Virulence and Evolutionary Ecology in the Entomopathogen Bacillus thuringiensis

Bacillus thuringiensis is an entomopathogen in the Bacillus cereus species group, and has been used as a biopesticide for over 50 years. Despite extensive use of B. thuringiensis, there remain questions over its specific ecology compared to other members of the B. cereus group which poses problems for its continued applied use. Tying entomopathogenic ecology to a specific clade within the B. cereus group will limit confusion between B. thuringiensis used in agriculture and more harmful strains. Better understanding of B. thuringiensis ecology can also be used to combat resistance in pest species through selective passaging. The ecology of B. thuringiensis was explored through competitions in Plutella xylostella (diamondback moth) larvae, which showed clade 2 B. thuringiensis have improved fitness in insects compared to clade 1 strains. Additionally, growth rates were compared in vitro, giving different thermal profiles for the two clades. Growth media preference was assessed for B. cereus group species with all favouring protein media over soil-based ones. Selective passaging explored the effects of relatedness and host background on virulence evolution. For relatedness, B. thuringiensis subsp. aizawai was passaged for five rounds in P. xylostella larvae with none, one or two bottlenecking events. These treatments failed to produce any increase in virulence. In the second, B. thuringiensis subsp. entomocidus was passaged either in Cry1Ac-resistant, Cry1Ac-susceptible, alternating rounds of each or coevolved P. xylostella, with all containing a mutagenesis step with ethyl methanesulfonate. Virulence increased in the resistant and coevolved treatments, confirming that resistance is best overcome by passaging in harder-to-kill hosts. The ecological and genetic distinctiveness of clade 2 B. thuringiensis suggests the species should be reclassified to solely this clade, which will limit safety concerns. Selective passaging can improve the virulence of strains, even if the underlying interactions are unknown; it can also provide insight into virulence evolution which would be lost when improving only at the protein level.Leverhulme Trus

Socioeconomic inequalities in survival and provision of neonatal care: population based study of very preterm infants

Objectives To assess socioeconomic inequalities in survival and provision of neonatal care among very preterm infants

‘I shall miss the company’: participants’ reflections on time-limited day centre programming

The social needs of frail or isolated older people are sometimes aided by referrals to day centres in the United Kingdom. Since the late 1940s, day centres have had a role to play promoting socialisation in later life. Additionally, attendance at day centres is often open ended, with participants only leaving due to moving to a nursing home or dying. In this study, the views of those attending time-limited day centre programmes in seven day centres in Northern Ireland have been sought in relation to their thoughts about the service as well as how they feel when it ends. Seventeen participants completed diaries for the programme duration and/or engaged in an interview process. Participants reflected on the social and educational benefits of attending but also recognised impositions in the centres that impinged upon individual choices and also the length of time they could remain. This study reveals that, in order to maintain socialisation, time-limited programmes must have clear follow-on strategies for participants. Additionally, respondents’ experiences reflect that a paternalistic model of care delivery remains in place that, whilst restrictive, reveals that access to the service is more specialised and not universal. Nevertheless, should day centres wish to remain relevant, it is important that service users are fully consulted about their desires and choices within the setting

First comparison of a global microphysical aerosol model with size-resolved observational aerosol statistics

International audienceA statistical synthesis of marine aerosol measurements from experiments in four different oceans is used to evaluate a global aerosol microphysics model (GLOMAP). We compare the model against observed size resolved particle concentrations, probability distributions, and the temporal persistence of different size particles. We attempt to explain the observed size distributions in terms of sulfate and sea spray and quantify the possible contributions of anthropogenic sulfate and carbonaceous material to the number and mass distribution. The model predicts a bimodal size distribution that agrees well with observations as a grand average over all regions, but there are large regional differences. Notably, observed Aitken mode number concentrations are more than a factor 10 higher than in the model for the N Atlantic but a factor 7 lower than the model in the NW Pacific. We also find that modelled Aitken mode and accumulation mode geometric mean diameters are generally smaller in the model by 10?30%. Comparison with observed free tropospheric Aitken mode distributions suggests that the model underpredicts growth of these particles during descent to the MBL. Recent observations of a substantial organic component of free tropospheric aerosol could explain this discrepancy. We find that anthropogenic continental material makes a substantial contribution to N Atlantic marine boundary layer (MBL) aerosol, with typically 60?90% of sulfate across the particle size range coming from anthropogenic sources, even if we analyse air that has spent an average of >120 h away from land. However, anthropogenic primary black carbon and organic carbon particles do not explain the large discrepancies in Aitken mode number. Several explanations for the discrepancy are suggested. The lack of lower atmospheric particle formation in the model may explain low N Atlantic particle concentrations. However, the observed and modelled particle persistence at Cape Grim in the Southern Ocean, does not reveal a diurnal cycle consistent with a photochemically driven local particle source. We also show that a physically based cloud drop activation scheme is needed to explain the observed change in accumulation mode geometric mean diameter with particle number

