Neutrophils in cancer: neutral no more

Neutrophils are indispensable antagonists of microbial infection and facilitators of wound healing. In the cancer setting, a newfound appreciation for neutrophils has come into view. The traditionally held belief that neutrophils are inert bystanders is being challenged by the recent literature. Emerging evidence indicates that tumours manipulate neutrophils, sometimes early in their differentiation process, to create diverse phenotypic and functional polarization states able to alter tumour behaviour. In this Review, we discuss the involvement of neutrophils in cancer initiation and progression, and their potential as clinical biomarkers and therapeutic targets

Examining the Applicability of Systems Theory to the Practical Understanding of Business Systems

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The Effect of Actinomycin D on the Early Embryos in the Full-sib and Random Mating Groups of Japanese Quail

本研究は近交による発生前期での胚死亡の原因に関する情報を得るために,代謝拮抗物質であるアクチノマイシンDが日本ウズラの近交群と無作為交配群における初期胚に及ぼす影響について検討した.実験に使用した日本ウズラは近交群1世代と6世代および無作為交配群である.アクチノマイシンDのLD50値の検討では,原液(2mg/70%エチルアルコール10m1)の5段階稀釈濃度が孵卵後48時間目の種卵の卵黄中に0.015ml注入された.次に無作為交配群でのLD50値が近交群と無作為交配群の種卵の卵黄中に注入された.この時の注入方法はLD50値検討の場合と同様とした.注入された種卵はさらに48時間孵卵し,胚死亡率,胚発育,胚奇形の出現率について検討した.胚奇形は7種類に任意に分類した.得られた結果は要約すると以下の通りである. 1.アクチノマイシンDのLD40値は近交群の1世代目では35.2μg,6世代目では29.0μg,一方無作為交配群では47.9μgとなり,近交群でのLD50値は近交世代に伴い急激な低下が認められた. 2.無作為交配群のLD50値を使用して検討した結果,近交群での胚死亡率は近交に伴い増加し,無作為交配群のものに比較して高い値を示した. 3.胚発育についてLD50値を使用して検討した結果,近交群では胚発育の遅延が著明であった.また,近交群では体の大きさと血管の形成に著しい影響が認められた. 4.胚奇形の出現率についてLD50値を使用して検討した結果,胚奇形の出現率は近交群が無作為交配群よりも有意に高い値を示した.分類された胚奇形の中で,尾芽の発育遅延・発育不全,無尾と発生不全・矮小の胚奇形の出現率は近交群,無作為交配群ともに高い値を示した.近交群でのこれらの胚奇形の出現率は無作為交配群の場合よりも高い値を示した. 5.以上の結果から,近交群では初期胚のタンパク合成に関与する代謝活性が低下し,そのため初期発生段階において胚死亡がひきおこされたものと考察した

Effects of Cations and thiol Compounds on the activity of Epidermal Aminopeptidase I

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Absorbent microbiopsy sampling and RNA extraction for minimally invasive, simultaneous blood and skin analysis

Conventional skin biopsy limits the clinical research that involves cosmetically sensitive areas or pediatric applications due to its invasiveness. Here, we describe the protocol for using an absorbent microneedle-based device, absorbent microbiopsy, for minimally invasive sampling of skin and blood mixture. Our goal is to help facilitate rapid progress in clinical research, the establishment of biomarkers for skin disease and reducing the risk for clinical research participants. In contrast to conventional skin biopsy techniques, the absorbent microbiopsy can be performed within seconds and does not require intensive training due to its simple design. In this report, we describe the use of absorbent microbiopsy, including loading and application, on a volunteer. Then, we show how to isolate RNA from the absorbed sample. Finally, we demonstrate the use of quantitative reverse transcription PCR (RT-qPCR) to quantify mRNA expression levels of both blood (CD3E and CD19) and skin (KRT14 and TYR). The methods that we describe utilize off the shelf kits and reagents. This protocol offers a minimally invasive approach for simultaneous sampling of skin and blood within the same absorbent microbiopsy matrix. We have found human ethics committees, clinicians and volunteers to be supportive of this approach to dermatological research.Benson U.W. Lei, Miko Yamada, Van L.T. Hoang, Paul J. Belt, Mark H. Moore, Lynlee L. Lin, Ross Flewell-Smith, Nhung Dang, Shoko Tomihara, Tarl W. Pro

Remote control and surveillance systems that utilize virtual instrument technology the Internet and a cellular phone

　We have developed PC-based remote control and surveillance systems that utilize the LabVIEW-based virtual instrument (VI) technology, the Internet and a cellular phone. The main VIs we have developed are “Remote Control VI for a Mobile Robot and a Robot Arm” and “Remote Surveillance and Warning VI”. In these VIs we devised a control system of mouse-clicking on camera images mounted on a remote browser. With this control system mis-operations of the VIs caused by the delay of image-communication between two remote sites can be eliminated

隠れマルコフモデルを用いたマウス状態の自動判定と2値マルコフモデルによるコンソミックマウス系統の特徴付け

要旨あり原著論

Different PDGF Receptor Dimers Drive Distinct Migration Modes of the Mouse Skin Fibroblast

Background/Aims: The migration of mesenchymal cells is a fundamental cellular process that has been implicated in many pathophysiological conditions and is induced by chemoattractants such as platelet-derived growth factors (PDGFs). However, the regulatory mechanisms shaping this migration remain to be elucidated. Methods: Here, we prepared mouse skin fibroblasts inactivated for different PDGF receptor genes and systematically measured their chemotactic responses within a gradient of different chemoattractants. Results: We found that PDGFRαβ and PDGFRββ dimers were strong inducers of random and directionally-persistent migration, respectively, that was sustained for up to 24 h. MAPK and PI3K were necessary to mediate random and directional migration, respectively. Directional migration was accompanied by abundant ventral stress fiber formation and consistent cell shape with less frequent formation of branch-like processes. Conclusion: This is the first systematic study that characterized the chemotaxis mediated by three-different types of PDGFR dimers in mesenchymal cell migration. Our data demonstrate that PDGFR dimer formation is the critical step to determine the specific mode of fibroblast chemotaxis, while the accompanying cytoskeletal remodeling might contribute to migration persistence

PRMT1-dependent regulation of RNA metabolism and DNA damage response sustains pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer that has remained clinically challenging to manage. Here we employ an RNAi-based in vivo functional genomics platform to determine epigenetic vulnerabilities across a panel of patient-derived PDAC models. Through this, we identify protein arginine methyltransferase 1 (PRMT1) as a critical dependency required for PDAC maintenance. Genetic and pharmacological studies validate the role of PRMT1 in maintaining PDAC growth. Mechanistically, using proteomic and transcriptomic analyses, we demonstrate that global inhibition of asymmetric arginine methylation impairs RNA metabolism, which includes RNA splicing, alternative polyadenylation, and transcription termination. This triggers a robust downregulation of multiple pathways involved in the DNA damage response, thereby promoting genomic instability and inhibiting tumor growth. Taken together, our data support PRMT1 as a compelling target in PDAC and informs a mechanism-based translational strategy for future therapeutic development. Statement of significance PDAC is a highly lethal cancer with limited therapeutic options. This study identified and characterized PRMT1-dependent regulation of RNA metabolism and coordination of key cellular processes required for PDAC tumor growth, defining a mechanism-based translational hypothesis for PRMT1 inhibitors