Striking a Chord: Dementia and Song

We have co-written this piece to relay what can be achieved with song and music in familial and non-familial settings when caring for a person with dementia. This article started as a conversation we had in the Wellcome Collection cafe in London to catch up with each other while Prabhjot was en route from Canada to India, to meet her father. We shared how dementia was becoming a part of our parents’ lives. This article is dedicated to the chords Prabhjot Parmar has struck with her father, Major Harbhajan Singh (25 Dec 1925 – 16 April 2018) and Nirmal Puwar has had the pleasure of sharing with her mother, Kartar Kaur. Both of us have been drawn to understanding how our own performance of song with our respective parent enabled them and us to maintain a register of connection. Song became a means of trying to keep striking a parental and musical chord. We aimed to connect by engendering ‘therapeutic atmospheres’ (Sonntag 2016) through song. We use song and music interchangeably, operating with performance as an umbrella term that includes gesture, utterance, dance, singing and playing musical instruments, for example. Two autoethnographic relational contributions provide a substantive basis to our article, each written by a researcher-carer-daughter, seeking to sustain contact with what remains in her parent living with dementia

Piper longum Linn. Extract inhibits TNF-α-induced expression of cell adhesion molecules by inhibiting NF-κB activation and microsomal lipid peroxidation

Recruitment of specific leukocyte subpopulations at the site of inflammation requires a series of cell adhesion molecule (CAM)-mediated interactions. The major CAMs, viz., intercellular adhesion molecule-1 (ICAM-1), VCAM-1 and E-selectin are expressed on endothelium in response to various cytokines or bacterial LPS. Here, we have evaluated the effect of Piper longum chloroform extract (PlCE) on TNF-α-induced expression of ICAM-1 on endothelial cells and on NADPH-catalyzed rat liver microsomal lipid peroxidation with a view to identify modulators for the expression of CAMs. We demonstrate that PlCE inhibits adhesion of neutrophils to endothelial monolayer. This inhibition is due to the ability of PlCE to significantly block the TNF-α-induced expression of CAMs, i.e. ICAM-1, VCAM-1 at 17.5 μg/ml concentration and E-selectin at 15 µg/ml concentration on human umbilical vein endothelial cells. The inhibition of ICAM-1, VCAM-1 and E-selectin by PlCE is mediated through inhibition of NF-κB in endothelial cells. To demonstrate the antioxidant activity of PlCE, we showed that PlCE inhibited the NADPH-catalyzed rat liver microsomal lipid peroxidation significantly. These results suggest a possible mechanism of anti-inflammatory as well as antioxidant activity of PlCE

Comparison of Protein Acetyltransferase Action of CRTAase with the Prototypes of HAT

Our laboratory is credited for the discovery of enzymatic acetylation of protein, a phenomenon unknown till we identified an enzyme termed acetoxy drug: protein transacetylase (TAase), catalyzing the transfer of acetyl group from polyphenolic acetates to receptor proteins (RP). Later, TAase was identified as calreticulin (CR), an endoplasmic reticulum luminal protein. CR was termed calreticulin transacetylase (CRTAase). Our persistent study revealed that CR like other families of histone acetyltransferases (HATs) such as p300, Rtt109, PCAF, and ESA1, undergoes autoacetylation. The autoacetylated CR was characterized as a stable intermediate in CRTAase catalyzed protein acetylation, and similar was the case with ESA1. The autoacetylation of CR like that of HATs was found to enhance protein-protein interaction. CR like HAT-1, CBP, and p300 mediated the acylation of RP utilizing acetyl CoA and propionyl CoA as the substrates. The similarities between CRTAase and HATs in mediating protein acylation are highlighted in this review

Comparison of Protein Acetyltransferase Action of CRTAase with the Prototypes of HAT

Our laboratory is credited for the discovery of enzymatic acetylation of protein, a phenomenon unknown till we identified an enzyme termed acetoxy drug: protein transacetylase (TAase), catalyzing the transfer of acetyl group from polyphenolic acetates to receptor proteins (RP). Later, TAase was identified as calreticulin (CR), an endoplasmic reticulum luminal protein. CR was termed calreticulin transacetylase (CRTAase). Our persistent study revealed that CR like other families of histone acetyltransferases (HATs) such as p300, Rtt109, PCAF, and ESA1, undergoes autoacetylation. The autoacetylated CR was characterized as a stable intermediate in CRTAase catalyzed protein acetylation, and similar was the case with ESA1. The autoacetylation of CR like that of HATs was found to enhance protein-protein interaction. CR like HAT-1, CBP, and p300 mediated the acylation of RP utilizing acetyl CoA and propionyl CoA as the substrates. The similarities between CRTAase and HATs in mediating protein acylation are highlighted in this review

Comparison of Protein Acetyltransferase Action of CRTAase with the Prototypes of HAT

Our laboratory is credited for the discovery of enzymatic acetylation of protein, a phenomenon unknown till we identified an enzyme termed acetoxy drug: protein transacetylase (TAase), catalyzing the transfer of acetyl group from polyphenolic acetates to receptor proteins (RP). Later, TAase was identified as calreticulin (CR), an endoplasmic reticulum luminal protein. CR was termed calreticulin transacetylase (CRTAase). Our persistent study revealed that CR like other families of histone acetyltransferases (HATs) such as p300, Rtt109, PCAF, and ESA1, undergoes autoacetylation. The autoacetylated CR was characterized as a stable intermediate in CRTAase catalyzed protein acetylation, and similar was the case with ESA1. The autoacetylation of CR like that of HATs was found to enhance protein-protein interaction. CR like HAT-1, CBP, and p300 mediated the acylation of RP utilizing acetyl CoA and propionyl CoA as the substrates. The similarities between CRTAase and HATs in mediating protein acylation are highlighted in this review

Autoacetylation of Purified Calreticulin Transacetylase Utilizing Acetoxycoumarin as the Acetyl Group Donor

Our earlier reports documented that calreticulin, a multifunctional Ca(2+)-binding protein in endoplasmic reticulum lumen, possessed protein acetyltransferase function termed Calreticulin Transacetylase (CRTAase). The autoacetylation of purified human placental CRTAase concomitant with the acetylation of receptor proteins by a model acetoxycoumarin, 7,8-Diacetoxy-4-methylcoumarin, was observed. Here, we have examined the autoacetylation property of CRTAase by immunoblotting and mass spectrometry. Ca(2+) was found to inhibit CRTAase activity. The inhibition of both autoacetylation of CRTAase as well as acetylation of the receptor protein was apparent when Ca(2+) was included in the reaction mixture as visualized by interaction with anti-acetyl lysine antibody. The acetylation of lysines residues: -48, -62, -64, -153, and -159 in N-domain and -206, -207, -209, and -238 in P-domain of CRTAase were located by high-performance liquid chromatography-electronspray ionization tandem mass spectrometry. Further, computer assisted protein structure modeling studies were undertaken to probe the effect of autoacetylation of CRTAase. Accordingly, the predicted CRTAase 3D model showed that all the loop regions of both N- and P-domain bear the acetylated lysines. Energy minimization of the acetylated residues revealed charge neutralization of lysines due to the N-epsilon-acetylation which may facilitate the interaction of CRTAase with the protein substrate and the subsequent transacetylase action