暑熱環境不適応による初期胚死滅の分子機構解明と熱帯畜産への応用

熱帯という地域の自然的・社会的諸条件(在地性)を出発点とする新しい畜産学の体系化、すなわち、熱帯畜産の創生を求め、本研究では家畜繁殖学領域からのひとつの試みとして、熱帯畜産の潜在的制約要因である母体の一過性体温上昇(過体温)に起因する種々の繁殖障害を取り上げ、その分子機構を明らかにしようとした。本年度は、研究代表者らが確立した動物実験モデルを用い、暑熱ストレスによる初期胚死滅の誘発および卵胞発育阻害の生理学的機序と分子機構の解明を試みた。その概要は以下のとおりである。1.暑熱ストレス性初期胚死滅に関わる酸化ストレス介在説の証明マウス実験モデルによって得られた上記の仮設を証明するため、抗酸化機能を持つメラトニンを暑熱負荷マウスに投与し、その効果を調べた、その結果、メラトニンは暑熱ストレスによる肝臓での過酸化脂質の増加、卵管での活性酸素の生成を抑制し、さらに初期胚死滅を一定度軽減することを明らかにした。2.暑熱ストレスによる卵胞閉鎖促進の生理的分子機構の解明ラット実験モデルを用い、過排卵反応に対する暑熱ストレスの影響について解析した。その結果、暑熱ストレスは発育卵胞中の顆粒層細胞におけるLH/FSH受容体の発現を強く抑制すること、また、これにより暑熱ストレス下で発育した卵胞ではアポトーシスが亢進することを明らかにした。(業績2)3.暑熱ストレスによる排卵抑制の生理的機序解明シバヤギ実験モデルを用い、上記2と同様の解析を試みた。その結果、シバヤギでも暑熱ストレスは卵胞発育、特にFSHによる選択的卵胞発育の過程を強く抑制すること、また、これにより暑熱ストレス下で選抜された前排卵卵胞は排卵せずに退行することを明らかにした。


INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS


Nuclear Physics Research With 5.5 Mev Van de Graaff  Accelerator


茶カテキンを受容する渋味センサーの同定

Principal Investigator：黒木 麻湖, Project Period (FY)：2013-04-01 – 2015-03-31, Research Category：Grant-in-Aid for JSPS Fellows, Section：国内, Research Field：Applied biochemistry

Japan Society for the Promotion of Science


Principal Investigator：富田 侑嗣, Project Period (FY)：1973, Research Category：Grant-in-Aid for Encouragement of Young Scientists (A), Research Field：Fluid engineering


Age Distribution of the Particulate Organic Carbon (POC) Discharged from Small Mountainous Rivers-- the Influence of Sediment Yield and Soil Residence Time

Abstract

Short, mountainous rivers dominate the fluvial supply of sediment to the western margin of North America and to the oceans in general.  As a result of rapid rates of landscape denudation and minimal sediment storage in these active margin systems, the particulate organic carbon (POC) discharged differs from that transported by larger rivers on passive margins.  Recent investigations of two rivers in California indicate they carry a bimodal mixture of modern and ancient particulate organic carbon (POC), derived almost equally from extant vegetation and from the kerogen of uplifted sedimentary rocks.  To a first approximation, soils are eroded in these systems before significant aging occurs or before the kerogen can be completely oxidized and replaced by modern material.  Based on these preliminary results, the balance between modern, ancient, and intermediate-aged POC carried by rivers is hypothesized to depend on the residence time of particles in the regolith.  To test this hypothesis, this investigation will characterize the suspended POC loads of six rivers that exhibit a three-order range of magnitude in sediment yield.  Four rivers (Siuslaw, Noyo, Russian, and Eel) drain portions of northern California and Oregon.  The Waipaoa and Waiapu rivers on the north island of New Zealand were chosen because of their extremely high sediment yields.  Bedrock POC will also be characterized in each of the watersheds.  The principle measurements, OC content, 13C/12C(d13C), and 14C/12C (?14C), will be made on bulk samples, as well as density- and size-fractionated subsamples, to determine the kerogen and modern C contents.  Additional studies of soil profiles in the Eel watershed will be conducted to further delineate weathering and OC replacement processes in the regolith.  The evolution of the POC pool from bedrock C to modern surficial material will be studied in thick horizons, to contrast with previous results from thin soil profiles.
	The results of this study will further understanding of the processes that regulate the quantity and character of OC transported from drainage basins to the ocean.  This study also addresses a key issue in the long-term biogeochemical cycle, namely how previously buried OC is recycled.  Interpretation of the sedimentary organic geochemical record of past environments, particularly on active margins, could be significantly improved by this investigation.


Centre of Excellence of Inverse Modelling and Imaging

Centre of Excellence in Programme 2018-2025, second stage 2016


BRAIN CONNECTS: Comprehensive regional projection map of marmoset with single axon and cell type resolution

NARRATIVE A major obstacle in basic and translational neuroscience is the lack of animal models that have brain structure and function closely related to the human brain. Such models are critical to our understanding to higher brain function as well as developing therapeutics for brain disorders. The goal of this proposal is to establish an integrated experimental-computational platform to create the first comprehensive brain-wide mesoscale connectivity map in a non-human primate. This will help bridge the gap between brain-wide mesoscale connectivity data available for the mouse from a decade of mapping efforts using modern techniques and the absence of comparable data in humans and NHP.


