Targeted ablation of oligodendrocytes induces axonal pathology independent of overt demyelination

The critical role of oligodendrocytes in producing and maintaining myelin that supports rapid axonal conduction in CNS neurons is well established. More recently, additional roles for oligodendrocytes have been posited, including provision of trophic factors and metabolic support for neurons. To investigate the functional consequences of oligodendrocyte loss, we have generated a transgenic mouse model of conditional oligodendrocyte ablation. In this model, oligodendrocytes are rendered selectively sensitive to exogenously administered diphtheria toxin (DT) by targeted expression of the diphtheria toxin receptor in oligodendrocytes. Administration of DT resulted in severe clinical dysfunction with an ascending spastic paralysis ultimately resulting in fatal respiratory impairment within 22 d of DT challenge. Pathologically, at this time point, mice exhibited a loss of ∼26% of oligodendrocyte cell bodies throughout the CNS. Oligodendrocyte cell-body loss was associated with moderate microglial activation, but no widespread myelin degradation. These changes were accompanied with acute axonal injury as characterized by structural and biochemical alterations at nodes of Ranvier and reduced somatosensory-evoked potentials. In summary, we have shown that a death signal initiated within oligodendrocytes results in subcellular changes and loss of key symbiotic interactions between the oligodendrocyte and the axons it ensheaths. This produces profound functional consequences that occur before the removal of the myelin membrane, i.e., in the absence of demyelination. These findings have clear implications for the understanding of the pathogenesis of diseases of the CNS such as multiple sclerosis in which the oligodendrocyte is potentially targeted

Finding wolf homesites: improving the efficacy of howl surveys to study wolves

Locating wolf (Canis lupus) homesites is valuable for understanding the foraging behavior, population dynamics, and reproductive ecology of wolves during summer. During this period wolf pack members (adults and pups) readily respond to simulated wolf howls (i.e., howl surveys), which allows researchers to estimate the location of the homesite via triangulation. Confirming the actual locations of homesites via ground truthing is labor intensive because of the error surrounding estimated locations. Our objectives were (1) to quantify observer error during howl surveys and compare amongst experience levels, (2) provide a simple method for locating homesites in the field by incorporating observer error, and (3) further document the value of this method for monitoring wolf packs throughout the summer. We located 17 homesites by howl surveys during 2015–2017 in the Greater Voyageurs Ecosystem, Minnesota, USA. Of 62 bearings taken by observers during howl surveys, bearings erred by an average of 7.6° ± 6.3° (SD). There was no difference in observer error between novice and experienced observers. A simple way to increase efficiency when searching for homesites is to search concentric areas (bands) based on estimated observer error, specifically by: (1) adding ±10° error bands around howl survey bearings when ≥3 bearings can be obtained, (2) ±10° and ±20° error bands when 2 bearings are obtained, and (3) ±10° and ±26° error bands when 1 bearing is obtained. By incorporating observer error and understanding how frequently and how far wolves move homesites, it is possible to monitor wolf packs and confirm most, if not all, homesites used by a pack from at least June until August without having a collared individual in a pack

MiR393 regulation of auxin signaling and redox-related components during acclimation to salinity in Arabidopsis

One of the most striking aspects of plant plasticity is the modulation of development in response to environmental changes. Plant growth and development largely depend on the phytohormone auxin that exerts its function through a partially redundant family of F-box receptors, the TIR1-AFBs. We have previously reported that the Arabidopsis double mutant tir1 afb2 is more tolerant to salt stress than wild-type plants and we hypothesized that down-regulation of auxin signaling might be part of Arabidopsis acclimation to salinity. In this work, we show that NaCl-mediated salt stress induces miR393 expression by enhancing the transcription of AtMIR393A and leads to a concomitant reduction in the levels of the TIR1 and AFB2 receptors. Consequently, NaCl triggers stabilization of Aux/IAA repressors leading to down-regulation of auxin signaling. Further, we report that miR393 is likely involved in repression of lateral root (LR) initiation, emergence and elongation during salinity, since the mir393ab mutant shows reduced inhibition of emergent and mature LR number and length upon NaCl-treatment. Additionally, mir393ab mutant plants have increased levels of reactive oxygen species (ROS) in LRs, and reduced ascorbate peroxidase (APX) enzymatic activity compared with wild-type plants during salinity. Thus, miR393 regulation of the TIR1 and AFB2 receptors could be a critical checkpoint between auxin signaling and specfic redoxassociated components in order to coordinate tissue and time-specific growth responses and tolerance during acclimation to salinity in Arabidopsis.Instituto de Fisiología Vegeta

Estimating the delay between host infection and disease (incubation period) and assessing its significance to the epidemiology of plant diseases.

