Where is the difference between the genomes of humans and annelids?

The first systematic investigation of an annelid genome has revealed that the genes of the marine worm Platynereis dumerilii are more closely related to those of vertebrates than to those of insects or nematodes. For hundreds of millions of years vertebrates have preserved exon-intron structures descended from their last common ancestor with the annelids.     

Crosstalk between translation and the aggresome–autophagy pathway

Many neurodegenerative disorders feature the presence of misfolded polypeptide-containing intracellular inclusion bodies biochemically and morphologically analogous to cellular aggresomes. However, it is largely unknown how misfolded polypeptides form aggresomes and are eventually cleared by the aggresome-macroautophagy/autophagy pathway, so-called aggrephagy. Our recent study revealed that when the ubiquitin-proteasome system is impaired, the accumulated misfolded polypeptides are selectively recognized and transported to the aggresome by a CED complex. This complex is composed of CTIF, originally identified as a specific factor for nuclear cap-binding protein complex (a heterodimer of NCBP1/CBP80 and NCBP2/CBP20)-dependent translation (CT), and its associated factors EEF1A1 and DCTN1. Aggresomal targeting of a misfolded polypeptide via the CED complex is accompanied by CTIF release from the CT complex and thereby inhibits CT efficiency. Therefore, our study provides new mechanistic insights into the crosstalk between translational inhibition and aggresome formation under the influence of a misfolded polypeptide.     

Molecular dynamics analysis of a second phosphate site in the hemoglobins of the seabird, south polar skua. Is there a site-site migratory mechanism along the central cavity?

Hemoglobin function is modulated by several non-heme ligands; among these effectors, organic phosphates generally bind to heterotropic sites with a one-to-one stoichiometry. The phosphate binding site of human hemoglobin is located at the interface between the two beta chains. An additional binding site for polyanions has been studied at the molecular level (Tamburrini, M., A. Riccio, M. Romano, B. Giardina, and G. di Prisco. 2000. Eur. J. Biochem. 267:6089-6098) in the hemoglobins of the south polar skua (Catharacta maccormicki). It is formed by a cluster of six positive charges of both alpha chains (Val-1, Lys-99, Arg-141); the two Lys-99alpha have an essential role in the site structure. The present investigation, carried out on skua deoxyhemoglobins by using a molecular dynamics approach, confirms the structural feasibility of the additional site, possibly having the role of an entry-leaving site, and leads to the proposal of a novel migration pathway for phosphate along the central cavity of hemoglobin from one binding site to the other, occurring according to the hypothesis of a site-site migratory mechanism, which may assign a functional role to the central cavity. The role of Lys-99alpha was further confirmed by molecular dynamics experiments on the mutant Lys-99alpha-->Ala in which, at the end of the simulation, the phosphate was external to the additional site.     

Do the evolutionary interactions between moths and bats promote niche partitioning between bats and birds?

Ecological theory suggests that the coexistence of species is promoted by the partitioning of available resources, as in dietary niche partitioning where predators partition prey. Yet, the mechanisms underlying dietary niche partitioning are not always clear. We used fecal DNA metabarcoding to investigate the diets of seven nocturnal insectivorous bird and bat species. Low diet overlap (2%–22%) supported resource partitioning among all species. Differences in diet corresponded with species identity, prey detection method, and foraging behavior of predators. Insects with ultrasonic hearing capabilities were consumed significantly more often by birds than bats, consistent with an evolved avoidance of echolocating strategies. In turn, bats consumed a greater proportion of noneared insects such as spruce budworms. Overall, our results suggest that evolutionary interactions among bats and moths translate to dietary niche partitioning and coexistence among bats and nocturnal birds.     

