Rab14 and its exchange factor FAM116 link endocytic recycling and adherens junction stability in migrating cells

Rab GTPases define the vesicle trafficking pathways underpinning cell polarization and migration. Here, we find that Rab4, Rab11, and Rab14 and the candidate Rab GDP-GTP exchange factors (GEFs) FAM116A and AVL9 are required for cell migration. Rab14 and its GEF FAM116A localize to and act on an intermediate compartment of the transferrin-recycling pathway prior to Rab11 and after Rab5 and Rab4. This Rab14 intermediate recycling compartment has specific functions in migrating cells discrete from early and recycling endosomes. Rab14-depleted cells show increased N-cadherin levels at junctional complexes and cannot resolve cell-cell junctions. This is due to decreased shedding of cell-surface N-cadherin by the ADAM family protease ADAM10/Kuzbanian. In FAM116A- and Rab14-depleted cells, ADAM10 accumulates in a transferrin-positive endocytic compartment, and the cell-surface level of ADAM10 is correspondingly reduced. FAM116 and Rab14 therefore define an endocytic recycling pathway needed for ADAM protease trafficking and regulation of cell-cell junctions.     

Do Termites Avoid Carcasses? Behavioral Responses Depend on the Nature of the Carcasses

Background

Undertaking behavior is a significant adaptation to social life in enclosed nests. Workers are known to remove dead colony members from the nest. Such behavior prevents the spread of pathogens that may be detrimental to a colony. To date, little is known about the ethological aspects of how termites deal with carcasses.

Methodology and Principal Findings

In this study, we tested the responses to carcasses of four species from different subterranean termite taxa: Coptotermes formosanus Shiraki and Reticulitermes speratus (Kolbe) (lower termites) and Microcerotermes crassus Snyder and Globitermes sulphureus Haviland (higher termites). We also used different types of carcasses (freshly killed, 1-, 3-, and 7-day-old, and oven-killed carcasses) and mutilated nestmates to investigate whether the termites exhibited any behavioral responses that were specific to carcasses in certain conditions. Some behavioral responses were performed specifically on certain types of carcasses or mutilated termites. C. formosanus and R. speratus exhibited the following behaviors: (1) the frequency and time spent in antennating, grooming, and carcass removal of freshly killed, 1-day-old, and oven-killed carcasses were high, but these behaviors decreased as the carcasses aged; (2) the termites repeatedly crawled under the aging carcass piles; and (3) only newly dead termites were consumed as a food source. In contrast, M. crassus and G. sulphureus workers performed relatively few behavioral acts. Our results cast a new light on the previous notion that termites are necrophobic in nature.

Conclusion

We conclude that the behavioral response towards carcasses depends largely on the nature of the carcasses and termite species, and the response is more complex than was previously thought. Such behavioral responses likely are associated with the threat posed to the colony by the carcasses and the feeding habits and nesting ecology of a given species.     

Electron paramagnetic resonance of nitrosylprotoheme dimethyl ester complexes with imidazole derivatives as model systems for nitrosylhemoproteins.

For the purpose of understanding the electron paramagnetic resonance (epr) spectral change of nitrosylhemoproteins under various conditions, the epr spectra for the model system have been analyzed. The model system consists of the nitrogen oxide complex of the iron(II) protoporphyrin IX dimethyl ester and various imidazole derivatives (three hindered and six unhindered imidazole derivatives). The results of the analysis indicate the existence of two molecular species in the model system, which differ in structure of the FeNO unit. These observations were compared with those for the nitrosylhemoproteins.     

Differential localization of 5-hydroxytryptamine3 and 5-hydroxytryptamine4 receptors in the human rectum

The functions of the 5-hydroxytryptamine3 (5-HT3) and 5-hydroxytryptamine4 (5-HT4) receptors in gastrointestinal tract are complex depending on the species and anatomical regions, and the localization of these receptors in the human rectum was unclear. We examined the localization of the 5-HT3 and 5-HT4 receptors in human rectum by in vitro receptor autoradiography using [125I](S)iodozacopride and [125I] SB207710 as a ligand, respectively. Specific [125I](S)iodozacopride binding sites were clearly evident in the myenteric plexus, whereas, low levels of [125I]SB207710 binding sites were distributed over the muscle but not to the myenteric plexus. The 5-HT3 receptor located on the myenteric plexus and the 5-HT4 receptor on the smooth muscle may participate in contractility and relaxation of human rectum, respectively.     

