Small Aggregates Research Articles

Estimating the heating of complex nanoparticle aggregates for magnetic hyperthermia.

Understanding and predicting the heat released by magnetic nanoparticles is central to magnetic hyperthermia treatment planning. In most cases, nanoparticles form aggregates when injected in living tissues, thereby altering their response to the applied alternating magnetic field and preventing the accurate prediction of the released heat. We performed a computational analysis to investigate the heat released by nanoparticle aggregates featuring different sizes and fractal geometry factors. By digitally mirroring aggregates seen in biological tissues, we found that the average heat released per particle stabilizes starting from moderately small aggregates, thereby facilitating making estimates for their larger counterparts. Additionally, we studied the heating performance of particle aggregates over a wide range of fractal parameters. We compared this result with the heat released by non-interacting nanoparticles to quantify the reduction of heating power after being instilled into tissues. This set of results can be used to estimate the expected heating in vivo based on the experimentally determined nanoparticle properties.

Phase equilibrium, dynamics and rheology of phospholipid-ethanol mixtures: a combined molecular dynamics, NMR and viscometry study.

Binary mixtures of ethanol and phospholipids DOPC and DOPE have been investigated in a composition range relevant for topical drug delivery applications. This was done using a combined computer simulation and experimental approach where molecular dynamics simulations of ethanol-lipid mixtures with different compositions were performed. Several key properties including diffusion coefficients, longitudinal relaxation times, and shear viscosity were computed. In addition, diffusion coefficients, viscosities and NMR longitudinal relaxation times were measured experimentally for comparison and in order to validate the results from simulation. Diffusion coefficients and relaxation times obtained from simulations are in good agreement with results from NMR and computed viscosities are in reasonable agreement with viscometry experiments indicating that the simulations provide a realistic description of the ethanol-phospholipid mixtures. Structural changes in the simulated systems were investigated using an analysis based on radial distribution functions. This showed that the structure of ethanol-DOPC mixtures remains essentially unchanged in the investigated concentration range while ethanol-DOPE mixtures undergo structural rearrangements with the tendency for forming small aggregates on the 100 ns time scale consisting of less than 10 lipids. Although our simulations and experiments indicate that no larger aggregates form, they also show that DOPE has stronger aggregation tendency than DOPC. This highlights the importance of the character of the lipid headgroup for lipid aggregation in ethanol and gives new insights into phase equilibrium, dynamics and rheology that could be valuable for the development of advanced topical drug delivery formulations.

STUDY OF A CONCRETE COLUMN FOR STABILITY UNDER ASYMMETRIC CORROSION

Reinforced concrete became widespread due to its many positive properties: durability, fire re-sistance, resistance to corrosive effects, high resistance to static and dynamic loads, low operating costs for maintaining buildings and structures, and relative cheapness of manufacturing. The presence of widespread large and small aggregate used in the production of reinforced concrete makes it applicable in all corners of the globe and even beyond its borders.The emergence and development of building structures, including reinforced concrete, is inextricably linked to the conditions of the material life of society, the development of productive forces. The appearance of reinforced concrete coincides with the period of accelerated development of industry, transport and trade in the second half of the 19th century. The period of emergence of reinforced concrete (1850-1885) is characterized by the appearance of the first structures made of reinforced concrete in France (Lam-bo, 1850; Quanier, 1854; gardener Monier, 1867-1880), England (Wilkinson, 1854), the USA (Hiatt, 1855-1877). Buildings and structures and their structures during operation experience force and non-force effects of the environment. With a symmetrical effect of the medium, centrally compressed rods remain centrally compressed, and with an extracenteral one, extracentric eccentricity appears. First, the rod experiences off-center compression. Further deformation will lead the rod to longitudinal bending, and under the action of a transverse load to longitudinal-transverse bending. In steel structures, the environment causes corrosion, in concrete ‒ corrosion and neutralization. In a physically linear formulation, these problems are solved, but it is necessary to take into account the real diagrams of steel and concrete, and to solve problems according to an unformed deformed scheme. Given the impact of the environment, new challenges arise with constructive and induced heterogeneity. Noncentrally compressed elements are part of statically definable and indeterminate structures: these are beams, threehinge systems, frames and trusses. This is a new topic, a new formulation of the question, tasks that require the development of new methods.

