New femoral remains of <i>Nacholapithecus kerioi</i>: Implications for intraspecific variation and Miocene hominoid evolution

The middle Miocene stem kenyapithecine Nacholapithecus kerioi (16-15 Ma; Nachola, Kenya) is represented by a large number of isolated fossil remains and one of the most complete skeletons in the hominoid fossil record (KNM-BG 35250). Multiple fieldwork seasons performed by Japanese-Kenyan teams during the last part of the 20th century resulted in the discovery of a large sample of Nacholapithecus fossils. Here, we describe the new femoral remains of Nacholapithecus. In well-preserved specimens, we evaluate sex differences and within-species variation using both qualitative and quantitative traits. We use these data to determine whether these specimens are morphologically similar to the species holotype KNM-BG 35250 (which shows some plastic deformation) and to compare Nacholapithecus with other Miocene hominoids and extant anthropoids to evaluate the distinctiveness of its femur. The new fossil evidence reaffirms previously reported descriptions of some distal femoral traits, namely the morphology of the patellar groove. However, results also show that relative femoral head size in Nacholapithecus is smaller, relative neck length is longer, and neck-shaft angle is lower than previously reported for KNM-BG 35250. These traits have a strong functional signal related to the hip joint kinematics, suggesting that the morphology of the proximal femur in Nacholapithecus might be functionally related to quadrupedal-like behaviors instead of more derived antipronograde locomotor modes. Results further demonstrate that other African Miocene apes (with the exception of Turkanapithecus kalakolensis) generally fall within the Nacholapithecus range of variation, whose overall femoral shape resembles that of Ekembo spp. and Equatorius africanus. Our results accord with the previously inferred locomotor repertoire of Nacholapithecus, indicating a combination of generalized arboreal quadrupedalism combined with other antipronograde behaviors (e.g., vertical climbing)

Serum Apolipoprotein M Levels are Correlated with Biomarkers of Coagulation

Background:Apolipoprotein M (ApoM) is bound to high-density lipoprotein (HDL) in plasma, and HDL has anticoagulation effects. However, the association between ApoM and biomarkers of coagulation was unclear. Therefore, we investigated relationships between ApoM and biomarkers of coagulation. Methods: Serum samples from 233 Japanese participants including with diabetes mellitus, hypertension, dyslipidemia, or healthy controls were analyzed. Serum ApoM levels were measured using Enzyme-Linked Immuno-Sorbent Assay(ELISA). Results:Analysis of all 233 participants showed that ApoM levels were positively correlated with age (r＝0.284, p＜0.001), total cholesterol (TC;r＝0.477, p＜0.001), HDL-cholesterol (HDL-C;r＝0.234, p＜0.001) and lowdensity lipoprotein cholesterol (LDL-C;r＝0.331, p＜0.001). Higher ApoM levels were correlated with shorter activated partial thromboplastin time(APTT;r＝－0.226,p＝0.001) and prothrombin time(PT,％;r＝0.326,p＜ 0.001). Separate analysis of the 115 healthy controls showed that ApoM levels were positively correlated with age, TC, HDL-C and LDL-C, and higher ApoM levels were correlated with shorter PT. Conclusion:Serum levels of ApoM may influence biomarkers of coagulation

Transventricular Preforniceal Approach Combined with Endoscopic Transnasal Surgery for a Giant Pituitary Adenoma: A Case Report and Literature Review

Giant pituitary adenomas carry significant surgical risks when treated with transsphenoidal approaches or the transcranial approach alone. Combined transsphenoidal and transcranial approaches have been reported; however, removing adenomas extending into the third ventricle may still be challenging. We report a case of giant pituitary adenoma expanding into the third ventricle, which was removed using a combined transventricular preforniceal approach and an endoscopic endonasal transsphenoidal surgery (ETSS). A 41-year-old man with headache, nausea, and a 1-week history of a visual field defect was transferred to our hospital. He had a disturbed left visual acuity, right homonymous hemianopia, and choked disc in both eyes. Preoperative magnetic resonance imaging revealed a giant pituitary adenoma with a maximum diameter of 55 mm extending from the intrasellar to the suprasellar region, thus occupying the entire third ventricle and causing hydrocephalus. The space between the anterior commissure and the fornix was expanded. The foramen of Monro was shifted backward due to compression by the tumor. He underwent maximum surgical resection using a combined transventricular preforniceal approach and ETSS. Considering technical demands and reliability, the intra- to suprasellar parts were removed by ETSS while the intraventricular part was removed through the preforniceal approach. The residual tumor in the right cavernous sinus and behind the anterior communicating artery was treated with stereotactic radiotherapy. One year after the operation, the patient leads an independent life. The combined technique of the preforniceal approach and ETSS provided a direct view of the entire third ventricle and hemostasis in the present case

