Invited Mini Review : The diverse roles of RNA polymerase II C-terminal domain phosphatase SCP1

( Harikrishna Reddy R ),( Hackyoung Kim ),( Kwangmo Noh ),( Young Jun Kim ) 생화학분자생물학회(구 한국생화학분자생물학회) 2014 BMB Reports Vol.47 No.4

RNA polymerase II carboxyl-terminal domain (pol II CTD) phosphatases are a newly emerging family of phosphatases that are members of DXDX (T/V). The subfamily includes Small CTD phosphatases, like SCP1, SCP2, SCP3, TIMM50, HSPC129 and UBLCP. Extensive study of SCP1 has elicited the diversified roles of the small C terminal domain phosphatase. The SCP1 plays a vital role in various biological activities, like neuronal gene silencing and preferential Ser5 dephosphorylation, acts as a cardiac hypertrophy inducer with the help of its intronic miRNAs, and has shown a key role in cell cycle regulation. This short review offers an explanation of the mechanism of action of small CTD phosphatases, in different biological activities and metabolic processes. [BMB Reports 2014; 47(4): 192-196]

Peripheral Inhibition of Small C-Terminal Domain Phosphatase 1 With Napthoquinone Analogs

Harikrishna Reddy Rallabandi,이동선,Jinmo Sung,김영준 대한화학회 2020 Bulletin of the Korean Chemical Society Vol.41 No.6

Small C-terminal domain phosphatase 1(SCP1)'s biological function is significant in many cellular activities. Still, a recent study on neuroglioma cells emphasized the requirement of negative regulation of SCP1 in cancer invasion suppression. Due to the structural conservation of C-terminal domain (CTD) phosphatases, we aimed to determine the peripherally targeting inhibitors, which reciprocally bind to an eccentric site on SCP1 using a multidisciplinary approach. From biochemical screening, we have identified two potential inhibitors, which showed twofold to threefold selectivity toward SCP1 compared to Dullard. Dullard was utilized as a negative control as it is a small CTD phosphatase that contains structural similarities to SCP1. Besides, from in silico approaches like protein?ligand docking and molecular dynamics analyses, we have successfully discovered two allosteric inhibitors of napthoquinone family compounds explicitly binding to the unique hydrophobic pocket of SCP1 from 1000 molecular dockings and 125?ns of dynamics simulation studies, respectively.

Identification of Female Specific Genes in the W Chromosome that are Expressed during Gonadal Differentiation in the Chicken

Harikrishna Reddy Rallabandi,Hyeon Yang,Yong Jin Jo,Hwi-Cheul Lee,Sung June Byun,이보람 한국가금학회 2019 韓國家禽學會誌 Vol.46 No.4

Avian sex determination system involves the male ZZ and female ZW chromosomes. However, very few studies are reported the expression, functional role and importance of genes on the W chromosome because of its small and highly heterochromatic genomic regions. Recent studies demonstrated that the W chromosome may have critical roles in physiology, sex determination and subsequent sexual differentiation in chickens. Therefore, gene annotation, including describing the expression and function of genes in the chicken W chromosome, is needed. In this study, we have searched the W chromosome of chickens and selected a total of 36 genes to evaluated their specific expression in the testis and ovary at various developmental stages such as embryonic day 6 (E6), hatch and adult. Interestingly, out of 36 genes in chicken W chromosome, we have found seven female-specific expression at E6.5 day, indicating that they are functionally related to female chicken gonadal differentiation. In addition, we have identified the stage specific gene expression from the sex specific genes. Furthermore, we analyzed the relative location of genes in the chicken W chromosome. Collectively, these results will contribute molecular insights into the sexual determination, differentiation and female development based on the W chromosome.