Synthesis and anti-bacterial/fungal activities of amphiphilic polysiloxanes primary ammonium salts

Amphiphilic cationic polymers are currently used as antimicrobial agents to disrupt microbial membranes with long-termed stability and low bio-toxicity. However, there are few studies on the relationship between molecular structure and antimicrobial properties of amphiphilic polymers containing primary amine salts against fungi. In this work, a series of polysiloxanes graft primary ammonium salts (PDMS-g-AH) with tunable molecular weights (3 kDa, 5 kDa, 8 kDa, and 10 kDa) and grafting ratios (50% and 75%) were synthesized via thiol-ene “click reaction”, and the effect of their structural parameters on the broad-spectrum inhibition of bacteria (Escherichia coli and Staphylococcus albus) and pathogenic fungi (Candida albicans), especially on two phytopathogenic fungi (Fusarium oxysporum f. sp. cubense race 4 (Foc4) and Rhizoctonia solani (R. solani)) were systematically assessed. The aggregation of polymers in water was characterized by the critical micelle concentration (CMC) values, zeta potentials, and particle sizes and distributions. All PDMS-g-AH had positive zeta-potential values and exhibited high micellar stability in water. At the same time, the aggregation characteristics of polymers are affected by the structure and molecular weight of polymers. Small aggregates and high zeta-potentials interacted easily with the microbial cell membranes, which affected the antimicrobial activity together. These results indicated that the block type of PDMS-g-AH, i.e., PDMS-b-AH, showed better antimicrobial activities than the random type (PDMS-co-AH), and the optimal antimicrobial activities were obtained for moderate polymer chain length (about 5 kDa). This work reveals the relationship between the chemical structure of PDMS-g-AH, their aggregation behavior in water as well as interaction with biological membranes during the sterilization process, which provides the potential applications as fungicidal agents for effectively controlling plant diseases, such as rice sheath blight and banana Fusarium wilt.

Ingression of the hydromedusa Neotima lucullana (delle chiaje, 1822) into the ecosystem of the Neretva river estuary (south-eastern Adriatic, Croatia

Hydromedusa Neotima lucullana is an endemic species of the Mediterranean Sea. In this study we document the first numerous and permanent occurrence of N. lucullana in the estuary of the Neretva River, an unusual habitat for this typical marine species. We provide COI barcode sequence of this species, which is also first genetic sequence ever published of N. lucullana. Weekly data on the occurrence and abundance of N. lucullana were obtained from reports and records of autonomous divers and local fishermen in the area from Opuzen to Metković from mid-June to the end of October 2021. The individuals were always located in the layer above the bottom with salinity between 35.2 and 38.2. The diameters of the jellyfish bells ranged from 15 mm to 72 mm, most of them between 40 mm and 58 mm. Differential development of the gonads was observed in all specimens larger than 25 mm. In mid-June, the specimens were common but solitary. A week later, the jellyfish were more frequent and in smaller aggregations. From late June to mid-September, the jellyfish were constantly observed in larger aggregations. Toward the autumn, the number of individuals gradually decreased, and by the last week of October, only single individuals were observed. Our results indicate significant changes in the ecosystem of the Neretva estuary and confirm the observed composition of zooplankton communities dominated by marine species in summer and autumn.

Atrial Natriuretic Peptide Associated with Cardiovascular Diseases Inhibits Amyloid-β Aggregation via Cross-Seeding.

