Regulation of angiogenesis by a non-canonical Wnt-Flt1 pathway in myeloid cells

Myeloid cells are a feature of most tissues. Here we show that during development, retinal myeloid cells (RMCs) produce Wnt ligands to regulate blood vessel branching. In the mouse retina, where angiogenesis occurs postnatally, somatic deletion in RMCs of the Wnt ligand transporter Wntless results in increased angiogenesis in the deeper layers. We also show that mutation of Wnt5a and Wnt11 results in increased angiogenesis and that these ligands elicit RMC responses via a non-canonical Wnt pathway. Using cultured myeloid-like cells and RMC somatic deletion of Flt1, we show that an effector of Wnt-dependent suppression of angiogenesis by RMCs is Flt1, a naturally occurring inhibitor of vascular endothelial growth factor (VEGF). These findings indicate that resident myeloid cells can use a non-canonical, Wnt-Flt1 pathway to suppress angiogenic branching.     

Theta-paced flickering between place-cell maps in the hippocampus

The ability to recall discrete memories is thought to depend on the formation of attractor states in recurrent neural networks. In such networks, representations can be reactivated reliably from subsets of the cues that were present when the memory was encoded, at the same time as interference from competing representations is minimized. Theoretical studies have pointed to the recurrent CA3 system of the hippocampus as a possible attractor network. Consistent with predictions from these studies, experiments have shown that place representations in CA3 and downstream CA1 tolerate small changes in the configuration of the environment but switch to uncorrelated representations when dissimilarities become larger. However, the kinetics supporting such network transitions, at the subsecond timescale, is poorly understood. Here we show in rats that instantaneous transformation of the spatial context does not change the hippocampal representation all at once but is followed by temporary bistability in the discharge activity of CA3 ensembles. Rather than sliding through a continuum of intermediate activity states, the CA3 network undergoes a short period of competitive flickering between preformed representations of the past and present environment before settling on the latter. Network flickers are extremely fast, often with complete replacement of the active ensemble from one theta cycle to the next. Within individual cycles, segregation is stronger towards the end, when firing starts to decline, pointing to the theta cycle as a temporal unit for expression of attractor states in the hippocampus. Repetition of pattern-completion processes across successive theta cycles may facilitate error correction and enhance discriminative power in the presence of weak and ambiguous input cues.     

Taking up statistical thermodynamics: Equilibrium fluctuations and irreversibility

The microscopic explanation of the physical phenomena represented by a macroscopic theory is often cast in terms of the reduction of the latter to a more fundamental theory, which represents the same phenomena at the microscopic level, albeit in an idealized way. In particular, the reduction of thermodynamics to statistical mechanics is a much discussed case-study in philosophy of physics. Based on the Generalized Nagel–Schaffner model, the alleged reductive explanation would be accomplished if one finds a corrected version of classical thermodynamics that can be strictly derived from statistical mechanics. That is the sense in which, according to Callender (1999, 2001), one should not take thermodynamics too seriously. Arguably, the sought-after revision is given by statistical thermodynamics, intended as a macroscopic theory equipped with a probabilistic law of equilibrium fluctuations. The present paper aims to evaluate this proposal. The upshot is that, while statistical thermodynamics enables one to re-define equilibrium so as to agree with Boltzmann entropy, it does not provide a definitive solution to the problem of explaining macroscopic irreversibility from a microscopic point of view.     

Dynamical Criticality: Overview and Open Questions

Systems that exhibit complex behaviours are often found in a particular dynamical condition, poised between order and disorder. This observation is at the core of the so-called criticality hypothesis, which states that systems in a dynamical regime between order and disorder attain the highest level of computational capabilities and achieve an optimal trade-off between robustness and flexibility. Recent results in cellular and evolutionary biology, neuroscience and computer science have revitalised the interest in the criticality hypothesis, emphasising its role as a viable candidate general law in adaptive complex systems. This paper provides an overview of the works on dynamical criticality that are — To the best of our knowledge — Particularly relevant for the criticality hypothesis. The authors review the main contributions concerning dynamics and information processing at the edge of chaos, and illustrate the main achievements in the study of critical dynamics in biological systems.Finally, the authors discuss open questions and propose an agenda for future work.     

Rab5 is necessary for the biogenesis of the endolysosomal system in vivo

An outstanding question is how cells control the number and size of membrane organelles. The small GTPase Rab5 has been proposed to be a master regulator of endosome biogenesis. Here, to test this hypothesis, we developed a mathematical model of endosome dependency on Rab5 and validated it by titrating down all three Rab5 isoforms in adult mouse liver using state-of-the-art RNA interference technology. Unexpectedly, the endocytic system was resilient to depletion of Rab5 and collapsed only when Rab5 decreased to a critical level. Loss of Rab5 below this threshold caused a marked reduction in the number of early endosomes, late endosomes and lysosomes, associated with a block of low-density lipoprotein endocytosis. Loss of endosomes caused failure to deliver apical proteins to the bile canaliculi, suggesting a requirement for polarized cargo sorting. Our results demonstrate for the first time, to our knowledge, the role of Rab5 as an endosome organizer in vivo and reveal the resilience mechanisms of the endocytic system.     

