Sod2 haploinsufficiency does not accelerate aging of telomere dysfunctional mice

Telomere shortening represents a causal factor of cellular senescence. At the same time, several lines of evidence indicate a pivotal role of oxidative DNA damage for the aging process in vivo. A causal connection between the two observations was suggested by experiments showing accelerated telomere shorting under conditions of oxidative stress in cultured cells, but has never been studied in vivo. We therefore have analysed whether an increase in mitochondrial derived oxidative stress in response to heterozygous deletion of superoxide dismutase (Sod2+/-) would exacerbate aging phenotypes in telomere dysfunctional (mTerc-/-) mice. Heterozygous deletion of Sod2 resulted in reduced SOD2 protein levels and increased oxidative stress in aging telomere dysfunctional mice, but this did not lead to an increase in basal levels of oxidative nuclear DNA damage, an accumulation of nuclear DNA breaks, or an increased rate of telomere shortening in the mice. Moreover, heterozygous deletion of Sod2 did not accelerate the depletion of stem cells and the impairment in organ maintenance in aging mTerc-/- mice. In agreement with these observations, Sod2 haploinsufficiency did not lead to a further reduction in lifespan of mTerc-/- mice. Together, these results indicate that a decrease in SOD2-dependent antioxidant defence does not exacerbate aging in the context of telomere dysfunction

Senataxin, defective in ataxia oculomotor apraxia type 2, is involved in the defense against oxidative DNA damage.

A defective response to DNA damage is observed in several human autosomal recessive ataxias with oculomotor apraxia, including ataxia-telangiectasia. We report that senataxin, defective in ataxia oculomotor apraxia (AOA) type 2, is a nuclear protein involved in the DNA damage response. AOA2 cells are sensitive to H2O2, camptothecin, and mitomycin C, but not to ionizing radiation, and sensitivity was rescued with full-length SETX cDNA. AOA2 cells exhibited constitutive oxidative DNA damage and enhanced chromosomal instability in response to H2O2. Rejoining of H2O2-induced DNA double-strand breaks (DSBs) was significantly reduced in AOA2 cells compared to controls, and there was no evidence for a defect in DNA single-strand break repair. This defect in DSB repair was corrected by full-length SETX cDNA. These results provide evidence that an additional member of the autosomal recessive AOA is also characterized by a defective response to DNA damage, which may contribute to the neurodegeneration seen in this syndrome

Common capacity-limited neural mechanisms of selective attention and spatial working memory encoding

One characteristic feature of visual working memory (WM) is its limited capacity, and selective attention has been implicated as limiting factor. A possible reason why attention constrains the number of items that can be encoded into WM is that the two processes share limited neural resources. Functional magnetic resonance imaging (fMRI) studies have indeed demonstrated commonalities between the neural substrates of WM and attention. Here we investigated whether such overlapping activations reflect interacting neural mechanisms that could result in capacity limitations. To independently manipulate the demands on attention and WM encoding within one single task, we combined visual search and delayed discrimination of spatial locations. Participants were presented with a search array and performed easy or difficult visual search in order to encode one, three or five positions of target items into WM. Our fMRI data revealed colocalised activation for attention‐demanding visual search and WM encoding in distributed posterior and frontal regions. However, further analysis yielded two patterns of results. Activity in prefrontal regions increased additively with increased demands on WM and attention, indicating regional overlap without functional interaction. Conversely, the WM load‐dependent activation in visual, parietal and premotor regions was severely reduced during high attentional demand. We interpret this interaction as indicating the sites of shared capacity‐limited neural resources. Our findings point to differential contributions of prefrontal and posterior regions to the common neural mechanisms that support spatial WM encoding and attention, providing new imaging evidence for attention‐based models of WM encoding

CK2 phosphorylation-dependent interaction between aprataxin and MDC1 in the DNA damage response

Aprataxin, defective in the neurodegenerative disorder ataxia oculomotor apraxia type 1, resolves abortive DNA ligation intermediates during DNA repair. Here, we demonstrate that aprataxin localizes at sites of DNA damage induced by high LET radiation and binds to mediator of DNA-damage checkpoint protein 1 (MDC1/NFBD1) through a phosphorylation-dependent interaction. This interaction is mediated via the aprataxin FHA domain and multiple casein kinase 2 di-phosphorylated S-D-T-D motifs in MDC1. X-ray structural and mutagenic analysis of aprataxin FHA domain, combined with modelling of the pSDpTD peptide interaction suggest an unusual FHA binding mechanism mediated by a cluster of basic residues at and around the canonical pT-docking site. Mutation of aprataxin FHA Arg29 prevented its interaction with MDC1 and recruitment to sites of DNA damage. These results indicate that aprataxin is involved not only in single strand break repair but also in the processing of a subset of double strand breaks presumably through its interaction with MDC1

