Mechanical unloading impairs keratinocyte migration and angiogenesis during cutaneous wound healing.

Although initially thought to improve an individual's ability to heal, mechanical unloading promoted by extended periods of bed rest has emerged as a contributing factor to delayed or aberrant tissue repair. Using a rat hindlimb unloading (HLU) model of hypogravity, we mimicked some aspects of physical inactivity by removing weight-bearing loads from the hindlimbs and producing a systemic cephalic fluid shift. This model simulates bed rest in that the animal undergoes physiological adaptations, resulting in a reduction in exercise capability, increased frequency of orthostatic intolerance, and a reduction in plasma volume. To investigate whether changes associated with prior prolonged bed rest correlate with impaired cutaneous wound healing, we examined wound closure, angiogenesis, and collagen content in day 2 to day 21 wounds from rats exposed to HLU 2 wk before excisional wounding. Wound closure was delayed in day 2 wounds from HLU rats compared with ambulatory controls. Although the levels of proangiogenic growth factors, fibroblast growth factor-2 (FGF-2), and vascular endothelial growth factor (VEGF) were similar between the two groups, wound vascularity was significantly reduced in day 7 wounds from HLU animals. To further examine this disparity, total collagen content was assessed but found to be similar between the two groups. Taken together, these results suggest that keratinocyte and endothelial cell function may be impaired during the wound healing process under periods of prolonged inactivity or bed rest.     

Interleukin-11 antagonizes Fas ligand-mediated apoptosis in IEC-18 intestinal epithelial crypt cells: role of MEK and Akt-dependent signaling

Interleukin-11 (IL-11) displays epithelial cytoprotective effects during intestinal injury. Antiapoptotic effects of IL-11 have been described, yet mechanisms remain unclear. Fas/CD95 death receptor signaling is upregulated in ulcerative colitis, leading to mucosal breakdown. We hypothesized that IL-11 inhibits Fas ligand (FasL)-mediated apoptosis in intestinal epithelia. Cell death was monitored in IEC-18 cells by microscopy, caspase and poly(ADP-ribose) polymerase cleavage, mitochondrial release of cytochrome c, and abundance of cytoplasmic oligonucleosomal DNA. RT-PCR was used to monitor Fas, cIAP1, cIAP2, XIAP, cFLIP, survivin, and Bcl-2 family members. Fas membrane expression was detected by immunoblot. Inhibitors of JAK2, phosphatidylinositol 3-kinase (PI3-kinase), Akt 1, MEK1 and MEK2, and p38 MAPK were used to delineate IL-11's antiapoptotic mechanisms. IL-11 did not alter Fas expression. Pretreatment with IL-11 for 24 h before FasL reduced cytoplasmic oligonucleosomal DNA by 63.2%. IL-11 also attenuated caspase-3, caspase-9, and poly(ADP-ribose) polymerase cleavage without affecting expression of activated caspase-8 p20 or cytochrome c release. IL-11 did not affect mRNA expression of the candidate antiapoptotic genes. The MEK1 and MEK2 inhibitors U-0126 and PD-98059 significantly attenuated the protection of IL-11 against caspase-3 and caspase-9 cleavage and cytoplasmic oligonucleosomal DNA accumulation. Although Akt inhibition reversed IL-11-mediated effects on caspase cleavage, it did not reverse the protective effects of IL-11 by DNA ELISA. We conclude that IL-11-dependent MEK1 and MEK2 signaling inhibits FasL-induced apoptosis. The lack of reversal of the IL-11 effect on DNA cleavage by Akt inhibition, despite antagonism of caspase cleavage, suggests that IL-11 inhibits caspase-independent cell death signaling by FasL in a MEK-dependent manner.     

Male reproductive investment and queen mating-frequency in fungus-growing ants

Sperm number and male accessory gland compounds are often importantdeterminants of male mating success but have been little studiedin social insects. This is because mating in social insectsis often difficult to manipulate experimentally, and first evidencefor an explicit influence of accessory gland secretions on malemating success in social insects was obtained only recently.Here we perform a comparative analysis of male sexual organsacross 11 species of attine fungus-growing ants, representingboth genera with single- and multiple-queen mating. We foundthat the general morphology of the male sexual organs was verysimilar across all species, but the relative sizes of the accessoryglands and the sperm-containing accessory testes vary significantlyacross species. Small testes and large accessory glands characterizespecies with singly mated queens, whereas the opposite is foundin species with multiply mated queens. However, in the socialparasite Acromyrmex insinuator, in which queens have secondarilyreverted to single mating, males have accessory gland characteristicsreminiscent of the lower attine ants, but without having significantlyreduced their investment in sperm production. We hypothesizethat the main function of accessory gland compounds in attineants is to monopolize male paternity in similar ways as knownfrom other social insects. This would imply that the evolutionof polyandry in the terminal clade of the fungus-growing ants(the leafcutter ants) has resulted in selection for decreasedinvestment by males in accessory gland secretions and increasedinvestment in sperm number, in response to sperm competitionfor sperm storage.     

