Hepaticoduodenostomy as a technique for biliary anastomosis in children with choledochal cyst: An experience with 31 cases

Objective The aim of this study was to investigate the efficacy and complications of hepaticoduodenostomy in the treatment of choledochal cyst in children. Summary background data The conventional treatment of choledochal cyst includes Roux-en-Y hepaticojejunostomy for biliary reconstruction. This procedure, however, disrupts normal bowel continuity and requires two anastomoses. We studied the technique of hepaticoduodenostomy as an effective alternative to this technique.Patients and methods A total of 31 children undergoing  hepatoduodenostomy for choledochal cyst over a period of 9 years were included in this study.Results The patients operated upon had outcomes similar to those treated by the Roux-en-Y technique in other studies.Conclusion Hepaticoduodenostomy is an effective alternative to the conventional Roux-en-Y anastomotic technique in cases of choledochal cyst in children. Keywords: choledochal cyst, hepaticoduodenostomy, pediatri

Festivals and deterioration of aquatic environment: A case study of Idol immersion in Tapi River, India

In the civil society different festivals are celebrated, these are the integral part of human life and many of festivals are religious, seasonal change and culturally important. The present study elucidated environmental impact of Ganesh idol immersion on water quality of Tapi River and for this purpose water samples were collected during different durations (pre immersion, during immersion and post immersion) from selected sampling stations or idol immersion points of Tapi River. The important water quality parameters like pH, temperature, dissolved oxygen, free carbon dioxide, total hardness, total alkalinity, biological oxygen demand, chemical oxygen demand, oil & grease and total calcium were analysed for the study. Result shows that dissolved oxygen was depleted while remaining parameter were increased during the idol immersion and it was concluded that aquatic ecosystem of Tapi river was deteriorated and pollution and nutrient load were increased due to these religious activities. The celebration of festivals and these religious activities can’t stop but pollution can reduce to save the river

CCAT2, a novel noncoding RNA mapping to 8q24, underlies metastatic progression and chromosomal instability in colon cancer

The functional roles of SNPs within the 8q24 gene desert in the cancer phenotype are not yet well understood. Here, we report that CCAT2, a novel long noncoding RNA transcript (lncRNA) encompassing the rs6983267 SNP, is highly overexpressed in microsatellite-stable colorectal cancer and promotes tumor growth, metastasis, and chromosomal instability. We demonstrate that MYC, miR-17-5p, and miR-20a are up-regulated by CCAT2 through TCF7L2-mediated transcriptional regulation. We further identify the physical interaction between CCAT2 and TCF7L2 resulting in an enhancement of WNT signaling activity. We show that CCAT2 is itself a WNT downstream target, which suggests the existence of a feedback loop. Finally, we demonstrate that the SNP status affects CCAT2 expression and the risk allele G produces more CCAT2 transcript. Our results support a new mechanism of MYC and WNT regulation by the novel lncRNA CCAT2 in colorectal cancer pathogenesis, and provide an alternative explanation of the SNP-conferred cancer risk

Preclinical efficacy studies of a novel nanoparticle-based formulation of paclitaxel that out-performs Abraxane

Poly-(γ-l-glutamylglutamine)–paclitaxel (PGG–PTX) is a novel polymer-based formulation of paclitaxel (PTX) in which the PTX is linked to the polymer via ester bonds. PGG–PTX is of interest because it spontaneously forms very small nanoparticles in plasma. In mouse models, PGG–PTX increased tumor exposure to PTX by 7.7-fold relative to that produced by PTX formulated in Cremophor. In this study, the efficacy of PGG–PTX was compared to that of Abraxane, an established nanoparticular formulation of PTX, in three different tumor models. Efficacy was quantified by delay in tumor growth of NCI H460 human lung cancer, 2008 human ovarian cancer and B16 melanoma xenografts growing in athymic mice following administration of equitoxic doses of PGG–PTX and Abraxane administered on either a single dose or every 7 day schedule. Toxicity was assessed by change in total body weight. The efficacy and toxicity of PGG–PTX was shown to increase with dose in the H460 model. PGG–PTX was ~1.5-fold less potent than Abraxane. PGG–PTX produced statistically significantly greater inhibition of tumor growth than Abraxane in all three tumor models when mice were given single equitoxic doses of drug. When given every 7 days for 3 doses, PGG–PTX produced greater inhibition of tumor growth while generating much less weight loss in mice bearing H460 tumors. PGG–PTX has activity that is superior to that of Abraxane in multiple tumor models. PGG–PTX has the potential to out-perform Abraxane in enhancing the delivery of PTX tumors while at the same time further reducing the toxicity of both single dose and weekly treatment regimens

