Vitamin D and neurocognitive dysfunction: Preventing “D”ecline?

A preponderance of evidence supports a role for vitamin D beyond the classical function in mineral homeostasis. Epidemiologic investigations have revealed a beneficial role of vitamin D in muscle function, cardiovascular health, diabetes, and cancer prevention. More recently, studies have suggested a potential beneficial role of vitamin D in cognitive function. Vitamin D exhibits functional attributes that may prove neuroprotective through antioxidative mechanisms, neuronal calcium regulation, immunomodulation, enhanced nerve conduction and detoxification mechanisms. Compelling evidence supports a beneficial role for the active form of vitamin D in the developing brain as well as in adult brain function. The vitamin D receptor and biosynthetic and degradative pathways for the hydroxylation of vitamin D have been found in the rodent brain; more recently these findings have been confirmed in humans. The vitamin D receptor and catalytic enzymes are colocalized in the areas of the brain involved in complex planning, processing, and the formation of new memories. These findings potentially implicate vitamin D in neurocognitive function.     

Mapping of within-species segregation distortion in Drosophila persimilis and hybrid sterility between D. persimilis and D. pseudoobscura

In contrast to the prevailing dogma in the 1990s, recent studies have suggested that an evolutionary history of segregation distortion within species may contribute to sterility in species hybrids. However, this recent work identified segregation distortion exclusively in species hybrids that may never have had an evolutionary history of segregation distortion in either parent species. We expand on previous work using a strain of Drosophila persimilis exhibiting segregation distortion within species to generate QTL maps for segregation distortion and hybrid sterility in crosses between D. persimilis and D. pseudoobscura. The maps localize regions along the XR contributing to both phenotypes, and they indicate one region of overlap between the two maps. This overlap could provide preliminary evidence for an association between segregation distortion within species and hybrid sterility, but the localizations are currently too broad to have confidence in this conclusion. This work is a first step towards possibly supporting a genetic conflict model of speciation in this system.     

Elite swimmers and the D allele of the ACE I/D polymorphism

A polymorphism of the human angiotensin-1-converting enzyme (ACE) gene has been identified in which the presence (insertion, I allele) of a 287-bp fragment rather than the absence (deletion, D allele) is associated with lower ACE activity. Several recent studies have shown an association of the I allele with endurance performance, it being found with excess frequency in elite distance runners, rowers and mountaineers. Other workers using heterogeneous cohorts of athletes from mixed sporting disciplines have found no such association. An increasing linear trend of I allele frequency with the distance run amongst Olympic runners and an excess of the D allele amongst sprinters led us to examine whether the ratio of I and D alleles in swimmers competing over different distances would also vary. Swimmers (n=120) from the European and Commonwealth championships and an American college team had their ACE genotype determined and their gene and allele frequencies compared with several control groups, the most closely age-matched of which were 1,248 military recruits. Of the 103 Caucasians, there was a significant excess of the D allele compared with this control group only in the truly elite swimmers of the European and Commonwealth championships (P=0.004). This association remained in those competing over shorter distances (P=0.005 for 400 m and below) but not in the longer events. These findings were confirmed in three further large control groups. A population association study testing whether a genetic marker (the ACE I/D polymorphism) occurs more frequently in cases (elite athletes) than in controls therefore requires a homogeneous cohort of subjects from the same sporting discipline.     

ExonVisualiser – application for visualization exon units in 2D and 3D protein structures

The web application oriented on identification and visualization of protein regions encoded by exons is presented. The Exon Visualiser can be used for visualisation on different levels of protein structure: at the primary (sequence) level and secondary structures level, as well as at the level of tertiary protein structure. The programme is suitable for processing data for all genes which have protein expressions deposited in the PDB database. The procedure steps implemented in the application: I) loading exons sequences and theirs coordinates from GenBank file as well as protein sequences: CDS from GenBank and aminoacid sequence from PDB II) consensus sequence creation (comparing amino acid sequences form PDB file with the CDS sequence from GenBank file) III) matching exon coordinates IV) visualisation in 2D and 3D protein structures. Presented web-tool among others provides the color-coded graphical display of protein sequences and chains in three dimensional protein structures which are correlated with the corresponding exons.

Availability

http://149.156.12.53/ExonVisualiser/     

Why There is a One-way Crossability Between D. melanogaster and D. simulans?

