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"Jensen, Benjamin"
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Cyber strategy : the evolving character of power and coercion
\"In 2011, the United States government declared a cyber attack as equal to an act of war, punishable with conventional military means. Cyber operations, cyber crime, and other forms of cyber activities directed by one state against another are now considered part of the normal relations range of combat and conflict, and the rising fear of cyber conflict has brought about a reorientation of military affairs. Despite the alarmist discussion surrounding the threat of cyber attack, the authors of this book (in a vein similar to Thomas Rid) argue that there is very little evidence that cyber war is, or is likely to become, a serious threat. What Valeriano and Maness provide in this manuscript is an empirically-grounded discussion of the reality of cyber conflict, based on an analysis of cyber incidents and disputes experienced by international states since 2001. They delineate patterns of cyber conflict to develop a larger theory of cyber war that gets at the processes leading to cyber conflict. They find that, in addition to being a little-used tactic, cyber incidents thus far have been of a rather low-level intensity and with few to no long-term effects. Interestingly, they also find that many cyber incidents are motivated by regional conflict. They argue that restraint is the norm in cyberspace and suggest there is evidence this norm can influence how the tactic is used in the future. In conclusion, the authors lay out a set of policy recommendations for proper defense against cyber threats that is built on restraint and regionalism\"-- Provided by publisher.
Book
Microbial activation of the GLP-2R mitigates gastrointestinal inflammation
There is an urgent need for sustainable protein sources to meet rising global nutritional demands. Here, we show that a commercially scalable microbial lysate from
Methylococcus capsulatus
Bath (McB), used as a dietary protein, orchestrates host-diet-microbe interactions that protect against gastrointestinal inflammation. McB administration rapidly reshapes the gut microbiota and upregulates microbial fermentation pathways, while robustly increasing peripherally induced regulatory T cells (pTregs) across intestinal regions, independent of the microbiota. In contrast, McB-driven induction of tolerogenic Th17 cells requires a functional microbiota with intact fermentation capacity. In models of mucositis and colitis, McB preserves villus architecture, restores mucosal integrity, and reduces disease severity. Mechanistically, these effects depend on microbial fermentation and functional GLP-2 receptor signalling, yet are independent of endogenous GLP-2 secretion, indicating a fermentation-driven molecular mimicry of GLP-2R activation. Collectively, our findings position microbial lysates as a sustainable nutritional strategy that improves gastrointestinal health through defined immune and microbial pathways.
Here, Yang-Jensen et al. demonstrate that a scalable microbial protein lysate from
Methylococcus capsulatus Bath
reshapes gut microbiota and T cells and, via fermentation-driven GLP-2 receptor mimicry, protects against gastrointestinal inflammation while providing sustainable protein nutrition
Journal Article
Aberrant intestinal microbiota in individuals with prediabetes
Aims/hypothesisIndividuals with type 2 diabetes have aberrant intestinal microbiota. However, recent studies suggest that metformin alters the composition and functional potential of gut microbiota, thereby interfering with the diabetes-related microbial signatures. We tested whether specific gut microbiota profiles are associated with prediabetes (defined as fasting plasma glucose of 6.1–7.0 mmol/l or HbA1c of 42–48 mmol/mol [6.0–6.5%]) and a range of clinical biomarkers of poor metabolic health.MethodsIn the present case–control study, we analysed the gut microbiota of 134 Danish adults with prediabetes, overweight, insulin resistance, dyslipidaemia and low-grade inflammation and 134 age- and sex-matched individuals with normal glucose regulation.ResultsWe found that five bacterial genera and 36 operational taxonomic units (OTUs) were differentially abundant between individuals with prediabetes and those with normal glucose regulation. At the genus level, the abundance of Clostridium was decreased (mean log2 fold change −0.64 (SEM 0.23), padj = 0.0497), whereas the abundances of Dorea, [Ruminococcus], Sutterella and Streptococcus were increased (mean log2 fold change 0.51 (SEM 0.12), padj = 5 × 10−4; 0.51 (SEM 0.11), padj = 1 × 10−4; 0.60 (SEM 0.21), padj = 0.0497; and 0.92 (SEM 0.21), padj = 4 × 10−4, respectively). The two OTUs that differed the most were a member of the order Clostridiales (OTU 146564) and Akkermansia muciniphila, which both displayed lower abundance among individuals with prediabetes (mean log2 fold change −1.74 (SEM 0.41), padj = 2 × 10−3 and −1.65 (SEM 0.34), padj = 4 × 10−4, respectively). Faecal transfer from donors with prediabetes or screen-detected, drug-naive type 2 diabetes to germfree Swiss Webster or conventional C57BL/6 J mice did not induce impaired glucose regulation in recipient mice.Conclusions/interpretationCollectively, our data show that individuals with prediabetes have aberrant intestinal microbiota characterised by a decreased abundance of the genus Clostridium and the mucin-degrading bacterium A. muciniphila. Our findings are comparable to observations in overt chronic diseases characterised by low-grade inflammation.
