Phospholipid flippases attenuate LPS-induced TLR4 signaling by mediating endocytic retrieval of Toll-like receptor 4

P4-ATPases are lipid flippases that catalyze the transport of phospholipids to create membrane phospholipid asymmetry and to initiate the biogenesis of transport vesicles. Here we show, for the first time, that lipid flippases are essential to dampen the inflammatory response and to mediate the endotoxin-induced endocytic retrieval of Toll-like receptor 4 (TLR4) in human macrophages. Depletion of CDC50A, the β-subunit that is crucial for the activity of multiple P4-ATPases, resulted in endotoxin-induced hypersecretion of proinflammatory cytokines, enhanced MAP kinase signaling and constitutive NF-κB activation. In addition, CDC50A-depleted THP-1 macrophages displayed reduced tolerance to endotoxin. Moreover, endotoxin-induced internalization of TLR4 was strongly reduced and coincided with impaired endosomal MyD88-independent signaling. The phenotype of CDC50A-depleted cells was also induced by separate knockdown of two P4-ATPases, namely ATP8B1 and ATP11A. We conclude that lipid flippases are novel elements of the innate immune response that are essential to attenuate the inflammatory response, possibly by mediating endotoxin-induced internalization of TLR4.     

The concept of intelligibility in modern physics (1948)

This is an English translation of Paul Feyerabend's earliest extant essay “Der Begriff der Verständlichkeit in der modernen Physik” (1948). In it, Feyerabend defends positivism as a progressive framework for scientific research in certain stages of scientific development. He argues that in physics visualizability (Anschaulichkeit) and intelligibility (Verständlichkeit) are time-conditioned concepts: what is deemed visualizable in the development of physical theories is relative to a specific historical context and changes over time. He concludes that from time to time the abandonment of visualizability is crucial for progress in physics, as it is conducive to major theory change, illustrating the point on the basis of advances in atomic theory.     

Swimming and bipedal bottom-running in the pig-nosed turtle Carettochelys insculpta Ramsay, 1886

The pig-nosed freshwater turtle Carettochelys insculpta Ramsay, 1886 has paddle-shaped foreflippers that resemble those of sea turtles. These turtles exhibit a wide range of swimming capabilities. As well as swimming by the action of synchronized foreflippers alone, they sometimes used alternate hindlimb action at the same time. They could swim by ipsilaterally synchronized action of all four limbs, or by hindlimb action alone (combined with stabilizer/lift function of the foreflippers). The turtles also showed flexibility in bottom-walking. Besides the ipsilaterally synchronized quadrupedal action characteristic of other freshwater turtles, they exhibited a bipedal walking mechanism never previously described. Propelled by alternate action of the hindlimbs, the animals held the head and plastron above the substratum, with the large foreflippers acting to provide anterior lift and stability against roll and yaw. Because both hindlimbs were sometimes off the substratum simultaneously during bipedal locomotion, their duty factors were < 0.5, implying a bipedal run.     

Dispersal and extraterritorial movements of swift foxes ( Vulpes velox ) in northwestern Texas

Dispersal plays an important role in the population dynamics of many carnivores, yet little information exists about the dispersal and movement patterns of swift foxes ( Vulpes velox ). We radio-collared and monitored 68 swift foxes for dispersal at 2 study sites in northwestern Texas from January 2002 to April 2004. Dispersal distance for juveniles (13.1 ± 0.3 km, s ), adults (10 ± 4.7 km) and transients (25.4 ± 9.1 km) did not differ by age class ( F = 1.49, df = 2, P = 0.24) or sex ( F = 0.23, df = 1, P = 0.63) but differed by study site ( F = 4.72, df = 1, P = 0.04). Mean dispersal distance from private ranches (PR) was greater than from National Grasslands (NG). Peak dispersal occurred during October– November (13 individuals) and January–February (7 individuals). Dispersal direction was influenced by land-use practices (i.e., toward rangelands and away from anthropogenic features). Direction of dispersal among foxes that occupied the NG was uniform ( n = 16, P = 0.08), whereas foxes from PR dispersed in a northwesterly direction ( n = 18, P ≤ 0.001) away from a town and croplands. Three resident adult foxes made extraterritorial movements. Distances of these movements ranged from 0.2 km to 11.4 km. Distance of extraterritorial movements did not differ by sex ( F = 0.05, P = 0.83), nor by duration of movement ( F = 1.11, P = 0.32). Knowledge of movement distances and patterns is important for conservation and protection of swift foxes and their habitats.     

