A mouse bone marrow stromal cell line, TBR-B, shows inducible expression of smooth muscle-specific genes

AbstractWe established an in vitro culture system which mimicked the differentiation pathway of smooth muscle cell, using TBR-B, a bone marrow stromal cell line derived from transgenic mice harboring temperature-sensitive SV40 large T-antigen gene. TBR-B cells have the potential to express smooth muscle-specific genes including h1-calponin, h-caldesmon, SM22α and α-actin, only after cultured in the differentiation medium for 2 weeks. The differentiation state of TBR-B was well controlled by using different culture medium. Using this cell line, we also found that ascorbic acid is a potent factor inducing the expression of h1-calponin and α-actin. TBR-B cells will serve as a useful tool for elucidating the regulatory mechanisms of smooth muscle-specific gene expression, and for identifying compounds that regulate the differentiation state of vascular smooth muscle cells

The mass spectrum of metal-free Stars resulting from photodissociation feedback: A scenario for the formation of low-mass population III stars

The initial mass function (IMF) of metal-free stars that form in the initial starburst of massive (virial temperatures >10^4K) metal-free protogalaxies is studied. In particular, we focus on the effect of H2 photodissociation by pre-existing stars on the fragmentation mass scale, presumedly determined by the Jeans mass at the end of the initial free-fall phase, i.e., at the so-called ``loitering phase,'' characterized by the local temperature minimum. Photodissociation diminishes the Jeans mass at the loitering phase, thereby reducing the fragmentation mass scale of primordial clouds. Thus, in a given cloud, far ultraviolet (FUV) radiation from the first star, which is supposedly very massive (about 10^3Msun), reduces the mass scale for subsequent fragmentation. Through a series of similar processes the IMF for metal-free stars is established. If FUV radiation exceeds a threshold level, the star-forming clumps collapse solely through atomic cooling. Correspondingly, the fragmentation scale drops discontinuously from a few time 10Msun to sub-solar scales. In compact clouds (>1.6kpc for clouds of gas mass 10^8Msun), this level of radiation field is attained, and sub-solar mass stars are formed even in a metal-free environment. Consequently, the IMF becomes bi-modal, with peaks at a few tenths of Msun and a few times 10Msun. The high-mass portion of the IMF is found to be a very steep function of the stellar mass, xi_high(m) being proportinal to m^{-5}. Therefore, the typical mass scale of metal-free stars is significantly smaller than that of the very first stars. Also we study the thermal instability in collapsing primordial prestellar clumps, and discuss why the thermal instability occuring during the three-body H2 formation does not appear to manifest itself in causing further fragmentation of such clumps.Comment: 34 pages, 6 figures, ApJ accepte

Lipoma in the Corpus Callosum Presenting with Epileptic Seizures Associated with Expanding Perifocal Edema: A Case Report and Literature Review

This report describes a rare case of a patient with lipoma presenting with epileptic seizures associated with expanding perifocal edema. The patient was a 48-year-old man who presented with loss of consciousness and convulsions. Magnetic resonance imaging (MRI) revealed a calcified mass in the corpus callosum with perifocal edema causing mass effect. An interhemispheric approach was used to biopsy the mass lesion. Histological examination revealed typical adipose cells, along with hamartomatous components. These components contained neurofilament and S-100-positive structures showing marked calcification. Fibrous cells immunoreactive for α-smooth muscle actin and epithelial membrane antigen proliferated with focal granulomatous inflammatory changes. MIB-1 index was approximately 5% in immature cells observed in granulomatous areas. We thus suspected a coexisting neoplastic component. The residual lesion persisted in a dormant state for 2 years following biopsy. Surgical resection of a lipoma is extremely difficult and potentially dangerous. However, in the present case, the lesion was accompanied by atypical, expanding, and perifocal edema. Surgical treatment was inevitable for the purpose of histological confirmation, considering differential diagnoses such as dermoid, epidermoid, and glioma. In the end, anticonvulsant therapy proved effective for controlling epileptic seizures

Group 2 innate lymphoid cells support hematopoietic recovery under stress conditions

The cell-cycle status of hematopoietic stem and progenitor cells (HSPCs) becomes activated following chemotherapy-induced stress, promoting bone marrow (BM) regeneration; however, the underlying molecular mechanism remains elusive. Here we show that BM-resident group 2 innate lymphoid cells (ILC2s) support the recovery of HSPCs from 5-fluorouracil (5-FU)-induced stress by secreting granulocyte-macrophage colony-stimulating factor (GM-CSF). Mechanistically, IL-33 released from chemosensitive B cell progenitors activates MyD88-mediated secretion of GM-CSF in ILC2, suggesting the existence of a B cell-ILC2 axis for maintaining hematopoietic homeostasis. GM-CSF knockout mice treated with 5-FU showed severe loss of myeloid lineage cells, causing lethality, which was rescued by transferring BM ILC2s from wild-type mice. Further, the adoptive transfer of ILC2s to 5-FU-treated mice accelerates hematopoietic recovery, while the reduction of ILC2s results in the opposite effect. Thus, ILC2s may function by "sensing" the damaged BM spaces and subsequently support hematopoietic recovery under stress conditions.Sudo T., Motomura Y., Okuzaki D., et al. Group 2 innate lymphoid cells support hematopoietic recovery under stress conditions. Journal of Experimental Medicine 218, e20200817 (2021); https://doi.org/10.1084/jem.20200817

