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The world honors victims of Paris attacks

Showing support with lights

San Francisco City Hall in the US state of California is lit up with blue, white and red, the colors of the French flag, following the Paris terror attacks. US Secretary of Defense Ashton Carter spoke on the phone with French Defense Minister Jean-Yves Le Drian on Saturday, saying the United States was "committed to helping France in any way" and that the two would remain in close contact.

The world honors victims of Paris attacks

"Our hearts break with yours"

"Tonight the sails of the Opera House will be lit in the blue, white red of the French flag. We mourn with you and stand with you, Paris," tweeted Mike Baird, premier of Australia's state of NSW. "Our hearts break with yours, Paris. But our spirits will never be broken," he wrote on Facebook. "Neither will our determination to stand together against these cowardly, evil acts of terror."

The world honors victims of Paris attacks

Reconsidering air strikes

The landmark CN Tower in Toronto was also lit with blue, white and red lights. Canadian PM Justin Trudeau said it was too soon to say whether the deadly attacks would prompt him to reconsider his pledge to withdraw Canada from air strikes against "Islamic State" militants in the Middle East. "Our hearts and thoughts and prayers go out to our French cousins in this dark and terrible time."

The world honors victims of Paris attacks

"Despicable attacks"

The High Roller at The LINQ Promenade on the Las Vegas Strip was also lit up with the blue, white and red colors. US President Barack Obama and German Chancellor Angela Merkel led a global chorus of solidarity with France. UN Secretary-General Ban Ki-moon condemned the "despicable attacks," while Pope Francis called the killings "inhuman."

The world honors victims of Paris attacks

Support from China

The Oriental Pearl TV Tower in Shanghai's Lujiazui financial district was bathed in the French flag colors for one hour on Saturday. Foreign Ministry spokesman Hong Lei said China was "deeply shocked" by the attacks and pledged solidarity with France in combating terrorism. "China resolutely supports France in maintaining its national security and stability and in attacking terrorism," Hong said.

The world honors victims of Paris attacks

Tourist sites affected

The Angel de la Independencia monument in Mexico City, a very popular tourist attraction, was also demonstrating its support and identification with the tragic events. At the same time, French authorities have closed the Eiffel Tower, the Louvre Museum and other top tourist sites in Paris until further notice following the deadly terror attacks.

The world honors victims of Paris attacks

Condolences from New Zealand

The Sky Tower in Auckland is to be lit up Saturday night in the colors of the French flag. New Zealand Prime Minister John Key spoke of his huge relief on hearing that daughter Stephie, an art student in Paris, was safe. Key also expressed his condolences to the people and government of France, saying that "our hearts go out to those involved and our thoughts are with them and their families."

The world honors victims of Paris attacks

Increasing security

The Senate building in Mexico City was also expressing solidarity with Paris by lighting its office lights in the colors of the French flag. France will increase security at French diplomatic missions and official buildings around the world, Foreign Minister Laurent Fabius said. French President Hollande has declared three days of mourning and raised the nation's security to the highest level.

The world honors victims of Paris attacks

Solidarity from 10,000 km away

From Taipei to Paris: Taiwan's landmark building Taipei 101 is lit up in blue, white and red. In France, hospital officials say at least 300 people were injured in Friday's attacks, of whom some 80 are in a critical condition. The "Islamic State" group has claimed responsibility, and a French national has been identified as one of the four men who stormed the Bataclan concert hall in one attack.

The world honors victims of Paris attacks

Sharing traumas

The One World Trade Center in New York, the skyscraper built on the site of the September 11 attacks of 2001, was also illuminated in the French national colors. World leaders united in sympathy and indignation, New York police increased security measures. A State Department spokesman has confirmed that Americans are among the injured in the attacks.

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Fig. 2

Effect of sildenafil citrate on the cortical infarct volumes and tissue loss measured 72h and 8days after pMCAo, respectively. Sildenafil citrate was given after pMCAo by a single intraperitoneal injection either with PBS or 0.5, 2.5, 10, and 15mg/kg sildenafil. a Cortical lesion at 72h. b Tissue loss at 8days. represents the mean. Note that the 15mg/kg dose is toxic by increasing the infarct volume. Each represents one animal. Data were assessed via an ANOVA, and when significant the results of the Newman-Keuls post-test are shown, **  < 0.01, ***  < 0.001 sildenafil dose vs PBS

Reactive astrogliosis manifested by a significant increase in GFAP immunoreactivity was clearly observed around the lesion in PBS-treated animals at 72h after pMCAo (Additional file Janelle Splendid tWCaMU
: Figure S4 and Additional file 1 : Figure S5A, B). Surprisingly, sildenafil significantly increased the prevalence of GFAP + cells at 10mg/kg. Conversely, sildenafil significantly reduced the number of GFAP + cells 8days after pMCAo as compared to PBS-treated animals. No significant difference was observed between PBS and 0.5mg/kg sildenafil treatment at either time point (Additional file 1 : Figure S4).