Electrophoretic study of cutthroat trout populations in Utah

Thirty - nine Utah streams were sampled for cutthroat trout. Of these, 31 contain cutthroat or cutthroat / rainbow hybrid populations. By using starch gel electrophoresis, these populations were segregated into three groups. One group consisted predominately of fish from the Sevier River (of the Bonneville Basin) and Colorado drainages. A second was primarily populations from the Bear River Drainage (Bonneville Basin) as well as some scattered populations along the Wasatch Front (Bonneville Basin). The third consisted of Wasatch Front populations and populations that have hybridized with rainbow trout. Since different subspecies of cutthroat trout are native to the Colorado and Bonneville drainages, one would expect the populations from within the Bonneville Basin to be more similar to one another and less similar to the Colorado River populations. That this did not occur raises questions concerning the evolutionary relationships of the subspecies and the populations. It is clear that at least a northern (Bear River) and southern (Sevier River) form of the Bonneville cutthroat exists. The Wasatch Front may represent an intermediate zone where these two forms intergrade. &nbsp;&nbsp;&nbsp;     

Recovery of Gambel oak after fire in central Utah

The height of oak ( Quercus gambelii Nutt.) stems was measured on several fire scars within the Uinta National Forest and vicinity and compared with the height of oak stems on adjacent, nonburned areas. A significant relationship exists between the recovery rate of oak after fire and elevation, with the recovery rate being greatest at low elevations. A trend also exists showing that recovery tends to be greater on south to westerly exposures than on north to easterly exposures.     

Evolutionary divergence in closely related populations of Mimulus guttatus (Scrophulariaceae)

The evolutionary divergence of five closely related populations of the yellow monkey flower. Mimulus guttatus was compared with the length of time the populations could have occupied the site and with the ability of the populations to intercross. Populations from the younger sites were found to be morphologically intermediate to populations from the older sites. Ability to intercross was not correlated with morphological divergence at this stage of evolution. &nbsp;     

Vascular flora of Kane Lake Cirque, Pioneer Mountains, Idaho

Kane Lake Cirque lies in the western Pioneer Mountains of south central Idaho. An inventory of the high elevation flora of the cirque revealed the presence of 180 vascular taxa representing 95 genera and 30 families. Five alpine taxa are here documented from Idaho for the first time: Carex incurviformis Mack., Draba fladnizensis Wilfen., Potentilla nivea L., Ranunculus gelidus Kar. & Kir., and Ranunculus pygmaeus Wahlenb. Kane Lake Cirque also contains populations of four additional alpine taxa considered to be of conservation concern in Idaho: Erigeron humilis Graham, Parnassia kotzebuei Cham., Saxifraga adscendens L., and Saxifraga cernua L.     