In the Drosophila melanogaster complex, females D. melanogaster mate relatively easily with males Drosophila simulans but the reciprocal cross is rare. The species sexual isolation is mainly based on chemical and acoustic signal exchanges between partners. The male side of this communication is investigated in this paper in order to understand the asymmetry. In D. melanogaster the acoustic signature is highly significant, and is synergistically reinforced by the chemical signal. In D. simulans the importance of the two signaling channels seems to be reversed. This could explain why D. simulans males produce less precise interpulse interval (IPI) mean value in the courtship song, which can readily overlap those of D. melanogaster. As the males of the two species use the same chemical key, D. simulans males could be recognized by D. melanogaster females as a conspecific.     

Two μ1,5-dicyanamide bridged 2D and 3D metal complexes formed by covalent bonding and weak interactions

One 2D and one 3D dicyanamide bridged complexes, [Cu(dca)₂(et₂-en)]_n (1) and [Mn(dca)₂(im)₂]_n (2) [dca=dicyanamide, et₂-en=N,N-diethyl-ethylenediamine, im=imidazole], have been synthesized. Both the complexes are 1D by covalent bonding but interchain H-bonding promotes dimensionality. Moreover, π-π interaction among the imidazole ligands also plays an important role to have an interlocked 3D structure for 2. Magnetic study of both the complexes shows weak antiferromagnetic interaction between the metal centers. The magnetic data have been fitted with appropriate equations yielding best fit parameters for 1: J=−0.58±0.02 cm⁻¹, g=2.11±0.01 with R=3.2×10⁻⁶ and for 2, J=−0.21 cm⁻¹, g=2.00 and R=5.6×10⁻⁴.     

The isolation and characterisation of gas-cylinder membranes and α-granules fromAnabaena flos-aquae D 124

Summary Gas-cylinder membranes and -granules were isolated from cells of the blue-green alga,Anabaena flos-aquae D 124. Gas-cylinder membranes, which are 1,100 Å wide after isolation, show striations having a periodicity of 50 Å. The membranes appear globular in section with a spacing of about 40 Å between globules. There are strong indications that the globules are proteinaceous with molecular weights of 22,000±2,000. Possible homologies of these membranes with viral coat protein are discussed. -granules were shown by a variety of techniques to be polysaccharide.     

Design and synthesis of new prostaglandin D₂ receptor antagonists

To identify new cost-effective prostaglandin D? (DP) receptor antagonists, a series of novel 3-benzoylaminophenylacetic acids were synthesized and biologically evaluated. Among those tested, some representative compounds were found to be orally available. Receptor selectivity and rat PK profiles were also evaluated. The structure-activity relationship (SAR) study is presented.     

Gasdermin D and Beyond – Gasdermin-mediated Pyroptosis in Bacterial Infections

The discovery of pyroptosis and its subsequent implications in infection and immunity has uncovered a new angle of host-defence against pathogen assault. At its most simple, gasdermin-mediated pyroptosis in bacterial infection would be expected to remove pathogens from the relative safety of the cytosol or pathogen containing vacuole/phagosome whilst inducing a rapid and effective immune response. Differences in gasdermin-mediated pyroptosis between cell types, stimulation conditions, pathogen and even animal species, however, make things more complex. The excessive inflammation associated with the pathogen-induced gasdermin-mediated pyroptosis contributes to a downward spiral in sepsis. With no currently approved effective treatment options for sepsis understanding how gasdermin-mediated pyroptotic pathways are regulated provides an opportunity to identify novel therapeutic candidates against this complex disease. In this review we cover recent advances in the field of gasdermin-mediated pyroptosis with a focus on bacterial infection and sepsis models in the context of humans and other animal species. Importantly we also consider why there is considerable redundancy set into these ancient immune pathways.     

Vitamin D and autoimmunity: is vitamin D status an environmental factor affecting autoimmune disease prevalence?

The environment in which the encounter of antigen with the immune system occurs determines whether tolerance, infectious immunity, or autoimmunity results. Geographical areas with low supplies of vitamin D (for example Scandinavia) correlate with regions with high incidences of multiple sclerosis, arthritis, and diabetes. The active form of vitamin D has been shown to suppress the development of autoimmunity in experimental animal models. Furthermore, vitamin D deficiency increases the severity of at least experimental autoimmune encephalomyelitis (mouse multiple sclerosis). Targets for vitamin D in the immune system have been identified, and the mechanisms of vitamin D-mediated immunoregulation are beginning to be understood. This review discusses the possibility that vitamin D status is an environmental factor, which by shaping the immune system affects the prevalence rate for autoimmune diseases such as multiple sclerosis, arthritis, and juvenile diabetes.     

