Urinary tract infections (UTIs) are a severe public health problem and are caused by a range of pathogens, but most commonly by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, ...Enterococcus faecalis and Staphylococcus saprophyticus. High recurrence rates and increasing antimicrobial resistance among uropathogens threaten to greatly increase the economic burden of these infections. In this Review, we discuss how basic science studies are elucidating the molecular details of the crosstalk that occurs at the host-pathogen interface, as well as the consequences of these interactions for the pathophysiology of UTIs. We also describe current efforts to translate this knowledge into new clinical treatments for UTIs.
Commentary: When to restore the rhythm Walker, Jennifer D.
The Journal of thoracic and cardiovascular surgery,
12/2023, Letnik:
166, Številka:
6
Journal Article
In the past few decades, the prevalence of obesity and type 2 diabetes mellitus (T2DM), as well as older individuals at risk for Alzheimer's disease (AD), has increased. While the consumption of ...diets high in fat (total and saturated) have been linked to increased risk of AD, diets rich in antioxidants, polyunsaturated fats, and omega-3 fatty acids are associated with decreased risk. Additionally, AD patients are at increased risk for developing T2DM. Recent research suggests that there are stronger similarities between AD and T2DM than have previously been considered. Here we review the neurocognitive and inflammatory effects of high-fat diet consumption, its relationship to AD, and the treatment potential of dietary interventions that may decrease risk of cognitive decline and other associated neuropathological changes, such as insulin resistance, oxidative stress, and chronic inflammatory processes.
Poly(lactic acid) (PLA) is a synthetic polyester that has shown extensive utility in tissue engineering. Synthesized either by ring opening polymerization or polycondensation, PLA hydrolytically ...degrades into lactic acid, a metabolic byproduct, making it suitable for medical applications. Specifically, PLA nanofibers have widened the possible uses of PLA scaffolds for regenerative medicine and drug delivery applications. The use of nanofibrous scaffolds imparts a host of desirable properties, including high surface area, biomimicry of native extracellular matrix architecture, and tuning of mechanical properties, all of which are important facets of designing scaffolds for a particular organ system. Additionally, nanofibrous PLA scaffolds hold great promise as drug delivery carriers, where fabrication parameters and drug-PLA compatibility greatly affect the drug release kinetics. In this review, we present the latest advances in the use of PLA nanofibrous scaffolds for musculoskeletal, nervous, cardiovascular, and cutaneous tissue engineering and offer perspectives on their future use.
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Group 2 innate lymphoid cells (ILC2s) release interleukin-13 (IL-13) during protective immunity to helminth infection and detrimentally during allergy and asthma. Using two mouse models to deplete ...ILC2s in vivo, we demonstrate that T helper 2 (Th2) cell responses are impaired in the absence of ILC2s. We show that MHCII-expressing ILC2s interact with antigen-specific T cells to instigate a dialog in which IL-2 production from T cells promotes ILC2 proliferation and IL-13 production. Deletion of MHCII renders IL-13-expressing ILC2s incapable of efficiently inducing Nippostrongylus brasiliensis expulsion. Thus, during transition to adaptive T cell-mediated immunity, the ILC2 and T cell crosstalk contributes to their mutual maintenance, expansion and cytokine production. This interaction appears to augment dendritic-cell-induced T cell activation and identifies a previously unappreciated pathway in the regulation of type-2 immunity.
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•Genetic ablation of ILC2s impairs type-2 immunity•MHCII-expressing ILC2s potentiate Th2 responses•IL-2 from T cells promotes ILC2 proliferation and expression of type-2 cytokines•MHCII and IL-13 expression by ILC2s is important for N. brasiliensis expulsion
Type-2 innate lymphoid cells proliferate and release interleukin-13 during protective immunity to helminth infection and detrimentally during allergy and asthma. McKenzie and colleagues establish that these activities are potentiated through an MHC class II-mediated dialogue with T cells.
