Expression and function of hypoxia inducible factor-1 alpha in human melanoma under non-hypoxic conditions

<p>Abstract</p> <p>Background</p> <p>Hypoxia inducible factor-1 alpha (HIF-1α) protein is rapidly degraded under normoxic conditions. When oxygen tensions fall HIF-1α protein stabilizes and transactivates genes involved in adaptation to hypoxic conditions. We have examined the normoxic expression of HIF-1α RNA and protein in normal human melanocytes and a series of human melanoma cell lines isolated from radial growth phase (RGP), vertical growth phase (VGP) and metastatic (MET) melanomas.</p> <p>Results</p> <p>HIF-1α mRNA and protein was increased in RGP vs melanocytes, VGP vs RGP and MET vs VGP melanoma cell lines. We also detected expression of a HIF-1α mRNA splice variant that lacks part of the oxygen-dependent regulation domain in WM1366 and WM9 melanoma cells. Over-expression of HIF-1α and its splice variant in the RGP cell line SbCl2 resulted in a small increase in soft agar colony formation and a large increase in matrigel invasion relative to control transfected cells. Knockdown of HIF-1α expression by siRNA in the MET WM9 melanoma cell line resulted in a large decrease in both soft agar colony formation and matrigel invasion relative to cells treated with non-specific siRNA. There is a high level of ERK1/2 phosphorylation in WM9 cells, indicating an activated Ras-Raf-MEK-ERK1/2 MAPK pathway. Treatment of WM9 cells with 30 μM U0126 MEK inhibitor, decreased ERK1/2 phosphorylation and resulted in a decrease in HIF-1α expression. However, a 24 h treatment with 10 μM U0126 totally eliminated Erk1/2 phosphorylation, but did not change HIF-1alpha levels. Furthermore, siRNA knockdown of MEK siRNA did not change HIF-1alpha levels.</p> <p>Conclusion</p> <p>We speculate that metabolic products of U0126 decrease HIF-1alpha expression through "off target" effects. Overall our data suggest that increased HIF-1α expression under normoxic conditions contributes to some of the malignant phenotypes exhibited by human melanoma cells. The expanded role of HIF-1α in melanoma biology increases its importance as a therapeutic target.</p

Kaolin shear thickening fluid reinforced UHMWPE composites for protective clothing

This study reports the designing and reinforcing of impact resistant textile composites using kaolin based shear thickening colloidal dispersions as the filler material. The reinforced fabric is targeted for the chest protection of cricketers. A shear thickening fluid (STF) has been prepared using kaolin and glycerol, at kaolin volume fractions of 34% and 38%. A combination of mixing techniques including mechanical blending and ultra-sonication are used to prepare the colloidal dispersions. Ultra high molecular weight polyethylene (UHMWPE) woven fabric structures are reinforced with the STF. The fabric coated with STF are then measured for their flexibility, and impact resistance using Shirley stiffness tester and a series of modified drop tower tests respectively. Kaolin STF at 38% volume fraction shows best results in impregnated fabric samples. STF reinforced fabrics provide better impact resistance with improved moisture absorption and flexibility in comparison to the conventional chest guard material

Reduced tillage, but not organic matter input, increased nematode diversity and food web stability in European long‐term field experiments

Soil nematode communities and food web indices can inform about the complexity, nutrient flows and decomposition pathways of soil food webs, reflecting soil quality. Relative abundance of nematode feeding and life‐history groups are used for calculating food web indices, i.e., maturity index (MI), enrichment index (EI), structure index (SI) and channel index (CI). Molecular methods to study nematode communities potentially offer advantages compared to traditional methods in terms of resolution, throughput, cost and time. In spite of such advantages, molecular data have not often been adopted so far to assess the effects of soil management on nematode communities and to calculate these food web indices. Here, we used high‐throughput amplicon sequencing to investigate the effects of tillage (conventional vs. reduced) and organic matter addition (low vs. high) on nematode communities and food web indices in 10 European long‐term field experiments and we assessed the relationship between nematode communities and soil parameters. We found that nematode communities were more strongly affected by tillage than by organic matter addition. Compared to conventional tillage, reduced tillage increased nematode diversity (23% higher Shannon diversity index), nematode community stability (12% higher MI), structure (24% higher SI), and the fungal decomposition channel (59% higher CI), and also the number of herbivorous nematodes (70% higher). Total and labile organic carbon, available K and microbial parameters explained nematode community structure. Our findings show that nematode communities are sensitive indicators of soil quality and that molecular profiling of nematode communities has the potential to reveal the effects of soil management on soil quality

RR-Parity Violation in Flavor Changing Neutral Current Processes and Top Quark Decays

We show that supersymmetric $R$-parity breaking ($\not R_p$) interactions always result in Flavor Changing Neutral Current (FCNC) processes. Within a single coupling scheme, these processes can be avoided in either the charge $+2/3$ or the charge $-1/3$ quark sector, but not both. These processes are used to place constraints on \Rp couplings. The constraints on the first and the second generations are better than those existing in the literature. The \Rp interactions may result in new top quark decays. Some of these violate electron-muon universality or produce a surplus of $b$ quark events in $t\bar{t}$ decays. Results from the CDF experiment are used to bound these \Rp couplings.Comment: LaTeX, 20 pages, spelling corrected from origina

