Molecular mechanisms of lesion-induced axonal sprouting in the corticofugal projection:the role of glial cells

After injury of the central nervous system(CNS),neuronal circuits are known to remodel for functional recovery.In general,there are two strategies for the remodeling:axonal regeneration and sprouting(Figure 1A).Axonal regeneration is re-growth of injured neurons themselves,but axons hardly regenerate in the adult mammalian CNS(Silver and Miller,2004).On the other hand,axonal sprouting is new growth from intact or spared neurons to the denervated target by forming axon collaterals,compensating for damaged circuits.This process is a more effective way for circuit remodeling,as it does not necessarily require long axonal elongation.

Evaluation of the Bending Loss of the Hollow Optical Fiber for Application of the Carbon Dioxide Laser to Endoscopic Therapy

Since carbon dioxide laser is excellent for incision, hemostasis, coagulation, and vaporization of soft tissues, it has been widely applied in clinical treatments as the laser knife. In these days, flexible thin hollow optical fibers transmitting mid-infrared light have been developed, and the application of carbon dioxide laser to endoscopic therapy has become possible. However, it is expected that the irradiation effect is influenced by the change in the laser power at the tip of the hollow optical fiber due to the change in the transmittance by the bending loss. The purpose of this research is to quantitatively evaluate the change in the output power and therapeutic effect by bending the hollow optical fiber in a gastrointestinal endoscope. The change in the transmittance of the hollow optical fiber due to the insertion of the fiber into the endoscope and bending of the head of the endoscope was measured. Then, the relationship between the irradiated laser power and the incision depth for a porcine stomach was investigated. As the results, the most significant decrease in the transmittance of the hollow optical fiber was caused by the insertion of the fiber into the instrument channel of the endoscope, and bending of the head of the endoscope with the angle of 90° decreased the output laser power and incision depth by 10% and 25%, respectively. Therefore, it was confirmed that the bending loss of the hollow optical fiber due to the bending of the head of the endoscope had no significant influence on the endoscopic therapy using the carbon dioxide laser.

Coagulation and ablation of biological soft tissue byquantum cascade laser with peak wavelength of 5.7μm

Molecules such as water,proteins and lipids that are contained in biological tissue absorb mid-infrared(MR)light,which allows such light to be used in laser surgical treatment.Esters,amides and water exhibit strong absorption bands in the 5-7μm wavelength range,but at present there are no lasers in clinical use that can emit in this range.Therefore,the present study focused on thequantum cascade laser(QCL),which is a new type of semiconductor laser that can emit at MIRwavelengths and has recentiy achieved high output power.A high-power QCL with a peakwavelength of 5.7μm was evaluated for use as a laser scalpel for ablating biological soft tissue.The interaction of the laser beam with chicken breast tissue was compared to a conventional CO_(2) laser,based on surface and cross-sectional images.The QCL was found to have sufficient power to ablate soft tissue,and its coagulation,carbonization and ablation effects were similar to those forthe CO_(2) laser.The QCL also induced comparable photothermal effects because it acted as apseudo-continuous wave laser due to its low peak power.A QCL can therefore be used as an effective laser scalpel,and also offers the possibility of less invasive treatment by targeting specificabsorption bands in t he MIR region.

Rotation of Biological Cells:Fundamentals and Applications

Cell rotation is one of the most important techniques for cell manipulation in modern bioscience,as it not only permits cell observation from any arbitrary angle,but also simplifies the procedures for analyzing the mechanical properties of cells,characterizing cell physiology,and performing microsurgery.Numerous approaches have been reported for rotating cells in a wide range of academic and industrial applications.Among them,the most popular are micro-robot-based direct contact manipulation and field-based non-contact methods(e.g.,optical,magnetic,electric,acoustic,and hydrodynamic methods).This review first summarizes the fundamental mechanisms,merits,and demerits of these six main groups of approaches,and then discusses their differences and limitations in detail.We aim to bridge the gap between each method and illustrate the development progress,current advances,and prospects in the field of cell rotation.

Observation of Atherosclerotic Plaque Phantoms through Saline or Blood Layers by Near-Infrared Hyperspectral Imaging

We observed atherosclerotic plaque phantoms using a novel near-infrared (NIR) hyperspectral imaging (HSI) technique. Data were obtained through saline or blood layers to simulate an angioscopic environment for the phantom. For the study, we developed a NIR-HSI system with an NIR supercontinuum light source and mercury-cadmium-telluride camera. Apparent spectral absorbance was obtained at wavelengths of 1150 - 2400 nm. Hyperspectral images of lipid were constructed using a spectral angle mapper algorithm. Bovine fat covered with saline or blood was observed using hyperspectral images at a wavelength around 1200 nm. Our results show that NIR-HSI is a promising angioscopic technique with the potential to identify lipid-rich plaques without clamping and saline injection.

