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The clinical and follow-up data on 520 non-diabetic patients less than 60 years of age who had a clinical diagnosis of arteriosclerosis obliterans of the lower extremities made at the Mayo Clinic in the period 1939 through 1948 were reviewed from the standpoint of pathogenesis, prognosis, and clinical course of the disease. The ratio of males to females was 11 to 1, and the mean concentration of plasma cholesterol in the male patients with arteriosclerosis obliterans was approximately 50 mg. per 100 ml. greater than that of either of 2 control groups of men without clinical evidence of atherosclerosis. The incidence of smoking among the men with this disease was higher than in a comparable group of men without it. Obesity was not commonly associated with arteriosclerosis obliterans, while hypertension was associated with the disease about 3 times as often as in a control group without the disease. The survival rate for patients with arteriosclerosis obliterans was less favorable than that of a normal population of a similar age and sex distribution, and the survival rate for patients with atherosclerotic aorto-iliac occlusion was significantly less favorable than that of patients with atherosclerotic occlusion of the femoral artery. In approximately three fourths of the patients who died, the cause of death was thought to be disease of the coronary arteries. The presence of atherosclerosis elsewhere than in the arteries supplying the extremities, as manifested by clinical coronary artery or cerebrovascular disease at the time of diagnosis, had an adverse effect on survival. Four per cent of the patients required amputation of a leg shortly after the diagnosis of arteriosclerosis obliterans was made at the clinic, and an additional 4.9 per cent subsequently required amputation during the 5-year period following the initial examination. Only 3.0 per cent of patients with intermittent claudication as the only symptom of their disease required an amputation during this period. Eleven and three-tenths per cent of patients who continued to smoke, but none who abstained from smoking, had amputations within 5 years. Since all patients of the series were treated before the advent of direct arterial surgery for segmental arterial occlusion, it is believed that the subsequent course of the disease in these patients may be used as a basis for comparative evaluation of results in patients subjected to direct arterial surgical procedures.

SummaryCLASP2 is a microtubule-associated protein that undergoes insulin-stimulated phosphorylation and co-localization with reorganized actin and GLUT4 at the plasma membrane.To gain insight to the role of CLASP2 in this system, we developed and successfully executed a streamlined interactome approach and built a CLASP2 protein network in 3T3-L1 adipocytes.Using two different commercially available antibodies for CLASP2 and an antibody for epitopetagged, overexpressed CLASP2, we performed multiple affinity purification coupled with mass spectrometry (AP-MS) experiments in combination with label-free quantitative proteomics and analyzed the data with the bioinformatics tool Significance Analysis of Interactome (SAINT). We discovered that CLASP2 co-immunoprecipitates (co-IPs) the novel protein SOGA1, the microtubule-associated protein kinase MARK2, and the microtubule/actin-regulating protein G2L1. The GTPase-activating proteins AGAP1 and AGAP3 were also enriched in the CLASP2 interactome, although subsequent AGAP3 and CLIP2 interactome analysis suggests a preference of AGAP3 for CLIP2. Follow-up MARK2 interactome analysis confirmed reciprocal co-IP of CLASP2 and also revealed MARK2 can co-IP SOGA1, glycogen synthase, and glycogenin.Investigating the SOGA1 interactome confirmed SOGA1 can reciprocal co-IP both CLASP2 and MARK2 as well as glycogen synthase and glycogenin. SOGA1 was confirmed to colocalize with CLASP2 and also with tubulin, which identifies SOGA1 as a new microtubule-associated protein.These results introduce the metabolic function of these proposed novel protein networks and their relationship with microtubules as new fields of cytoskeleton-associated protein biology. 5

The abbreviations used are: +TIP Plus-end tracking microtubule-associated protein AcK40 -tubulin lysine 40 acetylation AGAP3 Arf-GAP with GTPase, ANK repeat, and PH domain-containing protein 3 ANK ankyrin AP-MS affinity purification coupled with mass spectrometry BAS basal CAP-Gly cytoskeleton-associated protein Gly-rich CKAP5 cytoskeleton-associated protein 5 CLASP1 CLIP-associating protein 1 CLASP2 CLIP-associating protein 2 CLIP1/CLIP-170 CAP-Gly domain-containing linker protein 1 CLIP2/CLIP-115 CAP-Gly domain-containing linker protein 2 co-IP(s) co-immunoprecipitation(s) CTCF corrected total cell fluorescence CTRL control EB1 end binding protein 1 EB3 end binding protein 3

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