Development of a Laboratory Quality Management System for Food Testing to Meet th

RESEARCH & RELATED Other Project Information No. 8 Project Narrative After achieving accreditation to ISO/IEC 17025:2055 using assistance from this grant, the data generated by the IDPH laboratory from food testing will be of a quality comparable to other laboratories accredited to the same standard. The data generated will be accepted and used by both state and federal regulatory agencies for routine surveillance and during public health emergency situations such as food borne outbreaks. The data will be legally defensible for use during any enforcement or criminal actions as it can be shown to be generated using the requirements of an internationally recognized standard.


Brain energy metabolism in human experimental psychosis

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung


Increasing Fruit and Vegetable Intake Among Children

PUBLIC HEALTH RELEVANCE: This project will expand the duration of an empirically supported game-based intervention designed to increase healthy eating in elementary school cafeterias. The proposed expansion of the game will target three potential mediators of long-term healthy eating: intrinsic motivation, knowledge of the health benefits of a diet rich in fruit and vegetables, and dietary-choice self-efficacy. The project, if successful, will significantly impact the healthy eating habits of participating children and will support larger-scale implementation of this low-cost low- labor game at the state and national level.


TRAINING PROGRAM IN CHILDHOOD NEUROPSYCHIATRIC DISORDERS


遷移金属を含む低次元性化合物と有機分子との複合化による機能性材料の創製

本研究は、層状あるいは一次元的な構造の遷移金属を含む化合物をホストとし、この層間に電子受容、電子供与の性質を持つ有機分子、あるいは導電性高分子をインターカレーションさせ、遷移金属を含む低次元化合物と挿入された種々の性質を持つホストとの相互作用などによりホストとゲストのそれぞれが異なる機能を分担した新しいタイプの機能性材料を創製しようとするものである。本年度は、VPO_4・2H_2Oをホストに、アニリンおよびピロールをゲストとして、層間における導電性高分子の、インターカレーション・重合を試みた。ゲストは、液体、溶液(THF)および気相の状態でホストと反応させた。いずれのゲストにおいても反応後ホストの層間距離は変化し、種々の分析の結果層間でのポリアニリンおよびポリピロールの生成が認められた。アニリンとの反応においては、生成物の層間距離がホストのものより短いもの、層間距離が長くて水分子を共に含むもの、および広がった層間にアニリンのみを含むものの3種類の生成物が得られた。しかし、生成したポリアニリン量は少なく、また重合度の低いものであり、複合体および取り出した高分子の電気抵抗は非常に大きいみのであった。一方、ピロールをゲストとする場合にはいずれの状態のピロールとも生成物の層間距離がホストのそれより短いものが得られた。層間のピロール量は、気相、液体、溶液の順に大きくなり、また常に層間に水が共存した。アニリンの場合と比較すると、ピロールの場合はモノマー量も少なく、重合度も大きいようで、ホストに比べて非常によく電気を流すようになった。アニリンの場合は生成物の酸化状態の変化による電気伝導度の変化を、ピロールの場合はさらに合成条件を変化させて電気的性質との関連性を検討する必要がある。

Grant-in-Aid for General Scientific Research (C)


CELLULAR MECHANISMS OF NEUROENDOCRINE HORMONE SECRETION


Development of new periodontal tissue regeneration on therapyWith periostin.

Through alternative splicing, periostin exists in four different variants and isoforms, and is part of the extracellular matrix of bone, skeletal muscle, and periodontal tissues. In recent years, it has been reported to facilitate the revitalization of dysfunctional tissues. This research was carried out with the goal of using periostin for regenerative treatment. Periostin was extracted from the periodontal membrane of pigs and successfully detected with LC/MS/MS and western blot analysis. Next, its expressionwas confirmed at the genetic level in human periodontal membrane cells.


Architectures and Applications for Three-Dimensional Chip Multiprocessors

This project investigates multicore architectures, advanced design tools, and highly-parallel applications to exploit three-dimensional integrated circuits (3D ICs) for significantly higher performance and reduced power, compared to traditional two-dimensional multicore chips. The goal is to exploit and extend both dimensions into the next computational frontier: trillion Operations-per-Second (TeraOPS) performance with less than 10W of power dissipation. The project involves detailed tradeoff analyses of architectural alternatives, especially with respect to memory hierarchy and interconnection networks, in order to discover approaches that fully exploit the benefits of 3D integration. This analysis will be performed at both the architectural level and the physical design level, and tools will be developed to allow information and constraints to smoothly flow between these levels of abstraction, enabling new opportunities for collaboration between architects and chip designers.


Pathways to flourishing: leveraging Virtual Reality for cultivating compassion, resilience, social connectedness, and healthy habits in emerging adults facing chronic health challenges

Social Sciences and Humanities Research Council of Canada

New Frontiers in Research Fund - Exploration


Pharmacology and Physiology of Retinal Ganglion Cells

PUBLIC HEALTH RELEVANCE: The proposed experiments are designed to determine (i) whether light 'shapes' the visually driven signal output of the eye by altering the amplitude and duration of spikes propagating from the retina to the optic nerve, and (ii) whether these effects are mediated by activation of a calcium/calmodulin-dependent protein kinase in retinal ganglion cell axons. This is of basic and potentially clinical interest because calcium-dependent signaling cascades in adult ganglion cells differ from those in young postnatal animals. This implies age-dependent changes in the type of light responses that retinal ganglion cells generate, and in the modulation of ganglion cell signaling capacity as lighting conditions change during normal daylight.