The BRCA1/BARD1 heterodimer, a tumor suppressor complex with ubiquitin E3 ligase activity.

Although the protein product of the BRCA1 tumor suppressor gene has been implicated in a surprisingly diverse array of biological processes, the molecular mechanism by which BRCA1 loss promotes tumor formation remains unclear. Nonetheless, a pivotal advance has been achieved by recent studies that establish BRCA1 and its partner polypeptide BARD1 as enzymatic mediators of protein ubiquitination. The potent ubiquitin E3 ligase activity of the BRCA1/BARD1 heterodimer may be responsible for many of the biological properties attributed to BRCA1, including its ability to suppress tumor formation in normal cells.     

A Wandering Mind Does Not Stray Far from Home: The Value of Metacognition in Distant Search

When faced with a problem, how do individuals search for potential solutions? In this article, we explore the cognitive processes that lead to local search (i.e., identifying options closest to existing solutions) and distant search (i.e., identifying options of a qualitatively different nature than existing solutions). We suggest that mind wandering is likely to lead to local search because it operates by spreading activation from initial ideas to closely associated ideas. This reduces the likelihood of accessing a qualitatively different solution. However, instead of getting lost in thought, individuals can also step back and monitor their thoughts from a detached perspective. Such mindful metacognition, we suggest, is likely to lead to distant search because it redistributes activation away from initial ideas to other, less strongly associated, ideas. This hypothesis was confirmed across two studies. Thus, getting lost in thoughts is helpful when one is on the right track and needs only a local search whereas stepping back from thoughts is helpful when one needs distant search to produce a change in perspective.     

The artificial insemination of bumblebee queens

Summary: Artificial insemination (AI) is a technique to transfer instrumentally sperm from the male into the female's reproductive system. AI is widespread in vertebrates for economical animal breeding and for conservation biology. However, in invertebrates only a few cases of successful AI have been reported. In this paper we describe a new technique to artificially inseminate bumblebee queens (Bombus spp.). Males were dissected and the accessory testes were removed and washed in insect ringer. They were then opened and the outflowing sperm was picked up with a glass capillary mounted on a syringe. For the sperm transfer into the queen we adapted a standard apparatus used for honeybee inseminations. The queen was anaesthetized with CO₂, held in place by a queen holder and the sting chamber was opened using two hooks. The sperm containing glass capillary was introduced into the queen's sexual tract. The sperm was released into the bursa copulatrix very near the opening of the spermathecal duct of the queen. Inseminated queens were hibernated for 2 weeks and produced a normal colony under field conditions. Multiple inseminations proved to be successful since different patrilines could be detected in the worker offspring. Successful inseminations were performed for B. terrestris, B. lucorum and B. hypnorum.     

Characterization of the chirality of the monohydroxy-eicosatetraenoic acids produced by rat basophilic leukemia cells

Incubation of rat basophilic leukemia cells with exogenous arachidonic acid and permeabilizing concentrations of ethanol resulted in the production of 5-, 12-, and 15-hydroxyeicosatetraenoic acids. With chiral phase high performance liquid chromatography, it was demonstrated that the 5-hydroxyeicosatetraenoic acid had strict (S) stereospecificity while contrary to expectation, the 12- and the 15-hydroxyeicosatetraenoic acids were non-racemic mixtures of the stereoisomers with the S/R ratios averaging 8.6 and 2.2, respectively. If the strict (S) stereospecificity of mammalian lipoxygenases holds true, these results suggest that the 15- and 12-hydroxyeicosatetraenoic acids may be derived from non-lipoxygenase sources. Examination of the chirality of the oxygenase products of unsaturated fatty acids may be of value in defining the enzymes which are activated in vivo in pathological states.     

Hypercalcemia and disseminated histoplasmosis in an owl monkey

An adult male owl monkey (Aotus nancymai) had hypercalcemia associated with a disseminated case of histoplasmosis (Histoplasma capsulatum var. capsulatum). Histopathologic examination of tissues at necropsy showed moderate to marked numbers of small granulomas involving multiple organs. The granulomas contained numerous round, basophilic, intracellular structures, 1-2 microns in diameter, that stained positive in Periodic acid-Schiff and Gomori's methenamine silver tests. The hypercalcemia in this case was attributed to enhance conversion of dietary vitamin D to 1,25-dihydroxycholecalciferol by the granulomas.