Knowledge of the incubation period of infectious diseases (time between host infection and expression of disease symptoms) is crucial to our epidemiological understanding and the design of appropriate prevention and control policies. Plant diseases cause substantial damage to agricultural and arboricultural systems, but there is still very little information about how the incubation period varies within host populations. In this paper, we focus on the incubation period of soilborne plant pathogens, which are difficult to detect as they spread and infect the hosts underground and above-ground symptoms occur considerably later. We conducted experiments on Rhizoctonia solani in sugar beet, as an example patho-system, and used modelling approaches to estimate the incubation period distribution and demonstrate the impact of differing estimations on our epidemiological understanding of plant diseases. We present measurements of the incubation period obtained in field conditions, fit alternative probability models to the data, and show that the incubation period distribution changes with host age. By simulating spatially-explicit epidemiological models with different incubation-period distributions, we study the conditions for a significant time lag between epidemics of cryptic infection and the associated epidemics of symptomatic disease. We examine the sensitivity of this lag to differing distributional assumptions about the incubation period (i.e. exponential versus Gamma). We demonstrate that accurate information about the incubation period distribution of a pathosystem can be critical in assessing the true scale of pathogen invasion behind early disease symptoms in the field; likewise, it can be central to model-based prediction of epidemic risk and evaluation of disease management strategies. Our results highlight that reliance on observation of disease symptoms can cause significant delay in detection of soil-borne pathogen epidemics and mislead practitioners and epidemiologists about the timing, extent, and viability of disease control measures for limiting economic loss.ML thanks the Institut Technique français de la Betterave industrielle (ITB) for funding this project. CAG and JANF were funded by the UK’s Biotechnology and Biological Sciences Research Council (BBSRC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Effects of Water-Level Management on Nesting Success of Common Loons

Water-level management is widespread and illustrates how contemporary climate can interact directly and indirectly with numerous biological and abiotic factors to influence reproductive success of wildlife species. We studied common loons, an iconic waterbird sensitive to timing and magnitude of waterlevel changes during the breeding season, using a before-after-control-impact design on large lakes in Voyageurs National Park (Minnesota, USA), to assess the effect of anthropogenic changes in hydroregime on their nesting success and productivity. We examined multiple competing a priori hypotheses in an information-theoretic framework, and predicted that magnitude of changes in loon productivity would be greater in the Namakan Reservoir, where water-level management was altered to mimic a more natural hydroregime, than in Rainy Lake, where management remained relatively unchanged. We determined outcomes from 278 nests during 2004–2006 by performing boat-based visits every 3–5 days, and measuring hydrologic, vegetative, and microtopographic covariates. Relative to comparably collected data for 260 total loon pairs during 1983–1986, productivity (chicks hatched/territorial pair) increased 95% in the Namakan Reservoir between the 2 time periods. Nest success declined in both lakes over the 2 study periods but less so in the Namakan Reservoir than in Rainy Lake. Flooding was a primary cause of nest failures (though second nests were less likely to flood). Nest predation appears to have increased considerably between the 2 study periods. Top-ranked models suggested that timing of nest initiation, probability of nest flooding, probability of nest stranding, and probability of nest success were each related to 2–4 factors, including date of initiation, timing of initiation relative to peak water levels, changes in the elevation of the nest edge, maximum waterlevel change between initiation and peak water levels, and maximum water-level change between initiation and nest outcome. The top model for all variables except stranding each garnered \u3e82% of total model weight. Results demonstrate that water-level management can be altered to benefit productivity of common loons. However, nuanced interactions between land-use change, invasive species, human development, recreation, climate change, and recovery of top predators may often complicate both management decisions and interpretation of water-level impacts on wildlife

MiR393 regulation of auxin signaling and redox-related components during acclimation to salinity in Arabidopsis