Ectomycorrhizal fungal (EMF) communities vary among microhabitats, supporting a dominant role for deterministic processes in EMF community assemblage. EMF communities also differ between forest and ...clearcut environments, responding to this disturbance in a directional manner over time by returning to the species composition of the original forest. Accordingly, we examined EMF community composition on roots of spruce seedlings planted in three different microhabitats in forest and clearcut plots: decayed wood, mineral soil adjacent to downed wood, or control mineral soil, to determine the effect of retained downed wood on EMF communities over the medium and long term. If downed and decayed wood provide refuge habitat distinct from that of mineral soil, we would expect EMF communities on seedlings in woody habitats in clearcuts to be similar to those on seedlings planted in the adjacent forest. As expected, we found EMF species richness to be higher in forests than clearcuts (P ≤ 0.01), even though soil nutrient status did not differ greatly between the two plot types (P ≥ 0.05). Communities on forest seedlings were dominated by Tylospora spp., whereas those in clearcuts were dominated by Amphinema byssoides and Thelephora terrestris. Surprisingly, while substrate conditions varied among microsites (P ≤ 0.03), especially between decayed wood and mineral soil, EMF communities were not distinctly different among microhabitats. Our data suggest that niche partitioning by substrate does not occur among EMF species on very young seedlings in high elevation spruce-fir forests. Further, dispersal limitations shape EMF community assembly in clearcuts in these forests.
Methionine-1 (M1)-linked ubiquitin chains regulate the activity of NF-κB, immune homeostasis, and responses to infection. The importance of negative regulators of M1-linked chains in vivo remains ...poorly understood. Here, we show that the M1-specific deubiquitinase OTULIN is essential for preventing TNF-associated systemic inflammation in humans and mice. A homozygous hypomorphic mutation in human OTULIN causes a potentially fatal autoinflammatory condition termed OTULIN-related autoinflammatory syndrome (ORAS). Four independent OTULIN mouse models reveal that OTULIN deficiency in immune cells results in cell-type-specific effects, ranging from over-production of inflammatory cytokines and autoimmunity due to accumulation of M1-linked polyubiquitin and spontaneous NF-κB activation in myeloid cells to downregulation of M1-polyubiquitin signaling by degradation of LUBAC in B and T cells. Remarkably, treatment with anti-TNF neutralizing antibodies ameliorates inflammation in ORAS patients and rescues mouse phenotypes. Hence, OTULIN is critical for restraining life-threatening spontaneous inflammation and maintaining immune homeostasis.
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•Mutation of OTULIN causes OTULIN-related autoinflammatory syndrome (ORAS) in humans•Anti-TNF treatment reverses inflammation in ORAS patient and OTULIN-deficient mice•OTULIN deficiency deregulates M1-polyUb signaling and causes sterile inflammation•Loss of OTULIN has cell-type-specific effects on LUBAC abundance and signaling
A homozygous hypomorphic mutation in the deubiquitinase OTULIN causes a potentially fatal autoinflammatory disorder, which is reconciled in mouse models.
Studies that have examined the association between parenting behaviors and childhood post-traumatic stress disorder (PTSD) have yielded mixed findings. To clarify the role of parenting in childhood ...PTSD we conducted a systematic review and meta-analysis of 14 studies that investigated the association between parenting and youth PTSD symptoms (total n=4010). Negative parenting behaviors (e.g. overprotection, hostility) accounted for 5.3% of the variance in childhood PTSD symptoms. Positive parenting behaviors (e.g. warmth, support) account for 2.0% of variance. The negative and positive parenting and child PTSD symptom associations did not statistically differ in magnitude. Moderator analyses indicated that methodological factors and trauma variables may affect the association between parenting and child PTSD. Most studies relied upon questionnaire measures of general parenting style, and studies were predominantly cross-sectional with weaker evidence found in longitudinal studies. Given the small number of high quality studies available, only provisional recommendations about the role of parenting in childhood PTSD are made.
•Significant associations were found between parenting behaviors and childhood PTSD.•Parenting behavior accounted for 2.0–5.3% of the variance in child PTSD.•Both negative and positive parenting were significantly associated with child PTSD.•Positive and negative parenting effects did not differ statistically in magnitude.•Methodological and trauma factors moderated the parenting–child PTSD association.
Concerns about secondary use of data and limited opportunities for benefit-sharing have focused attention on the tension that Indigenous communities feel between (1) protecting Indigenous rights and ...interests in Indigenous data (including traditional knowledges) and (2) supporting open data, machine learning, broad data sharing, and big data initiatives. The International Indigenous Data Sovereignty Interest Group (within the Research Data Alliance) is a network of nation-state based Indigenous data sovereignty networks and individuals that developed the 'CARE Principles for Indigenous Data Governance' (Collective Benefit, Authority to Control, