Early Interferon-γ Production in Human Lymphocyte Subsets in Response to Nontyphoidal Salmonella Demonstrates Inherent Capacity in Innate Cells

Background Nontyphoidal Salmonellae frequently cause life-threatening bacteremia in sub-Saharan Africa. Young children and HIV-infected adults are particularly susceptible. High case-fatality rates and increasing antibiotic resistance require new approaches to the management of this disease. Impaired cellular immunity caused by defects in the T helper 1 pathway lead to intracellular disease with Salmonella that can be countered by IFNγ administration. This report identifies the lymphocyte subsets that produce IFNγ early in Salmonella infection. Methodology Intracellular cytokine staining was used to identify IFNγ production in blood lymphocyte subsets of ten healthy adults with antibodies to Salmonella (as evidence of immunity to Salmonella), in response to stimulation with live and heat-killed preparations of the D23580 invasive African isolate of Salmonella Typhimurium. The absolute number of IFNγ-producing cells in innate, innate-like and adaptive lymphocyte subpopulations was determined. Principal Findings Early IFNγ production was found in the innate/innate-like lymphocyte subsets: γδ-T cells, NK cells and NK-like T cells. Significantly higher percentages of such cells produced IFNγ compared to adaptive αβ-T cells (Student's t test, P<0.001 and ≤0.02 for each innate subset compared, respectively, with CD4+- and CD8+-T cells). The absolute numbers of IFNγ-producing cells showed similar differences. The proportion of IFNγ-producing γδ-T cells, but not other lymphocytes, was significantly higher when stimulated with live compared with heat-killed bacteria (P<0.0001). Conclusion/Significance Our findings indicate an inherent capacity of innate/innate-like lymphocyte subsets to produce IFNγ early in the response to Salmonella infection. This may serve to control intracellular infection and reduce the threat of extracellular spread of disease with bacteremia which becomes life-threatening in the absence of protective antibody. These innate cells may also help mitigate against the effect on IFNγ production of depletion of Salmonella-specific CD4+-T lymphocytes in HIV infection

Offsetting of CO₂ emissions by air capture in mine tailings at the Mount Keith Nickel Mine, Western Australia: Rates, controls and prospects for carbon neutral mining

The hydrated Mg-carbonate mineral, hydromagnesite [Mg₅(CO₃)₄(OH)₂•4H₂O], precipitates within mine tailings at the Mount Keith Nickel Mine, Western Australia as a direct result of mining operations. We have used quantitative mineralogical data and δ¹³C, δ¹⁸O and F¹⁴C isotopic data to quantify the amount of CO₂fixation and identify carbon sources. Our radiocarbon results indicate that at least 80% of carbon stored in hydromagnesite has been captured from the modern atmosphere. Stable isotopic results indicate that dissolution of atmospheric CO₂ into mine tailings water is kinetically limited, which suggests that the current rate of carbon mineralization could be accelerated. Reactive transport modeling is used to describe the observed variation in tailings mineralogy and to estimate rates of CO₂ fixation. Based on our assessment, approximately 39,800 t/yr of atmospheric CO₂ are being trapped and stored in tailings at Mount Keith. This represents an offsetting of approximately 11% of the mine's annual greenhouse gas emissions. Thus, passive sequestration via enhanced weathering of mineral waste can capture and store a significant amount of CO₂. Recommendations are made for changes to tailings management and ore processing practices that have potential to accelerate carbonation of tailings and further reduce or completely offset the net greenhouse gas emissions at Mount Keith and many other mines

A practical guide and perspectives on the use of experimental pain modalities with children and adolescents

Use of experimental pain is vital for addressing research questions that would otherwise be impossible to examine in the real world. Experimental induction of pain in children is highly scrutinized given the potential for harm and lack of direct benefit to a vulnerable population. However, its use has critically advanced our understanding of the mechanisms, assessment and treatment of pain in both healthy and chronically ill children. This article introduces various experimental pain modalities, including the cold pressor task, the water load symptom provocation test, thermal pain, pressure pain and conditioned pain modulation, and discusses their application for use with children and adolescents. It addresses practical implementation and ethical issues, as well as the advantages and disadvantages offered by each task. The incredible potential for future research is discussed given the array of experimental pain modalities now available to pediatric researchers

Sleep reactivation did not boost suppression-induced forgetting.