The band structure of BeTe - a combined experimental and theoretical study

Using angle-resolved synchrotron-radiation photoemission spectroscopy we have determined the dispersion of the valence bands of BeTe(100) along $\Gamma X$, i.e. the [100] direction. The measurements are analyzed with the aid of a first-principles calculation of the BeTe bulk band structure as well as of the photoemission peaks as given by the momentum conserving bulk transitions. Taking the calculated unoccupied bands as final states of the photoemission process, we obtain an excellent agreement between experimental and calculated spectra and a clear interpretation of almost all measured bands. In contrast, the free electron approximation for the final states fails to describe the BeTe bulk band structure along $\Gamma X$ properly.Comment: 21 pages plus 4 figure

Renormalization Group Induced Neutrino Mass in Supersymmetry without R-parity

We study supersymmetric models without R parity and with universal soft supersymmetry breaking terms. We show that as a result of the renormalization group flow of the parameters, a misalignment between the directions in field space of the down-type Higgs vacuum expectation value $v_d$ and of the $\mu$ term is always generated. This misalignment induces a mixing between the neutrinos and the neutralinos, resulting in one massive neutrino. By means of a simple approximate analytical expression, we study the dependence on the different parameters that contribute to the misalignment and to $m_\nu$. In large part of the parameter space this effect dominates over the standard one-loop contributions to $m_\nu$; we estimate 1 MeV \lsim m_\nu \lsim 1 GeV. Laboratory, cosmological and astrophysical constraints imply m_\nu \lsim 100 eV. To be phenomenologically viable, these models must be supplemented with some additional mechanism to ensure approximate alignment and to suppress $m_\nu$.Comment: 21 pages, LaTex. Few points clarified, results unchanged. Final version to appear on Physical Review

Models of Neutrino Masses and Baryogenesis

Majorana masses of the neutrino implies lepton number violation and is intimately related to the lepton asymmetry of the universe, which gets related to the baryon asymmetry of the universe in the presence of the sphalerons during the electroweak phase transition. Assuming that the baryon asymmetry of the universe is generated before the electroweak phase transition, it is possible to dicriminate different classes of models of neutrino masses. While see-saw mechanism and the triplet higgs mechanism are preferred, the Zee-type radiative models and the R-parity breaking models requires additional inputs to generate baryon asymmetry of the universe during the electroweak phase transition.Comment: 27 pages including 5 figures; Review article for Pramana: the Indian Journal of Physic

Metatranscriptomic Sequencing of Winter and Spring Planktonic Communities from Lake Erie, a Laurentian Great Lake

Previous reports suggest planktonic and under-ice winter microbial communities in Lake Erie are dominated by diatoms. Here, we report the assembled metatranscriptomes of 79 Lake Erie surface water microbial communities spanning both the winter (28 samples) and spring (51 samples) months over spatial, temporal, and climatic gradients in 2019 through 2020

Dissolution of Olivine, Siderite, and Basalt at 80 Deg C in 0.1 M H2SO4 in a Flow Through Process: Insights into Acidic Weathering on Mars

The occurrence of jarosite, other sulfates (e.g., Mg-and Ca-sulfates), and hematite along with silicic-lastic materials in outcrops of sedimentary materials at Meridiani Planum (MP) and detection of silica rich deposits in Gusev crater, Mars, are strong indicators of local acidic aqueous processes [1,2,3,4,5]. The formation of sediments at Meridiani Planum may have involved the evaporation of fluids derived from acid weathering of Martian basalts and subsequent diagenesis [6,7]. Also, our previous work on acid weathering of basaltic materials in a closed hydro-thermal system was focused on the mineralogy of the acid weathering products including the formation of jarosite and gray hematite spherules [8,9,10]. The object of this re-search is to extend our earlier qualitative work on acidic weathering of rocks to determine acidic dissolution rates of Mars analog basaltic materials at 80 C using a flow-thru reactor. We also characterized residual phases, including poorly crystalline or amorphous phases and precipitates, that remained after the treatments of olivine, siderite, and basalt which represent likely MP source rocks. This study is a stepping stone for a future simulation of the formation of MP rocks under a range of T and P

Low-Scale See-Saw Mechanisms for Light Neutrinos

Alternatives to the see-saw mechanism are explored in supersymmetric models with three right-handed or sterile neutrinos. Tree-level Yukawa couplings can be drastically suppressed in a natural way to give sub-eV Dirac neutrino masses. If, in addition, a B-L gauge symmetry broken at a large scale M_G is introduced, a wider range of possibilities opens up. The value of the right-handed neutrino mass M_R can be easily disentangled from that of M_G. Dirac and Majorana neutrino masses at the eV scale can be generated radiatively through the exchange of sneutrinos and neutralinos. Dirac masses m_D owe their smallness to the pattern of light-heavy scales in the neutralino mass matrix. The smallness of the Majorana masses m_L is linked to a similar see-saw pattern in the sneutrino mass matrix. Two distinct scenarios emerge. In the first, with very small or vanishing M_R, the physical neutrino eigenstates are, for each generation, either two light Majorana states with mixing angle ranging from very small to maximal, depending on the ratio m_D/M_R, or one light Dirac state. In the second scenario, with a large value of M_R, the physical eigenstates are two nearly unmixed Majorana states with masses \sim m_L and \sim M_R. In both cases, the (B-L)-breaking scale M_G is, in general, much smaller than that in the traditional see-saw mechanism.Comment: 31 pages, Latex, references added, version to appear in Phys. Rev.