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Malign ‘influence activities’ conducted by state and non-state adversaries are one of the most pressing security challenges facing democracies globally. Haroro J Ingram offers a framework through w...

Emerging digital tools have the potential to enable a new generation of qualitative and quantitative assessment of cognitive performance. Moreover, the ubiquity of consumer electronics, such as smartphones and tablets, can be harnessed to support large-scale self-assessed cognitive screening with benefit to healthcare systems and consumers. A wide variety of apps, wearables, and new digital technologies are either available or in development for the detection of mild cognitive impairment (MCI), a risk factor for dementia. Two categories of novel methodologies may be considered: passive technologies (which monitor a user’s behavior without active user input) and interactive assessments (which require active user input). Such examinations can be self-administered, supervised by a caregiver, or conducted by an informant at home or outside of a clinical setting. These direct-to-consumer tools have the potential to sidestep barriers associated with cognitive evaluation in primary care, thus improving access to cognitive assessments. Although direct-to-consumer cognitive assessment is associated with its own barriers, including test validation, user experience, and technological concerns, it is conceivable that these issues can be addressed so that a large-scale, self-assessed cognitive evaluation that would represent an initial cognitive screen may be feasible in the future.

V2O5 is of interest as a Mg intercalation electrode material for Mg batteries, both in its thermodynamically stable layered polymorph (α-V2O5) and in its metastable tunnel structure (ζ-V2O5). However, such oxide cathodes typically display poor Mg insertion/removal kinetics, with large voltage hysteresis. Herein, we report the synthesis and evaluation of nanosized (ca. 100 nm) ζ-V2O5 in Mg-ion cells, which displays significantly enhanced electrochemical kinetics compared to microsized ζ-V2O5. This effect results in a significant boost in stable discharge capacity (130 mA h g-1) compared to bulk ζ-V2O5 (70 mA h g-1), with reduced voltage hysteresis (1.0 V compared to 1.4 V). This study reveals significant advancements in the use of ζ-V2O5 for Mg-based energy storage and yields a better understanding of the kinetic limiting factors for reversible magnesiation reactions into such phases.

Despite improvement in clinical management, allogeneic hematopoietic stem cell transplantation (HSCT) is still hampered by high morbidity and mortality rates, mainly due to graft versus host disease (GvHD). Recently, it has been demonstrated that the allogeneic immune response might be influenced by external factors such as tissues microenvironment or host microbiota. Here we used high throughput metabolomics to analyze two cohorts of genotypically HLA-identical related recipient and donor pairs. Metabolomic profiles markedly differ between recipients and donors. At the onset of acute GvHD, in addition to host-derived metabolites, we identify significant variation in microbiota-derived metabolites, especially in aryl hydrocarbon receptor (AhR) ligands, bile acids and plasmalogens. Altogether, our findings support that the allogeneic immune response during acute GvHD might be influenced by bile acids and by the decreased production of AhR ligands by microbiota that could limit indoleamine 2,3-dioxygenase induction and influence allogeneic T cell reactivity., Graft versus host disease (GvHD) still hinders allogeneic hematopoietic stem cell transplantation. Here, the authors use metabolomics to analyze two cohorts of paired transplant recipients and donors, identifying significant differences in both host- and microbiota-derived metabolites.

PurposeThe purpose of this paper is to examine the labor market entry of real estate agents in the USA and the potential effect of occupational licensing on entry.Design/methodology/approachData from the 2012 to 2017 American Community Survey are linked to local housing price fluctuations from the Federal Housing Finance Agency for 100 large metro areas. The cost of entry associated with occupational licensing for new real estate agents is carefully measured for each market and interacted with housing fluctuations to investigate the role for barriers to entry.FindingsA 10 percent increase in housing prices is associated with a 4 percent increase in the number of agents. However, increased license stringency reduces the labor market response by 30 percent. The impact of licensing is stronger for women and younger workers.Originality/valueThis work contributes to the growing literature investigating the impact of occupational licensing on labor supply and entry in the USA, as well as potential impacts of regulation on dynamism and entrepreneurship. To the authors’ knowledge, this study is also the first to quantify the cost of occupational licensing in the real estate industry.

Due to their exceptional high energy density, lithium-ion batteries are of central importance in many modern electrical devices. A serious limitation, however, is the slow charging rate used to obtain the full capacity. Thus far, there have been no ways to increase the charging rate without losses in energy density and electrochemical performance. Here we show that the charging rate of a cathode can be dramatically increased via interaction with white light. We find that a direct exposure of light to an operating LiMn2O4 cathode during charging leads to a remarkable lowering of the battery charging time by a factor of two or more. This enhancement is enabled by the induction of a microsecond long-lived charge separated state, consisting of Mn4+ (hole) plus electron. This results in more oxidized metal centers and ejected lithium ions are created under light and with voltage bias. We anticipate that this discovery could pave the way to the development of new fast recharging battery technologies., Here the authors show that illumination of a lithium manganese oxide cathode can induce efficient charge-separation and electron transfer processes, thus giving rise to a new type of fast lithium-ion battery charging.