Journal Article
Cyber strategy : the evolving character of power and coercion
This book examines how states integrate cyber capabilities with other instruments of power to achieve foreign policy outcomes. Given North Korea’s use of cyber intrusions to threaten the international community and extort funds for its elites, Chinese espionage and the theft of government records through the Office of Personal Management (OPM) hack, and the Russian hack on the 2016 US election, this book is a timely contribution to debates about power and influence in the 21st century. Its goal is to understand how states apply cyber means to achieve political ends, a topic speculated and imagined, but investigated with very little analytical rigor. Following on Valeriano and Maness’s (2015) book, Cyber War versus Cyber Realities: Cyber Conflict in the International System, this new study explores how states apply cyber strategies, using empirical evidence and key theoretical insights largely missed by the academic and strategy community. It investigates cyber strategies in their integrated and isolated contexts, demonstrating that they are useful to managing escalation and sending ambiguous signals, but generally they fail to achieve coercive effect.
eBook
Human β-Defensin 2 Mediated Immune Modulation as Treatment for Experimental Colitis
Defensins represents an integral part of the innate immune system serving to ward off potential pathogens and to protect the intestinal barrier from microbial encroachment. In addition to their antimicrobial activities, defensins in general, and human β-defensin 2 (hBD2) in particular, also exhibit immunomodulatory capabilities. In this report, we assessed the therapeutic efficacy of systemically administered recombinant hBD2 to ameliorate intestinal inflammation in three distinct animal models of inflammatory bowel disease; i.e., chemically induced mucosal injury (DSS), loss of mucosal tolerance (TNBS), and T-cell transfer into immunodeficient recipient mice. Treatment efficacy was confirmed in all tested models, where systemically administered hBD2 mitigated inflammation, improved disease activity index, and hindered colitis-induced body weight loss on par with anti-TNF-α and steroids. Treatment of lipopolysaccharide (LPS)-activated human peripheral blood mononuclear cells with rhBD2 confirmed the immunomodulatory capacity in the circulatory compartment. Subsequent analyzes revealed dendritic cells (DCs) as the main target population. Suppression of LPS-induced inflammation was dependent on chemokine receptor 2 (CCR2) expression. Mechanistically, hBD2 engaged with CCR2 on its DC target cell to decrease NF-κB, and increase CREB phosphorylation, hence curbing inflammation. To our knowledge, this is the first study showing
efficacy of a systemically administered defensin in experimental disease.
Journal Article
Dietary fibre promotes chronic gut parasite infection via direct and time-dependent modulation of innate immunity
Background
Dietary fibre is an important regulator of the gut microbiome and is associated with many health benefits. However, high levels of fibre intake have also been reported to exacerbate some diseases.
Results
Here, we show that mice fed semi-synthetic diets supplemented with purified inulin fibre develop chronic infections with the parasitic whipworm
Trichuris muris
, concomitant with dysregulated innate antimicrobial defences, exacerbated mucosal inflammation, and altered tryptophan metabolism. Inhibition of tryptophan catabolism or neutralizing either IL-27 or IL-18 restored infection resistance. Inulin-fed mice developed gut microbiota dysbiosis during parasite infection, with Proteobacteria becoming dominant. However, despite drastic differences in gut microbiota compositions in control- and inulin-fed mice, microbiota transfer and depletion experiments demonstrated that dietary inulin triggered chronic
T. muris
infection in a microbiota-independent manner. Importantly, removing inulin from the diet within a critical immune development window rapidly restored anti-parasite immunity, indicating direct, time-dependent modulation of mucosal immune responses.
Conclusions
These data reveal
T. muris
-induced dysbiosis as a consequence rather than a causative factor of diet-driven changes in host susceptibility, and establish a direct link between dietary fibre and host defence at mucosal surfaces.