Both cardiovascular diseases (CVDs) and Alzheimer's disease (AD) share some common risk factors (e.g., age, obesity, oxidative stress, inflammation, hypertension) that contribute to their overlapping pathogenesis, indicating a "head-to-heart" pathological connection between CVDs and AD. To explore this potential connection at the protein level, we study the potential cross-seeding (heterotypic interactions) between CVD-associated atrial natriuretic peptide (ANP) and AD-associated β-amyloid (Aβ). Collective aggregation and cell assays demonstrate the cross-seeding of ANP with different Aβ species including monomers, oligomers, and fibrils with high binding affinity (KD = 1.234-1.797 μM) in a dose-dependent manner. Such ANP-induced cross-seeding also modifies the Aβ aggregation pathway, fibril morphology, and cell deposition pattern by inhibiting Aβ fibrillization from small aggregates, disassembling preformed Aβ fibrils, and alleviating Aβ-associated cytotoxicity. Finally, using transgenic C. elegans worms that express the human muscle-specific Aβ1-42, ANP can also effectively delay Aβ-induced worm paralysis, decrease Aβ plaques in worm brains, and reduce reactive oxygen species (ROS) production, confirming its in vivo inhibition ability to prevent neurodevelopmental toxicity in worms. This work discovers not only a new cross-seeding system between the two disease-related proteins but also a new finding that ANP possesses a new biological function as an Aβ inhibitor in the nonaggregated state.

Feasibility of diffuser-incorporated near-infrared trans-reflectance measurement for quantitative detection of microplastics captured in perfluorocarbon

A diffuser-incorporated near-infrared (NIR) trans-reflectance measurement is demonstrated for quantitative detection of polyethylene (PE) particles captured in perfluorohexane (PFH, C6F14). PFH effectively captures PE particles through its hydrophobicity and absorbs little NIR radiation, recommending it for use in background-free NIR detection of captured PE particles. A reflective metal disk was used to push the captured PE particles in PFH toward the bottom of the vial that contained the sample, and the trans-reflectance measurement was performed by illuminating NIR radiation from the bottom of the vial at 45o. Reproducibility is limited by the variation in the positions of small PE-particle aggregates at the water/PFH interface and the difficulty in ensuring full NIR sampling (coverage) of large aggregates. An effective way to secure improved reproducibility under these circumstances is illumination of broader and more uniform NIR radiation for measurement. For this purpose, a polytetrafluoroethylene (PTFE) disk was uniquely incorporated as a diffuser for the trans-reflectance measurement. Compared to the measurement with no diffuser, the diffuser-incorporated scheme produced more distinct PE peaks of low-quantity samples (0.1 and 0.2 mg) and enhanced the reproducibility in measurements of all the samples (0.1–4.0 mg of PE). As a result, the correlation between peak intensity and particle quantity was excellent (R2: 0.997), and a limit of detection of 0.07 mg was achieved.

The effect of covalent binding of phthalocyanine macrocycles with a cyclotriphosphazene spacer on the aggregation, NLO, and CT properties

This work is devoted to studying the aggregation effect on the nonlinear optical (NLO) and charge transport (CT) properties of low-symmetry phthalocyanines bearing a cyclotriphosphazene moiety, a monomer, and clamshell-type bis-phthalocyanine. FE-SEM and AFM studies revealed ordered nanoaggregation in these compounds, represented as repeating objects of regular configuration, globules (340–480 nm), which contain small aggregates inside their cavity, similar to smoothed polygons (ca. 40 nm). Such specificity is not characteristic of other functionalized phthalocyanines, which we dealt with earlier. A new spectral method for estimating the aggregation threshold based on the change in extinction with increasing concentration of solutions was also implemented, and the effect of aggregation on optical limiting was demonstrated. The behavior of isomers and rotamers of bis-phthalocyanine in the presence of electric fields of various strengths was investigated with the DFT calculations, and that partially corresponds to the impact of laser radiation on molecules. It was shown that the unusual behavior of the trans-isomer in FF-DFT calculations is the reason for the worsening of the NLO and CT characteristics of bis-phthalocyanine, in which the macrocycles are strapped through a phosphazene spacer. An advanced method of multiparametric analysis has been implemented to evaluate the NLO and CT properties of the dyes in general.