The Burkholderia genus encompasses many Gram-negative bacteria living in the rhizosphere. Some Burkholderia species can cause life-threatening human infections, highlighting the need for clinical interventions targeting specific lipopolysaccharide proteins. Burkholderia cenocepacia O-linked protein glycosylation has been reported, but the chemical structure of the O-glycan and the machinery required for its biosynthesis are unknown and could reveal potential therapeutic targets. Here, using bioinformatics approaches, gene-knockout mutants, purified recombinant proteins, LC-MS–based analyses of O-glycans, and NMR-based structural analyses, we identified a B. cenocepacia O-glycosylation (ogc) gene cluster necessary for synthesis, assembly, and membrane translocation of a lipid-linked O-glycan, as well as its structure, which consists of a β-Gal-(1,3)–α-GalNAc-(1,3)–β-GalNAc trisaccharide. We demonstrate that the ogc cluster is conserved in the Burkholderia genus, and we confirm the production of glycoproteins with similar glycans in the Burkholderia species: B. thailandensis, B. gladioli, and B. pseudomallei. Furthermore, we show that absence of protein O-glycosylation severely affects bacterial fitness and accelerates bacterial clearance in a Galleria mellonella larva infection model. Finally, our experiments revealed that patients infected with B. cenocepacia, Burkholderia multivorans, B. pseudomallei, or Burkholderia mallei develop O-glycan–specific antibodies. Together, these results highlight the importance of general protein O-glycosylation in the biology of the Burkholderia genus and its potential as a target for inhibition or immunotherapy approaches to control Burkholderia infections.

Over the last few years, there has been an increased interest in developing safe, next-generation battery systems that offer energy densities higher than those of lithium-based batteries. In this context, batteries based on multivalent-ions (Mg2+, Zn2+, Ca2+, and Al3+) have developed their own niche with their capability to achieve at least twice the energy density of monovalent-ion systems such as Li-ion and Na-ion batteries. Among the multivalent-ion battery candidates, magnesium (Mg) batteries appear to be the most viable choice to eventually replace the Li-ion technology because of the high electrode potential, superior safety, and high abundance of Mg-metal. However, the limited development in electrolytes and cathodes has prevented their commercialization to date. There is a lack of suitable electrolytes that can be used at high voltages required for Mg2+ insertion into cathode hosts. The limited compatibility of organic electrolytes with Mg-metal anode is also a challenge, which requires extensive studies of the metal/electrolyte interactions. Such studies over the last two decades were critical in developing state-of-the-art Mg electrolytes that possess voltage windows of >4.0 V and simultaneously be compatible with Mg-metal anodes. Here, we present a review on the development of Mg battery electrolytes, challenges that impede their performance, and promising strategies that have been adopted to address them. We believe that this comprehensive review covering all three categories of Mg electrolytes (liquids, polymers, and solids) would enable researchers to get a quick grasp of the prevailing challenges, and consequently motivate them to develop novel electrolyte candidates.

Introduction Discordance in kidney disease severity between affected relatives is a recognized feature of autosomal dominant polycystic kidney disease (ADPKD). Here, we report a systematic study of a large cohort of families to define the prevalence and clinical features of intrafamilial discordance in ADPKD. Methods The extended Toronto Genetic Epidemiology Study of Polycystic Kidney Disease (eTGESP) cohort includes 1390 patients from 612 unrelated families with ADPKD ascertained in a regional polycystic kidney disease center. All probands underwent comprehensive PKD1 and PKD2 mutation screening. Total kidney volume by magnetic resonance imaging (MRI) was available in 500 study patients. Results Based on (i) rate of estimated glomerular filtration rate (eGFR) decline, (ii) age at onset of end-stage renal disease (ESRD), and (iii) Mayo Clinic Imaging Classification (MCIC), 20% of patients were classified as having mild disease, and 33% as having severe disease. Intrafamilial ADPKD discordance with at least 1 mild and 1 severe case was observed in 43 of 371 (12%) families, at a similar frequency regardless of the responsible gene (PKD1/PKD2/no mutation detected) or mutation type (protein-truncating versus nontruncating). Intrafamilial discordance was more common in larger families and was present in 30% of families with more than 5 affected members. The heritability of age at onset of ESRD was similar between different mutation types. Conclusion Extreme kidney disease discordance is present in at least 12% of families with ADPKD, regardless of the underlying mutated gene or mutation class. Delineating genetic and environmental modifiers underlying the observed intrafamilial ADPKD variability will provide novel insights into the mechanisms of progression in ADPKD., Graphical abstract

Epidemiological field studies utilizing disease monitoring, spore trapping, and trap plants were conducted on rabbiteye blueberry (Vaccinium virgatum) between 2014 and 2017 to shed light on the epidemiology of Exobasidium leaf and fruit spot, an emerging disease in the southeastern United States caused by the fungus Exobasidium maculosum. Wash plating of field-collected blueberry tissue from the late dormant season through bud expansion showed that the pathogen overwintered epiphytically on blueberry plants in the field, most likely in its yeast-like conidial stage. Agrichemical applications during the dormant season altered epiphytic populations of the pathogen, which correlated directly with leaf spot incidence later in the spring. Disease monitoring of field plants and weekly exposure of potted trap plants revealed that young leaves at the mouse-ear stage were most susceptible to infection, that disease incidence on leaves progressed monocyclically, and that infection periods were associated with rainfall variables such as the number of days per week with ≥1.0 mm of rain or cumulative weekly rainfall. Weekly spore trapping with an Andersen sampler showed that airborne inoculum was detected only after sporulating leaf lesions producing basidiospores were present in the field, suggesting that the primary inoculum is not airborne. The first symptoms on young, green fruit were observed soon after petal fall (requiring removal of the waxy fruit layer to visualize lesions), and visible disease progress on fruit was delayed by 1 to 3 weeks relative to that on leaves. Fruit infection of field plants and trap plants occurred before airborne propagules were detected by spore trapping and before sporulating leaf lesions were present in the field. Hence, this study showed that fruit infections are initiated by the same initial inoculum as leaf infections but it was not possible to conclusively exclude the possibility of a contribution of basidiospore inoculum from leaf lesions to disease progress on later developing fruit. This is one of only a few studies addressing the epidemiology and disease cycle of an Exobasidium sp. in a pathosystem where artificial inoculation has not been possible to date.

While α-V2O5 has traditionally been considered as a promising oxide to reversibly intercalate high levels of Mg2+ at high potential, recent reports indicate that previously observed electrochemical...

In recent years the delivery of practical laboratories classes has been subjected to debate, with regards to pedagogical efficiency. Our aim was to develop a pre-laboratory online learning resource...

Using survey data from 2015 to 2018, this article analyses the occupational licensing wage premium in the United States. The estimates show a robust 4–6 per cent wage differential for licensed workers. This premium is robust to careful control for location/local labour market effects and occupation effects. The premium is also positive for the majority of individual occupations and groups of occupations estimated. Similar results are found using additional techniques, including a matching estimator and an analysis of border metropolitan statistical areas.

Sensory feedback has traditionally been considered critical for motor learning. While it has been shown that motor learning can occur in the absence of visual or somatosensory feedback, it is thought that at least one must be present. This assumption contrasts with literature demonstrating that motor imagery (MI) - the mental rehearsal of a movement - is capable of driving motor learning even though the lack of actual execution precludes sensory feedback related to movement. However, studies of MI typically employ simple tasks that do not require improvements in motor execution per se, suggesting that MI might improve task performance primarily through perceptual mechanisms. To avoid this limitation, we designed a novel motor task requiring the repeated execution of unfamiliar kinematic trajectories where learning was assessed through changes in the speed-accuracy function (SAF) across five sessions. General task performance was controlled for by assessing performance on randomly generated trajectories. Groups included physical practice (PP; with and without added visual feedback), MI, and perceptual control (PC), the latter of which only observed the trajectories. All groups performed physically on the final session. Upon the final session, the MI group performed better than the PC group, and better than initial session PP performance. These results suggest that motor learning occurred in the MI group despite the lack of sensory feedback related to the movement, and that this learning was not simply the result of perceptual learning. Our results question long-standing assumptions about MI based learning and the necessity of feedback in motor learning generally.

Conventionally, we expect the transport of intercalated species in battery active particles is limited by diffusion. MgCr2O4 has been identified as a candidate active material for the Mg batteries based on its theoretical Mg-storing capacity, high open circuit potential, and acceptable diffusion barrier for Mg-ion transport (1,2). However, when operated electrochemically, its performance does not match the promised potential (3). Motivated by these observations, we examine charge transport in dense MgCr2O4 pellets in an electrolyte-free setup to conclusively probe bulk Mg transport. We find that the ion transport in this material cannot be explained by using the conventional understanding. We propose a new theory that extends the conventional picture and accounts for the unusual behavior in MgCr2O4 (4). We further discuss the implications of this understanding for engineering active material particles in MgCr2O4 porous electrodes. References Canepa, P.; Sai Gautam, G.; Hannah, D. C.; Malik, R.; Liu, M.; Gallagher, K. G.; Persson, K. A.; Ceder, G. (2017) "Odyssey of Multivalent Cathode Materials: Open Questions and Future Challenges." Chem. Rev., 117 (5), 4287–4341. DOI: 10.1021/acs.chemrev.6b00614. Bayliss, R. D.; Key, B.; Sai Gautam, G.; Canepa, P.; Kwon, B. J.; Lapidus, S. H.; Dogan, F.; Adil, A. A.; Lipton, A. S.; Baker, P. J.; Ceder, G.; Vaughey, J. T.; Cabana, J. (2020) "Probing Mg Migration in Spinel Oxides." Chem. Mater., 32 (2), 663–670. DOI: 10.1021/acs.chemmater.9b02450. Hu, L.; Johnson, I. D.; Kim, S.; Nolis, G. M.; Freeland, J. W.; Yoo, H. D.; Fister, T. T.; McCafferty, L.; Ashton, T. E.; Darr, J. A.; Cabana, J. (2019) "Tailoring the Electrochemical Activity of Magnesium Chromium Oxide towards Mg Batteries through Control of Size and Crystal Structure." Nanoscale, 11 (2), 639–646. DOI: 10.1039/C8NR08347A. Johnson, I.D.; Mistry, A.; Yin, L.; Murphy, M.; Wolfman, M.; Fister, T. T.; Lapidus, S. H.; Cabana, J.; Srinivasan, V.; Ingram, B. J. (2022) "Investigating Charge Transport in MgCr2O4 Extends the Understanding of Battery Intercalation Hosts.", under review

In this paper, we describe 15 novel HLA alleles discovered and officially named in the calendar years 2019 through the first half of 2021.

