Understanding chromatin mechanisms involved in DNA damage and chemotherapeutic responses

One of the hallmarks of cancer is genomic instability driven by DNA damage. Cells respond to these genetic insults through chromatin-based mechanisms that repair the damage. Chromatin plays a pivotal role in protecting cells from genome and epigenome instability that drive cancer progression. Chromatin, a highly dynamic complex of DNA and proteins, undergoes structural and functional changes in response to cellular factors that are essential for replication, transcription, DNA damage responses (DDR) and repair. Chromatin structure and function are highly dependent on histone modifications. Histones are modified on distinct amino acids by post-translational modifications (PTMs). Delineating chromatin-regulated processes are fundamental for understanding the nuclear pathways that regulate access to, and protection of, our genetic and epigenetic information. The first part of my project focused on analyzing the contribution of a chromatin domain, the nucleosome acidic patch in regulating histone H2A/X ubiquitination and the DDR using in vitro and in vivo approaches. I established techniques to biochemically purify human recombinant histones and reconstituted nucleosome core particles (NCPs) containing WT or acidic patch mutant H2A/X for in vitro Ub assays with purified E3 ligases, RNF168 and RING1B/BMI1. Both E3s ubiquitinated H2A/X within WT NCPs but not mutant NCPs. Thus, this assay confirmed our hypothesis that the effect of the acidic patch mutation on H2AX/ H2Aub is direct and that it mediates site-specific ubiquitinations. I showed that the acidic patch interacting peptide LANA could compete with RNF168 and RING1B/BMI1 dependent H2AX/H2A Ub. In the second project, I tested how chromatin alters targeting of an anticancer drug using a cisplatin derivative that acts on the genome. I identified that cotreatment of cisplatin and the clinically approved drug Vorinostat/SAHA generated clusters of lesions that co-localized with translesion synthesis factors. However, I found that activated translesion synthesis no longer acted as a bypass mechanism but instead promoted apoptosis. These results demonstrated that pharmacological alterations of chromatin reprograms genome targeting with platinum drugs and, concomitantly, drug response. The third project for my thesis work involves functional analysis of the bromodomain containing TRIM proteins in DDR. These proteins belong to the bromodomain (BRD) family, which are the readers of PTM acetylation. I identified specific domains in TRIM24 required for its recruitment to damaged DNA and its dependency on other chromatin associated factors, namely, SUV39H1, KAT6B, TRIM28, TRIM33 that regulate TRIM24 dynamics in the context of DNA damage. I validated some interactors of TRIM24, TRIM28 and TRIM33 including the FACT and MCM complex. In summary, knowledge gained from these studies will help to understand how these BRD reader proteins promote the DDR within acetylated chromatin to preserve genome stability.Cellular and Molecular Biolog

Risks and benefits of two different entry techniques for laparoscopic gynecological surgeries

Background: Primary abdominal access still remains a challenge for laparoscopic surgery despite rapid advances. This study was conducted to prospectively analyse and compare risks and benefits of two different entry techniques namely, veress needle and direct trocar in laparoscopic gynaecological surgeries so as to obtain consensus on the optimal method to be followed to create pneumoperitoneum.Methods: This was a prospective randomized study conducted at Deen Dayal Upadhyay hospital, under Delhi government. During the period January 2014 to June 2016, 800 patients (20-65 years) operated laparoscopically by the same team of surgeons for various gynaecological conditions, were randomized in two groups: Veress needle group (VN) and Direct trocar group (DT). Each group comprised of 400 patients. Comparison of various parameters was done between the two groups.Results: Incidence of major complications in terms of visceral injuries was 0.75% (3/400) in DT group and nil in VN group. Open conversion rate (2/400 i. e. 0.5%) and number of attempts required to create pneumoperitoneum were also more in DT group. Failed access in previous surgery cases was 1.2% (1/38) in VN and 14.8% (4/27) in DT group. Incidence of port site bleeding (n=3) was also more in DT group. Although the incidence of minor complications such as extraperitoneal insufflations (n=5) and no. of failed access (n=6) were more in VN group, there was no incidence of any life-threatening complication.Conclusions: In our experience, there is clear evidence of advantage of using veress needle in preventing major complications. Veress needle is therefore safer, convenient and effective technique of creating pneumoperitoneum

Impact of Finite-Sized Aperture on the Performance of Differential Multihop DF-FSO Network

This paper investigates the differential binary modulation for decode-and-forward (DF) based relay-assisted free space optical (FSO) network under the effect of strong atmospheric turbulence together with misalignment error (ME). The atmospheric fading links experience K-distributed turbulence. First we derive novel closed form expression for average bit error rate (BER) and outage probability (OP) in terms of Meijer’s G function. Further, the OP of differential DF-FSO system with multiple relays is derived. We also analyze the asymptotic performance for the sake of getting the order of diversity and the coding gain. The power allotment term is utilized to examine the effect of different power allotment techniques on BER and OP. The simulation results have been used to validate the derived analytical results

A rare case of triplet heterotopic pregnancy with a live intrauterine and bilateral tubal ectopic

Heterotopic pregnancy (HP) is a condition characterized by the coexistence of an ectopic pregnancy (EP) with a viable intrauterine pregnancy (IUP). The occurrence of a triplet heterotopic pregnancy is an exceptionally rare medical condition. Hence, timely diagnosis and management are challenging, but essential to prevent mortality. Authors report the case of a young woman who presented with a heterotopic triplet pregnancy, after in-vitro fertilization (IVF), at 12 weeks of gestation. She had been misdiagnosed as a case of severe ovarian hyperstimulation syndrome but had a ruptured tubal ectopic on the right side and an unruptured ectopic on the left side. Both the ectopics were managed by performing an emergency laparotomy with bilateral salpingectomy. The live intrauterine pregnancy was continued till term with the delivery of a healthy baby. High clinical suspicion and timely treatment can preserve the intrauterine gestation thus, ensuring a successful outcome

