Modulation of DEG/ENaCs by Amphiphiles Suggests Sensitivity to Membrane Alterations

The bile acid-sensitive ion channel is activated by amphiphilic substances such as bile acids or artificial detergents via membrane alterations; however, the mechanism of membrane sensitivity of the bile acid-sensitive ion channel is not known. It has also not been systematically investigated whether other members of the degenerin/epithelial Na⁺ channel (DEG/ENaC) gene family are affected by amphiphilic compounds. Here, we show that DEG/ENaCs ASIC1a, ASIC3, ENaC, and the purinergic receptor P2X2 are modulated by a large number of different, structurally unrelated amphiphilic substances, namely the detergents N-lauroylsarcosine, Triton X-100, and β-octylglucoside; the fenamate flufenamic acid; the antipsychotic drug chlorpromazine; the natural phenol resveratrol; the chili pepper compound capsaicin; the loop diuretic furosemide; and the antiarrythmic agent verapamil. We determined the modification of membrane properties using large-angle x-ray diffraction experiments on model lipid bilayers, revealing that the amphiphilic compounds are positioned in a characteristic fashion either in the lipid tail group region or in the lipid head group region, demonstrating that they perturbed the membrane structure. Collectively, our results show that DEG/ENaCs and structurally related P2X receptors are modulated by diverse amphiphilic molecules. Furthermore, they suggest alterations of membrane properties by amphiphilic compounds as a mechanism contributing to modulation.     

<Emphasis Type="Italic">Fgf9</Emphasis><Superscript><Emphasis Type="Italic">Y162C</Emphasis></Superscript> Mutation Alters Information Processing and Social Memory in Mice

In neuropsychiatric diseases, such as major depression and anxiety, pathogenic vulnerability is partially dictated by a genetic predisposition. The search continues to define this genetic susceptibility and establish new genetic elements as potential therapeutic targets. The fibroblast growth factors (FGFs) could be interesting in this regard. This family of signaling molecules plays important roles in development while also functioning within the adult. This includes effects on aspects of brain function such as neurogenesis and synapse formation. Of this family, Fgf9 is expressed in the adult brain, but its functional role is less well defined. In this study, we examined the role of Fgf9 in different brain functions by analyzing the behavior of Fgf9 ^Y162C mutant mice, an Fgf9 allele without the confounding systemic effects of other Fgf9 genetic models. Here, we show that this mutation caused altered locomotor and exploratory reactivity to novel, mildly stressful environments. In addition, mutants showed heightened acoustic startle reactivity as well as impaired social discrimination memory. Notably, there was a substantial decrease in the level of adult olfactory bulb neurogenesis with no difference in hippocampal neurogenesis. Collectively, our findings indicate a role for the Fgf9 ^Y162C mutation in information processing and perception of aversive situations as well as in social memory. Thus, genetic alterations in Fgf9 could increase vulnerability to developing neuropsychiatric disease, and we propose the Fgf9 ^Y162C mutant mice as a valuable tool to study the predictive etiological aspects.     

Collagen biosynthesis anomalies in prolidase deficiency: effect of glycyl-L-proline on the degradation of newly synthesized collagen

Prolidase deficiency is a rare hereditary disease characterized by an iminodipeptiduria especially composed by glycyl-L-proline which is not further degraded. The study of collagen metabolism in fibroblast cultures from three prolidase-deficient patients showed an increase in the rapidly degraded collagen and a decrease in the proline pool. In order to elucidate the mechanism of this metabolic disturbance, glycyl-L-proline was added to the cell cultures. In the control cultures, the addition of this dipeptide caused an increase in the rapidly degraded collagen and a decrease in the proline pool. The effects on the patient fibroblasts depended on the severity of the deficiency. The metabolic function of the dipeptide glycyl-L-proline was discussed in the light of these results.     

Survival after pathogen exposure in group‐living insects: don't forget the stress of social isolation!

