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Drs. John and Ford reported in biomedicines that a variant transcript encoding receptor tyrosine kinase-like orphan receptor 1 (ROR1), namely ENST00000545203 or variant 3 (ROR1V3), was a predominant ROR1 transcript of neoplastic or normal cells in the Bioinformatic database, including GTEx and the 33 datasets from TCGA. Unlike the full-length ROR1 transcript, Drs. John and Ford deduced that ROR1V3 encoded a cytoplasmic ROR1 protein lacking an apparent signal peptide necessary for transport to the cell surface, which they presumed made it unlikely to function as a surface receptor for Wingless/Integrated (Wnt) factors. Moreover, they speculated that studies evaluating ROR1 via immunohistochemistry using any one of several anti-ROR1 mAbs actually may have detected cytoplasmic protein encoded by ROR1V3 and that anti-cancer therapies targeting surface ROR1 thus would be ineffective against "cytoplasmic ROR1-positive" cancers that express predominately ROR1V3. We generated lentivirus vectors driving the expression of full-length ROR1 or the ROR1v3 upstream of an internal ribosome entry site (IRES) of the gene encoding a red fluorescent reporter protein. Although we find that cells that express ROR1 have surface and cytoplasmic ROR1 protein, cells that express ROR1v3 neither have surface nor cytoplasmic ROR1, which is consistent with our finding that ROR1v3 lacks an in-frame initiation codon for ribosomal translation into protein. We conclude that the detection of ROR1 protein in various cancers cannot be ascribed to the expression of ROR1v3.
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INTRODUCTION: Recent evidence suggests that resistance training (RT) may reduce metabolic and cardiovascular disease risk. We investigated whether overweight/class I obese individuals by BMI classification with high strength fitness exhibit cardiovascular/metabolic phenotypes similar to those overweight/obese and untrained or those normal-weight with high strength fitness. METHODS: A total of 90 young males were categorized into three groups: overweight untrained (OU, n = 30, BMI > 27 kg·m⻲), overweight trained (OT, n = 30, BMI > 27 kg·m⻲, RT ≥ 4 d·wk⻹), and normal-weight trained (NT, n = 30, BMI < 25 kg·m⻲, RT ≥ 4 d·wk⻹). Participants were assessed for strength, body composition, central/peripheral blood pressures, arterial stiffness, and markers of cardiovascular and metabolic health. RESULTS: Body weight was similar in OT and OU and greater than NT (P < 0.00001), and fat mass was different in all groups (P < 0.001). Compared to OU, NT and OT groups exhibited higher relative strength (NT = 46.7%, OT = 44.4%, P < 0.00001), subendocardial viability ratio (NT = 21.0%, P < 0.001; OT = 17.0%, P < 0.01), and lower brachial/central blood pressures (NT P < 0.001; OT P ≤ 0.05); augmentation index and pulse-wave velocity were lower only in OT (P < 0.05). Total cholesterol, low-density lipoprotein (NT P < 0.01, OT P < 0.05), triglycerides (NT = -50.4%, OT = -41.8%, P < 0.001), oxidized LDL (NT = -39.8%, OT = -31.8%, P < 0.001), and CRP (NT = -63.7%, OT = -67.4%, P < 0.01) levels were lower and high-density lipoprotein (NT = 26.9%, OT = 21.4%, P < 0.001) levels were higher in NT and OT compared to OU. NT and OT also exhibited lower amylin (NT = -55.8%, OT = -40.8%) and leptin (NT = -84.6%, OT = -59.4%) and higher adiponectin (NT = 87.5%, P < 0.001; OT = 78.1%, P < 0.01) and sex hormone-binding globulin (NT = 124.4%, OT = 92.3%, P < 0.001). Despite greater total and trunk fat in OT compared with NT, other than glucose and insulin, which were lower in NT than in both OT and OU (OT P < 0.01, OU P < 0.001), OT did not exhibit any impaired biomarker/phenotype compared to NT. CONCLUSIONS: These findings provide evidence that overweight/class I obese individuals with high strength fitness exhibit metabolic/cardiovascular risk profiles similar to normal-weight, fit individuals rather than overweight/class I obese unfit individuals. Strength training may be important to metabolic and cardiovascular health.