Spontaneous Cardiac Hypertrophy in a Crl:CD(SD) Rat

Cardiac hypertrophy was observed in a 9-week-old Crl:CD(SD) rat that died unexpectedly. The animal was allocated to the control group of a toxicity study, and no abnormalities in its general conditions, body weight or food intake were observed. Necropsy revealed an increase in heart weight. Gross examination indicated cardiac enlargement with thickening of the right and left ventricular walls. Histopathological examination revealed hypertrophy of the cardiomyocytes in the right and left ventricular walls and the interventricular septum. Electron microscopic examination indicated bizarre nuclei and accumulation of an increased number of various sizes of mitochondria in the perinuclear region of the hypertrophied myocytes. Hypertrophied myocytes connected by intensely folded intercalated disks were also observed. Based on these findings, the animal was diagnosed with cardiac hypertrophy. This is the first case report of cardiac hypertrophy in this strain

A Case Report of a Malignant Fibrous Histiocytoma in a T-cell Receptor β Chain and p53 Double-knockout Mouse

A subcutaneous tumor was found in the right abdomen of a 16-week-old male TCRβ and p53 double-knockout mouse. The tumor had indistinct borders with the surrounding tissue. The cut surface after formalin fixation was pale yellowish white, partially dark red and partly white. Histologically, the tumor was composed of three distinct regions. The first region showed pleomorphic cells arranged in sheets. The second region showed spindle cells arranged in interlacing fascicles. The final region contained a mixture of the above mentioned two types of cells. Furthermore, a small amount of collagen fibers, round cells, multinucleated giant cells, and cells with eosinophilic granules were observed between these tumor cells. Immunohistochemical examination and electron microscopy identified that the pleomorphic cells and spindle cells were histiocytes and fibroblasts, respectively, and that the round cells were undifferentiated mesenchymal cells. Based on these findings, the tumor was diagnosed as a malignant fibrous histiocytoma

Using spin to understand the formation of LIGO's black holes

With the detection of four candidate binary black hole (BBH) mergers by the Advanced LIGO detectors thus far, it is becoming possible to constrain the properties of the BBH merger population in order to better understand the formation of these systems. Black hole (BH) spin orientations are one of the cleanest discriminators of formation history, with BHs in dynamically formed binaries in dense stellar environments expected to have spins distributed isotropically, in contrast to isolated populations where stellar evolution is expected to induce BH spins preferentially aligned with the orbital angular momentum. In this work we propose a simple, model-agnostic approach to characterizing the spin properties of LIGO's BBH population. Using measurements of the effective spin of the binaries, which is LIGO's best constrained spin parameter, we introduce a simple parameter to quantify the fraction of the population that is isotropically distributed, regardless of the spin magnitude distribution of the population. Once the orientation characteristics of the population have been determined, we show how measurements of effective spin can be used to directly constrain the underlying BH spin magnitude distribution. Although we find that the majority of the current effective spin measurements are too small to be informative, with LIGO's four BBH candidates we find a slight preference for an underlying population with aligned spins over one with isotropic spins (with an odds ratio of 1.1). We argue that it will be possible to distinguish symmetric and anti-symmetric populations at high confidence with tens of additional detections, although mixed populations may take significantly more detections to disentangle. We also derive preliminary spin magnitude distributions for LIGO's black holes, under the assumption of aligned or isotropic populations

Analysis of the anti-tumor mechanism of BRD4 inhibition in hepatocellular carcinoma

Bromodomain and extra terminal (BET) family proteins, which include BRD4, are readers of histone acetyl-lysines and key regulators of gene transcription. BRD4 inhibitors exert anti-tumor effects in various cancers, including hepatocellular carcinoma (HCC). We investigated the mechanism underlying the antitumor effects of BRD4 inhibition in HCC. We first tested the effects of the BRD4 inhibitor JQ1 in a series of 9 HCC cell lines and found that it strongly suppressed HCC cell proliferation by inducing cell cycle arrest and apoptosis. Gene expression microarray analysis revealed that JQ1 also induced marked changes in the gene expression profiles of HCC cells, and genes associated with cell cycle and apoptosis were significantly enriched among the affected genes. Notably, a number of cancer-related genes, including BCAT1, DDR1, GDF15, FANCD2, SENP1 and TYRO3, were strongly suppressed by JQ1 in HCC cells. We also confirmed BRD4 bound within the promoter regions of these genes, which suggests they are targets of BRD4 in HCC cells. JQ1 thus appears to exert its anti-tumor effects in HCC by suppressing multiple BRD4 target genes

Structural basis for the adaptation and function of chlorophyll f in photosystem I

