Immunofluorescent demonstration of pancreatic polypeptide (PP) in pancreas and digestive tube of bony and cartilaginous fish]

When antisera specific against bovine PP (BPP) were used, immunoreactive parenchymal cells were observed in the endocrine pancreas and in the gastro-intestinal tract of the teleost bony fish Cottus scorpius, as well as in the pancreas of the elasmobranchian cartilaginous fish Squalus acanthias. Of the two principal islets of Cottus, PP-cells were located selectively to that in the pyloric region.     

Drosophila odorant receptors are both ligand-gated and cyclic-nucleotide-activated cation channels

From worm to man, many odorant signals are perceived by the binding of volatile ligands to odorant receptors that belong to the G-protein-coupled receptor (GPCR) family. They couple to heterotrimeric G-proteins, most of which induce cAMP production. This second messenger then activates cyclic-nucleotide-gated ion channels to depolarize the olfactory receptor neuron, thus providing a signal for further neuronal processing. Recent findings, however, have challenged this concept of odorant signal transduction in insects, because their odorant receptors, which lack any sequence similarity to other GPCRs, are composed of conventional odorant receptors (for example, Or22a), dimerized with a ubiquitously expressed chaperone protein, such as Or83b in Drosophila. Or83b has a structure akin to GPCRs, but has an inverted orientation in the plasma membrane. However, G proteins are expressed in insect olfactory receptor neurons, and olfactory perception is modified by mutations affecting the cAMP transduction pathway. Here we show that application of odorants to mammalian cells co-expressing Or22a and Or83b results in non-selective cation currents activated by means of an ionotropic and a metabotropic pathway, and a subsequent increase in the intracellular Ca(2+) concentration. Expression of Or83b alone leads to functional ion channels not directly responding to odorants, but being directly activated by intracellular cAMP or cGMP. Insect odorant receptors thus form ligand-gated channels as well as complexes of odorant-sensing units and cyclic-nucleotide-activated non-selective cation channels. Thereby, they provide rapid and transient as well as sensitive and prolonged odorant signalling.     

Co-option of a default secretory pathway for plant immune responses

Cell-autonomous immunity is widespread in plant-fungus interactions and terminates fungal pathogenesis either at the cell surface or after pathogen entry. Although post-invasive resistance responses typically coincide with a self-contained cell death of plant cells undergoing attack by parasites, these cells survive pre-invasive defence. Mutational analysis in Arabidopsis identified PEN1 syntaxin as one component of two pre-invasive resistance pathways against ascomycete powdery mildew fungi. Here we show that plasma-membrane-resident PEN1 promiscuously forms SDS-resistant soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNARE) complexes together with the SNAP33 adaptor and a subset of vesicle-associated membrane proteins (VAMPs). PEN1-dependent disease resistance acts in vivo mainly through two functionally redundant VAMP72 subfamily members, VAMP721 and VAMP722. Unexpectedly, the same two VAMP proteins also operate redundantly in a default secretory pathway, suggesting dual functions in separate biological processes owing to evolutionary co-option of the default pathway for plant immunity. The disease resistance function of the secretory PEN1-SNAP33-VAMP721/722 complex and the pathogen-induced subcellular dynamics of its components are mechanistically reminiscent of immunological synapse formation in vertebrates, enabling execution of immune responses through focal secretion.     

Femtosecond time-delay X-ray holography

Extremely intense and ultrafast X-ray pulses from free-electron lasers offer unique opportunities to study fundamental aspects of complex transient phenomena in materials. Ultrafast time-resolved methods usually require highly synchronized pulses to initiate a transition and then probe it after a precisely defined time delay. In the X-ray regime, these methods are challenging because they require complex optical systems and diagnostics. Here we propose and apply a simple holographic measurement scheme, inspired by Newton's 'dusty mirror' experiment, to monitor the X-ray-induced explosion of microscopic objects. The sample is placed near an X-ray mirror; after the pulse traverses the sample, triggering the reaction, it is reflected back onto the sample by the mirror to probe this reaction. The delay is encoded in the resulting diffraction pattern to an accuracy of one femtosecond, and the structural change is holographically recorded with high resolution. We apply the technique to monitor the dynamics of polystyrene spheres in intense free-electron-laser pulses, and observe an explosion occurring well after the initial pulse. Our results support the notion that X-ray flash imaging can be used to achieve high resolution, beyond radiation damage limits for biological samples. With upcoming ultrafast X-ray sources we will be able to explore the three-dimensional dynamics of materials at the timescale of atomic motion.     