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Video Abstract
Journal Article
Mucosal transcriptomic landscape along the small and large intestines in individuals with and without type 2 diabetes
BackgroundA detailed mapping of functional differences among intestinal regions in healthy individuals remains incomplete. Identifying regional alterations in individuals with type 2 diabetes (T2D) could enhance our understanding of disease-related intestinal changes.ObjectiveTo characterise the transcriptomic landscape along the entire intestinal tract in healthy individuals and those with T2D, and to create a publicly accessible database for future research.DesignIn this observational study, mucosal biopsies were obtained from 16 sites along the intestinal tract through anterograde and retrograde double-balloon endoscopy in 12 individuals with T2D and 12 normoglycaemic matched healthy individuals. Full transcriptomic analysis was performed. Genes with significantly different expressions between intestinal regions were analysed in terms of their biological mechanisms in healthy individuals, while regional expression profiles were compared between individuals with and without T2D.ResultsIn healthy individuals, distinct gene clusters in the small and large intestines were associated with processes including immune response, mitochondrial activity and metabolism of organic substances. Individuals with T2D exhibited alterations in immune system activity and barrier permeability in the ileocaecal region and the large intestine.ConclusionOur study offers a detailed mapping of the transcriptomic landscape in the human intestinal tract, demonstrating regionalised gene expression profiles tied to critical biological processes. Notable alterations in immune system activity in the large intestine were observed in individuals with T2D. The publicly available database generated from this study (https://rnaseq.gubra.dk/) provides a valuable resource for exploring the mucosal transcriptome along the human intestinal tract.Trial registration numberNCT03044860
Journal Article
Targeting of Non-Dominant Antigens as a Vaccine Strategy to Broaden T-Cell Responses during Chronic Viral Infection
In this study, we compared adenoviral vaccine vectors with the capacity to induce equally potent immune responses against non-dominant and immunodominant epitopes of murine lymphocytic choriomeningitis virus (LCMV). Our results demonstrate that vaccination targeting non-dominant epitopes facilitates potent virus-induced T-cell responses against immunodominant epitopes during subsequent challenge with highly invasive virus. In contrast, when an immunodominant epitope was included in the vaccine, the T-cell response associated with viral challenge remained focussed on that epitope. Early after challenge with live virus, the CD8+ T cells specific for vaccine-encoded epitopes, displayed a phenotype typically associated with prolonged/persistent antigenic stimulation marked by high levels of KLRG-1, as compared to T cells reacting to epitopes not included in the vaccine. Notably, this association was lost over time in T cells specific for the dominant T cell epitopes, and these cells were fully capable of expanding in response to a new viral challenge. Overall, our data suggests a potential for broadening of the antiviral CD8+ T-cell response by selecting non-dominant antigens to be targeted by vaccination. In addition, our findings suggest that prior adenoviral vaccination is not likely to negatively impact the long-term and protective immune response induced and maintained by a vaccine-attenuated chronic viral infection.
Journal Article
Human α-Defensin 51–9 and Human β-Defensin 2 Improve Metabolic Parameters and Gut Barrier Function in Mice Fed a Western-Style Diet
Obesity and metabolic comorbidities are associated with gut permeability. While high-fructose and Western-style diet (WSD) disrupt intestinal barrier function, oral administration of human α-defensin 5 (HD5) and β-defensin 2 (hBD2) is believed to improve intestinal integrity and metabolic disorders. Eighty-four male C57BL/6J mice were fed a WSD or a control diet (CD) ± fructose (F) for 18 weeks. In week 13, mice were randomly divided into three intervention groups, receiving defensin fragment HD51–9, full-length hBD2, or bovine serum albumin (BSA)-control for six weeks. Subsequently, parameters of hepatic steatosis, glucose metabolism, and gut barrier function were assessed. WSDF increased body weight and hepatic steatosis (p < 0.01) compared to CD-fed mice, whereas peptide intervention decreased liver fat (p < 0.05) and number of hepatic lipid droplets (p < 0.01) compared to BSA-control. In addition, both peptides attenuated glucose intolerance by reducing blood glucose curves in WSDF-fed mice. Evaluation of gut barrier function revealed that HD51–9 and hBD2 improve intestinal integrity by upregulating tight junction and mucin expression. Moreover, peptide treatment restored ileal host defense peptides (HDP) expression, likely by modulating the Wnt, Myd88, p38, and Jak/STAT pathways. These findings strongly suggest that α- and β-defensin treatment improve hepatic steatosis, glucose metabolism, and gut barrier function.
Journal Article