Kinetic advantage of the interaction between the fatty acid β-oxidation enzymes and the complexes of the respiratory chain

Respiration-linked oxidation of 3-hydroxybutyryl-CoA, crotonyl-CoA and saturated fatty acyl (C₄, C₈ and C₁₄)-CoA esters was studied in different mitochondrial preparations. Oxidation of acyl-CoA esters was poor in intact mitochondria; however, it was significant, as well as, NAD⁺ and CoA-dependent in gently and in vigorously sonicated mitochondria. The respiration-linked oxidation of crotonyl-CoA and 3-hydroxybutyryl-CoA proceeded at much higher rates (over 700%) in gently disrupted mitochondria than in completely disrupted mitochondria. The redox dye-linked oxidation of crotonyl-CoA (with inhibited respiratory chain) was also higher in gently disrupted mitochondria (149%) than in disrupted ones. During the respiration-linked oxidation of 3-hydroxybutyryl-CoA the steady-state NADH concentrations in the reaction chamber were determined, and found to be 8 μM in gently sonicated and 15 μM in completely sonicated mitochondria in spite of the observation that the gently sonicated mitochondria oxidized the 3-hydroxybutyryl-CoA much faster than the completely sonicated mitochondria. The NAD⁺-dependence of 3-hydroxybutyryl-CoA oxidation showed that a much smaller NAD⁺ concentration was enough to half-saturate the reaction in gently disrupted mitochondria than in completely disrupted ones. Thus, these observations indicate the positive kinetic consequence of organization of β-oxidation enzyme in situ. Respiration-linked oxidation of bytyryl-, oxtanoyl- and palmitoyl-CoA was also studied and these CoA intermediates were oxidized at approx. 50% of the rate of crotonyl- and 3-hydroxybutyryl-CoA in the gently disrupted mitochondria. In vigorously disrupted mitochondria the oxidation rate of these saturated acyl-CoA intermediates was hardly detectable indicating that the connection between the acyl-CoA dehydrogenase and the respiratory chain had been disrupted.     

What is the relationship between the global structures of apo and holo proteins?

It is well known that ligand binding and release may induce a wide range of structural changes in a receptor protein, varying from small movements of loops or side chains in the binding pocket to large‐scale domain hinge‐bending and shear motions or even partial unfolding that facilitates the capture and release of a ligand. An interesting question is what in general are the conformational changes triggered by ligand binding? The aim of this work is analyze the magnitude of structural changes in a protein resulting from ligand binding to assess if the state of ligand binding needs to be included in template‐based protein structure prediction algorithms. To address this issue, a nonredundant dataset of 521 paired protein structures in the ligand‐free and ligand‐bound form was created and used to estimate the degree of both local and global structure similarity between the apo and holo forms. In most cases, the proteins undergo relatively small conformational rearrangements of their tertiary structure upon ligand binding/release (most root‐mean‐square‐deviations from native, RMSD, are <1 Å). However, a clear difference was observed between single‐ and multiple‐domain proteins. For the latter, RMSD changes greater than 1 Å and sometimes larger were found for almost 1/3 of the cases; these are mainly associated with large‐scale hinge‐bending movements of entire domains. The changes in the mutual orientation of individual domains in multiple‐domain proteins upon ligand binding were investigated using a mechanistic model based on mass‐weighted principal axes as well as interface buried surface calculations. Some preferences toward the anticipated mechanism of protein domain movements are predictable based on the examination of just the ligand‐free structural form. These results have applications to protein structure prediction, particularly in the context of protein domain assembly, if additional information concerning ligand binding is exploited. Proteins 2008. © 2007 Wiley‐Liss, Inc.     

