Translation of cytochrome f is autoregulated through the 5′ untranslated region of petA mRNA in Chlamydomonas chloroplasts

A process that we refer to as control by epistasy of synthesis (CES process) occurs during chloroplast protein biogenesis in Chlamydomonas reinhardtii: the synthesis of some chloroplast-encoded subunits, the CES subunits, is strongly attenuated when some other subunits from the same complex, the dominant subunits, are missing. Herein we investigate the molecular basis of the CES process for the biogenesis of the cytochrome b6f complex and show that negative autoregulation of cytochrome f translation occurs in the absence of other complex subunits. This autoregulation is mediated by an interaction, either direct or indirect, between the 5′ untranslated region of petA mRNA, which encodes cytochrome f, and the C-terminal domain of the unassembled protein. This model for the regulation of cytochrome f translation explains both the decreased rate of cytochrome f synthesis in vivo in the absence of its assembly partners and its increase in synthesis when significant accumulation of the C-terminal domain of the protein is prevented. When expressed from a chimeric mRNA containing the atpA 5′ untranslated region, cytochrome f no longer showed an assembly-dependent regulation of translation. Conversely, the level of antibiotic resistance conferred by a chimeric petA-aadA-rbcL gene was shown to depend on the state of assembly of cytochrome b6f complexes and on the accumulation of the C-terminal domain of cytochrome f. We discuss the possible ubiquity of the CES process in organellar protein biogenesis.

A cyclodextrin dimer with a photocleavable linker as a possible carrier for the photosensitizer in photodynamic tumor therapy

A cyclodextrin dimer has been synthesized with two β-cyclodextrins linked by a flexible chain containing a carbon–carbon double bond. This dimer binds and solubilizes a phthalocyanine-based photosensitizer that generates singlet oxygen on irradiation. When the complex is irradiated, the singlet oxygen cleaves the carbon–carbon link, and the cyclodextrins are released, liberating the photosensitizer into the light path. Ideas about how this phenomenon could be used to make photodynamic tumor therapy into a more selective process are described.

The joining (J) chain is present in invertebrates that do not express immunoglobulins.

Joining (J) chain is a component of polymeric, but not monomeric, immunoglobulin (Ig) molecules and may play a role in their polymerization and transport across epithelial cells. To date, study of the J chain has been confined to vertebrates that produce Ig and in which the J chain displays a considerable degree of structural homology. The role of the J chain in Ig polymerization has been questioned and, since the J chain can be expressed in lymphoid cells that do not produce Ig, it is possible that the J chain may have other functions. To explore this possibility, we have surveyed J-chain gene, mRNA, and protein expression by using reverse transcriptase-coupled PCR, Northern blot analysis, and immunoblot analysis in invertebrate species that do not produce Ig. We report that the J-chain gene is expressed in invertebrates (Mollusca, Annelida, Arthropoda, Echinodermata, and Holothuroidea), as well as in representative vertebrates (Mammalia, Teleostei, Amphibia). Furthermore, J-chain cDNA from the earthworm has a high degree of homology (68-76%) to human, mouse, and bovine J chains. Immunohistochemical studies reveal that the J chain is localized in the mucous cells of body surfaces, intestinal epithelial cells, and macrophage-like cells of the earthworm and slug. This study suggests that the J chain is a primitive polypeptide that arose before the evolution of Ig molecules and remains highly conserved in extent invertebrates and vertebrates.

Characterization of repetitive DNA in the Mycoplasma genitalium genome: possible role in the generation of antigenic variation.

We have characterized a family of repetitive DNA elements with homology to the MgPa cellular adhesion operon of Mycoplasma genitalium, a bacterium that has the smallest known genome of any free-living organism. One element, 2272 bp in length and flanked by DNA with no homology to MgPa, was completely sequenced. At least four others were partially sequenced. The complete element is a composite of six regions. Five of these regions show sequence similarity with nonadjacent segments of genes of the MgPa operon. The sixth region, located near the center of the element, is an A+T-rich sequence that has only been found in this repeat family. Open reading frames are present within the five individual regions showing sequence homology to MgPa and the adjacent open reading frame 3 (ORF3) gene. However, termination codons are found between adjacent regions of homology to the MgPa operon and in the A+T-rich sequence. Thus, these repetitive elements do not appear to be directly expressible protein coding sequences. The sequence of one region from five different repetitive elements was compared with the homologous region of the MgPa gene from the type strain G37 and four newly isolated M. genitalium strains. Recombination between repetitive elements of strain G37 and the MgPa operon can explain the majority of polymorphisms within our partial sequences of the MgPa genes of the new isolates. Therefore, we propose that the repetitive elements of M. genitalium provide a reservoir of sequence that contributes to antigenic variation in proteins of the MgPa cellular adhesion operon.