To study the effect of geopolymer concrete by using metakaolin & bottom ash

Ordinary Portland cement is such a well-liked binding element for making concrete. Cement's resourcefulness as compared to any other material in the structural field has made it an ever-rising requirement. The use of cement continues to grow because of its ability to regain its initial strength and gain in strength over a long period. The development of geopolymer concrete is the principal role against the manufacture of environmentally suited concrete. Geopolymer is a non-organic alumino-silicate blend to reduce geological compounds or industrial goods such as fly calx, clinker, chaff ash, etc. In this article, we have shown the mechanical properties and flexural strength of geopolymer concrete. When creating geopolymer concrete, we combined bottom ash and metakaolin with an alkali solution to combat environmental contamination issues. In this work, we view the impact of the blend of metakaolin within the exclusive significant and exclusive stratum area of metakaolin that is 2.5 and 20000 cm2/gm serially and bottom ash (industrial byproducts) as source stuff accounts for the remaining 20 % to the alkali activator we used to the sodium hydroxide (NaOH) flake with 95–97 % purity, Sodium silicate available in a liquid gel. The sodium silicate solution consists of 13.7 % of sodium oxide (Na2O), 29.4 % of silicon dioxide (SiO2), and 55.9 % of water by mass, we also adapt the small aggregate applied in this work as river sand and coarse aggregate prescribed by BIS 2386–1963. Also, the suitability of metakaolin and bottom ash mixed geopolymer concrete as a paver cube has been evaluated. The conjunction of such materials can defend the environment to the exquisite scope and rescue resources. Part of the review is to research the mechanical character of geopolymer concrete and discuss the application possibility of geopolymer concrete and attempt to create a handout for the sector and industry.

Biogeofilter with Hydrothermal Treated Stevensite Clay and Laccase Enzymes for Retention and Degradation of Tetracycline

The concentration of antibiotics in surface water is an issue of high concern. The present study aims to manufacture and evaluate a biogeofilter, with stevensite clay and enzymes immobilized on it, for the adsorption and degradation of tetracycline-based antibiotics. To retain the small particle aggregates of the clay in the filter, a hydrothermal treatment was applied to the stevensite, prior to compaction in pellets and its insertion into a cylindric cell, mixed with sand. The structure of the pellets avoids the loss of the clay material during the fluid transport through the porous medium. Several temperature treatments were applied to the pellets, but the treatment at 300 °C was revealed as the best option. Laccase enzymes were immobilized on the stevensite surface. Reactive transport experiments of tetracycline solutions were performed through the transport cells. The biogeofilter has a relevant adsorption capacity with a significant degradation factor. By modelling with STANMOD software, the hydrodynamic characteristics of the transport were determined and, therefore, the behaviour of a large-scale filter and transports of low tetracycline concentrations could be predicted. The results obtained are promising for irrigation systems at medium scale, as well as for the perspective of wastewater treatment plants at large scale.

Interacting active surfaces: A model for three-dimensional cell aggregates.

We introduce a modelling and simulation framework for cell aggregates in three dimensions based on interacting active surfaces. Cell mechanics is captured by a physical description of the acto-myosin cortex that includes cortical flows, viscous forces, active tensions, and bending moments. Cells interact with each other via short-range forces capturing the effect of adhesion molecules. We discretise the model equations using a finite element method, and provide a parallel implementation in C++. We discuss examples of application of this framework to small and medium-sized aggregates: we consider the shape and dynamics of a cell doublet, a planar cell sheet, and a growing cell aggregate. This framework opens the door to the systematic exploration of the cell to tissue-scale mechanics of cell aggregates, which plays a key role in the morphogenesis of embryos and organoids.

Comparative Characterization of Grain Protein Content and Composition by Chromatography-Based Separation Methods (SE-HPLC and RP-HPLC) of Ten Wheat Varieties Grown in Different Agro-Ecological Zones of Algeria

To characterize and compare the protein quality of ten durum wheat genotypes grown under three cropping modalities in Algeria (subhumid in Algiers, subhumid-semiarid in Constantine, and semiarid in Sétif), the protein profile of their kernels was performed by High-Performance Liquid Chromatography (SE-HPLC and RP-HPLC). The “variety” factor has a major impact, mainly on the insoluble fraction (Fi), on the gliadin/glutenin ratio, on the large and small glutenin aggregates (F1 and F2, respectively), and on ω-gliadins and high molecular weight albumins (F3). Conversely, the total protein content and the albumin-globulin fraction (F5) depend mainly on the environment. The α- β- and γ-gliadins (F4) are equally dependent on variety and environment. The subhumid-semiarid agroecological conditions of Constantine (SH-SA) favored an important accumulation of proteins (14.1%), particularly by an increased synthesis of omega gliadins and high-molecular-weight glutenin subunits (HMW-GS), compared to those of Algiers (SH) and Sétif (SA). For these latter environments, metabolic-type proteins are predominant, reflected in a higher F5 fraction (p < 0.05) (albumin and globulin), and significantly more alpha-beta and gamma gliadins. The use of chromatographic analyses to characterize wheat genotypes remains a reliable tool for breeding and variety promotion programs and can provide a better understanding of the ecophysiology of cereal crops.

