[Zn(phen)(O,N,O)(H2O)] and [Zn(phen)(O,N)(H2O)] with O,N,O?is?2,6-dipicolinate and N,O?is?l-threoninate: synthesis, characterization, and biomedical properties

Two ternary Zn(II) complexes, with 1,10-phenanthroline (phen) as the main ligand and a carboxylate-containing ligand [dipicolinate (dipico) or L-threoninate (L-Thr)] as the subsidiary ligand, were prepared and characterized by elemental analysis, Fourier transform IR, UV, and fluorescence spectroscopy, X-ray diffraction, molar conductivity, and electrospray ionization mass spectrometry. X-ray structure analysis shows that both [Zn(phen)(dipico)(H(2)O)]·H(2)O (1) and [Zn(phen)(L-Thr)(H(2)O)Cl]·2H(2)O (2) have octahedral geometry about the Zn(II) atom. Both complexes can inhibit topoisomerase I, and have better anticancer activity than cisplatin against nasopharyngeal cancer cell lines, HK1 and HONE-1, with concentrations causing 50?% inhibition of cell proliferation (IC(50)) in the low micromolar range. Complex 2 has the highest therapeutic index for HK1. Both Zn(II) complexes can induce cell death by apoptosis. Changing the subsidiary ligand in the Zn(II) complexes affects the UV-fluorescence spectral properties of the coordinated phen ligand, the binding affinity for some DNA sequences, nucleobase sequence-selective binding, the phase at which cell cycle progression was arrested for treated cancer cells, and their therapeutic index.     

Does size really matter? A comparative study on floral traits in orchids with two different pollination strategies

• The lock and key hypothesis assumes that male and female genitalia match in a unique system to prevent interspecific crosses. This hypothesis is largely investigated in animals, while there is a distinct lack of studies on plants. Nevertheless, we expect the lock and key hypothesis could apply to plants with complex floral morphologies, such as orchids.
• Here we apply a comparative approach to examine the variation of floral functional traits in food‐ and sex‐deceptive orchids. To understand if a specific deception strategy is related to a specific variation in floral traits evaluated the variation in sterile and fertile traits among species and subsequently examined the correlations between male and female reproductive organs of the same species with the aim of investigating the role of the lock and key hypothesis in deceptive orchids.
• Our results show that the functional morphology of fertile traits plays a pivotal role in limiting gene flow in species that grow in sympatry. In particular, it was observed that the Reproductive Standardisation Index (RSI) is significantly different in the two pollination strategies and that the correlation between pollinarium length and stigmatic cavity length is stronger in food‐deceptive species when compared to the sex‐deceptive species.
• These results reveal that the lock and key hypothesis contributes to maintain boundaries in plants with very complex floral morphology.

     

Using nitrification inhibitors to mitigate agricultural N2O emission: a double‐edged sword?

Nitrification inhibitors show promise in decreasing nitrous oxide (N₂O) emission from agricultural systems worldwide, but they may be much less effective than previously thought when both direct and indirect emissions are taken into account. Whilst nitrification inhibitors are effective at decreasing direct N₂O emission and nitrate (NO₃^–) leaching, limited studies suggest that they may increase ammonia (NH₃) volatilization and, subsequently, indirect N₂O emission. These dual effects are typically not considered when evaluating the inhibitors as a climate change mitigation tool. Here, we collate results from the literature that simultaneously examined the effects of nitrification inhibitors on N₂O and NH₃ emissions. We found that nitrification inhibitors decreased direct N₂O emission by 0.2–4.5 kg N₂O‐N ha^?1 (8–57%), but generally increased NH₃ emission by 0.2–18.7 kg NH₃‐N ha^?1 (3–65%). Taking into account the estimated indirect N₂O emission from deposited NH₃, the overall impact of nitrification inhibitors ranged from ?4.5 (reduction) to +0.5 (increase) kg N₂O‐N ha^?1. Our results suggest that the beneficial effect of nitrification inhibitors in decreasing direct N₂O emission can be undermined or even outweighed by an increase in NH₃ volatilization.     

Balanced translocations among couples with two or more spontaneous abortions: Are males and females equally likely to be carriers?