The Lutheran blood group glycoprotein, another member of the immunoglobulin superfamily, is widely expressed in human tissues and is developmentally regulated in human liver.

Glycoproteins expressing the Lutheran blood group antigens were isolated from human erythrocyte membranes and from human fetal liver. Amino acid sequence analyses allowed the design of redundant oligonucleotides that were used to generate a 459-bp, sequence-specific probe by PCR. A cDNA clone of 2400 bp was isolated from a human placental lambda gt 11 library and sequenced, and the deduced amino acid sequence was studied. The predicted mature protein is a type I membrane protein of 597 amino acids with five potential N-glycosylation sites. There are five disulfide-bonded, extracellular, immunoglobulin superfamily domains (two variable-region set and three constant-region set), a single hydrophobic, membrane-spanning domain, and a cytoplasmic domain of 59 residues. The overall structure is similar to that of the human tumor marker MUC 18 and the chicken neural adhesion molecule SC1. The extracellular domains and cytoplasmic domain contain consensus motifs for the binding of integrin and Src homology 3 domains, respectively, suggesting possible receptor and signal-transduction function. Immunostaining of human tissues demonstrated a wide distribution and provided evidence that the glycoprotein is under developmental control in liver and may also be regulated during differentiation in other tissues.

The ‘Unknown Knowns’ of the Global Gas Market. CEPS Essay No. 16, 16 October 2014

Energy markets evolve at least as quickly as the economies they fuel. But development unfolds at an irregular pace, with starts and stops often precipitated by seemingly unpredictable dynamics. Is it really impossible to forecast these ‘revolutions’, if the past can be seen as prologue? The answer might be in the way we look at future events; even if we accept that some events are unpredictable, we may be able to infer much more about the future trends through a broader reading of available data, thus revealing ‘unknown knowns’ that may be useful in understanding paradigm shifts ahead. This paper presents an analysis of the global gas market, offering views on what the most relevant ‘unknown knowns’ of today look like, and hypotheses about some of the possible game-changing events that the market is likely to face in the short to medium term.

"Where is the Wealth?" Echoing the King's 2014 speech in light of the delay in the implementation of the new Constitution. Arab Citizenship Review No. 16, 19 February 2016

In Morocco, the new Constitution promised by King Mohammed VI in 2011 has raised high expectations regarding the improvement of socio-economic standards in the country and the possible redistribution of national wealth in a more transparent and democratic way. Just like Tunisia and Egypt, Moroccan demonstrators of the 20 February Movement had taken to the streets to ask for more freedom and democracy, but also to call for social equality and an end to corruption. Many of the grievances and the claims raised by demonstrators fell within the domain of socio-economic rights. Even though it might still be early to take stock, five years down the road, it is possible to provide a fist assessment of the major changes in Morocco in the socio-economic area. The attempt is to analyse whether the improvements introduced by the new Constitution have met the expectations of the people standing up for their rights in the wake of the Arab Spring, or whether the Kingdom of Morocco has fallen short on its promise to undertake structural change.

A rogue is a rogue is a rogue: US foreign policy and the Korean nuclear crisis

Two nuclear crises recently haunted the Korean peninsula, one in 1993/4, the other in 2002/3. In each case the events-were strikingly similar: North Korea made public its ambition to acquire nuclear weapons and withdrew from the Nonproliferation Treaty. Then the situation rapidly deteriorated until the peninsular was literally on the verge of war. The dangers of North Korea's actions, often interpreted as nuclear brinkmanship, are evident. and much discussed, but not so the underlying patterns that have shaped the conflict in the first place. This article sheds light on some of them. It examines the role of the United States in the crisis, arguing that Washington's inability to see North Korea as anything but a threatening 'rogue state' seriously hinders both an adequate understanding and possible resolution of the conflict. Particularly significant is the current policy of pre-emptive strikes against rogue states, for it reinforces half a century of American nuclear threats towards North Korea. The problematic role of these threats has been largely obscured, not least because the highly technical discourse of security analysis has managed to present the strategic situation on the peninsula in a manner that attributes responsibility for the crisis solely to North Korea's actions, even if the situation is in reality far more complex and interactive.