Urolithin B: Two-way attack on IAPP proteotoxicity with implications for diabetes.

Diabetes is one of the major metabolic diseases worldwide. Despite being a complex systemic pathology, the aggregation and deposition of Islet Amyloid Polypeptide (IAPP), or amylin, is a recognized histopathological marker of the disease. Although IAPP proteotoxicity represents an important trigger of β-cell dysfunction and ultimately death, its exploitation as a therapeutic tool remains underdeveloped. The bioactivity of (poly)phenols towards inhibition of pathological protein aggregation is well known, however, most of the identified molecules have limited bioavailability. Using a strategy combining in silico, cell-free and cell studies, we scrutinized a unique in-house collection of (poly)phenol metabolites predicted to appear in the human circulation after (poly)phenols ingestion. We identified urolithin B as a potent inhibitor of IAPP aggregation and a powerful modulator of cell homeostasis pathways. Urolithin B was shown to affect IAPP aggregation pattern, delaying the formation of amyloid fibrils and altering their size and morphology. The molecular mechanisms underlying urolithin B-mediated protection include protein clearance pathways, mitochondrial function, and cell cycle ultimately rescuing IAPP-mediated cell dysfunction and death. In brief, our study uncovered urolithin B as a novel small molecule targeting IAPP pathological aggregation with potential to be exploited as a therapeutic tool for mitigating cellular dysfunction in diabetes. Resulting from the colonic metabolism of dietary ellagic acid in the human body, urolithin B bioactivity has the potential to be explored in nutritional, nutraceutical, and pharmacological perspectives.

Soil aggregate development and associated microbial metabolic limitations alter grassland carbon storage following livestock removal

Natural restoration of degraded grasslands following livestock removal changed soil nutrient and carbon concentrations, soil aggregate distributions, and patterns of extracellular enzyme activities. Here, we used an ecoenzymatic stoichiometry model to quantify microbial resource limitations in semiarid grassland soil aggregates at 0, 11, 26, and 36 years after livestock removal and linked these limitations to microbial carbon use efficiency (CUE), which was estimated from stoichiometry theory (CUEST). Overall, livestock removal altered the size distribution of soil aggregates, increased microbial resources and stimulated extracellular enzyme activities. Long-term livestock removal increased the proportion of small macroaggregates (2–0.25 mm). Microbial carbon (C) and phosphorus (P) limitations in soil aggregates declined to minimum levels at 26 years following livestock removal and then increased after 36 years, with an opposite trend for CUEST. Additionally, the greatest resource limitations to microorganisms were found in smaller aggregates (<2 mm) under long-term livestock removal. Random forest and structural equation models revealed that soil abiotic factors, especially total nitrogen and pH, were key determinants of microbial resource limitation in soil aggregates. Moreover, microbial C and P limitations had significant direct effects on the CUEST. Thus, increasing microbial metabolic limitations after long-term livestock removal could reduce microbial C turnover, potentially reducing soil C sequestration. Overall, this study revealed that livestock removal altered soil aggregate development as well as the allocation of resources in aggregates and consequent microbial resource limitations, providing information that may be useful for developing grassland management strategies to enhance C sequestration.