Combined Unilateral Hemilaminectomy and Thoracoscopic Resection of the Dumbbell-Shaped Thoracic Neurinoma: A Case Report

A 41-year-old woman complained of chest pain when coughing. Computed tomography and magnetic resonance imaging disclosed a homogenously enhanced tumor occupying the spinal canal at the Th7 level and extending into the right paravertebral space through the intervertebral foramen between Th7 and Th8. The tumor was successfully removed via a posterolateral approach using unilateral hemilaminectomy followed by thoracoscopic surgery. Since the tumor had a dumbbell shape, a combined approach was considered essential. The histological diagnosis was a thoracic neurinoma. Combined hemilaminectomy and thoracoscopic surgery may be a good alternative for the management of thoracic dumbbell-shaped tumors

Parkinson’s disease-associated iPLA2-VIA/PLA2G6 regulates neuronal functions and α-synuclein stability through membrane remodeling

Mutations in the iPLA2-VIA/PLA2G6 gene are responsible for PARK14-linked Parkinson’s disease (PD) with α-synucleinopathy. However, it is unclear how iPLA2-VIA mutations lead to α-synuclein (α-Syn) aggregation and dopaminergic (DA) neurodegeneration. Here, we report that iPLA2-VIA–deficient Drosophila exhibits defects in neurotransmission during early developmental stages and progressive cell loss throughout the brain, including degeneration of the DA neurons. Lipid analysis of brain tissues reveals that the acyl-chain length of phospholipids is shortened by iPLA2-VIA loss, which causes endoplasmic reticulum (ER) stress through membrane lipid disequilibrium. The introduction of wild-type human iPLA2-VIA or the mitochondria–ER contact site-resident protein C19orf12 in iPLA2-VIA–deficient flies rescues the phenotypes associated with altered lipid composition, ER stress, and DA neurodegeneration, whereas the introduction of a disease-associated missense mutant, iPLA2-VIA A80T, fails to suppress these phenotypes. The acceleration of α-Syn aggregation by iPLA2-VIA loss is suppressed by the administration of linoleic acid, correcting the brain lipid composition. Our findings suggest that membrane remodeling by iPLA2-VIA is required for the survival of DA neurons and α-Syn stability

Prognostic Impact of Hypoxia-Inducible miRNA-210

Objective. The aim of this study was to investigate the prognostic value of MicroRNA-210 (miR-210) expression in patients with non-small-cell lung cancer (NSCLC). Methods. We examined the miR-210 expression of samples of 80 patients, who underwent surgical resection at Fukushima Medical University from 2004 to 2007, by using quantitative RT-PCR. The relationship between miR-210 expression and clinicopathological factors as well as histological subtype was statistically analyzed. Results. miR-210 expression showed an inverse correlation with disease-free and overall survival in patients with NSCLC. Significant correlations were found between miR-210 expression and lymph node metastasis, late disease stages, and poor prognosis in patients with adenocarcinoma. Multivariate Cox analysis indicated that miR-210 expression was an independent prognostic factor for disease-free survival in patients with adenocarcinoma. Conclusions. We showed that miR-210 may be a prognostic biomarker for patients with NSCLC, especially for those with lung adenocarcinoma

The Nitric Oxide-Cyclic GMP Pathway Regulates FoxO and Alters Dopaminergic Neuron Survival in Drosophila

Activation of the forkhead box transcription factor FoxO is suggested to be involved in dopaminergic (DA) neurodegeneration in a Drosophila model of Parkinson's disease (PD), in which a PD gene product LRRK2 activates FoxO through phosphorylation. In the current study that combines Drosophila genetics and biochemical analysis, we show that cyclic guanosine monophosphate (cGMP)-dependent kinase II (cGKII) also phosphorylates FoxO at the same residue as LRRK2, and Drosophila orthologues of cGKII and LRRK2, DG2/For and dLRRK, respectively, enhance the neurotoxic activity of FoxO in an additive manner. Biochemical assays using mammalian cGKII and FoxO1 reveal that cGKII enhances the transcriptional activity of FoxO1 through phosphorylation of the FoxO1 S319 site in the same manner as LRRK2. A Drosophila FoxO mutant resistant to phosphorylation by DG2 and dLRRK (dFoxO S259A corresponding to human FoxO1 S319A) suppressed the neurotoxicity and improved motor dysfunction caused by co-expression of FoxO and DG2. Nitric oxide synthase (NOS) and soluble guanylyl cyclase (sGC) also increased FoxO's activity, whereas the administration of a NOS inhibitor L-NAME suppressed the loss of DA neurons in aged flies co-expressing FoxO and DG2. These results strongly suggest that the NO-FoxO axis contributes to DA neurodegeneration in LRRK2-linked PD