Teleology: yesterday,today, and tomorrow?

Teleological explanations in evolutionary biology, from Cuvier to the present (and into the future), depend on the metaphor of design for heuristic power and predictive fertility.     

Sucrose, sucrosyl oligosaccharides, and oxidative stress: scavenging and salvaging?

In nature, no single plant completes its life cycle withoutencountering environmental stress. When plant cells surpassstress threshold stimuli, chemically reactive oxygen species(ROS) are generated that can cause oxidative damage or act assignals. Plants have developed numerous ROS-scavenging systemsto minimize the cytotoxic effects of ROS. The role of sucrosyloligosaccharides (SOS), including fructans and the raffinosefamily oligosaccharides (RFOs), is well established during stressphysiology. They are believed to act as important membrane protectorsin planta. So far a putative role for sucrose and SOS duringoxidative stress has largely been neglected, as has the contributionof the vacuolar compartment. Recent studies suggest a link betweenSOS and oxidative defence and/or scavenging. SOS might be involvedin stabilizing membrane-associated peroxidases and NADPH oxidases,and SOS-derived radicals might fulfil an intermediate role inoxido-reduction reactions taking place in the vicinity of membranes.Here, these emerging features are discussed and perspectivesfor future research are provided. Key words: Fructan, oxidative stress, raffinose, ROS, sucrose, sucrosyl oligosaccharides Received 25 September 2008; Revised 20 October 2008 Accepted 23 October 2008     

Rapamycin and Ageing: When,for How Long,and How Much?

正The mechanistic target of rapamycin(mTOR)is a nutrient and growth factor responsive kinase that modulates lifespan in species from yeast to mice(Johnson et al.,2013b).mTOR exists in two complexes within cells,mTOR complexⅠ(mTORC1)and mTOR complex 2(mTORC2)(Laplante and Sabatini,2012).Abundant evidence suggests that mTORC1is the primary mTOR complex involved in regulating longevity:mutations that reduce the     

Schistosome monogamy: who,how, and why?

Schistosomes represent a unique animal model for comparative analyses of monogamy. Indeed, schistosomes are classified at the lowest taxonomical level of monogamous species and lack complex social interactions, which could alter our understanding of their unusual mating system. Elements discussed here include the fact that monogamy in schistosomes could be an ancestral state between hermaphroditism and polygyny or polygynandry and the occurrence of mate changes. In addition, hypotheses are proposed to explain monogamy in schistosomes (e.g. female dispersion, the need for paternal care, oviposition site limitation or aggressiveness, and mate guarding). We also propose future experimental and analytical approaches to improve our understanding of the schistosomes' mating system.     

Working Memory,Reasoning, and Task Switching Training: Transfer Effects,Limitations, and Great Expectations?

Although some studies have shown that cognitive training can produce improvements to untrained cognitive domains (far transfer), many others fail to show these effects, especially when it comes to improving fluid intelligence. The current study was designed to overcome several limitations of previous training studies by incorporating training expectancy assessments, an active control group, and “Mind Frontiers,” a video game-based mobile program comprised of six adaptive, cognitively demanding training tasks that have been found to lead to increased scores in fluid intelligence (Gf) tests. We hypothesize that such integrated training may lead to broad improvements in cognitive abilities by targeting aspects of working memory, executive function, reasoning, and problem solving. Ninety participants completed 20 hour-and-a-half long training sessions over four to five weeks, 45 of whom played Mind Frontiers and 45 of whom completed visual search and change detection tasks (active control). After training, the Mind Frontiers group improved in working memory n-back tests, a composite measure of perceptual speed, and a composite measure of reaction time in reasoning tests. No training-related improvements were found in reasoning accuracy or other working memory tests, nor in composite measures of episodic memory, selective attention, divided attention, and multi-tasking. Perceived self-improvement in the tested abilities did not differ between groups. A general expectancy difference in problem-solving was observed between groups, but this perceived benefit did not correlate with training-related improvement. In summary, although these findings provide modest evidence regarding the efficacy of an integrated cognitive training program, more research is needed to determine the utility of Mind Frontiers as a cognitive training tool.     

Consciousness: here,there and everywhere?

The science of consciousness has made great strides by focusing on the behavioural and neuronal correlates of experience. However, while such correlates are important for progress to occur, they are not enough if we are to understand even basic facts, for example, why the cerebral cortex gives rise to consciousness but the cerebellum does not, though it has even more neurons and appears to be just as complicated. Moreover, correlates are of little help in many instances where we would like to know if consciousness is present: patients with a few remaining islands of functioning cortex, preterm infants, non-mammalian species and machines that are rapidly outperforming people at driving, recognizing faces and objects, and answering difficult questions. To address these issues, we need not only more data but also a theory of consciousness—one that says what experience is and what type of physical systems can have it. Integrated information theory (IIT) does so by starting from experience itself via five phenomenological axioms: intrinsic existence, composition, information, integration and exclusion. From these it derives five postulates about the properties required of physical mechanisms to support consciousness. The theory provides a principled account of both the quantity and the quality of an individual experience (a quale), and a calculus to evaluate whether or not a particular physical system is conscious and of what. Moreover, IIT can explain a range of clinical and laboratory findings, makes a number of testable predictions and extrapolates to a number of problematic conditions. The theory holds that consciousness is a fundamental property possessed by physical systems having specific causal properties. It predicts that consciousness is graded, is common among biological organisms and can occur in some very simple systems. Conversely, it predicts that feed-forward networks, even complex ones, are not conscious, nor are aggregates such as groups of individuals or heaps of sand. Also, in sharp contrast to widespread functionalist beliefs, IIT implies that digital computers, even if their behaviour were to be functionally equivalent to ours, and even if they were to run faithful simulations of the human brain, would experience next to nothing.     

