Transmembrane semaphorin signalling controls laminar stratification in the mammalian retina

In the vertebrate retina, establishment of precise synaptic connections among distinct retinal neuron cell types is critical for processing visual information and for accurate visual perception. Retinal ganglion cells (RGCs), amacrine cells and bipolar cells establish stereotypic neurite arborization patterns to form functional neural circuits in the inner plexiform layer (IPL), a laminar region that is conventionally divided into five major parallel sublaminae. However, the molecular mechanisms governing distinct retinal subtype targeting to specific sublaminae within the IPL remain to be elucidated. Here we show that the transmembrane semaphorin Sema6A signals through its receptor PlexinA4 (PlexA4) to control lamina-specific neuronal stratification in the mouse retina. Expression analyses demonstrate that Sema6A and PlexA4 proteins are expressed in a complementary fashion in the developing retina: Sema6A in most ON sublaminae and PlexA4 in OFF sublaminae of the IPL. Mice with null mutations in PlexA4 or Sema6A exhibit severe defects in stereotypic lamina-specific neurite arborization of tyrosine hydroxylase (TH)-expressing dopaminergic amacrine cells, intrinsically photosensitive RGCs (ipRGCs) and calbindin-positive cells in the IPL. Sema6A and PlexA4 genetically interact in vivo for the regulation of dopaminergic amacrine cell laminar targeting. Therefore, neuronal targeting to subdivisions of the IPL in the mammalian retina is directed by repulsive transmembrane guidance cues present on neuronal processes.     

A novel protein family mediates Casparian strip formation in the endodermis

Polarized epithelia are fundamental to multicellular life. In animal epithelia, conserved junctional complexes establish membrane diffusion barriers, cellular adherence and sealing of the extracellular space. Plant cellular barriers are of independent evolutionary origin. The root endodermis strongly resembles a polarized epithelium and functions in nutrient uptake and stress resistance. Its defining features are the Casparian strips, belts of specialized cell wall material that generate an extracellular diffusion barrier. The mechanisms localizing Casparian strips are unknown. Here we identify and characterize a family of transmembrane proteins of previously unknown function. These 'CASPs' (Casparian strip membrane domain proteins) specifically mark a membrane domain that predicts the formation of Casparian strips. CASP1 displays numerous features required for a constituent of a plant junctional complex: it forms complexes with other CASPs; it becomes immobile upon localization; and it sediments like a large polymer. CASP double mutants display disorganized Casparian strips, demonstrating a role for CASPs in structuring and localizing this cell wall modification. To our knowledge, CASPs are the first molecular factors that are shown to establish a plasma membrane and extracellular diffusion barrier in plants, and represent a novel way of epithelial barrier formation in eukaryotes.     

Quantum storage of photonic entanglement in a crystal

Entanglement is the fundamental characteristic of quantum physics-much experimental effort is devoted to harnessing it between various physical systems. In particular, entanglement between light and material systems is interesting owing to their anticipated respective roles as 'flying' and stationary qubits in quantum information technologies (such as quantum repeaters and quantum networks). Here we report the demonstration of entanglement between a photon at a telecommunication wavelength (1,338?nm) and a single collective atomic excitation stored in a crystal. One photon from an energy-time entangled pair is mapped onto the crystal and then released into a well-defined spatial mode after a predetermined storage time. The other (telecommunication wavelength) photon is sent directly through a 50-metre fibre link to an analyser. Successful storage of entanglement in the crystal is proved by a violation of the Clauser-Horne-Shimony-Holt inequality by almost three standard deviations (S = 2.64?±?0.23). These results represent an important step towards quantum communication technologies based on solid-state devices. In particular, our resources pave the way for building multiplexed quantum repeaters for long-distance quantum networks.     

