Small Molecule Modifiers of In Vitro Manganese Transport Alter Toxicity In Vivo

Biological Trace Element Research - Manganese (Mn) is essential for several species and daily requirements are commonly met by an adequate diet. Mn overload may cause motor and psychiatric...     

Incorporation of mineral nitrogen into the soil food web as affected by plant community composition

Although nitrogen (N) deposition is increasing globally, N availability still limits many organisms, such as microorganisms and mesofauna. However, little is known to which extent soil organisms rely on mineral‐derived N and whether plant community composition modifies its incorporation into soil food webs. More diverse plant communities more effectively compete with microorganisms for mineral N likely reducing the incorporation of mineral‐derived N into soil food webs. We set up a field experiment in experimental grasslands with different levels of plant species and functional group richness. We labeled soil with ¹⁵NH₄ ¹⁵NO₃ and analyzed the incorporation of mineral‐derived ¹⁵N into soil microorganisms and mesofauna over 3 months. Mineral‐derived N incorporation decreased over time in all investigated organisms. Plant species richness and presence of legumes reduced the uptake of mineral‐derived N into microorganisms. In parallel, the incorporation of mineral‐derived ¹⁵N into mesofauna species declined with time and decreased with increasing plant species richness in the secondary decomposer springtail Ceratophysella sp. Effects of both plant species richness and functional group richness on other mesofauna species varied with time. The presence of grasses increased the ¹⁵N incorporation into Ceratophysella sp., but decreased it in the primary decomposer oribatid mite Tectocepheus velatus sarekensis. The results highlight that mineral N is quickly channeled into soil animal food webs via microorganisms irrespective of plant diversity. The amount of mineral‐derived N incorporated into soil animals, and the plant community properties affecting this incorporation, differed markedly between soil animal taxa, reflecting species‐specific use of food resources. Our results highlight that plant diversity and community composition alter the competition for N in soil and change the transfer of N across trophic levels in soil food webs, potentially leading to changes in soil animal population dynamics and community composition. Sustaining high plant diversity may buffer detrimental effects of elevated N deposition on soil biota.     

Phytochemical Study of Juglans regia L. Pericarps from Greece with a Chemotaxonomic Approach

Phytochemical research of different polarity extracts from green Juglans regia L. pericarps from Greece afforded 32 compounds: four pentacyclic triterpenes (1 – 4), three sesquiterpenes (5 – 7), four tetralones (8 – 11), two naphthoquinones (12 and 13), seven phenolic acids (14 – 20), one diarylheptanoid (21), one neo‐lignan (22), seven flavonoids (23 – 29), two phenylethanoids (30 and 31) and one hydrolysed tannin (32). Compounds 4 and 29 are isolated for the first time from the species, while compounds 3, 7, 20, 22, 23, 24, 25, 26, 28, 30 are reported for the first time in Juglandaceae. Chemotaxonomic significance of isolated compounds into Junglandaceae family is thoroughly discussed.     

Validation of the International Classification of Functioning, Disability and Health (ICF) Core Set for rheumatoid arthritis from the patient perspective using focus groups

Functioning is recognized as an important study outcome in rheumatoid arthritis (RA). The Comprehensive ICF Core Set for RA is an application of the International Classification of Functioning, Disability and Health (ICF) of the World Health Organisation with the purpose of representing the typical spectrum of functioning of patients with RA. To strengthen the patient perspective, persons with RA were explicitly involved in the validation of the Comprehensive ICF Core Set for RA using qualitative methodology. The objective of the study was twofold: to come forward with a proposal for the most appropriate methodology to validate Comprehensive ICF Core Sets from the patient perspective; and to add evidence to the validation of the Comprehensive ICF Core Set for RA from the perspective of patients. The specific aims were to explore the aspects of functioning and health important to patients with RA using two different focus group approaches (open approach and ICF-based approach) and to examine to what extent these aspects are represented by the current version of the Comprehensive ICF Core Set for RA. The sampling of patients followed the maximum variation strategy. Sample size was determined by saturation. The focus groups were digitally recorded and transcribed verbatim. The meaning condensation procedure was used for the data analysis. After qualitative data analysis, the resulting concepts were linked to ICF categories according to established linking rules. Forty-nine patients participated in ten focus groups (five in each approach). Of the 76 ICF categories contained in the Comprehensive ICF Core Set for RA, 65 were reported by the patients based on the open approach and 71 based on the ICF-based approach. Sixty-six additional categories (open approach, 41; ICF-based approach, 57) that are not covered in the Comprehensive ICF Core Set for RA were raised. The existing version of the Comprehensive ICF Core Set for RA could be confirmed almost entirely by the two different focus group approaches applied. Focus groups are a highly useful qualitative method to validate the Comprehensive ICF Core Set for RA from the patient perspective. The ICF-based approach seems to be the most appropriate technique.     

