Characterizing the antibody response to amustaline/glutathione pathogen-reduced red blood cells.

Background: The clinical significance of natural and treatment-emergent antibodies specific for amustaline/glutathione pathogen-reduced red blood cells (PRRBCs) is not known.

Study Design And Methods: A Phase 3, randomized clinical trial of PRRBCs (ReCePI) compared PRRBCs with conventional RBCs in cardiac or thoracic-aorta surgery. Subjects transfused during and for 7 days after surgery were screened for PRRBC-specific antibodies at baseline, 28 and 75 days post-surgery.

Combined clinical, structural, and cellular studies discriminate pathogenic and benign TRPV4 variants.

Dominant mutations in the calcium-permeable ion channel TRPV4 (transient receptor potential vanilloid 4) cause diverse and largely distinct channelopathies, including inherited forms of neuromuscular disease, skeletal dysplasias, and arthropathy. Pathogenic TRPV4 mutations cause gain of ion channel function and toxicity that can be rescued by small molecule TRPV4 antagonists in cellular and animal models, suggesting that TRPV4 antagonism could be therapeutic for patients. Numerous variants in TRPV4 have been detected with targeted and whole exome/genome sequencing, but for the vast majority, their pathogenicity remains unclear.

PCA062, a P-cadherin Targeting Antibody-Drug Conjugate, Displays Potent Antitumor Activity Against P-cadherin-expressing Malignancies.

The cell surface glycoprotein P-cadherin is highly expressed in a number of malignancies, including those arising in the epithelium of the bladder, breast, esophagus, lung, and upper aerodigestive system. PCA062 is a P-cadherin specific antibody-drug conjugate that utilizes the clinically validated SMCC-DM1 linker payload to mediate potent cytotoxicity in cell lines expressing high levels of P-cadherin , while displaying no specific activity in P-cadherin-negative cell lines. High cell surface P-cadherin is necessary, but not sufficient, to mediate PCA062 cytotoxicity.

Sarcolipin Exhibits Abundant RNA Transcription and Minimal Protein Expression in Horse Gluteal Muscle.

Ca regulation in equine muscle is important for horse performance, yet little is known about this species-specific regulation. We reported recently that horse encode unique gene and protein sequences for the sarcoplasmic reticulum (SR) Ca-transporting ATPase (SERCA) and the regulatory subunit sarcolipin (SLN). Here we quantified gene transcription and protein expression of SERCA and its inhibitory peptides in horse gluteus, as compared to commonly-studied rabbit skeletal muscle.

Purification of sarcoplasmic reticulum vesicles from horse gluteal muscle.

We have analyzed protein expression and enzyme activity of the sarcoplasmic reticulum Ca-transporting ATPase (SERCA) in horse gluteal muscle. Horses exhibit a high incidence of recurrent exertional rhabdomyolysis, with myosolic Ca proposed, but yet to be established, as the underlying cause. To better assess Ca regulatory mechanisms, we developed an improved protocol for isolating sarcoplasmic reticulum (SR) vesicles from horse skeletal muscle, based on mechanical homogenization and optimized parameters for differential centrifugation.