Influence of increasing D/A ratio on geometric and electronic properties of D–A-type copolymers

A series of D–A-type copolymers was designed and studied systematically for the purpose of gaining a deeper understanding of how the D/A ratio may influence the geometric and electronic properties when it varies from 2:1 to 6:1 by using DFT method. The results show that it has a significant effect on the bond length alternation, band gap, bandwidth and effective mass of carriers of the designed D–A-type copolymers. But its influence on the geometric and electronic properties shows something very different in degree when it increases from 2:1 to 4:1 and then increases further from 4:1 to 6:1. It is found that the effects of increasing D/A ratio on geometric and electronic properties are much stronger when the D/A ratio increases from 2:1 to 4:1 than when it further increases from 4:1 to 6:1. The theoretical results show that the polymers with a D/A ratio of 2:1 have much smaller effective mass of carriers and much wider bandwidth compared to those polymers with the D/A ratio of 4:1 and 6:1. Therefore, the designed D–A-type copolymers with a D/A ratio of 2:1 may actually be the better candidates for intrinsic conduction materials.     

Synthesis and 2D QSAR of O-sulphonated β-aminols derivatives as novel antifungal and antibacterial agents

Synthesis of a series of β-aminol derivatives using regioselective opening reaction catalyzed by SiO(2) (60-120mesh) and O-sulphonation in THF-KOH system, comprising tert-butoxycarbonyl at secondary nitrogen and evaluate for various stains of bacteria and fungi. SAR study of synthesized compound using backward regression analysis.     

The association between type D personality,and depression and anxiety ten years after PCI

Objective

There are indications that type D personality and depression are associated in patients treated with percutaneous coronary intervention (PCI). However, at present it is unclear whether this relationship holds in the long term. This study’s aim was to investigate the association between type D personality at 6 months post-PCI (baseline), and depression at 10-year follow-up. A secondary aim was to test the association between type D personality at baseline and anxiety at 10-year follow-up.

Methods

A cohort of surviving consecutive patients (N = 534) who underwent PCI between October 2001 and October 2002. Patients completed the type D personality scale (DS14) measuring type D personality at baseline, and the Hospital Anxiety and Depression Scale (HADS) measuring anxiety and depression at baseline and at 10 years post-PCI.

Results

At baseline, the prevalence of type D personality was 25?% (135/534). Type D personality patients were more often depressed (42?%) than non-type D personality patients (9?%). Response rate of anxiety and depression questionnaires at 10 years was 75?%. At 10-year follow-up, 31?% of type D personality patients were depressed versus 13?% of non-type D personality patients. After adjustments, baseline type D personality remained independently associated with depression at 10 years (OR = 3.69; 95?% CI [1.89–7.19]). Type D showed a similar association with anxiety at 10 years, albeit somewhat lower (OR = 2.72; 95?% CI [1.31–5.63]).

Conclusions

PCI patients with type D personality had a 3.69-fold increased risk for depression and a 2.72-fold increased risk for anxiety at 10 years of follow-up.

     

D3: The Dispersal and Diaspore Database – Baseline data and statistics on seed dispersal

Seed dispersal is hard to measure, and there is still a lack of knowledge about dispersal-related traits of plant species. Therefore, we developed D³, the Dispersal and Diaspore Database (available at www.seed-dispersal.info), which aims at simplifying ecological and evolutionary analyses by providing and integrating various items related to seed dispersal: empirical studies, functional traits, image analyses and ranking indices (quantifying the adaptation to dispersal modes).Currently, the database includes data for more than 5000 taxa and 33 items as well as digital images of diaspores (i.e. the dispersal units), seeds, fruits and infructescences. The included items cover common traits like diaspore mass, size, shape, terminal velocity and seed number per diaspore. Furthermore, we present newly or further developed items like ecomorphological categorizations of the diaspore and fruit as well as information from literature on prevailing dispersal modes. Finally, we introduce several items which are not covered in other databases yet: surface structure and form of the diaspore, the exposure of the diaspores in the infructescence and dispersal rankings. Dispersal rankings allow estimations of how well certain species are adapted to a specific dispersal mode in comparison to a larger species set. They are calculated as the percentile rank of an indicator of species’ dispersal potential in relation to a larger species set.Especially for the new and further developed items we outline the basic concepts in detail, describe the measurement and categorization methods and show how to interpret and integrate these data for single species as well as for larger species sets. Thereby, we calculate baseline statistics of seed dispersal of the Central European flora. We found that diaspores of 72% of the taxa show specializations related to long-distance dispersal, i.e. most often elongated appendages or nutrient-rich tissues. Diaspore masses, sizes and terminal velocities vary over several orders of magnitude and can be approximated by lognormal distributions.     