A major cost of group‐living is its inherent risk of pathogen infection. To limit this risk, many group‐living animals have developed the capability to prophylactically boost their immune system in the presence of group members and/or to mount collective defences against pathogens. These two phenomena, called density‐dependent prophylaxis and social immunity, respectively, are often used to explain why, in group‐living species, individuals survive better in groups than in isolation. However, this survival difference may also reflect an alternative and often overlooked process: a cost of social isolation on individuals’ capability to fight against infections. Here, we disentangled the effects of density‐dependent prophylaxis, social immunity and stress of social isolation on the survival after pathogen exposure in group‐living adults of the European earwig Forficula auricularia. By manipulating the presence of group members both before and after pathogen exposure, we demonstrated that the cost of being isolated after infection, but not the benefits of social immunity or density‐dependent prophylaxis, explained the survival of females. Specifically, females kept constantly in groups or constantly isolated had higher survival rates than females that were first in groups and then isolated after infection. Our results also showed that this cost of social isolation was absent in males and that social isolation did not reduce the survival of noninfected individuals. Overall, this study gives a new perspective on the role of pathogens in social evolution, as it suggests that an apparently nonadaptive, personal immune process may promote the maintenance of group‐living under pathogenic environments.     

Improving the performance of an aerobic membrane bioreactor (MBR) treating pharmaceutical wastewater with powdered activated carbon (PAC) addition

In this study, the effects of organic loading rate (OLR) and the addition of powdered activated carbon (PAC) on the performance and membrane fouling of MBR were conducted to treat real pharmaceutical process wastewater. Over 145 days of operation, the MBR system was operated at OLRs ranging from 1 to 2 kg COD m^?3 day^?1 without sludge wasting. The addition of PAC provided an improvement in the flux, despite an increase in the OLR:PAC ratio. The results demonstrated that the hybrid PAC-MBR system maintained a reduced amount of membrane fouling and steadily increased the removal performance of etodolac. PAC addition reduced the deposition of extracellular polymeric substance and organic matter on the membrane surface and resulted an increase in COD removal even at higher OLRs with low PAC addition. Membrane fouling mechanisms were investigated using combined adsorption fouling models. Modified fouling index values and normalized mass transfer coefficient values indicated that predominant fouling mechanism was cake adsorption.     

Juvenile hormone and regulation of dichotomous spermatogenesis during the larval diapause of the codling moth

Spermatogenesis ceases during diapause and resumes after diapause. A possible causal relationship between the regulation of these phenomena and the fluctuations of the juvenile hormone titre connected with the diapause was examined in the codling moth. Spermatocyte lysis and spermatogenesis arrest are directly and reversibly related to these fluctuations. They are induced in the last-larval instar by sole application of the juvenoid Altosid to the penultimate-instar larvae predetermined not to enter diapause. Conversely, allatectomy of early last-instar larvae predetermined to diapause induces renewal of spermatogenesis and disruption of diapause. However, the continuation of the arrest of the spermatogenesis during diapause is not directly related to the presence of a high titre of juvenile hormone. The arrest extends throughout diapause which may continue for months, although no juvenile hormone could be detected in the species after 35 days of larval diapause.     

Developmental stability and canalization of limb bones of brown haresLepus europaeus with varying levels of heterozygosity

We have studied fluctuating asymmetry (FA), as indicator of developmental stability, and between-individual variation, as surrogate of developmental canalization (DC), in long bones (humerus, ulna, radius, femur, tibia) of 72 wild-living adult-sized brown haresLepus europaeus Pallas, 1778 with variable individual heterozygosity (H).H was calculated from 13 polymorphic allozyme loci. According to the “over-dominance hypothesis”, we expected increased developmental stability and canalization at higherH-levels. But at the individual level we did not find any significant correlation between overall FA (FA_I) andH. Also, standard deviations (SD) of mean length (over both body sides) of bones did not differ between individuals from two intentionally created groups of hares, namely one with high and one with lowH. FA-indices and variances of FA-indices of bone lengths did not differ significantly when compared between two intentionally created groups of hares with high and low SD of bone lengths, respectively. These latter findings suggest that developmental stability and DC are two separate or partly separate mechanisms of developmental homeostasis in the studied appendicular skeleton, and thatH has no traceable effect on develop-mental homeostasis. If there is still such an effect, it should be clearly smaller than a possibly combined effect of (presently uncontrolled) environmental stressors.