89 research outputs found

    A method for volume stabilization of single, dye-doped water microdroplets with femtoliter resolution

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    A self-control mechanism that stabilizes the size of Rhodamine B-doped water microdroplets standing on a superhydrophobic surface is demonstrated. The mechanism relies on the interplay between the condensation rate that was kept constant and evaporation rate induced by laser excitation which critically depends on the size of the microdroplets. The radii of individual water microdroplets (>5 um) stayed within a few nanometers during long time periods (up to 455 seconds). By blocking the laser excitation for 500 msec, the stable volume of individual microdroplets was shown to change stepwise.Comment: to appear in the J. Op. Soc. Am.

    Transcription-replication conflicts: How they occur and how they are resolved

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    The frequent occurrence of transcription and DNA replication in cells results in many encounters, and thus conflicts, between the transcription and replication machineries. These conflicts constitute a major intrinsic source of genome instability, which is a hallmark of cancer cells. How the replication machinery progresses along a DNA molecule occupied by an RNA polymerase is an old question. Here we review recent data on the biological relevance of transcription-replication conflicts, and the factors and mechanisms that are involved in either preventing or resolving them, mainly in eukaryotes. On the basis of these data, we provide our current view of how transcription can generate obstacles to replication, including torsional stress and non-B DNA structures, and of the different cellular processes that have evolved to solve them

    Comparative study on cellular entry of incinerated ancient gold particles (Swarna Bhasma) and chemically synthesized gold particles

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    Gold nanoparticles (AuNPs) are used for a number of imaging and therapeutic applications in east and western part of the world. For thousands of years, the traditional Indian Ayurvedic approach to healing involves the use of incinerated gold ash, prepared with a variety of plant extracts and minerals depending on the region. Here, we describe the characterization of incinerated gold particles (IAuPs) in HeLa (human cells derived from cervical cancer) and HFF-1 (human foreskin fibroblast cells) in comparison to synthesized citrate-capped gold nanoparticles (AuNPs). We found that while individual IAuP crystallites are around 60 nm in size, they form large aggregates with a mean diameter of 4711.7 nm, some of which can enter cells. Fewer cells appeared to have IAuPs compared to AuNPs, although neither type of particle was toxic to cells. Imaging studies revealed that IAuPs were in vesicles, cytosol, or in the nucleus. We found that their nuclear accumulation likely occurred after nuclear envelope breakdown during cell division. We also found that larger IAuPs entered cells via macropinocytosis, while smaller particles entered via clathrin-dependent receptor-mediated endocytosis

    C9orf72 Expansion Disrupts ATM-mediated Chromosomal Break Repair

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    A hexanucleotide repeat expansion represents the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, though the mechanisms by which the expansion cause neurodegeneration are poorly understood. We report elevated levels of DNA/RNA hybrids (R-loops) and double-strand breaks (DSBs) in rodent neurons, human cells, and in C9orf72-ALS patient spinal cord tissues. Accumulation of endogenous DNA damage is concomitant with defective ATM-mediated DNA repair signalling and accumulation of protein-linked DNA breaks. We further reveal that defective ATM-mediated DNA repair is a consequence of p62 accumulation, which impairs H2A ubiquitylation and perturbs ATM signalling. Adeno-associated virus- mediated expression of C9orf72-related RNA and dipeptide repeats in the murine central nervous system causes elevated DSBs, ATM defects, and triggers neurodegeneration. These findings identify R-Loops, DSBs, and defective ATM-mediated repair as pathological consequences of C9orf72 expansions, and suggest that C9orf72-linked neurodegeneration is driven, at least in part, by genomic instability

    XRN2 Links Transcription Termination to DNA Damage and Replication Stress

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    We thank the Proteomics Core Facility. We thank Dr. Robert J. Crouch for providing us with GFP- and GFP-RNase H expression plasmids. We also thank Dr. Stephen H. Leppla for providing us with antibodies directed against RNA:DNA hybrids (R loops) (S9.6). We thank Novus Biologicals for generously providing XRN2 and Rrp45 antibodies. We also thank the members of the Boothman lab for critical reading of this manuscript.Author Summary Genomic instability is one of the primary causes of disease states, in particular cancer. One major cause of genomic instability is the formation of DNA double strand breaks (DSBs), which are one of the most dangerous types of DNA lesions the cell can encounter. If not repaired in a timely manner, one DSB can lead not only to cell death. If misrepaired, one DSB can lead to a hazardous chromosomal aberration, such as a translocation, that can eventually lead to cancer. The cell encounters and repairs DSBs that arise from naturally occurring cellular processes on a daily basis. A number of studies have demonstrated that aberrant structures that form during transcription under certain circumstances, in particular RNA:DNA hybrids (R loops), can lead to DSB formation and genomic instability, especially during DNA synthesis. Thus, it is important to understand how the cell responds and repairs transcription-mediated DNA damage in general and R loop-related DNA damage in particular. This paper both demonstrates that the XRN transcription termination factor links transcription and DNA damage, but also provides a better understanding of how the cell prevents transcription-related DNA damage.Yeshttp://www.plosgenetics.org/static/editorial#pee

