TNF-induced necroptosis and PARP-1-mediated necrosis represent distinct routes to programmed necrotic cell death

Programmed necrosis is important in many (patho)physiological settings. For specific therapeutic intervention, however, a better knowledge is required whether necrosis occurs through one single “core program” or through several independent pathways. Previously, the poly(ADP-ribose) polymerase (PARP) pathway has been suggested as a crucial element of tumor necrosis factor (TNF)-mediated necroptosis. Here, we show that TNF-induced necroptosis and the PARP pathway represent distinct and independent routes to programmed necrosis. First, DNA-alkylating agents such as 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) or methyl methanesulfonate rapidly activate the PARP pathway, whereas this is a late and secondary event in TNF-induced necroptosis. Second, inhibition of the PARP pathway does not protect against TNF-induced necroptosis, e.g., the PARP-1 inhibitor 3-AB prevented MNNG- but not TNF-induced adenosine-5′-triposphate depletion, translocation of apoptosis-inducing factor, and necrosis. Likewise, olaparib, a more potent and selective PARP-1 inhibitor failed to block TNF-induced necroptosis, identical to knockdown/knockout of PARP-1, pharmacologic and genetic interference with c-Jun N-terminal kinases and calpain/cathepsin proteases as further components of the PARP pathway. Third, interruption of TNF-induced necroptosis by interference with ceramide generation, RIP1 or RIP3 function or by the radical scavenger butylated hydroxyanisole did not prevent programmed necrosis through the PARP pathway. In summary, our results suggest that the currently established role of the PARP pathway in TNF-induced necroptosis needs to be revised, with consequences for the design of future therapeutic strategies.     

GPR39: a Zn<Superscript>2+</Superscript>-activated G protein-coupled receptor that regulates pancreatic,gastrointestinal and neuronal functions

GPR39 is a vertebrate G protein-coupled receptor related to the ghrelin/neurotensin receptor subfamily. The receptor is expressed in a range of tissues including the pancreas, gut/gastrointestinal tract, liver, kidney and in some regions of the brain. GPR39 was initially thought to be the cognitive receptor for the peptide hormone, obestatin. However, subsequent in vitro studies have failed to demonstrate binding of this peptide to the receptor. Zn²⁺ has been shown to be a potent stimulator of GPR39 activity via the Gα_q, Gα_12/13 and Gα_s pathways. The potency and specificity of Zn²⁺ in activating GPR39 suggest it to be a physiologically important agonist. GPR39 is now emerging as an important transducer of autocrine and paracrine Zn²⁺ signals, impacting upon cellular processes such as insulin secretion, gastric emptying, neurotransmission and epithelial repair. This review focuses on the molecular, structural and biological properties of GPR39 and its various physiological functions.     

Natural polyploidization within tetraploid and hexaploid populations of the desert shrub Atriplex confertifolia