Design and Implementation of Phase Locked Loop for Break-lock in Monopulse Receivers using Linear Frequency Modulation Interference Signal

Harikrishna Paik,N. N. Sastry,I. SantiPrabha 보안공학연구지원센터 2015 International Journal of Signal Processing, Image Vol.8 No.6

In this paper, the break-lock phenomenon of phase locked loop (PLL) in monopulse radar receiver for missile seeking applications is presented. The continuous wave radar echo and linear frequency modulated (LFM) interference signals are injected into the PLL simultaneously with an assumption that initially, the PLL locks on to the echo signal frequency. The PLL is assumed to be operating at an intermediate frequency (IF) of 50 MHz with a typical bandwidth of 200 kHz. The frequency deviation required to break-lock as a function of interference signal power and modulation rate is analyzed. The simulation results show that break-lock is achieved at a frequency deviation of 0.36 MHz for a typical LFM signal power of -14 dBm and 200 kHz modulation rate. The break-lock in the PLL is also estimated for selected values of LFM signal power and modulation rates, such as 300, 400 kHz, when the echo signal power at the PLL input is -10 and -14 dBm. The PLL with third order passive loop filter is modeled and designed using exact method. The computer simulation is carried out using visual system simulator (VSS) AWR software and potential conclusions are demonstrated.

β-Galactoside Prodrugs of Doxorubicin for Application in Antibody Directed Enzyme Prodrug Therapy/Prodrug MonoTherapy

HariKrishna Devalapally,Raghavendra Swamy Navath,Venkateshwarlu Yenamandra,RaghuRam Rao Akkinepally,Rama Krishna Devarakonda 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.6

Anthracycline antibiotics, particularly doxorubicin and daunorubicin, have been used extensively in the treatment of human malignancies. However cardiotoxicity and multidrug resistance are significant problems that limit the clinical efficacy of such agents. Rational design to avoid these side effects includes strategies such as drug targeting and prodrug synthesis. Described here are the synthesis and preliminary biological evaluation of the enzymatically activated two new prodrugs (6 & 11) of doxorubicin. These prodrugs were designed as potential candidates for selective chemotherapy in ADEPT or PMT strategies. They are constituted of a galactose moiety, a spacer and the cytotoxic drug and they differ by the type of spacer. The prodrugs were stable in a buffer, and the in vitro studies showed good detoxification and hydrolysis kinetics. As prodrug 11 was readily hydrolyzed, this could be a valuable candidate for further development.

(${\beta}$-Galactoside Prodrugs of Doxorubicin for Application in Antibody Directed Enzyme Prodrug Therapy/prodrug Mono Therapy

Devalapally, Harikrishna,Navath, Raghavendra Swamy,Yenamandra, Venkateshwarlu,Akkinepally, RaghuRam Rao,Devarakonda, Rama Krishna 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.6

Anthracycline antibiotics, particularly doxorubicin and daunorubicin, have been used extensively in the treatment of human malignancies. However cardiotoxicity and multidrug resistance are significant problems that limit the clinical efficacy of such agents. Rational design to avoid these side effects includes strategies such as drug targeting and prodrug synthesis. Described here are the synthesis and preliminary biological evaluation of the enzymatically activated two new prodrugs (6 & 11) of doxorubicin. These prodrugs were designed as potential candidates for selective chemotherapy in ADEPT or PMT strategies. They are constituted of a galactose moiety, a spacer and the cytotoxic drug and they differ by the type of spacer. The prodrugs were stable in a buffer, and the in vitro studies showed good detoxification and hydrolysis kinetics. As prodrug 11 was readily hydrolyzed, this could be a valuable candidate for further development.

Evaluation of Intestinal Epithelial Barrier Function in Inflammatory Bowel Diseases Using Murine Intestinal Organoids

Rallabandi Harikrishna Reddy,Yang Hyeon,Oh Keon Bong,Lee Hwi Cheul,변승준,이보람 한국조직공학과 재생의학회 2020 조직공학과 재생의학 Vol.17 No.5

Background: Intestinal organoids have evolved as potential molecular tools that could be used to study host-microbiome interactions, nutrient uptake, and drug screening. Gut epithelial barrier functions play a crucial role in health and diseases, especially in autoimmune diseases, such as inflammatory bowel diseases (IBDs), because they disrupt the epithelial mucosa and impair barrier function. Methods: In this study, we generated an in vitro IBD model based on dextran sodium sulfate (DSS) and intestinal organoids that could potentially be used to assess barrier integrity. Intestinal organoids were long-term cultivated and characterized with several specific markers, and the key functionality of paracellular permeability was determined using FITC-dextran 4 kDa. Intestinal organoids that had been treated with 2 µM DSS for 3 h were developed and the intestinal epithelial barrier function was sequentially evaluated. Results: The results indicated that the paracellular permeability represented epithelial characteristics and their barrier function had declined when they were exposed to FITC-dextran 4 kDa after DSS treatment. In addition, we analyzed the endogenous mRNA expression of pro-inflammatory cytokines and their downstream effector genes. The results demonstrated that the inflammatory cytokines genes significantly increased in inflamed organoids compared to the control, leading to epithelial barrier damage and dysfunction. Conclusion: The collective results showed that in vitro 3D organoids mimic in vivo tissue topology and functionality with minor limitations, and hence are helpful for testing disease models.

