Live imaging and single-cell analysis reveal differential dynamics of autophagy and apoptosis

Autophagy is induced by many cytotoxic stimuli but it is often unclear whether, under specific conditions, autophagy plays a prosurvival or a prodeath role. To answer this critical question we developed a novel methodology that employs automated live microscopy and image analysis to measure autophagy and apoptosis simultaneously in single cells. We used this approach to perform a systems-level analysis of pathway dynamics for both autophagy and apoptosis. We found that induction of autophagy in response to different stimuli is uniformly unimodal; in contrast, cells induce apoptosis in an all-or-none bimodal fashion. By tracking the fate of single cells we found that autophagy precedes apoptosis, and that within the same population apoptosis is delayed in cells that mount a stronger autophagy response. Inhibition of autophagy by knocking down ATG5 promoted apoptosis, thus confirming that autophagy plays a protective role. We anticipate that our single-cell approach will be a powerful tool for gaining a quantitative understanding of the complex regulation of autophagy, its influence on cell fate decisions and its relationship with other cellular pathways

Dynamic Nonlinear Effect on Lasing in a Random Medium

We have studied both experimentally and numerically the dynamic effect of nonlinearity on lasing in disordered medium. The third-order nonlinearity not only changes the frequency and size of lasing modes, but also modifies the laser emission intensity and laser pulse width. When the nonlinear response time is longer than the lifetime of the lasing mode, the nonlinearity changes the laser output through modifying the size of the lasing mode. When the nonlinear response is faster than the buildup of the lasing mode, positive nonlinearity always extracts more laser emission from the random medium due to the enhancement of single particle scattering

Introgression of bacterial blight (BB) resistance genes Xa7 and Xa21 into popular restorer line and their hybrids by molecular marker-assisted backcross (MABC) selection scheme

Yihui1577 is an elite restorer line widely used in hybrid rice production in China, however, both the restorer and their derived hybrids are susceptible to bacterial blight (BB) caused by Xathomonas oryzae pv. oryzae (Xoo). In order to overcome this problem, we had introgressed two resistant genes Xa7 and Xa21 into Yihui1577 by marker-assisted backcross (MABC) with foreground selection scheme to speed up the process. Six breeding lines with different BB resistance genes: HH1202 (Xa7), HH1203 (Xa7), HH1204 (Xa21), HH1205 (Xa21), HH1206 (Xa7+Xa21) and HH1207 (Xa7+Xa21) were selected and crossed with four CMS and one TGMS lines. Seven most virulent and prevalent Xoo strains (PXO61, PXO99, ZHE173, GD1358, FuJ, YN24 and HeN11) from the Philippines and different provinces of China were inoculated for evaluating the BB-resistance of the selected lines and their derived hybrids. The results reveal that the two lines and their derived hybrids with single resistance gene Xa7 were resistant against six of the seven Xoo strains, except for PXO99. The lines with single resistance gene Xa21 were only susceptible to the Xoo strain FuJ, but some of their derived hybrids were susceptible to the Xoo strains FuJ and GD1358. Interestingly, the pyramiding lines carrying the two resistance genes Xa7 and Xa21 and also their derived hybrids were resistant against all the seven Xoo strains. The data of agronomic and grain quality characteristics demonstrated that the selected lines were similar to that of the recurrent parent Yihui1577. Corrective measures taken by way of introgression of BB-resistance genes: Xa7 and Xa21 into the popular restorer line, Yihui1577 through MABC approach for enhancing the BB-resistance level was effective and timely.Keywords: Bacterial blight, resistance gene, Xa7 and Xa21, MABC, inoculation and reaction, agronomic traits, grain qualit

Differential miRNA expression in Rehmannia glutinosa plants subjected to continuous cropping

<p>Abstract</p> <p>Background</p> <p>The productivity of the medicinally significant perennial herb <it>Rehmannia glutinosa </it>is severely affected after the first year of cropping. While there is some information available describing the physiological and environmental causes of this yield decline, there is as yet no data regarding the changes in gene expression which occur when the species is continuously cropped.</p> <p>Results</p> <p>Using a massively parallel (Solexa) DNA sequencing platform, it was possible to identify and quantify the abundance of a large number of <it>R. glutinosa </it>miRNAs. We contrasted the miRNA content of first year crop plants with that of second year crop ones, and were able to show that of 89 conserved (belonging to 25 families) and six novel miRNAs (six families), 29 of the former and three of the latter were differentially expressed. The three novel miRNAs were predicted to target seven genes, and the 29 conserved ones 308 genes. The potential targets of 32 of these differentially expressed miRNAs involved in the main transcription regulation, plant development and signal transduction. A functional analysis of the differentially expressed miRNAs suggested that several of the proposed targets could be directly or indirectly responsible for the development of the tuberous root.</p> <p>Conclusion</p> <p>We have compared differential miRNAs expression in the first year crop (FP) <it>R. glutinosa </it>plants and second year crop (SP) ones. The outcome identifies some potential leads for understanding the molecular basis of the processes underlying the difficulty of maintaining the productivity of continuously cropped <it>R. glutinosa</it>.</p

