Modulation of drug-induced cytotoxicity by a bispecific monoclonal antibody that recognizes the epidermal growth factor receptor and doxorubicin

A hybrid hybridoma secreting a bispecific hybrid mAb (bsmAb), which recognizes both the epidermal growth factor receptor (EGF-R) and the drug doxorubicin, was produced by somatic hybridization of two hybridomas. The bsmAb obtained was able to retarget doxorubicin cytotoxicity in vitro specifically on EGF-R-positive cells exerting at the same time an antidotal effect on cells that did not overexpress the EGF-R. Distribution studies in mice indicate that the bsmAb selectively delivers the drug to tumour cells and modifies doxorubicin biodistribution with a statistically significant decrease of drug concentration in the intestine, which is the main target of early anthracycline toxicity. In keeping with this finding is the remarkable antidotal activity exerted by bsmAb in mice treated with doxorubiein, which is proved by retardation in loss of body weight and mortality. The effectiveness on tumour growth of the mAb followed by the administration of doxorubicin appears to be equal to that of the drug alone; however, the bsmAb exerts a remarkable antidotal activity.     

Patterns of cellular proliferation and migration in the developing tectum mesencephali of the frog Rana temporaria and the salamander Pleurodeles waltl

The development of the tectum mesencephali was studied in the frog Rana temporaria and the salamander Pleurodeles waltl by means of nuclear staining and by labeling of cells with bromodeoxyuridine (BrdU). The general spatial and temporal pattern of cell proliferation and cell migration is the same in both species, despite drastic differences in overall tectal morphology. However, the salamander species differs from the frog species by (1) a generally lower cell proliferation rate, (2) a reduction in the activity of the lateral proliferation zone, and (3) a reduction in the formation of superficial cellular layers. Because point (3) affects processes that occur late in ontogeny, our experiments provide evidence that the simple morphology of the tectum of Pleurodeles waltl, compared with the multilayered tectum of Rana, is a consequence of a paedomorphic alteration of the ancestral developmental pattern of the amphibian tectum.     

Wood distillate (pyroligneous acid) boosts nutritional traits of potato tubers

Potato is the fourth most widely consumed staple food in the world. This study investigated the effectiveness of 0.2% wood distillate (WD), a biostimulant derived from the pyrolysis of waste plant biomass, in boosting the nutritional quality of potato tubers. The results showed that application of WD significantly increased the content of soluble sugars (sucrose +56.3%; glucose +44.9%; fructose +62.2%), starch (+35.1%) and total carbohydrates (+16.8%). Antioxidants (total antioxidant power, polyphenols, flavonoids) and most mineral elements (K, Mg, Ca, Na, Fe, Zn) were not affected. A lower content of Cu (−17.8%) and P (−24.5%) was found in WD-treated potato.     

The distribution of coastal fish eDNA sequences in the Anthropocene

Aim

Coastal fishes have a fundamental role in marine ecosystem functioning and contributions to people, but face increasing threats due to climate change, habitat degradation and overexploitation. The extent to which human pressures are impacting coastal fish biodiversity in comparison with geographic and environmental factors at large spatial scale is still under scrutiny. Here, we took advantage of environmental DNA (eDNA) metabarcoding to investigate the relationship between fish biodiversity, including taxonomic and genetic components, and environmental but also socio-economic factors.

Location

Tropical, temperate and polar coastal areas.

Time period

Present day.

Major taxa studied

Marine fishes.

Methods

We analysed fish eDNA in 263 stations (samples) in 68 sites distributed across polar, temperate and tropical regions. We modelled the effect of environmental, geographic and socio-economic factors on α- and β-diversity. We then computed the partial effect of each factor on several fish biodiversity components using taxonomic molecular units (MOTU) and genetic sequences. We also investigated the relationship between fish genetic α- and β-diversity measured from our barcodes, and phylogenetic but also functional diversity.

Results

We show that fish eDNA MOTU and sequence α- and β-diversity have the strongest correlation with environmental factors on coastal ecosystems worldwide. However, our models also reveal a negative correlation between biodiversity and human dependence on marine ecosystems. In areas with high dependence, diversity of all fish, cryptobenthic fish and large fish MOTUs declined steeply. Finally, we show that a sequence diversity index, accounting for genetic distance between pairs of MOTUs, within and between communities, is a reliable proxy of phylogenetic and functional diversity.

Main conclusions

Together, our results demonstrate that short eDNA sequences can be used to assess climate and direct human impacts on marine biodiversity at large scale in the Anthropocene and can further be extended to investigate biodiversity in its phylogenetic and functional dimensions.     

A novel and high-throughput approach to assess photosynthetic thermal tolerance of kelp using chlorophyll α fluorometry

Foundation seaweed species are experiencing widespread declines and localized extinctions due to increased instability of sea surface temperature. Characterizing temperature thresholds are useful for predicting patterns of change and identifying species most vulnerable to extremes. Existing methods for characterizing seaweed thermal tolerance produce diverse metrics and are often time-consuming, making comparisons between species and techniques difficult, hindering insight into global patterns of change. Using three kelp species, we adapted a high-throughput method – previously used in terrestrial plant thermal biology – for use on kelps. This method employs temperature-dependent fluorescence (T–F₀) curves under heating or cooling regimes to determine the critical temperature (T_crit) of photosystem II (PSII), i.e., the breakpoint between slow and fast rise fluorescence response to changing temperature, enabling rapid assays of photosynthetic thermal tolerance using a standardized metric. This method enables characterization of T_crit for up to 48 samples per two-hour assay, demonstrating the capacity of T–F₀ curves for high-throughput assays of thermal tolerance. Temperature-dependent fluorescence curves and their derived metric, T_crit, may offer a timely and powerful new method for the field of phycology, enabling characterization and comparison of photosynthetic thermal tolerance of seaweeds across many populations, species, and biomes.     