Regulation of stem cell development during tissue remodeling

EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT


Relation of Population Density and Competition to Bee Behavior


高性能ペロブスカイト量子ドットLEDを指向した配位子開発

産学が連携した研究開発成果の展開/研究成果展開事業/研究成果最適展開支援プログラム(A-STEP)/機能検証フェーズ/試験研究タイプ


1435661
Noguera

Towards Energy Efficiency Through Low-DO Nitrification: Extending our Knowledge of Ammonia-Oxidizing Organisms

In wastewater treatment activated sludge is a common process.  Activated sludge is the single largest energy user because of the amount of oxygen that is needed to maintain aerobic (oxygen rich) conditions. This proposal seeks to identify and characterize the novel organisms that perform ammonia oxidation under low-DO conditions and thereby reducing the cost of the process. The hypothesis is that unrecognized ammonia-oxidizing organisms are likely responsible for nitrification in low-dissolved oxygen activated sludge systems.  If this study is successful it will result in a significant reduction in energy costs for many wastewater treatment plants in the Nation. The project will also allow the PIs to continue mentoring high school, undergraduate, and graduate students, and will fund the training of two PhD students from underrepresented groups in science and engineering.

Technically, the project is divided into three tasks which include; 1) screening  a collection of pure cultures isolated from a lab-scale reactor performing efficient nitrification, 2) focused on the identification of the abundant ammonia-oxidizing organisms in lab-scale reactors, and 3) conduct kinetic experiments to characterize the microbial communities in pilot-scale reactors coupling and treating primary effluent from a full scale wastewater treatment plant. The effective coupling of enhanced biological phosphorus removal and low-dissolved oxygen nitrification will be a transformative development, since aeration for nutrient removal can account for nearly half of the energy use. This project will enable development of new technologies that contribute to the wastewater industry's overarching goals of achieving energy neutrality and shifting the focus from waste treatment to resource recovery facilities.


PARTIAL TRAVEL SUPPORT FOR: MVLE WORKSHOP IN LONDON


WAFDO 2012 Educational and Training Seminar

Project Narrative Given the growing number of nationwide product recalls and large-scale foodborne illness outbreaks over recent years as well as national mandates to reform the nation's food safety system, it is critical that partners in food safety collaborate, build capacity, and work together to protect the public's health. The WAFDO educational conference facilitates such work, creating shared understanding, uniformity, and relationship that is critical to a successful system. With limited budgets in state and local programs, scholarships are critical to achieving maximum attendance.

WESTERN ASSOCIATION /FOOD/DRUG OFFICIALS


核-ミトコンドリア翻訳バランスによる老化・寿命の調節とミトコンドリアヌクレオイド

核とミトコンドリアにコードされる遺伝情報の翻訳のバランス（核-ミトコンドリア翻訳バランス）が老化や寿命に関与していることを示す報告が蓄積しているが、その調節機構は明らかになっていない。一方、研究代表者はミトコンドリア DNA（mtDNA）の量的維持機構に関与する因子の探索においてmtDNAシグナルが減少したスクリーニング陽性遺伝子として核遺伝子の翻訳に関するものを多数見出している。本研究では「核-ミトコンドリア翻訳バランスによる老化や寿命の調節においてmtDNAのヌクレオイド構造が何らかの役割を果たしているのではないか」との仮説を立て、検証する。

Japan Society for the Promotion of Science

Grant-in-Aid for Scientific Research (C)


ANDROGEN RECEPTOR REGULATION OF REPRODUCTIVE FUNCTION

UNIVERSITY OF NORTH CAROLINA CHAPEL HILL


腫瘍免疫の誘導と免疫宿主における腫瘍細胞排除の機構に関する研究

Principal Investigator：橋本 嘉幸, Project Period (FY)：1974, Research Category：Grant-in-Aid for Cancer Research


Developing a framework to individualize surgical decision-making for older adults with primary hyperparathyroidism

PROJECT NARRATIVE To make informed surgical treatment decisions, older adults and the providers who care for them must weigh the long-term benefits of surgery against the short-term health risks for an individual patient. However, counseling on the tradeoffs of surgical intervention too often rely on population average risk rather than individualized estimates of risks/benefits. This research will create decision support for the management of primary hyperparathyroidism in older adults and, in doing so, establish a framework for how to combine individualized risk prediction with stakeholder feedback to develop surgical decision support that will inform treatment recommendations for older adults and reduce long-term morbidity.