Effect of non-starch polysaccharides on the in vitro gastric digestion of soy-based milk alternatives

Non-starch polysaccharides (NSPs) are usually used as a thickener/stabilizer in food systems. Although NSPs are not digestible, they may impact the physicochemical behavior of gastric digestion. Various types of NSPs (anionic and neutral) with different molecular weights (Mw), including alginates, pectin, and guar gum, were incorporated into soy-based milk alternatives (SBMAs) at 0.2 or 0.1 wt% concentrations. The samples were digested by a semi-dynamic gastric model for 85 min, and their gastric behavior, microstructural changes, and emptying pattern of proteins were investigated. The length-scale dependent structural feature of gastric coagula determined the emptying rate. Soy proteins aggregated and formed large curds in the gastric vessel. The addition of NSPs led to fragmented curds, which emptied earlier. Confocal images revealed that embedded oil bodies coalesced within the protein coagula. High-Mw alginate formed gel particles in the gastric vessel. Soy proteins and pectin formed compact aggregates, emptying uniformly during digestion. Guar gum generated micro-phase separated small aggregates emptying at early stages of digestion. The Mw of polysaccharides, irrespective of their surface charge, significantly influenced the protein emptying rate by interfering with the growth of protein aggregates. The nutrient delivery rates of protein-stabilized emulsions can be controlled through the rational addition of NSPs with different physicochemical properties. • Soy proteins formed integrated large clots in semi-dynamic gastric digestion. • Non-starch polysaccharides (NSPs) led to fragmented clots emptied earlier. • High-molecular weight alginate formed gel particles in the gastric vessel. • Guar gum led to microphase-separated small protein aggregates. • The molecular weight of NSPs affected the protein emptying rate.

Tau protein profiling across brain of different tauopathies using high‐resolution mass spectrometry: quantification of isoforms and phosphorylations

AbstractBackgroundThe abnormal accumulation of the microtubule‐associated protein tau in the brain is the main contributing factor of a group of diseases called tauopathies, including Alzheimer’s disease (AD). Due to similarities, it is currently problematic to chemically characterize the tau pathology in these diseases. Our aim was to develop a multiplex assay to detect and quantify isoform‐specific peptides and phospho‐tau species in brain of different tauopathies, possibly holding disease‐specificity.MethodFrontal cortices from AD (n = 10), progressive supranuclear palsy (PSP, n = 11), Pick’s disease (PiD, n = 10), corticobasal degeneration (CBD, n = 10) and controls (n = 10) were processed to obtain a soluble (tris‐buffered saline, TBS) and a sarkosyl‐insoluble (SI) fraction. Fractions were immunoprecipitated using antibodies targeting all four tau regions. Tryptic peptides corresponding to isoforms and peptides carrying one, two or three phosphorylations were monitored by liquid chromatography/high‐resolution mass spectrometry, using isotope‐labelled protein and phospho‐peptide standards for quantification.ResultIn all samples, the 0N and 1N tau isoforms were most abundant. In the AD group we observed an increase of the 0N isoform in the SI fraction. The SI fraction also showed the 3R/4R isoform predominance characteristic of the different tauopathies, with the 3R being more abundant in PiD, 4R in PSP and CBD, while in AD and controls they had similar abundance. Further, in the SI fraction, peptides from the microtubule‐binding region (MTBR) were markedly more abundant in AD, indicating aggregation of these species (Fig.1). Compared to the TBS fractions, the SI fraction was enriched in double and triple‐phospho peptides (example in Fig.2), which were markedly increased in the AD group as compared to the other non‐AD tauopathies or the control.ConclusionThe novel assay here developed can identify isoform differences across tauopathies. The parallel investigation of TBS and SI fractions showed higher abundancy of phosphorylations and MTBR region in the SI fraction, possibly reflecting this fraction to contain an interphase between small aggregates and immunohistochemical inclusions. While the measurement of multiply phosphorylated peptides could clearly differentiate AD from the other tauopathies, none of them could discriminate between the non‐AD tauopathies. This further indicate that multiply phosphorylated peptides are highly disease relevant species for AD.