The Werner Syndrome Protein Suppresses Telomeric Instability Caused by Chromium (VI) Induced DNA Replication Stress

Telomeres protect the chromosome ends and consist of guanine-rich repeats coated by specialized proteins. Critically short telomeres are associated with disease, aging and cancer. Defects in telomere replication can lead to telomere loss, which can be prevented by telomerase-mediated telomere elongation or activities of the Werner syndrome helicase/exonuclease protein (WRN). Both telomerase and WRN attenuate cytotoxicity induced by the environmental carcinogen hexavalent chromium (Cr(VI)), which promotes replication stress and DNA polymerase arrest. However, it is not known whether Cr(VI)-induced replication stress impacts telomere integrity. Here we report that Cr(VI) exposure of human fibroblasts induced telomeric damage as indicated by phosphorylated H2AX (γH2AX) at telomeric foci. The induced γH2AX foci occurred in S-phase cells, which is indicative of replication fork stalling or collapse. Telomere fluorescence in situ hybridization (FISH) of metaphase chromosomes revealed that Cr(VI) exposure induced an increase in telomere loss and sister chromatid fusions that were rescued by telomerase activity. Human cells depleted for WRN protein exhibited a delayed reduction in telomeric and non-telomeric damage, indicated by γH2AX foci, during recovery from Cr(VI) exposure, consistent with WRN roles in repairing damaged replication forks. Telomere FISH of chromosome spreads revealed that WRN protects against Cr(VI)-induced telomere loss and downstream chromosome fusions, but does not prevent chromosome fusions that retain telomere sequence at the fusion point. Our studies indicate that environmentally induced replication stress leads to telomere loss and aberrations that are suppressed by telomerase-mediated telomere elongation or WRN functions in replication fork restoration

3D genomics across the tree of life reveals condensin II as a determinant of architecture type

We investigated genome folding across the eukaryotic tree of life. We find two types of three-dimensional(3D) genome architectures at the chromosome scale. Each type appears and disappears repeatedlyduring eukaryotic evolution. The type of genome architecture that an organism exhibits correlates with theabsence of condensin II subunits. Moreover, condensin II depletion converts the architecture of thehuman genome to a state resembling that seen in organisms such as fungi or mosquitoes. In this state,centromeres cluster together at nucleoli, and heterochromatin domains merge. We propose a physicalmodel in which lengthwise compaction of chromosomes by condensin II during mitosis determineschromosome-scale genome architecture, with effects that are retained during the subsequent interphase.This mechanism likely has been conserved since the last common ancestor of all eukaryotes.C.H. is supported by the Boehringer Ingelheim Fonds; C.H., Á.S.C., and B.D.R. are supported by an ERC CoG (772471, “CohesinLooping”); A.M.O.E. and B.D.R. are supported by the Dutch Research Council (NWO-Echo); and J.A.R. and R.H.M. are supported by the Dutch Cancer Society (KWF). T.v.S. and B.v.S. are supported by NIH Common Fund “4D Nucleome” Program grant U54DK107965. H.T. and E.d.W. are supported by an ERC StG (637597, “HAP-PHEN”). J.A.R., T.v.S., H.T., R.H.M., B.v.S., and E.d.W. are part of the Oncode Institute, which is partly financed by the Dutch Cancer Society. Work at the Center for Theoretical Biological Physics is sponsored by the NSF (grants PHY-2019745 and CHE-1614101) and by the Welch Foundation (grant C-1792). V.G.C. is funded by FAPESP (São Paulo State Research Foundation and Higher Education Personnel) grants 2016/13998-8 and 2017/09662-7. J.N.O. is a CPRIT Scholar in Cancer Research. E.L.A. was supported by an NSF Physics Frontiers Center Award (PHY-2019745), the Welch Foundation (Q-1866), a USDA Agriculture and Food Research Initiative grant (2017-05741), the Behavioral Plasticity Research Institute (NSF DBI-2021795), and an NIH Encyclopedia of DNA Elements Mapping Center Award (UM1HG009375). Hi-C data for the 24 species were created by the DNA Zoo Consortium (www.dnazoo.org). DNA Zoo is supported by Illumina, Inc.; IBM; and the Pawsey Supercomputing Center. P.K. is supported by the University of Western Australia. L.L.M. was supported by NIH (1R01NS114491) and NSF awards (1557923, 1548121, and 1645219) and the Human Frontiers Science Program (RGP0060/2017). The draft A. californica project was supported by NHGRI. J.L.G.-S. received funding from the ERC (grant agreement no. 740041), the Spanish Ministerio de Economía y Competitividad (grant no. BFU2016-74961-P), and the institutional grant Unidad de Excelencia María de Maeztu (MDM-2016-0687). R.D.K. is supported by NIH grant RO1DK121366. V.H. is supported by NIH grant NIH1P41HD071837. K.M. is supported by a MEXT grant (20H05936). M.C.W. is supported by the NIH grants R01AG045183, R01AT009050, R01AG062257, and DP1DK113644 and by the Welch Foundation. E.F. was supported by NHGR