Feasibility of Improved Attenuation Correction for SPECT Reconstruction in the Presence of Dense Materials Using Dual-Energy Virtual Monochromatic CT: A Phantom Study

Objective: Computed tomography (CT)-based attenuation correction (CTAC) offers the clear benefit of reliable reconstruction of single-photon emission computed tomography (SPECT) images through its ability to achieve object-specific attenuation maps, but artifacts from dense materials often deteriorate CTAC performance. Therefore, we investigate the feasibility of CTAC in the presence of dense materials using dual-energy virtual monochromatic CT data. Methods: A sodium pertechnetate-filled cylindrical uniform phantom, with a pair of undiluted iodine syringes attached, is scanned with a dual-source CT scanner to obtain both single-energy (120 kVp) polychromatic and dual-energy (80 kVp/140 kVp with tin filtering) virtual monochromatic CT images. The single-energy and the dual-energy CT images are then converted to attenuation maps at 141 keV. SPECT images are reconstructed from 99mTc emission data of the phantom using each single-energy and dual-energy attenuation map and incorporating CTAC procedure. A region-of-in- terest analysis is performed to quantitatively compare the attenuation maps between the single-energy and the dual-energy techniques, each at an iodine-free position and a position adjacent to the iodine solutions. Results: At the iodine-free position, the phantom provides a uniform distribution of attenuation maps in both the single-energy and the dual-energy techniques. In the presence of adjacent iodine solutions, however, severe artifacts appeare in the single-energy CT images. These artifacts make attenuation values fluctuate, resulting in erroneous pixel values in the CTAC SPECT images. In contrast, dual-energy CT strongly suppresses the artifacts and hence improves the uniformity of the attenuation maps and the resultant SPECT images. Conclusions: Dual-energy CT with virtual monochromatic reconstruction has the potential to substantially reduce artifacts arising from dense materials. It has the potential to improve the accuracy of attenuation maps and the resultant CTAC SPECT images.

BDNF pro-peptide：a novel synaptic modulator generated as an N-terminal fragment from the BDNF precursor by proteolytic processing

Most growth factors are initially synthesized as precursors and it was cleaved into bioactive mature domain and pro-domain.However,compared with the expression and function of bioactive mature domain,the biological role of the pro-domain is poorly understood.Unexpectedly,we found that the pro-domain（or pro-peptide）of brain-derived neurotrophic factor（BDNF）,which is well-known neurotrophic factor in brain,has a potential ability to facilitate hippocampal long-term depression.Furthermore,a BDNF polymorphism Val66Met,which substitute valine into methionine at 66 amino acid,impacted the biological activity of the BDNF pro-peptide.We lastly discuss the possible roles of BDNF and its pro-peptide in the generation of neural stem cells and progress of ischemia.

Enhanced vibrational resonance in a single neuron with chemical autapse for signal detection

Many animals can detect the multi-frequency signals from their external surroundings.The understanding for underlying mechanism of signal detection can apply the theory of vibrational resonance,in which the moderate high frequency driving can maximize the nonlinear system's response to the low frequency subthreshold signal.In this work,we study the roles of chemical autapse on the vibrational resonance in a single neuron for signal detection.We reveal that the vibrational resonance is strengthened significantly by the inhibitory autapse in the neuron,while it is weakened typically by the excitatory autapse.It is generally believed that the inhibitory synapse has a suppressive effect in neuronal dynamics.However,we find that the detection of the neuron to the low frequency subthreshold signal can be improved greatly by the inhibitory autapse.Our finding indicates that the inhibitory synapse may act constructively on the detection of weak signal in the brain and neuronal system.