The COVID-19 pandemic has led to temporary suspensions of many occupational licensing laws in an effort to manage surges in health care demand. The crisis highlights more general concerns about occupational licensing laws, yet convincing empirical evidence on the degree to which such laws have inhibited entry into health care professions is scarce. In this study, we indirectly examine how occupational licensing affects the choice to become an emergency medical technician (EMT) by exploiting the demand-side shock from the Affordable Care Act (ACA). We find suggestive evidence that while the demand-side shock from the ACA increased the likelihood of being an EMT, this effect was substantially moderated by more stringent occupational licensing laws. The implied effects for young individuals in the most careful specification suggests virtually complete offset;the ACA demand-side shock would increase entry by 18 percentage points, while occupational licensing restrictions reduce entry by a similar magnitude. © 2021 The Southern Economic Association.

Evolutionarily conserved signaling intermediate in Toll pathways (ECSIT) is a protein with roles in early development, activation of the transcription factor NF-κB, and production of mitochondrial reactive oxygen species (mROS) that facilitates clearance of intracellular bacteria like Salmonella. ECSIT is also an important assembly factor for mitochondrial complex I. Unlike the murine form of Ecsit (mEcsit), we demonstrate here that human ECSIT (hECSIT) is highly labile. To explore whether the instability of hECSIT affects functions previously ascribed to its murine counterpart, we created a potentially novel transgenic mouse in which the murine Ecsit gene is replaced by the human ECSIT gene. The humanized mouse has low levels of hECSIT protein, in keeping with its intrinsic instability. Whereas low-level expression of hECSIT was capable of fully compensating for mEcsit in its roles in early development and activation of the NF-κB pathway, macrophages from humanized mice showed impaired clearance of Salmonella that was associated with reduced production of mROS. Notably, severe cardiac hypertrophy was manifested in aging humanized mice, leading to premature death. The cellular and molecular basis of this phenotype was delineated by showing that low levels of human ECSIT protein led to a marked reduction in assembly and activity of mitochondrial complex I with impaired oxidative phosphorylation and reduced production of ATP. Cardiac tissue from humanized hECSIT mice also showed reduced mitochondrial fusion and more fission but impaired clearance of fragmented mitochondria. A cardiomyocyte-intrinsic role for Ecsit in mitochondrial function and cardioprotection is also demonstrated. We also show that cardiac fibrosis and damage in humans correlated with low expression of human ECSIT. In summary, our findings identify a role for ECSIT in cardioprotection, while generating a valuable experimental model to study mitochondrial dysfunction and cardiac pathophysiology.

α-V

The contribution of the gut microbiome to human health has long been established, with normal gut microbiota conferring protection against invasive pathogens. Antibiotics can disrupt the microbial balance of the gut, resulting in disease and the development of antimicrobial resistance. The effect of antibiotic administration route on gut dysbiosis remains under-studied to date, with conflicting evidence on the differential effects of oral and parenteral delivery. We have profiled the rat gut microbiome following treatment with commonly prescribed antibiotics (amoxicillin and levofloxacin), via either oral or intravenous administration. Fecal pellets were collected over a 13-day period and bacterial populations were analyzed by 16S rRNA gene sequencing. Significant dysbiosis was observed in all treatment groups, regardless of administration route. More profound dysbiotic effects were observed following amoxicillin treatment than those with levofloxacin, with population richness and diversity significantly reduced, regardless of delivery route. The effect on specific taxonomic groups was assessed, revealing significant disruption following treatment with both antibiotics. Enrichment of a number of groups containing known gut pathogens was observed, in particular, with amoxicillin, such as the family Enterobacteriaceae. Depletion of other commensal groups was also observed. The degree of dysbiosis was significantly reduced toward the end of the sampling period, as bacterial populations began to return to pretreatment composition. Richness and diversity levels appeared to return to pretreatment levels more quickly in intravenous groups, suggesting convenient parenteral delivery systems may have a role to play in reducing longer term gut dysbiosis in the treatment of infection.

First paragraph: Bushmeat (or ‘wild meat’, defined as the meat of wild animals) is a major source of protein for rural people across sub-Saharan Africa (Ingram et al., 2021), yet some species suffer unsustainable levels of exploitation often to meet the demands of increasing urban populations (Coad et al., 2019; Wilkie et al., 2016). As in the rest of Central Africa, Cameroon has a long history of bushmeat consumption and trade (Bahuchet & Ioveva, 1999; Randolph, 2016). Pangolins (Family: Manidae) have been one of the many groups of species exploited as they are highly valued for food and, in some countries, used as traditional remedies (Soewu et al., 2020). Pangolin meat is favoured for its taste and it remains commonly offered for sale in Cameroonian markets and restaurants (Ingram et al., 2018; Nguyen et al., 2021). Furthermore, Cameroon has become one of the major export countries for the illegal trade in pangolin scales from Africa to Asia (Ingram et al., 2019a), to supply the market for Asian traditional medicines, for example in traditional Chinese medicine (Wang et al., 2020). All African pangolin species are now considered to have declining population trends (Ingram et al., 2019b; Nixon et al., 2019; Pietersen et al., 2019a, 2019b).

