Foreign intelligence in the digital age. Navigating a state of ‘unpeace’.

Security and Global AffairsCybersecurity en cybergovernanc

High frequency burst firing of granule cells ensures transmission at the parallel fiber to purkinje cell synapse at the cost of temporal coding.

Cerebellar granule cells (GrCs) convey information from mossy fibers (MFs) to Purkinje cells (PCs) via their parallel fibers (PFs). MF to GrC signaling allows transmission of frequencies up to 1 kHz and GrCs themselves can also fire bursts of action potentials with instantaneous frequencies up to 1 kHz. So far, in the scientific literature no evidence has been shown that these high-frequency bursts also exist in awake, behaving animals. More so, it remains to be shown whether such high-frequency bursts can transmit temporally coded information from MFs to PCs and/or whether these patterns of activity contribute to the spatiotemporal filtering properties of the GrC layer. Here, we show that, upon sensory stimulation in both un-anesthetized rabbits and mice, GrCs can show bursts that consist of tens of spikes at instantaneous frequencies over 800 Hz. In vitro recordings from individual GrC-PC pairs following high-frequency stimulation revealed an overall low initial release probability of ~0.17. Nevertheless, high-frequency burst activity induced a short-lived facilitation to ensure signaling within the first few spikes, which was rapidly followed by a reduction in transmitter release. The facilitation rate among individual GrC-PC pairs was heterogeneously distributed and could be classified as either "reluctant" or "responsive" according to their release characteristics. Despite the variety of efficacy at individual connections, grouped activity in GrCs resulted in a linear relationship between PC response and PF burst duration at frequencies up to 300 Hz allowing rate coding to persist at the network level. Together, these findings support the hypothesis that the cerebellar granular layer acts as a spatiotemporal filter between MF input and PC output (D'Angelo and De Zeeuw, 2009)

Fatty fish and supplements are the greatest modifiable contributors to the serum 25-hydroxyvitamin D concentration in a multiethnic population

Objective: Because vitamin D synthesis is lower in a heavily pigmented skin than in a lighter skin, the relative contribution of determinants to the vitamin D concentration might differ between ethnic groups. The aim of this study was to assess the prevalence of vitamin D deficiency and the relative contribution of vitamin D consumption and exposure to sunlight to the vitamin D concentration in a multiethnic population. Design: Cross-sectional study. Patients A total of 613 adults aged 18-65 years from a random sample from general practices in the Netherlands (52 degrees N, 2003-05), stratified according to gender and ethnic group. Measurements Serum 25-hydroxyvitamin D [25(OH)D], PTH, ethnic group, sunlight exposure, consumption of foods and supplements rich in vitamin D. Results The prevalence (95% confidence interval) of vitamin D deficiency [serum 25(OH)D < 25 nmol/l] was higher in Turkish (41.3%; 32.5-50.1), Moroccan (36.5%; 26.9-46.1), Surinam South Asian (51.4%; 41.9-60.9), Surinam Creole (45.3%; 34.0-56.6), sub-Saharan African (19.3%; 9.1-29.5) and other adults (29.1%; 17.1-41.1) compared to the indigenous Dutch (5.9%; 1.3-10.5). Modifiable, significant determinants (standardized regression coefficients) for serum 25(OH)D concentration were: consumption of fatty fish (0.160), use of vitamin D supplements (0.142), area of uncovered skin (highest category 0.136; middle category 0.028), use of tanning bed (0.103), consumption of margarine (0.093) and preference for sun (0.089). We found no significant modification of ethnic group on the effect of sunlight determinants. Conclusion: Of the modifiable determinants, fatty fish and supplements are the greatest contributors to the serum 25(OH)D concentration in a multiethnic population.(aut. ref.

Odour-mediated orientation of beetles is influenced by age, sex and morph

The behaviour of insects is dictated by a combination of factors and may vary considerably between individuals, but small insects are often considered en masse and thus these differences can be overlooked. For example, the cowpea bruchid Callosobruchus maculatus F. exists naturally in two adult forms: the active (flight) form for dispersal, and the inactive (flightless), more fecund but shorter-lived form. Given that these morphs show dissimilar biology, it is possible that they differ in odour-mediated orientation and yet studies of this species frequently neglect to distinguish morph type, or are carried out only on the inactive morph. Along with sex and age of individual, adult morph could be an important variable determining the biology of this and similar species, informing studies on evolution, ecology and pest management. We used an olfactometer with motion-tracking to investigate whether the olfactory behaviour and orientation of C. maculatus towards infested and uninfested cowpeas and a plant-derived repellent compound, methyl salicylate, differed between morphs or sexes. We found significant differences between the behaviour of male and female beetles and beetles of different ages, as well as interactive effects of sex, morph and age, in response to both host and repellent odours. This study demonstrates that behavioural experiments on insects should control for sex and age, while also considering differences between adult morphs where present in insect species. This finding has broad implications for fundamental entomological research, particularly when exploring the relationships between physiology, behaviour and evolutionary biology, and the application of crop protection strategies

