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PDF file - 433KB, S1: CIP2A and SET levels are increased in some primary human pancreatic cancer samples. S2: Increased expression of PP2A inhibitors trend toward decreased PP2A activity, which trends toward increased Myc expression and Myc protein stabilization in pancreatic cancer cell lines. S3: OP449 treatment decreases c-Myc DNA binding and half-life in pancreatic cancer cell lines, and SET knockdown reduces OP449 sensitivity. S4: OP449 treatment reduces pancreatic cancer cell migration in vitro, proliferation in vivo, and increases tumor cell apoptosis in vivo.

Seminal discoveries have established that epigenetic modifications are important for driving tumor progression. Polycomb group (PcG) proteins are highly conserved epigenetic effectors that maintain, by posttranslational modification of histones, the silenced state of genes involved in critical biologic processes, including cellular development, stem cell plasticity, and tumor progression. PcG proteins are found in two multimeric protein complexes called Polycomb repressive complexes: PRC1 and PRC2. Enhancer of zeste homolog 2 (EZH2), catalytic core subunit of PRC2, epigenetically silences several tumor-suppressor genes by catalyzing the trimethylation of histone H3 at lysine 27, which serves as a docking site for DNA methyltransferases and histone deacetylases. Evidence suggests that overexpression of EZH2 is strongly associated with cancer progression and poor outcome in disparate cancers, including hematologic and epithelial malignancies. The regulatory circuit and molecular cues causing EZH2 deregulation vary in different cancer types. Therefore, this review provides a comprehensive overview on the oncogenic role of EZH2 during tumorigenesis and highlights the multifaceted role of EZH2, as either a transcriptional activator or repressor depending on the cellular context. Additional insight is provided on the recent understanding of the causes and consequences of EZH2 overexpression in specific cancer types. Finally, evidence is discussed on how EZH2 has emerged as a promising target in anticancer therapy and the prospects for targeting EZH2 without affecting global methylation status. Thus, a better understanding of the complex epigenetic regulatory network controlling EZH2 expression and target genes facilitates the design of novel therapeutic interventions. Mol Cancer Res; 12(5); 639–53. ©2014 AACR.

R-loops, or RNA:DNA hybrids, can induce DNA damage, which requires DNA repair factors including breast cancer type 1 susceptibility protein (BRCA1) to restore genomic integrity. To date, several pathogenic mutations have been found within the tandem BRCA1 carboxyl-terminal (BRCT) domains that mediate BRCA1 interactions with proteins and DNA in response to DNA damage. Here, we describe a nonrepair role of BRCA1 BRCT in suppressing ribosomal R-loops via two mechanisms. Through its RNA binding and annealing activities, BRCA1 BRCT facilitates the formation of double-stranded RNA between ribosomal RNA (rRNA) and antisense-rRNA (as-rRNA), hereby minimizing rRNA hybridization to ribosomal DNA to form R-loops. BRCA1 BRCT also promotes RNA polymerase I-dependent transcription of as-rRNA to enhance double-stranded rRNA (ds-rRNA) formation. In addition, BRCA1 BRCT-mediated as-rRNA production restricts rRNA maturation in unperturbed cells. Hence, impairing as-rRNA transcription and ds-rRNA formation due to BRCA1 BRCT deficiency deregulates rRNA processing and increases ribosomal R-loops and DNA breaks. Our results link ribosomal biogenesis dysfunction to BRCA1-associated genomic instability.

Silica gels are the significant commodity solid waste produced by organic laboratories and pharmaceutic industries. Although use of silica gels is continuously growing, the proper methods of re-utilizing silica waste are yet limited. Hence, it demands a non-traditional approach to transform these silica waste into some other useful products apart from using them as a well-known road construction materials. Hereby, we report the fabrication and applications of monolithic polymer-silica composites by ice-templating technique from laboratory waste silica-gels, using green approach. To the best of our knowledge, the fabrication of organic-inorganic hybrid sponges from the particles of hundreds of microns is not reported to date. Scaffolds S60, S120, S180, and S300, were prepared from laboratory discarded silica gels. The morphological, physicochemical, flame-retardant, and liquid absorbent properties of these self-standing scaffolds were analyzed. Results showed that the incorporation of silica particles in the scaffolds turned them into a flame-retardant sponge. These properties make the sponges ideal for making non-flammable cushions, applicable in automobiles, aircrafts, chemical laboratories, hospitals, and other areas of applications. Due to the large porous structures, these scaffolds possess excellent absorption properties and may absorb almost every kind of liquid ranging from oils to acids. Therefore, these scaffolds are also a remarkable absorber for oils and hazardous liquids spillage, such as acids, and can be used as foam for chemical packing applications.