Chromosome studies were performed on a series of 177 couples referred for genetic counseling following two or more spontaneous abortions to clarify the relationship between karyotype and fertility in males and females and to provide risk figures for genetic counseling. The results of these investigations, when combined with those in the literature, suggest that 2-3% of individuals in couples experiencing early fetal losses carry a balanced translocation and that this is not markedly influenced by the number of losses greater than two. Females are more likely than males to be the carrier, reflecting the fact that structural abnormalities of the chromosomes that are compatible with fertility in the female may be associated with sterility in the male. Karyotyping should be performed on both members of a couple following two spontaneous abortions and the products of conception should be studied whenever possible to begin to determine the biological basis of the association between parental rearrangement and fetal loss.     

Do major species concepts support one, two or more species within Cryptococcus neoformans?

Cryptococcus neoformans, the agent of cryptococcosis, had been considered a homogeneous species until 1949 when the existence of four serotypes was revealed based on the antigenic properties of its polysaccharide capsule. Such heterogeneity of the species, however, remained obscure until the two morphologically distinct teleomorphs of C. neoformans were discovered during the mid 1970s. The teleomorph Filobasidiella neoformans was found to be produced by strains of serotype A and D, and Filobasidiella bacillispora was found to be produced by strains of serotype B and C. Ensuing studies revealed numerous differences between the anamorphs of the two Filobasidiella species with regard to their ecology, epidemiology, pathobiology, biochemistry and genetics. At present, the etiologic agent of cryptococcosis is classified into two species, C. neoformans (serotypes A and D) and Cryptococcus gattii (serotypes B and C). Intraspecific genetic diversity has also been revealed as more genotyping methods have been applied for each serotype. As a result, the number of scientifically valid species within C. neoformans has become a controversial issue because of the differing opinions among taxonomists as to the appropriate definition of a species. There are three major species concepts that govern classification of organisms: phenetic (morphologic, phenotypic), biologic (interbreeding) and cladistic (evolutionary, phylogenetic). Classification of the two C. neoformans species has been based on the phenetic as well as the biologic species concept, which is also supported by the cladistic species concept. In this paper, we review and attest to the validity of the current two-species system in light of the three major species concepts.     

Molecular systems biology at the crossroads: to know less about more,or to know more about less?

Systems biology is a rapidly evolving discipline that endeavours to understand the detailed coordinated workings of entire organisms, with the ultimate goal to detect differences between health and disease, or to understand how cells or entire organisms react to the environment. The editorial provides a critical evaluation of what molecular systems analysis can and cannot accomplish with existing methodologies, and how systems biology needs to merge with reductionism to yield a more comprehensive and mechanistically insightful model of a cell or organism.     

For whom is it more beneficial to stop interactions with defectors: Cooperators or defectors?

Cooperation is a mysterious evolutionary phenomenon and its mechanisms require elucidation. When cooperators can stop interactions with defectors, the evolution of cooperation becomes possible; this is one mechanism that facilitates the evolution of cooperation. Here, stopping interactions with defectors is beneficial not only for cooperators but also for defectors. The question then arises, for whom is stopping interactions with defectors more beneficial: cooperators or defectors? By utilizing evolutionary game theory, I addressed this question using a two-player game involving four strategies: (1) cooperators who stop the interaction if the current partner is a defector, (2) cooperators who attempt to maintain a relationship with anyone, (3) defectors who stop the interaction if the current partner is a defector, and (4) defectors who attempt to maintain a relationship with anyone. Our results show that, at equilibrium, the ratio of cooperators who stop the interaction if the current partner is a defector to cooperators who attempt to maintain a relationship with anyone is larger than the ratio of defectors who stop the interaction if the current partner is a defector to defectors who attempt to maintain a relationship with anyone. Thus, cooperators rather than defectors are more likely to stop interactions with defectors at equilibrium. This result is consistent with a previous experimental study in which a positive correlation was detected between the degree of individuals’ cooperativeness and how accurately the individuals recognize whether other individuals are cooperators or defectors. Thus, the theoretical work presented in this study provides relevant insights into the natural phenomena of cooperation and recognition.     

Is urea pulsing in toadfish related to environmental O2 or CO2 levels?