How do miniature pigs discriminate between people?. Discrimination between people wearing coveralls of the same colour

Seven experiments were conducted on four miniature pigs to determine: (1) whether the pigs can discriminate between people wearing the same coloured clothing; (2) what cues they rely on if they could discriminate. For 2 weeks before the experiments began, the pigs were conditioned in a Y-maze to receive raisins from the rewarder wearing dark blue coveralls. They were then given the opportunity to choose the rewarder or non-rewarder in these experiments. Each session consisted of 20 trials. Successful discrimination was that the pig chose the rewarder at least 15 times in 20 trials (P<0.05: by chi(2)-test). In Experiment 1, both rewarder and non-rewarder wore dark blue coveralls. By 20 sessions, all pigs successfully identified the rewarder. In Experiment 2: (1) both wore coveralls of the same new colours or (2) one of them wore coveralls of new colours. They significantly preferred the rewarder even though the rewarder and/or non-rewarder wore coveralls of new colours. In Experiment 3, both wore dark blue coveralls but olfactory cues were obscured and auditory cues were not given. The pigs were able to identify the rewarder successfully irrespective of changing auditory and olfactory cues. In Experiment 4, both wore dark blue coveralls but covered part of their face and body in different ways. The correct response rate decreased when a part of the face and the whole body of the rewarder and non-rewarder were covered. In Experiment 5, both wore dark blue coveralls and changed their apparent body size by shifting sitting position. The correct response rate increased as the difference in body size between the experimenters increased. In Experiment 6, the distance between the experimenters and the pig was increased by 30cm increments. The correct response rate of each pig decreased as the experimenters receded from the pig, but performance varied among the pigs. In Experiment 7, the light intensity of the experimental room was reduced from 550 to 80lx and then to 20lx. The correct response rate of each pig decreased with the reduction in light intensity, but all the pigs discriminated the rewarder from the non-rewarder significantly even at 20lx.In conclusion, the pigs were able to discriminate between people wearing coveralls of the same colour after sufficient reinforcement. These results indicate that pigs are capable of using visual cues to discriminate between people.     

Overweight and poor? On the relationship between income and the body mass index

Contrary to conventional wisdom, NHANES data indicate that the poor have never had a statistically significant higher prevalence of overweight status at any time in the last 35 years. Despite this empirical evidence, the view that the poor are less healthy in terms of excess accumulation of fat persists. This paper provides evidence that conventional wisdom is reflecting important differences in the relationship between income and the body mass index. The first finding is based on distribution-sensitive measures of overweight which indicates that the severity of overweight has been higher for the poor than the nonpoor throughout the last 35 years. The second finding is from a newly introduced estimator, unconditional quantile regression (UQR), which provides a measure of the income-gradient in BMI at different points on the unconditional BMI distribution. The UQR estimator indicates that the strongest relationship between income and BMI is observed at the tails of the distribution. There is a statistically significant negative income gradient in BMI at the obesity threshold and some evidence of a positive gradient at the underweight threshold. Both of these UQR estimates imply that for those at the tails of the BMI distribution, increases in income are correlated with healthier BMI values.     

Can Infants Tell the Difference between Gold and Yellow?

There is a large literature focused on the color perception of matte surface. However, recent research showed that the component of surface specular reflection, such as glossiness, also affects categorical color perception. For instance, the color term “gold” was used to name high specular stimuli within a specific range of chromaticity, which overlaps with those of yellow and orange for low specular stimuli. In the present study, we investigated whether the component of surface specular reflectance affects the color perception of 5- to 8-month-old infants by using the preferential looking technique. In the first experiment, we conducted a simple test to determine whether infants perceive yellow and gold as the same color by comparing their preference for these colors over green. If the infants perceive yellow and gold as the same color, they would show similar preference scores over green. On the other hand, if infants show different preference scores over green, it indicates that infants do not perceive yellow and gold as the same color. Only the 7–8 month-old infants showed different preference scores for gold and yellow over green. This result indicates that the 7–8 month-old infants perceive gold and yellow as different colors. In Experiment 2, we eliminated the component of specular reflectance on the gold surface and presented it against green to infants. A similar preference score of yellow over green was obtained. This result suggests that the difference between the preference scores for gold and yellow over green in Experiment 1 was based on representations of glossiness.     