Microglia Prevent Beta-Amyloid Plaque Formation in the Early Stage of an Alzheimer\u27s Disease Mouse Model with Suppression of Glymphatic Clearance

BACKGROUND: Soluble beta-amyloid (Aβ) can be cleared from the brain through various mechanisms including enzymatic degradation, glial cell phagocytosis, transport across the blood-brain barrier, and glymphatic clearance. However, the relative contribution of each clearance system and their compensatory effects in delaying the pathological process of Alzheimer\u27s disease (AD) are currently unknown. METHODS: Fluorescent trace, immunofluorescence, and Western blot analyses were performed to compare glymphatic clearance ability and Aβ accumulation among 3-month-old APP695/PS1-dE9 transgenic (APP/PS1) mice, wild-type mice, aquaporin 4 knock out (AQP4−/−) mice, and AQP4−/−/APP/PS1 mice. The consequence of selectively eliminating microglial cells, or downregulating apolipoprotein E (apoE) expression, on Aβ burden, was also investigated in the frontal cortex of AQP4−/−/APP/PS1 mice and APP/PS1 mice. RESULTS: AQP4 deletion in APP/PS1 mice significantly exaggerated glymphatic clearance dysfunction, and intraneuronal accumulation of Aβ and apoE, although it did not lead to Aβ plaque deposition. Notably, microglia, but not astrocytes, increased activation and phagocytosis of Aβ in the cerebral cortex of AQP4−/−/APP/PS1 mice, compared with APP/PS1 mice. Selectively eliminating microglia in the frontal cortex via local injection of clodronate liposomes resulted in deposition of Aβ plaques in AQP4−/−/APP/PS1 mice, but not APP/PS1 mice. Moreover, knockdown of apoE reduced intraneuronal Aβ levels in both APP/PS1 mice and AQP4−/−/APP/PS1 mice, indicating an inhibitory effect of apoE on Aβ clearance. CONCLUSION: The above results suggest that the glymphatic system mediated Aβ and apoE clearance and microglia mediated Aβ degradation synergistically prevent Aβ plague formation in the early stages of the AD mouse model. Protecting one or both of them might be beneficial to delaying the onset of AD

Deletion of Aquaporin-4 in APP/PS1 Mice Exacerbates Brain Aβ Accumulation and Memory Deficits

BACKGROUND: Preventing or reducing amyloid-beta (Aβ) accumulation in the brain is an important therapeutic strategy for Alzheimer\u27s disease (AD). Recent studies showed that the water channel aquaporin-4 (AQP4) mediates soluble Aβ clearance from the brain parenchyma along the paravascular pathway. However the direct evidence for roles of AQP4 in the pathophysiology of AD remains absent. RESULTS: Here, we reported that the deletion of AQP4 exacerbated cognitive deficits of 12-moth old APP/PS1 mice, with increases in Aβ accumulation, cerebral amyloid angiopathy and loss of synaptic protein and brain-derived neurotrophic factor in the hippocampus and cortex. Furthermore, AQP4 deficiency increased atrophy of astrocytes with significant decreases in interleukin-1 beta and nonsignificant decreases in interleukin-6 and tumor necrosis factor-alpha in hippocampal and cerebral samples. CONCLUSIONS: These results suggest that AQP4 attenuates Aβ pathogenesis despite its potentially inflammatory side-effects, thus serving as a promising target for treating AD

Research and Suggestions on the Present Situation of Shared Bicycle Parking Spot on University Campus

As an important means of short-distance travel for college students, sharing bicycle parking and planning is particularly noteworthy. This requires not only considering the layout of buildings and environment on campus, but also systematically improving and designing with the combination of behavior characteristics and human factors. Based on the research and analysis of the current situation of sharing bicycles among college students, this paper puts forward some suggestions for improving the design of parking spaces in College campuses