Biomarker‐based development for optimized ACI‐24, a novel candidate vaccine for the treatment and prevention of Alzheimer’s disease

AbstractBackgroundAmyloid plaques and neurofibrillary tangles are the neuropathologic hallmarks of Alzheimer’s disease (AD) with the key constituents being Amyloid Beta (Abeta) and Tau protein, respectively. However, the initiation and propagation of neurodegeneration and neurotoxicity in Alzheimer’s disease remains incompletely understood despite recent important progress in clinical trials. It is apparent that small aggregates such as Abeta oligomers or fragments such as Abeta 1‐42 and pyroglutamate Abeta3‐42 (pGlu‐Abeta3‐42)) are of key importance for disease initiation with significant implications for translational medicine and success in clinical trial development.MethodACI‐24 is a vaccine targeting Abeta for the treatment and prevention of AD. Initial clinical data have demonstrated safety and an initial pharmacodynamic response, both in sporadic AD and people with Down syndrome (DS), a specifically vulnerable population predisposed to developing AD. Preclinical data have recently demonstrated that a new, optimized formulation of ACI‐24 has significantly improved immunogenicity against key toxic species, i.e., Abeta oligomers, Abeta 1‐42 and pGlu‐Abeta3‐42. Recent clinical trial results in AD, specifically with monoclonal antibodies targeting Abeta, have successfully employed translational biomarkers, including Amyloid PET, as key decision markers and predictors of clinical benefit.ResultWe present an innovative translational clinical trial design to understand the immunogenic properties of optimized ACI‐24 in sporadic AD and in people with DS. The biomarker‐based design, including multiple interim analyses, will enable (I) assessment of early safety and immunogenicity, (II) dose selection for early and meaningful readouts on translational biomarkers including Amyloid PET, (III) the safe transition into the more vulnerable DS population and (IV) informed transition into pivotal studies.ConclusionThe Alzheimer’s disease field needs new treatments and clinical trial approaches. Vaccination is a proven approach to managing diseases affecting global populations. The field of biomarker‐based translational medicine has been mobilized by the recent understanding of how to clinically evaluate targeting of toxic Abeta fragments and aggregates in trials using monoclonal antibodies. Here, we demonstrate how we utilize these advances in an innovative clinical trial design for an efficient, evidence‐based translational medicine approach to test optimized ACI‐24 as a novel Abeta vaccine candidate.

Effects of grazing on soil aggregate composition and stability in Stipa breviflora desert steppe

Grazing, one of the main grassland utilization modes, has notable impacts on grassland ecosystem structure and functions. However, the effects of long-term grazing on soil aggregate composition and stability are poorly understood. Based on a long-term grazing experiment platform in Inner Mongolia Stipa breviflora desert steppe established in 2004, with treatements of no grazing (control), light, moderate, and heavy grazing intensities, we studied the changes of soil aggregate composition and stability under different grazing intensities. With the measurement of relevant soil physical and chemical characteristics, we explored the main factors that affecting the stability of soil aggregates. The results showed that grazing significantly altered soil aggregate composition. Compared with control, the content of large aggregates (0.25-2 mm) was unchanged in light grazing but significantly decreased in treatments with moderate and heavy grazing intensities. Heavy grazing significantly decreased the content of small aggregates (0.053-0.25 mm), while light and moderate grazing significantly increased that of microaggregates (<0.053 mm). Soil aggregate stability was maintained at a high level under light grazing, but significantly decreased under moderate and heavy grazing treatments. Soil aggregate stability was positively correlated with macroaggregate content but negatively correlated with microaggregate content. Soil pH, bulk density, organic carbon and other physicochemical indices jointly contributed to the changes of soil aggregate composition and hence affect soil aggregate stability. In conclusion, our results showed that appropriate grazing could maintain high level of soil aggregate stability in desert steppe.

Gelling and emulsifying properties of tiger puffer (Takifugu rubripes) skin gelatin as manipulated by pH

The study investigated the modifications of gelling and emulsifying properties of tiger puffer skin gelatin (TPSG) by varying pH and the possible mechanism behind these modifications. ζ-potential analysis indicated the isoelectric point of TPSG was 6.5, and TPSG solution showed the largest particle size at pH6. Atomic force microscopy observation revealed that TPSG at pH 6 and 7 exhibited large size protein aggregates (370 and 340 nm) while TPSG at pH 4 and 9 showed small size irregular aggregates (<150 nm). FTIR analysis suggested that amide I band of TPSG at pH 6 and 7 was shifted to lower wavenumber. Secondary structure analysis suggested they contained high proportion of α-helix. The highest gel strength and gelling and cooling temperature were observed at pH 6, inconsistent with a gel microstructure characterized with dense network and small voids. Moreover, TPSG at pH 6 and 7 exhibited the lowest emulsion activity index but highest emulsion stability index. However, microscopic analysis found TPSG formed stable and small size emulsion droplets at pH 5 and 8. The results suggest that appropriate pH adjustment would provide good functional properties to TPSG.