GFP-tagged CFTR transgene is functional in the G551D cystic fibrosis mouse colon

Trafficking of the cystic fibrosis transmembrane conductance regulator (CFTR) is central to its function, with the most common mutation, DeltaF508, resulting in abnormal processing and trafficking. Therefore, there is a significant need to develop tools, which enable the trafficking of CFTR to be studied in vitro and in vivo. In previous studies it has been demonstrated that fusion of the green fluorescent protein (GFP) to the N-terminus of CFTR does lead to functional expression of CFTR chloride channels in epithelial cell lines. The aim of the present study was to examine whether it is possible to express GFP-tagged CFTR as a transgene in colonic and airway epithelial cells of cystic fibrosis (CF) mice and to correct the CF defect. Using the epithelial-specific human cytokeratin promoter K18, we generated bitransgenic mice cftr(G551D/G551D) K18-GFP-CFTR+/-, designated GFP mice. Transcripts for GFP-CFTR could be detected in bitransgenic mice by use of RT-PCR techniques. Expression of GFP-CFTR protein was detected specifically in the colonic epithelium by both direct GFP fluorescence and the use of an anti-GFP antibody. Ussing chamber studies showed that the ion transport defect in colon and airways observed in cftr(G551D/G551D) mice was partially corrected in the bitransgenic animals. Thus, K18-GFP-CFTR is functionally expressed in transgenic mice, which will be a valuable tool in studies on CFTR synthesis, processing and ion transport in native epithelial tissues.

Who owns the child in hospital? A preliminary discussion

Aim. To 'own' a person is considered an infringement of human rights, but we suggest that concepts of ownership influence interactions between parents and staff when a child is admitted to hospital. This paper aims to stimulate debate and contains an explanation of the exploration of the literature for research and discussion of ownership of the child. Method. A wide variety of library indexes, databases and populist media were examined although it was impossible to examine all literature which may have contained references to this topic, and, apart from databases which contained abstracts in English, we could not include literature written in any language other than English, Swedish, and Icelandic. Findings. We found no research that examines how concepts of ownership of a child affects communication between health professionals and parents and, ultimately, the delivery of health care. This paper begins discussion on the issues. Discussion. Historical literature shows that ownership of humans has been a part of many cultures, and parents were once considered to own their children. Ownership of another has legal connotations, for instance in guardianship struggles of children during marriage breakup and in ethical debates over surrogacy and products of assisted conception. Within health care, it becomes a contentious issue in transplantation of body parts, in discourse on autonomy and informed consent, and for religious groups who refuse blood transfusions. In health care, models such as family centred care and partnership in care depend on positive communication between parents and staff. If a hospital staff member feels that he/she owns a child for whom he/she is caring, then conflict between the staff member and the parents over who has the 'best interests of the child' at heart is possible. Conclusion. We encourage debate about concepts of who owns the hospitalized child - the parents or the staff? Should it be argued at all? Is the whole concept of ownership of another, be it adult or child, the ethical antithesis to modern beliefs about human rights? Comment on this issue is invited.

The estrogen receptor 1 G594A polymorphism is associated with migraine susceptibility in two independent case/control groups

Migraine is a painful and debilitating disorder with a significant genetic component. Steroid hormones, in particular estrogen, have long been considered to play a role in migraine, as variations in hormone levels are associated with migraine onset in many sufferers of the disorder. Steroid hormones mediate their activity via hormone receptors, which have a wide tissue distribution. Estrogen receptors have been localized to the brain in regions considered to be involved in migraine pathogenesis. Hence it is possible that genetic variation in the estrogen receptor gene may play a role in migraine susceptibility. This study thus examined the estrogen receptor 1 (ESRalpha) gene for a potential role in migraine pathogenesis and susceptibility. A population-based cohort of 224 migraine sufferers and 224 matched controls were genotyped for the G594A polymorphism located in exon 8 of the ESR1 gene. Statistical analysis indicated a significant difference between migraineurs and non-migraineurs in both the allele frequencies (P=0.003) and genotype distributions (P=0.008) in this sample. An independent follow-up study was then undertaken using this marker in an additional population-based cohort of 260 migraine sufferers and 260 matched controls. This resulted in a significant association between the two groups with regard to allele frequencies (P=8x10(-6)) and genotype distributions (P=4x10(-5)). Our findings support the hypothesis that genetic variation in hormone receptors, in particular the ESR1 gene, may play a role in migraine.