Dry eye disease (DED) is a multifactorial disorder of the ocular surface that results in ocular discomfort, visual disturbance and damage to the ocular surface. It is one of the most common complaints in daily ophthalmic practice. The greater prevalence of dry eye in women compared to men suggests that sex hormones may have a role in this condition. Sex hormones; estrogen and androgens influence production of all components of the tear film including aqueous layer, lipid layer, and mucin layer. Various mechanisms such as decrease in hormonal levels, shift in feedback mechanisms, and changes in receptor receptivity interplay to alter the ocular surface homeostasis and subsequently result in DED. The purpose of this review is to briefly outline current scientific evidence on the influence of androgen and estrogen on the lacrimal and meibomian glands as well as on the ocular surface epithelia including conjunctival goblet cells during reproductive and menopausal periods. This article also outlines the updates regarding role of gonadal hormones in the treatment of dry eye. Keywords: Dry Eye, Sex hormones, Estrogen, Androgen, Testosterone, Progesterone, Tear film, Meibomian gland, Lacrimal gland, Ocular surface, Menopause, HRT, Schirmer’s test.

Rapid industrialization and intensive agriculture activities have led to a rise in heavy metal contamination all over the world. Chhattisgarh (India) being an industrial state, the soil and water are thickly contaminated with heavy metals, especially from arsenic (As). In the present study, we isolated 108 arsenic-resistant bacteria (both from soil and water) from different arsenic-contaminated industrial and mining sites of Chhattisgarh to explore the bacterial gene pool. Further, we screened 24 potential isolates out of 108 for their ability to tolerate a high level of arsenic. The sequencing of the 16S rRNA gene of bacterial isolates revealed that all these samples belong to different diverse genera including Bacillus, Enterobacter, Klebsiella, Pantoea, Acinetobacter, Cronobacter, Pseudomonas and Agrobacterium. The metal tolerance ability was determined by amplification of arsB (arsenite efflux gene) and arsC (arsenate reductase gene) from chromosomal DNA of isolated RnASA11, which was identified as Klebsiella pneumoniae through in silico analysis. The bacterial strains RpSWA2 and RnASA11 were found to tolerate 600 mM As (V) and 30 mM As (III) but the growth of strain RpSWA2 was slower than RnASA11. Furthermore, atomic absorption spectroscopy (AAS) of the sample obtained from bioremediation assay revealed that Klebsiella pneumoniae RnASA11 was able to reduce the arsenic concentration significantly in the presence of arsenate (44%) and arsenite (38.8%) as compared to control.

This article is focussed on developing a novel hybrid modulation technique for matrix converter. The concept of singular value decomposition (SVD) is utilised to synthesise the intermediate fictiti...

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The coronavirus disease 2019 (COVID-19) pandemic has posed another serious threat, mucormycosis infection, affecting the maxilla and orbitocerebral region. This condition has not spared world population from its merciless claws. This article addresses the challenges faced by the maxillofacial surgeons in setting the protocols from preoperative diagnosis, surgical management to postoperative care, including short-term and long-term rehabilitation. To manage this relentlessly progressing condition, a multispecialty team approach is to be activated in diagnosing, managing, and rehabilitating the patients.The purpose of this clinical study is to document and analyze the clinical and demographic data, presentation of the lesion, the diagnostic methods followed for early clinical detection, and management of post COVID-19 midface mucormycosis. The article also discusses postoperative medical management and prosthetic rehabilitation.Most of the mucormycosis cases reporting to our center were treated and recovered patients of Severe Acute Respiratory Syndrome Coronavirus 2 infection. Thirty-four (n=34) case were operated for post COVID-19 midface mucormycosis between October 2020 and December 2021. Male to Female ratio is 1:42. The average age of the patients was 57.5 years. Maximum patients were in fifth and sixth decade of life. Maxilla was the involved bone. Treatment was primarily surgical debridement to extended or radical maxillectomy. All patients were treated with Liposomal Amphotericin B and tab posaconazole for 3 to 4 weeks depending upon the age, weight, and physiological state of the patients to attain an optimal cumulative load. Three patients succumbed to illness postoperatively (n=3, 1.02%). Average duration of hospital stay was 47 days. The average review period was 5.1 months.

