High photosynthetic capacity of Sahelian C3 and C4 plants

Photosynthesis Research - The semi-arid ecosystems of the African Sahel play an important role in the global carbon cycle and are among the most sensitive ecosystems to future environmental...     

The structural biology of the dynamin‐related proteins: New insights into a diverse,multitalented family

Dynamin‐related proteins are multidomain, mechanochemical GTPases that self‐assemble and orchestrate a wide array of cellular processes. Over the past decade, structural insights from X‐ray crystallography and cryo‐electron microscopy have reshaped our mechanistic understanding of these proteins. Here, we provide a historical perspective on these advances that highlights the structural attributes of different dynamin family members and explores how these characteristics affect GTP hydrolysis, conformational coupling and oligomerization. We also discuss a number of lingering challenges remaining in the field that suggest future directions of study.     

Budget Constraints Affect Male Rats’ Choices between Differently Priced Commodities

Demand theory can be applied to analyse how a human or animal consumer changes her selection of commodities within a certain budget in response to changes in price of those commodities. This change in consumption assessed over a range of prices is defined as demand elasticity. Previously, income-compensated and income-uncompensated price changes have been investigated using human and animal consumers, as demand theory predicts different elasticities for both conditions. However, in these studies, demand elasticity was only evaluated over the entirety of choices made from a budget. As compensating budgets changes the number of attainable commodities relative to uncompensated conditions, and thus the number of choices, it remained unclear whether budget compensation has a trivial effect on demand elasticity by simply sampling from a different total number of choices or has a direct effect on consumers’ sequential choice structure. If the budget context independently changes choices between commodities over and above price effects, this should become apparent when demand elasticity is assessed over choice sets of any reasonable size that are matched in choice opportunities between budget conditions. To gain more detailed insight in the sequential choice dynamics underlying differences in demand elasticity between budget conditions, we trained N=8 rat consumers to spend a daily budget by making a number of nosepokes to obtain two liquid commodities under different price regimes, in sessions with and without budget compensation. We confirmed that demand elasticity for both commodities differed between compensated and uncompensated budget conditions, also when the number of choices considered was matched, and showed that these elasticity differences emerge early in the sessions. These differences in demand elasticity were driven by a higher choice rate and an increased reselection bias for the preferred commodity in compensated compared to uncompensated budget conditions, suggesting a budget context effect on relative valuation.     

Glycation of Nail Proteins: From Basic Biochemical Findings to a Representative Marker for Diabetic Glycation-Associated Target Organ Damage

Background

Although assessment of glycated nail proteins may be a useful marker for monitoring of diabetes, their nature and formation are still poorly understood. Besides a detailed anatomical analysis of keratin glycation, the usefulness of glycated nail protein assessment for monitoring diabetic complications was investigated.

Methods

216 patients (94 males, 122 females; mean age ± standard deviation: 75.0 ± 8.7 years) were enrolled. Glycation of nail and eye lens proteins was assessed using a photometric nitroblue tetrazolium-based assay. Following chromatographic separation of extracted nail proteins, binding and nonbinding fractions were analyzed using one-dimensional gel electrophoresis. Using a hand piece containing a latch-type-bur, a meticulous cutting of the nail plate into superficial and deep layers was performed, followed by a differential analysis of fructosamine.

Results

Using SDS PAGE, four and two bands were identified among the nonglycated and glycated nail fraction respectively. Significantly lower fructosamine concentrations were found in the superficial nail layer (mean: 2.16 ± 1.37 μmol/g nails) in comparison with the deep layer (mean: 4.36 ± 2.55 μmol/g nails) (P<0.05). A significant higher amount of glycated eye lens proteins was found in diabetes mellitus patients (mean: 3.80 ± 1.57 μmol/g eye lens) in comparison with nondiabetics (mean: 3.35 ± 1.34 μmol/g eye lens) (P<0.05). A marked correlation was found between glycated nail and glycated eye lens proteins [y (glycated nail proteins) = 0.39 + 0.99 x (eye lens glycated proteins); r² = 0.58, P<0.001]. The concentration of glycated eye lens proteins and the HbA1c level were found to be predictors of the concentration of glycated nail proteins.

Conclusions

Glycation of nail proteins takes place in the deep layer of finger nails, which is in close contact with blood vessels and interstitial fluid. Glycation of nail proteins can be regarded as a representative marker for diabetic glycation-associated target organ damage.     

A Developmental Switch for Hebbian Plasticity

Hebbian forms of synaptic plasticity are required for the orderly development of sensory circuits in the brain and are powerful modulators of learning and memory in adulthood. During development, emergence of Hebbian plasticity leads to formation of functional circuits. By modeling the dynamics of neurotransmitter release during early postnatal cortical development we show that a developmentally regulated switch in vesicle exocytosis mode triggers associative (i.e. Hebbian) plasticity. Early in development spontaneous vesicle exocytosis (SVE), often considered as ''synaptic noise'', is important for homogenization of synaptic weights and maintenance of synaptic weights in the appropriate dynamic range. Our results demonstrate that SVE has a permissive, whereas subsequent evoked vesicle exocytosis (EVE) has an instructive role in the expression of Hebbian plasticity. A timed onset for Hebbian plasticity can be achieved by switching from SVE to EVE and the balance between SVE and EVE can control the effective rate of Hebbian plasticity. We further show that this developmental switch in neurotransmitter release mode enables maturation of spike-timing dependent plasticity. A mis-timed or inadequate SVE to EVE switch may lead to malformation of brain networks thereby contributing to the etiology of neurodevelopmental disorders.     

