The composition of human skin microbiome profoundly impacts host skin health and disease. However, the relationship between skin homeostasis or the development of skin diseases and daily changes in skin microbial composition is poorly understood. Longitudinal samplings at more frequent intervals would address this issue, while conventional sampling methods have technical difficulties, leading to limitations in sampling opportunities.
View Article and Find Full Text PDFMyoblast fusion is essential for skeletal muscle development, growth, and regeneration. However, the molecular mechanisms underlying myoblast fusion and differentiation are not fully understood. Previously, we reported that interleukin-4 (IL-4) promotes myoblast fusion; therefore, we hypothesized that IL-4 signaling might regulate the expression of the molecules involved in myoblast fusion.
View Article and Find Full Text PDFThe skin microbiota has been recognized to play an integral role in the physiology and pathology of the skin. The crosstalk between skin and the resident microbes has been extensively investigated using two-dimensional (2D) and three-dimensional (3D) cell cultures ; however, skin colonization by multiple species and the effects of interspecific interactions on the structure and function of skin remains to be elucidated. This study reports the establishment of a mixed infection model, incorporating both commensal () and pathogenic () bacteria, based on a 3D human epidermal model.
View Article and Find Full Text PDFBackground: The signal transducer and activator of transcription 6 (STAT6) transcription factor plays a vitally important role in immune cells, where it is activated mainly by interleukin-4 (IL-4). Because IL-4 is an essential cytokine for myotube formation, STAT6 might also be involved in myogenesis as part of IL-4 signaling. This study was conducted to elucidate the role of STAT6 in adult myogenesis in vitro and in vivo.
View Article and Find Full Text PDFObjective: This study examined the chronic effect of increased physical activity on postprandial triglycerides in older women.
Methods: Twenty-six women, aged 72 ± 5 years (mean ± SD), participated in this study. Participants in the physical activity group (n = 11) were asked to increase their activities above their usual lifestyle levels for 12 weeks.
Transient receptor potential vanilloid 4 (TRPV4) channel is a polymodal receptor activated by moderate heat and hypoosmolarity. TRPV4 expressed in the skin area contributes to several skin functions as a barrier to maintain internal body physiology and a transporter of external stimuli. The skin condition such as skin temperature and osmolarity varies with internal and external changes, and may influence the activity of TRPV4 contributing to skin physiology, thermal sensation, and thermoregulation.
View Article and Find Full Text PDFSynapse formation is achieved by various synaptic organizers. Although this process is highly regulated by neuronal activity, the underlying molecular mechanisms remain largely unclear. Here we show that Cbln1, a synaptic organizer of the C1q family, is released from lysosomes in axons but not dendrites of cerebellar granule cells in an activity- and Ca-dependent manner.
View Article and Find Full Text PDFLong-term depression (LTD) of AMPA-type glutamate receptor (AMPA receptor)-mediated synaptic transmission has been proposed as a cellular substrate for learning and memory. Although activity-induced AMPA receptor endocytosis is believed to underlie LTD, it remains largely unclear whether LTD and AMPA receptor endocytosis at specific synapses are causally linked to learning and memory in vivo. Here we developed a new optogenetic tool, termed PhotonSABER, which enabled the temporal, spatial, and cell-type-specific control of AMPA receptor endocytosis at active synapses, while the basal synaptic properties and other forms of synaptic plasticity were unaffected.
View Article and Find Full Text PDFAstrocytes regulate synaptic transmission through controlling neurotransmitter concentrations around synapses. Little is known, however, about their roles in neural circuit development. Here we report that Bergmann glia (BG), specialized cerebellar astrocytes that thoroughly enwrap Purkinje cells (PCs), are essential for synaptic organization in PCs through the action of the l-glutamate/l-aspartate transporter (GLAST).
View Article and Find Full Text PDFPluripotent human embryonic stem cells (hESCs) can differentiate into multiple cell lineages, thus, providing one of the best platforms to study molecular mechanisms during cell differentiation. Recently, we have reported rapid and efficient differentiation of hESCs into functional neurons by introducing a cocktail of synthetic mRNAs encoding five transcription factors (TFs): NEUROG1, NEUROG2, NEUROG3, NEUROD1, and NEUROD2. Here we further tested a possibility that even single transcription factors, when expressed ectopically, can differentiate hESCs into neurons.
View Article and Find Full Text PDFThe progress of microenvironment-mediated tumor progression in an artificial extracellular matrix explores the design criteria to understand the cancer progression mechanism and metastatic potential. This study was aimed at examining the combination of both surface topographies (fiber alignments) and different stiffness of polymeric substrates (PLLA and PCL) to evaluate the effects on the cellular morphologies, proliferation, motility, and gene expression regarding epithelial to mesenchymal transition (EMT) of two different types of breast cancer cells (MDA-MB-231 and MCF-7). The cellular morphologies (roundness and nuclear elongation factor), E-cadherin and vimentin expression, and cellular motility in terms of cellular migration speed, persistent time, and diffusivity have been comprehensively discussed.
