Chalcone-imidazolone conjugates induce apoptosis through DNA damage pathway by affecting telomeres

<p>Abstract</p> <p>Background</p> <p>Breast cancer is one of the most prevalent cancers in the world and more than one million women are diagnosed leading to 410,000 deaths every year. In our previous studies new chalcone-imidazolone conjugates were prepared and evaluated for their anticancer activity in a panel of 53 human tumor cell lines and the lead compounds identified were 6 and 8. This prompted us to investigate the mechanism of apoptotic event.</p> <p>Results</p> <p>Involvement of pro-apoptotic protein (Bax), active caspase-9 and cleavage of retinoblastoma protein was studied. Interestingly, the compounds caused upregulation of p21, check point proteins (Chk1, Chk2) and as well as their phosphorylated forms which are known to regulate the DNA damage pathway. Increased p53BP1 foci by immunolocalisation studies and TRF1 suggested the possible involvement of telomere and associated proteins in the apoptotic event. The telomeric protein such as TRF2 which is an important target for anticancer therapy against human breast cancer was extensively studied along with proteins involved in proper functioning of telomeres.</p> <p>Conclusions</p> <p>The apoptotic proteins such as Bax, active caspase-9 and cleaved RB are up-regulated in the compound treated cells revealing the apoptotic nature of the compounds. Down regulation of TRF2 and upregulation of the TRF1 as well as telomerase assay indicated the decrease in telomeric length revealing telomeric dysfunction and thereby controlling the rapid rate of cell proliferation. In summary, chalcone-imidazolone conjugates displayed significant DNA damage activity particularly at telomeres and caused both apoptosis and senescence-like growth arrest which suggested that these compounds have potential activity against breast carcinoma.</p

Effect of Benzothiazole based conjugates in causing apoptosis by Regulating p53, PTEN and MAP Kinase proteins affecting miR-195a and miR-101-1

<p>Abstract</p> <p>Background</p> <p>Hepatocellular carcinoma (HCC) accounts for majority of liver cancers and is the leading cause of cancer related death in Asia. Like any other cancer, HCC develops when there is a mutation to the cellular machinery that causes the cell to replicate at a higher rate and results in the loss of apoptosis. Therefore, a delicate balance between the expression of various genes involved in proliferation and apoptosis decide the ultimate fate of the cell to undergo rapid proliferation (cancer) or cell death.</p> <p>Results</p> <p>The benzothiazole based compounds exhibited effective cytotoxicity at 4 μM concentration and have shown G1 cell cycle arrest with decrease in levels of G1 cell cycle proteins such as cyclin D1 and Skp2. Involvement of tumour suppressor proteins such as PTEN and p53 was studied. Interestingly these compounds displayed decrease in the phosphorylated forms of AKT, p38 MAPK and ERK1/2 which play a vital role in cell proliferation. Compounds have exhibited strong and significant effect on the expression of micro RNAs such as miR-195a & miR-101-1 which regulate hepatic cell proliferation.</p> <p>Conclusions</p> <p>The cell cycle arrest and apoptotic inducing nature of these compounds was revealed by FACS, BrdU cell proliferation and tunel assays. Compounds affected both tumour suppressor proteins as well as proteins that are involved in active cell proliferation. Micro RNAs whose target is Cyclin D1 such as miR-195a and miR-101-1 that is required for growth of hepatoma cells was drastically affected. These compounds caused apoptosis by activating caspase-3 and PARP.</p

Synthesizing Forestry Images Conditioned on Plant Phenotype Using a Generative Adversarial Network

