Stimuli-Responsive magnetic nanoparticles for monoclonal antibody purification

Monoclonal antibodies (mAbs) are important therapeutic proteins. One of the challenges facing large-scale production of monoclonal antibodies is the capacity bottleneck in downstream processing, which can be circumvented by using magnetic stimuli-responsive polymer nanoparticles. In this work, stimuli-responsive magnetic particles composed of a magnetic poly(methyl methacrylate) core with a poly(N-isopropylacrylamide-co-acrylic acid) (P(NIPAM-co-AA)) shell cross-linked with N, N'-methylenebisacrylamide were prepared by miniemulsion polymerization. The particles were shown to have an average hydrodynamic diameter of 317 nm at 18°C, which decreased to 277 nm at 41°C due to the collapse of the thermo-responsive shell. The particles were superparamagnetic in behavior and exhibited a saturation magnetization of 12.6 emu/g. Subsequently, we evaluated the potential of these negatively charged stimuli-responsive magnetic particles in the purification of a monoclonal antibody from a diafiltered CHO cell culture supernatant by cation exchange. The adsorption of antibodies onto P(NIPAM-co-AA)-coated nanoparticles was highly selective and allowed for the recovery of approximately 94% of the mAb. Different elution strategies were employed providing highly pure mAb fractions with host cell protein (HCP) removal greater than 98%. By exploring the stimuli-responsive properties of the particles, shorter magnetic separation times were possible without significant differences in product yield and purity.     

Variation of Chemical Constituents and Antiradical Capacity of Nine Ferulago angulata Populations from Iran

The present study was designed to assess the influence of geographical factors on essential oil (EO) composition, along with antiradical potential and phytochemical contents of Ferulago angulata (Schltdl .) Boiss (Apiaceae) extracts for the first time. The aerial parts were hydrodistilled by Clevenger apparatus and subjected to gas chromatography coupled with flame ionization detector (GC/FID) and mass spectroscopy (GC/MS). The EO yields were significantly different from populations ‘Mongar’ (south‐slope, 3000 m) with 1.34±0.06 % and ‘Male‐Amiri’ (north slope, 2600 m) with 0.18±0.05 % of total oil. Thirty‐nine compounds were identified from the EOs of nine populations. α‐Pinene was the predominant component ranging from 20.84 to 49.06 % in ‘Gandomkar’ (north‐slope, 2500 m) and ‘Mongar’ (3000 m), respectively. The methanolic extract of ‘Mongar’ (north‐slope at 2500 m) possessed the highest total phenolic contents. Also, this population logically exhibited potent antiradical activity using both 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) and oxygen radical absorbance capacity (ORAC) assays with EC₅₀ of 42.07±4.12 μg/mL and 8.34±0.21 mmol Trolox® equivalents/g, respectively. Due to its moderate free‐radical scavenging potential and high α‐pinene content, the population ‘Mongar’ might be considered as a perspective raw material in food and phytopharmaceutical industries.     

Assessing lignocellulosic biomass production from crop residues in the European Union: Modelling,analysis of the current scenario and drivers of interannual variability

This study assesses crop residues in the EU from major crops using empirical models to predict crop residues from yield statistics; furthermore it analyses the inter‐annual variability of those estimates over the period 1998‐2015, identifying its main drivers across Europe. The models were constructed based on an exhaustive collection of experimental data from scientific papers for the crops: wheat, barley, rye, oats, triticale, rice, maize, sorghum, rapeseed, sunflower, soybean, potato and sugarbeet. We discuss the assumptions on the relationship between yield and the harvest index, adopted by previous studies, to interpret the experimental data, quantify the uncertainties of these models, and establish the premises to implement them at regional scale –i.e., NUTS level 3– within the EU. To cope this, we created a consolidated sub‐national statistical data along with an algorithm able to aggregate (figures are provided at country level) and disaggregate (production at 25 km grid is provided assupplementary material) estimates. The total lignocellulosic biomass production in the EU28 over the review period, according to our models, is 419 Mt, from which wheat is the major contributor (155 Mt). Our results show that maize and rapeseed are the two crops with the highest residue yield, respectively 8.9 and 8.6 t ha‐1. The spatial analysis revealed that these three crops, which, according to our results, are feedstocks highly suitable a priori for second generation biofuels in the EU and are unevenly distributed across Europe. Weather fluctuation was identified as the major driver in residue production from cereals, while, in the case of starch crops and oilseeds – which are predominant in northern Europe – corresponded to the marked production trend likely influenced by the agricultural policies and agro‐management over the review period. Our results, among others, could help to understand and quantify the ecological boundaries of the bioeconomy from agriculture.     