INTERNATIONAL JOURNAL OF PHARMACY & LIFE SCIENCES Study of useful climbers of Fatehpur, Uttar Pradesh, India

Abstract The survey of angiospermic climbers from Fatehpur recorded total 42 species under 29 genera belonging to 15 families. Maximum number of 16 species were recorded for dicotyledonous family Cucurbitaceae followed by Fabaceae and Convolvulaceae each with 06 species. Climbers were both wild and ornamental. Climbers constitute a large and important sector of ornamental horticulture. They also play a vital role in medicine and agriculture while some were used as edibles. . Some climbers' combinly serve various purposes. Local people had a unique knowledge to cure various human ailments using these climbers

Endometrial stromal sarcoma together with leiomyosarcoma in a single patient: a rare case report

Uterine sarcomas are relatively rare tumors of mesodermal origin. The three most common histological variants of uterine sarcoma are Leiomyosarcomas, Endometrial stromal sarcomas, and Carcinosarcomas. It is extremely uncommon to find the 2 variants in a single patient. Given the rarity of these tumors there are limited reports in the literature referring to the clinical management and final outcome of these cases. Our patient was a 60 year old post-menopausal women presented in the opd with post-menopausal bleeding. Ultrasound report showed a fibroid of around 8 by 8 cm fundal fibroid. Endometrial biopsy report showed low grade endometrial sarcoma while the CECT report showed leiomyosarcoma creating a dilemma in the diagnosis. Patient was then taken up for surgical exploration. The biopsy report confirmed the existence of both the types of tumor, a very rare finding

Medicinal importance of underground plant parts from Fatehpur district, Uttar Pradesh, India

Abstract Medico botanical investigation on underground plant parts utilised by the inhabitants for their health care in Fatehpur district of Uttar Pradesh,India was conducted. A total of 15 plant species distributed to 13 families are documented for their therapeutic uses. Most of the species are in local distribution and few species were cultivated in gardens. The study revealed that the area is rich in indigenous knowledge about the medicinal uses of plants. However, it is getting eroded rapidly due to modern cultural changes

A rare case of abdominal lymphangioma masquerading an adenaxal mass

Lymphangioma is an uncommon benign tumour of the lymphatic system. It can be localized (spleen, liver or thorax) or generalized. An abdominal location is exceptional (5%) and majority of cases occur in early childhood and it rarely presents in adulthood. Retroperitoneal lymphangioma account for less than 1% of all lymphangiomas here we present a rare case of retroperitoneal lymphangioma and patient presented as adenaxal mass

Inset-FED microstrip patch antenna for glucose detection using label-free microwave sensing mechanism

In this work, a real-time label-free microwave sensing mechanism for glucose concentration monitoring using a planar biosensor configured with an inset fed microstrip patch antenna has been demonstrated. A microstrip patch antenna with the resonating frequency of 1.45 GHz has been designed and is fabricated on the Flame Retardant (FR-4) substrate. Due to the intense electromagnetic field at the edges of the patch antenna, edge length has been used as the detecting area where the sample under test (SUT) interacts with the electromagnetic field. The Poly-Dimethyl-Siloxane (PDMS) with the trench in the centre has been employed as the sample holder. Here, the SUT is the glucose dissolved in DI (de-ionized) water with the concentration range of 0.2 to 0.6 g/mL. The dielectric constant dependency on the glucose concentration has been used as the distinguishing factor which results in a shift in the S-parameter. The experimentally measured RF parameters were observed closely which showed the shift in S11 magnitude from –40 to –15 dB and resonant frequency from 1.27 to 1.3 GHz w.r.t the SUT solution of 0.2 to 0.6 g/mL with linear regression coefficient of 0.881, and 0.983 respectively

Concept of Pandu Roga in context with Dhatu and Sara

The tissue systems of the body, in the Ayurveda view consist of seven kind of basic tissues or SaptaDhatus. Dhatus (bodily tissue) are what their nutrition makes them and, on these depend the normal states of functioning of the body. Saptadhatus are produced in a kind of progressive evolutionary metamorphosis, beginning with Rasa Dhatu (primary product of digested food) followed by Rakta (blood tissue), Mamsa (muscle tissue), Meda (fat tissue), Asthi (bone tissue), Majja (bone marrow) and ending with Sukra Dhatu (reproductive fluids), the previous Dhatu nourishes the next higher, They act as the substratum for each other. The continuously depleting Dhatus are maintained in the state of equilibrium by the food. This implies that the Dhatus are interdependent on each other as the increase or decrease in one shall lead to the increase or decrease in the other. In the case of Pandu, the Rakta-Kshaya (reduction) is due to the diminution of the Rasa by the increased Pitta (Dosha responsible for maintaining metabolic activities) or the failure of the Rasa Dhatu to produce the Rakta Poshaka part, i.e. the part of Rasa which nourishes the Rakta Dhatu. Reduction in Rasa, Rakta cause diminution of progressive Dhatus, quality (Sara) and quantity (Dhatu Kshaya) wise, making an individual Nihsara (insipid) and Alpa (lessened) in Rakta and Medadi Dhatus. So, the main objective of the study is to appraise and explore the status of Dhatu and Sara in Pandu Roga