The Nefarious Nexus of Noncoding RNAs in Cancer

The past decade has witnessed enormous progress, which has seen the noncoding RNAs (ncRNAs) turn from the so called dark matter RNA to critical functional molecules, influencing most physiological processes in development and disease contexts. Many ncRNAs interact with each other and are part of networks that influence the cell transcriptome and proteome and consequently the outcome of biological processes. The regulatory circuits controlled by ncRNAs have become increasingly more relevant in cancer. Further understanding of these complex network interactions and how ncRNAs are regulated, is paving the way for the identification of better therapeutic strategies in cancer

Mycophenolic acid (MPA) modulates host cellular autophagy progression in sub genomic dengue virus-2 replicon cells

Cellular autophagy (Macrophagy) is a self-degradative process, executed through the network of autophagy associated genes (ATGs) encoded proteins. Both in vitro and in vivo studies suggest that dengue virus (DENV) induces autophagy and supports the viral genome replication and translation. Therefore, the cellular autophagy induced by dengue virus can be a good target for antiviral drug development. The action of mycophenolic acid (MPA), a specific inhibitor of DENV replication, was investigated in the stable BHK-21/DENV2 replicon cells. The inhibition was mediated by enhanced degradation of autophagic substrates in stable BHK-21/DENV2 replicon cells as evidenced by a decrease in lapidated LC3 (LC3II) and p62 expression in the presence of MPA. In contrast, the results indicated that four gene sets, namely Trans membrane protein 74 (TMEM74), Unc-51-like kinase 2 (ULK2), Cathepsin D (CTSD) and Estrogen receptor 1 (ESR1) were upregulated in stable BHK-21/DENV2 replicon cells, due to the sustained dynamic replication of DENV2 genome. These ATGs involved in the pre-autophagosomal structure (PAS) formation, were suppressed in the presence MPA. Instead, MPA induced the expression of different set of autophagy genes such as ATG4, AKT1, APP, ATG16L1, ATG16L2, B2M and HPRT1. An enzyme involved in the nucleotide salvage pathway, HPRT1, was highly expressed in the presence of MPA. The study shows that DENV2 replication is dependent on PAS formation and is inhibited in the presence of MPA by enhancing the degradation of autophagic substrates and suppression of PAS formation. This study provides impetus in designing MPA analogues to effectively inhibit dengue viral replication

Targeting of Prosurvival Pathways as Therapeutic Approaches against Primary Effusion Lymphomas: Past, Present, and Future

Constitutively activated prosurvival pathways render cancer cells addicted to their effects. Consequently they turn out to be the Achilles’ heels whose inhibition can be exploited in anticancer therapy. Primary effusion lymphomas (PELs) are very aggressive non-Hodgkin’s B cell lymphomas, whose pathogenesis is strictly linked to Kaposi’s sarcoma herpesvirus (KSHV) infection. Here we summarized previous studies from our and other laboratories exploring the cytotoxic effect of drugs inhibiting the main prosurvival pathways activated in PEL cells. Moreover, the immunogenicity of cell death, in terms of dendritic cell (DC) activation and their potential side effect on DCs, is discussed

Cosmological singularities in non-canonical models of dark energy

The pursuit of unraveling the true essence of dark energy has become an immensely captivating endeavor in modern cosmology. Alongside the conventional cosmological constant approach, a diverse range of ideas has been proposed, encompassing scalar field-based models and various modified gravity approaches. A particularly intriguing notion involves exploring scalar field dark energy models within quantum gravitationally motivated cosmologies, with non-canonical theories standing out as a prominent candidate in this context. Hence, in this work, we investigate three widely recognized non-canonical scalar field dark energy models: phantom, quintom, and DBI dark energy models. By employing the Goriely-Hyde procedure, we demonstrate the presence of singularities in both finite and infinite time within these frameworks. and that these singularities can manifest regardless of the system's initial conditions. Moreover, we further establish how cosmological singularities of types I-IV can arise in all of these models. The work goes to show that non-canonical regimes for dark energy can allow for most of the prominent cosmological singularities for a variety of models.Comment: v2, matches the accepted version in PDU, 28 pages with no figure

