Alpha decay chains study for the recently observed superheavy element Z=117 within the Isospin Cluster Model

The recently observed $\alpha$-decay chains $^{293-294}117$ were produced by the fusion reactions with target $^{249}Bk$ and projectile $^{48}Ca$ at Dubna in Russia. The reported cross-sections for the mentioned reaction are $\sigma=0.5(+1.1,-0.4)$pb and $\sigma$=1.3(+1.5,-0.6)$pb$ at $E^{*}=35MeV$ and $E^{*}=39MeV$, respectively. The Q-values of $\alpha$-decay and the half-lives $Log_{10}T^{\alpha}_{1/2}$(s) are calculated for the $\alpha$-decay chains of $^{293-294}117$ nuclei, within the framework of Isospin Cluster Model (ICM). In the ICM model the proximity energy is improved by using the isospin dependent radius of parent, daughter and alpha particle. The binding energy $B(A_{i}, Z_{i})$ (i=1,2) of any nucleus of mass number A and atomic number Z was obtained from a phenomenological and more genaralized BW formula given by \cite{samanta02}. The calculated results in ICM are compared with the experimental results and other theoretical Macro-Microscopic(M-M), RMF(with NL3 and SFU Gold forces parameter) model calculations. The estimated values of $\alpha$-decay half-lives are in good agreement with the recent data. The ICM calculation is in favor of the persence of magic number at N=172

ETHNO-BOTANICAL STUDY OF MEDICINAL PLANTS OF PADDAR VALLEY OF JAMMU AND KASHMIR, INDIA

The Paddar Valley, historically known as Sapphire Valley situated in Kishtwar district, is a prime landmark in the Jammu region of J&K state and is known for its rich cultural and plant diversity because of diverse habitats such as rivers, streams, meadows and steep mountain slopes. The area located in the dry temperate region comprising typical vegetation which disappears completely on the eastern slopes, dominated by a variety of economical species which play an important role in the rural life. The inhabitants are dependent on plant resources for food, fuel, timber, shelter, fodder/forage, household articles and traditional medicines in treating diseases like malaria, cancer, gastro-intestinal ailments, etc. This paper deals with the observations on traditional therapeutic application by the inhabitants of Paddar Valley. The ethno-botanical information on medicinal plants would not only be useful in conservation of traditional cultures and biodiversity but also community health care and drug development. Exploration survey in Paddar Valley has revealed that people collect and sell these medicinal species through local intermediaries / contractors to earn their livelihood. But the scientific cultivation and appropriate post-harvest management would improve employment opportunity and income of local farmers in the region

Bio-chemical amelioration effects on physico-chemical dynamics of sodic soils under rice (Oryza sativa) –wheat (Triticum aestivum) cropping system

The effect of dhaincha (Sesbania aculeata) as first crop on physico-chemical dynamics and productivity of “B” class sodic soils was assessed on farmer’s field under rice-wheat cropping system to generate the knowledge of sodic soil management for increasing the soil and crop productivity for sustainable crop production in sodic soil environment. The experiment was laid out in randomized block design at ten sites having six treatment combinations of different doses of gypsum and green manuring with sesbania under two cropping sequences, i e sesbania-rice (Oryza sativa L.) -wheat (Triticum aestivum L.) and rice-wheat. Cultivation of sesbania with gypsum significantly decreased the surface soil pH from 9.3 to 8.6 and increased the hydraulic conductivity from 0.3 × 10-3 to 3.7 × 10-3 cm/hr and buildup of soil organic matter by increasing organic carbon content from 0.20 % to 0.22 % through growing of sesbania. Sesbania green manure also increased the available water content in the soil system, which enhanced soil moisture availability for longer period. As a result, rice crop yield increased by 16.2 % in sesbania-rice- wheat cropping system in comparison to rice–wheat cropping sequence because of synergistic effect of sesbania with gypsum. Consequently, residual effect of sesbania green manuring alone and in combination with gypsum significantly enhanced the wheat grain yield by 42.5 % and 72.5 % and 80% in T4, T5 and T6 treatments respectively during first year in sesbania–rice-wheat cropping sequence as compared to control. In consecutive second year, rice and wheat grain yields further enhanced by 8.1 % and 2.71% respectively, under sesbania –rice -wheat than that of rice –wheat cropping sequence. Under sesbania- rice- wheat and rice-wheat-sesbania cropping sequence, rice and wheat grain yield were similar. Hence, inclusion of Sesbania aculeata as green manure either before or after rice-wheat cropping sequence is equally better to improve the soil physical dynamics and crop productivity of ‘B’ class sodic soils in Indo-Gangetic region of Uttar Pradesh

Monoclonal Antibodies Recognizing the Non-Tandem Repeat Regions of the Human Mucin MUC4 in Pancreatic Cancer

