Patatin-like phospholipase domain-containing protein 3 and Liver Disease: Opportunities to Unravel Mechanisms Underlying Statistical Associations

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Discovering the effects of omega-3 and omega-6 fatty acids on allergy using a hek-blue cell line

In recent times, allergy has become a financial, physical andpsychological burden to the society as a whole. Allergic reactions can result in life-threatening situations causing morbidity and high economic cost. Therefore, more effective reagents are needed for allergy treatment. Literature suggests that a causal relationship exists between the intake of Omega-3/6 fatty acids such as DHA, EPA, DPA and AA and atopic individuals suffering from allergies. In an allergic cascade, cytokines IL-4 and IL-13 bind to IL-4 receptor (IL-4R), which activates the STAT6 phosphorylation pathway leading to gene activation of allergen-specific IgE production by B cells. The overall aim of this study is to characterise Omega-3/6 fatty acids and their effects on IgE production.

Theory and optimisation of 1.3 and 1.55 μm (Al)InGaAs metamorphic quantum well lasers

The use of InGaAs metamorphic buffer layers (MBLs) to facilitate the growth of lattice-mismatched heterostructures constitutes an attractive approach to developing long-wavelength semiconductor lasers on GaAs substrates, since they offer the improved carrier and optical confinement associated with GaAs-based materials. We present a theoretical study of GaAs-based 1.3 and 1.55 μm (Al)InGaAs quantum well (QW) lasers grown on InGaAs MBLs. We demonstrate that optimised 1.3 μm metamorphic devices offer low threshold current densities and high differential gain, which compare favourably with InP-based devices. Overall, our analysis highlights and quantifies the potential of metamorphic QWs for the development of GaAs-based long-wavelength semiconductor lasers, and also provides guidelines for the design of optimised devices.

Exploring the effects of omega-3 and omega-6 fatty Acids on allergy using a HEK-blue cell line.

BACKGROUND: Allergic reactions can result in life-threatening situations resulting in high economic costs and morbidity. Therefore, more effective reagents are needed for allergy treatment. A causal relationship has been suggested to exist between the intake of omega-3/6 fatty acids, such as docosahexanoic acid (DHA), eicosapentanoic acid (EPA), docosapentanoic acid (DPA) and arachidonic acid (AA), and atopic individuals suffering from allergies. In allergic cascades, the hallmark cytokine IL-4 bind to IL-4 receptor (IL-4R) and IL-13 binds to IL-13 receptor (IL-13R), this activates the STAT6 phosphorylation pathway leading to gene activation of allergen-specific IgE antibody production by B cells. The overall aim of this study was to characterize omega-3/6 fatty acids and their effects on STAT6 signaling pathway that results in IgE production in allergic individuals. METHODS: The fatty acids were tested in vitro with a HEK-Blue IL-4/IL-13 reporter cell line model, transfected with a reporter gene that produces an enzyme, secreted embryonic alkaline phosphatase (SEAP). SEAP acts as a substitute to IgE when cells are stimulated with bioactive cytokines IL-4 and/or IL-13. RESULTS: We have successfully used DHA, EPA and DPA in our studies that demonstrated a decrease in SEAP secretion, as opposed to an increase in SEAP secretion with AA treatment. A statistical Student's t-test revealed the significance of the results, confirming our initial hypothesis. CONCLUSION: We have successfully identified and characterised DHA, EPA, DPA and AA in our allergy model. While AA was a potent stimulator, DHA, EPA and DPA were potential inhibitors of IL-4R/IL-13R signalling, which regulates the STAT6 induced pathway in allergic cascades. Such findings are significant in the future design of dietary therapeutics for the treatment of allergies.

Thermotropic phase boundaries in classic ferroelectrics

High-performance piezoelectrics are lead-based solid solutions that exhibit a so-called morphotropic phase boundary, which separates two competing phases as a function of chemical composition; as a consequence, an intermediate low-symmetry phase with a strong piezoelectric effect arises. In search for environmentally sustainable lead-free alternatives that exhibit analogous characteristics, we use a network of competing domains to create similar conditions across thermal inter-ferroelectric transitions in simple, lead-free ferroelectrics such as BaTiO 3 and KNbO 3. Here we report the experimental observation of thermotropic phase boundaries in these classic ferroelectrics, through direct imaging of low-symmetry intermediate phases that exhibit large enhancements in the existing nonlinear optical and piezoelectric property coefficients. Furthermore, the symmetry lowering in these phases allows for new property coefficients that exceed all the existing coefficients in both parent phases. Discovering the thermotropic nature of thermal phase transitions in simple ferroelectrics thus presents unique opportunities for the design of 'green' high-performance materials.