Chlorophylls (Chl) play pivotal roles in energy capture, transfer and charge separation in photosynthesis. Among Chls functioning in oxygenic photosynthesis, Chl f is the most red-shifted type first found in a cyanobacterium Halomicronema hongdechloris. The location and function of Chl f in photosystems are not clear. Here we analyzed the high-resolution structures of photosystem I (PSI) core from H. hongdechloris grown under white or far-red light by cryo-electron microscopy. The structure showed that, far-red PSI binds 83 Chl a and 7 Chl f, and Chl f are associated at the periphery of PSI but not in the electron transfer chain. The appearance of Chl f is well correlated with the expression of PSI genes induced under far-red light. These results indicate that Chl f functions to harvest the far-red light and enhance uphill energy transfer, and changes in the gene sequences are essential for the binding of Chl f

A Case of Self-Limiting Crescentic Immunoglobulin A Glomerulonephritis Associated with Sternoclavicular Arthritis

Immunoglobulin (Ig) A glomerulonephritis (GN) is a heterogeneous disease affected by various factors. Genetic and other factors “hit” DNA, causing IgA malformation and ultimately glomerular injury. We describe a rare case of crescentic IgA GN with sternoclavicular (SC) arthritis in a 75-year-old woman. Despite active IgA GN with cellular crescents, the patient achieved remission of IgA GN without glucocorticoid therapy after remission of SC arthritis was achieved. Considering the patient’s clinical course, this case suggested a relationship between IgA GN and SC arthritis

Intracrine activity involving NAD-dependent circadian steroidogenic activity governs age-associated meibomian gland dysfunction

新たなイントラクライン機構を用いた加齢性眼疾患治療へ --眼局所のホルモンの加齢変化とサーカディアンリズムが鍵--. 京都大学プレスリリース. 2022-02-14.Canonically, hormones are produced in the endocrine organs and delivered to target tissues. However, for steroids, the concept of tissue intracrinology, whereby hormones are produced in the tissues where they exert their effect without release into circulation, has been proposed, but its role in physiology/disease remains unclear. The meibomian glands in the eyelids produce oil to prevent tear evaporation, which reduces with aging. Here, we demonstrate that (re)activation of local intracrine activity through nicotinamide adenine dinucleotide (NAD+)-dependent circadian 3β-hydroxyl-steroid dehydrogenase (3β-HSD) activity ameliorates age-associated meibomian gland dysfunction and accompanying evaporative dry eye disease. Genetic ablation of 3β-HSD nullified local steroidogenesis and led to atrophy of the meibomian gland. Conversely, reactivation of 3β-HSD activity by boosting its coenzyme NAD+ availability improved glandular cell proliferation and alleviated the dry eye disease phenotype. Both women and men express 3β-HSD in the meibomian gland. Enhancing local steroidogenesis may help combat age-associated meibomian gland dysfunction

Discovery of New Hydrothermal Activity and Chemosynthetic Fauna on the Central Indian Ridge at 18°–20°S

Indian Ocean hydrothermal vents are believed to represent a novel biogeographic province, and are host to many novel genera and families of animals, potentially indigenous to Indian Ocean hydrothermal systems. In particular, since its discovery in 2001, much attention has been paid to a so-called ‘scaly-foot’ gastropod because of its unique iron-sulfide-coated dermal sclerites and the chemosynthetic symbioses in its various tissues. Despite increasing interest in the faunal assemblages at Indian Ocean hydrothermal vents, only two hydrothermal vent fields have been investigated in the Indian Ocean. Here we report two newly discovered hydrothermal vent fields, the Dodo and Solitaire fields, which are located in the Central Indian Ridge (CIR) segments 16 and 15, respectively. Chemosynthetic faunal communities at the Dodo field are emaciated in size and composition. In contrast, at the Solitaire field, we observed faunal communities that potentially contained almost all genera found at CIR hydrothermal environments to date, and even identified previously unreported taxa. Moreover, a new morphotype of ‘scaly-foot’ gastropod has been found at the Solitaire field. The newly discovered ‘scaly-foot’ gastropod has similar morphological and anatomical features to the previously reported type that inhabits the Kairei field, and both types of ‘scaly-foot’ gastropods genetically belong to the same species according to analyses of their COI gene and nuclear SSU rRNA gene sequences. However, the new morphotype completely lacks an iron-sulfide coating on the sclerites, which had been believed to be a novel feature restricted to ‘scaly-foot’ gastropods. Our new findings at the two newly discovered hydrothermal vent sites provide important insights into the biodiversity and biogeography of vent-endemic ecosystems in the Indian Ocean