Elevation of intracellular calcium levels in neurons by nicotinic acetylcholine receptors

The recognition that intracellular free calcium serves as a ubiquitous intracellular signal has motivated efforts to elucidate mechanisms by which cells regulate calcium influx. One route of entry that may offer both spatial and temporal fine resolution for altering calcium levels is that provided by cation-permeable, ligand-gated ion channels. Biophysical measurements as well as calcium imaging techniques demonstrate that neuronal nicotinic acetylcholine receptors as a class have a high relative permeability to calcium; some subtypes equal or exceed all other known receptors in this respect. Activation of nicotinic receptors on neurons can produce substantial increases in intracellular calcium levels by direct passage of calcium through the receptor channel. When multiple classes of nicotinic receptors are expressed by the same neuron, each appears capable of increasing calcium in the cell but may differ with respect to location, temporal response, agonist sensitivity, or regulation in achieving it. As a result, nicotinic receptors must be considered strong candidates for signaling molecules through which neurons regulate a diverse array of cellular events.     

Exit fluence analysis using portal dosimetry in volumetric modulated arc therapy

AimIn measuring exit fluences, there are several sources of deviations which include the changes in the entrance fluence, changes in the detector response and patient orientation or geometry. The purpose of this work is to quantify these sources of errors.BackgroundThe use of the volumetric modulated arc therapy treatment with the help of image guidance in radiotherapy results in high accuracy of delivering complex dose distributions while sparing critical organs. The transit dosimetry has the potential of Verifying dose delivery by the linac, Multileaf collimator positional accuracy and the calculation of dose to a patient or phantom.Materials and methodsThe quantification of errors caused by a machine delivery is done by comparing static and arc picket fence test for 30 days. A RapidArc plan, created for the pelvis site was delivered without and with Rando phantom and exit portal images were acquired. The day to day dose variation were analysed by comparing the daily exit dose images during the course of treatment. The gamma criterion used for analysis is 3% dose difference and 3 mm distance to agreement with a threshold of 10% of maximum dose.ResultsThe maximum standard deviation for the static and arc picket fence test fields were 0.19 CU and 1.3 CU, respectively. The delivery of the RapidArc plans without a phantom shows the maximum standard deviation of 1.85 CU and the maximum gamma value of 0.59. The maximum gamma value for the RapidArc plan delivered with the phantom was found to be 1.2. The largest observed fluence deviation during the delivery to patient was 5.7% and the maximum standard deviation was 4.1 CU.ConclusionIt is found from this study that the variation due to patient anatomy and interfraction organ motion is significant.     

The p53-p21WAF1 checkpoint pathway plays a protective role in preventing DNA rereplication induced by abrogation of FOXF1 function

We previously identified FOXF1 as a potential tumor suppressor gene with an essential role in preventing DNA rereplication to maintain genomic stability, which is frequently inactivated in breast cancer through the epigenetic mechanism. Here we further addressed the role of the p53-p21^WAF1 checkpoint pathway in DNA rereplication induced by silencing of FOXF1. Knockdown of FOXF1 by small interference RNA (siRNA) rendered colorectal p53-null and p21^WAF1-null HCT116 cancer cells more susceptible to rereplication and apoptosis than the wild-type parental cells. In parental HCT116 cells with a functional p53 checkpoint, the p53-p21^WAF1 checkpoint pathway was activated upon FOXF1 knockdown, which was concurrent with suppression of the CDK2-Rb cascade and induction of G₁ arrest. In contrast, these events were not observed in FOXF1-depleted HCT116-p53−/− and HCT116-p21−/− cells, indicating that the p53-dependent checkpoint function is vital for inhibiting CDK2 to induce G₁ arrest and protect cells from rereplication. The pharmacologic inhibitor (caffeine) of ataxia telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3 related (ATR) protein kinases abolished activation of the p53-p21^WAF1 pathway upon FOXF1 knockdown, suggesting that suppression of FOXF1 function triggered the ATM/ATR-mediated DNA damage response. Cosilencing of p53 by siRNA synergistically enhanced the effect of FOXF1 depletion on the stimulation of DNA rereplication and apoptosis in wild-type HCT116. Finally, we show that FOXF1 expression is predominantly silenced in breast and colorectal cancer cell lines with inactive p53. Our study demonstrated that the p53-p21^WAF1 checkpoint pathway is an intrinsically protective mechanism to prevent DNA rereplication induced by silencing of FOXF1.     

Dung as a potential medium for inter-sexual chemical signaling in Asian elephants (Elephas maximus)

Chemical signaling is a prominent mode of male-female communication among elephants, especially during their sexually active periods. Studies on the Asian elephant in zoos have shown the significance of a urinary pheromone (Z7-12:Ac) in conveying the reproductive status of a female toward the opposite sex. We investigated the additional possibility of an inter-sexual chemical signal being conveyed through dung. Sixteen semi-captive adult male elephants were presented with dung samples of three female elephants in different reproductive phases. Each male was tested in 3 separate trials, within an interval of 1-3 days. The trials followed a double-blind pattern as the male and female elephants used in the trials were strangers, and the observer was not aware of the reproductive status of females during the period of bioassays. Males responded preferentially (P<0.005), in terms of higher frequency of sniff, check and place behavior toward the dung of females close to pre-ovulatory period (follicular-phase) as compared to those in post-ovulatory period (luteal-phase). The response toward the follicular phase samples declined over repeated trials though was still significantly higher than the corresponding response toward the non-ovulatory phase in each of the trials performed. This is the first study to show that male Asian elephants were able to distinguish the reproductive phase of the female by possibly detecting a pre-ovulatory pheromone released in dung.     

