The Region of Punjab: A Sufi Perspective With Particular Focus on Chishtiya Sufism

Medieval Punjab was amongst the first regions of South Asia to encounter the substantial impact of early Sufi mystics. This article aims to investigate the history of the Punjab from a Sufi perspective with particular focus on Chishtiya Sufism and its generous role in diverting the local community center of attention. For that, the prominent Chishti Sufi Dargahs of Baba Farid Ganj Shaker in Pakpattan is selected. The study tries to investigate Dargahs’ impact on the socio-cultural and religious set up of the Medieval Punjab. How did it influence another important religion of the region i.e. Sikh belief, paper tried to highlight this impact as well.

Computational Dynamics of Chemotherapy Induced Cognitive Dysfunction

Chemotherapy is the mainstay treatment option for clinical cancer management. The treatment however brings myriad of signs and symtoms one of which include cognitive dysfunction also known as chemobrain. Human cognitive tasks are primarily conducted by hippocampal neurons in brain. The process of cognition primarily involved learning and memory by synaptic plasticity. This plasticity is structured by the process of long term potentiation (LTP). Proteins involved in LTP can be affected by chemotherapy leading to chemobrain. This work involves computational study of molecular interactions mediated by various chemotherapeutic drugs on LTP. Moreover, the study secondarily involves characterization of immediate early gene NPAS4 activated by LTP and identification of its dimerization characterstics by MD simulation. This precedes a computational assessment of 65 chemotherapeutic drugs for their off-target interactions against the major proteins involved in neuronal long term potentiation pathway. The cancer chemo-drugs were subjected to induced-fit docking followed by scoring alignment and drug-targets interaction analysis. The results were further probed by electrostatic potential computation and ligand binding affinity prediction of the top complexes. The study identified novel off-target interactions by Dactinomycin, Temsirolimus, and Everolimus against NMDA, AMPA, PKA and ERK2, while Irinotecan, Bromocriptine and Dasatinib were top interacting drugs for CaMKII. Secondarily this work presents the structural characterization of NPAS4 which is a neurological stimulation dependent transcription factor, accountable for adjusting the verbalization of genes tangled in neurotransmission. Although NPAS4 role has been implicated in various neurological deficits, details about its tertiary structure are scarcely available. Therefore, we executed the Phylogenetic analysis followed by determination of order-disorder proportion of amino acids with hydrophobic and flexible characteristics. As no cytsallized structure of NPAS4 available till date, we also studied its crystallization propensity alongwith post translational modifications and protein binding areas. The NPAS4 3 dimensional model was predicted via utilization of various methods such as MUSTER, LOMET, RAPTOR-X, Phyre, ITASSER and SPARSKS-X. The best model was opted via the analysis of Q-Mean, Ramachandran Plot and PROSA. The opted model then underwent refinement via MODREFINER. Lastly, the NPAS4 interaction partners were determined via STRING database. The phylogenetic analysis of human NPAS4 gene suggested close resemblance with other primates like gibbons, chimpanzees and monkey. The phsysicohemical characteristics of NPAS4 demonstrated it to be an intrinsically disordered protein withordered region on N-terminal. The post translational modification inquiry suggested lack of acetylation and mannosylation sites. The PAS-A domain constituted 3 potential phosphorylation sites while the PAS-B domain harbored 1 phosphorylation site. The estimated NPAS4 tertiary structure suggested bHLH and PAS domain harbor tertiary structure whilst the rest of the protein relected disorder property. The protein protein interaction scrutiny unfolded NPAS4 interaction with numerous proteins engaged in nuclear transportation of protein to cytoplasm, neurodevelopmental pathologies and neuronal stimulation based gene transcription. Furthermore, the analysis also briefed direct involvement of protein involved in neuronal plasticity and survival. The present study can help in substantiating NPAS4 role in neuromodulation of cell signaling and survival pathways.