F#-Time, Functions and Processes: Towards Sustainable Investment Risk Benchmarks

‘I made a mistake’: Alan Greenspan (Financial Times: Alan Beattie and James Politi: Washington, 23rd October 2008). Such are the words of great men, for even in troubled times their self-effacing manner provides useful guidance. Whilst Mr Greenspan may feel this way, he is a product of his environment, one that has seen the cumulative development of financial instruments and strategies that have not been thought through as to their impact on a complex economy. Mainly this is because risk is thought to be discrete and the methods used to price it are flawed. To an engineer the control of a machine is built-in. Although the economy is not a machine, but an intensely connected complex of ever emerging businesses, the process of control needs to be structured in a similar manner. Pricing investment risk in this environment should never have been left to opaque institutions, or processes that do not recognise the co-dependencies of business and systemic functionality. To do so is to ignore the correlation of events in a highly connected world. These events are dynamic and conditional, whose outturns are unknowable. This does not mean unmanageable, but that the control process be built-in to businesses and government in a consistent manner, transparent yet using different parameters. Transparent means that data, assumptions and processes need to be monitored and published in timely manner. As far as accounting for results is concerned it should be recognised that budgeting and reporting to investors is founded on dynamic processes that are therefore changeable; usually out of date; and co-dependent upon others within a complex dynamic network that is both internal and external to the business. The works of Stafford Beer (Brain of the Firm, Heart of the Enterprise, Diagnosing the System) Fredrick Vestor (The Art of Interconnected Thinking) and others are examples of how to manage the internal dynamics of a business and point to a methodology that synthesises the approaches of investors such as Warren Buffett so that extreme outcomes such as the Credit-Crunch 2008 can be reduced in frequency but investors are free to ‘take their risks’. This research aims to compare two extreme events in the financial arena, the ‘Reinsurance Spiral of the late 1980s’ and the ‘2008 Credit-Crunch’, show their commonalities and propose methods that supply liquidity in all but gross systemic failure and allow investment risk to be more ably assessed and priced. It is not meant to be an exhaustive analysis but one focused on how ignoring the proper relationship of time, functions and processes brought about the current problem in both insurance and the capital markets and how a solution may be found. This research note offers an overview on the ongoing PhD research on the topic.

ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation

Malnutrition affects up to one billion people in the world and is a major cause of mortality. In many cases, malnutrition is associated with diarrhoea and intestinal inflammation, further contributing to morbidity and death. The mechanisms by which unbalanced dietary nutrients affect intestinal homeostasis are largely unknown. Here we report that deficiency in murine angiotensin I converting enzyme (peptidyl-dipeptidase A) 2 (Ace2), which encodes a key regulatory enzyme of the renin-angiotensin system (RAS), results in highly increased susceptibility to intestinal inflammation induced by epithelial damage. The RAS is known to be involved in acute lung failure, cardiovascular functions and SARS infections. Mechanistically, ACE2 has a RAS-independent function, regulating intestinal amino acid homeostasis, expression of antimicrobial peptides, and the ecology of the gut microbiome. Transplantation of the altered microbiota from Ace2 mutant mice into germ-free wild-type hosts was able to transmit the increased propensity to develop severe colitis. ACE2-dependent changes in epithelial immunity and the gut microbiota can be directly regulated by the dietary amino acid tryptophan. Our results identify ACE2 as a key regulator of dietary amino acid homeostasis, innate immunity, gut microbial ecology, and transmissible susceptibility to colitis. These results provide a molecular explanation for how amino acid malnutrition can cause intestinal inflammation and diarrhoea.     

Light-cone-like spreading of correlations in a quantum many-body system

In relativistic quantum field theory, information propagation is bounded by the speed of light. No such limit exists in the non-relativistic case, although in real physical systems, short-range interactions may be expected to restrict the propagation of information to finite velocities. The question of how fast correlations can spread in quantum many-body systems has been long studied. The existence of a maximal velocity, known as the Lieb-Robinson bound, has been shown theoretically to exist in several interacting many-body systems (for example, spins on a lattice)--such systems can be regarded as exhibiting an effective light cone that bounds the propagation speed of correlations. The existence of such a 'speed of light' has profound implications for condensed matter physics and quantum information, but has not been observed experimentally. Here we report the time-resolved detection of propagating correlations in an interacting quantum many-body system. By quenching a one-dimensional quantum gas in an optical lattice, we reveal how quasiparticle pairs transport correlations with a finite velocity across the system, resulting in an effective light cone for the quantum dynamics. Our results open perspectives for understanding the relaxation of closed quantum systems far from equilibrium, and for engineering the efficient quantum channels necessary for fast quantum computations.