Diel feeding rhythms, daily ration, and seasonal changes thereof in marbled flounder Pseudopleuronectes yokohamae

This paper aims to assess the diel feeding pattern and seasonal variation in the daily ration of immature and mature marbled flounder (Pseudopleuronectes yokohamae ). A day‐night collection by bottom trawls was conducted in Sendai Bay in July 2014. Marbled flounder (131–493 mm total length; Number of collected individuals = 1830, Number of analyzed individuals = 497) fed mainly on polychaetes during the day. At night, stomach content weight decreased with time, but the weight and proportion of bivalve siphons were consistently higher at night than during the day, suggesting nocturnal feeding by the flounder on bivalve siphons. Daily ration was greater in females (<300 mm: 2.6%–3.2% body weight; ≥300 mm: 1.5%–2.5%) than in males (<300 mm: 1.7%–2.6%; ≥300 mm: 1.3%–1.9%). Seasonal surveys were also carried out, and the greater ration in females than males were consistent throughout the year, suggesting that greater growth in females than males attributes to the greater food intake of females. The ration was highest in June, especially for large individuals, although water temperature in June was lower than that in September. These results indicate that the amount of food intake is related to the annual life cycle of the marbled flounder.This work was partly supported by the Stock Assessment Program of Fisheries Agency and Fisheries Research and Education Agency of Japan and the program “Project on Clarifying the Impact of Nuclear Substances” of the Fisheries Agency of Japan

Evaluation of transporter-mediated hepatobiliary transport of newly developed ¹⁸F-labeled pitavastatin derivative, PTV-F1, in rats by PET imaging

Quantitative evaluations of the functions of uptake and efflux transporters directly in vivo is desired to understand an efficient hepatobiliary transport of substrate drugs. Pitavastatin is a substrate of organic anion transporting polypeptides (OATPs) and canalicular efflux transporters; thus, it can be a suitable probe for positron-emission tomography (PET) imaging of hepatic transporter functions. To characterize the performance of [¹⁸F]PTV-F1, an analogue of pitavastatin, we investigated the impact of rifampicin (a typical OATP inhibitor) coadministration or Bcrp (breast cancer resistance protein) knockout on [¹⁸F]PTV-F1 hepatic uptake and efflux in rats by PET imaging. After intravenous administration, [¹⁸F]PTV-F1 selectively accumulated in the liver, and the radioactivity detected in plasma, liver, and bile mainly derived from the parent PTV-F1 during the PET study (∼40 min). Coadministration of rifampicin largely decreased the hepatic uptake of [¹⁸F]PTV-F1 by 73%. Because of its lower clearance in rats, [¹⁸F]PTV-F1 is more sensitive for monitoring changes in hepatic OATP1B function that other previously reported OATP1B PET probes. Rifampicin coadministration also significantly decreased the biliary excretion of radioactivity by 65%. Bcrp knockout did not show a significant impact on its biliary excretion.[¹⁸F]PTV-F1 enables quantitative analysis of the hepatobiliary transport system for organic anions

Utility of Nd isotope ratio as a tracer of marine animals : regional variation in coastal seas and causal factors

Isotopic compositions of animal tissue are an intrinsic marker commonly used to trace animal origins and migrations; however, few isotopes are effective for this purpose in marine environments, especially on a local scale. The isotope ratio of the lanthanoid element neodymium (Nd) is a promising tracer for coastal animal migrations. Neodymium derives from the same geologic materials as strontium, well known as an isotopic tracer (87Sr/86Sr) for terrestrial and anadromous animals. The advantage of the Nd isotope ratio (143Nd/144Nd, expressed as εNd) is that it varies greatly in the ocean according to the geology of the neighboring continents, whereas oceanic 87Sr/86Sr is highly uniform. This study explored the utility of the Nd isotope ratio as a marine tracer by investigating the variation of εNd preserved in tissues of coastal species, and the causes of that variation, in a region of northeastern Japan where the bedrock geology is highly variable. We measured εNd and 87Sr/86Sr in seawater, river water, and soft tissues of sedentary suspension feeders: the mussels Mytilus galloprovincialis and Mytilus coruscus and the oyster Crassostrea gigas. We also measured concentrations of three lanthanoids (La, Ce, and Pr) in shellfish bodies to determine whether the Nd in shellfish tissue was derived from solution in seawater or from suspended particulates. The εNd values in shellfish tissue varied regionally (−6 to +1), matching the ambient seawater, whereas all 87Sr/86Sr values were homogeneous and typical of seawater (0.7091–0.7092). The seawater εNd values were in turn correlated with those in the adjacent rivers, linking shellfish εNd to the geology of river catchments. The depletion of Ce compared to La and Pr (negative Ce anomaly) suggested that the Nd in shellfish was derived from the dissolved phase in seawater. Our results indicate that the distinct Nd isotope ratio derived from local geology is imprinted, through seawater, on the soft tissues of shellfish. This result underscores the potential of εNd as a tracer of coastal marine animals