An assessment of feral horse impacts on treeless drainage lines in the Australian Alps

The feral Horse (Equus caballus) is widespread across the Australian Alps. Feral horses degrade alpine and sub‐alpine ecosystems and damage habitat of a range of threatened species. Despite this, there is little published work to document the extent and severity of these impacts. This study investigated impacts of feral horses on treeless drainage lines at 186 sites across the Australian Alps. The study included sites in the Australian Capital Territory, New South Wales and Victoria. We assessed nine variables related to soil and stream stability and vegetation cover, which in turn influence ecosystem function and habitat quality. We found significant differences among horse‐occupied and horse‐free sites for all soil and stream stability variables assessed. For all variables assessed, the average score (and hence, condition) was worse in horse‐occupied areas. The sites in poorest condition were occupied by horses. Impacts from other mammalian herbivores species appeared to be minor. Management intervention is necessary if these impacts of feral horses are to be addressed.     

Hypoxia and its downstream targets in DMBA induced mammary carcinoma: protective role of Semecarpus anacardium nut extract

Tumors are usually exposed to a hypoxic microenvironment due to their irregular growth and abnormal vascular supply. Under hypoxia, gene regulation (selective activation and inactivation of genes) plays an important role in maintenance of tumor. Multiple hypoxic and angiogenic growth factors are expressed for tumor cell survival. In search of novel anticancer drug, Semecarpus anacardium nut extract (SA) was tried against breast cancer. Mammary carcinoma was induced in vivo by 7,12-dimethyl benz(a) anthracene (DMBA) (25mg/kg b.w., p.o.). Tumor development and vascular structures were accelerated by DMBA. Hypoxia inducible factor-1 alpha (HIF-1) was coexpressed with its downstream genes in mammary tissue. Cancer rats were then treated with S. anacardium nut extract (SA) (250mg/kg b.w., p.o.). Delay in the tumor growth was paralleled with a drastic reduction in vascularization by SA treatment. Activities of glycolytic enzymes were normalized with decreased expression of glucose transporter-1 and carbonic anhydrase IX by drug treatment. Inhibition of HIF-1, vascular endothelial growth factor and inducible nitric oxide synthase by SA may in part explain its antiangiogenic action. SA also inhibits endothelial cell proliferation by blocking the overexpressed survival cytokines. In conclusion, our study demonstrates that at least some part of the antitumor activity of SA is due to the suppression of hypoxic and angiogenic factors. The mechanism of this inhibition seems to be through an action of SA on expression of HIF-1 and its downstream targets.     

Affinity precipitation an option for early capture in bioprocessing

Affinity precipitation is a bioseparation technique where the affinity ligand is coupled to a stimuliresponsive polymer. Stimuli-responsive polymers show abrupt, yet reversible, phase transition (precipitation) in response to a small change in an environmental parameter. The corresponding ligand conjugates can be used to co-precipitate and thereby capture and isolate target molecules from complex solutions such as culture supernatants and cell lysates. The approach is compatible with a 'discardibles only' type of downstream process and can be scaled over several orders of magnitude. This report discusses the set-up and development of affinity precipitation procedures, the related instrumentation and scale up, as well as applications for the isolation of proteins and polynucleotides.     

Cats under cover: Habitat models indicate a high dependency on woodlands by Atlantic Forest felids

Four Neotropical small and medium felids—the ocelot, jaguarundi, margay, and southern tiger cat—have overlapping geographic distributions in the endangered Atlantic Forest. Local studies show that these felids avoid areas with high human impact, but the three smaller ones use human‐modified areas more frequently than do ocelots. To understand how landscape changes affect the habitat distribution of these four felids in the Atlantic Forest of Argentina, we used maximum entropy models to analyze the effect of environmental and anthropogenic factors. We estimated niche breadth and overlap among these felids. The conversion of the native forest to land uses without trees was the most important variable that determined the habitat distribution of the four species. For all four species, the optimal habitat covered about 1/3 of the study area and corresponds mainly to the native forest areas. Nearly 50% of these areas had some level of protection. The niche width was higher for the small felids than for ocelots. Niche overlap was high for all species pairs, but higher among the small felids and lower for each of these with the ocelot. The four felids were negatively affected by native forest loss, with ocelots being more sensitive than the smaller felids. The conversion of unprotected forest areas to other types of land uses would imply a greater habitat loss for these felids. The protection of current remnants of Atlantic Forest in Argentina is important for the long‐term conservation of the four felids. Abstract in Spanish is available with online material.     

Trace elements in coal

Trace elements can have profound adverse effects on the health of people burning coal in homes or living near coal deposits, coal mines, and coal-burning power plants. Trace elements such as arsenic emitted from coal-burning power plants in Europe and Asia have been shown to cause severe health problems. Perhaps the most widespread health problems are caused by domestic coal combustion in developing countries where millions of people suffer from fluorosis and thousands from arsenism. Better knowledge of coal quality characteristics may help to reduce some of these health problems. For example, information on concentrations and distributions of potentially toxic elements in coal may help delineate areas of a coal deposit to be avoided. Information on the modes of occurrence of these elements and the textural relations of the minerals in coal may help to predict the behavior of the potentially toxic trace metals during coal cleaning, combustion, weathering, and leaching.