The MUC4 mucin is a high molecular weight, membrane-bound, and highly glycosylated protein. It is a multi-domain protein that is putatively cleaved into a large mucin-like subunit (MUC4α) and a C-terminal growth-factor like subunit (MUC4β). MUC4 plays critical roles in physiological and pathological conditions and is aberrantly overexpressed in several cancers, including those of the pancreas, cervix, breast and lung. It is also a potential biomarker for the diagnosis, prognosis and progression of several malignancies. Further, MUC4 plays diverse functional roles in cancer initiation and progression as evident from its involvement in oncogenic transformation, proliferation, inhibition of apoptosis, motility and invasion, and resistance to chemotherapy in human cancer cells. We have previously generated a monoclonal antibody 8G7, which is directed against the TR region of MUC4, and has been extensively used to study the expression of MUC4 in several malignancies. Here, we describe the generation of anti-MUC4 antibodies directed against the non-TR regions of MUC4. Recombinant glutathione-S-transferase (GST)-fused MUC4α fragments, both upstream (MUC4α-N-Ter) and downstream (MUC4α-C-Ter) of the TR domain, were used as immunogens to immunize BALB/c mice. Following cell fusion, hybridomas were screened using the aforementioned recombinant proteins ad lysates from human pancreatic cell lines. Three anti MUC4α-N-Ter and one anti-MUC4α-C-Ter antibodies were characterized by several inmmunoassays including enzyme-linked immunosorbent assay (ELISA), immunoblotting, immunofluorescene, flow cytometry and immunoprecipitation using MUC4 expressing human pancreatic cancer cell lines. The antibodies also reacted with the MUC4 in human pancreatic tumor sections in immunohistochemical analysis. The new domain-specific anti-MUC4 antibodies will serve as important reagents to study the structure-function relationship of MUC4 domains and for the development of MUC4-based diagnostics and therapeutics

Disruption of FDPS/Rac1 Axis Radiosensitizes Pancreatic Ductal Adenocarcinoma by Attenuating DNA Damage Response and Immunosuppressive Signalling

BACKGROUND: Radiation therapy (RT) has a suboptimal effect in patients with pancreatic ductal adenocarcinoma (PDAC) due to intrinsic and acquired radioresistance (RR). Comprehensive bioinformatics and microarray analysis revealed that cholesterol biosynthesis (CBS) is involved in the RR of PDAC. We now tested the inhibition of the CBS pathway enzyme, farnesyl diphosphate synthase (FDPS), by zoledronic acid (Zol) to enhance radiation and activate immune cells. METHODS: We investigated the role of FDPS in PDAC RR using the following methods: in vitro cell-based assay, immunohistochemistry, immunofluorescence, immunoblot, cell-based cholesterol assay, RNA sequencing, tumouroids (KPC-murine and PDAC patient-derived), orthotopic models, and PDAC patient\u27s clinical study. FINDINGS: FDPS overexpression in PDAC tissues and cells (P \u3c 0.01 and P \u3c 0.05) is associated with poor RT response and survival (P = 0.024). CRISPR/Cas9 and pharmacological inhibition (Zol) of FDPS in human and mouse syngeneic PDAC cells in conjunction with RT conferred higher PDAC radiosensitivity in vitro (P \u3c 0.05, P \u3c 0.01, and P \u3c 0.001) and in vivo (P \u3c 0.05). Interestingly, murine (P = 0.01) and human (P = 0.0159) tumouroids treated with Zol+RT showed a significant growth reduction. Mechanistically, RNA-Seq analysis of the PDAC xenografts and patients-PBMCs revealed that Zol exerts radiosensitization by affecting Rac1 and Rho prenylation, thereby modulating DNA damage and radiation response signalling along with improved systemic immune cells activation. An ongoing phase I/II trial (NCT03073785) showed improved failure-free survival (FFS), enhanced immune cell activation, and decreased microenvironment-related genes upon Zol+RT treatment. INTERPRETATION: Our findings suggest that FDPS is a novel radiosensitization target for PDAC therapy. This study also provides a rationale to utilize Zol as a potential radiosensitizer and as an immunomodulator in PDAC and other cancers. FUNDING: National Institutes of Health (P50, P01, and R01)

Pathobiological Implications of MUC16 Expression in Pancreatic Cancer

MUC16 (CA125) belongs to a family of high-molecular weight O-glycosylated proteins known as mucins. While MUC16 is well known as a biomarker in ovarian cancer, its expression pattern in pancreatic cancer (PC), the fourth leading cause of cancer related deaths in the United States, remains unknown. The aim of our study was to analyze the expression of MUC16 during the initiation, progression and metastasis of PC for possible implication in PC diagnosis, prognosis and therapy. In this study, a microarray containing tissues from healthy and PC patients was used to investigate the differential protein expression of MUC16 in PC. MUC16 mRNA levels were also measured by RT-PCR in the normal human pancreatic, pancreatitis, and PC tissues. To investigate its expression pattern during PC metastasis, tissue samples from the primary pancreatic tumor and metastases (from the same patient) in the lymph nodes, liver, lung and omentum from Stage IV PC patients were analyzed. To determine its association in the initiation of PC, tissues from PC patients containing pre-neoplastic lesions of varying grades were stained for MUC16. Finally, MUC16 expression was analyzed in 18 human PC cell lines. MUC16 is not expressed in the normal pancreatic ducts and is strongly upregulated in PC and detected in pancreatitis tissue. It is first detected in the high-grade pre-neoplastic lesions preceding invasive adenocarcinoma, suggesting that its upregulation is a late event during the initiation of this disease. MUC16 expression appears to be stronger in metastatic lesions when compared to the primary tumor, suggesting a role in PC metastasis. We have also identified PC cell lines that express MUC16, which can be used in future studies to elucidate its functional role in PC. Altogether, our results reveal that MUC16 expression is significantly increased in PC and could play a potential role in the progression of this disease