Temporal subtraction CT with nonrigid image registration improves detection of bone metastases by radiologists: results of a large-scale observer study

To determine whether temporal subtraction (TS) CT obtained with non-rigid image registration improves detection of various bone metastases during serial clinical follow-up examinations by numerous radiologists. Six board-certified radiologists retrospectively scrutinized CT images for patients with history of malignancy sequentially. These radiologists selected 50 positive and 50 negative subjects with and without bone metastases, respectively. Furthermore, for each subject, they selected a pair of previous and current CT images satisfying predefined criteria by consensus. Previous images were non-rigidly transformed to match current images and subtracted from current images to automatically generate TS images. Subsequently, 18 radiologists independently interpreted the 100 CT image pairs to identify bone metastases, both without and with TS images, with each interpretation separated from the other by an interval of at least 30 days. Jackknife free-response receiver operating characteristics (JAFROC) analysis was conducted to assess observer performance. Compared with interpretation without TS images, interpretation with TS images was associated with a significantly higher mean figure of merit (0.710 vs. 0.658; JAFROC analysis, P = 0.0027). Mean sensitivity at lesion-based was significantly higher for interpretation with TS compared with that without TS (46.1% vs. 33.9%; P = 0.003). Mean false positive count per subject was also significantly higher for interpretation with TS than for that without TS (0.28 vs. 0.15; P < 0.001). At the subject-based, mean sensitivity was significantly higher for interpretation with TS images than that without TS images (73.2% vs. 65.4%; P = 0.003). There was no significant difference in mean specificity (0.93 vs. 0.95; P = 0.083). TS significantly improved overall performance in the detection of various bone metastases

TIGIT/CD155 axis mediates resistance to immunotherapy in patients with melanoma with the inflamed tumor microenvironment

Background Patients with cancer benefit from treatment with immune checkpoint inhibitors (ICIs), and those with an inflamed tumor microenvironment (TME) and/or high tumor mutation burden (TMB), particularly, tend to respond to ICIs; however, some patients fail, whereas others acquire resistance after initial response despite the inflamed TME and/or high TMB. We assessed the detailed biological mechanisms of resistance to ICIs such as programmed death 1 and/or cytotoxic T-lymphocyte-associated protein 4 blockade therapies using clinical samples. Methods We established four pairs of autologous tumor cell lines and tumor-infiltrating lymphocytes (TILs) from patients with melanoma treated with ICIs. These tumor cell lines and TILs were subjected to comprehensive analyses and in vitro functional assays. We assessed tumor volume and TILs in vivo mouse models to validate identified mechanism. Furthermore, we analyzed additional clinical samples from another large melanoma cohort. Results Two patients were super-responders, and the others acquired resistance: the first patient had a non-inflamed TME and acquired resistance due to the loss of the beta-2 microglobulin gene, and the other acquired resistance despite having inflamed TME and extremely high TMB which are reportedly predictive biomarkers. Tumor cell line and paired TIL analyses showed high CD155, TIGIT ligand, and TIGIT expression in the tumor cell line and tumor-infiltrating T cells, respectively. TIGIT blockade or CD155-deletion activated T cells in a functional assay using an autologous cell line and paired TILs from this patient. CD155 expression increased in surviving tumor cells after coculturing with TILs from a responder, which suppressed TIGIT+ T-cell activation. Consistently, TIGIT blockade or CD155-deletion could aid in overcoming resistance to ICIs in vivo mouse models. In clinical samples, CD155 was related to resistance to ICIs in patients with melanoma with an inflamed TME, including both primary and acquired resistance. Conclusions The TIGIT/CD155 axis mediates resistance to ICIs in patients with melanoma with an inflamed TME, promoting the development of TIGIT blockade therapies in such patients with cancer

