Opto-combinatorial indexing enables high-content transcriptomics by linking cell images and transcriptomes.

We introduce a simple integrated analysis method that links cellular phenotypic behaviour with single-cell RNA sequencing (scRNA-seq) by utilizing a combination of optical indices from cells and hydrogel beads. With our method, the combinations, referred to as joint colour codes, enable the link matching the optical combinations measured by conventional epi-fluorescence microscopy with the concatenated DNA molecular barcodes created by cell-hydrogel bead pairs and sequenced by next-generation sequencing. We validated our approach by demonstrating an accurate link between the cell image and scRNA-seq with mixed species experiments, longitudinal cell tagging by electroporation and lipofection, and gene expression analysis.

Microfluidic vascular formation model for assessing angiogenic capacities of single islets.

Pancreatic islet transplantation presents a promising therapy for individuals suffering from type 1 diabetes. To maintain the function of transplanted islets in vivo, it is imperative to induce angiogenesis. However, the mechanisms underlying angiogenesis triggered by islets remain unclear.

Secretory GFP reconstitution labeling of neighboring cells interrogates cell-cell interactions in metastatic niches.

Cancer cells inevitably interact with neighboring host tissue-resident cells during the process of metastatic colonization, establishing a metastatic niche to fuel their survival, growth, and invasion. However, the underlying mechanisms in the metastatic niche are yet to be fully elucidated owing to the lack of methodologies for comprehensively studying the mechanisms of cell-cell interactions in the niche. Here, we improve a split green fluorescent protein (GFP)-based genetically encoded system to develop secretory glycosylphosphatidylinositol-anchored reconstitution-activated proteins to highlight intercellular connections (sGRAPHIC) for efficient fluorescent labeling of tissue-resident cells that neighbor on and putatively interact with cancer cells in deep tissues.

Clinical usefulness of phase angle as an indicator of muscle wasting and malnutrition in inpatients with cardiovascular diseases.

Background and Objectives: Extracellular water is increased in patients with edema, such as those with chronic heart failure, and it is difficult to assess skeletal muscle mass with the skeletal muscle mass index when extracellular water is high. We investigated the relationship between phase angle and physical function, nutritional indices, and sarcopenia in patients with cardiovascular diseases, including chronic heart failure. Methods and Study Design: In 590 patients with cardiovascular diseases (372 men), handgrip strength, gait speed, and anterior mid-thigh muscle thickness by ultrasound were measured, and the skeletal muscle mass index, phase angle, and the extracellular water: total body water ratio were measured with a bioelectrical impedance analyzer, and presence of sarcopenia was evaluated.

The mechanosensitive ion channel PIEZO1 promotes satellite cell function in muscle regeneration.

Muscle satellite cells (MuSCs), myogenic stem cells in skeletal muscles, play an essential role in muscle regeneration. After skeletal muscle injury, quiescent MuSCs are activated to enter the cell cycle and proliferate, thereby initiating regeneration; however, the mechanisms that ensure successful MuSC division, including chromosome segregation, remain unclear. Here, we show that PIEZO1, a calcium ion (Ca)-permeable cation channel activated by membrane tension, mediates spontaneous Ca influx to control the regenerative function of MuSCs.

Gliding filament system giving both global orientational order and clusters in collective motion.

Emergence and collapse of coherent motions of self-propelled particles are affected more by particle motions and interactions than by their material or biological details. In the reconstructed systems of biofilaments and molecular motors, several types of collective motion including a global-order pattern emerge due to the alignment interaction. Meanwhile, earlier studies show that the alignment interaction of a binary collision of biofilaments is too weak to form the global order.

Blood Flow Restriction Increases the Neural Activation of the Knee Extensors During Very Low-Intensity Leg Extension Exercise in Cardiovascular Patients: A Pilot Study.

Blood flow restriction (BFR) has the potential to augment muscle activation, which underlies strengthening and hypertrophic effects of exercise on skeletal muscle. We quantified the effects of BFR on muscle activation in the rectus femoris (RF), the vastus lateralis (VL), and the vastus medialis (VM) in concentric and eccentric contraction phases of low-intensity (10% and 20% of one repetition maximum) leg extension in seven cardiovascular patients who performed leg extension in four conditions: at 10% and 20% intensities with and without BFR. Each condition consisted of three sets of 30 trials with 30 s of rest between sets and 5 min of rest between conditions.

Step Sizes and Rate Constants of Single-headed Cytoplasmic Dynein Measured with Optical Tweezers.

A power stroke of dynein is thought to be responsible for the stepping of dimeric dynein. However, the actual size of the displacement driven by a power stroke has not been directly measured. Here, the displacements of single-headed cytoplasmic dynein were measured by optical tweezers.

Carcinosarcoma, an atypical subset of gallbladder malignancies.

Carcinosarcoma represents an atypical subset of gallbladder malignancies, and sonographic imaging features have not yet been precisely defined. Previously reported cases have shown a heterogeneously echogenic solid mass protruding into and filling the gallbladder lumen. We present herein a case of carcinosarcoma and propose another finding suggestive of this tumor.

Non-destructive handling of individual chromatin fibers isolated from single cells in a microfluidic device utilizing an optically driven microtool.

We report a novel method for the non-destructive handling of, and biochemical experiments with, individual intact chromatin fibers, as well as their isolation from single cells, utilizing a specifically designed microfluidic device with an optically driven microtool under the microscope. Spheroplasts of recombinant fission yeast cells expressing fluorescent protein-tagged core histones were employed, and isolation of chromatin fibers was conducted by cell bursting via changing from isotonic conditions to hypotonic conditions in the microfluidic device. The isolation of chromatin fibers was confirmed by the fluorescent protein-tagged core histones involved in the chromatin fibers.