Broadband waveguide quantum memory for entangled photons

The reversible transfer of quantum states of light into and out of matter constitutes an important building block for future applications of quantum communication: it will allow the synchronization of quantum information, and the construction of quantum repeaters and quantum networks. Much effort has been devoted to the development of such quantum memories, the key property of which is the preservation of entanglement during storage. Here we report the reversible transfer of photon-photon entanglement into entanglement between a photon and a collective atomic excitation in a solid-state device. Towards this end, we employ a thulium-doped lithium niobate waveguide in conjunction with a photon-echo quantum memory protocol, and increase the spectral acceptance from the current maximum of 100?megahertz to 5?gigahertz. We assess the entanglement-preserving nature of our storage device through Bell inequality violations and by comparing the amount of entanglement contained in the detected photon pairs before and after the reversible transfer. These measurements show, within statistical error, a perfect mapping process. Our broadband quantum memory complements the family of robust, integrated lithium niobate devices. It simplifies frequency-matching of light with matter interfaces in advanced applications of quantum communication, bringing fully quantum-enabled networks a step closer.     

Species-specific responses of Late Quaternary megafauna to climate and humans

Despite decades of research, the roles of climate and humans in driving the dramatic extinctions of large-bodied mammals during the Late Quaternary period remain contentious. Here we use ancient DNA, species distribution models and the human fossil record to elucidate how climate and humans shaped the demographic history of woolly rhinoceros, woolly mammoth, wild horse, reindeer, bison and musk ox. We show that climate has been a major driver of population change over the past 50,000 years. However, each species responds differently to the effects of climatic shifts, habitat redistribution and human encroachment. Although climate change alone can explain the extinction of some species, such as Eurasian musk ox and woolly rhinoceros, a combination of climatic and anthropogenic effects appears to be responsible for the extinction of others, including Eurasian steppe bison and wild horse. We find no genetic signature or any distinctive range dynamics distinguishing extinct from surviving species, emphasizing the challenges associated with predicting future responses of extant mammals to climate and human-mediated habitat change.     

Low retinal noise in animals with low body temperature allows high visual sensitivity

The weakest pulse of light a human can detect sends about 100 photons through the pupil and produces 10-20 rhodopsin isomerizations in a small retinal area. It has been postulated that we cannot see single photons because of a retinal noise arising from randomly occurring thermal isomerizations. Direct recordings have since demonstrated the existence of electrical 'dark' rod events indistinguishable from photoisomerization signals. Their mean rate of occurrence is roughly consistent with the 'dark light' in psychophysical threshold experiments, and their thermal parameters justify an identification with thermal isomerizations. In the retina of amphibians, a small proportion of sensitive ganglion cells have a performance-limiting noise that is low enough to be well accounted for by these events. Here we study the performance of dark-adapted toads and frogs and show that the performance limit of visually guided behaviour is also set by thermal isomerizations. As visual sensitivity limited by thermal events should rise when the temperature falls, poikilothermous vertebrates living at low temperatures should then reach light sensitivities unattainable by mammals and birds with optical factors equal. Comparison of different species at different temperatures shows a correlation between absolute threshold intensities and estimated thermal isomerization rates in the retina.     

Active gamma-carboxylated human factor IX expressed using recombinant DNA techniques

Factor IX (Christmas factor), a vitamin K-dependent plasma protein made in the liver, functions in the middle phase of the intrinsic pathway of blood coagulation. A functional deficiency of factor IX underlies haemophilia B, a chromosome X-linked recessive disease for which the major therapeutic approach is replacement treatment using factor IX concentrates. The cloning and characterization of the gene for human factor IX would mean that human factor IX could be produced in greater yield and purity through using recombinant DNA techniques. We have now used a human factor IX cDNA clone, inserted into a vaccinia virus-derived vector, to infect human hepatoma cells which normally produce no factor IX, and mouse fibroblasts. Fully active factor IX was produced by the hepatoma cells, whereas the fibroblasts produced a protein less active than natural factor IX, even in the presence of high levels of vitamin K. Human factor IX is extensively post-translationally modified, and thus represents probably the most complex protein produced in active form by recombinant DNA techniques to date. Our study also illustrates the potential of vaccinia virus-based vectors for expressing significant amounts of complex, clinically useful proteins in eukaryotic cells, in addition to its already demonstrated usefulness for producing live recombinant vaccines.