PGC-based cryobanking, regeneration through germline chimera mating, and CRISPR/Cas9-mediated TYRP1 modification in indigenous Chinese chickens.

Primordial germ cells (PGCs) are vital for producing sperm and eggs and are crucial for conserving chicken germplasm and creating genetically modified chickens. However, efforts to use PGCs for preserving native chicken germplasm and genetic modification via CRISPR/Cas9 are limited. Here we show that we established 289 PGC lines from eight Chinese chicken populations with an 81.

Mammalian genome research resources available from the National BioResource Project in Japan.

Mammalian genome research has conventionally involved mice and rats as model organisms for humans. Given the recent advances in life science research, to understand complex and higher-order biological phenomena and to elucidate pathologies and develop therapies to promote human health and overcome diseases, it is necessary to utilize not only mice and rats but also other bioresources such as standardized genetic materials and appropriate cell lines in order to gain deeper molecular and cellular insights. The Japanese bioresource infrastructure program called the National BioResource Project (NBRP) systematically collects, preserves, controls the quality, and provides bioresources for use in life science research worldwide.

In vivo-stable bis-iminobiotin for targeted radionuclide delivery with the mutant streptavidin.

Targeted delivery of radionuclides to tumors is significant in theranostics applications for precision medicine. Pre-targeting, in which a tumor-targeting vehicle and a radionuclide-loaded effector small molecule are administered separately, holds promise since it can reduce unnecessary internal radiation exposure of healthy cells and can minimize radiation decay. The success of the pre-targeting delivery requires an in vivo-stable tumor-targeting vehicle selectively binding to tumor antigens and an in vivo-stable small molecule effector selectively binding to the vehicle accumulated on the tumor.

New insights into the role of microheterogeneity of ZP3 during structural maturation of the avian equivalent of mammalian zona pellucida.

The egg coat including mammalian zona pellucida (ZP) and the avian equivalent, i.e., inner-perivitelline layer (IPVL), is a specialized extracellular matrix being composed of the ZP glycoproteins and surrounds both pre-ovulatory oocytes and ovulated egg cells in vertebrates.

Determination of brain tumor recurrence using C-methionine positron emission tomography after radiotherapy.

We conducted a prospective multicenter trial to compare the usefulness of C-methionine (MET) and F-fluorodeoxyglucose (FDG) positron emission tomography (PET) for identifying tumor recurrence. Patients with clinically suspected tumor recurrence after radiotherapy underwent both C-MET and F-FDG PET. When a lesion showed a visually detected uptake of either tracer, it was surgically resected for histopathological analysis.

Integrated PET/MRI scanner with oxygen-15 labeled gases for quantification of cerebral blood flow, cerebral blood volume, cerebral oxygen extraction fraction and cerebral metabolic rate of oxygen.

Objectives: Measurement of cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO) by PET with oxygen-15 labeled gases is useful for diagnosis and treatment planning in cases of chronic occlusive cerebrovascular disease. In the present study, CBF, CBV, OEF and CMRO were measured using the integrated design of PET/MRI scanner system. This is a first attempt to measure cerebral perfusion and oxygen metabolism using PET/MRI with oxygen-15 labeled gases.

Regulatory mechanism of chicken lysozyme gene expression in oviducts examined using transgenic technology.

The use of promoters that strongly express target genes in the chicken oviduct is beneficial for the production of proteinaceous materials into egg white by transgenic chickens. To examine the regulatory mechanisms of chicken lysozyme gene expression in vivo, genetically manipulated chickens that express human erythropoietin under the control of a lysozyme promoter-enhancer were established. By using several deletion mutants of the promoter-flanking region, we found that a -1.

Primordial germ cell-specific expression of eGFP in transgenic chickens.

PR domain zinc finger protein 14 (PRDM14) plays an essential role in the development of primordial germ cells (PGCs) in mice. However, its functions in avian species remain unclear. In the present study, we used CRISPR/Cas9 to edit the PRDM14 locus in chickens in order to demonstrate its importance in development.

