Severe defect in thymic development in an insertional mutant mouse model

Transgenic mice were generated expressing NK1.1, an NK cell-associated receptor, under control of the human CD2 promoter. Unexpectedly, one of the founder lines, Tg66, showed a marked defect in thymic development characterized by disorganized architecture and small size. Mapping of the transgene insertion by fluorescence in situ hybridization revealed integration in chromosome 2, band G. Already from postnatal day 3, the thymic architecture was disturbed with a preferential loss of cortical thymic epithelial cells, a feature that became more pronounced over time. Compared with wild-type mice, total thymic cell numbers decreased dramatically between 10 and 20 days of age. Thymocytes isolated from adult Tg66 mice were predominantly immature double-negative cells, indicating a block in thymic development at an early stage of differentiation. Consequently, Tg66 mice had reduced numbers of peripheral CD4(+) and CD8(+) T cells. Bone marrow from Tg66 mice readily reconstituted thymi of irradiated wild-type as well as RAG-deficient mice. This indicates that the primary defect in Tg66 mice resided in nonhemopoietic stromal cells of the thymus. The phenotype is observed in mice heterozygous for the insertion and does not resemble any known mutations affecting thymic development. Preliminary studies in mice homozygous for transgene insertion reveal a more accelerated and pronounced phenotype suggesting a semidominant effect. The Tg66 mice may serve as a useful model to identify genes regulating thymic epithelial cell differentiation, thymic development, and function.     

In vivo construction of recombinant molecules within the Caenorhabditis elegans germ line using short regions of terminal homology

Homologous recombination provides a means for the in vivo construction of recombinant DNA molecules that may be problematic to assemble in vitro. We have investigated the efficiency of recombination within the Caenorhabditis elegans germ line as a function of the length of homology between recombining molecules. Our findings indicate that recombination can occur between molecules that share only 10 bp of terminal homology, and that 25 bp is sufficient to mediate relatively high levels of recombination. Recombination occurs with lower efficiency when the location of the homologous segment is subterminal or internal. As in yeast, recombination can also be mediated by either single- or double-stranded bridging oligonucleotides. We find that ligation between cohesive ends is highly efficient and does not require that the ends be phosphorylated; furthermore, precise intermolecular ligation between injected molecules that have blunt ends can also occur within the germ line.     

Preferences for masculinity in male bodies change across the menstrual cycle

In human females cyclic shifts in preference have been documented for odour and physical and behavioral male traits. Women prefer the smell of dominant males, more masculine male faces and men behaving more dominantly when at peak fertility than at other times in their menstrual cycle. Here we examine variation in preferences for body sexual dimorphism. Across two studies, both between- and within-participant, we show that women prefer greater masculinity in male bodies at times when their fertility is likely highest, in the follicular phase of their cycle. Shifts were seen when rating for a short-term but not when rating for a long-term relationship. In line with studies showing similar effects for facial sexual dimorphism, we also show that women prefer greater masculinity when they think themselves attractive than when they think themselves less attractive. These results indicate that women's preferences for sexual dimorphism in male bodies follow a similar pattern as found for sexual dimorphism and dominance in other domains and such differences in preference may serve a similar function. Cyclic preferences could influence women to select partners when most likely to become pregnant that possess traits that may be most likely to maximize their offspring's quality via attraction to masculinity or serve to help acquire investment via attraction to femininity.     

Characterization of a Polycyclic Aromatic Hydrocarbon-Degrading Microbial Consortium from a Petrochemical Sludge Landfarming Site

Anthracene, phenanthrene, and pyrene are polycyclic aromatic hydrocarbon (PAHs) that display both mutagenic and carcinogenic properties. They are recalcitrant to microbial degradation in soil and water due to their complex molecular structure and low solubility in water. This study presents the characterization of an efficient PAH (anthracene, phenanthrene, and pyrene)-degrading microbial consortium, isolated from a petrochemical sludge landfarming site. Soil samples collected at the landfarming area were used as inoculum in Warburg flasks containing soil spiked with 250 mg kg^-1 of anthracene. The soil sample with the highest production of CO₂-C in 176 days was used in liquid mineral medium for further enrichment of anthracene degraders. The microbial consortium degraded 48%, 67%, and 22% of the anthracene, phenanthrene, and pyrene in the mineral medium, respectively, after 30 days of incubation. Six bacteria, identified by 16S rRNA sequencing as Mycobacterium fortuitum, Bacillus cereus, Microbacterium sp., Gordonia polyisoprenivorans, two Microbacteriaceae bacteria, and a fungus identified as Fusarium oxysporum were isolated from the enrichment culture. The consortium and its monoculture isolates utilized a variety of hydrocarbons including PAHs (pyrene, anthracene, phenanthrene, and naftalene), monoaromatics hydrocarbons (benzene, ethylbenzene, toluene, and xylene), aliphatic hydrocarbons (1-decene, 1-octene, and hexane), hydrocarbon mixtures (gasoline and diesel oil), intermediary metabolites of PAHs degradation (catechol, gentisic acid, salicylic acid, and dihydroxybenzoic acid) and ethanol for growth. Biosurfactant production by the isolates was assessed by an emulsification index and reduction of the surface tension in the mineral medium. Significant emulsification was observed with the isolates, indicating production of high-molecular-weigh surfactants. The high PAH degradation rates, the wide spectrum of hydrocarbons utilization, and emulsification capacities of the microbial consortium and its member microbes indicate that they can be used for biotreatment and bioaugumentation of soils contaminated with PAHs.     