The study was conducted at the College of Agriculture and Research Station, Indira Gandhi Krishi Vishwavidylaya, Janjgir- Champa (Chhattisgarh), during the year 2017-18 Rabi Season to Study the Influence of Rhizobium and phosphate solubilizing bacteria on the performance of field-grown Lathyrus (Lathyrus sativus L) under climatic conditions of Chhattisgarh plains. In the present investigation total of 8 treatments T1 -Control (No inoculum no fertilizer), T2- Recommended Dose of Fertilizer RDF(N:P: K::20:40:20), T3- Rhi.HG-25 (Std.) + PSB-H-27 (Std.), T4 Rhi.HG-25 + Korba PSB-118, T5 - Rhi.L-3 Lathyrus + PSB-H-27, T6 Rhi.L-3 Lathyrus + Korba PSB-118, T7- Rhi.L-11 Lathyrus + PSB-H-27 , T8 Rhi.L-11 Lathyrus + Korba PSB-118. Recommended Dose of Fertilizer (RDF) T2 recorded maximum and significantly higher value of plant height over rest of the treatments at 45, 60 DAS and at maturity except T7 (Rhi.L-11 Lathyrus + PSB-H-27) treatment which was statistically similar at maturity. A general perusal of the data of the fresh plant reveals that T2 (Recommended Dose of Fertilizer, RDF) recorded the maximum and significantly higher value of fresh weight over the rest of the treatments at a later stage of crop growth i.e 60 DAS and at harvest. A critical perusal of the nodule count data revealed that treatment T8 (Rhi.L-11Lathyrus+ KorbaPSB-118) was found superior over all the treatments showing the superiority of combined use of local strains over other strains and RDF. In case of grain yield the maximum grain yield were observed in 1451.39 kg/ha due to application of T8 (Rhi.L-11Lathyrus+ KorbaPSB-118) followed by T2 RDF 1415.28 kg/ha, T4 (Rhi.HG-25 +KorbaPSB-118)1388.89 kg/ha, T7 (Rhi.L-11 Lathyrus+ PSB-H-27)1344.44 kg/ha, T6 (Rhi.L-3 Lathyrus­ + PSB-H-27)706.94 kg/ha, 12.77 kg/ha, T5 (Rhi.L-3 Lathyrus+ PSB-H-27) 1216.67 kg/ha, T3 (Rhi.HG-25 + PSB-H-27) 1219.94kg/ha. Maximum grain yield was observed due to the application of effective local strains of rhizobia and PSB which also enhanced the nodulation activity due to an increase in the available soil phosphorus. The maximum and significantly higher value of grain yield straw yield (1118.06 kg/ha) was observed due to treatment T8 (Rhi.L-11 Lathyrus+ Korba-PSB-118) which was statistically superior over all the treatments except T2 RDF.

The ADP-ribosylhydrolase ARH3 plays a key role in DNA damage repair, digesting poly(ADP-ribose) and removing ADP-ribose from serine residues of the substrates. Specific inhibitors that selectively target ARH3 would be a useful tool to examine DNA damage repair, as well as a possible strategy for tumor suppression. However, efforts to date have not identified any suitable compounds. Here, we used in silico and biochemistry screening to search for ARH3 inhibitors. We discovered a small molecule compound named ARH3 inhibitor 26 (AI26) as, to our knowledge, the first ARH3 inhibitor. AI26 binds to the catalytic pocket of ARH3 and inhibits the enzymatic activity of ARH3 with an estimated IC(50) of ∼2.41 μm in vitro. Moreover, hydrolysis of DNA damage–induced ADP-ribosylation was clearly inhibited when cells were pretreated with AI26, leading to defects in DNA damage repair. In addition, tumor cells with DNA damage repair defects were hypersensitive to AI26 treatment, as well as combinations of AI26 and other DNA-damaging agents such as camptothecin and doxorubicin. Collectively, these results reveal not only a chemical probe to study ARH3-mediated DNA damage repair but also a chemotherapeutic strategy for tumor suppression.