Reconciling the temperature dependence of respiration across timescales and ecosystem types

Ecosystem respiration is the biotic conversion of organic carbon to carbon dioxide by all of the organisms in an ecosystem, including both consumers and primary producers. Respiration exhibits an exponential temperature dependence at the subcellular and individual levels, but at the ecosystem level respiration can be modified by many variables including community abundance and biomass, which vary substantially among ecosystems. Despite its importance for predicting the responses of the biosphere to climate change, it is as yet unknown whether the temperature dependence of ecosystem respiration varies systematically between aquatic and terrestrial environments. Here we use the largest database of respiratory measurements yet compiled to show that the sensitivity of ecosystem respiration to seasonal changes in temperature is remarkably similar for diverse environments encompassing lakes, rivers, estuaries, the open ocean and forested and non-forested terrestrial ecosystems, with an average activation energy similar to that of the respiratory complex (approximately 0.65?electronvolts (eV)). By contrast, annual ecosystem respiration shows a substantially greater temperature dependence across aquatic (approximately 0.65?eV) versus terrestrial ecosystems (approximately 0.32?eV) that span broad geographic gradients in temperature. Using a model derived from metabolic theory, these findings can be reconciled by similarities in the biochemical kinetics of metabolism at the subcellular level, and fundamental differences in the importance of other variables besides temperature—such as primary productivity and allochthonous carbon inputs—on the structure of aquatic and terrestrial biota at the community level.     

Iron meteorites as remnants of planetesimals formed in the terrestrial planet region

Iron meteorites are core fragments from differentiated and subsequently disrupted planetesimals. The parent bodies are usually assumed to have formed in the main asteroid belt, which is the source of most meteorites. Observational evidence, however, does not indicate that differentiated bodies or their fragments were ever common there. This view is also difficult to reconcile with the fact that the parent bodies of iron meteorites were as small as 20 km in diameter and that they formed 1-2 Myr earlier than the parent bodies of the ordinary chondrites. Here we show that the iron-meteorite parent bodies most probably formed in the terrestrial planet region. Fast accretion times there allowed small planetesimals to melt early in Solar System history by the decay of short-lived radionuclides (such as 26Al, 60Fe). The protoplanets emerging from this population not only induced collisional evolution among the remaining planetesimals but also scattered some of the survivors into the main belt, where they stayed for billions of years before escaping via a combination of collisions, Yarkovsky thermal forces, and resonances. We predict that some asteroids are main-belt interlopers (such as (4) Vesta). A select few may even be remnants of the long-lost precursor material that formed the Earth.     

Rescue of a deficiency in ATP synthesis by transfer of MTATP6, a mitochondrial DNA-encoded gene, to the nucleus

A T-->G transversion at nt 8993 in mitochondrial DNA of MTATP6 (encoding ATPase 6 of complex V of the respiratory chain) causes impaired mitochondrial ATP synthesis in two related mitochondrial disorders: neuropathy, ataxia and retinitis pigmentosa and maternally inherited Leigh syndrome. To overcome the biochemical defect, we expressed wildtype ATPase 6 protein allotopically from nucleus-transfected constructs encoding an amino-terminal mitochondrial targeting signal appended to a recoded ATPase 6 gene (made compatible with the universal genetic code) that also contained a carboxy-terminal FLAG epitope tag. After transfection of human cells, the precursor polypeptide was expressed, imported into and processed within mitochondria, and incorporated into complex V. Allotopic expression of stably transfected constructs in cytoplasmic hybrids (cybrids) homoplasmic with respect to the 8993T-->G mutation showed a significantly improved recovery after growth in selective medium as well as a significant increase in ATP synthesis. This is the first successful demonstration of allotopic expression of an mtDNA-encoded polypeptide in mammalian cells and could form the basis of a genetic approach to treat a number of human mitochondrial disorders.     

Single-substrate liquid-crystal displays by photo-enforced stratification

Data visualization plays a crucial role in our society, as illustrated by the many displays that surround us. In the future, displays may become even more pervasive, ranging from individually addressable image-rendering wall hangings to data displays integrated in clothes. Liquid-crystal displays (LCDs) provide most of the flat-panel displays currently used. To keep pace with the ever-increasing possibilities afforded by developments in information technology, we need to develop manufacturing processes that will make LCDs cheaper and larger, with more freedom in design. Existing batch processes for making and filling LCD cells are relatively expensive, with size and shape limitations. Here we report a cost-effective, single-substrate technique in which a coated film is transformed into a polymer-covered liquid-crystal layer. This approach is based on photo-enforced stratification: a two-step photopolymerization-induced phase separation of a liquid-crystal blend and a polymer precursor. The process leads to the formation of micrometre-sized containers filled with a switchable liquid-crystal phase. In this way, displays can be produced on a variety of substrates using current coating technology. The developed process may be an important step towards new technologies such as 'display-on-anything' and 'paintable displays'.     

Terahertz semiconductor-heterostructure laser

Semiconductor devices have become indispensable for generating electromagnetic radiation in everyday applications. Visible and infrared diode lasers are at the core of information technology, and at the other end of the spectrum, microwave and radio-frequency emitters enable wireless communications. But the terahertz region (1-10 THz; 1 THz = 10(12) Hz) between these ranges has remained largely underdeveloped, despite the identification of various possible applications--for example, chemical detection, astronomy and medical imaging. Progress in this area has been hampered by the lack of compact, low-consumption, solid-state terahertz sources. Here we report a monolithic terahertz injection laser that is based on interminiband transitions in the conduction band of a semiconductor (GaAs/AlGaAs) heterostructure. The prototype demonstrated emits a single mode at 4.4 THz, and already shows high output powers of more than 2 mW with low threshold current densities of about a few hundred A cm(-2) up to 50 K. These results are very promising for extending the present laser concept to continuous-wave and high-temperature operation, which would lead to implementation in practical photonic systems.