Drosophila MARF1 ensures proper oocyte maturation by regulating nanos expression.

Meiosis and oocyte maturation are tightly regulated processes. The meiosis arrest female 1 (MARF1) gene is essential for meiotic progression in animals; however, its detailed function remains unclear. In this study, we examined the molecular mechanism of dMarf1, a Drosophila homolog of MARF1 encoding an OST and RNA Recognition Motif (RRM) -containing protein for meiotic progression and oocyte maturation. Although oogenesis progressed in females carrying a dMarf1 loss-of-function allele, the dMarf1 mutant oocytes were found to contain arrested meiotic spindles or disrupted microtubule structures, indicating that the transition from meiosis I to II was compromised in these oocytes. The expression of the full-length dMarf1 transgene, but none of the variants lacking the OST and RRM motifs or the 47 conserved C-terminal residues among insect groups, rescued the meiotic defect in dMarf1 mutant oocytes. Our results indicate that these conserved residues are important for dMarf1 function. Immunoprecipitation of Myc-dMarf1 revealed that several mRNAs are bound to dMarf1. Of those, the protein expression of nanos (nos), but not its mRNA, was affected in the absence of dMarf1. In the control, the expression of Nos protein became downregulated during the late stages of oogenesis, while it remained high in dMarf1 mutant oocytes. We propose that dMarf1 translationally represses nos by binding to its mRNA. Furthermore, the downregulation of Nos induces cycB expression, which in turn activates the CycB/Cdk1 complex at the onset of oocyte maturation

コウクウ ヘンペイ ジョウヒ ガンサイボウ ニ タイスル フッカ ピリミジンケイ ケイコウ コウガンザイ TS-1 ト ホウシャセン トノ ヘイヨウ コウカ ノ カイセキ

Background: TS-1 is a new oral anti-neoplastic agent which can inhibit cell growth and induce apoptosis in certain types of cancer cells including gastric carcinomas, colorectal carcinomas, and oral squamous cell carcinomas. However, the combined effects of TS-1 and radiation on oral squamous cell carcinomas have not yet been clarified. Purpose: We evaluated anti-tumor effect of TS-1 in combination with radiation both in vitro and in vivo against a human oral squamous cell carcinoma cell line, and investigated the mechanism of apoptosis enhancing activity by the combination with TS-1 and radiation. Materials and Methods: A human oral squamous cell carcinoma cell line, B88, was used in vitro and in vivo xenografts of nude mice. In in vitro analysis, attached cells were treated with TS-1 (50μg/ml) for 1h and then irradiated (3, 6, 9, 12, 15 Gy), or they were treated with TS-1 for 1h after radiation. Cell survival was determined by MTT assay and clonogenic assay. In in vivo analysis, TS-1 (10mg/kg) was administered orally 1h before radiation (1.5 Gy), or 1h after radiation for five consecutive days. Apoptotic cells were detected by TdT-mediated dUTP-biotin nick end labeling method. Phosphorylated-Akt/protein kinase B (PKB) was examined by Western blotting. Expressions of Rad50, Ku70, Ku80 and catalytic subunit of DNA-dependent protein kinase in xenograft tumors were investigated by immunohistochemistry. Results: TS-1 in combination with radiation has a remarkable effect on decreasing in vitro cell growth. In vitro clonogenic survival experiments demonstrated the dose enhancement ratio of 1.22 (radiation+TS-1), or 1.45 (TS-1+radiation) in B88 cells. In addition, the combined treatment of TS-1 and radiation resulted in an increased DNA fragmentation by detecting Hoechst 33258 staining, and suppressing the activation of Akt/PKB. Moreover, apoptosis of the cells by combined treatment of TS-1 and radiation was associated with generation of reactive oxygen/nitrogen species and the activation of caspase-8, caspase-9 and caspase-3. The combination of TS-1 and radiation was more effective than either agent alone in in vivo nude mouse model. Moreover, TS-1 administration before radiation was more effective than TS-1 administration after radiation. Futhermore, the combination of TS-1 and radiation could induce apoptosis significantly than either agent alone. Conclusions: These data demonstrate that the combination of TS-1 and fractionated radiotherapy is more effective against a human oral squamous cell carcinoma cell than either agent alone, and that TS-1 administration before radiation is more effective than after radiation, suggesting a potential clinical applicability of combination treatment of TS-1 and radiation in oral squamous cell carcinoma therapies