CK2 phosphorylation-dependent interaction between aprataxin and MDC1 in the DNA damage response

Aprataxin, defective in the neurodegenerative disorder ataxia oculomotor apraxia type 1, resolves abortive DNA ligation intermediates during DNA repair. Here, we demonstrate that aprataxin localizes at sites of DNA damage induced by high LET radiation and binds to mediator of DNA-damage checkpoint protein 1 (MDC1/NFBD1) through a phosphorylation-dependent interaction. This interaction is mediated via the aprataxin FHA domain and multiple casein kinase 2 di-phosphorylated S-D-T-D motifs in MDC1. X-ray structural and mutagenic analysis of aprataxin FHA domain, combined with modelling of the pSDpTD peptide interaction suggest an unusual FHA binding mechanism mediated by a cluster of basic residues at and around the canonical pT-docking site. Mutation of aprataxin FHA Arg29 prevented its interaction with MDC1 and recruitment to sites of DNA damage. These results indicate that aprataxin is involved not only in single strand break repair but also in the processing of a subset of double strand breaks presumably through its interaction with MDC1

Multiple ecosystem services from field margin vegetation for ecological sustainability in agriculture: scientific evidence and knowledge gaps

Background: Field margin and non-crop vegetation in agricultural systems are potential ecosystem services providers because they offer semi-natural habitats for both below and above ground animal groups such as soil organisms, small mammals, birds and arthropods that are service supplying units. They are considered as a target area for enhancing farm biodiversity. Methodology: To explore the multiple potential benefits of these semi-natural habitats and to identify research trends and knowledge gaps globally, a review was carried out following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 235 publications from the year 2000 to 2016 in the Scopus and Web of Science databases were reviewed. Results: The literature showed an increasing trend in the number of published articles over time with European studies leading in the proportion of studies conducted, followed by North America, Asia, South America, Africa and Australia. Several functional groups of organisms were studied from field margin and non-crop vegetation around agricultural lands including natural enemies (37%), insect pests (22%), birds (17%), pollinators (16%), soil macro fauna (4%) and small mammals (4%). Ecosystem services derived from the field margin included natural pest regulation, pollination, nutrient cycling and reduced offsite erosion. Some field margin plants were reported to host detrimental crop pests, a major ecosystem dis-service, potentially leading to increased pest infestation in the field. Conclusion: The majority of studies revealed the importance of field margin and non-crop vegetation around arable fields in enhancing ecosystem biodiversity. Promotion of field margin plants that selectively enhance the population of beneficial organisms would support sustainable food security rather than simply boosting plant diversity. Our analyses also highlight that agro-ecological studies remain largely overlooked in some regions

Endonuclease G preferentially cleaves 5-hydroxymethylcytosine-modified DNA creating a substrate for recombination

5-hydroxymethylcytosine (5hmC) has been suggested to be involved in various nucleic acid transactions and cellular processes, including transcriptional regulation, demethylation of 5-methylcytosine and stem cell pluripotency. We have identified an activity that preferentially catalyzes the cleavage of double-stranded 5hmC-modified DNA. Using biochemical methods we purified this activity from mouse liver extracts and demonstrate that the enzyme responsible for the cleavage of 5hmC-modified DNA is Endonuclease G (EndoG). We show that recombinant EndoG preferentially recognizes and cleaves a core sequence when one specific cytosine within that core sequence is hydroxymethylated. Additionally, we provide in vivo evidence that EndoG catalyzes the formation of double-stranded DNA breaks and that this cleavage is dependent upon the core sequence, EndoG and 5hmC. Finally, we demonstrate that the 5hmC modification can promote conservative recombination in an EndoG-dependent manner

A man-machine interface for PC-controlled injection moulding /

In parallel to the development of a PC-control system for injection moulding, a workable user interface for man-machine communication was developed.The hardware includes an IBM PC/AT, PS/2 model 70. A real-time multi-task operating system, QNX 4.0 (Quantum Software Sys. Ltd.) was installed to run applications programmed in the language C (WATCOM Sys. Inc.).A top-down structure was adopted, comprising menus, warnings, and directives.The user interface includes three tasks to run concurrently, the main-task, the real-time machine-status display task, and the task to display the current barrel-heater temperatures.Four controller types, a digital PID and three discrete controllers, the total of cycles for the machine to run, and operating modes can be specified by scrolling sub-menus.All data processed on the loading, editing, and saving level, are character strings that will be converted to appropriate data types just before machine activation.Inter-task communication is accomplished by sharing global memory segments between display tasks and the tasks in charge for data acquisition and control.The interface tasks do not exert a large claim on system resources