In this work, we establish Ramanujan–Mordell type formulas associated to certain quadratic forms of discriminants 20k or 32k. In the end, a remark is given to illustrate potential extensions to other related cases.

Drug resistance is one of the trademark features of Cancer Stem Cells (CSCs). We and others have recently shown that paucity of functional death receptors (DR4/5) on the cell surface of tumour cells is one of the major reasons for drug resistance, but their involvement in the context of in CSCs is poorly understood. By harnessing CSC specific cytotoxic function of salinomycin, we discovered a critical role of epigenetic modulator EZH2 in regulating the expression of DRs in colon CSCs. Our unbiased proteome profiler array approach followed by ChIP analysis of salinomycin treated cells indicated that the expression of DRs, especially DR4 is epigenetically repressed in colon CSCs. Concurrently, EZH2 knockdown demonstrated increased expression of DR4/DR5, significant reduction of CSC phenotypes such as spheroid formation in-vitro and tumorigenic potential in-vivo in colon cancer. TCGA data analysis of human colon cancer clinical samples shows strong inverse correlation between EZH2 and DR4. Taken together, this study provides an insight about epigenetic regulation of DR4 in colon CSCs and advocates that drug-resistant colon cancer can be therapeutically targeted by combining TRAIL and small molecule EZH2 inhibitors.

Despite their ubiquitous expression, the inheritance of monoallelic germline mutations in breast cancer susceptibility gene type 1 or 2 (BRCA1/2) poses tissue-specific variations in cancer risks and primarily associate with familial breast and ovarian cancers. The molecular basis of this tissue-specific tumor incidence remains unknown and intriguing to cancer researchers. A plethora of recent reports support the idea that several nongenetic factors present in the tissue microenvironment could induce tumors in the mutant BRCA1/2 background. This Opinion article summarizes the recent advances on tissue-specific carcinogens and their complex crosstalk with the compromised DNA repair machinery of BRCA1/2-mutant cells. Finally, we present our perspective on the therapeutic and chemopreventive interpretations of these developments.

Ten-eleven translocation (TET) family enzymes (TET1, TET2, and TET3) oxidize 5-methylcytosine (5mC) and generate 5-hydroxymethylcytosine (5hmC) marks on the genome. Each TET protein also interacts with specific binding partners and partly plays their role independent of catalytic activity. Although the basic role of TET enzymes is well established now, the molecular mechanism and specific contribution of their catalytic and noncatalytic domains remain elusive. Here, by combining in silico and biochemical screening strategy, we have identified a small molecule compound, C35, as a first-in-class TET inhibitor that specifically blocks their catalytic activities. Using this inhibitor, we explored the enzymatic function of TET proteins during somatic cell reprogramming. Interestingly, we found that C35-mediated TET inactivation increased the efficiency of somatic cell programming without affecting TET complexes. Using high-throughput mRNA sequencing, we found that by targeting 5hmC repressive marks in the promoter regions, C35-mediated TET inhibition activates the transcription of the BMP-SMAD-ID signaling pathway, which may be responsible for promoting somatic cell reprogramming. These results suggest that C35 is an important tool for inducing somatic cell reprogramming, as well as for dissecting the other biological functions of TET enzymatic activities without affecting their other nonenzymatic roles.

The introduction of an efficient and precious platinum (Pt) free counter electrode (CE) for dye-sensitized solar cells (DSSCs) is an important aspect to address. In this report, we have employed na...

Nucleosomal histones are barriers to the DNA repair process particularly at DNA double-strand breaks (DSBs). However, the molecular mechanism by which these histone barriers are removed from the sites of DNA damage remains elusive. Here, we have generated a single specific inducible DSB in the cells and systematically examined the histone removal process at the DNA lesion. We found that histone removal occurred immediately following DNA damage and could extend up to a range of few kilobases from the lesion. To examine the molecular mechanism underlying DNA damage-induced histone removal, we screened histone modifications and found that histone ADP-ribosylation was associated with histone removal at DNA lesions. PARP inhibitor treatment suppressed the immediate histone eviction at DNA lesions. Moreover, we examined histone chaperones and found that the FACT complex recognized ADP-ribosylated histones and mediated the removal of histones in response to DNA damage. Taken together, our results reveal a pathway that regulates early histone barrier removal at DNA lesions. It may also explain the mechanism by which PARP inhibitor regulates early DNA damage repair.