miRNA/siRNA-directed pathway to produce noncoding piRNAs from endogenous protein-coding regions ensures Drosophila spermatogenesis

PIWI-interacting RNA (piRNA) pathways control transposable elements (TEs) and endogenous genes, playing important roles in animal gamete formation. However, the underlying piRNA biogenesis mechanisms remain elusive. Here, we show that endogenous protein coding sequences (CDSs), which are normally used for translation, serve as origins of noncoding piRNA biogenesis in Drosophila melanogaster testes. The product, namely, CDS-piRNAs, formed silencing complexes with Aubergine (Aub) in germ cells. Proximity proteome and functional analyses show that CDS-piRNAs and cluster/TE-piRNAs are distinct species occupying Aub, the former loading selectively relies on chaperone Cyclophilin 40. Moreover, Argonaute 2 (Ago2) and Dicer-2 activities were found critical for CDS-piRNA production. We provide evidence that Ago2-bound short interfering RNAs (siRNAs) and microRNAs (miRNAs) specify precursors to be processed into piRNAs.We further demonstrate that Aub is crucial in spermatid differentiation, regulating chromatins through mRNA cleavage. Collectively, our data illustrate a unique strategy used by male germ line, expanding piRNA repertoire for silencing of endogenous genes during spermatogenesis.Iki T., Kawaguchi S., Kai T.. miRNA/siRNA-directed pathway to produce noncoding piRNAs from endogenous protein-coding regions ensures Drosophila spermatogenesis. Science Advances 9, eadh0397 (2023); https://doi.org/10.1126/sciadv.adh0397

Removing Diethylphthalate (DEP) from Water Systems using Zeolites and Mesoporous Materials

In order to remove diethylphthalate (DEP) molecules from water systems, zeolites of faujasite (FAU), ferrierite (FER), mordenite (MOR), and mesoporous silica (MCM-41) were employed in this study. 1H nuclear-magnetic-resonance (NMR) spectra showed that FAU was effective in eliminating DEP from aqueous solutions. In addition, solid-state 1H NMR spectra with a magic-angle-spinning (MAS) rate of 30 kHz revealed that a larger amount of DEP was adsorbed on FAUs with higher Si/Al ratios. Our NMR spectra also showed that a chemical shift of the signal assigned to water molecules adsorbed on the FAUs is linked to the amount of DEP adsorption. 1H MAS NMR spectra also revealed that DEP molecules prefer to adsorb on the four-membered ring site rather than the center or/and window of the supercage in FAUs. Since porous materials are frequently present in ground and water systems such as rivers, ponds, and lakes, this study also showed that DEP could adsorb onto soils in aquatic environments and remain in the water system for a long time

Cystic Lymphangioma of the Pancreas with Spontaneous Rupture: Report of a Case

Lymphangioma is a benign and congenital malformation of the lymphatic system. Most lymphangiomas are preferentially located in the head and neck region. The abdominal organs are uncommon sites of origin. Several cases of lymphangioma in abdominal organs were reported, however, the pancreas is one of the rarest origins. Generally, intra-abdominal lymphangioma is asymptomatic and found incidentally, but in some cases, the patient complains of abdominal distension or a palpable mass. We describe the case of a 38-year-old male who presented with sudden-onset upper abdominal pain. Rupture of a cystic tumor of the pancreatic head was suspected, based on the findings of computed tomography, magnetic resonance imaging and endoscopic ultrasonography. Subtotal stomach-preserving pancreaticoduodenectomy was undertaken. The tumor, which was 4 × 4.5 × 8 cm in size, was pathologically diagnosed as a cystic lymphangioma. In conclusion, pancreatic lymphangioma is mostly asymptomatic, a ruptured case causing ‘acute abdomen’ has never been reported. Since lymphangioma is benign, it could be observed with accurate diagnosis. The surgical indication would be limited to cases of symptomatic lymphangiomas