Establishment of Novel High-Standard Chemiluminescent Assay for NTPase in Two Protozoans and Its High-Throughput Screening

Toxoplasma gondii is a major protozoan parasite and infects human and many other warm-blooded animals. The infection leads to Toxoplasmosis, a serious issue in AIDS patients, organ transplant recipients and pregnant women. Neospora caninum, another type of protozoa, is closely related to Toxoplasma gondii. Infections of the protozoa in animals also causes serious diseases such as Encephalomyelitis and Myositis-Polyradiculitis in dogs or abortion in cows. Both Toxoplasma gondii and Neospora caninum have similar nucleoside triphosphate hydrolases (NTPase), NcNTPase and TgNTPase-I in Neospora caninum and Toxoplasma gondii, respectively. These possibly play important roles in propagation and survival. Thus, we targeted the enzymes for drug discovery and tried to establish a novel high-standard assay by a combination of original biochemical enzyme assay and fluorescent assay to determine ADP content. We then validated whether or not it can be applied to high-throughput screening (HTS). Then, it fulfilled criterion to carry out HTS in both of the enzymes. In order to identify small molecules having inhibitory effects on the protozoan enzyme, we also performed HTS using two synthetic compound libraries and an extract library derived from marine bacteria and then, identified 19 compounds and 6 extracts. Nagasaki University collected many extracts from over 18,000 marine bacteria found in local Omura bay, and continues to compile an extensive collection of synthetic compounds from numerous drug libraries established by Japanese chemists

Novel Reporter System Monitoring IL-18 Specific Signaling Can Be Applied to High-Throughput Screening

Very recently, the immunotherapies against cancer, autoimmune diseases, and infection have been feasible and promising. Thus, we have examined the possibility whether or not human gamma delta T cells can be applied for the novel immunotherapies. We previously established the cells stably maintaining NFkB-driven human secreted embryonic alkaline phosphatase (SEAP) expression. The cells can be used to determine the transcription activity of NFkB with high-standard dynamic range and accuracy. Because IL-18 is a kind of cytokines that enhances cytotoxicity and activity of human gamma delta T cells through NFkB activation, we have focused on the activity and signaling of IL-18. In this study, we modified the previous reporter cell that can determine the transcription activity of NFkB to express two subunits consisted of human IL-18 receptor. The modified cells secreted SEAP in response to treatment with human recombinant IL-18 in a concentration-dependent manner. We also observed the concentration-dependently enhancement of NFkB activity in the cells treated with mouse recombinant IL-18 although the affinity was lower compared to human recombinant IL-18. We also previously established the cells stably expressing and secreting human recombinant IL-18 and then validated whether or not the conditioned medium from the cells activate NFkB transcription activity using this assay. Our university has kept collecting many extracts from over 18,000 marine bacteria in our local sea around Omura bay-fungi, plants for Chinese herbal medicine, and so on-and also have kept gathering synthetic compounds from many Japanese chemists as drug libraries. Finally, in order to identify drugs mimicking IL-18 biological activity or possessing inhibitory effects on IL-18-induced NFkB, we demonstrated drug screening using number of extracts derived from marine bacteria and synthetic compounds

A multi-targeted approach to suppress tumor-promoting inflammation

Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-κB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes

Poster Session: Abstracts

The 3rd International Symposium on Carcinogenic Spiral & International Symposium on Tumor Biology in Kanazawa, [DATE]: January 24(Thu)-25(Fri),2013, [Place]:Kanazawa Excel Hotel Tpkyu, Kanazawa, Japan, [Organizers]:Infection/Inflammation-Assisted Acceleration of the Carcinogenic Spiral and its Alteration through Vector Conversion of the Host Response to Tumors / Scientific Research on Innovative Areas, a MEXT Grant-in Aid Projec

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements