation failed to identify the possible mode of inheritance due to the lack of complete litter information.
Conclusion and Clinical Importance
This finding suggests that further genetic investigation of the potential region of interest on CFA X should be considered in order to identify the causal mutation as well as develop a genetic test to eliminate the disease from this breed.
l-Asparaginase is an important component in the treatment of acute lymphoblastic leukemia in children. Its antineoplastic activity toward malignant cells is due to their characteristic nature in slow ...synthesis of l-asparagine (Asn), which causes starvation for this amino acid, while normal cells are protected from Asn starvation due to their ability to produce this amino acid. The relative selectivity with regard to the metabolism of malignant cells forces to look for novel asparaginase with little glutaminase-producing systems compared to existing enzyme. In this investigation, the role of the extracellular asparaginase enzyme produced by an isolated bacterial strain was studied. Biochemical characterization denoted that this isolated bacterial strain belongs to the Bacillus circulans species. The strain was tested for l-asparaginase production, and it was observed that, under an optimized environment, this isolate produces a maximum of 85 IU ml⁻¹ within 24-h incubation. This enzyme showed less (60%) glutaminase activity compared to commercial Erwinia sp. l-asparaginase. The partially purified enzyme showed an approximate molecular weight of 140 kDa. This enzyme potency in terms of antineoplastic activity was analyzed against the cancer cells, CCRF-CEM. Flow cytometry experiments indicated an increase of sub-G1 cell population when the cells were treated with l-asparaginase.
The continuous increase in the number of new chemicals as well as the discharges of solid and liquid wastes triggered the need for simple and inexpensive bioassays for routine testing. In recent ...years, there has been increasing development of methods (particularly rapid tests) for testing environmental samples. This paper describes the quick toxic evaluation of an organophosphorus insecticide, acephate (
O,
S-dimethyl acetylphosphoramidothioate) on
Paramecium caudatum for acute and sub-acute toxicity studies with reference to morphology, behaviour, and its generation time. The lethal concentrations for 10
min and 2
h were determined by probit method, as 500
mg
L
−1 and 300
mg
L
−1, respectively. Higher concentrations of 10
min exposure caused cell lysis with disintegration of cell membrane and precipitation of protoplasm. Combination of conventional light microscopy and computerized video tracking systems were used to study the locomotor behaviour of paramecia. The test organism was under stress and exhibited an initial increase and subsequent decrease in the swimming speed when exposed to 1/4, 1/2, 3/4, and LC
50 concentrations for 10
min (125, 250, 375, and 500
mg
L
−1, respectively). Similar changes were also noticed when paramecia were exposed to LC
50 for 2
h. In a separate set of experiments, the number of generations and generation time in 24
h was evaluated with respect to the different sub-lethal concentrations (30, 60, 120, and 240
mg
L
−1). The number of generations decreased and generation time extended significantly in a concentration dependent manner. The results indicate that the Paramecium toxicity assay could be used as a complimentary system to rapidly elucidate the cytotoxic potential of insecticides. The major advantages associated with these tests are: they are inexpensive, simple, user-friendly, space saving, and seem to be attractive alternatives to conventional bioassays.
We demonstrate effects of nanotubes buckling and debonding in octadecylamine (ODA) derivatized single wall carbon nanotubes (SWCNT)/epoxy nanocomposites under mechanical and thermal loads uniquely ...detected by means of Raman spectroscopy and documented by TEM imaging. It is shown that ODA functionalization of SWCNTs provides weak sidewall interactions between the nanotubes and epoxy matrix, which make axially compressed ODA-SWCNTs susceptible to buckling. The feasibility of ODA-SWCNTs buckling in epoxy matrix is also supported by the structural mechanics calculations.
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