Heparan sulfate proteoglycan is an important attachment factor for cell entry of Akabane and Schmallenberg viruses

Akabane (AKAV) and Schmallenberg (SBV) viruses are Orthobunyavirus transmitted by arthropod vectors with a broad cellular tropism in vitro as well as in vivo Both AKAV and SBV cause arthrogryposis-hydranencephaly syndrome in ruminants. The main cellular receptor and attachment factor for entry of these orthobunyaviruses are unknown. Here, we found that AKAV and SBV infections were inhibited by the addition of heparin or enzymatic removal of cell surface heparan sulfates. To confirm this finding, we prepared heparan sulfate proteoglycan (HSPG)-knockout (KO) cells by using a CRISPR/Cas9 system and measured the binding quantities of these viruses to cell surfaces. We observed a substantial reduction in AKAV and SBV binding to cells, limiting the infections by these viruses. These data demonstrate that HSPGs are important cellular attachment factors for AKAV and SBV, at least in vitro, to promote virus replication in susceptive cells. Importance: AKAV and SBV are the etiological agents of arthrogryposis-hydranencephaly syndrome in ruminants, which causes considerable economic losses in the livestock industry. Here, we identified heparan sulfate proteoglycan as a major cellular attachment factor for the entry of AKAV and SBV. Moreover, we found that heparin is a strong inhibitor of AKAV and SBV infections. Revealing the molecular mechanisms of virus-host interactions is critical in order to understand virus biology and develop novel live attenuated vaccines

Impact of astrophysical effects on the dark matter mass constraint with 21cm intensity mapping

We present an innovative approach to constraining the non-cold dark matter model using a convolutional neural network (CNN). We perform a suite of hydrodynamic simulations with varying dark matter particle masses and generate mock 21cm radio intensity maps to trace the dark matter distribution. Our proposed method complements the traditional power spectrum analysis. We compare our CNN classification results with those from the power spectrum of the differential brightness temperature map of 21cm radiation, and find that the CNN outperforms the latter. Moreover, we investigate the impact of baryonic physics on the dark matter model constraint, including star formation, self-shielding of HI gas, and UV background model. We find that these effects may introduce some contamination in the dark matter constraint, but they are insignificant when compared to the realistic system noise of the SKA instruments.Comment: 17 pages, 12 figure

Development of highly efficient sulfur-doped TiO2 photocatalysts hybridized with graphitic carbon nitride

Graphitic carbon nitride (g-C3N4) has attracted much attention as a metal-free semiconductor having visible-light absorption and relatively high chemical stability. In the present study, we hybridized g-C3N4 with sulfur-doped TiO2, which is a visible light-responsive photocatalyst with high oxidation ability, in order to improve photocatalytic activity under visible-light irradiation. Hybrid photocatalysts were prepared by three methods: agate mortar, sonication, and planetary mill. Activities of the hybrid photocatalysts depended on the mixing method. The sample prepared by a planetary mill showed the highest photocatalytic activity, 4-times higher than that of sulfur-doped TiO2. We concluded that the high activity of the hybridized sample under visible-light irradiation is induced by charge transfer between the two photocatalysts mimicking the Z-scheme in photosynthesis

Web-Based Personalized Nutrition System for Delivering Dietary Feedback Based on Behavior Change Techniques: Development and Pilot Study among Dietitians

Given the complex and varied nature of individual characteristics influencing dietary behaviors, personalized dietary advice may be more effective than generalized “one-size-fits-all” advice. In this paper, we describe a web-based personalized nutrition system for improving the quality of overall diet in the general adult population. The development process included identification of appropriate behavior change techniques, modification of dietary assessment method (Meal-based Diet History Questionnaire; MDHQ), selection of dietary components, and a personalized dietary feedback tool. A pilot study was conducted online among 255 dietitians. Each completed the MDHQ, received his/her own dietary feedback report, and evaluated the relevance of the report based on 12 questions using a 5-point Likert scale from “totally disagree” (score 1) to “totally agree” (score 5). The mean value of overall acceptability score of dietary feedback report was 4.2. The acceptability score was, on average, higher in plausible energy reporters (compared with implausible energy reporters), participants who printed out the report (compared with those who did not), and those spending ≥20 min to read the report (compared with those spending <20 min). This is the first attempt to develop a web-based personalized nutrition system in Japan, where dietitians were broadly supportive of the dietary feedback report

Monetary Diet Cost is Associated with not only Favorable but also Unfavorable Aspects of Diet in Pregnant Japanese Women: The Osaka Maternal and Child Health Study

While several observational studies in European countries have shown that higher monetary diet cost is associated with healthier diets, information on the relationship of cost to diet quality in other countries is sparse, including Japan. This cross-sectional study examined the association between monetary diet cost and dietary intake in a group of pregnant Japanese women. Subjects were 596 pregnant Japanese housewives. Dietary intake was estimated using a validated, self-administered, comprehensive diet history questionnaire. Monetary diet cost was calculated using retail food prices. Values of monetary diet cost and nutrient and food intake were energy-adjusted using the density method. Monetary diet cost was associated positively with the intake of protein, total fat, saturated fatty acids, dietary fiber, cholesterol, sodium, potassium, calcium, magnesium, iron, vitamins A, D, E, C, and folate, and inversely with that of carbohydrate. For foods, cost was associated positively with the intake of potatoes, pulses and nuts, fish and shellfish, meat, dairy products, vegetables, and fruits, and inversely with that of rice and bread. No association was seen for noodles, confectioneries and sugars, fats and oils, or eggs. Cost was also associated inversely with dietary energy density. In conclusion, monetary diet cost was associated with not only favorable aspects of diet, including a higher intake of dietary fiber, key vitamins and minerals, fruits, and vegetables and lower dietary energy density, but also unfavorable aspects, including a higher intake of fat and sodium and lower intake of carbohydrate and rice, in a group of pregnant Japanese women

Combination treatment with recombinant methioninase enables temozolomide to arrest a BRAF V600E melanoma in a patient-derived orthotopic xenograft (PDOX) mouse model.