核酸ドメインのコンホメーション解析

DNAの塩基配列決定法の進歩によって、遺伝子のもつ情報が塩基配列という形で明らかにされてきた。この塩基配列の中には生物が必要とする蛋白質のアミノ酸配列情報の他に、情報伝達の開始、停止、制御等の信号情報が含まれている。本研究はこのような情報をもつ核酸のドメイン構造に重点をおき、塩基配列に依存したコンフォメーションを解析し、情報発現にかかわる蛋白質との相互作用を通じてその分子機構を明らかにしようとする。本年度の成果は次の通りである。1.mRNAの開始に関する先導配列の統計的な解析から、原核生物ではSD配列と開始コドン周辺の2個所、真核生物では開始コドン周辺が開始RNA、リボゾーム集合体を作る結合部位と推定された。2.λファージのリプレッサー結合部位の配列をもつ17塩基のオリゴマーは末端とAT対の部分が比較的動きやすいことがNMRの測定から推定された。またDNA結合蛋白CROの認識塩基配列が推定された。3.オリゴヌクレオチドの結晶解析による温度因子の測定から局所的な動的挙動が塩基配列によってちがうことがわかった。またZ型,B型,A型の構造の特徴を表面積から解析した。4.tRNAのアンチコドンループ,ローループ内特定塩基を化学修飾し、アミノ酸選択性の変化を調べた。tRNAのL型は機能上重要である。別々のtRNAの一部を入れ替えるキメラtRNAを作った。5.塩基配列を基礎としてRNAのとりうる2次構造予測法を開発し、2次構造の安定性地図を作った。これによりmRNAの局所構造予測を行った。6.核酸のコンフォメーションを鎖に沿った2面角で表現する方法を検討し、束縄條件を入れれば1つの2面角でよいことがわかった。この角を動かし、らさんの伸縮運動、ストランド分離をグラフィクスで示した。7.mRNAから作られる蛋白質のアミノ酸組成と2次構造の間に強い相関があり、構造型が予測できることがわかった。

Grant-in-Aid for Special Project Research


Patient-Oriented Research to Improve Geriatric Care-K24


Novel methodologies for conformational sampling and QM/MM simulations in complex systems

Mark E. Tuckerman of New York University is supported by the Theoretical and Computational Chemistry program to develop and implement methods based on specialized variable transformations that are capable of sampling the conformational equilibria of complex systems.  This approach reduces the effects of energy barriers without altering thermodynamic and equilibrium properties.  Applications of these methods include small peptides as test cases, and fast-folding proteins.  A second theme of the research is to develop pseudopotentials appropriate for use in quantum mechanical/molecular mechanical (QM/MM) methods.  An initial application of this method is to study the catalytic mechanism of the enzyme histone deacetylase, which is linked to various types of cancer.  This work is having a broad impact in developing sampling and search algorithms for bio-simulations.  Codes developed in this research, as well as a database of pseudopotentials, are freely available on the PI''s web site.  Research results are incorporated into the classroom at the undergraduate and graduate level.  Outreach to the community includes non-technical talks to students and faculty at regional middle schools, high school, colleges and universities.


Proposal for Screening & Treatment for Sexually Transmitted Infectious (STI's)...


細胞内蛋白質分解と選択的神経細胞死の発生機構の関連性

脳神経細胞の病的細胞死および細胞不死化において、細胞内蛋白質分解との関連性を解析した。昨年度は、神経線維腫症2型の病因蛋白merlinがカルパインで過剰分解されて不活化される機構を髄膜腫・神経鞘腫で証明した。今年度は、ユビキチンシステムの中でも神経細胞で特徴的な発現を認める分子群について解析を行った。ユビキチンライゲース(E3酵素)では神経疾患であるアンジェルマン症候群の病因蛋白質E6AP、神経分化で特異的に発現低下するNedd4、ユビキチン結合酵素(E2酵素)ではE2-25K/HIP2、ユビキチンC末端ヒドロラーゼではUCHL1/PGP9.5である。酵母のTwo-hybridシステムによる結合蛋白質の同定を行った。蛋白分解が神経細胞機能の制御および疾患の成立に広く関わることを明らかにした。

Grant-in-Aid for Scientific Research on Priority Areas (A)


MULTI-TARGETED RNAI THERAPEUTICS FOR TREATMENT OF LUNG CANCER (NSCLC)

7. Project Narrative Multi-targeted RNAi Therapeutics for Treatment of Non-Small-Cell Lung Carcinoma (NSCLC) Lung cancer is the leading cause of cancer-related death in the United States and is responsible for over 160,000 patient deaths from their lung cancer this year, more than that of breast, colorectal, prostate, colon and other cancers combined. There is a tremendous unmet need for treatment of Non-Small-Cell lung cancer, represent 85% of all lung cancer patients. In this proposal, we use a novel RNAi technology approach to develop a multi-targeted siRNA therapeutics for NSCLC treatment. The HKP and PTL nanoparticle technologies will greatly enhance systemic delivery of this siRNA cocktail therapeutics, targeting EGFR, VEGF, Cox-2 or PDGF oncogenic genes. Combining this siRNA drug with current targeted therapeutics of small molecule and monoclonal antibodies will provide us a powerful weapon to fight this deadly disease, NSCLC.