Purpose/Objective(s) Accelerated Partial Breast Irradiation (APBI) is a valid treatment option for women with early-stage breast cancer (BC) who meet the “suitable” criteria per ASTRO APBI guidelines. Magnetic Resonance Imaging guided APBI (MRgAPBI) results in less set up uncertainty and possibly tighter planning target volume (PTV) margins. This study aims to report MRgAPBI treatment outcomes and patient reported cosmesis. Materials/Methods This IRB approved retrospective study included early-stage BC patients who underwent lumpectomy with or without sentinel lymph node biopsy and were treated consecutively at our institution with MRgAPBI between 2018 and 2020, with a minimum follow up of 6 months. Charts were reviewed for patient and tumor characteristics, APBI induced adverse events, and treatment outcomes. Patients reported their breast appearance as “Poor, Fair, Good, or Excellent”, two weeks after APBI completion and at their last follow up. Results The study included 19 eligible patients. Mean patients age was 72 years old (range 51 – 89), 68% had invasive ductal carcinoma (IDC), and 32% had ductal carcinoma in-situ. Mean tumor size was 9 mm (range 4-16 mm), 53%, 37%, and 10% had grade 1, 2, and 3 disease respectively. All patients had ER / PR positive disease, all IDC patients had HER2 negative disease, and a median Ki67 of 5% (range 1 – 60%). In patients with IDC, 8%, 69%, and 23% had stage pT1a, pT1b, and pT1c respectively. All patients had lymph node negative disease. Mean closest surgical margin was 5.75 mm (range 3-11 mm). 32% of patients received 30 Gy in 5 once daily fractions of 6 Gy given every other day, and 68% received 38.5 Gy in twice daily fractions of 3.85 Gy. All patients’ plans met the dose constraints including the ratio of volume receiving at least 95% of the prescription dose to the whole breast target volume ( Conclusion MRgAPBI in our early single institution experience is an effective and well tolerated treatment modality for women with early-stage BC who meet “suitable” criteria per ASTRO APBI guidelines. All patients reported their cosmetic outcomes as good or excellent and none had local, regional or distant recurrence at a median follow up of 18 months. Longer follow up and larger cohorts are required.

The Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) prohibits commercial trans-national trade in pangolin specimens. However, African pangolins are continually trafficked to Asia for traditional medicine, with Nigeria considered a key hub. Using reported Nigeria-linked pangolin seizure data and interviews with Nigerian law enforcement officials, we a) characterised Nigeria's involvement in global pangolin trafficking January 2010–September 2021, particularly observing trafficking trends after pangolin's CITES Appendix I listing; b) estimated the minimum number of pangolins whose scales are in Nigeria-linked seizures January 2010–September 2021, and; c) assessed ongoing efforts within Nigeria to curb pangolin trafficking. Nigeria-linked seizures involved 190,407 kg of pangolin derivatives (99.9% scales) from a minimum of 799,343 pangolins (95% confidence interval; 625,944-996,353) of four species (see caveats in Methods). All shipments confiscated in transit were destined for Asia, with a rapid increase in the mass of maritime shipments over time. Furthermore, stockpiling of pangolin derivatives for overseas shipment is perhaps a prominent trafficking model in Nigeria. Nigeria's law enforcement efforts improved from 2017, the same year Nigeria apparently began playing a hub role. The impact of pangolin's CITES Appendix I listing on pangolin trafficking was unclear, as the marked rise in seizures from 2017 when the listing became effective, coincided with improvements in Nigerian law enforcement efforts. COVID-19–induced travel restrictions likely reduced trafficking activities in 2020 but activities may have fully resumed in 2021. This study provides new information to inform effective enforcement and policy formulation efforts to protect African pangolins., Highlights • We characterised Nigeria-linked pangolin trafficking using three types of data. • Nigeria-linked seizures (2010-Sept 2021) involved 190,407 kg of pangolin specimens. • These seizures contained scales from a minimum of ~0.8 million pangolins. • CITES Appendix I listing of pangolins may not have reduced trafficking. • Combining multiple data types enhances illegal wildlife trade research.

After decades of cyclical peace agreement failures and war in Mindanao, the establishment of the Bangsamoro Autonomous Region of Muslim Mindanao (BARMM) in early 2019 brought the best hope for sustainable peace and stability in living memory. But the problems within the BARMM and Mindanao more broadly are immense. A trifecta of stigma, shame, and fear is regularly identified as levers exploited by peace spoilers to not only recruit and mobilize from local communities but obstruct disengagement and reintegration efforts. The widespread and intergenerational experiences of trauma across Mindanao hang like an invisible pall over almost every aspect of life. The dynamics of stigma, shame, and fear in Mindanao tend to be multidimensional in that they may emerge from a range of sources and multidirectional in their effect, as different sources of stigma, shame, and fear can push and pull individuals and groups in different ways. Stigma, shame, and fear may act as obstacles but also opportunities that need to be understood and appropriately harnessed in disengagement and reintegration initiatives. This policy note offers a framework of recommendations that are largely grounded in peacebuilding approaches.

