公開日:2022/07/06 / 最終更新日:2022/07/06

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The sulfonylurea (SU) tolbutamide induces tyrosine phosphorylation of the low-density lipoprotein receptor (LDLr) in vitro, an effect which may be important in its ability to induce cellular toxicity. The present study was undertaken to determine whether this effect is mimicked by other SU drugs, and if it extends to the protein kinase C (PKC)-dependent pathway. Using Western blotting and in situ immunocytochemistry, we found that glibenclamide (a prototypical SU drug) inhibited tyrosine phosphorylation of the LDLr and selectively inhibited its translocation to the plasma membrane. This effect was mimicked by tolbutamide, but not by phenformin. Glibenclamide is the prototype SU drug used most widely for treating non-insulin-dependent diabetes mellitus. Its ability to inhibit PKC-dependent pathways suggests that it may be an alternative or adjunct to insulin in the treatment of this disease.Q:

Purpose of not specifying template arguments for member functions of templated classes

I have come across this snippet in many codes and I don’t understand the purpose of this. Could someone explain with an example?
template class F : public Pimpl
{
public:
void func() {… } // Does not make this any more templatized
};

From what I understand, the foo and bar functions are implicitly instantiated in this case and we don’t need to specify T for either of the functions. Also, the class F inherits from Pimpl, so it is always instantiated.

A:

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A study of astrocytes and microglia in the hippocampus and PFC of depressed individuals found the expressions of the two cell types increased in parallel with the increase in the intensity of depressive symptoms.\[[@ref29]\] This raises the question about the functional relevance of microglial changes in the brain. On the one hand, the increased number and size of microglial cells can contribute to the synaptic pruning of unrequired synapses,\[[@ref29]\] which is a well-known effect of stress.\[[@ref30]\] On the other hand, there is evidence that activation of microglial cells might actually be neuroprotective, even when they are highly activated, because of the release of an array of neurotrophic factors, including brain-derived neurotrophic factor, nerve growth factor, and vascular endothelial growth factor.\[[@ref31]\]

The role of immune markers in clinical therapy of depression is still a matter of investigation. A meta-analysis of published randomized controlled trials showed that imipramine, tricyclic antidepressants, and fluoxetine significantly reduced the serum levels of proinflammatory and nitric oxide-related markers. In contrast, studies assessing the effects of electroconvulsive therapy showed mixed results.\[[@ref32]\] Serum levels of IL-6 were significantly decreased after both ECT and antidepressant treatment,\[[@ref33]\] and serum levels of IL-10 were significantly increased after combined ECT and fluoxetine treatment.\[[@ref34]\]

Among inflammatory markers, IL-6 is a particularly good candidate for a mediator of rapid antidepressant effects because of its effect on the activity of the HPA axis
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Another time, a girl was “brutally raped” by three classmates in a basement. They laughed as they beat her with sticks, a broom, and a belt. The girl tried to flee, but the boys blocked the stairs.

These girls — all of them teenagers at the time — were not strangers in town. They were classmates. They went to the same school. They lived in the same house with each other.

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While every year there are students who are abused and harassed at school, a new report issued Monday in New Jersey gives a fuller picture of the extent of such abuse.

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