Is the functional interaction between adenosine A2A receptors and metabotropic glutamate 5 receptors a general mechanism in the brain? Differences and similarities between the striatum and the hippocampus

The aim of the present paper was to examine, in a comparative way, the occurrence and the mechanisms of the interactions between adenosine A_2A receptors (A_2ARs) and metabotropic glutamate 5 receptors (mGlu5Rs) in the hippocampus and the striatum. In rat hippocampal and corticostriatal slices, combined ineffective doses of the mGlu5R agonist 2-chloro-5-hydroxyphenylglycine (CHPG) and the A_2AR agonist CGS 21680 synergistically reduced the slope of excitatory postsynaptic field potentials (fEPSPs) recorded in CA1 and the amplitude of field potentials (FPs) recorded in the dorsomedial striatum. The cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway appeared to be involved in the effects of CGS 21680 in corticostriatal but not in hippocampal slices. In both areas, a postsynaptic locus of interaction appeared more likely. N-methyl-D-aspartate (NMDA) reduced the fEPSP slope and FP amplitude in hippocampal and corticostriatal slices, respectively. Such an effect was significantly potentiated by CHPG in both areas. Interestingly, the A_2AR antagonist ZM 241385 significantly reduced the NMDA-potentiating effect of CHPG. In primary cultures of rat hippocampal and striatal neurons (ED 17, DIV 14), CHPG significantly potentiated NMDA-induced lactate dehydrogenase (LDH) release. Again, such an effect was prevented by ZM 241385. Our results show that A_2A and mGlu5 receptors functionally interact both in the hippocampus and in the striatum, even though different mechanisms seem to be involved in the two areas. The ability of A_2ARs to control mGlu5R-dependent effects may thus be a general feature of A_2ARs in different brain regions (irrespective of their density) and may represent an additional target for the development of therapeutic strategies against neurological disorders.     

Analysis of the potential evapotranspiration demands in the Czech Republic between 1961–1990

Dynamics of the evapotranspirational demands in the Czech Republic within three decades from 1961 to 1990 has been studied. The determination of the levels of influence of the respective natural components depends on the regionalized modelling techniques. The project of regionalized modelling is theoretically based on the potential evapotranspiration values (ET ₀) calculated by FAO methodology (eqs. 1, 2) and the series of temperature and rainfall observations obtained by climatologic stations during a 30-year period from 1961 to 1990 and its relation to the absolute altimetric. The DMR-2 military digital elevation model of the Czech Republic relief consisting of a regular network of points with their altitudes specified in meters was used for the purpose of regionalized modelling. One step of the network in the S-42 coordinate system with the Gauss conforms cylindrical projection is equal to 100 meters; this implies that the smallest area for which the data can be processed is 1 hectare. The digital relief model can be linked to both direct (temperature, precipitation) and derived (evapotranspiration) quantities, which is one of the many novelties of regionalized modelling. The climatic data used in regionalized modelling records daily measurements were obtained by 85 climatologic and rainfall-monitoring stations from 1961 to 1990. Our results showed an appreciable decrease of the most drying area (ratio P/ET₀ up to 0.755) in the last decade 1981–90; half as less amounts compared with the previous decade 1971–80 (about 500,000 hectares). On the other hand, an apparent increase (more than 500,000 hectares in comparison with the previous decade 1971–80) of the wettest area (ratio P/ET₀ over 1.508) through the last decade was observed. Both first decades 1961–70 and 1971–80 look similar. The project mentioned in this article has made it possible to create models for the different time intervals which have showed higher reliability for heterogeneous application.     

Nicotine: the link between cigarette smoking and the progression of renal injury?