The neurochemical, serotonin (5-hydroxytryptamine; 5-HT) is involved in the regulation of toadfish pulsatile urea excretion as well as the teleost hypoxia response. Thus, the goal of this study was to determine whether environmental conditions that activate branchial chemoreceptors also trigger pulsatile urea excretion in toadfish, since environmental dissolved oxygen levels in a typical toadfish habitat show significant diel fluctuations, often reaching hypoxic conditions at dawn. Toadfish were fitted with arterial, venous and/or buccal catheters and were exposed to various environmental conditions, and/or injected with the O(2) chemoreceptor agonist NaCN or the 5-HT(2) receptor agonist alpha-methyl-5HT. Arterial PO(2), as well as ammonia and urea excretion were monitored. Natural fluctuations in arterial PO(2) levels in toadfish did not correlate with the occurrence of a urea pulse. Chronic exposure (24 h) of toadfish to hyperoxia was without effect on nitrogen excretion, however, exposure to hypoxia caused a significant reduction in the frequency of urea pulses, and exposure to hypercapnia resulted in a reduction in the percentage of nitrogen waste excreted as urea. Of toadfish exposed acutely to hypoxia, 20% pulsed within 1 h, whereas none pulsed after normoxic or hypercapnic treatments. Furthermore, 20% of fish injected intravenously with NaCN pulsed within 1 h of injection, but no fish pulsed after injection of NaCN into the buccal cavity. To test whether environmental conditions affected 5-HT(2) receptors, toadfish were injected with alpha-methyl-5HT, which elicits urea pulses in toadfish. No significant differences in pulse size occurred among the various environmental treatments. Our findings suggest that neither the environmental conditions of hypoxia, hyperoxia or hypercapnia, nor direct branchial chemoreceptor activation by NaCN play a major role in the regulation of pulsatile urea excretion in toadfish.     

Coeliac disease in children and adolescents with type 1 diabetes mellitus: to screen or not, to treat or not?

Coeliac disease is more prevalent in individuals with type 1 diabetes mellitus than in the normal population. It often presents in an atypical or silent form. Specific autoantibodies are found in almost all cases. Untreated coeliac disease may be associated with long-term health risks, so screening and early treatment with a gluten-free diet seem to be justified. However, extended follow-up is needed to document the clinical benefits of screening and treatment in diabetic patients.     

Liebig’s law of the minimum applied to a greenhouse gas: alleviation of P-limitation reduces soil N2O emission

Background and aims

Emission of the greenhouse gas (GHG) nitrous oxide (N₂O) are strongly affected by nitrogen (N) fertilizer application rates. However, the role of other nutrients through stoichiometric relations with N has hardly been studied. We tested whether phosphorus (P) availability affects N₂O emission. We hypothesized that alleviation of plant P-limitation reduces N₂O emission through lowering soil mineral N concentrations.

Methods

We tested our hypothesis in a pot experiment with maize (Zea mays L.) growing on a P-limiting soil/sand mixture. Treatment factors included P and N fertilization and inoculation with Arbuscular Mycorrhizal Fungi (AMF; which can increase P uptake).

Results

Both N and P fertilization, as well as their interaction significantly (P?<?0.01) affected N₂O emission. Highest N₂O emissions (2.38 kg N₂O-N ha^?1) were measured at highest N application rates without P fertilization or AMF. At the highest N application rate, N₂O fluxes were lowest (0.71 kg N₂O-N ha^?1) with both P fertilization and AMF. The N₂O emission factors decreased with 50 % when P fertilization was applied.

Conclusions

Our results illustrate the importance of the judicious use of all nutrients to minimize N₂O emission, and thereby further underline the intimate link between sound agronomic practice and prudent soil GHG management.     

Might the observed α2A-adrenoreceptor agonism or antagonism of allyphenyline analogues be ascribed to different molecular conformations?

