New discovery of the oldest maize weevils in the world from Jomon potteries, Japan

The maize weevil (_Sitophilus zeamais_) and rice weevil (_Sitophilus oryzae_) are two of the most damaging insects for stored grains, and are characteristic species of ancient Japan. Both species and the granary weevil (_Sitophilus granarius_) are common elsewhere in the world, but the natural distribution of maize and rice weevils is restricted to the Old World^1^. Japanese archaeological records contain a few maize weevil fossils after the Middle Yayoi period (ca. 2000 aBP)^2^. However, since evidence of weevils was discovered as impressions in Jomon potsherds in 2004^3^, many weevil impressions have been found. The oldest is from the Late Jomon (ca. 4000 to 3200 aBP). These findings and other archaeological evidence suggest that the maize weevil invaded Japan from Korea, accompanying the spread of rice cultivation^4^. However, in 2010 we discovered older weevil impressions dating to ca. 9000 aBP. These specimens are the oldest harmful insects discovered from archaeological sites around the world. The new discovery is valuable for future entomological research because such specimens are absent from the fossil record. It is also archaeologically and culturally interesting because this provides evidence of harmful insects living in Jomon villages. However, the new discovery raises the question of what these weevils infested: did cereal cultivation exist 9000 years ago? We have no persuasive answer, but hope one will be provided by future interdisciplinary collaborations among geneticists, entomologists, and archaeologists

Evolution of Synchrotron X-rays in Supernova Remnants

A systematic study of the synchrotron X-ray emission from supernova remnants (SNRs) has been conducted. We selected a total of 12 SNRs whose synchrotron X-ray spectral parameters are available in the literature with reasonable accuracy, and studied how their luminosities change as a function of radius. It is found that the synchrotron X-ray luminosity tends to drop especially when the SNRs become larger than ~5 pc, despite large scatter. This may be explained by the change of spectral shape caused by the decrease of the synchrotron roll-off energy. A simple evolutionary model of the X-ray luminosity is proposed and is found to reproduce the observed data approximately, with reasonable model parameters. According to the model, the total energy of accelerated electrons is estimated to be 10^(47-48) ergs, which is well below the supernova explosion energy. The maximum energies of accelerated electrons and protons are also discussed.Comment: 6 pages, 2 figures, ApJ, in pres

Improvement of biodistribution profile of a radiogallium-labeled, αvβ6 integrin-targeting peptide probe by incorporation of negatively charged amino acids

Objective Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers. Since αvβ6 integrin has been reported as a promising target for PDAC diagnosis, we previously developed H-Cys(mal-NOTA-67Ga)-(Gly)6-A20FMDV2-NH2 ([67Ga]CG6) as an αvβ6 integrin-targeting probe. Although [67Ga]CG6 specifically binds to αvβ6 integrin-positive xenografts, the uptake of [67Ga]CG6 in the organs surrounding the pancreas, such as the liver and spleen, was comparable to that in the αvβ6 integrin-positive xenografts. We hypothesized that the undesirable accumulation of [67Ga]CG6 in those organs was caused by the positive charges of [67Ga]CG6 (+ 3). In this study, we aimed to decrease [67Ga]CG6 uptake in the liver and spleen by reducing the electric charges of the probe. Methods We synthesized H-Cys(mal-NOTA-67Ga)-(Asp)6-A20FMDV2-NH2 ([67Ga]CD6) and evaluated its affinity to αvβ6 integrin via in vitro competitive binding assay. Isoelectric points of the probes were determined by electrophoresis. Biodistribution study, autoradiography, and immunostaining for β6 integrin were conducted using αvβ6 integrin-positive and negative tumor-bearing mice. Results In vitro competitive binding assay showed that the alteration of the linker had a negligible impact on the affinity of [67Ga]CG6 to αvβ6 integrin. The results of electrophoresis revealed that [67Ga]CG6 was positively charged whereas [67Ga]CD6 was negatively charged. In the biodistribution study, the uptake of [67Ga]CD6 in the αvβ6 integrin-positive xenografts was significantly higher than that in the αvβ6 integrin-negative ones at 60 and 120 min. The uptake of [67Ga]CD6 in the liver and spleen was more than two-fold lower than that of [67Ga]CG6 at both time points. In the immunohistochemistry study, the radioactivity accumulated areas in the autoradiogram of the αvβ6 integrin-positive xenograft roughly coincided with β6 integrin-expressing areas. Conclusion We have successfully reduced the nonspecific uptake in the liver and spleen by altering the linker amino acid from G6 to D6. [67Ga]CD6 overcame the drawbacks of [67Ga]CG6 in its biodistribution