De novo protein fold families expand the designable ligand binding site space

A major challenge in designing proteins de novo to bind user-defined ligands with high affinity is finding backbones structures into which a new binding site geometry can be engineered with high precision. Recent advances in methods to generate protein fold families de novo have expanded the space of accessible protein structures, but it is not clear to what extend de novo proteins with diverse geometries also expand the space of designable ligand binding functions. We constructed a library of 25,806 high-quality ligand binding sites and developed a fast protocol to place (“match”) these binding sites into both naturally occurring and de novo protein families with two fold topologies: Rossman and NTF2. Each matching step involves engineering new binding site residues into each protein “scaffold”, which is distinct from the problem of comparing already existing binding pockets. 5,896 and 7,475 binding sites could be matched to the Rossmann and NTF2 fold families, respectively. De novo designed Rossman and NTF2 protein families can support 1,791 and 678 binding sites that cannot be matched to naturally existing structures with the same topologies, respectively. While the number of protein residues in ligand binding sites is the major determinant of matching success, ligand size and primary sequence separation of binding site residues also play important roles. The number of matched binding sites are power law functions of the number of members in a fold family. Our results suggest that de novo sampling of geometric variations on diverse fold topologies can significantly expand the space of designable ligand binding sites for a wealth of possible new protein functions.     

Effects of extreme habitat conditions on otolith morphology: a case study on extremophile live bearing fishes (Poecilia mexicana, P. sulphuraria)

Our study was designed to evaluate if, and to what extent, restrictive environmental conditions affect otolith morphology. As a model, we chose two extremophile livebearing fishes: (i) Poecilia mexicana, a widespread species in various Mexican freshwater habitats, with locally adapted populations thriving in habitats characterized by the presence of one (or both) of the natural stressors hydrogen sulphide and darkness, and (ii) the closely related Poecilia sulphuraria living in a highly sulphidic habitat (Baños del Azufre). All three otolith types (lapilli, sagittae, and asterisci) of P. mexicana showed a decrease in size ranging from the non-sulphidic cave habitat (Cueva Luna Azufre), to non-sulphidic surface habitats, to the sulphidic cave (Cueva del Azufre), to sulphidic surface habitats (El Azufre), to P. sulphuraria. Although we found a distinct differentiation between ecotypes with respect to their otolith morphology, no clear-cut pattern of trait evolution along the two ecological gradients was discernible. Otoliths from extremophiles captured in the wild revealed only slight similarities to aberrant otoliths found in captive-bred fish. We therefore hypothesize that extremophile fishes have developed coping mechanisms enabling them to avoid aberrant otolith growth – an otherwise common phenomenon in fishes reared under stressful conditions.     

New reactive extraction systems for separation of bio-succinic acid

Biotechnologically produced succinic acid has the potential to displace maleic acid and its uses and to become an important feedstock for the chemical industry. In addition to optimized production strains and fermentation processes, an efficient separation of succinic acid from the aqueous fermentation broth is indispensable to compete with the current petrochemical production processes. In this context, high molecular weight amines are known to be effective extractants for organic acids. For this reason, as a first step of isolation and purification, the reactive extraction of succinic acid was studied by mixing aqueous succinic acid solutions with 448 different amine–solvent mixtures as extraction agents (mixer-settler studies). The extraction agents consist either of one amine and one solvent (208 reactive extraction systems) or two amines and two solvents (240 reactive extraction systems). Maximum extraction yields of succinic acid from an aqueous solution with 423 mM succinic acid at pH 2.0 were obtained with more than 95% yield with trihexylamine solved in 1-octanol or with dihexylamine and diisooctylamine solved in 1-octanol and 1-hexanol. Applying these optimized reactive extraction systems with Escherichia coli fermentation broth resulted in extraction yields of 78–85% due to the increased ionic strength of the fermentation supernatant and the co-extraction of other organic acids (e.g., lactic acid and acetic acid), which represent typical fermentation byproducts.     

New roles for ubiquitin in the assembly and function of neuronal circuits

A series of recent papers highlight a prominent role for ubiquitin in the formation and function of neural circuits. These new results focus attention on the molecular remodeling that occurs at various decision points in the life of growth cones and synapses.     

Naturally occurring fragments from two distinct regions of the prostatic acid phosphatase form amyloidogenic enhancers of HIV infection

Semen is the major vector for HIV-1 transmission. We previously isolated C-proximal fragments of the prostatic acid phosphatase (PAP) from semen which formed amyloid fibrils that potently enhanced HIV infection. Here, we used the same methodology and identified another amyloidogenic peptide. Surprisingly, this peptide is derived from an N-proximal fragment of PAP (PAP85-120) and forms, similar to the C-proximal fragments, positively charged fibrillar structures that increase virion attachment to cells. Our results provide a first example for amyloid formation by fragments of distinct regions of the same precursor and further emphasize the possible importance of amyloidogenic peptides in HIV transmission.