Role of Gremlins in the Aortic Arch of Spontaneously Hypertensive and Hyperlipidemic Rats

Atherosclerosis is a lifestyle-related disease that plays a major role in cardiovascular disease. Recently, we found that gene expression of Gremlin 2, an antagonist of bone morphogenetic protein (BMP), was significantly increased in the aorta of spontaneously hypertensive and hyperlipidemic rats (SHHRs) fed a high-fat, 30% sucrose solution diet (HFDS). However, the role of Gremlin 1 (Grem1) and Gremlin 2 (Grem2) in the aortic arch of rats under hypertensive, hyperlipidemic, and hyperglycemic conditions remains unclear. Therefore, in the present study we investigated the molecular role of Gremlins in the aorta of SHHRs. Four-month-old male Sprague-Dawley rats and SHHRs were fed a normal diet or the HFDS ad libitum for 4 months. Then, gene and protein expression was analyzed using quantitative polymerase chain reaction and western blotting, respectively. Grem1 and Grem2 protein expression was increased, whereas phosphorylated Smad1/5 protein expression was low, in the aorta of SHHRs fed the HFDS. In addition, the expression of the downstream gene targets of BMP, namely inhibitor of DNA binding 1 (Id1) and atonal homolog 8 (Atoh8), was decreased in aortas of SHHRs fed the HFDS. Furthermore, mRNA expression of Snail, α-smooth muscle actin (αSMA), and Fibronectin was increased in SHHRs fed the HFDS. These findings suggest that upregulation of Gremlins attenuates the activation of BMP signaling, which contributes to fibrogenesis of the aorta

Investigation of Cell Migration and Invasion Using Real-time Cell Analysis, as well as the Association with Matrix Metalloproteinase-9 in Oral Squamous Cell Carcinomas

The recently developed technology of real-time cell analysis (RTCA) was designed to analyze cell migration and invasion in vitro. In this study, we investigated these cellular factors in oral squamous cell carcinomas (OSCCs) of the tongue and floor of the mouth with RTCA. We also examined the associated matrix metalloproteinases (MMPs) and integrins. We used the cell lines SCC-4 and SAS, which are human poorly differentiated OSCCs from the tongue, and HO-1-u-1, which are human poorly differentiated OSCCs from the floor of the mouth. Using RTCA, cell migration was assessed on fibronectin–coated CIM-Plates, and invasion was assessed on fibronectin- and matrigel-coated CIM-Plates. SCC-4 cells demonstrated a high ability for cell migration and invasion compared with SAS and HO-1-u-1 cells. The SCC-4 cells also expressed high levels of MMP-9 and integrin α1 mRNA compared with SAS and HO-1-u-1 cells. The MMP inhibitor Marimastat blocked migration and invasion of all OSCCs. The findings suggest that MMP-9 is associated with cell migration and invasion in OSCCs, and indicate that RTCA will be useful for analyzing the metastatic capability of OSCCs and developing more effective new drugs for this disease

