Another-regulin regulates cardiomyocyte calcium handling via integration of neuroendocrine signaling with SERCA2a activity.

Calcium (Ca) dysregulation is a hallmark feature of cardiovascular disease. Intracellular Ca regulation is essential for proper heart function and is controlled by the sarco/endoplasmic reticulum Ca ATPase (SERCA2a). Another-regulin (ALN) is a newly discovered cardiomyocyte-expressed SERCA2a inhibitor, suggesting cardiomyocyte Ca-handling is more complex than previously appreciated.

Microproteins: Overlooked regulators of physiology and disease.

Ongoing efforts to generate a complete and accurate annotation of the genome have revealed a significant blind spot for small proteins (<100 amino acids) originating from short open reading frames (sORFs). The recent discovery of numerous sORF-encoded proteins, termed microproteins, that play diverse roles in critical cellular processes has ignited the field of microprotein biology. Large-scale efforts are currently underway to identify sORF-encoded microproteins in diverse cell-types and tissues and specialized methods and tools have been developed to aid in their discovery, validation, and functional characterization.

An Integrated Approach for Microprotein Identification and Sequence Analysis.

Next-generation sequencing (NGS) has propelled the field of genomics forward and produced whole genome sequences for numerous animal species and model organisms. However, despite this wealth of sequence information, comprehensive gene annotation efforts have proven challenging, especially for small proteins. Notably, conventional protein annotation methods were designed to intentionally exclude putative proteins encoded by short open reading frames (sORFs) less than 300 nucleotides in length to filter out the exponentially higher number of spurious noncoding sORFs throughout the genome.

Bone Morphogenetic Protein Signaling Is Required for Aortic Valve Calcification.

Objective: Calcific aortic valve disease (CAVD) is the most prevalent type of heart valve disease, affecting ≈2% of the US population. CAVD is characterized by the presence of calcific nodules, resulting in aortic valve (AoV) stenosis; however, the underlying mechanisms driving disease remain unknown. Studies of human diseased AoV provide initial evidence that bone morphogenetic protein (BMP) signaling, essential for normal bone formation, is activated during CAVD.