Disruption of fusion results in mitochondrial heterogeneity and dysfunction

Mitochondria undergo continual cycles of fusion and fission, and the balance of these opposing processes regulates mitochondrial morphology. Paradoxically, cells invest many resources to maintain tubular mitochondrial morphology, when reducing both fusion and fission simultaneously achieves the same end. This observation suggests a requirement for mitochondrial fusion, beyond maintenance of organelle morphology. Here, we show that cells with targeted null mutations in Mfn1 or Mfn2 retained low levels of mitochondrial fusion and escaped major cellular dysfunction. Analysis of these mutant cells showed that both homotypic and heterotypic interactions of Mfns are capable of fusion. In contrast, cells lacking both Mfn1 and Mfn2 completely lacked mitochondrial fusion and showed severe cellular defects, including poor cell growth, widespread heterogeneity of mitochondrial membrane potential, and decreased cellular respiration. Disruption of OPA1 by RNAi also blocked all mitochondrial fusion and resulted in similar cellular defects. These defects in Mfn-null or OPA1-RNAi mammalian cells were corrected upon restoration of mitochondrial fusion, unlike the irreversible defects found in fzo yeast. In contrast, fragmentation of mitochondria, without severe loss of fusion, did not result in such cellular defects. Our results showed that key cellular functions decline as mitochondrial fusion is progressively abrogated

An O(n^5) algorithm for MFE prediction of kissing hairpins and 4-chains in nucleic acids

Efficient methods for prediction of minimum free energy (MFE) nucleic secondary structures are widely used, both to better understand structure and function of biological RNAs and to design novel nano-structures. Here, we present a new algorithm for MFE secondary structure prediction, which significantly expands the class of structures that can be handled in O(n^5) time. Our algorithm can handle H-type pseudoknotted structures, kissing hairpins, and chains of four overlapping stems, as well as nested substructures of these types

Organic school food policies are supportive for healthier eating behaviours – results from an observational study in Danish schools

Purpose – The purpose of this study was to examine whether organic food intervention strategies in Danish school meal systems can support the development of healthier eating patterns among pupils. Design/methodology/approach – This paper investigates the interrelation between the two trends: healthy eating and organic consumption. The study was undertaken among school food coordinators through a web-based questionnaire in selected Danish public primary schools. Food strategies of “organic” schools were compared to those of “non organic” schools. The questionnaire explored the attitudes, policies/intentions and actions in relation to organic and healthy foods served in the schools. Findings – Results indicate that organic food intervention strategies can be supportive for strategies to increase the healthiness of school eating patterns. Social implications – The municipalities and other public bodies increasingly recognize their responsibility to support sustainable food production methods, such as organic agriculture, by choosing this kind of foods in public institutions. Originality/value – This paper provides the organic food strategies in schools that may increase the availability of healthier food options and promote healthy eating habits for pupils

A note on uniform power connectivity in the SINR model

In this paper we study the connectivity problem for wireless networks under the Signal to Interference plus Noise Ratio (SINR) model. Given a set of radio transmitters distributed in some area, we seek to build a directed strongly connected communication graph, and compute an edge coloring of this graph such that the transmitter-receiver pairs in each color class can communicate simultaneously. Depending on the interference model, more or less colors, corresponding to the number of frequencies or time slots, are necessary. We consider the SINR model that compares the received power of a signal at a receiver to the sum of the strength of other signals plus ambient noise . The strength of a signal is assumed to fade polynomially with the distance from the sender, depending on the so-called path-loss exponent $\alpha$. We show that, when all transmitters use the same power, the number of colors needed is constant in one-dimensional grids if $\alpha>1$ as well as in two-dimensional grids if $\alpha>2$. For smaller path-loss exponents and two-dimensional grids we prove upper and lower bounds in the order of $\mathcal{O}(\log n)$ and $\Omega(\log n/\log\log n)$ for $\alpha=2$ and $\Theta(n^{2/\alpha-1})$ for $\alpha<2$ respectively. If nodes are distributed uniformly at random on the interval $[0,1]$, a \emph{regular} coloring of $\mathcal{O}(\log n)$ colors guarantees connectivity, while $\Omega(\log \log n)$ colors are required for any coloring.Comment: 13 page

A Dynamin-3 Spliced Variant Modulates the Actin/Cortactin-Dependent Morphogenesis of Dendritic Spines

Immature dendrites extend many actin-rich filopodial structures that can be replaced by synapse-containing dendritic spines as the neuron matures. The large GTPase dynamin-3 (Dyn3) is a component of the postsynapse in hippocampal neurons but its function is undefined. Here, we demonstrate that a specific Dyn3 variant (Dyn3baa) promotes the formation of immature dendritic filopodia in cultured neurons. This effect is dependent upon Dyn3 GTPase activity and a direct interaction with the F-actin-binding protein cortactin. Consistent with these findings, Dyn3baa binds to cortactin with a 200% higher affinity than Dyn3aaa, a near identical isoform that does not induce dendritic filopodia when expressed in cultured neurons. Finally, levels of Dyn3baa-encoding mRNA are tightly regulated during neuronal maturation and are markedly upregulated during synaptogenesis. Together, these findings provide the first evidence that an enhanced interaction between a specific Dyn3 splice variant and cortactin modulate actin-membrane dynamics in developing neurons to regulate the morphogenesis of dendritic spines. Supplementary material available online at http://jcs.biologists.org/cgi/content/full/118/6/1279/DC

Genome-wide screen for genes involved in Caenorhabditis elegans developmentally timed sleep

In Caenorhabditis elegans, Notch signaling regulates developmentally timed sleep during the transition from L4 larval stage to adulthood (L4/A) . To identify core sleep pathways and to find genes acting downstream of Notch signaling, we undertook the first genome-wide, classical genetic screen focused on C. elegans developmentally timed sleep. To increase screen efficiency, we first looked for mutations that suppressed inappropriate anachronistic sleep in adult hsp::osm-11 animals overexpressing the Notch coligand OSM-11 after heat shock. We retained suppressor lines that also had defects in L4/A developmentally timed sleep, without heat shock overexpression of the Notch coligand. Sixteen suppressor lines with defects in developmentally timed sleep were identified. One line carried a new allele of goa-1; loss of GOA-1 Gαo decreased C. elegans sleep. Another line carried a new allele of gpb-2, encoding a Gβ5 protein; Gβ5 proteins have not been previously implicated in sleep. In other scenarios, Gβ5 GPB-2 acts with regulators of G protein signaling (RGS proteins) EAT-16 and EGL-10 to terminate either EGL-30 Gαq signaling or GOA-1 Gαo signaling, respectively. We found that loss of Gβ5 GPB-2 or RGS EAT-16 decreased L4/A sleep. By contrast, EGL-10 loss had no impact. Instead, loss of RGS-1 and RGS-2 increased sleep. Combined, our results suggest that, in the context of L4/A sleep, GPB-2 predominantly acts with EAT-16 RGS to inhibit EGL-30 Gαq signaling. These results confirm the importance of G protein signaling in sleep and demonstrate that these core sleep pathways function genetically downstream of the Notch signaling events promoting sleep