Louis-Fran├žois de Boufflers

Louis François de Boufflers, Duke of Boufflers was a French soldier. He was named marshal of France. Louis-François bore several titles, but was known as the Chevalier Boufflers, he is known as the Duc de Boufflers and Comte de Cagny. Louis-François was born at Crillon in Oise on 10 January 1644, he entered the army and saw service in 1663 at the siege of Marsal, becoming colonel of dragoons in 1669. In the conquest of Lorraine, he served under the Marshal de Créqui. In the Dutch Republic, he served under Henri de la Tour d'Auvergne, Vicomte de Turenne distinguishing himself by his skill and bravery, he was a brigadier, in 1677 he became maréchal de camp. He served throughout the campaigns of the time with increasing distinction, in 1681 became lieutenant-general, he commanded the French army on the Moselle, which opened the War of the Grand Alliance with a series of victories. On 15 October 1688, he took the important fortress Mainz, the Aureum caput regni, with 20,000 soldiers he led a corps to the Sambre, reinforced François Henri de Montmorency, Duke of Piney on the eve of the Battle of Fleurus.

In 1691, he acted as lieutenant-general under the king in person. He was present with the king at the siege of Namur in 1692, took part in the victory of Steinkirk. For his services he was raised in 1692 to the rank of Marshal of France, in 1694 was made a duke. In 1693, he married Catherine Charlotte de Gramont. In 1694, he was appointed governor of the town of Lille, he was besieged in Namur in 1695, only surrendered to his besiegers after he had lost 8,000 of his 13,000 men. In the conferences which terminated in the Peace of Ryswick he had a principal share. During the following war, when Lille was threatened with a siege by John Churchill, 1st Duke of Marlborough and Prince Eugène of Savoy, Boufflers was appointed to the command, made a most gallant resistance of three months, he was honoured by the king for his defence of Lille, as if he had been victorious. It was indeed a species of triumph. In 1708 he was made a peer of France. In 1709, when the affairs of France were threatened with the most urgent danger, Boufflers offered to serve under his junior, Claude Louis Hector de Villars, Marshal-Duke of Villars, was with him at the Battle of Malplaquet.

Here he displayed the highest skill, after Villars was wounded he conducted the retreat of the French army without losing either cannon or prisoners. He died at Fontainebleau on 22 August 1711, he married daughter of Antoine Charles de Gramont, Duke of Gramont. They had one son. Joseph Marie de Boufflers, Duke of Boufflers had children. Baynes, T. S. ed. "Louis Francois, Duc de Bouflers", Encyclopædia Britannica, 4, New York: Charles Scribner's Sons, p. 169 Chisholm, Hugh, ed. "Boufflers, Louis François", Encyclopædia Britannica, 4, Cambridge University Press, p. 315

Shiga toxin

Shiga toxins are a family of related toxins with two major groups, Stx1 and Stx2, expressed by genes considered to be part of the genome of lambdoid prophages. The toxins are named after Kiyoshi Shiga, who first described the bacterial origin of dysentery caused by Shigella dysenteriae. Shiga-like toxin is a historical term for identical toxins produced by Escherichia coli; the most common sources for Shiga toxin are the bacteria S. dysenteriae and some serotypes of Escherichia coli, which includes serotypes O157:H7, O104:H4. Microbiologists use many terms to differentiate more than one unique form. Many of these terms are used interchangeably. Shiga toxin type 1 and type 2 are the Shiga toxins produced by some E. coli strains. Stx-1 differs by only one amino acid. Stx-2 shares 56% sequence identity with Stx-1. Cytotoxins – an archaic denotation for Stx – is used in a broad sense. Verocytotoxins/verotoxins – a seldom-used term for Stx – is from the hypersensitivity of Vero cells to Stx; the term Shiga-like toxins is another antiquated term which arose prior to the understanding that Shiga and Shiga-like toxins were identical.

The toxin is named after Kiyoshi Shiga, who discovered S. dysenteriae in 1897. In 1977, researchers in Ottawa, Ontario discovered the Shiga toxin produced by Shigella dysenteriae in a line of E. coli. The E. coli version of the toxin was named "verotoxin" because of its ability to kill Vero cells in culture. Shortly after, the verotoxin was referred to as Shiga-like toxin because of its similarities to Shiga toxin, it has been suggested by some researchers that the gene coding for Shiga-like toxin comes from a toxin-converting lambdoid bacteriophage, such as H-19B or 933W, inserted into the bacteria's chromosome via transduction. Phylogenetic studies of the diversity of E. coli suggest that it may have been easy for Shiga toxin to transduce into certain strains of E. coli, because Shigella is itself a subgenus of Escherichia. Being closer relatives of Shigella dysenteriae than of the typical E. coli, it is not at all unusual that toxins similar to that of S. dysenteriae are produced by these strains.

As microbiology advances, the historical variation in nomenclature is giving way to recognizing all of these molecules as "versions of the same toxin" rather than "different toxins." The toxin requires specific receptors on the cells' surface in order to attach and enter the cell. Symptoms of Shiga toxin ingestion include abdominal pain as well as watery diarrhea. Severe life-threatening cases are characterized by hemorrhagic colitis; the toxin is associated with hemolytic-uremic syndrome. The toxin is effective against small blood vessels, such as found in the digestive tract, the kidney, lungs, but not against large vessels such as the arteries or major veins. A specific target for the toxin appears to the vascular endothelium of the glomerulus; this is the filtering structure, a key to the function of the kidney. Destroying these structures leads to kidney failure and the development of the deadly and debilitating hemolytic uremic syndrome. Food poisoning with Shiga toxin also has effects on the lungs and the nervous system.

The B subunits of the toxin bind to a component of the cell membrane known as glycolipid globotriaosylceramide. Binding of the subunit B to Gb3 causes induction of narrow tubular membrane invaginations, which drives formation of inward membrane tubules for the bacterial uptake into the cell; these tubules are essential for uptake into the host cell. The Shiga toxin is transferred to the cytosol via Golgi network and ER. From the Golgi toxin is trafficked to the ER. Shiga toxins act to inhibit protein synthesis within target cells by a mechanism similar to that of ricin. After entering a cell via a macropinosome, the protein cleaves a specific adenine nucleobase from the 28S RNA of the 60S subunit of the ribosome, thereby halting protein synthesis; as they act on the lining of the blood vessels, the vascular endothelium, a breakdown of the lining and hemorrhage occurs. The first response is a bloody diarrhea; this is because Shiga toxin is taken in with contaminated food or water. The bacterial Shiga toxin can be used for targeted therapy of gastric cancer, because this tumor entity expresses the receptor of the Shiga toxin.

For this purpose an unspecific chemotherapeutical is conjugated to the B-subunit to make it specific. In this way only the tumor cells, but not healthy cells, are destroyed during therapy; the toxin is one of the AB5 toxins. The B subunit is a pentamer that binds to specific glycolipids on the host cell globotriaosylceramide. Following this, the A subunit is cleaved into two parts; the A1 component binds to the ribosome, disrupting protein synthesis. Stx-2 has been found to be about 400 times more toxic than Stx-1. Gb3 is, for unknown reasons, present in greater amounts in renal epithelial tissues, to which the renal toxicity of Shiga toxin may be attributed. Gb3 is found in central nervous system neurons and endothelium, which may lead to neurotoxicity. Stx-2 is known to