Aging-Dependent Loss of Connectivity in Alzheimer's Model Mice with Rescue by mGluR5 Modulator.

Amyloid accumulation in Alzheimer's disease (AD) is associated with synaptic damage and altered connectivity in brain networks. While measures of amyloid accumulation and biochemical changes in mouse models have utility for translational studies of certain therapeutics, preclinical analysis of altered brain connectivity using clinically relevant fMRI measures has not been well developed for agents intended to improve neural networks. Here, we conduct a longitudinal study in a double knock-in mouse model for AD ( App NL-G-F /hMapt ), monitoring brain connectivity by means of resting-state fMRI. While the 4-month-old AD mice are indistinguishable from wild-type controls (WT), decreased connectivity in the default-mode network is significant for the AD mice relative to WT mice by 6 months of age and is pronounced by 9 months of age. In a second cohort of 20-month-old mice with persistent functional connectivity deficits for AD relative to WT, we assess the impact of two-months of oral treatment with a silent allosteric modulator of mGluR5 (BMS-984923) known to rescue synaptic density. Functional connectivity deficits in the aged AD mice are reversed by the mGluR5-directed treatment. The longitudinal application of fMRI has enabled us to define the preclinical time trajectory of AD-related changes in functional connectivity, and to demonstrate a translatable metric for monitoring disease emergence, progression, and response to synapse-rescuing treatment.

Observation of fragmentation of a spinor Bose-Einstein condensate.

Weakly interacting Bose gases usually form Bose-Einstein condensates in which most particles occupy the same single-particle state. However, when this state cannot realize a continuous symmetry of the many-body Hamiltonian, a fragmented condensate exhibiting the expected symmetry may emerge. Here, we produced a three-fragment condensate for a mesoscopic spin-1 gas of about 100 atoms, with anti-ferromagnetic interactions and vanishing collective spin. Using a spin-resolved detection approaching single-atom resolution, we show that the reconstructed state is close to the expected many-body ground state, whereas one-body observables are the same as for a completely mixed state. Our results highlight how the interplay between symmetry and interactions generates entanglement in a mesoscopic quantum system.

From Many-Body Oscillations to Thermalization in an Isolated Spinor Gas.

The dynamics of a many-body system can take many forms, from a purely reversible evolution to fast thermalization. Here we show experimentally and numerically that an assembly of spin-1 atoms all in the same spatial mode allows one to explore this wide variety of behaviors. When the system can be described by a Bogoliubov analysis, the relevant energy spectrum is linear and leads to undamped oscillations of many-body observables. Outside this regime, the nonlinearity of the spectrum leads to irreversibility, characterized by a universal behavior. When the integrability of the Hamiltonian is broken, a chaotic dynamics emerges and leads to thermalization, in agreement with the eigenstate thermalization hypothesis paradigm.

Probing Spin Correlations in a Bose-Einstein Condensate Near the Single-Atom Level.

Using parametric conversion induced by a Shapiro-type resonance, we produce and characterize a two-mode squeezed vacuum state in a sodium spin 1 Bose-Einstein condensate. Spin-changing collisions generate correlated pairs of atoms in the m=±1 Zeeman states out of a condensate with initially all atoms in m=0. A novel fluorescence imaging technique with sensitivity ΔN∼1.6 atom enables us to demonstrate the role of quantum fluctuations in the initial dynamics and to characterize the full distribution of the final state. Assuming that all atoms share the same spatial wave function, we infer a squeezing parameter of 15.3 dB.

Umbilicus application of Huobi Powder for ED with kidney deficiency dampness: A randomized controlled clinical trial / 中华男科学杂志

Objective@#To prove the clinical efficacy of umbilicus application of Huobi Powder for the treatment of erectile dysfunction (ED) with the traditional Chinese medicine (TCM) syndrome of kidney deficiency dampness by related clinical indexes.@*METHODS@#This randomized controlled double-blind clinical study included 72 ED patients with the TCM syndrome of kidney deficiency dampness treated by 12-hour application of Huobi Powder (the trial group, n = 36) or placebo (the control group, n = 36) to the umbilicus qd for 28 consecutive days. We recorded the IIEF-5 and Erection Quality Scale (EQS) scores, TCM syndrome indexes, radial rigidity of the erectile penis, and the angle of penile erection before and after treatment. We established a database with the collected data and performed statistical analysis with the SPSS21.0 software.@*RESULTS@#Statistically significant differences were observed after treatment between the trial and control groups in the TCM syndrome-based efficacy (69.44% vs 36.11%, P 0.05).@*CONCLUSIONS@#Umbilicus application of Huobi Powder has a definite clinical effect on ED with the TCM syndrome of kidney deficiency dampness.

[Evaluation of heart impact in the 100 m extreme intensity sport using near-infrared non-invasive muscle oxygen detecting device and sports heart rate detection technology].