Nitro-substituted tetrahydroindolizines and homologs: Design,kinetics, and mechanism of α-glucosidase inhibition

A series of 1-[(methylsulfonyl)methyl]-2-nitro-5,6,7,8-tetrahydroindolizines and homologs were designed, prepared, and evaluated as non-sugar-type α-glucosidase inhibitors. The inhibitory activity appeared to be related to cyclo homologation with the best congeners being tetrahydroindolizines. The introduction of a methoxycarbonyl group as an additional hydrogen bond acceptor into the exocyclic methylene group was beneficial affording the most potent congener 3e (half maximal inhibitory concentration, IC₅₀ = 8.0 ± 0.1 μM) which displayed 25-fold higher inhibitory activity than 1-deoxynojirimycin (2, IC₅₀ = 203 ± 9 μM)—the reference compound. Kinetic analysis indicated that compound 3e is a mixed inhibitor with preference for the free enzyme over the α-glucosidase–substrate complex (K_i,free = 3.6 μM; K_i,bound = 7.6 μM). Molecular docking experiments were in agreement with kinetic results indicating reliable interactions with both the catalytic cleft and other sites. Circular dichroism spectroscopy studies suggested that the inhibition exerted by 3e may involve changes in the secondary structure of the enzyme. Considering the relatively low molecular weight of 3e together with its high fraction of sp³ hybridized carbon atoms, this nitro-substituted tetrahydroindolizine may be considered as a good starting point towards new leads in the area of α-glucosidase inhibitors.     

Protein–Protein Docking: Past,Present, and Future

The Protein Journal - The biological significance of proteins attracted the scientific community in exploring their characteristics. The studies shed light on the interaction patterns and functions...     

Signalling sphingomyelinases: which, where, how and why?

A major lipid signalling pathway in mammalian cells implicates the activation of sphingomyelinase (SMase), which upon cell stimulation hydrolyses the ubiquitous sphingophospholipid sphingomyelin to ceramide. This review summarizes our current knowledge on the nature and regulation of signalling SMase(s). Because of the controversy on the identity of this(these) phospholipase(s), the roles of various SMases in cell signalling are discussed. Special attention is also given to the subcellular site of action of signalling SMases and to the cellular factors that positively or negatively control their activity. These regulating agents include lipids (arachidonic acid, diacylglycerol and ceramide), kinases, proteases, glutathione and other proteins.     

The β-lactam antibiotics: past, present, and future

The discovery and development of the -lactam antibiotics are among the most powerful and successful achievements of modern science and technology. Since Fleming's accidental discovery of the penicillin-producing mold, seventy years of steady progress has followed, and today the -lactam group of compounds are the most successful example of natural product application and chemotherapy. Following on the heels of penicillin production by Penicillium chrysogenum came the discoveries of cephalosporin formation by Cephalosporium acremonium, cephamycin, clavam and carbapenem production by actinomycetes, and monocyclic -lactam production by actinomycetes and unicellular bacteria. Each one of these groups has yielded medically-useful products and has contributed to the reduction of pain and suffering of people throughout the world. Research on the microbiology, biochemistry, genetics and chemistry of these compounds have continued up to the present with major contributions being made by both individual and collaborative groups from industry and academia. The discovery of penicillin not only led to the era of the wonder drugs but provided the most important antibiotics available to medicine. Continued efforts have resulted in the improvement of these compounds with respect to potency, breadth of spectrum, activity against resistant pathogens, stability and pharmacokinetic properties. On the research front, major advances are being made on structural and regulatory biosynthetic genes and metabolic engineering of the pathways involved. New semisynthetic compounds especially those designed to combat resistance development are being examined in the clinic, and unusual non-antibiotic activities of these compounds are being pursued. Although seventy years of age, the -lactams are not yet ready for retirement.     

Achieving disbelief: thought styles,microbial variation,and American and British epidemiology, 1900–1940

The role of bacterial variation in the waxing and waning of epidemics was a subject of lively debate in late nineteenth and early twentieth-century bacteriology and epidemiology. The notion that changes in bacterial virulence were responsible for the rise and fall of epidemic diseases was an often-voiced, but little investigated hypothesis made by late nineteenth-century epidemiologists. It was one of the first hypotheses to be tested by scientists who attempted to study epidemiological questions using laboratory methods. This paper examines how two groups of experimental epidemiologists, the British group led by W. W. C. Topley and Major Greenwood, and an American group directed by Leslie T. Webster at the Rockefeller Institute, studied the role of variations in bacterial virulence in the course of laboratory epidemics of mouse typhoid. Relying on Ludwik Fleck’s concept of thought styles and thought collectives, the paper analyzes the fundamental conceptual differences between these two groups of researchers and analyzes the kinds of innovations they introduced as they attempted to integrate bacteriological and epidemiological approaches. The paper shows that the stylistic differences between the two groups can be understood better in the context of the institutional histories and disciplinary relations of epidemiology and bacteriology in the two countries.     

Barley β-Galactosidase: Structure, Function, Heterogeneity, and Gene Origin

Barley (Hordeum vulgare) β-galactosidase is composed of a large (45 kDa) and a small (33 kDa) polypeptide. N-terminal sequencing of the polypeptides and antibody reactivity data place the barley enzyme and heterodimeric plant β-galactosidases from jack bean, maize, and wheat in family 35 of the glycosyl hydrolases. Sequence analysis indicates the existence of a subfamily of genes coding for polypeptide precursors that are cleaved to produce the two subunits in heterodimeric β-galactosidases. The heterogeneity of the barley holoenzyme is related, but not restricted, to the N-glycosylation of the small polypeptide. Both polypeptides are essential for the catalytic activity of the enzyme.