No association between complement factor H gene polymorphism and exudative age-related macular degeneration in Japanese

Age-related macular degeneration (ARMD) is the leading cause of blindness in the elderly population not only Western but also Asian industrial countries. In Caucasian, a polymorphism of the complement factor H gene (CFH), the C allele of rs1061170 (Y402H), was established as the first strong genetic factor for excursively exudative type of ARMD. In this study, we performed an extensive sequencing of the 22 exons in the CFH gene by recruiting 146 exudative ARMD patients and 105 normal controls of Japanese origin and identified 61 polymorphisms. We found that the frequency of the C allele of rs1061170 (Y402H) is much lower (0.04) in Japanese controls than in Caucasians (0.45). No case disease susceptibility to exudative ARMD was noted for rs1061170 (Y402H) (χ ² = 3.19, P _corr = 0.423), or other 12 single nucleotide polymorphisms (SNPs) whose frequency is greater than 0.05. When haplotypes were inferred for 13 SNPs (these 12 SNPs with a frequency greater than 0.05 and rs1061170), three haplotypes whose pattern was similar to those in Caucasians were identified but with substantial difference in frequency. Again we failed to identify genetic association between Japanese exudative ARMD and any of the haplotypes including the J1 haplotype which was shown to be susceptible to ARMD in Caucasians (χ ² = 3.92, P _corr = 0.157). CFH does not appear to be a primary hereditary contributor to ARMD in Japanese. The absence of CFH contribution to ARMD in Japanese may correlate with the findings in ethnic differences of ARMD phenotypes.Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users.This work was accomplished by equal contribution of two groups organized by the last two authors.     

Spatial coexistence of phytoplankton species in ecological timescale

The species diversity of phytoplankton is usually very high in wild aquatic systems, as seen in the paradox of plankton. Coexistence of many competitive phytoplankton species is extremely common in nature. However, experiments and mathematical theories show that interspecific competition often leads to the extinction of most inferior species. Here, we present a lattice version of a multi-species Lotka–Volterra competition model to demonstrate the importance of local interaction. Its mathematical equilibrium is the exclusion of all but one superior species. However, temporal coexistence of many competitive species is possible in an ecological time scale if interactions are local instead of global. This implies that the time scale is elongated many orders when interactions are local. Extremely high species diversity of phytoplankton in aquatic systems may be maintained by spatial coexistence in an ecological time scale.Tatsuo Miyazaki, Kei-ichi Tainaka, and Jin Yoshimura contributed equally to this study.     

Differences in the binding modes of phytochelatin to cadmium (II) and Zinc(II) ions

An ¹H NMR (nuclear magnetic resonance) spectroscopic structural analysis of Cd²⁺ complexes formed with the pentapeptide phytochelatin, (NH₃)⁺−(ψ-Glu-Cys)₂−Gly−COO−(PC₂), at a pH of 7.5 showed that the two thiol groups of the Cys residues and either the carbonyl or amide group of the peptide bond between Glu1 and Cys1 act as possible donor groups in the complexes at Cd²⁺/PC₂ ratios up to 0.4. As the ratio increases, the carboxylate group of Glu2 and either the carbonyl or amide group of the peptide bond between Cys1 and Glu2 comes to serve as a donor group. The manner in which Cd²⁺ forms complexes with PC₂ is distinctly different from Zn²⁺ and might account for the role of phytochelatin in Cd²⁺ detoxification. Electron absorption spectrometry demonstrated that the Cd²⁺ complexes are coordinated in a tetrahedral fashion by four thiol groups and that several sulfur atoms might bridge Cd²⁺ ions, resulting in the formation of polynuclear complexes. This contrasts with Zn²⁺ complex formation, which consists exclusively of a 1:1 complex.     

Detection of HIV-1 p24 at Attomole Level by Ultrasensitive ELISA with Thio-NAD Cycling

To reduce the window period between HIV-1 infection and the ability to diagnose it, a fourth-generation immunoassay including the detection of HIV-1 p24 antigen has been developed. However, because the commercially available systems for this assay use special, high-cost instruments to measure, for example, chemiluminescence, it is performed only by diagnostics companies and hub hospitals. To overcome this limitation, we applied an ultrasensitive ELISA coupled with a thio-NAD cycling, which is based on a usual enzyme immunoassay without special instruments, to detect HIV-1 p24. The p24 detection limit by our ultrasensitive ELISA was 0.0065 IU/assay (i.e., ca. 10^-18 moles/assay). Because HIV-1 p24 antigen is thought to be present in the virion in much greater numbers than viral RNA copies, the value of 10^-18 moles of the p24/assay corresponds to ca. 10³ copies of the HIV-1 RNA/assay. That is, our ultrasensitive ELISA is chasing the detection limit (10² copies/assay) obtained by PCR-based nucleic acid testing (NAT) with a margin of only one different order. Further, the detection limit by our ultrasensitive ELISA is less than that mandated for a CE-marked HIV antigen/antibody assay. An additional recovery test using blood supported the reliability of our ultrasensitive ELISA.     

Autoregulation of Osteocyte Sema3A Orchestrates Estrogen Action and Counteracts Bone Aging

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