Plant phenology and phenotype prediction using remote sensing data is increasingly gaining the attention of the plant science community to improve agricultural productivity. In this work, we generate synthetic forestry images that satisfy certain phenotypic attributes, viz. canopy greenness. The greenness index of plants describes a particular vegetation type in a mixed forest. Our objective is to develop a Generative Adversarial Network (GAN) to synthesize forestry images conditioned on this continuous attribute, i.e., greenness of vegetation, over a specific region of interest. The training data is based on the automated digital camera imagery provided by the National Ecological Observatory Network (NEON) and processed by the PhenoCam Network. The synthetic images generated by our method are also used to predict another phenotypic attribute, viz., redness of plants. The Structural SIMilarity (SSIM) index is utilized to assess the quality of the synthetic images. The greenness and redness indices of the generated synthetic images are compared against that of the original images using Root Mean Squared Error (RMSE) in order to evaluate their accuracy and integrity. Moreover, the generalizability and scalability of our proposed GAN model is determined by effectively transforming it to generate synthetic images for other forest sites and vegetation types

Urological disorders and pregnancy: An overall experience

Aim: Pregnancy is an anatomical and physiological altered state and the presence of various urological problems not only aggravates the disease itself, but also results in unfavourable pregnancy outcome. Aim is to highlight obstetric outcome in pregnant women with urological problems. Materials and Methods: Longitudinal prospective cohort study conducted in tertiary care hospital, IPGME and R, Kolkata from Jan 2011 to Dec 2012. All pregnant women with urological problems were included as subjects. Results: A total of 33 subjects were followed up throughout their antenatal period. Among them majority (72.72%) presented with hydro nephrosis followed by hydroureter (60.6%), PUJ obstruction and pyelonephritis each with incidence of 15.15%, then urolithiasis (12.12%), nephrolithiasis (6.06%) and renal abscess (12.12%). Interventions required were DJ stenting (72.72%), pyeloplasty (15.15%) and others were RURSL, abscess drainage and ATT. The pregnancy outcome was complicated with preterm labor in majority of patients (45.45%), oligohydramnious (18.18%), PIH (9.09%) and still birth (6.06%). Twenty four live birth were there. Majority required NICU admissions as predominantly prematurity was an important concern. Majority women with hydronephrosis underwent DJ stenting. Conclusion: Preterm labor is an important obstetric concern. Vaginal delivery is the choicest mode of termination and LSCS can be reserved for obstetric reason. DJ stenting is safe and practical approach for continuation of pregnancy with hydronephrosis. Regular follow up, vigilant antenatal care and multidisciplinary approach from urologist, obstetrician and neonatologist will bring out successful pregnancy outcome

Granulated deep learning and Z-numbers in motion detection and object recognition

The article deals with the problems of motion detection, object recognition, and scene description using deep learning in the framework of granular computing and Z-numbers. Since deep learning is computationally intensive, whereas granular computing, on the other hand, leads to computation gain, a judicious integration of their merits is made so as to make the learning mechanism computationally efficient. Further, it is shown how the concept of z-numbers can be used to quantify the abstraction of semantic information in interpreting a scene, where subjectivity is of major concern, through recognition of its constituting objects. The system, thus developed, involves recognition of both static objects in the background and moving objects in foreground separately. Rough set theoretic granular computing is adopted where rough lower and upper approximations are used in defining object and background models. During deep learning, instead of scanning the entire image pixel by pixel in the convolution layer, we scan only the representative pixel of each granule. This results in a significant gain in computation time. Arbitrary-shaped and sized granules, as expected, perform better than regular-shaped rectangular granules or fixed-sized granules. The method of tracking is able to deal efficiently with various challenging cases, e.g., tracking partially overlapped objects and suddenly appeared objects. Overall, the granulated system shows a balanced trade-off between speed and accuracy as compared to pixel level learning in tracking and recognition. The concept of using Z-numbers, in providing a granulated linguistic description of a scene, is unique. This gives a more natural interpretation of object recognition in terms of certainty toward scene understanding