Time-resolved photoelectron angular distributions from nonadiabatically aligned CO2 molecules with SX-FEL at SACLA

Weperformed time-resolved photoelectron spectroscopy of valence orbitals of alignedCO2 molecules using the femtosecond soft x-ray free-electron laser and the synchronized near-infrared laser. By properly ordering the individual single-shot ion images, we successfully obtained the photoelectron angular distributions (PADs) of theCO2 molecules aligned in the laboratory frame (LF). The simulations using the dipole matrix elements due to the time dependent density functional theory calculations well reproduce the experimental PADs by considering the axis distributions of the molecules. The simulations further suggest that, when the degrees of alignment can be increased up to \ue1 cos2 q\uf1 > 0.8, themolecular geometries during photochemical reactions can be extracted fromthe measured LFPADs once the accurate matrix elements are given by the calculations

Ultrafast Control of Crystal Structure in a Topological Charge-Density-Wave Material

Optical control of crystal structures is a promising route to change physical properties including topological nature of a targeting material. Time-resolved X-ray diffraction measurements using the X-ray free-electron laser are performed to study the ultrafast lattice dynamics of VTe$_2$, which shows a unique charge-density-wave (CDW) ordering coupled to the topological surface states as a first-order phase transition. A significant oscillation of the CDW amplitude mode is observed at a superlattice reflection as well as Bragg reflections. The frequency of the oscillation is independent of the fluence of the pumping laser, which is prominent to the CDW ordering of the first-order phase transition. Furthermore, the timescale of the photoinduced 1$T^{\prime\prime}$ to 1$T$ phase transition is independent of the period of the CDW amplitude mode

PD-1 blockade therapy promotes infiltration of tumor-attacking exhausted T cell clonotypes

PD-1 blockade exerts clinical efficacy against various types of cancer by reinvigorating T cells that directly attack tumor cells (tumor-specific T cells) in the tumor microenvironment (TME), and tumor-infiltrating lymphocytes (TILs) also comprise nonspecific bystander T cells. Here, using single-cell sequencing, we show that TILs include skewed T cell clonotypes, which are characterized by exhaustion (T-ex) or nonexhaustion signatures (Tnon-ex). Among skewed clonotypes, those in the T-ex, but not those in the Tnon-ex, cluster respond to autologous tumor cell lines. After PD-1 blockade, non-preexisting tumor-specific clonotypes in the T-ex cluster appear in the TME. Tumor-draining lymph nodes (TDLNs) without metastasis harbor a considerable number of such clonotypes, whereas these clonotypes are rarely detected in peripheral blood. We propose that tumor-infiltrating skewed T cell clonotypes with an exhausted phenotype directly attack tumor cells and that PD-1 blockade can promote infiltration of such T-ex clonotypes, mainly from TDLNs

Real-time 3D Photoacoustic Visualization System with a Wide Field of View for Imaging Human Limbs [version 2; referees: 2 approved]

Background: A breast-specific photoacoustic imaging (PAI) system prototype equipped with a hemispherical detector array (HDA) has been reported as a promising system configuration for providing high morphological reproducibility for vascular structures in living bodies. Methods: To image the vasculature of human limbs, a newly designed PAI system prototype (PAI-05) with an HDA with a higher density sensor arrangement was developed. The basic device configuration mimicked that of a previously reported breast-specific PAI system. A new imaging table and a holding tray for imaging a subject's limb were adopted. Results: The device’s performance was verified using a phantom. Contrast of 8.5 was obtained at a depth of 2 cm, and the viewing angle reached up to 70 degrees, showing sufficient performance for limb imaging. An arbitrary wavelength was set, and a reasonable PA signal intensity dependent on the wavelength was obtained. To prove the concept of imaging human limbs, various parts of the subject were scanned. High-quality still images of a living human with a wider size than that previously reported were obtained by scanning within the horizontal plane and averaging the images. The maximum field of view (FOV) was 270 mm × 180 mm. Even in movie mode, one-shot 3D volumetric data were obtained in an FOV range of 20 mm in diameter, which is larger than values in previous reports. By continuously acquiring these images, we were able to produce motion pictures. Conclusion: We developed a PAI prototype system equipped with an HDA suitable for imaging limbs. As a result, the subject could be scanned over a wide range while in a more comfortable position, and high-quality still images and motion pictures could be obtained