Piccoliite, NaCaMn3+2(AsO4)2O(OH), a new arsenate from the manganese deposits of Montaldo di Mondovì and Valletta, Piedmont, Italy

AbstractPiccoliite, ideally NaCaMn3+2(AsO4)2O(OH), is a new mineral discovered in the Fe–Mn ore hosted in metaquartzites of the Montaldo di Mondovì mine, Corsaglia Valley, Cuneo Province, Piedmont, Italy. It occurs as small and rare black crystals and aggregates hosted by a matrix of quartz, associated with calcite and berzeliite/manganberzeliite. It has been also found in the Valletta mine near Canosio, Maira Valley, Cuneo Province, Piedmont, Italy, where it occurs embedded in quartz associated with grandaite, hematite, tilasite/adelite and rarely thorianite. The mineral is opaque (thin splinters may be very dark red), with brown streak and has a resinous to vitreous lustre. It is brittle with irregular fracture. No cleavage has been observed. The measured Mohs hardness is ~5–5.5. Piccoliite is non fluorescent. The calculated density is 4.08 g⋅cm–3. Chemical spot analyses by electron microprobe analysis using wavelength dispersive spectroscopy resulted in the empirical formula (based on 10 anions per formula unit) (Na0.64Ca0.35)Σ0.99(Ca0.75Na0.24)Σ0.99(Mn3+1.08Fe3+0.59Mg0.20Ca0.10)Σ1.97(As2.03V0.03Si0.01)Σ2.07O9(OH) and (Na0.53Ca0.47)Σ1.00(Ca0.76Na0.23Sr0.01)Σ1.00(Mn3+0.63Fe3+0.49Mg0.48Mn4+0.34Ca0.06)Σ2.00(As1.97P0.01Si0.01)Σ1.99O9(OH) for the Montaldo di Mondovì and Valletta samples, respectively. The mineral is orthorhombic, Pbcm, with single-crystal unit-cell parameters a = 8.8761(9), b = 7.5190(8), c = 11.689(1) Å and V = 780.1(1) Å3 (Montaldo di Mondovì sample) and a = 8.8889(2), b = 7.5269(1), c = 11.6795(2) Å, V = 781.43(2) Å3 (Valletta sample) with Z = 4. The seven strongest powder X-ray diffraction lines for the sample from Montaldo di Mondovì are [d Å (Irel; hkl)]: 4.85 (57; 102), 3.470 (59; 120, 113), 3.167 (100; 022), 2.742 (30; 310, 213), 2.683 (53; 311, 023), 2.580 (50; 222, 114) and 2.325 (19; 320, 214, 223). The crystal structure (R1 = 0.0250 for 1554 unique reflections for the Montaldo di Mondovì sample and 0.0260 for 3242 unique reflections for the Valletta sample) has MnO5(OH) octahedra forming edge-shared dimers; these dimers are connected through corner-sharing, forming two-up-two-down [[6]M2([4]TO4)4φ2] chains [M = Mn; T = As; φ = O(OH)] running along [001]. These chains are bonded in the a and b directions by sharing corners with AsO4 tetrahedra, giving rise to a framework of tetrahedra and octahedra hosting seven-coordinated Ca2+ and Na+ cations. The crystal structure of piccoliite is closely related to that of pilawite-(Y) as well as to carminite-group minerals that also show the same type of chains but with different linkage. The mineral is named after the mineral collectors Gian Paolo Piccoli and Gian Carlo Piccoli (father and son) (1926–1996 and b. 1953, respectively), the latter having discovered the type material at the Montaldo di Mondovì mine.