Is the increase in coronary events on Mondays an artifact?

Background: The aim of this article was to investigate the size and possible causes of the reported excess in coronary events on Mondays. Methods: We conducted a metaanalysis of data from the World Health Organization (WHO) MONICA Project, which monitored trends and determinants in cardiovascular disease. The MONICA Project was undertaken in 21 countries from 1980 to 1995. Results: We found a small overall excess rate of coronary events on Mondays. In a population experiencing 100 events per week, we estimate there would be approximately I more event on Monday than on any other day. Hierarchical logistic regression showed that the Monday excess was greater in centers with less thorough data collection procedures. Conclusions: The excess of coronary events on Mondays is probably an artifact resulting from events with uncertain dates being coded as taking place on Mondays.

Alternatives to peace keeping in Korea: the role of non-state actors and face-to-face encounters

Korea is one of the world's most volatile areas, not least because traditional UN mediation and peacekeeping missions are impossible. Having intervened in the Korean War on behalf of the southern side, the UN is a party to the conflict, rather than a neutral arbiter. The situation is particularly problematic because political interactions are characterized by a high degree of state-control over security policy. In both parts of the peninsula the state has, at least until recently, exercised the exclusive right to deal with the opponent on the other side of the hermetically divided peninsula. Given these domestic and international constrains, alternative approaches to conflict resolution are urgently needed. The recently proliferating literature on human security offers possible solutions, for it urges policy makers to view security beyond the conventional military-based defence of the state and its territory. Using such a conceptual framework, the essay assesses the potential significance non-state interactions between North and South, particularly those that promote communication, information exchange and face-to-face encounters. Even though these interactions remain limited, they are of crucial importance, for they provide an opportunity to reduce the stereotypical threat images that continue to fuel conflict on the peninsula.

The Desert of the Real in Spec Ops: The Line. A Study of Simultaneous Hyperreal Experiences by Protagonist and Player : A Study of Simultaneous Hyperreal Experiences by Protagonist and Player

As an anomaly on the market of military shooters of the 21st century, Spec Ops: The Line entails a journey of undetermined realities and modern warfare consequences. In this study, the narrative is analyzed from the perspective of Jean Baudrillard’s idea that simulations have replaced our conception of reality. Both the protagonist and the player of Spec Ops will unavoidably descend into a state of the hyperreal. They experience multiple possible realities within the game narrative and end up unable to comprehend what has transpired. The hyperreal is defined as the state in which it is impossible to discern reality from simulation. The simulation of reality has proliferated itself into being the reality, and the original has been lost. The excessive use of violence, direct approach of the player through a break with the 4th wall and a deceitful narrator contribute to this loss of reality within the game. Although the game represents simulacra, being a simulation in itself, the object of study is the coexisting state of hyperreal shared between protagonist and player when comprehending events in the game. In the end, neither part can understand or discern with any certainty what transpired within the game.

An investigation into the use of knowledge representation in computer-integrated manufacturing

In a certain automobile factory, batch-painting of the body types in colours is controlled by an allocation system. This tries to balance production with orders, whilst making optimally-sized batches of colours. Sequences of cars entering painting cannot be optimised for easy selection of colour and batch size. `Over-production' is not allowed, in order to reduce buffer stocks of unsold vehicles. Paint quality is degraded by random effects. This thesis describes a toolkit which supports IKBS in an object-centred formalism. The intended domain of use for the toolkit is flexible manufacturing. A sizeable application program was developed, using the toolkit, to test the validity of the IKBS approach in solving the real manufacturing problem above, for which an existing conventional program was already being used. A detailed statistical analysis of the operating circumstances of the program was made to evaluate the likely need for the more flexible type of program for which the toolkit was intended. The IKBS program captures the many disparate and conflicting constraints in the scheduling knowledge and emulates the behaviour of the program installed in the factory. In the factory system, many possible, newly-discovered, heuristics would be awkward to represent and it would be impossible to make many new extensions. The representation scheme is capable of admitting changes to the knowledge, relying on the inherent encapsulating properties of object-centres programming to protect and isolate data. The object-centred scheme is supported by an enhancement of the `C' programming language and runs under BSD 4.2 UNIX. The structuring technique, using objects, provides a mechanism for separating control of expression of rule-based knowledge from the knowledge itself and allowing explicit `contexts', within which appropriate expression of knowledge can be done. Facilities are provided for acquisition of knowledge in a consistent manner.