Prevalence and correlates of alcohol consumption among African Americans


OCEAN BOTTOM INSTRUMENTATION  APPLIED TO THE PROBLEM OF EARTHQUAKE PREDICTION


Kutikuladifferenzierung im Embryo der Taufliege Drosophila melanogaster

Der Einbau und das Ordnen von Proteinen, Lipiden, Chitin und phenolischen Substanzen zu horizontalen Schichten ist essentiell für die Funktion der Gliedertierkutikula als Exoskelett und physische Barriere. Während die Verteilung dieser Komponenten und die Histologie der Kutikula von wegweisenden Wissenschaftern wie V. Wigglesworth, A. Neville und M. Locke sehr gut beschrieben ist, stehen wir erst am Anfang der Forschung um die genetischen und molekularen Mechanismen der Kutikuladifferenzierung. In den letzten drei Jahren hat meine Gruppe zwei neue Pfade entdeckt, die für die Ausbildung von hydrologischen Eigenschaften der Kutikula notwendig sind. Ein Pfad wird vom ABC-Transporter Olof definiert, den wir in einem RNAi-Experiment gefunden haben. Olof wird für die Integrität der Kutikulaoberfläche gebraucht, die laut V. Wigglesworth aus dem Lipid-Protein Komplex Cuticulin besteht und das Tier vor Austrocknung schützt. Folglich trocknen olof-mutante Larven schnell aus. Basierend auf diesen Phänotyp kann man mutmaßen, daß Olof die Lieferung von Cuticulin-Lipiden über die apikale Plasmamembran vermittelt. Die Protein-Komponente von Cuticulin könnte Axel sein, ein extrazelluläres Protein, das wir ebenfalls in diesem Projekt identifiziert haben. Die olof- und axel-mutanten Phänotypen sind in der Tat identisch. In den nächsten zwei Jahren werde ich die Olof-Substrate anhand von Massenspektrometrie und NMR sowie die Funktion von Axel als Cuticulin-Protein untersuchen. Des Weiteren haben wir ein Dityrosin-Netzwerk in der Kutikula als Antagonist des hydrostatischen Innendrucks entdeckt. Die Konstruktion dieser Komponente ist Häm-abhängig, da Häm-reduzierte Larven verringerte Dityrosin-Mengen aufweisen und ihre Kutikula zerbricht, wodurch sie massiv Wasser verlieren. In vorläufigen Experimenten haben wir herausgefunden, daß Dityrosine bereits in Vesikeln innerhalb der Zelle gebildet werden. Um die molekularen Mechanismen der Dityrosinylierung zu verstehen, wollen wir das dafür verantwortliche Häm-Enzym in einem RNAi-Experiment identifizieren und den Verkehr der Dityrosin-Vesikeln und möglichen Zielproteinen wie Proresilin in einer Reihe von Sekretions-Mutanten aufzeigen. Neben diesen neuen Ansätzen interessiere ich mich für die Kontrolle der zeitlichen Abfolge der Kutikuladifferenzierung auf Sekretions- und Transkriptionsebene. In einem kompakten Projekt werde ich die bereits angedeutete Funktion des p24 Proteins Éclair während der Sortierung von Kutikulaproteinen analysieren. Darüber hinaus soll die Signatur der regulatorischen Sequenzen im Promoterbereich von Kutikulagenen bioinformatisch dechiffriert werden. Insbesondere soll in diesen Regionen nach Bindestellen für Grainyhead und Ekdyson-induzierte Transkriptionsfaktoren gesucht werden. Zusätzlich wird nach konservierten DNA-Motiven gefahndet, die in der Nachbarschaft dieser Bindestellen gehäuft vorkommen. Die Bedeutung dieser Promotoren wird in Expressionsexperimenten in transgenen Fliegen getestet.


SECRETORY MECHANISMS IN THE SALIVARY GLANDS

UNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT


Cooperation of Estrogen and Adrenergic Receptors in Cardiovascular Function: Mechanism and Impact

Cardiovascular disease poses a significant threat to women, particularly after menopause, due to reduced estrogen levels. This research aims to shed light on the role of the G protein-coupled estrogen receptor (GPER) in regulating rapid and non-genomic cardiovascular responses. The study will explore the interaction between GPER and  beta-adrenergic receptors (ßARs), which are involved in the body's "fight or flight" response. The researcher will investigate how these receptors trigger specific signaling pathways, either stimulating cardiovascular functions through stimulatory G protein (Gs) or dampening them via inhibitory G proteins (Gi).
The project's first aim is to uncover the molecular basis of the selective coupling of ßARs to Gs or Gi. Using computer modeling, different neurotransmitters like norepinephrine and epinephrine will be docked to active models of ßAR subtypes (ß1AR and ß2AR). The ligand-bound ßARs will then be coupled to Gs and Gi proteins to understand the conformational and energetic preferences that dictate ligand selectivity and receptor-G protein interactions.
In the second aim, the researcher will construct an atomistic models of GPER using homology modeling and artificial intelligence programs such as AlphaFold. The model will be docked with different estrogen forms (E1, E2, E3) to study estrogen binding affinities and specificities.  GPER models will also be used to examine the receptor's selectivity for Gs and Gi. Enhanced sampling molecular dynamics simulations will be used to provide quantitative insights into estrogen binding and GPER-G protein interactions.
The third aim involves incorporating the GPER signaling pathway into a kinetic functional model of ventricular cardiomyocytes  to predict sex-specific cardiovascular dysregulation, especially in females. By adjusting estrogen levels based on female age, the researcher will make predictions related to age-related risk factors for cardiovascular diseases.
This project's significance lies in understanding how GPER and  ßARs interact at the molecular level, and how estrogen's non-genomic effects impact cardiovascular functions. The results could pave the way for more targeted therapies that mimic estrogen's positive effects, potentially benefiting women after menopause. Additionally, this research may contribute to sex-specific treatments for cardiovascular diseases, considering the differences between male and female cardiac physiology.