单分子纳米生物技术

生物分子需要相互协调组成各种分子机器,例如:分子马达、细胞信号处理器、DNA转录机、蛋白质合成器等,来实现他们负责的各种生理功能。一方面,这些分子机器的功能对于环境改变有着很强的适应性,这种适应性对于生物体和生物系统的稳定来说是必须的。另一方面,由于分子机器的大小只有几纳米并且结构具有可变性,它们的运转倾向于受到热扰动的影响具有随机性,此外,分子机器所利用的输入能量的水平与平均热运动能量k_BT近似,分子机器可以高效地将热噪声的能量转化利用于行使其功能,对于这些能量的利用效率也很高,这与人造机器运转所需能量远远高于热运动能量相比有着十分显著的差别。因此,分子机器的潜在机理比人造机器复杂了许多。近些年来,随着单分子探测技术和纳米技术在生命科学的各个领域的广泛应用,使得生物分子的动力学性质,以及以往被隐藏在系综平均结果后的单个分子机器运转规律逐渐被揭示。我们研究的目标是希望通过揭示分子机器的独特运转规律进而能够了解、掌握具有适应性的生物系统中包含的工程学原理。本文综述了我们所作的一些关于分子马达、酶促反应、蛋白质动力学和细胞信号转导的单分子探测试验,并且讨论了热涨落(噪声)是怎样在具有独特的运转规律的生物分子机器中起到正效应,进而允许生物系统具有可变性和适应性的。

Highly Selective Photodynamic Therapy with a Short Drug-Light Interval Using a Cytotoxic Photosensitizer Porphyrus Envelope for Drug-Resistant Prostate Cancer Cells

Background: Photodynamic therapy (PDT) is a less invasive cancer treatment using photochemical reactions induced by light irradiation to a photosensitizer (PS). Highly selective PDT with fast accumulation of the PS in target site might be a promising treatment option for drug-resistant prostate cancer facing high incidence rate of elderly men who have no effective treatment options and require a minimally invasive treatment. Hemagglutinating virus of Japan envelope (HVJ-E) allows selective and fast drug delivery to the drug-resistant prostate cancer cells via rapid cell membrane fusion. PS named porphyrus envelope (PE) has been developed by insertion of lipidated protoporphyrin IX (PpIX lipid) into HVJ-E. In this study, we investigated the optimal conditions for PE preparation and laser irradiation for highly selective PDT using PE with a short drug-light interval. Materials and Methods: Human hormon refractory prostate cancer cell line PC-3 and human normal prostate epithelial cell line PNT2 were cultured. PpIX lipid uptake and cytotoxicity of PDT in the cells incubated with PE for 10 min were evaluated by measuring fluorescence intensity and by using a cell counting reagent 24 h after PDT, respectively. Results: PpIX lipid uptake and cytotoxicity of PDT were increased with PpIX lipid concentration. Cytotoxicity of PDT using PE was more than 9 times as strong as that with PpIX lipid and PpIX induced by 5-aminolevulinic acid. Much stronger cytotoxicity was induced in PC-3 cells than PNT2 cells with the ratio of cell death rate for cancer to normal cells up to 4.64 ± 0.09. Conclusions: Fast PS delivery with HVJ-E allows highly selective PDT with a short drug-light interval. Therefore, PDT using PE has a potential to shorten treatment period and reduce side effects of PDT.

Combining Motor Imagery and Action Observation with Vibratory Stimulation Increases Corticomotor Excitability in Healthy Young Adults

Vibratory stimulation but also motor imagery and action observation can induce corticomotor modulation, as a bottom-up stimulus and top-down stimuli, respectively. However, it remains unknown whether the combination of motor imagery, action observation, and vibratory stimulation can effectively increase corticomotor excitability. This study aimed to investigate the effect of motor imagery and/or action observation, in the presence or absence of vibratory stimulation, on the corticomotor excitability of healthy young adults. Vibratory stimulation was provided to the palm of the right hand. Action observation consisted in viewing a movie of someone else’s finger flexion and extension movements. The imagery condition required the participants to imagine they were moving their fingers while viewing the movie and attempting to move their fingers in accordance with the movie. Eleven right-handed healthy young adults were asked to perform six conditions randomly: 1) vibratory stimulation, imagery, and action observation, 2) vibratory stimulation and action observation, 3) vibratory stimulation and viewing of a blank screen, 4) imagery and action observation, 5) action observation, and 6) viewing of a blank screen. Single-pulse transcranial magnetic stimulation was conducted to assess corticomotor excitability and the peak-to-peak amplitude of the motor evoked potentials. The results showed that vibratory stimulation increases corticospinal excitability. The findings further revealed that performing motor imagery while viewing finger movement is more effective at inducing an augmentation of corticomotor excitability compared to action observation alone. Thus, the combination of motor imagery, action observation, and vibratory stimulation can effectively augment corticomotor excitability.