Fig. 3

Effect of sildenafil citrate on the density of microglia/macrophages cells and COX-2 expression at 72h after pMCAo. a Quantitative analysis of tomato-lectin (,  = 6–7 per group) in PBS, Sil-0.5, and Sil-10 (mg/kg)-treated animals. b–d Localization and quantification of COX-2 cells in the core and/or the penumbra in PBS- and sildenafil-treated animals. **  < 0.01, *** < 0.001, sildenafil vs PBS treatment.  < 0.01,  < 0.001, sildenafil 0.5 vs sildenafil 10. Scale bar represents 100μm (b) and 50μm ()

Fig. 4

Gene expression of microglia/macrophage M1-like markers in PBS- and sildenafil ()-treated animals, 72h and 8days after pMCAo. M1 markers were measured in the ipsilateral () and contralateral () sides in PBS () and sil-10 () animals. Data are mean ± SEM. Data were assessed via an ANOVA, and when significant, the results of the Newman-Keuls post-test are shown; * < 0.05, and *** < 0.001, compared to PBS

Fig. 5

Gene expression of microglia/macrophage M2-like markers in PBS- and sildenafil ()-treated animals, 72h and 8days after pMCAo. M2 markers were measured in the ipsilateral () and contralateral () side in PBS- () and sil-10 () animals. Data are mean ± SEM. Data were assessed via an ANOVA, and when significant, the results of the Newman-Keuls post-test are shown; * < 0.05, ** < 0.01, and *** < 0.001, compared to PBS

Fig. 6

Effect of sildenafil on the number of Iba-1-positive microglia and M2 and M1 phenotypes 8days after pMCAo. a Typical example of double fluorescence labeling in the cortical penumbra for Iba-1 and Arg-1 and Iba-1 and COX-2 cells in a PBS-treated animal. Note that almost Iba-1 cells are co-stained with COX-2 marker (), which is not the case for double-stained Iba-1-Arg-1 cells. b–d Quantification of the number of Iba-1, Iba-1-COX-2, and Iba-1-Arg-1 microglia cells in PBS-treated and sildenafil-treated (0.5 and 10mg/kg) animals. Data are mean ± SEM. Data were assessed via an ANOVA, and when significant, the results of the Newman-Keuls post-test are shown. * < 0.05, ** < 0.01, sildenafil vs PBS treatment

Fig. 7

3D confocal analysis of double-labeled microglia and vessels after pMCAo and PBS and/or sildenafil (0.5mg/kg) treatment. a Co-localization of M1 (COX-2 in ) and M2 (MRC-1 in ) markers in the leptomeningeal membranes, 72h after ischemia. b MRC-1 (in ) is present in the perivascular microglia (in ). c Co-localization of M1 (COX-2 in ) and M2 (Arg-1 in ) markers in the leptomeningeal membranes 8days after pMCAo, in a PBS-treated animal. Scale bar represents 10μm (a–c)

To further address the effect of sildenafil treatment on M1 and M2 markers, we examined the co-localization of Iba-1 + (a marker for both M1 and M2 microglia/macrophages) with either the M2-like marker Arg-1 (Fig. Hanzo S New Balance GG8dva0OkR
, upper panel) or the M1-like marker COX-2 (Fig. 6a , lower panel) in the cortical penumbra. While a global decrease of Iba-1 + microglia/macrophage was observed by sildenafil irrespective of dosage (Fig. 6b ), an increase of Iba-1 + Arg-1 + double-positive M2 microglia/macrophage was observed at 10 but not 0.5mg/kg (Fig. Pair O Dice Canvas SlipOn Shoes WAKhBomegq
), suggesting that a high dosage of sildenafil was required for microglia/macrophages to obtain the M2 status. Interestingly, sildenafil decreased the number of Iba-1 + COX-2 + double-positive M1 microglia/macrophages irrespective of dosage (Fig. 6d ), suggesting it does not only affect phenotype polarization and that a lower dose threshold is required for inhibition of neurotoxic M1-type than for activation of neuroprotective M2-type microglia/macrophages.

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