Regulation of EGF receptor signaling by the MARVEL domain-containing protein CKLFSF8

It is known that chemokine-like factor superfamily 8 (CKLFSF8), a member of the CKLF superfamily, has four putative transmembrane regions and a MARVEL domain. Its structure is similar to TM4SF11 (plasmolipin) and widely distributed in normal tissue. However, its function is not yet known. We show here that CKLFSF8 is associated with the epidermal growth factor receptor (EGFR) and that ectopic expression of CKLFSF8 in several cell lines suppresses EGF-induced cell proliferation, whereas knockdown of CKLFSF8 by siRNA promotes cell proliferation. In cells overexpressing CKLFSF8, the initial activation of EGFR was not affected, but subsequent desensitization of EGF-induced signaling occurred rapidly. This attenuation was correlated with an increased rate of receptor endocytosis. In contrast, knockdown of CKLFSF8 by siCKLFSF8 delayed EGFR endocytosis. These results identify CKLFSF8 as a novel regulator of EGF-induced signaling and indicate that the association of EGFR with four transmembrane proteins is critical for EGFR desensitization.     

Psychological and physiological effect in humans of touching plant foliage - using the semantic differential method and cerebral activity as indicators

Background

Numerous studies have reported on the healing powers of plants and nature, but there have not been so many instances of experimental research. In particular, there are very few psychological and physiological studies using tactile stimuli. This study examines the psychological and physiological effects of touching plant foliage by using an evaluation profile of the subjects’ impressions and investigating cerebral blood flow.

Methods

The subjects were 14 young Japanese men aged from 21 to 27 years (mean ± standard deviation: 23.6 ± 2.4). With their eyes closed, the subjects touched four different tactile samples including a leaf of natural pothos (Epipremnum aureum). The physiological indices were compared before and after each stimulus. Psychological indices were obtained using a ‘semantic differential’ method.

Results

The fabric stimulus gave people ‘soft’ and ‘rough’ impressions, ‘kind’, ‘peaceful’ and ‘pleasant’ feelings psychologically, and a sense of physiological calm. On the other hand, the metal stimulus gave people ‘cold’, ‘smooth’ and ‘hard’ impressions and an image of something ‘artificial’. The metal stimulus caused a stress response in human cerebral blood flow although its evaluation in terms of ‘pleasant or unpleasant’ was neutral. There were no remarkable differences between the stimuli of natural and artificial pothos compared with other types of stimulus psychologically. However, only the natural pothos stimulus showed a sense of physiological calm in the same appearance as the fabric stimulus.

Conclusions

This study shows that people experience an unconscious calming reaction to touching a plant. It is to be concluded that plants are an indispensable element of the human environment.     

Two into One Won’t Go: Conceptual, Clinical, Ethical and Legal Impedimenta to the Convergence of CAM and Orthodox Medicine

The convergence of complementary and alternative medicine (CAM) and evidence-based medicine (EBM) is a prominent feature of healthcare in western countries, but it is currently undertheorised, and its implications have been insufficiently considered. Two models of convergence are described – the totally integrated evidence-based model (TI) and the multicultural-pluralistic model (MP). Both models are being incorporated into general medical practice. Against the background of the reasons for the increasing utilisation of CAM by the public and by general practitioners, TI-convergence is supported and MP-convergence is rejected. MP-convergence is epistemologically and clinically incoherent, and it cannot be regulated. It is also inconsistent with developments in the legal determination of the standard of care for both diagnosis/treatment and disclosure. These claims concerning MP-convergence are justified by the fact that science is not a member of the group of perspectives or world-views which postmodernism treats as equally valid, and this is especially important for healthcare.     

Regulation of the Rev1–pol ζ complex during bypass of a DNA interstrand cross‐link

DNA interstrand cross‐links (ICLs) are repaired in S phase by a complex, multistep mechanism involving translesion DNA polymerases. After replication forks collide with an ICL, the leading strand approaches to within one nucleotide of the ICL (“approach”), a nucleotide is inserted across from the unhooked lesion (“insertion”), and the leading strand is extended beyond the lesion (“extension”). How DNA polymerases bypass the ICL is incompletely understood. Here, we use repair of a site‐specific ICL in Xenopus egg extracts to study the mechanism of lesion bypass. Deep sequencing of ICL repair products showed that the approach and extension steps are largely error‐free. However, a short mutagenic tract is introduced in the vicinity of the lesion, with a maximum mutation frequency of ~1%. Our data further suggest that approach is performed by a replicative polymerase, while extension involves a complex of Rev1 and DNA polymerase ζ. Rev1–pol ζ recruitment requires the Fanconi anemia core complex but not FancI–FancD2. Our results begin to illuminate how lesion bypass is integrated with chromosomal DNA replication to limit ICL repair‐associated mutagenesis.     

Recovery of mechano-electrical transduction in rat cochlear hair bundles after postnatal destruction of the stereociliar cross-links

Mechano-electrical transduction (MET) in the stereocilia of outer hair cells (OHCs) was studied in newborn Wistar rats using scanning electron microscopy to investigate the stereociliar cross-links, Nomarski laser differential interferometry to investigate stereociliar stiffness and by testing the functionality of the MET channels by recording the entry of fluorescent dye, FM1-43, into stereocilia. Preparations were taken from rats on their day of birth (P0) or 1–4 days later (P1–P4). Hair bundles developed from the base to the apex and from the inner to outer OHC rows. MET channel responses were detected in apical coil OHCs on P1. To study the possible recovery of MET after disrupting the cross-links, the same investigations were performed after the application of Ca²⁺ chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA) and allowing the treated samples to recover in culture medium for 0–20 h. We found that the structure and function were abolished by BAPTA. In P0–P1 samples, structural recovery was complete and the open probability of MET channels reached control values. In P3–P4 samples, complete recovery only occurred in OHCs of the outermost row. Although our results demonstrate an enormous recovery potential of OHCs in the postnatal period, the structural component restricts the potential for therapy in patients.     

Antenna-predominant and male-biased CSP19 of Sesamia inferens is able to bind the female sex pheromones and host plant volatiles

Insect chemosensory proteins (CSPs) are proposed to capture and transport hydrophobic chemicals across the sensillum lymph to olfactory receptors (ORs), but this has not been clarified in moths. In this study, we built on our previously reported segment sequence work and cloned the full length CSP19 gene (SinfCSP19) from the antennae of Sesamia inferens by using rapid amplification of cDNA ends. Quantitative real time-PCR (qPCR) assays indicated that the gene was expressed in a unique profile, i.e. predominant in antennae and significantly higher in male than in female. To explore the function, recombinant SinfCSP19 was expressed in Escherichia coli cells and purified by Ni–ion affinity chromatography. Binding affinities of the recombinant SinfCSP19 with 39 plant volatiles, 3 sex pheromone components and 10 pheromone analogs were measured using fluorescent competitive binding assays. The results showed that 6 plant volatiles displayed high binding affinities to SinfCSP19 (Ki = 2.12–8.75 μM), and more interesting, the 3 sex pheromone components and analogs showed even higher binding to SinfCSP19 (Ki = 0.49–1.78 μM). Those results suggest that SinfCSP19 plays a role in reception of female sex pheromones of S. inferens and host plant volatiles.