Sensation seeking and men's face preferences

Findings from previous studies suggest that only men who are in good physical condition can afford to pursue high-risk activities and that men who engage in high-risk activities are considered particularly attractive by women. Here, we show that men's interest in high-sensation activities, a personality trait that is known to increase the likelihood of those individuals engaging in high-risk behaviors, is positively related to the strength of their preferences for femininity in women's faces (Studies 1–3) but is not related to the strength of their preferences for femininity in men's faces (Study 2). We discuss these findings as evidence for potentially adaptive condition-dependent mate preferences, whereby men who exhibit signals of high quality demonstrate particularly strong preferences for facial cues of reproductive and medical health in potential mates because they are more likely than lower-quality men to succeed in acquiring such partners.     

Protease-sensitive fluorescent nanofibers

We report the design and synthesis of enzyme-responsive nanofibers. The fibers are composed of self-assembled hydrophobic beta-sheet peptides incorporating protease-sensitive domains, fluorescent reporters, and hydrophilic poly(ethylene glycol) (PEG) units. Using urokinase plasminogen activator (uPA) as a model system, nanofibers were developed to release fluorescent fragments upon uPA incubation. These protease-sensitive nanofibers may have considerable biomedical applications as diagnostic sensors or for protease-assisted drug deliveries.     

Enhancement of intravesical delivery with Syn3 potentiates interferon-α2b gene therapy for superficial bladder cancer

Intravesical administration of interferon alpha-2b protein (IFN) has been successfully used in the treatment of patients with superficial bladder tumors. Local dosing of IFN minimizes well-known systemic side effects of the drug, but exposure to bladder tumors is limited by the duration of instillation and transient concentrations achieved in the urothelium. Intravesical delivery of the gene encoding interferon results in an alternative strategy for IFN-based therapy of the disease, enabling sustained exposure of IFN protein that results from production by tumor and non-tumor cells in the urothelium. Efficient gene delivery and expression of IFN has been achieved using a recombinant adenovirus gene delivery system (rAd-IFN) in conjunction with the novel small molecule excipient Syn3. Studies with rAd-IFN/Syn3 in animal models result in urine concentrations of IFN that persisted for weeks and correlated with potent anti-tumor effects. The objective of this review is to communicate the rationale and preclinical findings that support ongoing clinical investigation of intravesical rAd-IFN/Syn3 in superficial bladder cancer.     

Medroxyprogesterone acetate prevents the cardioprotective and anti-inflammatory effects of 17beta-estradiol in an in vivo model of myocardial ischemia and reperfusion

Previous studies demonstrated the protective effects of estrogen administration in models of cardiovascular disease. However, there is a discrepancy between these data and those from the recent clinical trials with hormone replacement therapy in menopausal women. One possible explanation for the divergent results is the addition of progestin to the hormone regimen in the Women's Health Initiative and the Heart and Estrogen/Progestin Replacement Study trials. The aim of the present study was to examine the effects of a combination of 17beta-estradiol (E(2), 20 microg) and medroxyprogesterone acetate (MPA, 80 microg) on infarct size in New Zealand White rabbits. Infarct size as a percentage of the area at risk was significantly reduced by administration of E(2) 30 min before induction of myocardial ischemia compared with vehicle (19.5 +/- 3.1 vs. 55.7 +/- 2.6%, P < 0.001). However, E(2) + MPA failed to elicit a reduction in infarct size (52.5 +/- 4.6%), and MPA had no effect (50.8 +/- 2.6%). E(2) also reduced serum levels of cardiac troponin I, immune complex deposition in myocardial tissue, activation of the complement system, and lipid peroxidation. All these effects were reversed by MPA. The results suggest that MPA antagonizes the infarct-sparing effects of E(2), possibly through modulation of the immune response after ischemia and reperfusion.