Using spin to understand the formation of LIGO's black holes

With the detection of four candidate binary black hole (BBH) mergers by the Advanced LIGO detectors thus far, it is becoming possible to constrain the properties of the BBH merger population in order to better understand the formation of these systems. Black hole (BH) spin orientations are one of the cleanest discriminators of formation history, with BHs in dynamically formed binaries in dense stellar environments expected to have spins distributed isotropically, in contrast to isolated populations where stellar evolution is expected to induce BH spins preferentially aligned with the orbital angular momentum. In this work we propose a simple, model-agnostic approach to characterizing the spin properties of LIGO's BBH population. Using measurements of the effective spin of the binaries, which is LIGO's best constrained spin parameter, we introduce a simple parameter to quantify the fraction of the population that is isotropically distributed, regardless of the spin magnitude distribution of the population. Once the orientation characteristics of the population have been determined, we show how measurements of effective spin can be used to directly constrain the underlying BH spin magnitude distribution. Although we find that the majority of the current effective spin measurements are too small to be informative, with LIGO's four BBH candidates we find a slight preference for an underlying population with aligned spins over one with isotropic spins (with an odds ratio of 1.1). We argue that it will be possible to distinguish symmetric and anti-symmetric populations at high confidence with tens of additional detections, although mixed populations may take significantly more detections to disentangle. We also derive preliminary spin magnitude distributions for LIGO's black holes, under the assumption of aligned or isotropic populations

Quantification of Cell Migration and Invasion, and Their Association with Periostin in Anaplastic Thyroid Cancer, Using a Real-time Cell Analyzer

Anaplastic thyroid cancer (ATC) is known to be a highly malignant cancer of the thyroid with a high mortality rate. In a previous study, we used real-time cell analysis (RTCA) to analyze cell migration and invasion of oral squamous cell carcinomas (OSCCs) of the tongue and floor of the mouth. In the present study, we investigated cell migration and invasion of ATC using RTCA, as well as their association with periostin, matrix metalloproteinases (MMPs), and integrins. Experiments were performed on TCO-1 and HTC/C3 cells, which are human ATC cell lines. OSCC cell lines were used for comparison. Using the cell analysis system, cell migration was assessed on fibronectin-coated CIM-Plates, whereas invasion was assessed on fibronectin- and matrigel-coated CIM-Plates. SCC-4 cells exhibited high cell migration and invasion activity compared with other OSCC cell lines. TCO-1 cells exhibited equivalent cell invasion but stronger migration than SCC-4 cells. Although TCO-1 cells had strong invasive activity, they did not express MMP-9, unlike SCC-4 cells. Conversely, periostin expression was high in TCO-1 cells. Therefore, periostin expression appears to be associated with the cell migration and invasion activity of ATC. The RTCA system will be useful for the analysis of the metastatic characteristics of ATC in head and neck cancer

Vildagliptin Improves Glucose Tolerance and Decreases Plasma Triglycerides in Sprague-Dawley Rats

The number of patients with lifestyle-related diseases, including type 2 diabetes, is increasing. The onset of type 2 diabetes can be prevented by dietary and exercise interventions, as well as drug therapy. Dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists have attracted attention recently as treatments for diabetes, and incretin hormones have been reported to have a protective effect on pancreatic β-cells. It is not clear whether vildagliptin (VIL) can prevent the progression of lifestyle-related disease. Thus, in the present study, Sprague-Dawley rats were fed a high-fat diet with sucrose water (HFDS) to determine whether VIL could inhibit deterioration in glucose tolerance and improve other biomarkers of lipid disorder. Four-month-old male Sprague-Dawley rats were divided into three groups (n = 7 in each group); one group was fed a normal diet for 4 months, whereas the remaining two groups were fed the HFDS, with or without VIL for 4 months. When rats were 7 months of age, they were subjected to an intraperitoneal glucose tolerance test (IPGTT); biomarkers of lipid disorder were measured in 8-month-old rats. There was a decrease in the glucose spike in the IPGTT 10min after loading in the HFDS + VIL group and plasma triglyceride (TG) levels were significantly lower in these rats compared with the HFDS group. The decreased TG levels in HFDS + VIL rats were accompanied by decreases in plasma chylomicron levels. These results suggest that VIL can prophylactically inhibit decreases in pancreatic β-cell function in type 2 diabetes and reduce the risk of cardiovascular disease due to high TG levels. Thus, VIL administration may contribute to the prevention of lifestyle-related disease