Anti-PARM1 monoclonal antibody, clone FQS21110

BackgroundProstate androgen-regulated mucin-like protein 1 (PARM1) is a pro-proliferative and anti-apoptotic glycoprotein involved in the endoplasmic reticulum (ER) stress response. A single nucleotide polymorphism in the coding region of PARM1 has been associated with competence of bovine embryos to develop to the blastocyst stage. Here we tested the importance of PARM1 for development by evaluating consequences of reducing PARM1 mRNA abundance on embryonic development and differentiation, gene expression and resistance to ER stress.ResultsKnockdown of PARM1 using an anti-PARM1 GapmeR did not affect competence of embryos to develop into blastocysts but decreased the number of trophectoderm (TE) cells in the blastocyst and tended to increase the number of cells in the blastocyst inner cell mass (ICM). Treatment of embryos with anti-PARM1 GapmeR affected expression of 4 and 3 of 90 genes evaluated at the compact-morula and blastocyst stage of development at days 5.5 and 7.5 after fertilization, respectively. In morulae, treatment increased expression of DAB2, INADL, and STAT3 and decreased expression of CCR2. At the blastocyst stage, knockdown of PARM1 increased expression of PECAM and TEAD4 and decreased expression of CCR7. The potential role of PARM1 in ER stress response was determined by evaluating effects of knockdown of PARM1 on development of embryos after exposure to heat shock or tunicamycin and on expression of ATF6, DDIT3 and EIF2AK3 at the compact morula and blastocyst stages. Both heat shock and tunicamycin reduced the percent of embryos becoming a blastocyst but response was unaffected by PARM1 knockdown. Similarly, there was no effect of knockdown on steady-state amounts of ATF6, DDIT3 or EIF2AK3.ConclusionPARM1 participates in formation of TE and ICM cells in early embryonic development but there is no evidence for the role of PARM1 in the ER stress response.

Soldiers regularly transport loads weighing >20 kg at slow speeds for long durations. These tasks elicit high energetic costs through increased positive work generated by knee and ankle muscles, which may increase risk of muscular fatigue and decrease combat readiness. This study aimed to determine how modifying where load is borne changes lower-limb joint mechanical work production, and if load magnitude and/or walking speed also affect work production. Twenty Australian soldiers participated, donning a total of 12 body armor variations: six different body armor systems (one standard-issue, two commercially available [cARM1-2], and three prototypes [pARM1-3]), each worn with two different load magnitudes (15 and 30 kg). For each armor variation, participants completed treadmill walking at two speeds (1.51 and 1.83 m/s). Three-dimensional motion capture and force plate data were acquired and used to estimate joint angles and moments from inverse kinematics and dynamics, respectively. Subsequently, hip, knee, and ankle joint work and power were computed and compared between armor types and walking speeds. Positive joint work over the stance phase significantly increased with walking speed and carried load, accompanied by 2.3-2.6% shifts in total positive work production from the ankle to the hip (p < 0.05). Compared to using cARM1 with 15 kg carried load, carrying 30 kg resulted in significantly greater hip contribution to total lower-limb positive work, while knee and ankle work decreased. Substantial increases in hip joint contributions to total lower-limb positive work that occur with increases in walking speed and load magnitude highlight the importance of hip musculature to load carriage walking. (C) 2018 Elsevier Ltd. All rights reserved.