Structure-Based Virtual Screening of Protein Tyrosine Phosphatase Inhibitors: Significance, Challenges, and Solutions

( Rallabandi Harikrishna Reddy ),( Hackyoung Kim ),( Seungbin Cha ),( Bongsoo Lee ),( Young Jun Kim ) 한국미생물 · 생명공학회 2017 Journal of microbiology and biotechnology Vol.27 No.5

Phosphorylation, a critical mechanism in biological systems, is estimated to be indispensable for about 30% of key biological activities, such as cell cycle progression, migration, and division. It is synergistically balanced by kinases and phosphatases, and any deviation from this balance leads to disease conditions. Pathway or biological activity-based abnormalities in phosphorylation and the type of involved phosphatase influence the outcome, and cause diverse diseases ranging from diabetes, rheumatoid arthritis, and numerous cancers. Protein tyrosine phosphatases (PTPs) are of prime importance in the process of dephosphorylation and catalyze several biological functions. Abnormal PTP activities are reported to result in several human diseases. Consequently, there is an increased demand for potential PTP inhibitory small molecules. Several strategies in structure-based drug designing techniques for potential inhibitory small molecules of PTPs have been explored along with traditional drug designing methods in order to overcome the hurdles in PTP inhibitor discovery. In this review, we discuss druggable PTPs and structure-based virtual screening efforts for successful PTP inhibitor design.

Wind tunnel investigations on aerodynamics of a 2:1 rectangular section for various angles of wind incidence

Keerthana, M.,Harikrishna, P. Techno-Press 2017 Wind and Structures, An International Journal (WAS Vol.25 No.3

Multivariate fluctuating pressures acting on a 2:1 rectangular section (2-D) with dimensions of 9 cm by 4.5 cm has been studied using wind tunnel experiments under uniform and smooth flow condition for various angles of wind incidence. Based on the variation of mean pressure coefficient distributions along the circumference of the rectangular section with angle of wind incidence, and with the aid of skin friction coefficients, three distinct flow regimes with two transition regimes have been identified. Further, variations of mean drag and lift coefficients, Strouhal number with angles of wind incidence have been studied. The applicability of Universal Strouhal number based on vortex street similarity of wakes in bluff bodies to the 2:1 rectangular section has been studied for different angles of wind incidence. The spatio-temporal correlation features of the measured pressure data have been studied using Proper Orthogonal Decomposition (POD) technique. The contribution of individual POD modes to the aerodynamic force components, viz, drag and lift, have been studied. It has been demonstrated that individual POD modes can be associated to different physical phenomena, which contribute to the overall aerodynamic forces.

Segmentation Analysis of Domestic Tourists – A Case Study

Rajat Rastogi,Harikrishna M.,Ajit Patil 대한토목학회 2015 KSCE JOURNAL OF CIVIL ENGINEERING Vol.19 No.5

This paper presents the segmentation analysis of domestic leisure tourists in India. Samples were taken from visitors to 6 cities categorised by ‘leisure value’ and the population was further segmented based on ‘household income’ and ‘trip frequency’. Key salient features were substantial numbers of tourists belonging to middle-income group, and major share going to train. Logit analysis was carried out. NL structure was justified for seven categorisations out of nine. The proposed sub-categorisation was found to be significant and statically different then the parent population. Factors like household income, comfort and convenience of use of a travel mode, service levels in travel modes, budgetary constraints, presence of children and older persons in a family and affordability of travel mode were found to be influencing the leisure travel. Consideration set got influenced by user and destination connectivity. Frequency of travel was affected by economic affordability and status of the tourist. Value of travel time kept shifting judiciously across the sub-categories. The tourists valued their time highly if visiting spiritual locations or made less number of leisure trips in a year. Middle income group was found aspiring to avail higher facilities on leisure travel and was willing to pay more for the same. Policy initiatives are proposed based on the work. The approach is applicable to any city across the countries, which has either cultural, religious or waterfront value.