Prostate Cancer Detected by Choroidal Tumor and Complete Response to Hormonal Therapy: Case Report and Literature Review of 24 Patients With Choroidal Metastasis From Prostate Cancer

Metastatic choroidal tumors derived from prostate cancer are rare. In this study, we report a patient who manifested a choroidal tumor as the initial presenting sign of prostate cancer and review 23 patients with choroidal metastasis of prostate cancer in the literature to answer a clinical question how the choroidal metastases would respond to hormonal therapy. A 73-year-old man presented with a choroidal tumor in the right eye. He was in good health and had no previous history except for current hemodialysis in 3 years due to chronic renal failure as a sequel to glomerulonephritis. With the diagnosis of a probable metastatic tumor, positron emission tomography was performed to disclose high-uptake sites in multiple bones, lymph nodes, and the prostate, together with multiple nodular lesions in bilateral lungs on computed tomography (CT) scan. Serum prostate-specific antigen (PSA) was elevated to 541 ng/mL, which supported prostate cancer as the primary site. He had degarelix injection, and the choroidal tumor resolved rapidly and became flat degeneration in a month. Prostate biopsy showed poorly differentiated adenocarcinoma, and he underwent surgical castration. He had no medication until 3 years later when he showed gradual increase of serum PSA up to 6.05 ng/mL and multiple bony metastases on CT scan. Bicalutamide, switched to enzalutamide and then to abiraterone, led to the undetectable level of serum PSA until the last visit with no relapse of the choroidal metastasis, 6.8 years after the initial visit. In the literature review of 24 patients with choroidal metastasis of prostate cancer, including this patient, 8 patients presented a choroidal tumor as the initial sign and the choroidal lesions mostly showed complete response to hormonal therapy. Among 13 patients who were frequently in the course of hormonal therapy, choroidal metastases showed complete or partial response to external beam radiation to the eye in 11 patients and episcleral plaque radiotherapy in 2 patients. In conclusion, metastatic choroidal tumors of prostate cancer would show good response to hormonal therapy when the therapy has not been initiated. Hormone-resistant choroidal metastases in the therapeutic course of prostate cancer could be managed successfully by external beam radiation to the eye

miR-1 and Tooth Development

Many genes encoding growth factors, receptors, and transcription factors are induced by the epithelial-mesenchymal interaction during tooth development. Recently, numerous functions of microRNAs (miRNAs) are reportedly involved in organogenesis and disease. miRNAs regulate gene expression by inhibiting translation and destabilizing mRNAs. However, the expression and function of miRNAs in tooth development remain poorly understood. This study aimed to analyze the expression of miRNAs produced during tooth development using a microarray system to clarify the role of miRNAs in dental development. miR-1 showed a unique expression pattern in the developing tooth. miR-1 expression in the tooth germ peaked on embryonic day 16.5, decreasing gradually on postnatal days 1 and 3. An in situ hybridization assay revealed that miR-1 is expressed at the cervical loop of the dental epithelium. The expression of miR-1 and connexin (Cx) 43, a target of miR-1, were inversely correlated both in vitro and in vivo. Knockdown of miR-1 induced the expression of Cx43 in dental epithelial cells. Interestingly, cells with miR-1 downregulation proliferated slower than the control cells. Immunocytochemistry revealed that Cx43 in cells with miR-1 knockdown formed both cell-cell gap junctions and hemichannels at the plasma membrane. Furthermore, the rate of ATP release was higher in cells with miR-1 knockdown than in control cells. Furthermore, Cx43 downregulation in developing molars was observed in Epiprofin-knockout mice, along with the induction of miR-1 expression. These results suggest that the expression pattern of Cx43 is modulated by miR-1 to control cell proliferation activity during dental epithelial cell differentiation