Parallel cousin marriages in Madras, Tamil Nadu: new trends in Dravidian kinship

The frequency distribution of various consanguineous marriages was studied in the city of Madras, Tamil Nadu, South India. Parallel first cousin marriages (PFC) were found to occur in appreciable frequencies in all caste groups of Hindus. While it has been generally believed that PFC marriages among Hindus are mere exceptions and are usually not tolerated, our data show that they can no longer be treated as exceptions. The high frequency (27 per cent) of PFC marriages in some Hindu communities necessitates in-depth studies to elucidate the forces at work which go against the very fundamentals of Dravidian kinship.     

Decreased fasting serum glucogenic amino acids with a higher compared to normal protein diet during energy restriction in women: a randomized controlled trial

Dietary protein alters circulating amino acid (AAs) levels and higher protein intake (HP) is one means of losing weight. We examined 34 overweight and obese women (57 ± 4 years) during 6 months of energy restriction (7.3 ± 3.8% weight loss) divided into groups consuming either normal protein (NP; 18.6 energy% protein) or HP (24.3 energy% protein). There was a reduction in fasting serum glucogenic AAs (p = 0.015) that also associated with greater weight loss (p < 0.05) in the HP group, but not in the NP group. These findings have implications for nutrient prioritization during energy restriction.

     

Effect of photoperiod,light intensity and carbon sources on biomass and lipid productivities of Isochrysis galbana

Biomass and lipid productivities of Isochrysis galbana were optimized using nutrients of molasses (4, 8, 12 g l^?1), glucose (4, 8, 12 g l^?1), glycerol (4, 8, 12 g l^?1) and yeast extract (2 g l^?1). Combinations of carbon sources at different ratios were evaluated in which the alga was grown at three different light intensities (50, 100 and 150 μmol m^?2 s^?1) under the influence of three different photoperiod cycles (12/12, 18/6 and 24/0 h light/dark). A maximum cell density of 8.35 g l^?1 with 32 % (w/w) lipid was achieved for mixotrophic growth at 100 μmol m^?2 s^?1 and 18/6 h light/dark with molasses/glucose (20:80 w/w). Mixotrophic cultivation using molasses, glucose and glycerol was thus effective for the cultivation of I. galbana.     

A New lncRNA,APTR, Associates with and Represses the CDKN1A/p21 Promoter by Recruiting Polycomb Proteins

Long noncoding RNAs (lncRNAs) have emerged as a major regulator of cell physiology, but many of which have no known function. CDKN1A/p21 is an important inhibitor of the cell-cycle, regulator of the DNA damage response and effector of the tumor suppressor p53, playing a crucial role in tumor development and prevention. In order to identify a regulator for tumor progression, we performed an siRNA screen of human lncRNAs required for cell proliferation, and identified a novel lncRNA, APTR, that acts in trans to repress the CDKN1A/p21 promoter independent of p53 to promote cell proliferation. APTR associates with the promoter of CDKN1A/p21 and this association requires a complementary-Alu sequence encoded in APTR. A different module of APTR associates with and recruits the Polycomb repressive complex 2 (PRC2) to epigenetically repress the p21 promoter. A decrease in APTR is necessary for the induction of p21 after heat stress and DNA damage by doxorubicin, and the levels of APTR and p21 are anti-correlated in human glioblastomas. Our data identify a new regulator of the cell-cycle inhibitor CDKN1A/p21 that acts as a proliferative factor in cancer cell lines and in glioblastomas and demonstrate that Alu elements present in lncRNAs can contribute to targeting regulatory lncRNAs to promoters.     

A study on the correlation between plan complexity and gamma index analysis in patient specific quality assurance of volumetric modulated arc therapy

Aim

To evaluate the new Octavius 4D system for patient specific quality assurance and to study the correlation between plan complexity and gamma index analysis in patient specific quality assurance of VMAT using the Octavius 4D system.

Background

McNiven (2010) proposed a study to evaluate the utility of a complexity metric, the Modulation Complexity Score, to evaluate the relationship of the metric with deliverability in IMRT.

Materials and methods

Evaluation of the Octavius 4D system was carried out by gamma evaluation of user defined MLC created patterns and AAPM TG 119 benchmark plans. The relationship between plan complexity expressed as Modulation Complexity Score (MCS) and the gamma index analysis was established by a planar and volumetric gamma analysis of 106 clinically approved VMAT patient plans of different sites.

Results

Average volumetric 3D global gamma evaluation (3 mm/3%) results for the evaluation plans was 97.41% for 6 MV X-rays and 98.30% for 15 MV X-rays. Average MCS values for the head and neck, pelvic and thoracic plans were 0.2224, 0.3615 and 0.1874. Average volumetric 3D global gamma analysis (3 mm/3%) results for the head and neck, pelvic and thoracic VMAT plans were 95.45%, 97.51% and 96.98%, respectively. Out of 90 correlation analyses between the MCS and gamma passing rate, only 3 had the r value greater than 0.5.

Conclusions

The Octavius 4D system is a suitable device for patient specific pretreatment QA. Global and local gamma analysis results showed a weak correlation with the MCS.