Programmed death in yeast as adaptation?

During recent years, several pieces of indirect evidence of a programmed death in yeast have been published. Among them there are observations that some mammalian pro- or anti-apoptotic proteins induce or prevent the death of yeast; some toxic compounds kill yeast at lower concentrations if protein synthesis is operative; this death, as well as the death due to certain mutations, shows some apoptotic markers. In April 2002, the yeast programmed death concept received direct support. Madeo et al. [Madeo et al., Mol. Cell 9 (2002) 911-917] disclosed a caspase which is activated by H(2)O(2) or aging and is required for the protein-synthesis-dependent death of yeast. Thus, a specific apoptosis-mediating protein was identified for the first time in Saccharomyces cerevisiae. Independently, Severin and Hyman [Severin, F.F., Hyman, A.A., Curr. Biol. 12 (2002) R233-R235] discovered that death of yeast, induced by a high level of a pheromone, is programmed. In particular, the death was found to be prevented by cycloheximide and cyclosporin A. It required mitochondrial DNA, cytochrome c and the pheromone-initiated protein kinase cascade. When haploids of opposite mating types were mixed, some cells died, the inhibitory pattern being the same as in the case of the killing by pheromone. Inhibition of mating proved to be favorable for death. Thus, pheromone not only activates mating but also eliminates yeast cells failing to mate. Such an effect should (i) stimulate switch of the yeast population from vegetative to sexual reproduction, and (ii) shorten the life span and, hence, accelerate changing of generations. As a result, the probability of appearance of new traits could be enhanced when ambient conditions turned for the worse.     

Are seat belt restraints as effective in school age children as in adults? A prospective crash study

ObjectiveTo study effectiveness of seat belts for protecting school age children in road vehicle crashes.DesignCrash examinations by trained investigators.SettingTen Canadian university based crash investigation centres.Subjects470 children aged 4-14 years, with 168 selected for detailed analysis, and 1301 adults.ResultsOverall, 40% (189/470) of children were unbelted. Of the 335 children in cars driven by belted adults, 73 (22%) were unbelted. The odds of sustaining fatal or moderately severe injury (injury severity score ⩾4) for children in the front passenger seat was more than nine times higher for unbelted children than for belted ones (odds ratio 9.8 (95% confidence interval 2.4 to 39.4)) and for those in the rear left seat was more than two times higher for unbelted than for belted children (2.6 (1.1 to 5.9)). The protection afforded by seat belts compared favourably with the results for adults in the same seat positions (odds ratios for unbelted v belted adults of 2.4 and 2.7 for front and rear seat passengers respectively).ConclusionsSeat belts helped to protect school age children from injury in road vehicle crashes. However, 40% of children were unbelted. Despite standard seat belts being designed for adults, school age children were at least as well protected as adults.

What is already known on this topic

Although child restraints protect young children in road vehicle crashes, it is not known whether standard seat belts used by school age children work as wellSchool age children are often unbelted in cars

What this study adds

Data from detailed crash assessments indicate that seat belts protected children at least as well as adultsAdults were more likely than children to be belted, and 22% of children travelling with belted drivers were unbelted     

Malarial parasites as geographical markers in migratory birds?

We tested the hypothesis that malarial parasites (Plasmodium and Haemoproteus) of black-throated blue warblers (Dendroica caerulescens) provide sufficient geographical signal to track population movements between the warbler's breeding and wintering habitats in North America. Our results from 1083 warblers sampled across the species' breeding range indicate that parasite lineages are geographically widespread and do not provide site-specific information. The wide distribution of malarial parasites probably reflects postnatal dispersal of their hosts as well as mixing of breeding populations on the wintering range. When compared to geographically structured parasites of sedentary Caribbean songbirds, patterns of malarial infections in black-throated blue warblers suggest that host-malaria dynamics of migratory and sedentary bird populations may be subject to contrasting selection pressures.     

β-Propeller Blades as Ancestral Peptides in Protein Evolution

Proteins of the β-propeller fold are ubiquitous in nature and widely used as structural scaffolds for ligand binding and enzymatic activity. This fold comprises between four and twelve four-stranded β-meanders, the so called blades that are arranged circularly around a central funnel-shaped pore. Despite the large size range of β-propellers, their blades frequently show sequence similarity indicative of a common ancestry and it has been proposed that the majority of β-propellers arose divergently by amplification and diversification of an ancestral blade. Given the structural versatility of β-propellers and the hypothesis that the first folded proteins evolved from a simpler set of peptides, we investigated whether this blade may have given rise to other folds as well. Using sequence comparisons, we identified proteins of four other folds as potential homologs of β-propellers: the luminal domain of inositol-requiring enzyme 1 (IRE1-LD), type II β-prisms, β-pinwheels, and WW domains. Because, with increasing evolutionary distance and decreasing sequence length, the statistical significance of sequence comparisons becomes progressively harder to distinguish from the background of convergent similarities, we complemented our analyses with a new method that evaluates possible homology based on the correlation between sequence and structure similarity. Our results indicate a homologous relationship of IRE1-LD and type II β-prisms with β-propellers, and an analogous one for β-pinwheels and WW domains. Whereas IRE1-LD most likely originated by fold-changing mutations from a fully formed PQQ motif β-propeller, type II β-prisms originated by amplification and differentiation of a single blade, possibly also of the PQQ type. We conclude that both β-propellers and type II β-prisms arose by independent amplification of a blade-sized fragment, which represents a remnant of an ancient peptide world.     

