Human AK2 links intracellular bioenergetic redistribution to the fate of hematopoietic progenitors

AK2 is an adenylate phosphotransferase that localizes at the intermembrane spaces of the mitochondria, and its mutations cause a severe combined immunodeficiency with neutrophil maturation arrest named reticular dysgenesis (RD). Although the dysfunction of hematopoietic stem cells (HSCs) has been implicated, earlier developmental events that affect the fate of HSCs and/or hematopoietic progenitors have not been reported. Here, we used RD-patient-derived induced pluripotent stem cells (iPSCs) as a model of AK2-deficient human cells. Hematopoietic differentiation from RD-iPSCs was profoundly impaired. RD-iPSC-derived hemoangiogenic progenitor cells (HAPCs) showed decreased ATP distribution in the nucleus and altered global transcriptional profiles. Thus, AK2 has a stage-specific role in maintaining the ATP supply to the nucleus during hematopoietic differentiation, which affects the transcriptional profiles necessary for controlling the fate of multipotential HAPCs. Our data suggest that maintaining the appropriate energy level of each organelle by the intracellular redistribution of ATP is important for controlling the fate of progenitor cells

A novel biomarker TERTmRNA is applicable for early detection of hepatoma

<p>Abstract</p> <p>Backgrounds</p> <p>We previously reported a highly sensitive method for serum human telomerase reverse transcriptase (hTERT) mRNA for hepatocellular carcinoma (HCC). α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) are good markers for HCC. In this study, we verified the significance of hTERTmRNA in a large scale multi-centered trial, collating quantified values with clinical course.</p> <p>Methods</p> <p>In 638 subjects including 303 patients with HCC, 89 with chronic hepatitis (CH), 45 with liver cirrhosis (LC) and 201 healthy individuals, we quantified serum hTERTmRNA using the real-time RT-PCR. We examined its sensitivity and specificity in HCC diagnosis, clinical significance, ROC curve analysis in comparison with other tumor markers, and its correlations with the clinical parameters using Pearson relative test and multivariate analyses. Furthermore, we performed a prospective and comparative study to observe the change of biomarkers, including hTERTmRNA in HCC patients receiving anti-cancer therapies.</p> <p>Results</p> <p>hTERTmRNA was demonstrated to be independently correlated with clinical parameters; tumor size and tumor differentiation (P < 0.001, each). The sensitivity/specificity of hTERTmRNA in HCC diagnosis showed 90.2%/85.4% for hTERT. hTERTmRNA proved to be superior to AFP, AFP-L3, and DCP in the diagnosis and underwent an indisputable change in response to therapy. The detection rate of small HCC by hTERTmRNA was superior to the other markers.</p> <p>Conclusions</p> <p>hTERTmRNA is superior to conventional tumor markers in the diagnosis and recurrence of HCC at an early stage.</p

Tactile Feels in Grasping/Cutting Processes with Scissors

Understanding the dynamic phenomena in grasping/cutting processes with scissors is important for the design of surgical robots and virtual reality systems. Here, we show the relationship between the mechanical stimuli and tactile sensations when forceps or scissors are used. Nineteen subjects grasped or cut objects and evaluated the tactile sensations in each of the processes. To conduct the tactile and mechanical evaluation simultaneously, subjects operated scissors that were fixed to a mechanical evaluation system. When subjects grasped urethane resin, stainless steel plate, and adhesive tape, soft, hard, and sticky feels were perceived, respectively. Dry, hard, and creaking feels were perceived in the paper cutting process. In addition, we observed four characteristic tangential force profiles in the processes. Regression analysis suggests the following findings: Hardness is perceived by the change of force and blade movement when the scissors make contact with the object. Stickiness is caused by the increase and decrease of force at the moment of peeling when the scissors break contact with the object. The cutting sensation is affected by fine force fluctuations during the scissors closing and the rapidly decreased force at the moment of cutting completion

Scissors-Type Haptic Device Using Magnetorheological Fluid Containing Iron Nanoparticles

The mechanical ability and usefulness of simulation systems can be improved by combining a tactile display with a remote control or medical simulation systems. In this study, a scissors-type haptic device containing magnetorheological fluid (MR fluid) in its fulcrum is developed. We evaluate the mechanical response to the applied voltage and realize the presence of mechanical stimuli when a subject grasps or cuts the corresponding objects. When the magnetic field around the MR fluid is controlled by an electric voltage of 150&#8315;500 mV, the torque linearly increases from 0.007 &#177; 0.000 to 0.016 &#177; 0.000 N m. The device can provide tactile stimuli with 0.1 s of resolution. We also determined the voltage profiles based on typical force profiles obtained during grasping/cutting processes and evaluated the torque using a mechanical evaluation system. Features of the force profiles related to the soft and sticky feels were reconstructed well