The Drosophila ninaE gene encodes an opsin

The Drosophila ninaE gene was isolated by a multistep protocol on the basis of its homology to bovine opsin cDNA. The gene encodes the major visual pigment protein (opsin) contained in Drosophila photoreceptor cells R1-R6. The coding sequence is interrupted by four short introns. The positions of three introns are conserved with respect to positions in mammalian opsin genes. The nucleotide sequence has intermittent regions of homology to bovine opsin coding sequences. The deduced amino acid sequence reveals significant homology to vertebrate opsins; there is strong conservation of the retinal binding site and two other regions. The predicted protein secondary structure strikingly resembles that of mammalian opsins. We conclude the Drosophila and vertebrate opsin genes are derived from a common ancestor.     

Interaction of cycloheximide and light on chlorophyll content and chloroplast ultrastructure inBrassica campestris

Cycloheximide retarded the loss of chlorophyll from detached komatsuna (Brassica campestris cv. Komatsuna) leaves during incubation in the dark but promoted its loss in light. Cycloheximide-induced chlorophyll bleaching in light was prevented by some active oxygen scavengers. Chloroplast envelopes of cycloheximide-treated leaves incubated in both the dark and light were destroyed within 48 h. The grana of cycloheximide-treated leaves incubated in light were dilated.     

Contrast transfer function of the visual system]

Visually evoked potentials were used to determine the spatial contrast response function of the visual system and the visual acuity of the pigeon. The spatial contrast response describes the relationship between the contrast in a pattern of vertical stripes, whose luminance is a function of position, and the amplitude of the visually evoked response at various spatial frequencies for a given temporal frequency (pattern reversal frequency); it indicates how particular spatial frequencies are attenuated in the visual system. The visually evoked responses were recorded using monopolar stainless steel electrodes inserted into the stratum griseum superficiale of the optic tectum; the depth of penetration was determined on the basis of a stereotactic atlas. The stimulus patterns were generated on a video monitor placed 75 cm in front of the animal's eye perpendicular to the optic axis. The spatial contrast response function measured at 10% contrast and 0.5 Hz reversal frequency shows a peak at a spatial frequency of 0.5 c/deg, corresponding to 1 degree of visual angle, and decreases progressively at higher spatial frequencies. The high-frequency limit (cut-off frequency) for resolution of sinusoidal gratings, estimated from the contrast response function, is 15.5 c/deg, corresponding to a visual acuity of 1.9 min of arc.     

Centrilobular emphysema and coronary artery calcification: mediation analysis in the SPIROMICS cohort

Background

Chronic obstructive pulmonary disease (COPD) is associated with a two-to-five fold increase in the risk of coronary artery disease independent of shared risk factors. This association is hypothesized to be mediated by systemic inflammation but this link has not been established.

Methods

We included 300 participants enrolled in the SPIROMICS cohort, 75 each of lifetime non-smokers, smokers without airflow obstruction, mild-moderate COPD, and severe-very severe COPD. We quantified emphysema and airway disease on computed tomography, characterized visual emphysema subtypes (centrilobular and paraseptal) and airway disease, and used the Weston visual score to quantify coronary artery calcification (CAC). We used the Sobel test to determine whether markers of systemic inflammation mediated a link between spirometric and radiographic features of COPD and CAC.

Results

FEV₁/FVC but not quantitative emphysema or airway wall thickening was associated with CAC (p?=?0.036), after adjustment for demographics, diabetes mellitus, hypertension, statin use, and CT scanner type. To explain this discordance, we examined visual subtypes of emphysema and airway disease, and found that centrilobular emphysema but not paraseptal emphysema or bronchial thickening was independently associated with CAC (p?=?0.019). MMP3, VCAM1, CXCL5 and CXCL9 mediated 8, 8, 7 and 16% of the association between FEV₁/FVC and CAC, respectively. Similar biomarkers partially mediated the association between centrilobular emphysema and CAC.

Conclusions

The association between airflow obstruction and coronary calcification is driven primarily by the centrilobular subtype of emphysema, and is linked through bioactive molecules implicated in the pathogenesis of atherosclerosis.

Trial Registration

ClinicalTrials.gov: Identifier: NCT01969344.

     

Joint species distribution modelling for spatio‐temporal occurrence and ordinal abundance data

Aim

Species distribution models are important tools used to study the distribution and abundance of organisms relative to abiotic variables. Dynamic local interactions among species in a community can affect abundance. The abundance of a single species may not be at equilibrium with the environment for spreading invasive species and species that are range shifting because of climate change. Innovation : We develop methods for incorporating temporal processes into a spatial joint species distribution model for presence/absence and ordinal abundance data. We model non‐equilibrium conditions via a temporal random effect and temporal dynamics with a vector‐autoregressive process allowing for intra‐ and interspecific dependence between co‐occurring species. The autoregressive term captures how the abundance of each species can enhance or inhibit its own subsequent abundance or the subsequent abundance of other species in the community and is well suited for a ‘community modules’ approach of strongly interacting species within a food web. R code is provided for fitting multispecies models within a Bayesian framework for ordinal data with any number of locations, time points, covariates and ordinal categories.