DENDRITIC CELL DIFFERENTIATION BLOCKED BY PRIMARY EFFUSION LYMPHOMA-RELEASED FACTORS IS PARTIALLY RESTORED BY INHIBITION OF P38 MAPK

To better understand the molecular mechanisms underlying the dendritic cell (DC) defects in cancer, we analyzed which signaling pathway is implicated in the abnormal monocyte differentiation into DC determined by the presence of Primary effusion lymphoma (PEL) released factors. Our results indicate that the DC, obtained in this condition, together with phenotypic abnormalities and reduced allostimulatory function, showed hyperphosphorylation of signal transducer and activator of transcription 3 (STAT3) and p38 mitogen-activated protein kinase (MAPK) molecules, in comparison to the DC differentiated in the absence of PEL-released factors. The inhibition of p38 MAPK but not of STAT3 phosphorylation, with specific inhibitors, was able to revert the effect of the PEL-released factors on the DC phenotype. This study suggests that p38 MAPK signaling pathway is an important contributor to the abnormal differentiation of DC in PEL

Paternally inherited trisomy at D21S11 and mutation at DXS10135 microsatellite marker in a case of fetus paternity establishment

AbstractThe case of establishment of paternity of an aborted fetus was examined with 15 autosomal STR markers. The genotype of the fetus was X at amelogenin marker and showed inheritance of both the alleles of father at D21S11 marker, thus displaying unusual tri-allelic pattern. The cases where mutation in any of biparental autosomal STR markers is observed, the use of additional STR marker system is recommended. On testing all the three samples with 12 X-STR markers, all the maternal and paternal alleles were accounted in the female fetus except at DXS10135 marker. The genotypes of mother, fetus and father at DXS10135 were 20, 22; 20, 20 and 21, which confirmed mutation of the paternal allele in the female fetus. The paternal allele contracted from 21 to 20. The allele peak heights of D21S11 and DXS10135 markers were also examined to rule out the possibility of any false allele. The probability of paternity was 0.99999999, which confirmed the paternity of the fetus. This paper presents unusual occurrence of mutation observed with two multiplex STR systems, with AmpflSTR identifier plus Kit (Applied Biosystems, Foster City, CA) and Investigator Argus X-12 multiplex kit (Qiagen, Germany), thus suggesting forensic DNA experts on high alert while interpreting the DNA test results

Eco-holobiont : a new concept to identify drivers of host-associated microorganisms

Host microbiomes play a critical role in host fitness and health. Whilst the current 'holobiont' concept framework has greatly expanded eco-evolutionary and functional understanding of host-microbiome interactions, the important role of biotic interactions and microbial loop (compositional linkage between soil, plant and animal) in shaping host-microbiome are poorly understood. We proposed an 'eco-holobiont' concept to fill the knowledge gap

Ahmedabad tolerance induction protocol and chronic renal allograft dysfunction: pathologic observations and clinical implications