Human-Mediated Emergence as a Weed and Invasive Radiation in the Wild of the CD Genome Allotetraploid Rice Species (Oryza, Poaceae) in the Neotropics

BACKGROUND: The genus Oryza is being used as a model in plant genomic studies although there are several issues still to be resolved regarding the spatio-temporal evolution of this ancient genus. Particularly contentious is whether undated transoceanic natural dispersal or recent human interference has been the principal agent determining its present distribution and differentiation. In this context, we studied the origin and distribution history of the allotetraploid CD rice genome. It is endemic to the Neotropics but the genus is thought to have originated in the Paleotropics, and there is relatively little genetic divergence between some orthologous sequences of the C genome component and their Old World counterparts. METHODOLOGY/PRINCIPAL FINDINGS: Because of its allotetraploidy, there are several potential pitfalls in trying to date the formation of the CD genome using molecular data and this could lead to erroneous estimates. Therefore, we rather chose to rely on historical evidence to determine whether or not the CD genome was present in the Neotropics before the arrival of Columbus. We searched early collections of herbarium specimens and studied the reports of explorers of the tropical Americas for references to rice. In spite of numerous collectors traveling inland and collecting Oryza, plants determined as CD genome species were not observed away from cultivated rice fields until 1869. Various arguments suggest that they only consisted of weedy forms until that time. CONCLUSIONS/SIGNIFICANCE: The spatio-temporal distribution of herbarium collections fits a simple biogeographical scenario for the emergence in cultivated rice fields followed by radiation in the wild of the CD genome in the Neotropics during the last four centuries. This probably occurred from species introduced to the Americas by humans and we found no evidence that the CD genome pre-existed in the Old World. We therefore propose a new evolutionary hypothesis for such a recent origin of the CD genome. Moreover, we exemplify how an historical approach can provide potentially important information and help to disentangle the timing of evolutionary events in the history of the Oryza genomes

Control of chromosome stability by the \u3b2-TrCP\u2013REST\u2013Mad2 axis

REST/NRSF (repressor-element-1-silencing transcription factor/ neuron-restrictive silencing factor) negatively regulates the tran- scription of genes containing RE1 sites1,2. REST is expressed in non-neuronal cells and stem/progenitor neuronal cells, in which it inhibits the expression of neuron-specific genes. Overexpression of REST is frequently found in human medulloblastomas and neuroblastomas3\u20137, in which it is thought to maintain the stem character of tumour cells. Neural stem cells forced to express REST and c-Myc fail to differentiate and give rise to tumours in the mouse cerebellum3. Expression of a splice variant of REST that lacks the carboxy terminus has been associated with neuronal tumours and small-cell lung carcinomas8\u201310, and a frameshift mutant (REST-FS), which is also truncated at the C terminus, has oncogenic properties11. Here we show, by using an unbiased screen, that REST is an interactor of the F-box protein b-TrCP. REST is degraded by means of the ubiquitin ligase SCFb-TrCP dur- ing the G2 phase of the cell cycle to allow transcriptional derepres- sion of Mad2, an essential component of the spindle assembly checkpoint. The expression in cultured cells of a stable REST mutant, which is unable to bind b-TrCP, inhibited Mad2 expres- sion and resulted in a phenotype analogous to that observed in Mad21/2 cells. In particular, we observed defects that were con- sistent with faulty activation of the spindle checkpoint, such as shortened mitosis, premature sister-chromatid separation, chro- mosome bridges and mis-segregation in anaphase, tetraploidy, and faster mitotic slippage in the presence of a spindle inhibitor. An indistinguishable phenotype was observed by expressing the oncogenic REST-FS mutant11, which does not bind b-TrCP. Thus, SCFb-TrCP-dependent degradation of REST during G2 permits the optimal activation of the spindle checkpoint, and consequently it is required for the fidelity of mitosis. The high levels of REST or its truncated variants found in certain human tumours may contri- bute to cellular transformation by promoting genomic instability