Mid-Infrared Pulsed Laser Lithotripsy with a Tunable Laser Using Difference-Frequency Generation

A novel technique of lithotripsy was investigated with a mid-infrared tunable pulsed laser using difference-frequency generation (DFG). Human gallstone samples obtained from 24 patients were analyzed with their infrared absorption spectra. It was found that the principal components of the gallstones were different for the different patients and that the gallstone samples used in this research could be classified into four groups, i.e., mixed stones, calcium bilirubinate stones, cholesterol stones, and calcium carbonate stones. In addition, some gallstone samples had different compositions within the single stone. The mid-infrared laser tunable within a wavelength range of 5.5 - 10 μm was irradiated to the cholesterol stones at two different wavelengths of 6.83 and 6.03 μm, where the cholesterol stones had relatively strong and weak absorption peaks, respectively. As the result, the cholesterol stones were more efficiently ablated at the wavelength of 6.83 μm with the strong absorption peak. Therefore, it is suggested that the gallstones could be efficiently ablated by tuning the wavelength of the laser to the strong absorption peak of the gallstones. The higher efficiency of the ablation using the characteristic absorption peaks should lead to the safer treatment without damage to the surrounding normal tissues. In order to identify the composition of the gallstones in the patients, endoscopic and spectroscopic diagnosis using the DFG laser and an optical fiber probe made with two hollow optical fibers and a diamond attenuation total reflection prism should be useful. The absorption spectrum of the gallstones in the patients could be measured by measuring the energy of the DFG laser transmitted through the optical fiber probe and by scanning the wavelength of the DFG laser.

Structural Flexibility Enables Alternative Maturation, ARGONAUTE Sorting and Activities of miR168, a Global Gene Silencing Regulator in Plants

In eukaryotes, the RNase-Ⅲ Dicer often produces length/sequence microRNA （miRNA） variants, called ＂isomiRs＂, owing to intrinsic structural/sequence determinants of the miRNA precursors （pre-miRNAs）. In this study, we combined biophysics, genetics and biochemistry approaches to study Arabidopsis miR168, the key feedback regulator of central plant silencing effector protein ARGONAUTE1 （AGO1）. We identified a motif conserved among plant premiR168 orthologs, which enables flexible internal basepairing underlying at least three metastable structural configurations. These configurations promote alternative, accurate Dicer cleavage events generating length and structural isomiR168 variants with distinctive AGO sorting properties and modes of action. Among these isomiR168s, a duplex with a 22-nt guide strand exhibits strikingly preferential affinity for AGO10, the closest AGO1 paralog. The 22-nt miR168-AGO10 complex antagonizes AGO1 accumulation in part via ＂transitive RNAi＂, a silencing-amplification process, to maintain appropriate AGO1 cellular homeostasis. Furthermore, we found that the tombusviral P19 silencing-suppressor protein displays markedly weaker affinity for the 22-nt form among its isomiR168 cargoes, thereby promoting AGO10-directed suppression of AGOl-mediated antiviral silencing. Taken together, these findings indicate that structural flexibility, a previously overlooked property of premiRNAs, considerably increases the versatility and regulatory potential of individual MIRNA genes, and that some pathogens might have evolved the capacity or mechanisms to usurp this property.

CREB-binding proteins (CBP) as a transcriptional coactivator of GATA-2

The GATA family consists of six members, GATA 1-6. In this study, we focused on GATA-2, which is expressed predominantly in hematopoietic progenitor cells and plays the key role in keeping these cells in the undifferentiated status. CREB-binding proteins (CBP) are essential transcriptional coacti- vators for a large number of regulated DNA-binding transcription factors, including GATA-1. But there have been no reports on whether CBP is still a co-activator of GATA-2. Here, we used the immunopre- cipitation and pull-down experiments to show that the GATA-2 and CBP were physically binding to- gether, and clarified the binding sites CH1, CH3 , CH452 and CT1430 in CBP and N-finger, C-finger and N-C-finger in GATA-2. Luciferase assay results in our experiment indicated that CBP could increase GATA-2 transcriptional activity in the dose-dependent manner. GATA-1 is mainly expressed in differen- tiated hematopoietic cells, but still has overlap expression with GATA-2. CBP is a coactivator of GATA-2 and GATA-1. The investigation on the mechanism that could decide whether CBP binds to GATA-2 to keep hematopoietic cells in the progenitor status or to GATA-1 to start differentiation will be a very in- teresting and very meaningful project in the near future.