Effect of wall thickness on the ferroelastic domain size of BaTiO3

Extremely regular self-organized patterns of 90^o ferroelastic domains have been reported in freestanding single crystal thin films of ferroelectric BaTiO₃. Lukyanchuk et al. [Phys Rev B 79, 144111 (2009)] have recently shown that the domain size as a function of thickness for such free standing films can be well described assuming that the domains are due to stress caused by a surface tension layer that does not undergo the paraelectric–ferroelectric transition. From the starting point of Lukyanchuk’s model, it is shown here that the ‘‘universal’’relationship between domain size and domain wall thickness previously observed in ferroelectrics, ferromagnets and multiferroics is also valid for ferroelastic domains.Further analysis of experimental data also shows that the domain wall thickness can vary considerably (an order of magnitude) from sample to sample even for the same material (BaTiO₃), in spite of which the domain size scaling model is still valid, provided that the correct,sample dependent, domain wall thickness is used.

Raman spectroscopic study of the uranyl carbonate mineral čejkaite and its comparison with synthetic trigonal Na4[UO2(CO3)3]

Raman and infrared spectroscopies were used to characterise two samples of triclinic ejkaite Na4[UO2(CO3)3] and its synthetic trigonal analogue. The v3 (UO2)2+ mode is not Raman active, whereas both the v3 and v1 (UO2)2+ modes are infrared active. U--O bond lengths in uranyls were calculated from the spectra obtained and compared with bond lengths derived from crystal structure analyses. From the higher number of bands related to the uranyl and carbonate vibrations, the presence of symmetrically distinct (UO2)2+ and (CO3)2- units in both structures is proposed.

Partial agonists of the [alpha]3[beta]4[ast] neuronal nicotinic acetylcholine receptor reduce ethanol consumption and seeking in rats

Alcohol use disorders (AUDs) impact millions of individuals and there remain few effective treatment strategies. Despite evidence that neuronal nicotinic acetylcholine receptors (nAChRs) have a role in AUDs, it has not been established which subtypes of the nAChR are involved. Recent human genetic association studies have implicated the gene cluster CHRNA3-CHRNA5-CHRNB4 encoding the α3, α5, and β4 subunits of the nAChR in susceptibility to develop nicotine and alcohol dependence; however, their role in ethanol-mediated behaviors is unknown due to the lack of suitable and selective research tools. To determine the role of the α3, and β4 subunits of the nAChR in ethanol self-administration, we developed and characterized high-affinity partial agonists at α3β4 nAChRs, CP-601932, and PF-4575180. Both CP-601932 and PF-4575180 selectively decrease ethanol but not sucrose consumption and operant self-administration following long-term exposure. We show that the functional potencies of CP-601932 and PF-4575180 at α3β4 nAChRs correlate with their unbound rat brain concentrations, suggesting that the effects on ethanol self-administration are mediated via interaction with α3β4 nAChRs. Also varenicline, an approved smoking cessation aid previously shown to decrease ethanol consumption and seeking in rats and mice, reduces ethanol intake at unbound brain concentrations that allow functional interactions with α3β4 nAChRs. Furthermore, the selective α4β2(*) nAChR antagonist, DHβE, did not reduce ethanol intake. Together, these data provide further support for the human genetic association studies, implicating CHRNA3 and CHRNB4 genes in ethanol-mediated behaviors. CP-601932 has been shown to be safe in humans and may represent a potential novel treatment for AUDs.

SEM-EDX, Raman and infrared spectroscopic characterization of the phosphate mineral frondelite (Mn2+)(Fe3+)4(PO4)3(OH)5

We have analyzed a frondelite mineral sample from the Cigana mine, located in the municipality of Conselheiro Pena, a well-known pegmatite in Brazil. In the Cigana pegmatite, secondary phosphates, namely eosphorite, fairfieldite, fluorapatite, frondelite, gormanite, hureaulite, lithiophilite, reddingite and vivianite are common minerals in miarolitic cavities and in massive blocks after triphylite. The chemical formula was determined as (Mn0.68, Fe0.32)(Fe3+)3,72(PO4)3.17(OH)4.99. The structure of the mineral was assessed using vibrational spectroscopy. Bands attributed to the stretching and bending modes of PO4 3- and HOPO3 3- units were identified. The observation of multiple bands supports the concept of symmetry reduction of the phosphate anion in the frondelite structure. Sharp Raman and infrared bands at 3581 cm−1 is assigned to the OH stretching vibration. Broad Raman bands at 3063, 3529 and 3365 cm−1 are attributed to water stretching vibrational modes.

