Amplified centrosomes may underlie aggressive disease course in pancreatic ductal adenocarcinoma

Centrosome amplification (CA), the presence of centrosomes that are abnormally numerous or enlarged, is a well-established driver of tumor initiation and progression associated with poor prognosis across a diversity of malignancies. Pancreatic ductal adenocarcinoma (PDAC) carries one of the most dismal prognoses of all cancer types. A majority of these tumors are characterized by numerical and structural centrosomal aberrations, but it is unknown how CA contributes to the disease and patient outcomes. In this study, we sought to determine whether CA was associated with worse clinical outcomes, poor prognostic indicators, markers of epithelial-mesenchymal transition (EMT), and ethnicity in PDAC. We also evaluated whether CA could precipitate more aggressive phenotypes in a panel of cultured PDAC cell lines. Using publicly available microarray data, we found that increased expression of genes whose dysregulation promotes CA was associated with worse overall survival and increased EMT marker expression in PDAC. Quantitative analysis of centrosomal profiles in PDAC cell lines and tissue sections uncovered varying levels of CA, and the expression of CA markers was associated with the expression of EMT markers. We induced CA in PDAC cells and found that CA empowered them with enhanced invasive and migratory capabilities. In addition, we discovered that PDACs from African American (AA) patients exhibited a greater extent of both numerical and structural CA than PDACs from European American (EA) patients. Taken together, these findings suggest that CA may fuel a more aggressive disease course in PDAC patients.     

Lipid droplet-associated proteins (LDAPs) are involved in the compartmentalization of lipophilic compounds in plant cells

While lipid droplets have traditionally been considered as inert sites for the storage of triacylglycerols and sterol esters, they are now recognized as dynamic and functionally diverse organelles involved in energy homeostasis, lipid signaling, and stress responses. Unlike most other organelles, lipid droplets are delineated by a half-unit membrane whose protein constituents are poorly understood, except in the specialized case of oleosins, which are associated with seed lipid droplets. Recently, we identified a new class of lipid-droplet associated proteins called LDAPs that localize specifically to the lipid droplet surface within plant cells and share extensive sequence similarity with the small rubber particle proteins (SRPPs) found in rubber-accumulating plants. Here, we provide additional evidence for a role of LDAPs in lipid accumulation in oil-rich fruit tissues, and further explore the functional relationships between LDAPs and SRPPs. In addition, we propose that the larger LDAP/SRPP protein family plays important roles in the compartmentalization of lipophilic compounds, including triacylglycerols and polyisoprenoids, into lipid droplets within plant cells. Potential roles in lipid droplet biogenesis and function of these proteins also are discussed.     

Green approach for nanoparticle biosynthesis by fungi: current trends and applications

In recent years, the green approach of nanoparticle synthesis by biological entities has been gaining great interest over various other physico-chemical methods, which are laden with many disadvantages. The important challenging issues in current nanotechnology include the development of reliable experimental techniques for the synthesis of nanoparticles of different compositions and sizes along with high monodispersity. Biological systems offer unique promising features to tailor nanomaterials with predefined properties. Fungi are the favorite choice of microorganisms due to the wide variety of advantages they offer over bacteria, yeast, actinomycetes, plants, and other physico-chemical techniques. The use of microorganisms for the deliberate synthesis of nanoparticles is a fairly new and exciting area of research with considerable potential for further development. This review describes an overview of the current green approaches for the synthesis of nanoparticles with particular emphasis on fungi, which are gaining worldwide popularity as nano-factories for the green synthesis of nanoparticles.     

Liquid state fermentation of apple pomace sludge for the production of ligninolytic enzymes and liberation of polyphenolic compounds

Ligninolytic enzyme production and polyphenolic compound extraction by liquid-state culture of Phanerochaete chrysosporium ATCC 24275 was investigated by employing apple pomace sludge and synthetic medium. Different physico-chemical and biological parameters namely viscosity, zeta potential and particle size, viability and enzyme production were investigated. The ligninolytic enzyme production was higher in apple pomace sludge (45 U/l of laccase, 220 U/l of MnP and 6.5 U/l of LiP) than in synthetic medium (17 U/l of laccase, 37 U/l of MnP and 6 U/l). These maximal activities were found during the stationary and decline phase. It was also found that enzyme production was strongly correlated with P. chrysoporium viability in both synthetic medium and apple pomace sludge. Moreover, physico-chemical parameters, such as particle size, zeta potential and viscosity were strongly correlated to the viability of P. chrysosporium and to the ligninolytic enzyme production. An increase in polyphenol content extracted by acetone (383–720 mg GAE/l) was observed during fermentation of apple pomace and it was found that the polyphenol content extracted by ethanol increased ～1.5 fold until 67 h of fermentation and later it decreased. It was found that antioxidant activity increased to 35% and eventually decreased based on the change in the polyphenol content.     