Soil-to-atmosphere methane (CH4) fluxes are dependent on opposing microbial processes of production and consumption. Here we use a soil–vegetation gradient in an Australian sub-alpine ecosystem to examine links between composition of soil microbial communities, and the fluxes of greenhouse gases they regulate. For each soil/vegetation type (forest, grassland, and bog), we measured carbon dioxide (CO2) and CH4 fluxes and their production/consumption at 5 cm intervals to a depth of 30 cm. All soils were sources of CO2, ranging from 49 to 93 mg CO2 m−2 h−1. Forest soils were strong net sinks for CH4, at rates of up to −413 µg CH4 m−2 h−1. Grassland soils varied, with some soils acting as sources and some as sinks, but overall averaged −97 µg CH4 m−2 h−1. Bog soils were net sources of CH4 (+340 µg CH4 m−2 h−1). Methanotrophs were dominated by USCα in forest and grassland soils, and Candidatus Methylomirabilis in the bog soils. Methylocystis were also detected at relatively low abundance in all soils. Our study suggests that there is a disproportionately large contribution of these ecosystems to the global soil CH4 sink, which highlights our dependence on soil ecosystem services in remote locations driven by unique populations of soil microbes. It is paramount to explore and understand these remote, hard-to-reach ecosystems to better understand biogeochemical cycles that underpin global sustainability.

COVID-19 has affected almost every aspect of society including freshwater fisheries fieldwork. Our study quantified the effects of the pandemic on fisheries fieldwork in the United States. We administered a survey to fisheries chiefs in all 50 states to assess the pandemic's impact on fisheries fieldwork. Of the 37 participants, 91% reported the pandemic affected their fieldwork and 92% adapted their sampling methods in response to the pandemic. Common adaptation strategies included using personal protective equipment (100%), practicing social distancing (97%), using smaller crews (82%), and developing contingency plans (51%). Based on the survey results, we identified potential challenges to adaptations and offered strategies to improve them. Strategies we identified include adopting novel data collection techniques, finding new positions for temporary employees, and publicly sharing contingency plans. Ultimately, this paper offers novel guidance on how fisheries professionals can best move forward with fieldwork during a time of crisis.

Astrocytes play active roles at synapses and can monitor, respond, and adapt to local synaptic activity. To investigate this relationship, more tools that can selectively activate native G protein signaling pathways in astrocytes with both spatial and temporal precision are needed. Here, we tested AAV8-GFAP-Optoα1AR-eYFP (Optoα1AR), a viral vector to enable activation of Gq signaling in astrocytes via light-sensitive α1-adrenergic receptors. To determine if stimulating astrocytic Optoα1AR modulates hippocampal synaptic transmission, recordings were made in CA1 pyramidal cells with surrounding astrocytes expressing Optoα1AR, channelrhodopsin (ChR2), or GFP. Both high-frequency (20 Hz, 45-ms light pulses, 5 mW, 5 min) and low-frequency (0.5 Hz, 1-s pulses at increasing 1, 5, and 10 mW intensities, 90 s per intensity) blue light stimulation were tested. 20 Hz Optoα1AR stimulation increased both inhibitory and excitatory postsynaptic current (IPSC and EPSC) frequency, and the mIPSC effect was largely reversible within 20 min. By contrast, low-frequency stimulation of Optoα1AR did not modulate either IPSCs or EPSCs, whereas the same stimulation of astrocytic ChR2 was effective. These data demonstrate that Optoα1AR activation in astrocytes changes synaptic excitation and inhibition in a stimulation-sensitive manner, demonstrating the efficacy and utility of GFAP-Optoα1AR as a tool in studying astrocyte-neuron interactions.

Background. Elevated levels of the cysteine protease cathepsin S (CatS) are associated with chronic mucoobstructive lung diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). We have previously demonstrated that prophylactic treatment with a CatS inhibitor from birth reduces inflammation, mucus plugging, and lung tissue damage in juvenile β-epithelial Na+ channel-overexpressing transgenic (βENaC-Tg) mice with chronic inflammatory mucoobstructive lung disease. In this study, we build upon this work to examine the effects of therapeutic intervention with a CatS inhibitor in adult βENaC-Tg mice with established disease. Methods. βENaC-Tg mice and wild-type (WT) littermates were treated with a CatS inhibitor from 4 to 6 weeks of age, and CatS-/-βENaC-Tg mice were analysed at 6 weeks of age. Bronchoalveolar lavage (BAL) fluid inflammatory cell counts were quantified, and lung tissue destruction and mucus obstruction were analysed histologically. Results. At 6 weeks of age, βENaC-Tg mice developed significant airway inflammation, lung tissue damage, and mucus plugging when compared to WT mice. CatS-/-βENaC-Tg mice and βENaC-Tg mice receiving inhibitor had significantly reduced airway mononuclear and polymorphonuclear (PMN) cell counts as well as mucus plugging. However, in contrast to CatS-/-βENaC-Tg mice, therapeutic inhibition of CatS in βENaC-Tg mice had no effect on established emphysema-like lung tissue damage. Conclusions. These results suggest that while early CatS targeting may be required to prevent the onset and progression of lung tissue damage, therapeutic CatS targeting effectively inhibited airway inflammation and mucus obstruction. These results indicate the important role CatS may play in the pathogenesis and progression of mucoobstructive lung disease.

