Cryptochrome-dependent magnetoreception in a heteropteran insect continues even after 24†h in darkness.

Sensitivity to magnetic fields is dependent on the intensity and color of light in several animal species. The light-dependent magnetoreception working model points to cryptochrome (Cry) as a protein cooperating with its co-factor flavin, which possibly becomes magnetically susceptible upon excitation by light. The type of Cry involved and what pair of magnetosensitive radicals are responsible is still elusive. Therefore, we developed a conditioning assay for the firebug Pyrrhocoris apterus, an insect species that possesses only the mammalian cryptochrome (Cry II). Here, using the engineered Cry II null mutant, we show that: (i) vertebrate-like Cry II is an essential component of the magnetoreception response, and (ii) magnetic conditioning continues even after 25 h in darkness. The light-dependent and dark-persisting magnetoreception based on Cry II may inspire new perspectives in magnetoreception and cryptochrome research.

Progressive Oncological Surgery Is Associated with Increased Curative Resection Rates and Improved Survival in Metastatic Colorectal Cancer.

BACKGROUND: Secondary resection rates in first-line chemotherapy trials for metastatic colorectal cancer (mCRC) remain below 15%, representing a clear contrast to reports by specialised surgical centres, where progressive liver, peritoneal-surface, and pulmonary surgery increased access to curative-intent treatment. We present a long-term evaluation of oncosurgical management in a single-centre, analysing the aggregate effect of gradual implementation of surgical subspecialties and systemic treatments on mCRC patients' resection rates and prognosis. METHODS: Patients with newly diagnosed mCRC from 2003 to 2014 were retrospectively categorised into palliative treatment (PAT) and curative intent surgery (CIS) and three time periods were analysed for treatment changes and factors associated with survival. RESULTS: Four hundred-twenty patients were treated (PAT:250/CIS:170). Over time periods, the number of presenting patients remained consistent, whereas curative resection rates increased from 29% to 55%, facilitated by an increment of patients undergoing hepatectomy (21 to 35%), pulmonary surgery (6 to 17%), and peritonectomy/intraoperative chemotherapy (0 to 8%). Also, recently, significantly more multi-line systemic treatments were applied. The median survival markedly improved from 21.9 months (2003⁻2006; 95% confidence interval (CI) 17.3⁻26.5) to 36.5 months (2011⁻2014; 95% CI 26.6⁻46.4; p = 0.018). PAT was a significant factor of poor survival and diagnosis of mCRC in the latest time period was independently associated with a distinctly lower risk for palliative treatment (odds ratio 0.15). CONCLUSIONS: In modern eras of medical oncology, achieving appropriate resection rates through utilization of state-of-the-art oncological surgery by dedicated experts represents a cornerstone for long-term survival in mCRC.

Concentrations of Thirteen Trace Metals in Scales of Three Nototheniid Fishes from Antarctica (James Ross Island, Antarctic Peninsula).

In this study, we assessed concentrations of 13 trace metals in the scales of Notothenia coriiceps, Trematomus bernacchii and Gobionotothen gibberifrons caught off the coast of James Ross Island (Antarctic Peninsula). Overall, our results for scales broadly match those of previous studies using different fish and different organs, with most metals found at trace levels and manganese, aluminium, iron and zinc occurring at high levels in all species. This suggests that scales can serve as a useful, non-invasive bioindicator of long-term contamination in Antarctic fishes. High accumulation of manganese, aluminium, iron and zinc is largely due to high levels in sediments associated with nearby active volcanic sites. Manganese, vanadium and aluminium showed significant positive bioaccumulation in T. bernacchii (along with non-significant positive accumulation of iron, zinc, cobalt and chromium), most likely due to greater dietary specialisation on sediment feeding benthic prey and higher trophic species. Levels of significance in bioaccumulation regressions were strongly affected by large-scale variation in the data, driven largely by individual differences in diet and/or changes in habitat use and sex differences associated with life stage and reproductive status. Increased levels of both airborne deposition and precipitation and meltwater runoff associated with climate change may be further adding to the already high levels of manganese, aluminium, iron and zinc in Antarctic Peninsula sediments. Further long-term studies are encouraged to elucidate mechanisms of uptake (especially for aluminium and iron) and possible intra- and interspecific impacts of climate change on the delicate Antarctic food web.

How Swift Is Cry-Mediated Magnetoreception? Conditioning in an American Cockroach Shows Sub-second Response.

Diverse animal species perceive Earth's magnetism and use their magnetic sense to orientate and navigate. Even non-migrating insects such as fruit flies and cockroaches have been shown to exploit the flavoprotein Cryptochrome (Cry) as a likely magnetic direction sensor; however, the transduction mechanism remains unknown. In order to work as a system to steer insect flight or control locomotion, the magnetic sense must transmit the signal from the receptor cells to the brain at a similar speed to other sensory systems, presumably within hundreds of milliseconds or less. So far, no electrophysiological or behavioral study has tackled the problem of the transduction delay in case of Cry-mediated magnetoreception specifically. Here, using a novel aversive conditioning assay on an American cockroach, we show that magnetic transduction is executed within a sub-second time span. A series of inter-stimulus intervals between conditioned stimuli (magnetic North rotation) and unconditioned aversive stimuli (hot air flow) provides original evidence that Cry-mediated magnetic transduction is sufficiently rapid to mediate insect orientation.