Cognitive Flexibility: A Default Mode Perspective

The intra/extradimensional set-shifting task (IED) provides a reliable assessment of cognitive flexibility, the shifting of attention to select behaviorally relevant stimuli in a given context. Impairments in this domain were previously reported in patients with altered neurotransmitter systems such as schizophrenia and Parkinson's disease. Consequently, corticostriatal connections were implicated in the mediation of this function. In addition, parts of the default mode network (DMN), namely the medial prefrontal and posterior cingulate/precuneus cortices, are also being progressively described in association with set-shifting paradigms. Nevertheless, a definitive link between cognitive flexibility and DMN connectivity remains to be established. To this end, we related resting state functional magnetic resonance imaging (fMRI)-based functional connectivity of DMN with IED task performance in a healthy population, measured outside the scanner. The results demonstrated that greater posterior cingulate cortex/precuneus (DMN) connectivity with the ventromedial striatopallidum at rest correlated with fewer total adjusted errors on the IED task. This finding points to a relationship between DMN and basal ganglia connectivity for cognitive flexibility, further highlighting this network's potential role in adaptive human cognition.The Evelyn Trust (RUAG/018) supported this research. Additionally, DV received funding from the Yousef Jameel Academic Program; DKM is funded by the NIHR Cambridge Biomedical Centre (RCZB/004), and an NIHR Senior Investigator Award (RCZB/014), and EAS is supported by the Stephen Erskine Fellowship Queens’ College, Cambridge. We would also like to thank Dr. Guy Williams and Victoria Lupson and the rest of the staff in the Wolfson Brain Imaging Centre (WBIC) at Addenbrooke’s Hospital for their assistance in scanning. Finally, we thank all the participants for their contribution to this studyThis is the author accepted manuscript. The final version is available from Mary Ann Liebert via http://dx.doi.org/10.1089/brain.2015.038

Evaluation of a global aerosol microphysics model against size-resolved particle statistics in the marine atmosphere

A statistical synthesis of marine aerosol measurements from experiments in four different oceans is used to evaluate a global aerosol microphysics model (GLOMAP). We compare the model against observed size resolved particle concentrations, probability distributions, and the temporal persistence of different size particles. We attempt to explain the observed sub-micrometre size distributions in terms of sulfate and sea spray and quantify the possible contributions of anthropogenic sulfate and carbonaceous material to the number and mass distribution. The model predicts a bimodal size distribution that agrees well with observations as a grand average over all regions, but there are large regional differences. Notably, observed Aitken mode number concentrations are more than a factor 10 higher than in the model for the N Atlantic but a factor 7 lower than the model in the NW Pacific. We also find that modelled Aitken mode and accumulation mode geometric mean diameters are generally smaller in the model by 10–30%. Comparison with observed free tropospheric Aitken mode distributions suggests that the model underpredicts growth of these particles during descent to the marine boundary layer (MBL). Recent observations of a substantial organic component of free tropospheric aerosol could explain this discrepancy. We find that anthropogenic continental material makes a substantial contribution to N Atlantic MBL aerosol, with typically 60–90% of sulfate across the particle size range coming from anthropogenic sources, even if we analyse air that has spent an average of >120 h away from land. However, anthropogenic primary black carbon and organic carbon particles (at the emission size and quantity assumed here) do not explain the large discrepancies in Aitken mode number. Several explanations for the discrepancy are suggested. The lack of lower atmospheric particle formation in the model may explain low N Atlantic particle concentrations. However, the observed and modelled particle persistence at Cape Grim in the Southern Ocean, does not reveal a diurnal cycle consistent with a photochemically driven local particle source. We also show that a physically based cloud drop activation scheme better explains the observed change in accumulation mode geometric mean diameter with particle number