Dependency on fossil fuels raises an economic and ecological concern that has urged to look for alternative sources of energy. Bio-refinery concept is one of the alternate frameworks for the biomass conversion into biofuel and other value-added by-products. The present work illustrates importance of an oleaginous yeast Rhodotorula pacifica INDKK in an integrated bio-refinery field by utilizing renewable sugars generated from lignocellulosic biomass. The maximum 11.8 g/L lipid titer, 210.4 mg/L β-carotene and 7.1 g animal feed were produced by R. pacifica INDKK in bioreactor containing 5% (v/v) molasses supplemented with enzymatically hydrolyzed and alkali-pretreated sugarcane bagasse hydrolysate (35% v/v). Furthermore, xylooligosaccharides (20.6 g/L), a beneficial prebiotics were also produced from the hemicellulosic fraction separated after alkali pretreatment of bagasse. This novel concept of integrated yeast bio-refinery for concomitant production of biodiesel and multiple value-added products with minimum waste generation is proposed as a sustainable and profitable process.

Triple-Negative Breast Cancer (TNBC) has a poor prognosis and adverse clinical outcomes among all breast cancer subtypes as there is no available targeted therapy. Overexpression of Enhancer of zeste homolog 2 (EZH2) has been shown to correlate with TNBC’s poor prognosis, but the contribution of EZH2 catalytic (H3K27me3) versus non-catalytic EZH2 (NC-EZH2) function in TNBC progression remains elusive. We reveal that selective hyper-activation of functional EZH2 (H3K27me3) over NC-EZH2 alters TNBC metastatic landscape and fosters its peritoneal metastasis, particularly splenic. Instead of H3K27me3-mediated repression of gene expression; here, it promotes KRT14 transcription by attenuating binding of repressor SP1 to its promoter. Further, KRT14 loss significantly reduces TNBC migration, invasion, and peritoneal metastasis. Consistently, human TNBC metastasis displays positive correlation between H3K27me3 and KRT14 levels. Finally, EZH2 knockdown or H3K27me3 inhibition by EPZ6438 reduces TNBC peritoneal metastasis. Altogether, our preclinical findings suggest a rationale for targeting TNBC with EZH2 inhibitors.

Chemokine receptor CXCR4 overexpression in solid tumors has been strongly associated with poor prognosis and adverse clinical outcome. However, blockade of CXCL12-CXCR4 signaling axis by inhibitors like Nox-A12, FDA approved CXCR4 inhibitor drug AMD3100 have shown limited clinical success in cancer treatment. Therefore, exclusive contribution of CXCR4-CXCL12 signaling in pro-tumorigenic function is questionable. In our pursuit to understand the impact of chemokine signaling in carcinogenesis, we reveal that instead of CXCR4-CXCL12 signaling, presence of CXCR4 intracellular protein augments paclitaxel resistance and pro-tumorigenic functions. In search of pro-apoptotic mechanisms for CXCR4 mediated drug resistance; we discover that DR5 is a new selective target of CXCR4 in breast and colon cancer. Further, we detect that CXCR4 directs the differential recruitment of transcription factors p53 and YY1 to the promoter of DR5 in course of its transcriptional repression. Remarkably, inhibiting CXCR4-ligand-mediated signals completely fails to block the above phenotype. Overexpression of different mutant versions of CXCR4 lacking signal transduction capabilities also result in marked downregulation of DR5 expression in colon cancer indeed confirms the reverse relationship between DR5 and intracellular CXCR4 protein expression. Irrespective of CXCR4 surface expression, by utilizing stable gain and loss of function approaches, we observe that intracellular CXCR4 protein selectively resists and sensitizes colon cancer cells against paclitaxel therapy in vitro and in vivo. Finally, performing TCGA data mining and using human breast cancer patient samples, we demonstrate that expression of CXCR4 and DR5 are inversely regulated. Together, our data suggest that targeting CXCR4 intracellular protein may be critical to dampen the pro-tumorigenic functions of CXCR4.