Parameter optimization for production of ligninolytic enzymes using agro-industrial wastes by response surface method

Lignin and manganese peroxidase (LiP, MnP) and laccase production by Phanerocheate chrysosporium was optimized by response surface methodology for brewery waste and apple pomace. The effect of moisture, copper sulphate, and veratryl alcohol (VA) concentrations on enzyme production was studied. Moisture and VA had significant positive effect on MnP and LiP production and the viability of P. chrysosporium (p < 0.05) and copper sulphate produced a negative effect. However, moisture and copper sulphate had a significant positive (p < 0.05) effect on laccase production, but VA had an insignificant positive effect (p < 0.05). Higher values of MnP, LiP and viability of P. chrysosporium on apple pomace (1287.5 U MnP/gds (units/gram dry substrate), 305 U LiP/gds, and 10.38 Log 10 viability) and brewery waste (792 U MnP/gds and 9.83 Log 10 viability) were obtained with 80% moisture, 3 mmol/kg VA, and 0.5 mmol/kg copper. LiP production in brewery waste (7.87 U/gds) was maximal at 70% moisture, 2 mmol/kg VA, and 1 mmol/kg copper. Higher production of laccase in apple pomace (789 U/gds) and brewery waste (841 U/gds) were obtained with 80% moisture, 3 mmol/kg VA, and 1.5 mmol/kg copper. Thus, moisture along with VA and copper sulphate was pertinent for the production of ligninolytic enzymes and increased cell viability.     

Poly(ADP-Ribose) Polymerase 1–Sirtuin 1 Functional Interplay Regulates LPS-Mediated High Mobility Group Box 1 Secretion

Pathophysiological conditions that lead to the release of the prototypic damage-associated molecular pattern molecule high mobility group box 1 (HMGB1) also result in activation of poly(ADP-ribose) polymerase 1 (PARP1; now known as ADP-ribosyl transferase 1 [ARTD1]). Persistent activation of PARP1 promotes energy failure and cell death. The role of poly(ADP-ribosyl)ation in HMGB1 release has been explored previously; however, PARP1 is a versatile enzyme and performs several other functions including cross-talk with another nicotinamide adenine dinucleotide- (NAD⁺) dependent member of the Class III histone deacetylases (HDACs), sirtuin-1 (SIRT1). Previously, it has been shown that the hyperacetylation of HMGB1 is a seminal event prior to its secretion, a process that also is dependent on HDACs. Therefore, in this study, we seek to determine if PARP1 inhibition alters LPS-mediated HMGB1 hyperacetylation and subsequent secretion due to its effect on SIRT1. We demonstrate in an in vitro model that LPS treatment leads to hyperacetylated HMGB1 with concomitant reduction in nuclear HDAC activity. Treatment with PARP1 inhibitors mitigates the LPS-mediated reduction in nuclear HDAC activity and decreases HMGB1 acetylation. By utilizing an NAD⁺-based mechanism, PARP1 inhibition increases the activity of SIRT1. Consequently, there is an increased nuclear retention and decreased extracellular secretion of HMGB1. We also demonstrate that PARP1 physically interacts with SIRT1. Further confirmation of this data was obtained in a murine model of sepsis, that is, administration of PJ-34, a specific PARP1 inhibitor, led to decreased serum HMGB1 concentrations in mice subjected to cecal ligation and puncture (CLP) as compared with untreated mice. In conclusion, our study provides new insights in understanding the molecular mechanisms of HMGB1 secretion in sepsis.     

Efficiencies of selected biotreatments for the remediation of PAH in diluted bitumen contaminated soil microcosms

Unconventional oils such as diluted bitumen from oil sands differs from most of conventional oils in terms of physiochemical properties and PAHs composition. This raises concerns regarding the effectiveness of current remediation strategies and protocols originally developed for conventional oil. Here we evaluated the efficiency of different biotreatment approaches, such as fungi inoculation (bioaugmentation), sludge addition (bioaugmentation/biostimulation), perennial grasses plantation (phytoremediation) and their combinations as well as natural attenuation (as control condition), for the remediation of soil contaminated by synthetic crude oil (a product of diluted bitumen) in laboratory microcosms. We specifically monitored the PAHs loss percentage (alkylated PAHs and unsubstituted 16 EPA Priority PAHs), the residue of PAHs and evaluated the ecotoxicity of soil after treatment. All treatments were highly efficient with more than?~?80% of ∑PAHs loss after 60 days. Distinctive loss efficiencies between light PAHs (≤?3 rings,?~?96% average loss) and heavy PAHs (4–6 rings,?~?29% average loss) were observed. The lowest average PAHs residue (0.10?±?0.02 mg·kg^?1, for an initial concentration of 0.29?±?0.12 mg·kg^?1) was achieved with the “sludge—plants (grasses)” combination. Sludge addition was the only treatment that achieved significantly lower ecotoxicity (3%?±?4% of growth inhibition of L. sativa) than the control (natural attenuation, 13%?±?4% of inhibition). Sludge addition, grasses plantation and “sludge—fungi combination” treatments could result in lower PAH exposure (than other treatments) in post-treated soil when using the Canadian Soil Quality Guidelines for the protection of environmental and human health for potentially carcinogenic and other PAHs.