COMMD1-mediated ubiquitination regulates CFTR trafficking

The CFTR (cystic fibrosis transmembrane conductance regulator) protein is a large polytopic protein whose biogenesis is inefficient. To better understand the regulation of CFTR processing and trafficking, we conducted a genetic screen that identified COMMD1 as a new CFTR partner. COMMD1 is a protein associated with multiple cellular pathways, including the regulation of hepatic copper excretion, sodium uptake through interaction with ENaC (epithelial sodium channel) and NF-kappaB signaling. In this study, we show that COMMD1 interacts with CFTR in cells expressing both proteins endogenously. This interaction promotes CFTR cell surface expression as assessed by biotinylation experiments in heterologously expressing cells through regulation of CFTR ubiquitination. In summary, our data demonstrate that CFTR is protected from ubiquitination by COMMD1, which sustains CFTR expression at the plasma membrane. Thus, increasing COMMD1 expression may provide an approach to simultaneously inhibit ENaC absorption and enhance CFTR trafficking, two major issues in cystic fibrosis.     

Separation of protein and fatty acids from tuna viscera using supercritical carbon dioxide

Supercritical carbon dioxide extraction was investigated as a method for removing lipids and bad flavor from tuna viscera. To find the optimum conditions, different experimental variables, such as pressure, temperature, flow rate of solvent and sample size, were evaluated for the effective removal of lipids and the undesirable smell. Ethanol was used as the entrainer, with a 3% by vol CO₂ flow rate. By increasing the pressure at constant temperature, the efficiency of the lipid removal was improved and the protein was concentrated without denaturalization. The main fatty acids extracted from the tuna viscera were palmitic acid (16∶0), heptadecanoic acid (17∶1), oleic acid (18∶1) and docosahexaenoic acid (22∶6). The major amino acids in the tuna viscera treated by supercritical carbon dioxide were glutamic acid, leucine and lysine, and the free amino acids werel-proline, taurine andl-α-aminoadipic acid.     

Guano exposed: Impact of aerobic conditions on bat fecal microbiota

Bats and their associated guano microbiota provide important terrestrial and subterranean ecosystem services and serve as a reservoir for a wide range of epizootic and zoonotic diseases. Unfortunately, large‐scale studies of bats and their guano microbiotas are limited by the time and cost of sample collection, which requires specially trained individuals to work at night to capture bats when they are most active. Indirectly surveying bat gut microbiota through guano deposits could be a more cost‐effective alternative, but it must first be established whether the postdefecation exposure to an aerobic environment has a large impact on the guano microbial community. A number of recent studies on mammalian feces have shown that the impact of aerobic exposure is highly species specific; therefore, it is difficult to predict how exposure will affect the bat guano microbiota without empirical data. In our study, we collected fresh guano samples from 24 individuals of 10 bat species that are common throughout the arid environments of the American southwest and subjected the samples to 0, 1, and 12 hr of exposure. The biodiversity decreased rapidly after the shift from an anaerobic to an aerobic environment—much faster than previously reported in mammalian species. However, the relative composition of the core guano microbiota remained stable and, using highly sensitive targeted PCR methods, we found that pathogens present in the original, non‐exposed samples could still be recovered after 12 hr of exposure. These results suggest that with careful sample analysis protocols, a more efficient passive collection strategy is feasible; for example, guano could be collected on tarps placed near the roost entrance. Such passive collection methods would greatly reduce the cost of sample collection by allowing more sites or roosts to be surveyed with a fraction of trained personnel, time, and effort investments needed.     