α-Chymotrypsin shows higher activity in water as well as organic solvents after three phase partitioning

Alpha-Chymotrypsin was found to show a 119% increase in activity after three phase partitioning. The k_cat/K_m of the partitioned enzyme (TPP-C) for hydrolysis of Bz-Tyr-OEt in aqueous medium at 25°C was found to be 48.3×10⁴ mM^?1 min^?1 as compared to the corresponding value of 17.7×10⁴ mM^?1 min^?1 for the untreated control (C). The λ_max of the fluorescence emission spectrum of TPP-C showed 178% increase in the quantum yield when compared to C. TPP-C showed a 2.94 and 3.58 fold increase (as compared to C) in initial rates for formation of the ester Ac-Phe-OEt (from Ac-Phe and ethanol) in low water containing toluene and n-octane, respectively. It was found that TPP-C also showed the phenomenon of pH memory. At 5% (v v^?1) water (in t-amyl alcohol), while no esterification was observed with C, TPP-C still showed significant level of esterification activity.

Bz-Tyr-OEt, Benzoyl tyrosine ethyl ester; Ac-Phe, N-acetyl phenylalanine; Ac-Phe-OEt, N-acetyl phenylalanine ethyl ester; TPP, Three phase partitioning; C, Untreated α-chymotrypsin; TPP-C, α-Chymotrypsin subjected to TPP; k_cat, Catalytic efficiency; K_m, Michaelis constant     

Antidepressant drugs in the elderly: Are the indications as long term as the treatment?

In a community study of 761 people aged 70 years and over 45 (5·9%) were found to be taking long term tricyclic antidepressants. Forty four were compared with matched controls. There was no evidence that tricyclic antidepressants were being used to compensate for poor physical health or function. Twenty subjects had a clear history of depression; three of these required additional treatment and five might have coped without continued drug treatment. Twelve of the remainder had started treatment with tricyclic antidepressants as hypnotics and 11 as a trial because of suspected depression. They had continued taking the drugs over a long period.Regular review of both the adequacy of and the necessity for continued treatment with tricyclic antidepressants in the elderly is recommended.     

The use of β-galactosidase as a tracer in immunocytochemistry

Summary A new immunocytochemical method using -galactosidase as a tracer is described. The positive staining appears blue on an unstained background. The present method has the high sensitivity and specificity of the immunoperoxidase method and appears to be a practical alternative. The substrate has no carcinogenic activity. Staining is permanent and the sections can be dehydrated and mounted in synthetic media. Enzyme and substrate solutions are stable for several months.     

Transnational Corporations as ‘Keystone Actors’ in Marine Ecosystems

Keystone species have a disproportionate influence on the structure and function of ecosystems. Here we analyze whether a keystone-like pattern can be observed in the relationship between transnational corporations and marine ecosystems globally. We show how thirteen corporations control 11-16% of the global marine catch (9-13 million tons) and 19-40% of the largest and most valuable stocks, including species that play important roles in their respective ecosystem. They dominate all segments of seafood production, operate through an extensive global network of subsidiaries and are profoundly involved in fisheries and aquaculture decision-making. Based on our findings, we define these companies as keystone actors of the Anthropocene. The phenomenon of keystone actors represents an increasingly important feature of the human-dominated world. Sustainable leadership by keystone actors could result in cascading effects throughout the entire seafood industry and enable a critical transition towards improved management of marine living resources and ecosystems.     

Does diacylglycerol serve as a signaling molecule in plants?

Diacylglycerol (DAG) is an important signaling phospholipid in animals, specifically binding to the C1 domain of proteins such as protein kinase C. In most plant species, however, DAG is present at low abundance, and no interacting proteins have yet been identified. As a result, it has been proposed that the signaling function of DAG has been discarded by plants during their evolution. In this mini-review, we summarize the accumulating experimental evidence which supports that notion that changes in DAG content in response to particular cues are a feature of plant cells. This behavior suggests that DAG does indeed act as a signaling molecule during plant development and in response to certain environmental stimuli.     