Process Drivers, Inter-Model Spread, and the Path Forward: A Review of Amplified Arctic Warming

This is the final version. Available on open access from Frontiers Media via the DOI in this recordArctic amplification (AA) is a coupled atmosphere-sea ice-ocean process. This understanding has evolved from the early concept of AA, as a consequence of snow-ice line progressions, through more than a century of research that has clarified the relevant processes and driving mechanisms of AA. The predictions made by early modeling studies, namely the fall/winter maximum, bottom-heavy structure, the prominence of surface albedo feedback, and the importance of stable stratification have withstood the scrutiny of multi-decadal observations and more complex models. Yet, the uncertainty in Arctic climate projections is larger than in any other region of the planet, making the assessment of high-impact, near-term regional changes difficult or impossible. Reducing this large spread in Arctic climate projections requires a quantitative process understanding. This manuscript aims to build such an understanding by synthesizing current knowledge of AA and to produce a set of recommendations to guide future research. It briefly reviews the history of AA science, summarizes observed Arctic changes, discusses modeling approaches and feedback diagnostics, and assesses the current understanding of the most relevant feedbacks to AA. These sections culminate in a conceptual model of the fundamental physical mechanisms causing AA and a collection of recommendations to accelerate progress towards reduced uncertainty in Arctic climate projections. Our conceptual model highlights the need to account for local feedback and remote process interactions within the context of the annual cycle to constrain projected AA. We recommend raising the priority of Arctic climate sensitivity research, improving the accuracy of Arctic surface energy budget observations, rethinking climate feedback definitions, coordinating new model experiments and intercomparisons, and further investigating the role of episodic variability in AA.NASANatural Sciences and Engineering Research Council of Canada (NSERC)US National Science foundationAlfred P. Sloan FoundationNatural Environment Research Council (NERC

Maternal corticotropin-releasing hormone is associated with LEP DNA methylation at birth and in childhood: an epigenome-wide study in Project Viva

BackgroundCorticotropin-releasing hormone (CRH) plays a central role in regulating the secretion of cortisol which controls a wide range of biological processes. Fetuses overexposed to cortisol have increased risks of disease in later life. DNA methylation may be the underlying association between prenatal cortisol exposure and health effects. We investigated associations between maternal CRH levels and epigenome-wide DNA methylation of cord blood in offsprings and evaluated whether these associations persisted into mid-childhood.MethodsWe investigated mother-child pairs enrolled in the prospective Project Viva pre-birth cohort. We measured DNA methylation in 257 umbilical cord blood samples using the HumanMethylation450 Bead Chip. We tested associations of maternal CRH concentration with cord blood cells DNA methylation, adjusting the model for maternal age at enrollment, education, maternal race/ethnicity, maternal smoking status, pre-pregnancy body mass index, parity, gestational age at delivery, child sex, and cell-type composition in cord blood. We further examined the persistence of associations between maternal CRH levels and DNA methylation in children's blood cells collected at mid-childhood (n = 239, age: 6.7-10.3 years) additionally adjusting for the children's age at blood drawn.ResultsMaternal CRH levels are associated with DNA methylation variability in cord blood cells at 96 individual CpG sites (False Discovery Rate &lt;0.05). Among the 96 CpG sites, we identified 3 CpGs located near the LEP gene. Regional analyses confirmed the association between maternal CRH and DNA methylation near LEP. Moreover, higher maternal CRH levels were associated with higher blood-cell DNA methylation of the promoter region of LEP in mid-childhood (P &lt; 0.05, β = 0.64, SE = 0.30).ConclusionIn our cohort, maternal CRH was associated with DNA methylation levels in newborns at multiple loci, notably in the LEP gene promoter. The association between maternal CRH and LEP DNA methylation levels persisted into mid-childhood

The disruption of JEN1 from Candida albicans impairs the transport of lactate

A lactate permease was biochemically identified in Candida albicans RM1000 presenting the following kinetic parameters at pH 5.0: Km 0.33 ± 0.09 mM and Vmax 0.85± 0.06 nmol s-1 mg dry wt-1. Lactate uptake was competitively inhibited by pyruvic and propionic acids; acetic acid behaved as a non-competitive substrate. An ORF homologous to Saccharomyces cerevisiae gene JEN1 was identified (CaJEN1). Deletions of both CaJEN1 alleles of C. albicans (resulting strain CPK2) resulted in the loss of all measurable lactate permease activity. No CaJEN1 mRNA was detectable in glucose-grown cells neither activity for the lactate transporter. In a medium containing lactic acid, CaJEN1 mRNA was detected in the RM1000 strain, and no expression was found in cells of CPK2 strain. In a strain deleted in the CaCAT8 genes the expression of CaJEN1 was significantly reduced, suggesting the role of this gene as an activator for CaJEN1 expression. Both in C. albicans and in S. cerevisiae cells CaJEN1-GFP fusion was expressed and targeted to the plasma membrane. The native CaJEN1 was not functional in a S. cerevisiae jen1Δ strain. Changing ser217-CTG codon (encoding leucine in S. cerevisiae) to a TCC codon restored the permease activity in S. cerevisiae, proving that the CaJEN1 gene codes for a monocarboxylate transporter.Deutsche Forschungsgemeinschaft (SFB 579).Fundação para a Ciência e a Tecnologia (FCT) - Programa Operacional “Ciência, Tecnologia, Inovação” (POCTI) - POCTI/1999/BME/36625 (Eixo 2, Medida 2.3, QCAIII-FEDER) , SFRH/BD/4699/2001 , PRAXIS XXI/BD/18198/98