Endothelin/endothelin-B receptor signals regulate ventricle-directed interkinetic nuclear migration of cerebral cortical neural progenitors.

We determined the expression profile of ∼300 G protein-coupled receptors (GPCRs) in embryonic cortical neural progenitor cells (NPCs) and identified a number of highly expressed GPCRs, among which endothelin-B receptor (ET(B)-R) was expressed at the highest level. We also revealed that endothelins (ETs) were predominantly expressed in CD31-positive endothelial cells of the embryonic cerebral cortex. Activation of ET(B)-R induced NPC assembly in vitro by promoting fibronectin-dependent-motility and N-cadherin-associated cell contact.

Identification of a novel chemical potentiator and inhibitors of UCH-L1 by in silico drug screening.

Ubiquitin-C-terminal hydrolase L1 (UCH-L1) is a de-ubiquitinating enzyme expressed in the brain and reproductive tissues as well as certain cancers. The hydrolase activity of UCH-L1 has been implicated in Alzheimer's disease and cancer invasion; therefore, it may represent a therapeutic target for these diseases. The present study was undertaken to identify novel chemical modulators for the hydrolase activity of UCH-L1.

Microcirculatory alteration in low-grade gastric mucosa-associated lymphoma by Helicobacter heilmannii infection: its relation to vascular endothelial growth factor and cyclooxygenase-2.

Background: There are clinical reports that Helicobacter heilmannii, as well as Helicobacter pylori, has been clinically reported to cause gastric low-grade mucosa-associated lymphoid tissue-type (MALT) lymphoma, although its precise mechanism remains to be clarified. Thus, the present study was undertaken to elucidate the alteration of the microcirculatory structure and the relation to angiogenetic factors in mice infected with H. heilmannii for 3 and 6 months.

Visceral fat thickness in overweight men correlates with alterations in serum fatty acid composition.

Background: We examined relationships between visceral fat amount and alterations in serum fatty acid composition, both of which represent critical factors in the development of metabolic syndrome.

Methods: Correlations were analyzed between visceral fat thickness as measured by ultrasonography and proportions of individual fatty acids in 21 normal-weight and 24 overweight Japanese men.

Results: Significant associations were identified in overweight subjects.

Identification of novel chemical inhibitors for ubiquitin C-terminal hydrolase-L3 by virtual screening.

UCH-L3 (ubiquitin C-terminal hydrolase-L3) is a de-ubiquitinating enzyme that is a component of the ubiquitin-proteasome system and known to be involved in programmed cell death. A previous study of high-throughput drug screening identified an isatin derivative as a UCH-L3 inhibitor. In this study, we attempted to identify a novel inhibitor with a different structural basis.

Alpha 1-adrenoceptor agonists protect against stress-induced death of neural progenitor cells.

Here, we show that alpha(1)-adrenoceptor agonists suppress stress-induced death of mouse embryonic brain-derived neural progenitor cells (NPCs). NPCs highly expressed both alpha(1A)- and alpha(1B)-adrenoceptor genes, whereas the gene encoding alpha(1D)-adrenoceptor was expressed at low levels. Application of the alpha(1)-adrenoceptor agonists phenylephrine and cirazoline significantly promoted cell survival of embryonic NPCs that had been exposed to stress, as measured by a lactate dehydrogenase release assay, but had no remarkable effect on differentiation of the NPCs.

Increased apoptosis and angiogenesis in gastric low-grade mucosa-associated lymphoid tissue-type lymphoma by Helicobacter heilmannii infection in C57/BL6 mice.

Helicobacter heilmannii has been reported to cause gastric low-grade mucosa-associated lymphoid tissue-type (MALT) lymphoma, but its precise pathophysiological mechanism remains to be clarified. We recently established a model of gastric B-cell MALT lymphoma in C57BL/6 mice by means of peroral infection of H. heilmannii primarily obtained from cynomolgus monkeys.

Neuroprotective role of bradykinin because of the attenuation of pro-inflammatory cytokine release from activated microglia.

Bradykinin (BK) has been reported to be a mediator of brain damage in acute insults. Receptors for BK have been identified on microglia, the pathologic sensors of the brain. Here, we report that BK attenuated lipopolysaccharide (LPS)-induced release of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta from microglial cells, thus acting as an anti-inflammatory mediator in the brain.

"Candidatus Helicobacter heilmannii" from a cynomolgus monkey induces gastric mucosa-associated lymphoid tissue lymphomas in C57BL/6 mice.

Both Helicobacter pylori and "Candidatus Helicobacter heilmannii" infections are associated with peptic ulcers, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue (MALT) lymphomas. However, good animal models of H. pylori clinical diseases are rare.

Solo/Trio8, a membrane-associated short isoform of Trio, modulates endosome dynamics and neurite elongation.

With DNA microarrays, we identified a gene, termed Solo, that is downregulated in the cerebellum of Purkinje cell degeneration mutant mice. Solo is a mouse homologue of rat Trio8-one of multiple Trio isoforms recently identified in rat brain. Solo/Trio8 contains N-terminal sec14-like and spectrin-like repeat domains followed by a single guanine nucleotide exchange factor 1 (GEF1) domain, but it lacks the C-terminal GEF2, immunoglobulin-like, and kinase domains that are typical of Trio.

Parkin potentiates ATP-induced currents due to activation of P2X receptors in PC12 cells.

Loss-of-function mutations of the parkin gene causes an autosomal recessive juvenile-onset form of Parkinson's disease (AR-JP). Parkin was shown to function as a RING-type E3 ubiquitin protein ligase. However, the function of parkin in neuronal cells remains elusive.