<p>Abstract</p> <p>Background</p> <p>Chronic Renal Allograft Dysfunction (CRAD) is responsible for a large number of graft failures. We have abrogated acute T-cell rejections using Ahmedabad Tolerance Induction Protocol (ATIP) with hematopoietic stem cell transplantation (HSCT) under non-myeloablative conditioning pre-transplant. However B-cell mediated rejections and CRAD continue to haunt us. We carried out retrospective analysis of renal allograft biopsies performed in the last 4 years to evaluate the effect of ATIP on CRAD.</p> <p>Materials and methods</p> <p>Biopsies diagnosed as per modified Banff criteria belonged to 2 groups: ATIP under low dose immunosuppression of cyclosporine/Azathioprine/Mycofenolate mofetil+ Prednisolone, subjected to donor leucocyte transfusion, anti-T/B cell antibodies, low dose target specific irradiation, cyclophosphamide, cyclosporin followed by HSCT pre-transplant; controls who opted out of ATIP were transplanted under standard triple drug immunosuppression. Demographics of both groups were comparable.</p> <p>Results</p> <p>Incidence of chronic changes was higher in controls (17.5%) vs. 10.98% in ATIP over a mean follow up of 151.9 months in the former and 130.9 months in the latter. Proteinuria and hypertension were higher in controls (48.4%) vs. ATIP (32.7%) with chronic transplant glomerulopathy, focal global sclerosis in 67.7% in controls vs. 46.7% in ATIP, acute on chronic T/B cell rejection in 51.6% controls vs. 28.1% ATIP, with peritubular capillary C4d deposits in 19.4% controls vs. 1.9% ATIP biopsies. Acute on chronic calcineurin inhibitor toxicity was higher in ATIP (71.9%) vs. 48.4% in controls.</p> <p>Conclusion</p> <p>Chronic immune injury was less with ATIP vs controls as compared to a higher incidence of chronic calcineurin inhibitor toxicity in the former.</p

Effect of crop residue addition on soil organic carbon priming as influenced by temperature and soil properties

Priming of soil organic carbon (SOC) is a crucial factor in ecosystem carbon balance. Despite its increasing importance in the changing global climate, the extent of influence of temperature and soil properties on the priming effect remains unclear. Here, soil priming was investigated using 13C labeled wheat residues in two cultivated, subtropical (Vertisol) and semi-arid (Luvisol), soils of Australia at four incubation temperatures (13, 23, 33 and 43 °C). The priming effect was computed from respired CO2 and associated δ13C, which were measured periodically over the 52-day incubation period. Wheat residue addition resulted in greater priming effect in the Luvisol (1.17 to 2.37% of SOC) than the Vertisol (0.02 to 1.56% of SOC). The priming of SOC was the highest at 23 °C in the Luvisol, and at 43 °C in the Vertsiol, which indicates a variable positive priming effect of temperature in different soil types. Wheat residue addition significantly increased the temperature sensitivity (Q10) of SOC mineralization in the Vertisol at temperature ranges below 33 °C (i.e., 13–23 and 23–33 °C) and had no significant effect in the Luvisol. A negative correlation was observed between temperature and the Q10 values. Across soils, the Q10 of residue C was lower than SOC suggesting that soil C is more vulnerable to climatic warming. This work demonstrates that the magnitude of SOC priming by wheat residue and Q10 of SOC mineralization varied significantly with soil type (Luvsiol &gt; Vertisol) and incubation conditions (temperature and time). Given the current trend towards increasing atmospheric temperatures, future studies should evaluate temperature effects on the priming of different pools of SOC induced by crop residue in different agro-ecosystems

Effect of flocculating agents on solubility behavior of calcium sulfate dihydrate (gypsum) in aqueous sodium chloride system and solution properties at 35 °C

The effect of addition of flocculating agents, viz., alum (KAl(SO4)2·12H2O) (up to 10 wt%) and polyaluminum chloride ([Al(OH)aClb]n, a &gt;1.05; n~15) (up to 6 wt%) on the solubility behavior of calcium sulfate dihydrate (gypsum, CaSO4·2H2O) in aqueous NaCl solutions has been examined at 35 °C. The solubility of CaSO4·2H2O decreases with the addition of alum while it increases with the addition of polyaluminum chloride without any significant shift in solubility maximum. Density (ρ) and speed of sound (u) have also been determined for the quaternary systems (CaSO4·2H2O+NaCl+alum/PAC+H2O) at 35 °C and used to estimate solution isentropic compressibility (κs) and ion-hydration (nh) characteristics. Empirical equations describing the s, ρ, u and κs as a function of solution composition are presented.