Sleep's role in memory consolidation is widely acknowledged, but its role in weakening memories is still debated. Memory weakening is evolutionary beneficial and makes an integral contribution to cognition. We sought evidence on whether sleep-based memory reactivation can facilitate memory suppression. Participants learned pairs of associable words (e.g., DIET-CREAM) and were then exposed to hint words (e.g., DIET) and instructed to either recall ("think") or suppress ("no-think") the corresponding target words (e.g., CREAM). As expected, suppression impaired retention when tested immediately after a 90-min nap. To test if reactivation could selectively enhance memory suppression during sleep, we unobtrusively presented one of two sounds conveying suppression instructions during sleep, followed by hint words. Results showed that targeted memory reactivation did not enhance suppression-induced forgetting. Although not predicted, post-hoc analyses revealed that sleep cues strengthened memory, but only for suppressed pairs that were weakly encoded before sleep. The results leave open the question of whether memory suppression can be augmented during sleep, but suggest strategies for future studies manipulating memory suppression during sleep. Additionally, our findings support the notion that sleep reactivation is particularly beneficial for weakly encoded information, which may be prioritized for consolidation

Multivariate patterns of brain-behavior associations across the adult lifespan

The nature of brain-behavior covariations with increasing age is poorly understood. In the current study, we used a multivariate approach to investigate the covariation between behavioral-health variables and brain features across adulthood. We recruited healthy adults aged 20–73 years-old (29 younger, mean age = 25.6 years; 30 older, mean age = 62.5 years), and collected structural and functional MRI (s/fMRI) during a resting-state and three tasks. From the sMRI, we extracted cortical thickness and subcortical volumes; from the fMRI, we extracted activation peaks and functional network connectivity (FNC) for each task. We conducted canonical correlation analyses between behavioral-health variables and the sMRI, or the fMRI variables, across all participants. We found significant covariations for both types of neuroimaging phenotypes (ps = 0.0004) across all individuals, with cognitive capacity and age being the largest opposite contributors. We further identified different variables contributing to the models across phenotypes and age groups. Particularly, we found behavior was associated with different neuroimaging patterns between the younger and older groups. Higher cognitive capacity was supported by activation and FNC within the executive networks in the younger adults, while it was supported by the visual networks’ FNC in the older adults. This study highlights how the brain-behavior covariations vary across adulthood and provides further support that cognitive performance relies on regional recruitment that differs between older and younger individuals

Sleep reactivation did not boost suppression-induced forgetting.

Sleep's role in memory consolidation is widely acknowledged, but its role in weakening memories is still debated. Memory weakening is evolutionary beneficial and makes an integral contribution to cognition. We sought evidence on whether sleep-based memory reactivation can facilitate memory suppression. Participants learned pairs of associable words (e.g., DIET-CREAM) and were then exposed to hint words (e.g., DIET) and instructed to either recall ("think") or suppress ("no-think") the corresponding target words (e.g., CREAM). As expected, suppression impaired retention when tested immediately after a 90-min nap. To test if reactivation could selectively enhance memory suppression during sleep, we unobtrusively presented one of two sounds conveying suppression instructions during sleep, followed by hint words. Results showed that targeted memory reactivation did not enhance suppression-induced forgetting. Although not predicted, post-hoc analyses revealed that sleep cues strengthened memory, but only for suppressed pairs that were weakly encoded before sleep. The results leave open the question of whether memory suppression can be augmented during sleep, but suggest strategies for future studies manipulating memory suppression during sleep. Additionally, our findings support the notion that sleep reactivation is particularly beneficial for weakly encoded information, which may be prioritized for consolidation

Hyperk\"ahler torsion structures invariant by nilpotent Lie groups

We study HKT structures on nilpotent Lie groups and on associated nilmanifolds. We exhibit three weak HKT structures on $\R^8$ which are homogeneous with respect to extensions of Heisenberg type Lie groups. The corresponding hypercomplex structures are of a special kind, called abelian. We prove that on any 2-step nilpotent Lie group all invariant HKT structures arise from abelian hypercomplex structures. Furthermore, we use a correspondence between abelian hypercomplex structures and subspaces of ${\frak sp}(n)$ to produce continuous families of compact and noncompact of manifolds carrying non isometric HKT structures. Finally, geometrical properties of invariant HKT structures on 2-step nilpotent Lie groups are obtained.Comment: LateX, 12 page

Resourcing a Mosaic Force: Lessons from an Acquisition Wargame

Symposium PresentationApproved for public release; distribution is unlimited

Resourcing a Mosaic Force: Lesions from an Acquisition Wargame

Excerpt from the Proceedings of the Nineteenth Annual Acquisition Research SymposiumDARPA has an ambitious vision for Mosaic Warfare, conceived by its Strategic Technology Office (STO) leadership as both a warfighting concept and a means to greatly accelerate capability development and fielding. Although the success of Mosaic depends on DARPA advancing multiple technologies, the Mosaic vision is inherently more challenging to “transition” than is a program or technology. Anticipating this challenge, DARPA sponsored RAND to examine the opportunities and challenges associated with developing and fielding a Mosaic force under existing or alternative governance models and management processes, as would be required for the vision to move from DARPA to widespread acceptance by DoD. To this end, RAND designed and executed a policy game that immersed participants in the task of fielding a Mosaic and required them to operate within the authorities, responsibilities, and constraints of the existing and an alternative governance model. This article presents select findings on the capacity of the existing acquisition resourcing system (i.e., the Planning, Programming, Budgeting, and Execution [or PPBE] process) to exploit STO’s vision of Mosaic Warfare.Approved for public release; distribution is unlimited