Main conclusions

We model ordinal abundance data of two invasive insects (hemlock woolly adelgid and elongate hemlock scale) that share a host tree and were undergoing northwards range expansion in the eastern U.S.A. during the period 1997–2011. Accounting for range expansion and high inter‐annual variability in abundance led to improved estimation of the species–environment relationships. We would have erroneously concluded that winter temperatures did not affect scale abundance had we not accounted for the range expansion of scale. The autoregressive component revealed weak evidence for commensalism, in which adelgid may have predisposed hemlock stands for subsequent infestation by scale. Residual spatial dependence indicated that an unmeasured variable additionally affected scale abundance. Our robust modelling approach could provide similar insights for other community modules of co‐occurring species.     

Soluble glycoprotein 130 is inversely related to severity of coronary atherosclerosis

Purpose: Recent studies indicate that the effects of interleukin 6 (IL-6) realized via soluble IL-6 receptor (sIL-6R) facilitate the development of various pathological processes. Soluble gp130 (sgp130) is a naturally occurring inhibitor of signal transduction via this pathway. In this study, we assessed the relationship between circulating levels of IL-6, sIL-6R and sgp130 and severity of coronary atherosclerosis in patients with stable coronary artery disease (CAD).

Methods: Plasma levels of IL-6, sIL-6R and sgp130 were measured in patients with atherosclerotic coronary lesions (n?=?128, group 1) and with intact coronary arteries (n?=?48, group 2). The severity of coronary atherosclerosis was evaluated by the number of affected arteries and by Gensini Score index.

Results: Circulating IL-6 levels in group 1 were significantly higher than those in group 2. The levels of sIL-6R did not differ considerably in both the groups. The levels of sgp130 in group 1 were significantly lower than in group 2. A negative correlation has been revealed between sgp130 levels and the number of affected coronary arteries and Gensini Score index.

Conclusions: Serum concentration of sgp130 in patients with stable CAD is inversely related to severity of coronary damage. Low sgp130 level may serve as an additional indicator of coronary atherosclerosis severity.     

In vitro and in vivo accumulation of magnetic nanoporous silica nanoparticles on implant materials with different magnetic properties

Background

In orthopedic surgery, implant-associated infections are still a major problem. For the improvement of the selective therapy in the infection area, magnetic nanoparticles as drug carriers are promising when used in combination with magnetizable implants and an externally applied magnetic field. These implants principally increase the strength of the magnetic field resulting in an enhanced accumulation of the drug loaded particles in the target area and therewith a reduction of the needed amount and the risk of undesirable side effects. In the present study magnetic nanoporous silica core–shell nanoparticles, modified with fluorophores (fluorescein isothiocyanate/FITC or rhodamine B isothiocyanate/RITC) and poly(ethylene glycol) (PEG), were used in combination with metallic plates of different magnetic properties and with a magnetic field. In vitro and in vivo experiments were performed to investigate particle accumulation and retention and their biocompatibility.

Results

Spherical magnetic silica core–shell nanoparticles with reproducible superparamagnetic behavior and high porosity were synthesized. Based on in vitro proliferation and viability tests the modification with organic fluorophores and PEG led to highly biocompatible fluorescent particles, and good dispersibility. In a circular tube system martensitic steel 1.4112 showed superior accumulation and retention of the magnetic particles in comparison to ferritic steel 1.4521 and a Ti90Al6V4 control. In vivo tests in a mouse model where the nanoparticles were injected subcutaneously showed the good biocompatibility of the magnetic silica nanoparticles and their accumulation on the surface of a metallic plate, which had been implanted before, and in the surrounding tissue.

Conclusion

With their superparamagnetic properties and their high porosity, multifunctional magnetic nanoporous silica nanoparticles are ideal candidates as drug carriers. In combination with their good biocompatibility in vitro, they have ideal properties for an implant directed magnetic drug targeting. Missing adverse clinical and histological effects proved the good biocompatibility in vivo. Accumulation and retention of the nanoparticles could be influenced by the magnetic properties of the implanted plates; a remanent martensitic steel plate significantly improved both values in vitro. Therefore, the use of magnetizable implant materials in combination with the magnetic nanoparticles has promising potential for the selective treatment of implant-associated infections.