Quantitative evaluation of perceived depth of transparently-visualized medical 3D data presented with a multi-view 3D display

Transparent visualization is used in many fields because it can visualize not only the frontal object but also other important objects behind it.Although in many situations,it would be very important for the 3D structures of the visualized transparent images to be perceived as they are simulated,little is known quantitatively as to how such transparent 3D structures are perceived.To address this question,in the present study,we conducted a psychophysical experiment in which the observers reported the perceived depth magnitude of a transparent object in medical images,presented with a multiview 3D display.For the visualization,we employed a stochastic point-based rendering(SPBR)method,which was developed recently as a technique for efficient transparentrendering.Perceived depth of the transparent object was smaller than the simulated depth.We found,however,that such depth underestimation can be alleviated to some extent by(1)applying luminance gradient inherent in the SPBR method,(2)employing high opacities,and(3)introducing binocular disparity and motion parallax produced by a multi-view 3D display.

Liver cell therapies:cellular sources and grafting strategies

The liver has a complex cellular composition and a remarkable regenerative capacity.The primary cell types in the liver are two parenchymal cell populations,hepatocytes and cholangiocytes,that perform most of the functions of the liver and that are helped through interactions with non-parenchymal cell types comprising stellate cells,endothelia and various hemopoietic cell populations.The regulation of the cells in the liver is mediated by an insoluble complex of proteins and carbohydrates,the extracellular matrix,working synergistically with soluble paracrine and systemic signals.In recent years,with the rapid development of genetic sequencing technologies,research on the liver’s cellular composition and its regulatory mechanisms during various conditions has been extensively explored.Meanwhile breakthroughs in strategies for cell transplantation are enabling a future in which there can be a rescue of patients with end-stage liver diseases,offering potential solutions to the chronic shortage of livers and alternatives to liver transplantation.This review will focus on the cellular mechanisms of liver homeostasis and how to select ideal sources of cells to be transplanted to achieve liver regeneration and repair.Recent advances are summarized for promoting the treatment of end-stage liver diseases by forms of cell transplantation that now include grafting strategies.

Xyloglucan for Generating Tensile Stress to Bend Tree Stem

In response to environmental variation, angiosperm trees bend their stems by forming tension wood, which consists of a cellulose-rich G （gelatinous）-Iayer in the walls of fiber cells and generates abnormal tensile stress in the secondary xylem. We produced transgenic poplar plants overexpressing several endoglycanases to reduce each specific polysaccharide in the cell wall, as the secondary xylem consists of primary and secondary wall layers. When placed horizontally, the basal regions of stems of transgenic poplars overexpressing xyloglucanase alone could not bend upward due to low strain in the tension side of the xylem. In the wild-type plants, xyloglucan was found in the inner surface of G-layers during multiple layering. In situ xyloglucan endotransglucosylase （XET） activity showed that the incorporation of whole xyloglucan, potentially for wall tightening, began at the inner surface layers S1 and S2 and was retained throughout G-layer development, while the incorporation of xyloglucan heptasaccharide （XXXG） for wall loosening occurred in the primary wall of the expanding zone. We propose that the xyloglucan network is reinforced by XET to form a further connection between wall-bound and secreted xyloglucans in order to withstand the tensile stress created within the cellulose G-layer micro fibrils.

PLoSONE：研究揭示去甲肾上腺素改善视力机制

去甲肾上腺素是依赖于动物的行为环境和生理状态的大脑分泌出的一种神经调节物（neuromodulator，也被称作神经调质）。并且通过调控大脑活动来影响许多各种不同的生理功能。它可能最好被称作为一种调节心率和血液流量的激素。而且很多药物，如广为人知的θ-阻断剂，靶向它的效应。它也调节视觉系统。

SPECIES-AREA RELATIONSHIP FOR POWER-LAW SPECIES ABUNDANCE DISTRIBUTION

We studied the mathematical relations between species abundance distributions （SADs） and species-area relationships （SARs） and found that a power-law SAR can be generally derived from a power-law SAD without a special assumption such as the ＂canonical hypothesis＂. In the present analysis, an SAR-exponent is obtained as a function of an SAD-exponent for a finite number of species. We also studied the inverse problem, from SARs to SADs, and found that a power-SAD can be derived from a power-SAR under the condition that the functional form of the corresponding SAD is invariant for changes in the number of species. We also discuss general relationships among lognormal SADs, the broken-stick model （exponential SADs）, linear SARs and logarithmic SARs. These results suggest the existence of a common mechanism for SADs and SARs, which could prove a useful tool for theoretical and experimental studies on biodiversity and species coexistence.