Triple Negative Breast Cancer (TNBC) is known to have poor prognosis and adverse clinical outcome among all breast cancer subtypes due to the absence of available targeted therapy for it. Emerging literature indicates that epigenetic reprogramming is now appreciated as a driving force for TNBC pathophysiology. High expression of epigenetic modulator EZH2 (Enhancer of zeste homolog 2) has been shown to correlate with TNBC poor prognosis but the contribution of EZH2 catalytic (H3K27me3) versus non-catalytic EZH2 (NC-EZH2) function in TNBC growth and progression remains elusive. In the process of dissecting the impact of H3K27me3 versus NC-EZH2 function in TNBC pathogenesis, we reveal that selective hyperactivation of H3K27me3 over NC-EZH2 not only promotes TNBC metastasis but also alters the metastatic landscape of TNBC. Using extensive in- vivo live animal imaging, we present conclusive evidence that peritoneal metastasis, particularly splenic metastasis of TNBC is governed by H3K27me3. Transcriptome analyses of hyperactive H3K27me3 cells lead us to discover Cytokeratin-14 (KRT14) as a new target of H3K27me3. Unlike classical H3K27me3 mediated suppression of gene expression, here; we observe that H3K27me3 enhances KRT14 transcription by attenuating the binding of transcriptional repressor Sp1 to its promoter. Further, loss of KRT14 significantly reduces TNBC migration, invasion and splenic metastasis. Finally, genetic ablation of EZH2 or pharmacological inhibition of EZH2 catalytic function by FDA approved drug tazemetostat (EPZ6438) robustly inhibits TNBC peritoneal metastasis. Altogether, our preclinical findings posit a rational insight for the clinical development of H3K27me3 inhibitor like tazemetostat as a targeted therapy against TNBC.

Chronic Myelomonocytic Leukemia (CMML) is a clonal hematologic disorder of older individuals characterized by monocytosis and increased risk of progression to acute myeloid leukemia (AML). Although CMML is characterized by relatively low genetic complexity consistent with clonal expansion, loss-of-function mutations in ten-eleven translocation 2 (TET2) protein are frequent and reported in almost 60% of CMML cases. Consistent with this finding, deletion of the Tet2 gene in mice leads to CMML-like disease. TET2 restrains inflammatory signals through various means, for instance by directly suppressing the expression of the IL6 gene in mouse myeloid cells by recruiting histone deacetylases. Conversely, the levels of pre-inflammatory cytokines including IL6 correlate with pre-leukemic proliferation of Tet2-deficient mouse monocytes and other myeloid cells, suggesting that Tet2 deficiency increases IL-6 expression and increased IL-6 expression in turn drives the proliferation of Tet2-deficient myeloid-lineage cells in a positive feedback loop. This scenario may operate in CMML patients, who show increased levels of inflammatory cytokines and increased expression of interferon-induced genes compared to age-matched healthy individuals. To gain insight into the connection between inflammation caused by TET deficiency and monocyte hyperproliferation, we set up cultures of bone marrow derived macrophages (BMDMs) from inducible TET deficient mice. Using this model, we found that TET-deficient BMDMs show increased proliferation compared to wild type controls; moreover, LPS stimulation leads to significantly increased expression of IL6 and IL1b in TET-deficient BMDMs. Our previous RNA sequencing of expanded TET-deficient myeloid cells in vivo showed that TET deficiency correlated with increased expression of transposable elements (TEs) and induced a DNA damage response, leading us to hypothesize that TET deficiency and increased TE expression may activate DNA and RNA sensing pathways and induce sterile inflammation. I am currently using several molecular approaches to delineate the potential connection of TET deficiency with endogenous inflammation in CMML. There is growing evidence that TET deficiency or non-specific inhibition of TET enzymes in CD8 T cells can potentiate anti-tumor responses. I am now asking whether the TET deficiency-inflammation axis I observe in BMDMs might also enhance anti-tumor responses by increasing proinflammatory responses and hence T cell recruitment and anti-tumor activity. Citation Format: Anup Kumar Singh, Atsushi Onodera, Hugo Sepulveda, Carlos Angel, Anjana Rao. Connecting TET2 deficiency with inflammation in CMML and anti-tumor responses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6320.

In his unpublished manuscript on the partition and tau functions, Ramanujan obtained several striking congruences for the partition function p ( n ) , the number of unrestricted partitions of n. The most notable of them are p ( 5 n + 4 ) ≡ 0 ( mod 5 ) and p ( 7 n + 5 ) ≡ 0 ( mod 7 ) which holds for all positive integers n. More surprisingly, Ramanujan obtained certain identities between q-series from which the above congruences follow as consequences. In this paper, we adopt Ramanujan's approach and prove an identity which witnesses another famous Ramanujan congruence, namely, p ( 11 n + 6 ) ≡ 0 ( mod 11 ) and also establish some new identities for the generating functions for p ( 17 n + 5 ) , p ( 19 n + 7 ) and p ( 23 n + 1 ) . We also find explicit evaluations for F p ( q ) in the cases p = 17 , 19 , 23 where F p is the function appearing in Ramanujan's circular summation formula.