Detection of mRNA for nuclear receptor co-activators 1 and 3 in archival breast cancer tissue and surrounding stroma : a tissue expression study

Before the age of 75 years, approximately 10% of women will be diagnosed with breast cancer, one of the most common malignancies and a leading cause of death among women. The objective of this study was to determine if expression of the nuclear receptor coactivators 1 and 3 (NCoA1 and NCoA3) varied in breast cancer grades. RNA was extracted from 25 breast tumours and transcribed into cDNA which underwent semi-quantitative polymerase chain reaction, normalised using 18S. Analysis indicated that an expression change for NCoA1 in cancer grades and estrogen receptor alpha negative tissue (P= 0.028 and 0.001 respectively). NCoA1 expression increased in grade 3 and estrogen receptor alpha negative tumours, compared to controls. NCoA3 showed a similar, but not significant, trend in grade and a non-significant decrease in estrogen receptor alpha negative tissues. Expression of NCoA1 in late stage and estrogen receptor alpha negative breast tumours may have implications to breast cancer treatment, particularly in the area of manipulation of hormone signalling systems in advanced tumours.

Integrin αvβ3 mediates upregulation of epidermal growth-factor receptor expression and activity in human ovarian cancer cells

Upon overexpression of integrin αvβ3 and its engagement by vitronectin, we previously showed enhanced adhesion, proliferation, and motility of human ovarian cancer cells. By studying differential expression of genes possibly related to these tumor biological events, we identified the epidermal growth-factor receptor (EGF-R) to be under control of αvβ3 expression levels. Thus in the present study we characterized αvβ3-dependent changes of EGF-R and found significant upregulation of its expression and activity which was reflected by prominent changes of EGF-R promoter activity. Upon disruption of DNA-binding motifs for the transcription factors p53, ETF, the repressor ETR, p50, and c-rel, respectively, we sought to identify DNA elements contributing to αvβ3-mediated EGF-R promoter induction. Both, the p53- and ETF-mutant, while exhibiting considerably lower EGF-R promoter activity than the wild type promoter, retained inducibility by αvβ3. Mutation of the repressor motif ETR, as expected, enhanced EGF-R promoter activity with a further moderate increase upon αvβ3 elevation. The p50-mutant displayed EGF-R promoter activity almost comparable to that of the wild type promoter with no impairment of induction by αvβ3. However, the activity of an EGF-R promoter mutant displaying a disrupted c-rel-binding motif did not only prominently decline, but, moreover, was not longer responsive to enhanced αvβ3, involving this DNA element in αvβ3-dependent EGF-R upregulation. Moreover, αvβ3 did not only increase the EGF-R but, moreover, also led to obvious co-clustering on the cancer cell surface. By studying αvβ3/EGF-R-effects on the focal adhesion kinase (FAK) and the mitogen activated protein kinases (MAPK) p44/42 (erk−1/erk−2), having important functions in synergistic crosstalk between integrins and growth-factor receptors, we found for both significant enhancement of expression and activity upon αvβ3/VN interaction and cell stimulation by EGF. Upregulation of the EGF-R by integrin αvβ3, both receptor molecules with a well-defined role as targets for cancer treatment, might represent an additional mechanism to adapt synergistic receptor signaling and crosstalk in response to an altered tumor cell microenvironment during ovarian cancer progression.

Bimolecular interaction of Insulin-Like Growth Factor (IGF) binding protein-2 with αvβ3 negatively modulates IGF-I-Mediated migration and tumor growth

Both the integrin and insulin-like growth factor binding protein (IGFBP) families independently play important roles in modulating tumor cell growth and progression. We present evidence for a specific cell surface localization and a bimolecular interaction between the αvβ3 integrin and IGFBP-2. The interaction, which could be specifically perturbed using vitronectin and αvβ3 blocking antibodies, was shown to modulate IGF-mediated cellular migration responses. Moreover, this interaction was observed in vivo and correlated with reduced tumor size of the human breast cancer cells, MCF-7β3, which overexpressed the αvβ3 integrin. Collectively, these results indicate that αvβ3 and IGFBP-2 act cooperatively in a negative regulatory manner to reduce tumor growth and the migratory potential of breast cancer cells.