We recently reported that the α(2)-adrenoreceptor (AR) ligand allyphenyline (9) significantly enhanced morphine analgesia (due to its α(2C)-AR agonism), was devoid of sedative side effects (due to its α(2A)-AR antagonism), prevented and reversed morphine tolerance and dependence. To highlight the molecular characteristics compatible with this behaviour and to obtain novel agents potentially useful in chronic pain and opioid addiction management, the allyl group of 9 was replaced by substituents of moderate steric bulk (MR) and positive or negative lipophilic (π) and electronic (σ) contributions in all the possible combinations. Effective novel α(2C)-agonists/α(2A)-antagonists (2, 3, 10, 12, and 17) were obtained. This study also demonstrated that contradictory combinations of the physicochemical parameters were similarly able to induce the α(2A)-activation. Since we had previously observed that the absolute configuration affected only the potency, but not the functional profile of the ligands, we hypothesized that the α(2A)-activation was governed by a ligand preferred conformation. From a structural overlay investigation it emerged that an extended conformation appeared to be associated with dual α(2C)-agonism/α(2A)-antagonism, whereas a folded conformation associated with α(2C)-/α(2A)-agonism.     

The Decision to Vaccinate or Not during the H1N1 Pandemic: Selecting the Lesser of Two Evils?

Background

With the release of the H1N1 vaccine, there was much controversy surrounding its use despite strong encouragements to be vaccinated in the media. Though studies have examined factors influencing people''s decision to be vaccinated, few have focused on how general beliefs about the world or where an individual gathers information might influence that decision.

Methodology/Principal Findings

A cross-sectional web-based survey (N = 817) was conducted during the H1N1 outbreak after the vaccine was available. Variables examined included sociodemographic information, health related behaviours, specific beliefs concerning the H1N1 virus and its vaccine, as well as general beliefs, such as fear of contamination, intolerance of uncertainty, emotional states, coping behaviour, and the source of information concerning the virus. Three converging statistical methods were used to examine the associations – analysis of variance, logistic regression, and recursive partition modelling. The most consistent and strongest association was that negative beliefs about the H1N1 vaccine (e.g. fear of its side effects) was related to the decision not to be vaccinated, whereas beliefs about the dangers of the H1N1 virus was related to the decision to be vaccinated. Most notably, having very strong negative beliefs about the vaccine was a more powerful predictor than even strong beliefs about the dangers of the H1N1 virus. Furthermore, obtaining information from the Internet, as compared to more traditional sources of information (e.g., TV, newspapers) was related to the decision not to be vaccinated.

Conclusions/Significance

These results are consistent with the Health Belief Model. Importantly they suggest that during future pandemics public health officials should not only discuss the dangers of the pandemic but also (i) take additional steps to reassure the public about the safety of vaccines and (ii) monitor the information disseminated over the Internet rather than strictly relying on the more traditional mass media.     

Effect of two intermediate electron donors, NADPH and FADH2, on Spirulina Δ6-desaturase co-expressed with two different immediate electron donors, cytochrome b 5 and ferredoxin, in Escherichia coli

When the gene desD encoding Spirulina Δ⁶-desaturase was heterologously expressed in E. coli, the enzyme was expressed without the ability to function. However, when this enzyme was co-expressed with an immediate electron donor, i.e. the cytochrome b ₅ domain from Mucor rouxii, the results showed the production of GLA (γ-linolenic acid), the product of the reaction catalyzed by Δ⁶-desaturase. The results revealed that in E. coli cells, where cytochrome b ₅ is absent and ferredoxin, a natural electron donor of Δ⁶-desaturase, is present at a very low level, the cytochrome b ₅ domain can complement for the function of ferredoxin in the host cells. In the present study, the Spirulina-ferredoxin gene was cloned and co-expressed with the Δ⁶-desaturase in E. coli. In comparison to the co-expression of cytochrome b ₅ with the Δ⁶-desaturase, the co-expression with ferredoxin did not cause any differences in the GLA level. Moreover, the cultures containing the Δ⁶-desaturase co-expressed with cytochrome b ₅ and ferredoxin were exogenously supplied with the intermediate electron donors, NADPH (nicotinamide adenine dinucleotide phosphate, reduced form) and FADH₂ (flavin adenine dinucleotide, reduced form), respectively. The GLA level in these host cells increased drastically, by approximately 50%, compared to the cells without the intermediate electron donors. The data indicated that besides the level of immediate electron donors, the level of intermediate electron donors is also critical for GLA production. Therefore, if the pools of the immediate and intermediate electron donors in the cells are manipulated, the GLA production in the heterologous host will be affected.