One of the most striking aspects of plant plasticity is the modulation of development in response to environmental changes. Plant growth and development largely depend on the phytohormone auxin that exerts its function through a partially redundant family of F-box receptors, the TIR1-AFBs. We have previously reported that the Arabidopsis double mutant tir1 afb2 is more tolerant to salt stress than wild-type plants and we hypothesized that down-regulation of auxin signaling might be part of Arabidopsis acclimation to salinity. In this work, we show that NaCl-mediated salt stress induces miR393 expression by enhancing the transcription of AtMIR393A and leads to a concomitant reduction in the levels of the TIR1 and AFB2 receptors. Consequently, NaCl triggers stabilization of Aux/IAA repressors leading to down-regulation of auxin signaling. Further, we report that miR393 is likely involved in repression of lateral root (LR) initiation, emergence and elongation during salinity, since the mir393ab mutant shows reduced inhibition of emergent and mature LR number and length upon NaCl-treatment. Additionally, mir393ab mutant plants have increased levels of reactive oxygen species (ROS) in LRs, and reduced ascorbate peroxidase (APX) enzymatic activity compared with wild-type plants during salinity. Thus, miR393 regulation of the TIR1 and AFB2 receptors could be a critical checkpoint between auxin signaling and specfic redoxassociated components in order to coordinate tissue and time-specific growth responses and tolerance during acclimation to salinity in Arabidopsis.Instituto de Fisiología Vegeta

Big Data to Knowledge Analytics Reveals the Zika Virus Epidemic as Only One of Multiple Factors Contributing to a Year-Over-Year 28-Fold Increase in Microcephaly Incidence

During the 2015–2016 Zika Virus (ZIKV) epidemic in Brazil, the geographical distributions of ZIKV infection and microcephaly outbreaks did not align. This raised doubts about the virus as the single cause of the microcephaly outbreak and led to research hypotheses of alternative explanatory factors, such as environmental variables and factors, agrochemical use, or immunizations. We investigated context and the intermediate and structural determinants of health inequalities, as well as social environment factors, to determine their interaction with ZIKV-positive- and ZIKV-negative-related microcephaly. The results revealed the identification of 382 associations among 382 nonredundant variables of Zika surveillance, including multiple determinants of environmental public health factors and variables obtained from 5565 municipalities in Brazil. This study compared those factors and variables directly associated with microcephaly incidence positive to ZIKV and those associated with microcephaly incidence negative to ZIKV, respectively, and mapped them in case and control subnetworks. The subnetworks of factors and variables associated with low birth weight and birthweight where birth incidence served as an additional control were also mapped. Non-significant differences in factors and variables were observed, as were weights of associations between microcephaly incidence, both positive and negative to ZIKV, which revealed diagnostic inaccuracies that translated to the underestimation of the scope of the ZIKV outbreak. A detailed analysis of the patterns of association does not support a finding that vaccinations contributed to microcephaly, but it does raise concerns about the use of agrochemicals as a potential factor in the observed neurotoxicity arising from the presence of heavy metals in the environment and microcephaly not associated with ZIKV. Summary: A comparative network inferential analysis of the patterns of variables and factors associated with Zika virus infections in Brazil during 2015–2016 coinciding with a microcephaly epidemic identified multiple contributing determinants. This study advances our understanding of the cumulative interactive effects of exposures to chemical and non-chemical stressors in the built, natural, physical, and social environments on adverse pregnancy and health outcomes in vulnerable populations

Onset of infectiousness explains differences in transmissibility across Mycobacterium tuberculosis lineages

Mycobacterium tuberculosis complex (MTBC) lineages show substantial variability in virulence, but the epidemiological consequences of this variability have not been studied in detail. Here, we aimed for a lineage-specific epidemiological characterization by applying phylodynamic models to genomic data from different countries, representing the most abundant MTBC lineages. Our results suggest that all lineages are associated with similar durations and levels of infectiousness, resulting in similar reproductive numbers. However, L1 and L6 are associated with a delayed onset of infectiousness, leading to longer periods between subsequent transmission events. Together, our findings highlight the role of MTBC genetic diversity in tuberculosis disease progression and transmission

Self-authorship and creative industries workers’ career decision-making

Career decision-making is arguably at its most complex within professions where work is precarious and career calling is strong. This article reports from a study that examined the career decision-making of creative industries workers, for whom career decisions can impact psychological well-being and identity just as much as they impact individuals’ work and career. The respondents were 693 creative industries workers who used a largely open-ended survey to create in-depth reflections on formative moments and career decision-making. Analysis involved the theoretical model of self-authorship, which provides a way of understanding how people employ their sense of self to make meaning of their experiences. The self-authorship process emerged as a complex, non-linear and consistent feature of career decision-making. Theoretical contributions include a non-linear view of self-authorship that exposes the authorship of visible and covert multiple selves prompted by both proactive and reactive identity work

On the Introduction of Automatic Program Repair in Bloomberg

A key to the success of Automatic Program Repair techniques is how easily they can be used in an industrial setting. In this article, we describe a collaboration by a team from four UK-based universities with Bloomberg (London) in implementing automatic, high-quality fixes to its code base. We explain the motivation for adopting APR, the mechanics of the prototype tool that was built, and the practicalities of integrating APR into existing systems. IEE