    The effect of nanoparticles on the surface hydrophobicity of polystyrene

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    The surface hydrophobicity of polystyrene-nanoparticle nanocomposites has been investigated as a function of the nanoparticle content. The addition of hydrophobically coated nanoparticles in polystyrene increased the contact angle θ of a water drop with respect to that on polystyrene surface due to change of surface composition and/or surface roughness. When the nanoparticles dispersed well in the polymer, cosθ\cos\theta decreased linearly with increasing amount of nanoparticles indicating a composite surface consisting of smooth polystyrene regions and rough nanoparticle regions. In case of formation of nanoparticle aggregates in polystyrene, cosθ\cos\theta decreased sharply at a critical concentration of nanoparticles. The observed behaviour was modeled in terms of a transition from Wenzel regime to Cassie-Baxter regime at a critical roughness length scale below which the Laplace pressure prevented the penetration of the water drop into the surface undulations. We argue that multiple length scales are needed below the critical roughness length scale to increase the contact angle further by decreasing the fraction of surface area of solid material (increasing the fraction of surface area of air) underlying the water drop

    A forgotten disease "Leprae" and limb lesions

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    Leprae, which is a forgotten infectious disease, presents with primary findings of skin lesions and peripheral nerve lesions. Neuropathic ulcers are frequently found and may cause deformities, particularly in the extremities. It should not be forgotten that malignant tumors seen on the floor of chronic ulcers can also be seen on the floor of neuropathic ulcers depending on leprae. In our study, a 61-year-old male patient with an ulcerated and unhealed lesion in the volar surface of the second finger of his right hand that existed for approximately 6 months is presented. Although leprae is not common these days, early defect repairs will prevent osteomyelitis and sequelae of amputation, depending on the malignancy in these patients. © 2016 Turkish Society of Plastic Reconstructive, and Aesthetic Surgery

    The effect of 1?,25(OH)2D3 vitamin over oxidative stress and biochemical parameters in rats where Type 1 diabetes is formed by streptozotocin

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    PubMed ID: 18976933Introduction: The 1?,25-dihydroxyvitamin D3 [1?,25(OH)2D3] plays an essential role in mineral balance but has also been recognized as a powerful modulator of immune response. We aimed to examine the effect of the 1?,25(OH)2D3 treatment on insulin/c-peptide, catalase, superoxide dismutase (SOD), and blood glucose in rats that take streptozotocin (STZ). Methods: Forty pieces of male rats of Albino family whose average weights were 261.00±07.62 g were used in the study. Rats were made diabetic by giving STZ of 40 mg/kg during 5 days through intraperitoneal path. Some of the diabetic group and nondiabetic group were received 1?,25(OH)2D3. The levels of SOD, insulin, c-peptide, glucose, SOD, and catalase were measured at the zero, second, fourth, and sixth weeks. Results: Erythrocyte SOD levels didn't show a significant difference at the end of the sixth week in all groups when compared to the beginning. While erythrocyte catalase levels didn't show a significant difference in nondiabetic control and nondiabetic with vitamin D, and diabetic with vitamin D groups at the end of sixth week when compared to the beginning, a significant measurement was made in diabetic without vitamin D group. Maximal insulinitis scoring values were observed in diabetic without vitamin D that didn't receive 1?,25(OH)2D3 treatment. Conclusion: The highness of insulin and c-peptide levels in the group that received treatment when compared to other groups and the lowness of oxidative markers such as SOD, catalase in this study can be explained by the fact that 1?,25(OH)2D3 treatment prevents the intervention of apoptosis mechanism. Crown Copyright © 2009

    Effects of ozone pretreatment on viability of random pattern skin flaps in rats

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    Background: Medical ozone is a chemical agent that consists of three oxygen atoms and has antioxidant, angiogenic and vasodilator effects. This study evaluated the effects of medical ozone pre-treatment on flap survival. Materials and methods: Rats were divided into four groups of 10 rats each and a 9 × 3 cm McFarlane flap was used. Sham group: Neither surgical nor ozone pretreatment was used. Control group: No pretreatment was used after surgery. Preoperative ozone group: Preoperative 1 mg/kg ozone was given intraperitoneally for 7 days. No pretreatment was used after surgery. Postoperative ozone Group: Postoperative 1 mg/kg ozone was given intraperitoneally for 7 days. After postoperative 1 week, all groups were evaluated by surface area measurement, histopathology and electron microscopy. Results: With the experimental McFarlane flap model, the experimental groups had better surface area measurements, along with histopathological and electron microscopic results when compared with the control group. Conclusion: Medical ozone had positive effects on flap survival due to its antioxidant, angiogenic and vasodilator qualities. © 2015 Informa Healthcare.Declaration of interest: This study was supported by the office of scientific research projects of Yüzüncü Yıl University
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