APC Inhibits Ligand-Independent Wnt Signaling by the Clathrin Endocytic Pathway

1. Download high-res image (220KB)
2. Download full-size image

     

Donor–Acceptor–Acceptor's Molecules for Vacuum‐Deposited Organic Photovoltaics with Efficiency Exceeding 9%

Three vacuum‐deposited donor–acceptor–acceptor (d–a–a') small molecule donors are studied with different side chains attached to an asymmetric heterotetracene donor block for use in high efficiency organic photovoltaics (OPVs). The donor with an isobutyl side chain yields the highest crystal packing density compared to molecules with 2‐ethylhexyl or n‐butyl chains, leading to the largest absorption coefficient and short circuit current in an OPV. It also exhibits a higher fill factor, consistent with its preferred out‐of‐plane molecular π–π stacking arrangement that facilitates charge transport in the direction perpendicular to the substrate. A power conversion efficiency of 9.3 ± 0.5% is achieved under 1 sun intensity, AM 1.5 G simulated solar illumination, which is significantly higher than 7.5 ± 0.4% of the other two molecules. These results indicate that side chain modification of d–a–a' small molecules offers an effective approach to control the crystal packing configuration, thereby improving the device performance.     

Genome-wide analysis of the Chinese sturgeon sox gene family: identification,characterisation and expression profiles of different tissues

The sox family is assumed to be responsible for a number of developmental systems. Genome sequencing technology makes it possible to scan sox genes and conduct characteristic analyses of different species. In fish, full characterisation of sox genes at the genome-wide level has been reported for pufferfish Takifugu rubripes, medaka Oryzias latipes, tilapia Oreochromis niloticus and channel catfish Ictalurus punctatus. However, no systematic investigation of the sox family in sturgeons (Acipenseridae) has been reported to date. This study conducted genome-wide identification of the sox genes in the Chinese sturgeon Acipenser sinensis and profiled their tissue distribution between male and female individuals. In total, 19 sox genes were identified, including soxb1, b2, c, d, e, f and h, in the Chinese sturgeon. Genomic structure analysis indicated relatively conserved exon–intron structures in each sox group and phylogenetic analysis supported the previous classification of the sox family. Most of the sox genes showed a tissue-specific expression pattern, indicating the possible involvement of Chinese sturgeon sox genes at different developmental processes such as cardiac and gonadal development. This study provides a comprehensive resource of Chinese sturgeon sox genes and enables a better understanding of the evolution and function of the sox family.     

Negative BOLD fMRI response in the visual cortex carries precise stimulus-specific information

Sustained positive BOLD (blood oxygen level-dependent) activity is employed extensively in functional magnetic resonance imaging (fMRI) studies as evidence for task or stimulus-specific neural responses. However, the presence of sustained negative BOLD activity (i.e., sustained responses that are lower than the fixation baseline) has remained more difficult to interpret. Some studies suggest that it results from local "blood stealing" wherein blood is diverted to neurally active regions without a concomitant change of neural activity in the negative BOLD regions. However, other evidence suggests that negative BOLD is a result of local neural suppression. In both cases, regions of negative BOLD response are usually interpreted as carrying relatively little, if any, stimulus-specific information (hence the predominant reliance on positive BOLD activity in fMRI). Here we show that the negative BOLD response resulting from visual stimulation can carry high information content that is stimulus-specific. Using a general linear model (GLM), we contrasted standard flickering stimuli to a fixation baseline and found regions of the visual cortex that displayed a sustained negative BOLD response, consistent with several previous studies. Within these negative BOLD regions, we compared patterns of fMRI activity generated by flickering Gabors that were systematically shifted in position. As the Gabors were shifted further from each other, the correlation in the spatial pattern of activity across a population of voxels (such as the population of V1 voxels that displayed a negative BOLD response) decreased significantly. Despite the fact that the BOLD signal was significantly negative (lower than fixation baseline), these regions were able to discriminate objects separated by less than 0.5 deg (at approximately 10 deg eccentricity). The results suggest that meaningful, stimulus-specific processing occurs even in regions that display a strong negative BOLD response.     

Looking for trouble: a search for developmental defects of the hypothalamus

The hypothalamus is a critical integrator of several homeostatic processes that are required for the survival of vertebrates. Disruption of the development of the hypothalamus thus has the potential of perturbing important physiological processes with lifelong consequences. We review current knowledge about how cell types are specified and circuits are formed within the developing hypothalamus. We emphasize the potential clinical impact of the perturbations of these pathways using the regulation of energy balance as a model. We predict that disruption of hypothalamic development is a common, previously unsuspected cause of disorders of homeostatic processes such as obesity and high blood pressure.