Participation of (p)ppGpp molecules in the formation of “stringent response” in bacteria,as well as in the biosynthesis of antibiotics and morphological differentiation in actinomycetes

Stringent response is a pleiotropic physiological response of cells caused by deficiency of aminoacetylated tRNAs and, correspondingly, by the arrest of protein synthesis. This response can experimentally be induced by amino acid deficiency in a culture medium and limitation of the aminoacylation capacity of tRNA molecules even in the presence of the respective amino acids in the cell. Many traits of this response indicate its dependence on the accumulation of ppGpp molecules. There are links between the growth rate of actinomycetes and the biosynthesis of secondary metabolites by the bacteria. In particular, it has been established that the introduction of additional relA gene copies of the ppGpp synthetase can affect the production of antibiotics in streptomycetes. The survey presents the authors’ own experimental data obtained in the studies on the effect of heterologous relA gene expression in Streptomyces nogalater, the nogalamycin producer.     

Fish–duck interactions in boreal lakes in Finland as reflected by abundance correlations

We studied the hypothesis that fish play an important role in lake use by ducks (pairs and broods) in boreal lakes. The study was based on densities of different duck and fish species in 28 boreal lakes in southern Finland. We focused on the three most common duck species (mallard Anas platyrhynchos, green-winged teal A. crecca and common goldeneye Bucephala clangula) and on the three most common fish species (perch Perca fluviatilis, roach Rutilus rutilus and pike Esox lucius) in the region. We considered both competitive and predatory interactions between ducks and fish, the perch and roach being potential competitors with ducks and the pike a potential predator of ducks. We found a negative association between green-winged teal brood density and total fish density, the other duck species having only a weak association with total fish density. When the three fish species were considered separately, a negative association, suggesting food competition, was found between perch, green-winged teal and goldeneye, whereas the role of roach as a food competitor seemed to be of minor importance. We did not find any clear signs of predatory effects of pike on ducks. Our results suggest that food competition is a more important factor than pike predation in affecting lake use by ducks in oligotrophic boreal environments in southern Finland.     

GSK-3β as a driving force in ovarian cancer

Ovarian cancer is one of the most lethal malignancies in women. Identification of new therapeutic targets would provide opportunities for developing potentially more effective treatment regimes. In the July issue of Cell Research, Cao et al. reports that glycogen synthase kinase-3β （GSK-3β） plays an important role in positively regulating the proliferation of human ovarian cancer cells, and thus it may represent such a target [ 1 ]. GSK-3β is a serine/threonine kinase that is known to be involved in regulation of β-catenin signaling, where it participates in the formation of a multi-component destruction complex that promotes the phosphorylation and subsequent degradation of β-catenin. Given that overactive β-catenin signaling is involved in many forms of human cancer, this classic mode of GSK-3β action should qualify it as a ＂tumor suppressor＂. Intriguingly, however, two recent studies have implicated that GSK-3β may actually play a pro-tumor role in pancreatic and colorectal cancers [2, 3]. Since ovarian tumors often exhibit increased expression of GSK-3β, these recent findings prompted Cao et al. to examine the potential role of GSK-3β in ovarian cancer cells.     

Do Uric Acid Deposits in Zooxanthellae Function as Eye-Spots?

The symbiosis between zooxanthellae (dinoflagellate genus Symbiodinium) and corals is a fundamental basis of tropical marine ecosystems. However the physiological interactions of the hosts and symbionts are poorly understood. Recently, intracellular crystalline deposits in Symbiodinium were revealed to be uric acid functioning for nutrient storage. This is the first exploration of these enigmatic crystalline materials that had previously been misidentified as oxalic acid, providing new insights into the nutritional strategies of Symbiodinium in oligotrophic tropical waters. However, we believe these deposits also function as eye-spots on the basis of light and electron microscopic observations of motile cells of cultured Symbiodinium. The cells possessed crystalline deposit clusters in rows with each row 100–150 nm thick corresponding to 1/4 the wavelength of light and making them suitable for maximum wave interference and reflection of light. Crystalline clusters in cells observed with a light microscope strongly refracted and polarized light, and reflected or absorbed short wavelength light. The facts that purines, including uric acid, have been identified as the main constituents of light reflectors in many organisms, and that the photoreceptor protein, opsin, was detected in our Symbiodinium strain, support the idea that uric acid deposits in Symbiodinium motile cells may function as a component of an eye-spot.     

Primary prevention with the ICD in clinical practice: not as straightforward as the guidelines suggest?

At first sight, guidelines for implantation of an implantable cardioverter defibrillator (ICD) for primary prevention of sudden cardiac death in patients with left ventricular systolic dysfunction seem unambiguous. There are clear cut-off values for ejection fraction, and functional class. However, determination of the ejection fraction itself is not unambiguous, and other risk factors for sudden death that may have a profound effect on risk are not used for decision-making. Furthermore, to obtain a clinically significant impact on survival, expected longevity is important as it can greatly compromise the benefit in elderly patients but underestimate the long-term potential of ICD therapy in younger patients. (Neth Heart J 2009; 17:107–10.)