Nature of socioeconomic inequalities in neonatal mortality: population based study

Objective To investigate time trends in socioeconomic inequalities in cause specific neonatal mortality in order to assess changing patterns in mortality due to different causes, particularly prematurity, and identify key areas of focus for future intervention strategies

Default Mode Dynamics for Global Functional Integration.

UNLABELLED: The default mode network (DMN) has been traditionally assumed to hinder behavioral performance in externally focused, goal-directed paradigms and to provide no active contribution to human cognition. However, recent evidence suggests greater DMN activity in an array of tasks, especially those that involve self-referential and memory-based processing. Although data that robustly demonstrate a comprehensive functional role for DMN remains relatively scarce, the global workspace framework, which implicates the DMN in global information integration for conscious processing, can potentially provide an explanation for the broad range of higher-order paradigms that report DMN involvement. We used graph theoretical measures to assess the contribution of the DMN to global functional connectivity dynamics in 22 healthy volunteers during an fMRI-based n-back working-memory paradigm with parametric increases in difficulty. Our predominant finding is that brain modularity decreases with greater task demands, thus adapting a more global workspace configuration, in direct relation to increases in reaction times to correct responses. Flexible default mode regions dynamically switch community memberships and display significant changes in their nodal participation coefficient and strength, which may reflect the observed whole-brain changes in functional connectivity architecture. These findings have important implications for our understanding of healthy brain function, as they suggest a central role for the DMN in higher cognitive processing. SIGNIFICANCE STATEMENT: The default mode network (DMN) has been shown to increase its activity during the absence of external stimulation, and hence was historically assumed to disengage during goal-directed tasks. Recent evidence, however, implicates the DMN in self-referential and memory-based processing. We provide robust evidence for this network's active contribution to working memory by revealing dynamic reconfiguration in its interactions with other networks and offer an explanation within the global workspace theoretical framework. These promising findings may help redefine our understanding of the exact DMN role in human cognition.This research was supported by the Evelyn Trust (RUAG/018). In addition, DV received funding from the Yousef Jameel Academic Program; DKM is supported by the NIHR Cambridge Biomedical Centre (RCZB/004), and an NIHR Senior Investigator Award (RCZB/014), and EAS is funded by the Stephen Erskine Fellowship Queens’ College Cambridge.This is the author accepted manuscript. The final version is available from Society for Neuroscience via http://dx.doi.org/10.1523/JNEUROSCI.2135-15.201

Spectral Diversity in Default Mode Network Connectivity Reflects Behavioral State.

Default mode network (DMN) functional connectivity is thought to occur primarily in low frequencies (<0.1 Hz), resulting in most studies removing high frequencies during data preprocessing. In contrast, subtractive task analyses include high frequencies, as these are thought to be task relevant. An emerging line of research explores resting fMRI data at higher-frequency bands, examining the possibility that functional connectivity is a multiband phenomenon. Furthermore, recent studies suggest DMN involvement in cognitive processing; however, without a systematic investigation of DMN connectivity during tasks, its functional contribution to cognition cannot be fully understood. We bridged these concurrent lines of research by examining the contribution of high frequencies in the relationship between DMN and dorsal attention network at rest and during task execution. Our findings revealed that the inclusion of high frequencies alters between network connectivity, resulting in reduced anticorrelation and increased positive connectivity between DMN and dorsal attention network. Critically, increased positive connectivity was observed only during tasks, suggesting an important role for high-frequency fluctuations in functional integration. Moreover, within-DMN connectivity during task execution correlated with RT only when high frequencies were included. These results show that DMN does not simply deactivate during task execution and suggest active recruitment while performing cognitively demanding paradigms