Snooker Structure-Based Pharmacophore Model Explains Differences in Agonist and Blocker Binding to Bitter Receptor hTAS2R39

The human bitter taste receptor hTAS2R39 can be activated by many dietary (iso)flavonoids. Furthermore, hTAS2R39 activity can be blocked by 6-methoxyflavanones, 4’-fluoro-6-methoxyflavanone in particular. A structure-based pharmacophore model of the hTAS2R39 binding pocket was built using Snooker software, which has been used successfully before for drug design of GPCRs of the rhodopsin subfamily. For the validation of the model, two sets of compounds, both of which contained actives and inactives, were used: (i) an (iso)flavonoid-dedicated set, and (ii) a more generic, structurally diverse set. Agonists were characterized by their linear binding geometry and the fact that they bound deeply in the hTAS2R39 pocket, mapping the hydrogen donor feature based on T5.45 and N3.36, analogues of which have been proposed to play a key role in activation of GPCRs. Blockers lack hydrogen-bond donors enabling contact to the receptor. Furthermore, they had a crooked geometry, which could sterically hinder movement of the TM domains upon receptor activation. Our results reveal characteristics of hTAS2R39 agonist and bitter blocker binding, which might facilitate the development of blockers suitable to counter the bitterness of dietary hTAS2R39 agonists in food applications.     

Vitamin C deficiency: more than just a nutritional disorder

Although vitamin C deficiency and scurvy are generally considered as pure nutritional disorders, only a minority of the vitamin C concentration is determined by food intake. In the presence of transition metals (iron and copper), the antiscorbutic factor shifts from an antioxidant to a pro-oxidant function. Haptoglobin (Hp) is a plasma α-2 glycoprotein characterized by 3 common phenotypes (Hp 1-1, Hp 2-1 and Hp 2-2). Its free hemoglobin (Hb)-binding capacity prevents Hb-driven oxidative damage. When the antioxidant capacity of Hp is insufficient, its role is taken over by hemopexin (heme-binding protein) and by vitamin C (free radical scavenger). The Hp 2-2 phenotype has a lower capacity to inhibit oxidation and vitamin C depletion. In this article, two consequences of this major finding are tackled. The Hp polymorphism is an important non-nutritional modifying factor in the pathogenesis of vitamin C deficiency and scurvy, which may explain the success of long-range human migration by the natural selection of some populations characterized by high Hp 1 allele frequencies. Moreover, we propose tailoring the recommended dietary allowance (RDA) values of vitamin C, taking into consideration the Hp phenotype dependency.     

Strategy for purification and mass spectrometry identification of SELDI peaks corresponding to low-abundance plasma and serum proteins

Analysis by SELDI-TOF-MS of low abundance proteins makes it possible to select peaks as candidate biomarkers. Our aim was to define a purification strategy to optimise identification by MS of peaks detected by SELDI-TOF-MS from plasma or serum, regardless of any treatment by a combinatorial peptide ligand library (CPLL). We describe 2 principal steps in purification. First, choosing the appropriate sample containing the selected peak requires setting up a databank that records all the m/z peaks detected from samples in different conditions. Second, the specific purification process must be chosen: separation was achieved with either chromatographic columns or liquid-phase isoelectric focusing, both combined when appropriate with reverse-phase chromatography. After purification, peaks were separated by gel electrophoresis and the candidate proteins were analyzed by nano-liquid-chromatography-MS/MS. We chose 4m/z peaks (9400, 13,571, 13,800 and 15,557) selected for their differential expression between two conditions, as examples to explain the different strategies of purification, and we successfully identified 3 of them. Despite some limitations, our strategy to purify and identify peaks selected from SELDI-TOF-MS analysis was effective.     

Spore killing in the fungus Podospora anserina: a connection between meiotic drive and vegetative incompatibility?

Fungi in which the haploid nuclei resulting from meiosis are linearly arranged in asci provide unique opportunities to analyse abnormal segregation. Any meiotic drive system in such fungi will be observed in a cross between a driving and a sensitive strain as spore killing: the degeneration of half the ascospores in a certain proportion of the asci. In a sample of some 100 strains isolated from a single natural population we have discovered at least six different meiotic drive elements (van der Gaag et al., 2000). Here we report results of research that was aimed at elucidating a possible correlation between meiotic drive and vegetative incompatibility in eight different Spore killer strains from this population. We show that there is a strong correlation between these two phenotypes, although the precise genetic nature of the correlation is not yet clear. We discuss the implications of our results for the understanding of the population genetics of meiotic drive in Podospora.