Using continuous two wavelength near-infrared technology to detect the variation in the consistency of oxygen hemoglobin in the muscle and the sports heart rate wireless real time collection technology, we devised the real time muscle tissue oxygenation and instantaneous heart rate experiment scheme and implemented it for the process of the 100 m run with two parameters given simultaneously. The experiment shows that the concentration of the oxygen hemoglobin in the muscle tissue continues decreasing after the end of the 100 m run, and the time interval between the moment when the concentration of the oxygen hemoglobin attains the minimum value and the moment when the athletes finish the 100 m run is (6.65 +/- 1.10) sec; while the heart rate continues increasing after the end of the 100 m run, and the time interval between the moment when the heart rate attains the maximum value and the moment when the athletes finish the 100 m run is (8.00 +/- 1.57) sec. The results show that the two wavelength near-infrared tissue oxygenation detection technology and the sports heart rate real time collection equipment can accurately measure the sports tissue oxygenation and the heart rate in the extreme intensity sport, and reveal the process of muscle oxygen transportation and consumption and its dynamic character with the heart rate in the extreme intensity sport.

Kir6.2DeltaC26 channel traffics to plasma membrane by constitutive exocytosis.

Adenosine triphosphate (ATP)-sensitive K+ (KATP) channels regulate many cellular functions by coupling the metabolic state of the cell to the changes in membrane potential. Truncation of C-terminal 26 amino acid residues of Kir6.2 protein (Kir6.2DeltaC26) deletes its endoplasmic reticulum retention signal, allowing functional expression of Kir6.2 in the absence of sulfonylurea receptor subunit. pEGFP-Kir6.2DeltaC26 and pKir6.2DeltaC26-IRES2-EGFP expression plasmids were constructed and transfected into HEK293 cells. We identified that Kir6.2DeltaC26 was localized on the plasma membrane and trafficked to the plasmalemma by means of constitutive exocytosis of Kir6.2DeltaC26 transport vesicles, using epi-fluorescence and total internal reflection fluorescence microscopy. Our electrophysiological data showed that Kir6.2DeltaC26 alone expressed KATP currents, whereas EGFP-Kir6.2DeltaC26 fusion protein displayed no KATP channel activity.

[Design of software for fluorescence microscopy system to measure cytosolic free calcium in living cell].

OBJECTIVE: To design software based on the double-wavelength fluorescence microscopy to measure cytosolic free calcium ([Ca2+]i) in living cell. METHOD: Through analyzing the work principles of monochromator, the function relation between output wavelength and voltage was obtained. Based on the analysis results as the arithmetic of the software, the application was developed in the integration development environment of VC ++ 6.0, by using the framework of Microsoft Foundation Class Library (MFC) and multithread technology. RESULT: The authors has realized the software and constructed a fluorescence microscopy system using the software, PC, monochromator, fluorescence microscope, MPT and data acquisition to measure the [Ca2+]i in single living beta cell. CONCLUSION: Using this software, the [Ca2+]i in living cell can be detected. It has been proved to be an effective tool for the research in cellular biophysics.

[Use of three-dimensional fluorescence deconvolution microscopy for study of spatial distribution of secretory vesicles in living cells].

A three-dimensional image of a living cell is helpful for cell secretion study. In this report, the three-dimensional fluorescence deconvolution microscopy for observing living cells was studied, because this technique can obtain a quick three-dimensional imaging with minimal fluorescence quenching and cytotoxicity for living cell observation. The property of three-dimensional point spread function (PSF) of imaging system was analyzed. The relationship between experimental and theoretical PSF was illustrated, and the theoretical PSF was proved that it could reflect the principle of imaging system with NA 1.65 objective in use. Three-dimensional deconvolution algorithm in this report was proved effective by well-defined three-dimensional specimens. Furthermore, the rat pancreatic beta cell secretory vesicles labeled by acridine orange was observed by using this technique. Results showed that the blurring induced by out-of-focus light was removed by the deconvolution algorithm effectively, under current experiment conditions (with NA 1.65 objective) the experimental PSF approximated the theoretical PSF very well, and deconvolved living cell images exhibited the spatial distribution of the secretory vesicles clearly.

Na+ channel inactivation: a comparative study between pancreatic islet beta-cells and adrenal chromaffin cells in rat.

A comparative study was carried out on the inactivation of Na+ channels in two types of endocrine cells in rats, beta-cells and adrenal chromaffin cells (ACCs), using patch-clamp techniques. The beta-cells were very sensitive to hyperpolarization; the Na+ currents increased ninefold when the holding potential was shifted from -70 mV to -120 mV. ACCs were not sensitive to hyperpolarization. The half-inactivation voltages were -90 mV (rat beta-cells) and -62 mV (ACCs). The time constant for recovery from inactivation at -70 mV was 10.5 times slower in beta-cells (60 ms) than in ACCs (5.7 ms). The rate of Na+-channel inactivation at physiological resting potential was more than three times slower in beta-cells than in ACCs. Na+ influx through Na+ channels had no effect on the secretory machinery in rat beta-cells. However, these 'silent Na+ channels' could contribute to the generation of action potentials in some conditions, such as when the cell is hyperpolarized. It is concluded that the fractional availability of Na+ channels in beta-cells at a holding potential of -70 mV is about 15 % of that in ACCs. This value in rat beta-cells is larger than that observed in mouse (0 %), but is smaller than those observed in human or dog (90 %).