In addition, retrograde transport serves a quality control function, by shuttling misfolded proteins back into the ER or retaining them within the Golgi itself until proper protein folding and maturation is completed. The activity of protein-modifying enzymes, like glycosyltransferases and glycosidases, relies on the lumenal pH of the Golgi apparatus. Cisternal pH becomes increasingly acidic (lower pH) with progression from cis- to trans- regions of the Golgi. Disruption of decreasing pH can impart significant effects on the efficiency and sequence of glycosylation events. Maintenance of the pH gradient across the Golgi is instrumental for proper post-translational modification of proteins prior to secretion. Retrograde transport and pH regulation are therefore vital to the proper functioning of the Golgi apparatus. Genetic causes of WSS
Patients with both missense and/or nonsense mutations of the ATP6V0A2 gene have been shown to phenotypically express wrinkly skin syndrome (WSS) or autosomal recessive cutis laxa type II (ARCL II) (another cutis laxa disorder). Some consider WSS to be a milder variant of ARCL II, but the genetic causes of WSS are not yet known. A large number of patients with WSS and ARCL II show a loss-of-function in the a2-subunit. These mutations in ATP6V0A2 are associated with defective glycan biosynthesis and defective Golgi apparatus structure. However, the exact mechanism of how mutations in the ATP6V0A2 gene lead to these effects is unclear. Aberrant Golgi functioning and clinical symptoms of WSS
WSS is characterized by defects in the elastic fiber system that comprises the extracellular matrix of epidermal cells.
Normocytic anemia is a type of anemia and is a common issue that occurs for men and women typically over 85 years old. Its prevalence increases with age, reaching 44 percent in men older than 85 years. The most common type of normocytic anemia is anemia of chronic disease. Classification
A normocytic anemia is when the red blood cells (RBCs) are of normal size. Normocytic anemia is defined when the mean corpuscular volume (MCV) is between 80 and 100 femtolitres (fL), which is within the normal and expected range. However, the hematocrit and hemoglobin are decreased. In contrast, microcytic anemias are defined as an anemia with a mean corpuscular volume (MCV) less than 80 fL and macrocytic anemias have a mean corpuscular volume over 100 fL. Diagnosis
To aid with determining the underlying cause of the normocytic anemia, a lab test is done on reticulocyte count. A reticulocyte count that is high, normal or low will aid with the classification process. A high reticulocyte count signifies that bone marrow processes are normal. A low reticulocyte count would signify there is a problem at the level of the bone marrow, which produce the stem cells. Acute blood loss would result in a high reticulocyte count, as bone marrow processes are normal and the bone marrow responds accordingly to the bodys need for blood.