Shadscale ( Atriplex confertifolia ) is a wind-pollinated dioecious shrub of western North America with an unusual development of apparently autoploid races, showing all even ploidy levels from 2x to 12x (base x = 9). Of these, tetraploid races are the most frequently encountered, with octoploids the next most common, and hexaploids being much less common. In this study, the occurrence of neopolyploid individuals within tetraploid and hexaploid populations of shadscale was examined at natural sites in order to investigate the pathways by which octoploids may be formed and to find a possible explanation for the predominance of octoploids over hexaploids. The frequencies of apparent neopolyploid individuals among adults and the frequencies of their backcrosses were tabulated, as was the occurrence of neopolyploidy among seeds of female plants from some of the same populations. The neopolyploids encountered in these surveys were almost exclusively those expected from unions involving single unreduced gametes. 6x presumed neopolyploid plants were observed in tetraploid populations at a frequency of 0.20%, and 6x seeds were observed at a frequency of 1.91%. Within examined hexaploid populations, 9x adults were not encountered, but 9x seeds were observed at a rate of 0.52%. Evidence was obtained for the operation of some postulated autoploid pathways for generation of octoploids, but these routes did not operate at rates comparable to those for the production of hexaploids. Although the question needs to be studied by genetic methods, the most probable reason for scarcity of hexaploids in nature appears to be that some tetraploid races are diploidized, which would result in irregularities of meiosis in their neohexaploids and a failure to form new races due to infertility and inviability. El &ldquo;shadscale&rdquo; ( Atriplex confertifolia ) es un arbusto dioico del oeste de Norteam&eacute;rica polinizado por el viento que exhibe el desarrollo inusual de razas aparentemente poliploides, con todos los niveles pares de ploid&iacute;a desde 2x hasta 12x (x base = 9). De &eacute;stos, los m&aacute;s comunes son los tetraploides y luego los octoploides. Los hexaploides son mucho menos comunes. En este estudio, examinamos la presencia de individuos neopoliploides entre poblaciones tetraploides y hexaploides del shadscale en sitios naturales para investigar los medios por los cuales se pueden formar los octoploides y para encontrar una posible explicaci&oacute;n para el predominio de los octoploides sobre los hexaploides. Tabulamos la frecuencia de individuos aparentemente neopoliploides entre adultos y su descendencia retrocruzada, as&iacute; como la presencia de neopoliploides entre semillas de las plantas femeninas de algunas de las mismas poblaciones. Los neopoliploides encontrados en estos muestreos fueron casi exclusivamente los que se esperar&iacute;an de la uni&oacute;n de un gameto no reducido y un gameto reducido. Observamos plantas 6x presunta mente neopoliploides en poblaciones tetraploides con una frecuencia del 0.20%, o del 1.91% en las semillas. Entre las poblaciones examinadas de hexaploides, no encontramos adultos 9x, aunque los observamos con una frecuencia del 0.52% en las semillas. Obtuvimos evidencia de la operaci&oacute;n de algunos procesos autoploides postulados para explicar la generaci&oacute;n de octoploides, pero estos procesos no operan a frecuencias comparables a aquellas para la producci&oacute;n de hexaploides. Aunque es preciso investigar el tema mediante m&eacute;todos gen&eacute;ticos, la causa m&aacute;s probable para la escasez de los hexaploides en entornos naturales parece ser que algunas razas tetraploides son diploidizadas, produciendo irregularidades mei&oacute;ticas en sus neohexaploides, los cuales no logran formar razas nuevas debido a su infertilidad o inviabilidad.     

Beaver herbivory of willow under two flow regimes: a comparative study on the Green and Yampa rivers

The effect of flow regulation on plant-herbivore ecology has received very little attention, despite the fact that flow regulation can alter both plant and animal abundance and environmental factors that mediate interactions between them. To determine how regulated flows have impacted beaver ( Castor Canadensis ) and sandbar willow ( Salix exigua ) ecology, we first quantified the abundance and mapped the spatial distribution of sandbar willow on alluvial sections of the flow-regulated Green River and free-flowing Yampa River in northwestern Colorado. We then established 16 and 15 plots (1 m x 2.7 m) in patches of willow on the Green and Yampa Rivers, respectively, to determine whether rates of beaver herbivory of willow differed between rivers (Green versus Yampa River), seasons (fall-winter versus spring-summer), and years (spring 1998-spring 1999 versus spring 1999-spring 2000). Areal extent of willow was similar on each river, but Green River willow patches were smaller and more numerous. Beavers cut more stems during fall and winter than spring and summer and cut over 6 times more stems (percentage basis) on the Green River than on the Yampa River. We attribute the between-river difference in herbivory to higher availability of willow, greater beaver density, and lower availability of young Fremont cottonwood ( Populus deltoids subsp. wislizenii ; an alternative food source) on the Green River. Flow regulation increased willow availability to beaver by promoting the formation of island patches that are continuously adjacent to water and feature a perimeter with a relatively high proportion of willow interfacing with water.     