View Article and Find Full Text PDFEfficient differentiation of human pluripotent stem cells (hPSCs) into neurons is paramount for disease modeling, drug screening, and cell transplantation therapy in regenerative medicine. In this manuscript, we report the capability of five transcription factors (TFs) toward this aim: NEUROG1, NEUROG2, NEUROG3, NEUROD1, and NEUROD2. In contrast to previous methods that have shortcomings in their speed and efficiency, a cocktail of these TFs as synthetic mRNAs can differentiate hPSCs into neurons in 7 days, judged by calcium imaging and electrophysiology.
View Article and Find Full Text PDFA 58-year-old man was diagnosed with accelerated phase chronic myelogenous leukemia (CML). He was treated with dasatinib and followed-up; 6 months later, he achieved a complete molecular response. Seventeen months after this therapy, he developed pancytopenia, and was examined.
View Article and Find Full Text PDFUnlabelled: The cerebellum is thought to be involved in cognitive functions in addition to its well established role in motor coordination and motor learning in humans. Cerebellin 1 (Cbln1) is predominantly expressed in cerebellar granule cells and plays a crucial role in the formation and function of parallel fiber-Purkinje cell synapses. Although genes encoding Cbln1 and its postsynaptic receptor, the delta2 glutamate receptor (GluD2), are suggested to be associated with autistic-like traits and many psychiatric disorders, whether such cognitive impairments are caused by cerebellar dysfunction remains unclear.
View Article and Find Full Text PDFClin Lymphoma Myeloma Leuk
January 2017
Background: Mogamulizumab, a defucosylated humanized monoclonal antibody targeting C-C chemokine receptor 4, recently became available for the treatment of adult T-cell leukemia/lymphoma (ATL). We conducted a multicenter retrospective study of the efficacy of mogamulizumab in ATL treatment in patients on Hokkaido Island, Japan.
Materials And Methods: A total of 125 patients with ATL treated from January 2010 to December 2014 in 20 hospitals affiliated with the Hokkaido Hematology Study Group were enrolled in the present retrospective study.
Ionotropic glutamate receptor (iGluR) family members are integrated into supramolecular complexes that modulate their location and function at excitatory synapses. However, a lack of structural information beyond isolated receptors or fragments thereof currently limits the mechanistic understanding of physiological iGluR signaling. Here, we report structural and functional analyses of the prototypical molecular bridge linking postsynaptic iGluR δ2 (GluD2) and presynaptic β-neurexin 1 (β-NRX1) via Cbln1, a C1q-like synaptic organizer.
View Article and Find Full Text PDFNeuronal networks are dynamically modified by selective synapse pruning during development and adulthood. However, how certain connections win the competition with others and are subsequently maintained is not fully understood. Here, we show that C1ql1, a member of the C1q family of proteins, is provided by climbing fibers (CFs) and serves as a crucial anterograde signal to determine and maintain the single-winner CF in the mouse cerebellum throughout development and adulthood.
View Article and Find Full Text PDFCentral venous catheter-related blood stream infections (CR-BSIs) are a serious complication in patients with hematological malignancies. However, it remains unclear whether there is a difference in the rate of CR-BSI associated with the conventional type of central venous catheters (cCVCs) and peripherally inserted CVCs (PICCs) in such patients. To address this question, we retrospectively investigated the incidence of CR-BSIs associated with PICCs versus cCVCs in patients with hematological malignancies.
View Article and Find Full Text PDFFollowing the introduction of rituximab, the long-term overall survival (OS) rate of advanced-stage follicular lymphoma (FL) cases was expected to improve after the introduction of rituximab: however, there is a lack of large-scale survey data in Asia due to the relatively low incidence of FL. We conducted a retrospective survey to assess the treatment outcomes in patients with newly diagnosed advanced-stage FL in 29 institutions in Hokkaido from January 2001 to December 2010. The total number of patients was 443 (men 47.
View Article and Find Full Text PDFBackground: The common marmoset (Callithrix jacchus) is a New World primate sharing many similarities with humans. Recently developed technology for generating transgenic marmosets has opened new avenues for faithful recapitulation of human diseases, which could not be achieved in rodent models. However, the longer lifespan of common marmosets compared with rodents may result in an extended period for in vivo analysis of common marmoset disease models.
View Article and Find Full Text PDFLong-term changes in synaptic transmission in the central nervous system, such as long-term potentiation and long-term depression (LTD), are believed to underlie learning and memory in vivo. Despite intensive research, the precise molecular mechanisms underlying these phenomena have remained unclear. LTD is most commonly caused by the endocytosis of postsynaptic AMPA-type glutamate receptors, triggered by activity-induced serine phosphorylation of the GluA2 subunit.
View Article and Find Full Text PDFThe formation of excitatory and inhibitory synapses must be tightly coordinated to establish functional neuronal circuitry during development. In the cerebellum, the formation of excitatory synapses between parallel fibers and Purkinje cells is strongly induced by Cbln1, which is released from parallel fibers and binds to the postsynaptic δ2 glutamate receptor (GluD2). However, Cbln1's role, if any, in inhibitory synapse formation has been unknown.
View Article and Find Full Text PDFThe delay eyeblink conditioning (EBC) is a cerebellum-dependent type of associative motor learning. However, the exact roles played by the various cerebellar synapses, as well as the underlying molecular mechanisms, remain to be determined. It is also unclear whether long-term potentiation (LTP) or long-term depression (LTD) at parallel fiber (PF)-Purkinje cell (PC) synapses is involved in EBC.
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