Calpain 3, the "gatekeeper" of proper sarcomere assembly, turnover and maintenance.

Calpain 3 is a member of the calpain family of calcium-dependent intracellular proteases. Thirteen years ago it was discovered that mutations in calpain 3 (CAPN3) result in an autosomal recessive and progressive form of limb girdle muscular dystrophy called limb girdle muscular dystrophy type 2A. While calpain 3 mRNA is expressed at high levels in muscle and appears to have some role in developmental processes, muscles of patients and mice lacking calpain 3 still form apparently normal muscle during prenatal development; thus, a functional calpain 3 protease is not mandatory for muscle to form in vivo but it is a pre-requisite for muscle to remain healthy. Despite intensive research in this field, the physiological substrates of the calpain 3 protein (hereafter referred to as CAPN3) and its alternatively spliced isoforms remain elusive. The existence of these multiple isoforms complicates the search for the physiological functions of CAPN3 and its pathophysiological role. In this review, we summarize the genetic and biochemical evidence that point to loss of function of the full-length isoform of CAPN3, also known as p94, as the pathogenic isoform. We also argue that its natural substrates must reside in its proximity within the sarcomere where it is stored in an inactive state anchored to titin. We further propose that CAPN3 has many attributes that make it ideally suited as a sensor of sarcomeric integrity and function, involved in its repair and maintenance. Loss of these CAPN3-mediated activities can explain the "progressive" development of muscular dystrophy.

Histoire militaire de la France de 1643 à 1871 / par Emile Simond,...

Collection : Petite Bibliothèque de l'armée française ; 2, 1-2

Laws of the territory of Iowa passed at the extra session of the legislative assembly : begun and held in the city of Burlington on the first Monday in July in the year of our Lord one thousand eight hundred and forty. 1840

The extra session of the 1840 legislative assembly listing all of the territorial laws of Iowa. The dates of approval of the acts are listed after each one and a brief index is included. This is the 1902 reprint by the Historical Department of Iowa.

Condition of the State of Iowa, 1888 (22nd General Assembly)

A transcript of the Condition of the State of Iowa speech by Governor Larrabee delivered at the State Capitol.

Condition of the State of Iowa, 1902 (29nd General Assembly)

A transcript of the Condition of the State of Iowa speech by Governor Shaw delivered at the State Capitol.

Condition of the State of Iowa, 1904 (30th General Assembly)

A transcript of the Condition of the State of Iowa speech by Governor Cummins delivered at the State Capitol.

Condition of the State of Iowa, 1906 (31st General Assembly)

A transcript of the Condition of the State of Iowa speech by Governor Cummins delivered at the State Capitol.

Condition of the State of Iowa, 1923 (40th General Assembly)

A transcript of the Condition of the State of Iowa speech by Governor Kendall delivered at the State Capitol.

Condition of the State of Iowa, 1927 (42nd General Assembly)

A transcript of the Condition of the State of Iowa speech by Governor Hammill delivered at the State Capitol.

Condition of the State of Iowa, 1929 (43rd General Assembly)

A transcript of the Condition of the State of Iowa speech by Governor Hammill delivered at the State Capitol.

Condition of the State of Iowa, 1931 (44th General Assembly)

A transcript of the Condition of the State of Iowa speech by Governor Hammill delivered at the State Capitol.

Condition of the State of Iowa, 1933 (45th General Assembly)

A transcript of the Condition of the State of Iowa speech by Governor Turner delivered at the State Capitol.

Condition of the State of Iowa, 1935 (46th General Assembly)

A transcript of the Condition of the State of Iowa speech by Governor Herring delivered at the State Capitol.

Condition of the State of Iowa, 1937 (47th General Assembly)

A transcript of the Condition of the State of Iowa speech by Governor Herring delivered at the State Capitol.

Condition of the State of Iowa, 1939 (48th General Assembly)

A transcript of the Condition of the State of Iowa speech by Governor Kraschel delivered at the State Capitol.