Preliminary Evaluation of Astatine-211-Labeled Bombesin Derivatives for Targeted Alpha Therapy.

There are various diagnostic and therapeutic agents for prostate cancer using bombesin (BBN) derivatives, but astatine-211 (At)-labeled BBN derivatives have yet to be studied. This study presented a preliminary evaluation of At-labeled BBN derivative. Several nonradioactive iodine-introduced BBN derivatives (IB-BBNs) with different linkers were synthesized and their binding affinities measured.

Biodistribution and internal radiation dosimetry of a novel probe for thymidine phosphorylase imaging, [I]IIMU, in healthy volunteers.

Objective: We evaluated the radiation dosage, biodistribution, human safety, and tolerability of the injection of a single dose of [I] 5-iodo-6-[(2-iminoimidazolidinyl)methyl]uracil (IIMU), a new radiotracer targeting thymidine phosphorylase (TP), in healthy volunteers.

Methods: Potential participants were tested at our hospital to confirm their eligibility. Two healthy male adults passed the screening tests.

Siglec-F is induced by granulocyte-macrophage colony-stimulating factor and enhances interleukin-4-induced expression of arginase-1 in mouse macrophages.

Siglecs are cell surface lectins that recognize sialic acids and are primarily expressed in hematopoietic cells. Previous studies showed that some Siglecs regulate macrophage function. In the present study, we examined the induction and putative roles of mouse Siglec-F in bone-marrow-derived macrophages in mice.

Biodistribution and radiation dosimetry of the novel hypoxia PET probe [F]DiFA and comparison with [F]FMISO.

Background: To facilitate hypoxia imaging in a clinical setting, we developed 1-(2,2-dihydroxymethyl-3-[F]-fluoropropyl)-2-nitroimidazole ([F]DiFA) as a new tracer that targets tumor hypoxia with its lower lipophilicity and efficient radiosynthesis. Here, we evaluated the radiation dosage, biodistribution, human safety, tolerability, and early elimination after the injection of [F]DiFA in healthy subjects, and we performed a preliminary clinical study of patients with malignant tumors in a comparison with [F]fluoromisonidazole ([F]FMISO).

Results: The single administration of [F]DiFA in 8 healthy male adults caused neither adverse events nor abnormal clinical findings.

PRDM14 and BLIMP1 control the development of chicken primordial germ cells.

The differentiation of primordial germ cells (PGCs) is a fundamental step in development. PR domain-containing protein 14 (PRDM14) and B lymphocyte-induced maturation protein 1 (BLIMP1) play pivotal roles in mouse PGC specification. In the present study, we assessed the roles of chicken orthologs of PRDM14 and BLIMP1 in PGC development.

Comparative evaluation of [F]DiFA and its analogs as novel hypoxia positron emission tomography and [F]FMISO as the standard.

Introduction: Hypoxia, a common feature of most solid tumors, is an important predictor of tumor progression and resistance to radiotherapy. We developed a novel hypoxia imaging probe with optimal biological characteristics for use in clinical settings.

Methods: We designed and synthesized several new hypoxia probes with additional hydrophilic characteristics compared to [F]fluoromisonidazole ([F]FMISO).

A Novel PET Probe "[F]DiFA" Accumulates in Hypoxic Region via Glutathione Conjugation Following Reductive Metabolism.

Purpose: Hypoxia in tumor has close relationship with angiogenesis and tumor progression. Previously, we developed 2,2-dihydroxymethyl-3-[F]fluoropropyl-2-nitroimidazole ([F]DiFA) as a novel positron emission tomography (PET) probe for diagnosis of hypoxia. In this study, we elucidated whether the accumulation of [F]DiFA in cells is dependent on the hypoxic state and revealed how [F]DiFA accumulates in hypoxic cells in combination with imaging mass spectrometry (IMS).