Genetic interaction mapping informs integrative structure determination of protein complexes

Determining structures of protein complexes is crucial for understanding cellular functions. Here, we describe an integrative structure determination approach that relies on in vivo measurements of genetic interactions. We construct phenotypic profiles for point mutations crossed against gene deletions or exposed to environmental perturbations, followed by converting similarities between two profiles into an upper bound on the distance between the mutated residues. We determine the structure of the yeast histone H3-H4 complex based on similar to 500,000 genetic interactions of 350 mutants. We then apply the method to subunits Rpb1-Rpb2 of yeast RNA polymerase II and subunits RpoB-RpoC of bacterial RNA polymerase. The accuracy is comparable to that based on chemical cross-links; using restraints from both genetic interactions and cross-links further improves model accuracy and precision. The approach provides an efficient means to augment integrative structure determination with in vivo observations

Retrotransposon vectors for gene delivery in plants

<p>Abstract</p> <p>Background</p> <p>Retrotransposons are abundant components of plant genomes, and although some plant retrotransposons have been used as insertional mutagens, these mobile genetic elements have not been widely exploited for plant genome manipulation. In vertebrates and yeast, retrotransposons and retroviruses are routinely altered to carry additional genes that are copied into complementary (c)DNA through reverse transcription. Integration of cDNA results in gene delivery; recombination of cDNA with homologous chromosomal sequences can create targeted gene modifications. Plant retrotransposon-based vectors, therefore, may provide new opportunities for plant genome engineering.</p> <p>Results</p> <p>A retrotransposon vector system was developed for gene delivery in plants based on the Tnt1 element from <it>Nicotiana tabacum</it>. Mini-Tnt1 transfer vectors were constructed that lack coding sequences yet retain the 5' and 3' long terminal repeats (LTRs) and adjacent <it>cis </it>sequences required for reverse transcription. The internal coding region of Tnt1 was replaced with a neomycin phosphotransferase gene to monitor replication by reverse transcription. Two different mini-Tnt1 s were developed: one with the native 5' LTR and the other with a chimeric 5' LTR that had the first 233 bp replaced by the CaMV 35 S promoter. After transfer into tobacco protoplasts, both vectors undergo retrotransposition using GAG and POL proteins provided in <it>trans </it>by endogenous Tnt1 elements. The transposition frequencies of mini-Tnt1 vectors are comparable with native Tnt1 elements, and like the native elements, insertion sites are within or near coding sequences. In this paper, we provide evidence that template switching occurs during mini-Tnt1 reverse transcription, indicating that multiple copies of Tnt1 mRNA are packaged into virus-like particles.</p> <p>Conclusions</p> <p>Our data demonstrate that mini-Tnt1 vectors can replicate efficiently in tobacco cells using GAG and POL proteins provided in <it>trans </it>by native Tnt1 elements. This suggests that helper Tnt1 constructs can be developed to enable a Tnt1-based two-component vector system that could be used in other plant species. Such a vector system may prove useful for gene delivery or the production of cDNA that can serve as a donor molecule for gene modification through homologous recombination.</p

Parallel laboratory evolution and rational debugging reveal genomic plasticity to S. cerevisiae synthetic chromosome XIV defects

Synthetic chromosome engineering is a complex process due to the need to identify and repair growth defects and deal with combinatorial gene essentiality when rearranging chromosomes. To alleviate these issues, we have demonstrated novel approaches for repairing and rearranging synthetic Saccharomyces cerevisiae genomes. We have designed, constructed, and restored wild-type fitness to a synthetic 753,096-bp version of S. cerevisiae chromosome XIV as part of the Synthetic Yeast Genome project. In parallel to the use of rational engineering approaches to restore wild-type fitness, we used adaptive laboratory evolution to generate a general growth-defect-suppressor rearrangement in the form of increased TAR1 copy number. We also extended the utility of the synthetic chromosome recombination and modification by loxPsym-mediated evolution (SCRaMbLE) system by engineering synthetic-wild-type tetraploid hybrid strains that buffer against essential gene loss, highlighting the plasticity of the S. cerevisiae genome in the presence of rational and non-rational modifications. </p