     

Arable weed seed bank of grassland on former arable fields in mountain regions

The changes in agricultural practice during the last century resulted in high-input farming in lowlands and the abandonment of crop fields in marginally profitable mountain regions. In Switzerland abandoned fields were converted into grassland. These fields had a rich historical flora and the few still existing fields still belong to the most species rich. As many arable weeds produce persistent seeds, abandoned fields should have a high potential to promote rare and threatened arable plants if tilled again. To test this hypothesis we collected 21 soil samples down to 20 cm depth in each the centre and the border of 38 abandoned fields. The centre and border samples of each field were each pooled, and afterwards the present seeds washed out. These seeds were then sown in pots and germination monitored in a greenhouse during six months. A total of 119 plant species were identified. Of these, 48 species were typical arable weeds and only one was red listed in Switzerland. The number of arable weeds per former field was lower at higher altitudes. Hence, the surveyed meadows have a small potential to promote threatened arable weeds if tilled again. Likely, some seeds were no longer viable because the fields were not tilled for a too long. If on newly established conservation fields no threatened species grow spontaneously after a few years, the reintroduction of desired plant species should be considered. The source of the seeds should preferably be a nearby species pool.     

AT 101 induces early mitochondrial dysfunction and HMOX1 (heme oxygenase 1) to trigger mitophagic cell death in glioma cells

In most cases, macroautophagy/autophagy serves to alleviate cellular stress and acts in a pro-survival manner. However, the effects of autophagy are highly contextual, and autophagic cell death (ACD) is emerging as an alternative paradigm of (stress- and drug-induced) cell demise. AT 101 ([-]-gossypol), a natural compound from cotton seeds, induces ACD in glioma cells as confirmed here by CRISPR/Cas9 knockout of ATG5 that partially, but significantly rescued cell survival following AT 101 treatment. Global proteomic analysis of AT 101-treated U87MG and U343 glioma cells revealed a robust decrease in mitochondrial protein clusters, whereas HMOX1 (heme oxygenase 1) was strongly upregulated. AT 101 rapidly triggered mitochondrial membrane depolarization, engulfment of mitochondria within autophagosomes and a significant reduction of mitochondrial mass and proteins that did not depend on the presence of BAX and BAK1. Conversely, AT 101-induced reduction of mitochondrial mass could be reversed by inhibiting autophagy with wortmannin, bafilomycin A₁ and chloroquine. Silencing of HMOX1 and the mitophagy receptors BNIP3 (BCL2 interacting protein 3) and BNIP3L (BCL2 interacting protein 3 like) significantly attenuated AT 101-dependent mitophagy and cell death. Collectively, these data suggest that early mitochondrial dysfunction and HMOX1 overactivation synergize to trigger lethal mitophagy, which contributes to the cell killing effects of AT 101 in glioma cells.

Abbreviations: ACD, autophagic cell death; ACN, acetonitrile; AT 101, (-)-gossypol; BAF, bafilomycin A₁; BAK1, BCL2-antagonist/killer 1; BAX, BCL2-associated X protein; BH3, BCL2 homology region 3; BNIP3, BCL2 interacting protein 3; BNIP3L, BCL2 interacting protein 3 like; BP, Biological Process; CCCP, carbonyl cyanide m-chlorophenyl hydrazone; CC, Cellular Component; Con, control; CQ, chloroquine; CRISPR, clustered regularly interspaced short palindromic repeats; DMEM, Dulbecco’s Modified Eagle Medium; DTT, 1,4-dithiothreitol; EM, electron microscopy; ER, endoplasmatic reticulum; FACS, fluorescence-activated cell sorting; FBS, fetal bovine serum; FCCP, carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone; GO, Gene Ontology; HAcO, acetic acid; HMOX1, heme oxygenase 1; DKO, double knockout; LC-MS/MS, liquid chromatography coupled to tandem mass spectrometry; LPL, lipoprotein lipase, MEFs, mouse embryonic fibroblasts; mPTP, mitochondrial permeability transition pore; MTG, MitoTracker Green FM; mt-mKeima, mito-mKeima; MT-ND1, mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 1; PBS, phosphate-buffered saline; PE, phosphatidylethanolamine; PI, propidium iodide; PRKN, parkin RBR E3 ubiquitin protein ligase; SDS, sodium dodecyl sulfate; SQSTM1/p62, sequestome 1; STS, staurosporine; sgRNA, single guide RNA; SILAC, stable isotope labeling with amino acids in cell culture; TFA, trifluoroacetic acid, TMRM, tetramethylrhodamine methyl ester perchlorate; WM, wortmannin; WT, wild-type     

Phytochemical review of the lichen genus <Emphasis Type="Italic">Stereocaulon</Emphasis> (Fam. Stereocaulaceae) and related pharmacological activities highlighted by a focus on nine species

The Stereocaulon genus is one of the fruticose lichen groups distributed worldwide from tropical zones to polar zones. However, the scientific study of this tricky genus is still limited, making it a challenge to study the group further. Detailed morphological studies are essential to discriminate closely shaped species which is illustrated through personal data focused on phyllocladia, apothecia and spores of nine species. Secondary metabolites isolated from Stereocaulon species are mostly some depsides, depsidones, diphenylethers and dibenzofurans which can have a taxonomic value. The use of Stereocaulon lichens as a traditional medicine in several regions of the world and pharmacological studies of extracts and isolated compounds have been compiled. Biological activities as cytotoxic, anti-inflammatory, antibacterial, antifungal or antioxidant are reported.