In-DTPA-d-Phe-Asp-d-Phe-octreotide exhibits higher tumor accumulation and lower renal radioactivity than In-DTPA-d-Phe-octreotide.

Introduction: In-DTPA-d-Phe-octreotide scintigraphy is an important method of detecting neuroendocrine tumors. We previously reported that a new derivative of In-DTPA-d-Phe-octreotide, In-DTPA-d-Phe-Asp-d-Phe-octreotide, accomplished the reduction of prolonged renal accumulation of radioactivity. The aim of this study was to evaluate the tumor accumulation of In-DTPA-d-Phe-Asp-d-Phe-octreotide in vitro and in vivo by comparing it with In-DTPA-d-Phe-octreotide.

Changes in tumor oxygen state after sorafenib therapy evaluated by F-fluoromisonidazole hypoxia imaging of renal cell carcinoma xenografts.

A mechanistic dissociation exists between tumor starvation and vascular normalization after antiangiogenic therapy. Thus, improved understanding of tumor responses (tumor starvation or vascular normalization) is important for optimizing treatment strategies. F-fluoromisonidazole (F-FMISO) is widely used for imaging tumor hypoxia.

FMISO accumulation in tumor is dependent on glutathione conjugation capacity in addition to hypoxic state.

Objective: F-fluoromisonidazole (FMISO), a well-known PET imaging probe for diagnosis of hypoxia, is believed to accumulate in hypoxic cells via covalent binding with macromolecules after reduction of the nitro group. Previously, we showed the majority of F-FMISO was incorporated into low-molecular-weight metabolites in hypoxic tumors, and the glutathione conjugate of reduced FMISO (amino-FMISO-GS) distributed in the tumor hypoxic regions as revealed by imaging mass spectrometry (IMS). The present study was conducted to clarify whether FMISO is metabolized to amino-FMISO-GS within tumor cells and how amino-FMISO-GS contributes to FMISO accumulation in hypoxic cells.

Molecular cloning of chicken TET family genes and role of chicken TET1 in erythropoiesis.

Ten-eleven translocation (TET) methylcytosine dioxygenase has potential as an active eraser to regulate the genomic DNA methylation status. We herein cloned chicken TET (cTET) family genes, and confirmed their functions. Quantitative reverse-transcription PCR showed that cTET1 was strongly expressed in erythrocytes throughout development.

Redesign of negatively charged In-DTPA-octreotide derivative to reduce renal radioactivity.

Introduction: Radiolabeled octreotide derivatives have been studied as diagnostic and therapeutic agents for somatostatin receptor-positive tumors. To prevent unnecessary radiation exposure during their clinical application, the present study aimed to develop radiolabeled peptides which could reduce radioactivity levels in the kidney at both early and late post-injection time points by introducing a negative charge with an acidic amino acid such as L-aspartic acid (Asp) at a suitable position in In-DTPA-conjugated octreotide derivatives.

Methods: Biodistribution of the radioactivity was evaluated in normal mice after administration of a novel radiolabeled peptide by a counting method.

Characterization of chicken interferon-inducible transmembrane protein-10.

Interferon-inducible transmembrane protein (IFITM) family proteins are antivirus factors. In the present study, we examined the expression pattern of chicken IFITM10 using quantitative reverse transcription-polymerase chain reaction. In adult chickens, IFITM10 levels were markedly lower than those of IFITM3, which exhibits antivirus activity.

Immunoglobulin G (IgG)-Based Imaging Probe Accumulates in M1 Macrophage-Infiltrated Atherosclerotic Plaques Independent of IgG Target Molecule Expression.

Purpose: Vulnerable plaques are key factors for ischemic diseases. Thus, their precise detection is necessary for the diagnosis of such diseases. Immunoglobulin G (IgG)-based imaging probes have been developed for imaging biomolecules related to plaque formation for the diagnosis of atherosclerosis.