measuring-crop-motility-and-food-passaging-in-drosophila

Measuring Crop Motility and Food Passaging in <em>Drosophila</em>

Most animals use the gastrointestinal (GI) tract to digest food. The movement of the ingested food in the GI tract is essential for nutrient absorption. ...

yangzhou university

Yangzhou University

Identifying cancer driver genes and exploring their functions are essential and the most urgent need in basic cancer research. Developing efficient methods to differentiate between driver and passenger somatic mutations revealed from large-scale cancer genome sequencing data is critical to cancer driver gene discovery. Here, we compared distinct features of SNP with SNV data in detail and found that the weighted ratio of SNV to SNP (termed as WVPR) is an excellent indicator for cancer driver genes. The power of WVPR was validated by accurate predictions of known drivers. We ranked most of human genes by WVPR and did functional analyses on the list. The results demonstrate that driver genes are usually highly enriched in chromatin organization related genes/pathways. And some protein complexes, such as histone acetyltransferase, histone methyltransferase, telomerase, centrosome, sin3 and U12-type spliceosomal complexes, are hot spots of driver mutations. Furthermore, this study identified many new potential driver genes (e.g. NTRK3 and ZIC4) and pathways including oxidative phosphorylation pathway, which were not deemed by previous methods. Taken together, our study not only developed a method to identify cancer driver genes/pathways but also provided new insights into molecular mechanisms of cancer development. 

Genome-wide prediction of cancer driver genes based on SNP and cancer SNV data.

Gestational diabetemellitus (GDM) is a condition whereby a mother's glucose tolerance is impaired with onset or first recognition during pregnancy which is not either type 1 or type 2 diabetes mellitus. Oxidative stress plays an essential role in diabetes, however, whether it also includes in GDM has not been fully clarified. Therefore, we investigated the changes of oxidative stress biomarkers and their relationship with pregnancy outcomes in patients with GDM. The serum and placenta were collected for absorbance-based assay and immunohistochemistry assay (IHC). The patients' clinical information was collected and the pregnancy outcome was tracked. It was found that elder age is a risk factor to result in GDM. Moreover, GDM patients showed poor clinical factors or outcomes including higher prepregnancy weight and BMI value, premature delivery, higher rates of cesarean delivery, macrosomia, premature rupture of fetal membranes (PROM). Increasing serum MDA level and decline GSH and SOD levels were observed in GDM patients. Meanwhile, HO-1, Nrf2 and NQO1 overexpressed in GDM placental tissues. In the GDM group, MDA level was negatively associated with prepregnancy weight, while, SOD level was positively correlated with neonatal birth weight. We found an intensive relationship between SOD content and preterm birth in the GDM group. There is no significant difference between the level of MDA/GSH and neonatal birth weight as well as preterm birth. MDA, GSH and SOD levels were not associated with an increased risk of cesarean delivery or PROM. This study indicates aberrant expression of oxidative stress related proteins affects the pregnancy outcome of GDM patients.

Aberrant expression of oxidative stress related proteins affects the pregnancy outcome of gestational diabetes mellitus patients.

Progestins has been used widely for endometrial cancer (EC) patients. However, long term use of high dose progestin often lead to progestin resistance. Our previous studies have demonstrated that metformin reversed progestin resistance through the downregulation of the expression of glyoxalase I (GLOI) in type I endometrial cancer. Recent studies have demonstrated the role of Ten-eleven translocation 1 (TET1) in endometrial cancer, but the physiological role of TET1 in GLOI-mediated progestin resistance has been poorly addressed. Immunohistochemistry was used to detect the expression of TET1, GLOI and 5hmC in various endometrium. Western blot was carried out to analyses TET1 and GLOI expression with different treatment. Cell counting kit-8 was used to evaluate cell proliferation after various treatment. Dot blot assay and HMeDIP assay were performed to detect global hydroxmethylation levels and hydroxymethylation levels in GLOI gene respectively. In current study, we found that metformin effectively sensitized progestin in endometrial cancer cell lines through the down regulation of the expression of TET1 and GLOI. Interestingly, the exogenous increase of TET1 expression enhanced total 5hmC level and hydroxymethylation modification in glyoxalase I promoter region. This effect was abated by metformin treatment. Moreover, the expression profile of TET1 and glyoxalase I in various endometrial tissue parallelized with 5hmC level. Therefore, this finding suggests that metformin sensitized progestin in endometrial cancer through the TET1-5hmC-GLOI signaling pathway.

Metformin sensitizes endometrial cancer cells to progestin by targeting TET1 to downregulate glyoxalase I expression.

The TORC1 regulator GATOR1/SEACIT controls meiotic entry and early meiotic events in yeast. However, how metabolic pathways influence meiotic progression in metazoans remains poorly understood. Here we examine the role of the TORC1 regulators GATOR1 and GATOR2 in the response to meiotic double-stranded breaks (DSB) during  oogenesis. We find that in mutants of the GATOR2 component , meiotic DSBs trigger the constitutive downregulation of TORC1 activity and a permanent arrest in oocyte growth. Conversely, in GATOR1 mutants, high TORC1 activity results in the delayed repair of meiotic DSBs and the hyperactivation of p53. Unexpectedly, we found that GATOR1 inhibits retrotransposon expression in the presence of meiotic DSBs in a pathway that functions in parallel to p53. Thus, our studies have revealed a link between oocyte metabolism, the repair of meiotic DSBs and retrotransposon expression.

The GATOR complex regulates an essential response to meiotic double-stranded breaks in .

Aging and age-related diseases occur in almost all organisms. Recently, it was discovered that the inhibition of target of rapamycin complex 1 (TORC1), a conserved complex that mediates nutrient status and cell metabolism, can extend an individual's lifespan and inhibit age-related diseases in many model organisms. However, the mechanism whereby TORC1 affects aging remains elusive. Here, we use a loss-of-function mutation in , a component of GATOR1 that mediates amino acid levels and inhibits TORC1 activity, to investigate the effect of increased TORC1 activity on the occurrence of age-related digestive dysfunction in . We found that the  mutation decreased  lifespan. Furthermore, the  mutant had a distended crop, with food accumulation at an early age. Interestingly, the inappropriate food distribution and digestion along with decreased crop contraction in  mutant can be rescued by decreasing TORC1 activity. In addition, -mutant flies exhibited age-related phenotypes in the midgut, including short gut length, a high rate of intestinal stem cell proliferation, and metabolic dysfunction, which could be rescued by inhibiting TORC1 activity. Our findings showed that the gastrointestinal tract aging process is accelerated in -mutant flies, owing to high TORC1 activity, which suggested that TORC1 promotes digestive tract senescence.

Article	Year
Genome-wide prediction of cancer driver genes based on SNP and cancer SNV data. American journal of cancer research\| PubMed ID: 25057442	2014
Aberrant expression of oxidative stress related proteins affects the pregnancy outcome of gestational diabetes mellitus patients. American journal of translational research\| PubMed ID: 30787985	2019
Metformin sensitizes endometrial cancer cells to progestin by targeting TET1 to downregulate glyoxalase I expression. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie\| PubMed ID: 30849641	2019
The GATOR complex regulates an essential response to meiotic double-stranded breaks in . eLife\| PubMed ID: 31650955	2019
The TORC1 inhibitor Nprl2 protects age-related digestive function in . Aging\| PubMed ID: 31712450	2019

Youheng Wei

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