Mate sampling in a natural population of Pecos gambusia, Gambusia nobilis

Normal 0 false false false MicrosoftInternetExplorer4 st1\:*{behavior:url(#ieooui) } /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman"; mso-ansi-language:#0400; mso-fareast-language:#0400; mso-bidi-language:#0400;} Much research has been conducted on the mating systems of poeciliid fish in aquaria; however, there are fewer studies that examine mate sampling of these fish in the wild. In general, male poeciliids are characterized as being unselective in their mate choices and will attempt to copulate with seemingly all available females. Females are selective, copulate infrequently, and are often pursued by &ldquo;ardent&rdquo; males who may force copulations. To avoid male harassment, females in aquaria will often shelter from males among other females in shoals. Here, we examined the mate-sampling behaviors of male and female Pecos gambusia Gambusia nobilis by following individuals swimming in an outflow pool of Diamond Y Spring in southwestern Texas. In most cases, a male approached a solitary female, followed her briefly, and then left for no apparent reason. Approaching a number of females increased the likelihood that the male would follow one, and the longer a male followed a female, the more likely he was to copulate with her. As females were larger and faster than males, they could avoid males by swimming away from them. We found no evidence of the persistent males that harass seemingly unreceptive females as seen under aquarium conditions, nor did we see females join a shoal to stop pursuit by males. However, the activity of one male following a female did appear to attract other males who would compete to follow and attempt copulation. This competition might ensure that only superior males gain reproductive opportunities. Se han investigado extensamente los sistemas de apareamiento de pec&iacute;lidos en acuario; no obstante, hay relativamente pocos estudios que examinan la elecci&oacute;n de pareja de estos peces en su h&aacute;bitat natural. Los pec&iacute;lidos machos no suelen ser selectivos en su elecci&oacute;n de pareja y parecen intentar copular con todas las hembras que est&eacute;n a su alcance. Las hembras son selectivas, no copulan frecuentemente y a menudo las persiguen machos excitados que pueden copular con ellas forzadamente. Para evitar el acosamiento de los machos, en acuario las hembras a menudo se refugian de los machos entre otras hembras en bancos. Para este estudio, examinamos el comportamiento de elecci&oacute;n de pareja de gambusias de pecos ( Gambusia nobilis ) machos y hembras al observar algunos individuos en un remanso del Diamond Y Spring en el suroeste de Texas. En la mayor&iacute;a de los casos, el macho se acercaba a una hembra solitaria, la segu&iacute;a brevemente y luego se alejaba sin motivo aparente. El acercarse a varias hembras aumentaba la probabilidad de que persiguiera a una de ellas, y cuanto m&aacute;s la segu&iacute;a, m&aacute;s probable era que copulara con ella. Dado que las hembras son m&aacute;s grandes y m&aacute;s r&aacute;pidas que los machos, pod&iacute;an eludirlos si no correspond&iacute;an. No observamos machos persistentes que acosaran hembras aparentemente poco receptivas como se ha documentado en acuario, ni tampoco vimos hembras que se unieran a bancos para evitar la persecuci&oacute;n de machos. Pero cuando un macho persegu&iacute;a una hembra, parec&iacute;a atraer otros, los cuales compet&iacute;an entre s&iacute; para seguirla e intentar copular con ella. Esta competencia podr&iacute;a garantizar que solo los machos superiores tengan oportunidades reproductivas.     

Soil properties associated with vegetation patches in a Pinus ponderosa —bunchgrass mosaic

Since Euro-American settlement, fire exclusion and other factors have dramatically altered interior western coniferous forests. Once open and parklike, present-day structure in many southwestern Pinus ponderosa forests consists of dense stands of young, small-diameter trees, with small patches of larger, old trees, and relict open bunchgrass areas. Our objectives were to assess differences in soil properties associated with these different vegetation patches. We examined soil morphological characteristics, pH, organic C concentration, total N concentration, C:N ratio, and phytolith concentration from profiles within 6 transects (18 soil pedons) crossing patches of dense stands of small diameter trees, patches of old-growth trees, and open grassy areas. Results indicate that old-growth plots had significantly lower A horizon pH and thicker O horizons than grass plots. In general, we found vegetation patches had statistically similar C and N concentrations and C:N ratios for A and B horizons; however, C in the A horizon was positively correlated with O horizon accumulation ( r 2 = 0.79). Greater accumulation of organic C in the A horizon of forested areas contrasts with commonly reported results from mesic, mid-continental prairie-forest ecosystems but is typical for many arid, semiarid, and humid savanna ecosystems. Phytolith concentration was similar among old-growth pine, dense younger pine, and open grassy plots; the lack of a spatial pattern in phytolith distribution could indicate that grass cover was more spatially continuous in the past. Additionally, this interpretation is consistent with current theories regarding historical vegetation change in these forests.