LuAG:Pr3+-porphyrin based nanohybrid system for singlet oxygen production: Toward the next generation of PDTX drugs.

A highly prospective drug for the X-ray induced photodynamic therapy (PDTX), LuAG:Pr3+@SiO2-PpIX nanocomposite, was successfully prepared by a three step process: photo-induced precipitation of the Lu3Al5O12:Pr3+ (LuAG:Pr3+) core, sol-gel technique for amorphous silica coating, and a biofunctionalization by attaching the protoporphyrin IX (PpIX) molecules. The synthesis procedure provides three-layer nanocomposite with uniform shells covering an intensely luminescent core. Room temperature radioluminescence (RT RL) spectra as well as photoluminescence (RT PL) steady-state and time resolved spectra of the material confirm the non-radiative energy transfer from the core Pr3+ ions to the PpIX outer layer. First, excitation of Pr3+ ions results in the red luminescence of PpIX. Second, the decay measurements exhibit clear evidence of mentioned non-radiative energy transfer (ET). The singlet oxygen generation in the system was demonstrated by the 3'-(p-aminophenyl) fluorescein (APF) chemical probe sensitive to the singlet oxygen presence. The RT PL spectra of an X-ray irradiated material with the APF probe manifest the formation of singlet oxygen due to which enhanced luminescence around 530 nm is observed. Quenching studies, using NaN3 as an 1O2 inhibitor, also confirm the presence of 1O2 in the system and rule out the parasitic reaction with OH radicals. To summarize, presented features of LuAG:Pr3+@SiO2-PpIX nanocomposite indicate its considerable potential for PDTX application.

At the crossroad of photochemistry and radiation chemistry: formation of hydroxyl radicals in diluted aqueous solutions exposed to ultraviolet radiation.

Formation yields of ˙OH radicals were precisely determined in aqueous solutions of coumarin-3-carboxylic acid and ferrous sulfate (i.e., Fricke dosimeter) exposed to 253.7 nm radiation delivered from a continuous source. Quantum yield of ˙OH radicals was determined as ∼0.08, i.e., roughly one out of twelve photons, efficiently absorbed in UV-illuminated solutions, produced one ˙OH radical. Energetically, a water molecule should undergo a correlated action of at least two 4.9 eV photons delivering enough energy for direct H-OH dissociation (5.0-5.4 eV). We suggest a mechanism based on an interaction of two water molecules, both in long-living triplet states. An intermolecular transfer of excitation energy provided a sufficient amount of energy for the dissociation of one water molecule into ˙OH and H˙ radicals. In an aqueous solution of phospholipids, quantum yields of hydroperoxides formed under these irradiation conditions decreased with total effectively absorbed energy (i.e. a dose), similar to the radiation chemical yields obtained during an exposure to ionizing radiation, such as gamma rays from radionuclide sources. Under 253.7 nm irradiation, one ˙OH radical causes a peroxidation of 34 phospholipid molecules. This implicates chain mechanism of the reaction.

Degradation of phospholipids under different types of irradiation and varying oxygen saturation.

The effects of different types of radiation on the formation of peroxide forms of 2-dioleoyl-sn-glycero-3-phosphocholine were studied under various conditions. For the irradiation, an aqueous solution of small unilamellar vesicles was prepared. Variations in parameters such as the dose rate and molecular oxygen saturation levels were evaluated. Our study suggests that the mechanism of the peroxides formation process remains unchanged under irradiation by accelerated electrons, gamma and accelerated protons. The values of radiation chemical yields of the peroxidic form depend on the type of radiation, dose rate, and the saturation of molecular oxygen. The level of oxygen saturation strongly affects the values of radiation chemical yields as well, as the dissolved oxygen is an important agent participating in peroxidation and it is a source of free radicals during the radiolysis. The values of radiation chemical yields strongly suggest that the mechanism of radiation-induced peroxidation of phosphatidylcholines does not proceed via chain reaction.

Cryptochrome 2 mediates directional magnetoreception in cockroaches.

The ability to perceive geomagnetic fields (GMFs) represents a fascinating biological phenomenon. Studies on transgenic flies have provided evidence that photosensitive Cryptochromes (Cry) are involved in the response to magnetic fields (MFs). However, none of the studies tackled the problem of whether the Cry-dependent magnetosensitivity is coupled to the sole MF presence or to the direction of MF vector. In this study, we used gene silencing and a directional MF to show that mammalian-like Cry2 is necessary for a genuine directional response to periodic rotations of the GMF vector in two insect species. Longer wavelengths of light required higher photon fluxes for a detectable behavioral response, and a sharp detection border was present in the cyan/green spectral region. Both observations are consistent with involvement of the FADox, FAD(•-) and FADH(-) redox forms of flavin. The response was lost upon covering the eyes, demonstrating that the signal is perceived in the eye region. Immunohistochemical staining detected Cry2 in the hemispherical layer of laminal glia cells underneath the retina. Together, these findings identified the eye-localized Cry2 as an indispensable component and a likely photoreceptor of the directional GMF response. Our study is thus a clear step forward in deciphering the in vivo effects of GMF and supports the interaction of underlying mechanism with the visual system.