Dynamical Transition of Water in the Grooves of DNA Duplex at Low Temperature

At low temperature (below its freezing/melting temperature), liquid water under confinement is known to exhibit anomalous dynamical features. Here we study structure and dynamics of water in the grooves of a long DNA duplex using molecular dynamics simulations with TIP5P potential at low temperature. We find signatures of a dynamical transition in both translational and orientational dynamics of water molecules in both the major and the minor grooves of a DNA duplex. The transition occurs at a slightly higher temperature (TGL ≈ 255 K) than the temperature at which the bulk water is found to undergo a dynamical transition, which for the TIP5P potential is at 247 K. Groove water, however, exhibits markedly different temperature dependence of its properties from the bulk. Entropy calculations reveal that the minor groove water is ordered even at room temperature, and the transition at T ≈ 255 K can be characterized as a strong-to-strong dynamical transition. Confinement of water in the grooves of DNA favors the formation of a low density four-coordinated state (as a consequence of enthalpy−entropy balance) that makes the liquid−liquid transition stronger. The low temperature water is characterized by pronounced tetrahedral order, as manifested in the sharp rise near 109° in the O−O−O angle distribution. We find that the Adams−Gibbs relation between configurational entropy and translational diffusion holds quite well when the two quantities are plotted together in a master plot for different region of aqueous DNA duplex (bulk, major, and minor grooves) at different temperatures. The activation energy for the transfer of water molecules between different regions of DNA is found to be weakly dependent on temperature.by Subrata Pal et al.

Regulation of Cell Proliferation and Migration by miR-203 via GAS41/miR-10b Axis in Human Glioblastoma Cells

<div><p>Glioma amplified sequence 41(GAS41) is a potent transcription factor that play a crucial role in cell proliferation and survival. In glioblastoma, the expression of GAS41 at both transcriptional and post transcriptional level needs to be tightly maintained in response to cellular signals. Micro RNAs (miRNA) are small non coding RNA that act as important regulators for modulating the expression of various target genes. Studies have shown that several miRNAs play role in the post-transcriptional regulation of GAS41. Here we identified GAS41 as a novel target for endogenous miR-203 and demonstrate an inverse correlation of miR-203 expression with GAS41 in glioma cell lines (HNGC2 and U87). Over expression of miR-203 negatively regulates GAS41 expression in U87 and HNGC2 cell lines. Moreover, miR-203 restrained miR-10b action by suppressing GAS41. GAS41 is essential for repressing p53 in tumor suppressor pathway during cell proliferation. Enforced expression of GAS41 produced contradictory effect on miR-203 but was able to enhance p53 tumor suppressor pathway associated protein. It was also found that miR-203 maintains the stability of p53 as knock down of p53 expression using siRNA resulted in down regulation of pri-miR and mature miR-203 expression. Conversely reconstitution of miR-203 expression induced apoptosis and inhibited migratory property of glioma cells. Taken together, we show that miR-203 is a key negative regulator of GAS41 and acts as tumor suppressor microRNA in glioma.</p></div

miR-203 dispensable for p53 stabilization.

<p><b>(A)</b> Co immunoprecipitation studies using antip53 antibody in HNGC2 and U87 cells transfected with empty vector and miR-203 construct for 24 hr.The p53/MDM2 complex and the input was detected by westernblot. <b>(B)</b> Real time PCR analysis of p53 mRNA expression in HNGC2 and U87 cells transfected with p53 siRNA (p53si) and scrambled siRNA(scrsi) as control. GAPDH used for normalization. Bars represent RQ (2^-ddct) of p53 expression normalized with GAPDH. ***represent the significant lable with p value <0.001 vs control.All experiments were conducted for at least three times. <b>(C)</b>Western blot analysis showing the level of p53 expression in HNGC2 and U87 cells transiently transfected with scrambled siRNA and p53 siRNA. β-actin <b>is</b> used as gel loading control <b>(D)</b> Quantitative PCR analysis of pri-miR-203 and mature miR-203 in cells introduced with scrambled siRNA (scrsi) and p53 siRNA (p53 si). Bars represent RQ (2^-ddct) of pri-miR-203 and mature miR-203 expression normalized with U6. *** represents p value <0.001,**represent p value< 0.01,*represent p value <0.05. All the above experiments were performed in triplicates</p