Endocrine therapies are standard-of-care treatments for estrogen receptor (ER) positive breast cancer. However, patients with ER+ breast cancer develop resistance to these therapies and most relapsed patients die with endocrine-resistant metastatic disease. Here we show that resistance to the ER degrader, fulvestrant, is accompanied by epigenetic activation of the transcriptional co-activator VGLL1. Rewiring of the epigenome in therapy resistant cells also results in increased binding of the transcription factor TEAD4. Through interaction with TEAD4, VGLL1 induces the expression of genes implicated in cell proliferation in the resistant cells. We demonstrate that VGLL1 is necessary for the growth of fulvestrant-resistant breast cancer cells. Pharmacological disruption of VGLL1/TEAD4 interaction blocked growth of fulvestrant-resistant cells, accompanied by inhibition of VGLL1/TEAD transcriptional programmes. Furthermore, we identify EGFR as an important downstream VGLL1 target, whereby VGLL1-directed EGFR upregulation sensitises fulvestrant-resistant breast cancer cells to EGFR inhibitors. Taken together, our findings identify VGLL1 as a key transcriptional driver in endocrine-resistant breast cancer and identify new therapeutic approaches for advanced breast cancer patients.

In the present study, bacterial isolates were screened for arsenic resistance efficiency. Environmental isolates were isolated from arsenic-rich soil samples (i.e., from Rajnandgaon district of Chhattisgarh state, India). Amplification and sequencing of 16S rRNA gene revealed that the isolates were of Bacillus firmus RSN1, Brevibacterium senegalense RSN2, Enterobacter cloacae RSN3, Stenotrophomonas pavanii RSN6, Achromobacter mucicolens RSN7, and Ochrobactrum intermedium RSN10. Arsenite efflux gene (arsB) was successfully amplified in E. cloacae RSN3. Atomic absorption spectroscopy (AAS) analysis showed an absorption of 32.22% arsenic by the RSN3 strain. Furthermore, results of scanning electron microscopy (SEM) for morphological variations revealed an initial increase in the cell size at 1 mM sodium arsenate; however, it was decreased at 10 mM concentration in comparison to control. This change of the cell size in different metal concentrations was due to the uptake and expulsion of the metal from the cell, which also confirmed the arsenite efflux system.

Drug resistance is one of the trademark features of Cancer Stem Cells (CSCs). We and others have recently shown that paucity of functional death receptors (DR4/5) on the cell surface of tumor cells is one of the major reasons for drug resistance, but their involvement in the context of in CSCs is poorly understood. By harnessing CSC specific cytotoxic function of salinomycin, we discovered a critical role of epigenetic modulator EZH2 in regulating the expression of DRs in colon CSCs. Our unbiased proteome profiler array approach followed by ChIP analysis of salinomycin treated cells indicated that the expression of DRs, especially DR4 is epigenetically repressed in colon CSCs. Concurrently, EZH2 knockdown demonstrated increased expression of DR4/DR5, significant reduction of CSC phenotype such as spheroid formation in-vitro and tumorigenic potential in-vivo in colon cancer. TCGA data analysis of human colon cancer clinical samples shows strong inverse correlation between EZH2 and DR4. Taken together, this study provides an insight about epigenetic regulation of DR4 in colon CSCs and advocates that drug resistant colon cancer can be therapeutically targeted by combining TRAIL and small molecule EZH2 inhibitors.

Chickpea (Cicer arietinum L.) is the third most important food legume in the world; its annual production is nearly about 11.5 million tons with an estimated land area of 14.56 million hectares. The chickpea is a multifunction crop and has huge nutritional value. From a microbiological point of view, it is a legume crop and harbor rhizobia in its root in the form of nodules. The chickpea also has a diverse microbial population including both bacterial and fungal species. These microbial communities especially bacterial genera play an important role in its growth and protection. In this chapter, we will discuss these microbial communities and their role in chickpea growth.