An excessive requirement for methionine termed methionine dependence, appears to be a general metabolic defect in cancer. We have previously shown that cancer-cell growth can be selectively arrested by methionine deprivation such as with recombinant methioninase (rMETase). The present study used a previously-established patient-derived orthotopic xenograft (PDOX) nude mouse model of BRAF V600E-mutant melanoma to determine the efficacy of rMETase in combination with a first-line melanoma drug, temozolomide (TEM). In the present study 40 melanoma PDOX mouse models were randomized into four groups of 10 mice each: untreated control (n=10); TEM (25 mg/kg, oral 14 consecutive days, n=10); rMETase (100 units, intraperitoneal 14 consecutive days, n=10); combination TEM + rMETase (TEM: 25 mg/kg, oral rMETase: 100 units, intraperitoneal 14 consecutive days, n=10). All treatments inhibited tumor growth compared to untreated control (TEM: p=0.0081, rMETase: p=0.0037, TEM-rMETase: p=0.0024) on day 14 after initiation. However, the combination therapy of TEM and rMETase was significantly more efficacious than either mono-therapy (TEM: p=0.0051, rMETase: p=0.0051). The present study is the first demonstrating the efficacy of rMETase combination therapy in a PDOX model, suggesting potential clinical development, especially in recalcitrant cancers such as melanoma, where rMETase may enhance first-line therapy

A patient-derived orthotopic xenograft (PDOX) mouse model of a cisplatinum-resistant osteosarcoma lung metastasis that was sensitive to temozolomide and trabectedin: implications for precision oncology.

In the present study, we evaluated the efficacy of trabectedin (TRAB) and temozolomide (TEM) compared to cisplatinum (CDDP) on a patient-derived orthotopic xenogrraft (PDOX) of a lung-metastasis from an osteosarcoma of a patient who failed CDDP therapy. Osteosarcoma resected from the patient was implanted orthotopically in the distal femur of mice to establish PDOX models which were randomized into the following groups when tumor volume reached approximately 100 mm3: G1, control without treatment; G2, CDDP (6 mg/kg, intraperitoneal injection, weekly, for 2 weeks); G3, TRAB (0.15 mg/kg, intravenous injection, weekly, for 2 weeks); G4, TEM (25 mg/kg, oral, daily, for 14 days). Tumor sizes and body weight were measured with calipers and a digital balance twice a week. On day 14 after initiation of treatment, TEM and TRAB, but not CDDP, significantly inhibited tumor volume compared to untreated control: control (G1): 814.5±258.8 mm3; CDDP (G2): 608.6±126.9 mm3, TRAB (G3): 286.6±133.0 mm3; TEM (G4): 182.9±69.1 mm3. CDDP vs. control, p=0.07; TRAB vs. control, p=0.0004; TEM vs. control p =0.0002; TRAB vs. CDDP, p =0.0002; TEM vs. CDDP, p =0.00003. The results of the present study show that a PDOX model of an osteosarcoma lung-metastasis that recurred after adjuvant CDDP-treatment has identified potentially, highly-effective drugs for this recalcitrant disease, while precisely maintaining the CDDP resistance of the tumor in the patient, thereby demonstrating the potential of the osteosarcoma PDOX model for precision oncology

Trabectedin arrests a doxorubicin-resistant PDGFRA-activated liposarcoma patient-derived orthotopic xenograft (PDOX) nude mouse model.

BACKGROUND:Pleomorphic liposarcoma (PLPS) is a rare, heterogeneous and an aggressive variant of liposarcoma. Therefore, individualized therapy is urgently needed. Our recent reports suggest that trabectedin (TRAB) is effective against several patient-derived orthotopic xenograft (PDOX) mouse models. Here, we compared the efficacy of first-line therapy, doxorubicin (DOX), and TRAB in a platelet-derived growth factor receptor-α (PDGFRA)-amplified PLPS. METHODS:We used a fresh sample of PLPS tumor derived from a 68-year-old male patient diagnosed with a recurrent PLPS. Subcutaneous implantation of tumor tissue was performed in a nude mouse. After three weeks of implantation, tumor tissues were isolated and cut into small pieces. To match the patient a PDGFRA-amplified PLPS PDOX was created in the biceps femoris of nude mice. Mice were randomized into three groups: Group 1 (G1), control (untreated); Group 2 (G2), DOX-treated; Group 3 (G3), TRAB-treated. Measurement was done twice a week for tumor width, length, and mouse body weight. RESULTS:The PLPS PDOX&nbsp;showed&nbsp;resistance towards DOX. However, TRAB could arrest the PLPS (p &lt; 0.05 compared&nbsp;to control; p &lt; 0.05 compared to DOX) without any significant changes in body-weight. CONCLUSIONS:The data presented here suggest that for the individual patient the PLPS PDOX model could specifically distinguish both effective and ineffective drugs. This is especially crucial for PLPS because effective&nbsp;first-line therapy is harder to establish if it is not individualized