Vegetation response to fire and postburn seeding treatments in juniper woodlands of the Grand Staircase-Escalante National Monument, Utah

We compared 3 naturally ignited burns with unburned sites in the Grand Staircase-Escalante National Monument. Each burn site was restored with native and nonnative seed mixes, restored with native seeds only, or regenerated naturally. In general, burned sites had significantly lower native species richness (1.8 vs. 2.9 species), native species cover (11% vs. 22.5%), and soil crust cover (4.1% vs. 15%) than unburned sites. Most burned plots, seeded or not, had significantly higher average nonnative species richness and cover and lower average native species richness and cover than unburned sites. Regression tree analyses suggest site variation was equally important to rehabilitation results as seeding treatments. Low native species richness and cover, high soil C, and low cover of biological soil crusts may facilitate increased nonnative species richness and cover. Our study also found that unburned sites in the region had equally high cover of nonnative species compared with the rest of the Monument. Cheatgrass ( Bromus tectorum ) dominated both burned and unburned sites. Despite the invasion of cheatgrass, unburned sites still maintain higher native species richness; however, the high cover of cheatgrass may increase fire frequency, further reduce native species richness and cover, and ultimately change vegetation composition in juniper woodlands.     

Breeding populations of Swainson's Hawks, Red-Tailed Hawks, and Golden Eagles in north central Oregon: 1975-1982 and 1999

Populations of breeding Swainson's Hawks ( Buteo swainsoni ), Red-tailed Hawks ( B. jamaicensis ), and Golden Eagles ( Aquila chrysaetos ) present in 1999 were compared with populations present between 1975 and 1982 at a 129-km 2 site in north central Oregon. Populations of Red-tailed Hawks and Golden Eagles remained unchanged, but the number of Swainson's Hawks pairs increased from 15 to 17. In 1999 Golden Eagles used nests occupied between 1975 and 1982, and 7 of 31 pairs of Red-tailed Hawks used nests occupied in earlier years. No Swainson's Hawks nested in trees occupied earlier. Few changes in territorial boundaries were detected.     

Drumming behavior and life history notes of a high-altitude Colorado population of the stonefly Isoperla petersoni Needham

Late instar nymphs and adults of a Colorado Hudsonian zone population of Isoperla petersoni Needham and Christenson were studied during the summer and early fall months of 1998, when stream temperature ranged from 3.3° C to 8.9° C. Early and middle instar nymphs were absent from July to October, and nymphs attained maximum size in mid-August during the 2nd week of adult field presence, suggesting a univoltine-slow life cycle. Nymphs were carnivorous and fed primarily on chironomid larvae. Adults were present from August to mid-October, with peak numbers of adult males and females occurring in mid-September and late September, respectively. Fecundity of field-collected females averaged 94.1 ± 45.15 eggs per female in September ( N = 81) and decreased to 85.2 ± 57.6 in October ( N = 12). Drumming duets were 2-way (male-female), and female answers followed male calls (nonoverlapped) or began before completion of the male call (overlapped). Male calls averaged 11.1 ± 2.09 beats and female answers averaged 6.2 ± 2.99, with mean intervals of 118 and 58 ms, respectively. The average number of female answer beats increased from 5.3 ± 2.56 when duets were nonoverlapped, to 6.6 ± 3.08 when overlapped.     

Photosynthesis by isolated chloroplasts of Sorghum vulgare.

The ambiguous location of photosynthetic carboxylases of mesophyll and bundle sheath chloroplasts of sorghum was investigated after successful homogeneous preparation. The phosphoenol pyruvate carboxylase was found as a particulate enzyme in the mesophyll cell chloroplasts and ribulose 1,5-biphosphate carboxylase in the stroma of the bundle sheath cell chloroplasts. Extensive characterization was carried out on these 2 enzymes for better understanding of the enzyme action.     

Common variants at 11p13 are associated with susceptibility to tuberculosis

After imputation of data from the 1000 Genomes Project into a genome-wide dataset of Ghanaian individuals with tuberculosis and controls, we identified a resistance locus on chromosome 11p13 downstream of the WT1 gene (encoding Wilms tumor 1). The strongest signal was obtained at the rs2057178 SNP (P = 2.63 × 10(-9)). Replication in Gambian, Indonesian and Russian tuberculosis case-control study cohorts increased the significance level for the association with this SNP to P = 2.57 × 10(-11).