The Regents of the University of California, on Behalf of its Davis Campus


Unpublizierte BogazkoyFragmente: Edition und Forschung (II)

Trotz des kontinuierlichen Veröffentlichungsprozesses der hethitischen Keilschrifttafeln sind noch unveröffentlichte Fragmente aus der Hauptstadt Bogazkoy / Hattusa. Versehen mit Siglum “Bo” stammen sie aus den frühen deutsch-osmanischen Ausgrabungen zwischen 1906 und 1912 und wurden zu Reinigungs- und Konservierungszwecken an das Staatliche Museum in Berlin geschickt. Nach dem Zweiten Weltkrieg wurden die Tafeln weiterhin von der Deutschen Demokratischen Republik aufbewahrt und es dauerte Jahre, bis sie in 1987 in die Türkei zurückgebracht wurden. Die Anzahl dieser Fragmente beträgt 7.300 und einige von ihnen wurden ediert, aber die Hälfte von ihnen bleibt weder veröffentlicht noch studiert. Diese Tontafeln stehen den Forschern nur in dem Maße zur Verfügung, wie sie in der Sekundärliteratur zitiert werden. Die unveröffentlichten Tontafeln, die in die Türkei zurückgebracht wurden, sollten von einem Team türkischer Hethitologen veröffentlicht werden. Nach einer Entscheidung des Kulturministeriums der Türkei im Jahr 2010 wurde ein neues Team gebildet, um an diesen Bo-Fragmenten zu arbeiten. Der Antragsteller erhielt eine Einladung, ein Teil dieses Projekts zu werden, und er führt seit 2010 wissenschaftliche Aktivitäten durch. Als Ergebnis seiner Forschung wurden zwei Bücher (Chicago Hittite Dictionary Supplements 2 und 3) und einige Artikel veröffentlicht. Wie in seinen früheren Phasen wird sich das vorgeschlagene Projekt weiterhin auf diese Gruppe epigraphischen Materials konzentrieren. Die Verwendung der unveröffentlichten Bo-Fragmente ist in den letzten dreißig Jahren zu einem wesentlichen Problem in der Hethitologie geworden. In diesem Sinne wären die Edition und Erforschung des betreffenden epigraphischen Materials ein willkommenes Ergebnis einer gemeinsamen deutsch-türkischen wissenschaftlichen Arbeit. Darüber hinaus wird das vorgeschlagene Projekt eine einzigartige, in der Tat die einzige Möglichkeit sein, einen leichten Zugang zu den Bo-Fragmenten zu haben, da die offiziellen Behörden im Ankara-Museum nur den türkischen Gelehrten die Erlaubnis erteilen, dieses unveröffentlichte Material zu verwenden. Der Antragsteller und seine Mitarbeiter, die türkische Staatsbürger sind und die Veröffentlichungsrechte für die in Frage kommenden Tontafeln besitzen, werden von diesem Problem nicht betroffen sein. Wie in den vorherigen Fällen werden die Forschungsergebnisse als gedrucktes Material veröffentlicht, d.h. als Monographien in der Reihe der Chicago Hittite Dictionary Supplements, und auch als digitale Version derselben Veröffentlichung, die als kostenloser Download von der Website des Oriental Institutes. Der Antragsteller plant noch eine Reihe von Artikeln in deutscher Sprache zu verfassen, die die wichtigsten Forschungsergebnisse, z. B. neu erworbene philologische und kontextuelle Informationen aus den unveröffentlichten Bo-Fragmenten zur hethitischen Sprache, Geschichte und Kultur, zu den Gelehrten zugänglich machen.


SOFTWARE FOR EVOLUTION BASED FUNCTIONAL GENOMICS


CONTAMINATION OF NAVAL SKEET RANGES


PKA modulation of hedgehog: mouse medulloblastoma model


Principal Investigator：石井 永, Project Period (FY)：1974, Research Category：Grant-in-Aid for General Scientific Research (C), Research Field：Chemical pharmacy


The Role of CD200R1 Signalling in the Regulation of Skin Inflammation.

The aim of this project is to determine the role of CD200R1 in skin immunity. CD200R1 is expressed by immune cells and engagement with the ligand, CD200, suppresses immune responses in various tissues. However, the role of CD200R1 in skin has not been fully elucidated. My preliminary data show lower levels of CD200 expression in psoriatic versus healthy skin, and the absence of CD200R1 results in exacerbated disease in a pre-clinical model of psoriasis. I also demonstrate novel CD200R1 expre ssion in innate lymphoid cells suggesting that CD200R1 regulates the activity of this important cell type. This project will identify the cell types in which CD200R1 expression is required to suppress skin inflammation and importantly, if exogenous CD200R1 activation suppresses skin inflammation. I will determine whether CD200R1 regulates the initiation, or promotes the resolution of skin inflammation. Also the project will determine the role of CD200R1 in suppressing immune responses against co mmensal microbes, and the role of these microbes in a pre-clinical model of psoriasis. This project will define the role of CD200R1 in regulating skin immunity, which will inform future therapeutic efforts, while providing essential insight into the regulation of inflammatory responses in skin.


