Characteristics of Sleep–Wakefulness Cycle and Circadian Activity in the Lesser Mouse-Deer (Tragulus kanchil)

Doklady Biological Sciences - The pattern of sleep and circadian activity of the lesser mouse-deer (Tragulus kanchil) that is the smallest (body mass between 1.5 and 2.2 kg) representative of the...     

A novel allele of the Arabidopsis thaliana MACPF protein CAD1 results in deregulated immune signaling

Immune recognition in plants is governed by two major classes of receptors: pattern recognition receptors (PRRs) and nucleotide-binding leucine-rich repeat receptors (NLRs). Located at the cell surface, PRRs bind extracellular ligands originating from microbes (indicative of “non-self”) or damaged plant cells (indicative of “infected-self”), and trigger signaling cascades to protect against infection. Located intracellularly, NLRs sense pathogen-induced physiological changes and trigger localized cell death and systemic resistance. Immune responses are under tight regulation in order to maintain homeostasis and promote plant health. In a forward-genetic screen to identify regulators of PRR-mediated immune signaling, we identified a novel allele of the membrane-attack complex and perforin (MACPF)-motif containing protein CONSTITUTIVE ACTIVE DEFENSE 1 (CAD1) resulting from a missense mutation in a conserved N-terminal cysteine. We show that cad1-5 mutants display deregulated immune signaling and symptoms of autoimmunity dependent on the lipase-like protein ENHANCED DISEASE SUSCEPTIBILITY 1 (EDS1), suggesting that CAD1 integrity is monitored by the plant immune system. We further demonstrate that CAD1 localizes to both the cytosol and plasma membrane using confocal microscopy and subcellular fractionation. Our results offer new insights into immune homeostasis and provide tools to further decipher the intriguing role of MACPF proteins in plants.     

Conditional and domain‐specific inactivation of the Tsc2 gene in neural progenitor cells

Tuberous sclerosis complex (TSC) is a genetic disease characterized by multiorgan benign tumors as well as neurological manifestations. Epilepsy and autism are two of the more prevalent neurological complications and are usually severe. TSC is caused by mutations in either the TSC1 (encodes hamartin) or the TSC2 (encodes tuberin) genes with TSC2 mutations being associated with worse outcomes. Tuberin contains a highly conserved GTPase‐activating protein (GAP) domain that indirectly inhibits mammalian target of rapamycin complex 1 (mTORC1). mTORC1 dysregulation is currently thought to cause much of the pathogenesis in TSC but mTORC1‐independent mechanisms may also contribute. We generated a novel conditional allele of Tsc2 by flanking exons 36 and 37 with loxP sites. Mice homozygous for this knock‐in Tsc2 allele are viable and fertile with normal appearing growth and development. Exposure to Cre recombinase then creates an in‐frame deletion involving critical residues of the GAP domain. Homozygous conditional mutant mice generated using Emx1^Cre have increased cortical mTORC1 signaling, severe developmental brain anomalies, seizures, and die within 3 weeks. We found that the normal levels of the mutant Tsc2 mRNA, though GAP‐deficient tuberin protein, appear unstable and rapidly degraded. This novel animal model will allow further study of tuberin function including the requirement of the GAP domain for protein stability. genesis 51:284–292. © 2013 Wiley Periodicals, Inc.     

Will You Accept the Government's Friend Request? Social Networks and Privacy Concerns

Participating in social network websites entails voluntarily sharing private information, and the explosive growth of social network websites over the last decade suggests shifting views on privacy. Concurrently, new anti-terrorism laws, such as the USA Patriot Act, ask citizens to surrender substantial claim to privacy in the name of greater security. I address two important questions regarding individuals'' views on privacy raised by these trends. First, how does prompting individuals to consider security concerns affect their views on government actions that jeopardize privacy? Second, does the use of social network websites alter the effect of prompted security concerns? I posit that prompting individuals to consider security concerns does lead to an increased willingness to accept government actions that jeopardize privacy, but that frequent users of websites like Facebook are less likely to be swayed by prompted security concerns. An embedded survey experiment provides support for both parts of my claim.     