Cigarette smoke (CS) is the most important source of preventable morbidity and mortality in the United States. Recent clinical studies have suggested that, in addition to being a major cardiovascular risk factor, CS promotes the progression of kidney disease. The mechanisms by which CS promotes the progression of chronic kidney disease have not been elucidated. Here we demonstrate for the first time that human mesangial cells (MCs) are endowed with the nicotinic ACh receptors (nAChRs) alpha4, alpha5, alpha7, beta2, beta3, and beta4. Studies performed in other cell types have shown that these nAChRs are ionotropic receptors that function as agonist-regulated Ca(2+) channels. Nicotine induced MC proliferation in a dose-dependent manner. At 10 (-7) M, a concentration found in the plasma of active smokers, nicotine induced MC proliferation [control, 1,328 +/- 50 vs. nicotine, 2,761 +/- 90 counts/minute (cpm); P < 0.05] and increased the synthesis of fibronectin (50%), a critical matrix component involved in the progression of chronic kidney disease. We and others have shown that, in response to PKC activation, MC synthesize reactive oxygen species (ROS) via NADPH oxidase. In the current studies we demonstrate that PKC inhibition as well as diphenyleneiodonium and apocynin, two inhibitors of NADPH oxidase, prevented the effects of nicotine on MC proliferation and fibronectin production, hence establishing ROS as second messengers of the actions of nicotine. Furthermore, nicotine increased the production of ROS as assessed by 2',7'-dichlorofluorescein diacetate fluorescence [control, 184.4 +/- 26 vs. nicotine, 281.5 +/- 26 arbitrary fluorescence units (AFU); n = 5 experiments, P < 0.05]. These studies unveil previously unrecognized mechanisms that indict nicotine, a component of CS, as an agent that may accelerate and promote the progression of kidney disease.     

Structural characterization of the interactions between palladin and α-actinin

The interaction between α-actinin and palladin, two actin-cross-linking proteins, is essential for proper bidirectional targeting of these proteins. As a first step toward understanding the role of this complex in organizing cytoskeletal actin, we have characterized binding interactions between the EF-hand domain of α-actinin (Act-EF34) and peptides derived from palladin and generated an NMR-derived structural model for the Act-EF34/palladin peptide complex. The critical binding site residues are similar to an α-actinin binding motif previously suggested for the complex between Act-EF34 and titin Z-repeats. The structure-based model of the Act-EF34/palladin peptide complex expands our understanding of binding specificity between the scaffold protein α-actinin and various ligands, which appears to require an α-helical motif containing four hydrophobic residues, common to many α-actinin ligands. We also provide evidence that the Family X mutation in palladin, associated with a highly penetrant form of pancreatic cancer, does not interfere with α-actinin binding.     

Connectivity between Catalytic Landscapes of the Metallo-β-Lactamase Superfamily

The expansion of functions in an enzyme superfamily is thought to occur through recruitment of latent promiscuous functions within existing enzymes. Thus, the promiscuous activities of enzymes represent connections between different catalytic landscapes and provide an additional layer of evolutionary connectivity between functional families alongside their sequence and structural relationships. Functional connectivity has been observed between individual functional families; however, little is known about how catalytic landscapes are connected throughout a highly diverged superfamily. Here, we describe a superfamily-wide analysis of evolutionary and functional connectivity in the metallo-β-lactamase (MBL) superfamily. We investigated evolutionary connections between functional families and related evolutionary to functional connectivity; 24 enzymes from 15 distinct functional families were challenged against 10 catalytically distinct reactions. We revealed that enzymes of this superfamily are generally promiscuous, as each enzyme catalyzes on average 1.5 reactions in addition to its native one. Catalytic landscapes in the MBL superfamily overlap substantially; each reaction is connected on average to 3.7 other reactions whereas some connections appear to be unrelated to recent evolutionary events and occur between chemically distinct reactions. These findings support the idea that the highly distinct reactions in the MBL superfamily could have evolved from a common ancestor traversing a continuous network via promiscuous enzymes. Several functional connections (e.g., the lactonase/phosphotriesterase and phosphonatase/phosphodiesterase/arylsulfatase reactions) are also observed in structurally and evolutionary distinct superfamilies, suggesting that these catalytic landscapes are substantially connected. Our results show that new enzymatic functions could evolve rapidly from the current diversity of enzymes and range of promiscuous activities.