No summary - Aucun sommaire

Natural Sciences and Engineering Research Council of Canada


Addressing the Ethical Component of Growing Inequality and Extreme Poverty Through Hegels Philosophy of Social Freedom

Social Sciences and Humanities Research Council of Canada

Canada Graduate Scholarships - Michael Smith Foreign Study Supplements


Development of a Novel Environmentally Friendly Electrolytic System Using Solid-Supported Bases and Its Application

We have successfully developed a novel environmentally friendly electrolytic system based on the acid-base reactions between protic solvents or carboxylic acids as substrates and solid-supported bases. Furthermore, we have successfully applied the electrolytic system using solid-supported bases to a flow cell and parallel electrosynthesis. On the other hand, in the series of studies, we found that solid-supported bases are not oxidized at the anode. On the basis of the finding, we proposed the concept of site isolation in organic electrosynthesis. It can be defined as solid-supported reagents are not subject to electrochemical destruction at electrodes.

Japan Society for the Promotion of Science


Supporting and measuring youth well-being in a community music education program


Clinical Research on Non-Alcoholic Steatohepatitis


Caracterização genética de suínos locais de Angola e sua relação com suídeos selvagens em simpatria - introgressão entre  espécies e implicações na adaptação


Conversion degree and hardness of resin cement under indirect restorations.

Fundação de Amparo à Pesquisa do Estado de São Paulo

Universidade Estadual Paulista (UNESP). Campus de São José dos Campos. Faculdade de Odontologia (FOSJC)


E/BETA THALASSEMIA--NATURAL HISTORY &RESPONSE TO CHEMO


Physicians' Perceptions, Attitudes, and Communication of E-Cigarettes (PACE)

PUBLIC HEALTH RELEVANCE:  The purpose of this research project is to provide an understanding of physicians' knowledge and attitudes towards e-cigarettes. The relevance of the proposed research to public health is to provide information about current tobacco harm reduction beliefs and practices that may impact public health on the frontline, and to identify impactful ways of communicating about these products with physicians in the future.


The Connecticut Agricultural Experiment Station 123 HUNTINGTON STREET BOX 1106 NEW, HAVEN CONNECTICUT 06504 Founded 1875 Putting science to work for society RFA-FD-10-003 Food Safety and Security Monitoring Project (U18) FERN Chemical Laboratories Please see the included PHS 398 Research Plan, 2. Research Plan Attachments for the full project narrative for the proposal entitled "Continuation of FERN Activities at the Connecticut Agricultural Experiment Station (CAES)." Included in that document are the research objectives in response to the four key project areas, as well as background and justification for funding the current proposal. Also included is a detailed description of CAES performance during the last five years as a FDA FERN cCAP Laboratory. Phone: (203) 974-8500 Fax: (203) 974-8502  Toll Free: 1-(877) 855-2237  Web Page: www.caes.state.ct.us An Equal Opportunity Provider


Function of SMAD7 in growth and differentiation of skeletal muscle

A variety of muscle diseases and ageing related muscle wasting result from a loss of muscle mass. We have discovered a gene called Smad7 which regulates skeletal muscle growth. So far these observations have been made in cultured muscle cells. In the proposed work we would like to develop this work further to understand how Smad7 has this effect on muscle cells and also to determine whether it fulfills the same function in living animals.


EFFECTIVENESS AND OUTCOMES OF NON-CARDIAC SURGERY


I  examined and compared the novels of Marie-Vieux Chauvet, Pauline Melville and those of Edwidge Danticat. As the novels written by the above three authors have rarely been discussed in relation to environmental issues in the Caribbean, my analysis of these texts demonstrates three writers' continuous concern for the environment and predicament of the women. Connecting and comparing these novels written by three writers would  reveal not only their insights into the environmental issues in the Caribbean but also foreground important aspects of Caribbean literature.  Above all, my research has offered a new perspective on a relatively known author, Edwidge Danticat,  that she has received a great influence from a prominent Haitian literary figure, Marie-Vieux Chauvet, and her writings are written in conversations with Chauvet.


HTS assays for the methylerythritol-4-phosphate pathway

The goal of this proposal is to develop high throughput screens to identify inhibitors of the methylerythritol 4- phosphate biosynthetic bacteria in Mycobacterium tuberculosis, which will potentially generate new lead compounds and eventually new drugs for the treatment of tuberculosis.


Role of lipid droplet protein in obesity and diabetes

8. Project Narrative Lipids play an important role for proper functions of insulin producing beta cells by serving as energy source and as signaling molecules to increase insulin secretion. However, unregulated accumulation of lipids damages beta cells resulting in type 2 diabetes. By examining how intracellular trafficking of lipids are regulated by protein termed perilipins to achieve effective use of lipids within cells and to prevent accumulation of toxic lipids, the study will provide an important knowledge for the prevention of type 2 diabetes.


Generation of mature human embryonic stem cell-derived left ventricular cardiomyocytes for transplantation in a large animal model

Project Narrative Myocardial infarction (MI) leads to irreversible loss of cardiomyocytes with subsequent scar formation. Human embryonic stem cells (hESCs) are capable of self-renewal and can generate all cell types including cardiomyocytes. In this proposal, we plan to use hESCs to generate left ventricular cardiomyocytes, promote their maturation in a dish, and deliver them into MI pig infarct model to investigate their engraftment and monitor functional improvement of the heart after transplantation.