DARC and D6: silent partners in chemokine regulation?

Chemokine receptors adorn the surface of leukocytes and other cell types ready to translate the extracellular chemokine environment into functional cellular outcomes. However, there are several molecules that, in many respects, look like chemokine receptors, but which do not have the ability to confer chemotactic potential to cell lines. This apparent silence spurred the search for signalling-independent functions and led to the development of new paradigms of chemokine regulation. In this review, we summarise the experimental basis for these ideas focussing on DARC and D6, the most studied members of this group of molecules. We discuss data generated using in vitro systems and genetically deficient mice, include results from observational human studies, and summarise the key findings of recent research. We take a critical look at current models of in vivo function highlighting important gaps in our knowledge and demonstrating that there is still much to find out about these enigmatic molecules.     

Pharmacological Characterization of Mammalian D1 and D2 Dopamine Receptors Expressed in Drosophila Schneider‐2 Cells

Abstract

Mammalian D₁ and D₂ dopamine receptors were stably expressed in Drosophila Schneider‐2 (S2) cells and screened for their pharmacological properties. Saturable, dose‐dependent, high affinity binding of the D₁‐selective antagonist [³H]SCH‐23390 was detected only in membranes from S2 cells induced to express rat dopamine D₁ receptors, while saturable, dose‐dependent, high affinity binding of the D₂‐selective antagonist [³H]methylspiperone was detected only in membranes from S2 cells induced to express rat dopamine D₂ receptors. No specific binding of either radioligand could be detected in membranes isolated from uninduced or untransfected S2 cells. Both dopamine D₁ and D₂ receptor subtypes displayed the appropriate stereoselective binding of enantiomers of the nonselective antagonist butaclamol. Each receptor subtype also displayed the appropriate agonist stereoselectivities. The dopamine D₁ receptor bound the (+)‐enantiomer of the D₁‐selective agonist SKF38393 with higher affinity than the (?)‐enantiomer, while the dopamine D₂ receptor bound the (?)‐enantiomer of the D₂‐selective agonist norpropylapomorphine with higher affinity than the (+)‐enantiomer. At both receptor subtypes, dopamine binding was best characterized as occurring to a single low affinity site. In addition, the low affinity dopamine binding was also found to be insensitive to GTPγS and magnesium ions. Overall, the pharmacological profiles of mammalian dopamine D₁ and D₂ receptors expressed in Drosophila S2 cells is comparable to those observed for these same receptors when they are expressed in mammalian cell lines. A notable distinction is that there is no evidence for the coupling of insect G proteins to mammalian dopamine receptors. These results suggest that the S2 cell insect G system may provide a convenient source of pharmacologically active mammalian D₁ and D₂ dopamine receptors free of promiscuous G protein contaminants.     

Measurement of HN-Hα J couplings in calcium-free calmodulin using new 2D and 3D water-flip-back methods

Summary Two new methods are described for the measurement of three-bond J_H ^NHcouplings in proteins isotopically enriched with ¹⁵N. Both methods leave the water magnetization in an unsaturated state, parallel to the z-axis, and therefore offer significant enhancements in sensitivity for rapidly exchanging backbone amide protons. The J couplings can be measured either from a set of constant-time 2D ¹H-¹⁵N HMQC spectra, which are modulated in intensity by J_H ^NH, or from a water-flip-back version of the 3D HNHA experiment. The method is demonstrated for a sample of calcium-free calmodulin. Residues Lys⁷⁵-Asp⁸⁰ have J_H ^NHvalues in the 6–7 Hz range, suggesting that a break in the central helix occurs at the same position as previously observed in solution NMR studies of Ca²⁺-ligated calmodulin.