Charismatic leaders have often emerged at the forefront of Sunni jihadist groups. Three factors are important for understanding this trend. First, the role of perceptions of crisis among potential supporters. Second, Sunni jihadist charismatic figures emerge as antagonists to mainstream religious and political authorities. Third, they typically build on the “charismatic capital” of predecessors in a form of routinization called “transformative charisma.” This chapter explores the interplay of these factors in the example of Anwar al-Awlaki (1971–2011), the American-born al-Qaida spokesman, to demonstrate the utility of charismatic leadership theory and the importance of charismatic figures in the evolution of Sunni jihadism.

Students’ experience of learning, relating and belonging are crucial to their participation in school. With ever growing concern about young people’s mental health and levels of informal and formal exclusion it is timely to investigate how schools can be supported in meeting the social and psychological needs of learners. The focus of this paper is the development of a questionnaire to investigate the relationship between pupils’ experience of belonging and the barriers they encounter in the school setting. Our aim was to test out the tool prior to full standardisation. Data was collected from 722 students across four secondary schools. Four factors were identified within the scale with one factor, that which measured emotional security and comfort, demonstrating moderate correlations to all other scales indicating that it had an underlying relationships to different aspects of the school environment. Students who disclosed SEND had a greater likelihood of demonstrating low connectedness than would be expected by chance alone, with some differences in the degree to which particular items were predictive of overall levels of connectedness.

Soil-to-atmosphere methane (CH4) fluxes are dependent on opposing microbial processes of production and consumption. Here we use a soil-vegetation gradient in an Australian sub-alpine ecosystem to examine links between composition of soil microbial communities, and the fluxes of greenhouse gases they regulate. For each soil-vegetation type (forest, grassland, and bog), we measured carbon dioxide (CO2) and CH4 fluxes and their production/consumption at 5-cm intervals to a depth of 30 cm. All soils were sources of CO2, ranging from 49-93 mg CO2 m-2 h-1. Forest soils were strong net sinks for CH4 at rates up to −413 µg CH4 m-2 h-1. Grassland soils varied with some soils acting as sources and some as sinks, but overall averaged −97 µg CH4 m-2 h-1. Bog soils were net sources of CH4 (+340 µg CH4 m-2 h-1). Methanotrophs were dominated by USCα in forest and grassland soils, and Candidatus Methylomirabilis sp. in the bog soils. Methylocystis were also detected at relatively low abundance. The potential disproportionately large contribution of these ecosystems to global CH4 oxidation, and poorly understood microbial community regulating it, highlight our dependence on soil ecosystem services in remote locations can be driven by a unique population of soil microbes.Originality-Significance Statement(Identify the key aspects of originality and significance that place the work within the top 10% of current research in environmental microbiology)Novel methanotrophic bacteria have been discovered in recent years, but few studies have examined the total known diversity of methanotrophs together with the net flux of CH4 from soils. We used an ecosystem with a vegetation-soil gradient in the sub-alpine regions of Australia (with extremely strong consumption of atmospheric CH4) to examine microbial and abiotic drivers of CH4 fluxes across this gradient. Recently characterized methanotrophs, either USCα in forest and grassland soils, or oxygenic Candidatus Methylomirabilis sp. in the bog soil were dominant. Methanotrophs belonging to the families Methylococcaceae and Methylocystaceae represented only a small minority of the methanotrophs in this ecosystem.

V2O5 is of interest as a Mg intercalation electrode material for Mg batteries, both in its thermodynamically stable layered polymorph (α-V2O5) and in its metastable tunnel structure (ζ-V2O5). However, such oxide cathodes typically display poor Mg insertion/removal kinetics, with large voltage hysteresis. Herein, we report the synthesis and evaluation of nanosized (ca. 100 nm) ζ-V2O5 in Mg-ion cells, which displays significantly enhanced electrochemical kinetics compared to microsized ζ-V2O5. This effect results in a significant boost in stable discharge capacity (130 mA h g-1) compared to bulk ζ-V2O5 (70 mA h g-1), with reduced voltage hysteresis (1.0 V compared to 1.4 V). This study reveals significant advancements in the use of ζ-V2O5 for Mg-based energy storage and yields a better understanding of the kinetic limiting factors for reversible magnesiation reactions into such phases.

Only 10 years remain to achieve all Sustainable Development Goals (SDGs) globally, so there is a growing need to increase the effectiveness and efficiency of action by targeting multiple SDGs. The SDGs were conceived as an ‘indivisible whole’, but interactions between SDGs need to be better understood. Several previous assessments have begun to explore interactions including synergies and possible conflicts between the SDGs, and differ widely in their conclusions. Although some highlight the role of the more environmentally-focused SDGs in underpinning sustainable development, none specifically focuses on environment–human linkages. Assessing interactions between SDGs, and the influence of environment on them can make an important contribution to informing decisions in 2020 and beyond. Here, we review previous assessments of interactions among SDGs, apply an influence matrix to assess pairwise interactions between all SDGs, and show how viewing these from the perspective of environment–human linkages can influence the outcome. Environment, and environment–human linkages, influence most interactions between SDGs. Our action-focused assessment enables decision makers to focus environmental management to have the greatest impacts and to identify opportunities to build on synergies and reduce trade-offs between particular SDGs. It may enable sectoral decision makers to seek support from environment managers for achieving their goals. We explore cross-cutting issues and the relevance and potential application of our approach in supporting decision making for progress to achieve the SDGs.