AMPK Is a Negative Regulator of the Warburg Effect and Suppresses Tumor Growth In Vivo

1. Download : Download high-res image (85KB)
2. Download : Download full-size image

Highlights? Loss of AMPKα1 cooperates with the Myc oncogene to accelerate lymphomagenesis ? AMPKα dysfunction enhances aerobic glycolysis (Warburg effect) ? Inhibiting HIF-1α reverses the metabolic effects of AMPKα loss ? HIF-1α mediates the growth advantage of tumors with reduced AMPK signaling     

Seascape genetics of the stalked kelp Pterygophora californica and comparative population genetics in the Santa Barbara Channel

We conducted a population genetic analysis of the stalked kelp, Pterygophora californica, in the Santa Barbara Channel, California, USA. The results were compared with previous work on the genetic differentiation of giant kelp, Macrocystis pyrifera, in the same region. These two sympatric kelps not only share many life history and dispersal characteristics but also differ in that dislodged P. californica does not produce floating rafts with buoyant fertile sporophytes, commonly observed for M. pyrifera. We used a comparative population genetic approach with these two species to test the hypothesis that the ability to produce floating rafts increases the genetic connectivity among kelp patches in the Santa Barbara Channel. We quantified the association of habitat continuity and oceanographic distance with the genetic differentiation observed in stalked kelp, like previously conducted for giant kelp. We compared both overall (across all patches) and pairwise (between patches) genetic differentiation. We found that oceanographic transit time, habitat continuity, and geographic distance were all associated with genetic connectivity in P. californica, supporting similar previous findings for M. pyrifera. Controlling for differences in heterozygosity between kelp species using Jost's D_EST, we showed that global differentiation and pairwise differentiation were similar among patches between the two kelp species, indicating that they have similar dispersal capabilities despite their differences in rafting ability. These results suggest that rafting sporophytes do not play a significant role in effective dispersal of M. pyrifera at ecologically relevant spatial and temporal scales.     

Transfer of Natural Micro Structures to Bionic Lightweight Design Proposals

The abstraction of complex biological lightweight structure features into a producible technical component is a funda- mental step within the transfer of design principles from nature to technical lightweight solutions. A major obstacle for the transfer of natural lightweight structures to technical solutions is their peculiar geometry. Since natural lightweight structures possess irregularities and often have extremely complex forms due to elaborate growth processes, it is usually necessary to simplify their design principles. This step of simplification/abstraction has been used in different biomimetic methods, but so far, it has an arbitrary component, i.e. it crucially depends on the competence of the person who executes the abstraction. This paper describes a new method for abstraction and specialization of natural micro structures for technical lightweight compo- nents. The new method generates stable lightweight design principles by using topology optimization within a design space of preselected biological archetypes such as diatoms or radiolarian. The resulting solutions are adapted to the technical load cases and production processes, can be created in a large variety, and may be further optimized e.g. by using parametric optimization.     

Economic Evaluation of Multisystemic Therapy for Young People at Risk for Continuing Criminal Activity in the UK

Objective

To evaluate whether multisystemic therapy (MST) is more cost-effective than statutory interventions that are currently available for young offenders in England.

Method

A cost-offset evaluation of MST based on data from a randomised controlled trial conducted in North London, England, comparing MST with usual services provided by two youth offending teams (YOT). Service costs were compared to cost savings in terms of rates of criminal re-offending.

Results

108 adolescents, aged 11–17 years, were randomly allocated to MST+YOT (n = 56) or YOT alone (n = 52). Reductions in offending were evident in both groups, but were higher in the MST+YOT group. At 18-month follow-up, the MST+YOT group cost less in terms of criminal activity (£9,425 versus £11,715, p = 0.456). The MST+YOT group were significantly cheaper in terms of YOT services than the YOT group (£3,402 versus £4,619, p = 0.006), but more expensive including the cost of MST, although not significantly so (£5,687 versus £4,619, p = 0.195). The net benefit per young person for the 18-month follow-up was estimated to be £1,222 (95% CI −£5,838 to £8,283).

Conclusions

The results reported in this study support the finding that MST+YOT has scope for cost-savings when compared to YOT alone. However, the limitations of the study in terms of method of economic evaluation, outcome measures used and data quality support the need for further research.