34 research outputs found
Astrocytes actively support long-range molecular clock synchronization of segregated neuronal populations
In mammals, the suprachiasmatic nucleus of the hypothalamus is the master circadian pacemaker that synchronizes the clocks in the central nervous system and periphery, thus orchestrating rhythms throughout the body. However, little is known about how so many cellular clocks within and across brain circuits can be effectively synchronized. In this work, we investigated the implication of two possible pathways: (i) astrocytes-mediated synchronization and (ii) neuronal paracrine factors-mediated synchronization. By taking advantage of a lab-on-a-chip microfluidic device developed in our laboratory, here we report that both pathways are involved. We found the paracrine factors-mediated synchronization of molecular clocks is diffusion-limited and, in our device, effective only in case of a short distance between neuronal populations. Interestingly, interconnecting astrocytes define an active signaling channel that can synchronize molecular clocks of neuronal populations also at longer distances. At mechanism level, we found that astrocytes-mediated synchronization involves both GABA and glutamate, while neuronal paracrine factors-mediated synchronization occurs through GABA signaling. These findings identify a previously unknown role of astrocytes as active cells that might distribute long-range signals to synchronize the brain clocks, thus further strengthening the importance of reciprocal interactions between glial and neuronal cells in the context of circadian circuitry
Local hyperthyroidism promotes pancreatic acinar cell proliferation during acute pancreatitis
Proliferation of pancreatic acinar cells is a critical process in the pathophysiology of pancreatic diseases, because limited or defective proliferation is associated with organ dysfunction and patient morbidity. In this context, elucidating the signalling pathways that trigger and sustain acinar proliferation is pivotal to develop therapeutic interventions promoting the regenerative process of the organ.In this study we used genetic and pharmacological approaches to manipulate both local and systemic levels of thyroid hormones to elucidate their role in acinar proliferation following caerulein‐mediated acute pancreatitis in mice. In addition, molecular mechanisms mediating the effects of thyroid hormones were identified by genetic and pharmacological inactivation of selected signalling pathways.In this study we demonstrated that levels of the thyroid hormone 3,3’,5‐triodo‐L‐thyronine (T3) transiently increased in the pancreas during acute pancreatitis. Moreover, by using genetic and pharmacological approaches to manipulate both local and systemic levels of thyroid hormones, we showed that T3 was required to promote proliferation of pancreatic acinar cells, without affecting the extent of tissue damage or inflammatory infiltration.Finally, upon genetic and pharmacological inactivation of selected signalling pathways, we demonstrated that T3 exerted its mitogenic effect on acinar cells via a tightly controlled action on different molecular effectors, including histone deacetylase, AKT, and TGFβ signalling.In conclusion, our data suggest that local availability of T3 in the pancreas is required to promote acinar cell proliferation and provide the rationale to exploit thyroid hormone signalling to enhance pancreatic regeneration
Nano-Crystalline &Amorphous Silicon PhotoTransistor Performance Analysis
In this thesis, we compared electrical performance and stability of a novel nanocrystalline Si (nc-Si) thin film phototransistor (TFT) phototransistor and a regular amorphous silicon (a-Si:H) TFT phototransistor for large area imaging applications. The electrical performance parameters of nc-Si TFT phototransistor were extracted from the electrical (current-voltage) testing in dark and under illumination. The field-effect mobility is found to be around 1.2 cm2V-1s-1, the threshold voltage around 3.9V and the sub-threshold voltage slope around 0.47V/Dec. Optical properties of nc-Si TFT phototransistor have been evaluated under the green light illumination in the range of 1014 – 1017 lum, and the photocurrent gain and the external quantum efficiency were extracted from the experimental results. By comparing the results with those for a-Si:H TFTs measured under the same conditions, we found that nc-Si TFT has higher photo current gain under low illumination intensity, 5 ×1014 to 7 ×1015 lum. This thesis shows the relations bewteen the photo current gain, the external quantum efficiency, TFT drain and TFT gate bias; the photo current gain and the external quantum efficiency can be controlled by the Vds and the Vgs
Derivation of Pre-oligodendrocytes from Human Endometrial Stromal Cells by Using Overexpression of MicroRNA 338
Role of type 2 deiodinase in response to acute lung injury (ALI) in mice
Thyroid hormone (TH) metabolism, mediated by deiodinase types 1, 2, and 3 (D1, D2, and D3) is profoundly affected by acute illness. We examined the role of TH metabolism during ventilator-induced lung injury (VILI) in mice. Mice exposed to VILI recapitulated the serum TH findings of acute illness, namely a decrease in 3,5,3′-triiodothyronine (T3) and thyroid-stimulating hormone and an increase in reverse T3. Both D2 immunoreactivity and D2 enzymatic activity were increased significantly. D1 and D3 activity did not change. Using D2 knockout (D2KO) mice, we determined whether the increase in D2 was an adaptive response. Although similar changes in serum TH levels were observed in D2KO and WT mice, D2KO mice exhibited greater susceptibility to VILI than WT mice, as evidenced by poorer alveoli integrity and quantified by lung chemokine and cytokine mRNA induction. These data suggest that an increase in lung D2 is protective against VILI. Similar findings of increased inflammatory markers were found in hypothyroid WT mice exposed to VILI compared with euthyroid mice, indicating that the lungs were functionally hypothyroid. Treatment of D2KO mice with T3 reversed many of the lung chemokine and cytokine profiles seen in response to VILI, demonstrating a role for T3 in the treatment of lung injury. We conclude that TH metabolism in the lung is linked to the response to inflammatory injury and speculate that D2 exerts its protective effect by making more TH available to the injured lung tissue