Background Elevated levels of the cysteine protease cathepsin S (CatS) are associated with chronic mucoobstructive lung diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). We have previously demonstrated that prophylactic treatment with a CatS inhibitor from birth reduces inflammation, mucus plugging, and lung tissue damage in juvenile β-epithelial Na+ channel-overexpressing transgenic (βENaC-Tg) mice with chronic inflammatory mucoobstructive lung disease. In this study, we build upon this work to examine the effects of therapeutic intervention with a CatS inhibitor in adult βENaC-Tg mice with established disease. Methods βENaC-Tg mice and wild-type (WT) littermates were treated with a CatS inhibitor from 4 to 6 weeks of age, and CatS−/−βENaC-Tg mice were analysed at 6 weeks of age. Bronchoalveolar lavage (BAL) fluid inflammatory cell counts were quantified, and lung tissue destruction and mucus obstruction were analysed histologically. Results At 6 weeks of age, βENaC-Tg mice developed significant airway inflammation, lung tissue damage, and mucus plugging when compared to WT mice. CatS−/−βENaC-Tg mice and βENaC-Tg mice receiving inhibitor had significantly reduced airway mononuclear and polymorphonuclear (PMN) cell counts as well as mucus plugging. However, in contrast to CatS−/−βENaC-Tg mice, therapeutic inhibition of CatS in βENaC-Tg mice had no effect on established emphysema-like lung tissue damage. Conclusions These results suggest that while early CatS targeting may be required to prevent the onset and progression of lung tissue damage, therapeutic CatS targeting effectively inhibited airway inflammation and mucus obstruction. These results indicate the important role CatS may play in the pathogenesis and progression of mucoobstructive lung disease.

According to the first Statute of Westminster, the law was administered that the peace of the land might be maintained in all points, and common right be done to all. The radical Norman Yoke theorists were to challenge the very basis of this doctrine, but even among more conformist thinkers in the early seventeenth century, the principle that the laws of England were beneficent was often accepted only with considerable qualification. In this period, recognizances were widely used in proceedings against criminals and other malefactors, and those which were certified to Wiltshire quarter sessions have survived. Moreover, the conditions of life in small communities probably helped to shield local people from the strict legal consequences of certain types of illegal behaviour. A court baron could function not only as customary court dealing with matters of tenure among the copyholders, but also as common law tribunal; and some manorial courts were still serving as forum for civil suits in this period.

We recently described a protein O-glycosylation pathway conserved in all species of the Burkholderia genus that results in synthesis and incorporation of a trisaccharide glycan to membrane-exported proteins. Here, we exploited this system to construct and evaluate a diagnostic tool for glanders. Burkholderia mallei, the causative agent of glanders, is a highly infectious and fatal zoonotic pathogen that mainly infects horses, mules, donkeys and occasionally humans. A highly sensitive and specific diagnostic tool is crucial for the control, elimination and eradication of B. mallei infections. We constructed plasmids carrying synthetic genes encoding a modified, previously unannotated Burkholderia glycoprotein containing three glycosylation sequons fused to the cholera toxin B-subunit. The resulting proteins were glycosylated in the B. cenocepacia K56-2 parental strain, but not in glycosylation-deficient mutants, as determined by SDS-PAGE and fluorescent lectin blots. One of these glycoproteins was used as an antigen in ELISA and western blots to screen a panel of serum samples collected from glanders-infected and healthy horses previously investigated by complement fixation test and indirect ELISA based on a semi-purified fraction of B. mallei. We show that ELISA and western blot assays based on our glycoprotein antigen provide 100 % specificity, with a sensitivity greater than 88%. The glycoprotein antigen was recognized by serum samples collected from patients infected with B. pseudomallei, B. mallei, B. multivorans and B. cenocepacia. Our results indicate that protein O-glycosylation in Burkholderia can be exploited as a biomarker for diagnosis of Burkholderia-associated infections.IMPORTANCEGlanders is a severe zoonotic disease caused by the Gram-negative bacterium Burkholderia mallei, which affects horses, mules and donkeys, as well as humans. B. mallei is also considered a category B biothreat agent. Due to insufficient pathognomonic symptoms in the early stages of glanders, diagnosis can be difficult. Complement fixation is the most accurate and reliable serological test prescribed by the World Organization for Animal Health; however, this test has a considerable number of false-positive results. We have recently described a conserved protein O-glycosylation pathway present in all species of the Burkholderia genus; we also demonstrated that Burkholderia-infected humans develop anti-glycan antibodies. Here, we exploited this system to construct and evaluate a synthetic glycoengineered protein antigen as a diagnostic tool for glanders. Our results show 100 % specificity in the detection of antibodies from infected horses, indicating that protein O-glycosylation in Burkholderia can be exploited as a biomarker for diagnosis of Burkholderia-associated infections.