Comparative LCA studies of simulated HMF biorefineries from maize and miscanthus as an example of first- and second-generation biomass as a tool for process development

5-Hydroxymethylfurfural (HMF) is a versatile platform chemical for a fossil free, bio-based chemical industry. HMF can be produced by using fructose as a feedstock. Using edible, first-generation biomass to produce chemicals has been questioned in terms of potential competition with food supply. Second-generation biomass like miscanthus could be an alternative. However, there is a lack of information if second-generation lignocellulosic biomass is a more sustainable feedstock to produce HMF. Therefore, a life cycle assessment was performed in this study to determine the environmental impacts of HMF production from miscanthus and to compare it with HMF from high-fructose corn syrup (HFCS). HFCS from either Hungary or Baden-Württemberg (Germany) was considered. Compared to the HFCS biorefineries the miscanthus concept is producing less emissions in all impact categories studied, except land occupation. Overall, the production and usage of second-generation biomass could be especially beneficial in areas where the use of N fertilizers is restricted. Besides, conclusions for the further development of the on-farm biorefinery concept were elaborated. For this purpose, process simulations from a previous study were used. Results of the previous study in terms of TEA and the current LCA study in terms of environmental sustainability indicate that the lignin depolymerization unit in the miscanthus biorefinery has to be improved. The scenario without lignin depolymerization performs better in all impact categories. The authors recommend to not further convert the lignin to products like phenol and other aromatic compounds. The results of the contribution analyses show that the major impact in the HMF production is caused by the auxiliary materials in the separation units and the required heat. Further technical development should focus on efficient heat as well as solvent use and solvent recovery. At this point further optimizations will lead to reduced emissions and costs at the same time.     

Novel Miscanthus hybrids: Modelling productivity on marginal land in Europe using dynamics of canopy development determined by light interception

New biomass crop hybrids for bioeconomic expansion require yield projections to determine their potential for strategic land use planning in the face of global challenges. Our biomass growth simulation incorporates radiation interception and conversion efficiency. Models often use leaf area to predict interception which is demanding to determine accurately, so instead we use low-cost rapid light interception measurements using a simple laboratory-made line ceptometer and relate the dynamics of canopy closure to thermal time, and to measurements of biomass. We apply the model to project the European biomass potentials of new market-ready hybrids for 2020–2030. Field measurements are easier to collect, the calibration is seasonally dynamic and reduces influence of weather variation between field sites. The model obtained is conservative, being calibrated by crops of varying establishment and varying maturity on less productive (marginal) land. This results in conservative projections of miscanthus hybrids for 2020–2030 based on 10% land use conversion of the least (productive) grassland and arable for farm diversification, which show a European potential of 80.7–89.7 Mt year⁻¹ biomass, with potential for 1.2–1.3 EJ year⁻¹ energy and 36.3–40.3 Mt year⁻¹ carbon capture, with seeded Miscanthus sacchariflorus × sinensis displaying highest yield potential. Simulated biomass projections must be viewed in light of the field measurements on less productive land with high soil water deficits. We are attempting to model the results from an ambitious and novel project combining new hybrids across Europe with agronomy which has not been perfected on less productive sites. Nevertheless, at the time of energy sourcing issues, seed-propagated miscanthus hybrids for the upscaled provision of bioenergy offer an alternative source of renewable energy. If European countries provide incentives for growers to invest, seeded hybrids can improve product availability and biomass yields over the current commercial miscanthus variety.     

Attempts to Determine the Roles of Visual and Olfactory Inputs in Initial Orientation and Homing of Pigeons over Familiar Terrain

The role of familiar visual landmarks in pigeon homing is still unsettled. If they are involved, they must be thought to be utilized in parallel with olfactory signals. In order to recognize the effectiveness of either one of the input channels separately, vision and olfaction, it is therefore necessary to interfere with both of them. Pigeons were temporarily deprived of image vision by spectacles made of translucent white paper, producing a condition called V^- as compared with the largely unimpaired condition V⁺. Access to olfactory signals was temporarily prohibited by charcoal filters before release and nasal anaesthesia upon release, resulting in condition O^- versus unimpaired smelling of natural air in O⁺. Prior to the test releases, all the participating pigeons had been made familiar with the two or four test sites (and with other sites in the area) by training flights. According to decreasing levels of initial homeward orientation and homing performance, the four combinations of treatments are to be arranged in the following order: V⁺O⁺, V⁺O^-, V^-O⁺, V^-O^-. In the last type, no trace of initial homeward orientation remained, indicating that at least one of the two input channels need be functional to enable home-related orientation. Over well known terrain, either alone seems to be more or less sufficient. The results are indicative but not definitely conclusive. Effects of visual impairment on behavioural activities in general cannot clearly be separated from orientation-specific effects. Therefore, and because many pigeons refuse to fly in V^- condition or fail to provide useful data, we stopped applying this method.