Agonist & Antagonist Activity and Binding on the TMD of hT1R3

PUBLIC HEALTH RELEVANCE: There is today in the affluent countries of the world an epidemic of obesity, insulin-resistant diabetes and diet-related disorders. This is only made worse by our species evolutionary love affair with high- carbohydrate/energy-rich sweet foods. Taste perception and taste preference undoubtedly contribute to sweet-seeking behavior and food consumption. The identification of T1R2+T1R3 as the sweet receptor provides the target for intercession in modifying a behavior, which is maladaptive because of the plentiful food in affluent countries. Understanding the sweet receptor at a molecular level will enable the design of better low calorie sweeteners.


Stressors and their impact on health related addictions: smoking, drinking, BMI


Electric Field and Capillary Effects on Drop Circulation    And Mass Transfer


Molecular Study of Specific Intermolecular Interactions of Sugar Chains and Metastasis Mechanism of Cancer Cell

In this study, in order to investigate the interaction between sugar chains and proteins, we constructed a model sugar chain surface and trace the interaction between sugar chains and proteins at the molecular level to clarify the structure. First, we investigated the structure of the model sugar chain surface and its interaction with water, and obtained results suggesting that there are two types of hydrogen-bonding sites with different hydrogen bonding properties. We investigated the interaction between sugar chains and proteins, which was the original purpose, and tried to obtain structural information, but it was not clear because the signal derived from sugar chains could not be clearly detected.

Japan Society for the Promotion of Science

Grant-in-Aid for Challenging Research (Exploratory)

National Institute for Materials Science


Targeting the Notch3 Mutation to Cure Lehman Syndrome

PROJECT NARRATIVE  The work proposed will target the genetic mutation in models of human disease, as a means to treat and cure a rare but devastating clinical disorder. The work will form the basis for treating other genetic disorders affecting the skeleton.

UNIVERSITY OF CONNECTICUT SCH OF MED/DNT


The role of microRNA in maturation of tendon /ligament

The purpose of this study is to examine the role of microRNA (miRNA) in the development and maturation of tendon/ligament using Scleraxis-Cre knock-in:Dicer flox mice. We performed miRNA expression profiling using achilles tendon tissues and Achilles tendon-derived cells. Several miRNAs highly expressed in Achilles tendon. To examine the role of miRNAs in development and maturation of tendon/ligament, we generated Scleraxis-Cre knock-in:Dicer flox mice. Dicer is one of the most important enzyme in miRNA biogenesis. Scleraxis-Cre knock-in:Dicer flox mice showed impaired tendon maturation and healing. Highly expressed miRNAs in tendon were decreased in achilles tendon of these mice. Thus, these data suggest that miRNA play an important role in maturation and healing of tendon/ligament.

Grant-in-Aid for Challenging Exploratory Research


Lead-free halide perovskite memristors modified with buffer layers for sustainable and high-performance neuromorphic computing

The World's digital transformation generates vast amounts of data daily. Conventional computing technologies face serious challenges in efficiently handling all this information, leading to high energy consumption. Neuromorphic computing offers a more efficient solution by designing systems inspired by the structure and function of the human brain, which processes information in parallel with minimal energy consumption. A key component in this technology is the memristor, a novel electronic element that mimics the synapses and spiking processes of neurons. The memristors containing lead-based halide perovskites (Pb-HPs) are among the best-performing, but the presence of toxic Pb hinders their practical application.
MemSusPer aims to develop sustainable, Pb-free HP memristor devices with high performance, stability, reproducibility, and low energy consumption. This will be achieved through two main strategies: (1) enhancing the quality of the perovskite films, and (2) using novel buffer layer materials, such as organic mixed ionic electronic conductors, to regulate the ions migration and induce new energy-efficient activation/deactivation mechanisms. I will conduct the research at the Institute of Advanced Materials (University Jaume I, Spain) with the guidance of Prof. Antonio Guerrero, a leading expert in the field. To validate the developed technology, a 4x4 memristor array will be fabricated using the advanced infrastructure of the Institute of Emerging Technologies (Hellenic Mediterranean University, Greece). MemSusPer is committed to advancing next-generation neuromorphic computing, which is not only high-performing but also eco-friendly, contributing to the green and digital transitions prioritised in the European Union's agenda. The multidisciplinarity and high impact of MemSusPer, combined with the training component of the MSCA-PF, will help me become a tenured independent researcher, expand my expertise, and strengthen my academic profile and networks.


MULTIDISCIPLINARY APPROACHES TUMOR IMMUNOLOGY


NIH INTRAMURAL NRSA INSTITUTIONAL TRAINING PROGRAM


Creatine Safety and Efficacy in HD: Coordination and Statistical Supplement


Opening up lexicons of early modern English

Social Sciences and Humanities Research Council of Canada


Feature extraction for biometric image using extended relational graph and neural network approach

従来の生体情報特徴量抽出手法では、生体情報画像の局所的な特徴のみ注目していた。本研究では、特徴抽出の精度向上のためには大局的生体情報が必要と考えた。そこで、生体情報画像のテクスチャを拡張関係グラフとして抽象化しグラフから大局的な生体情報を抽出する手法を提案した。次に局所的/大局的生体情報を組み合わせ、指紋特徴抽出、虹彩領域抽出の2分野に対して本手法を組み込んだ手法を試行した。実際に実験結果から本手法の有効性を確認した。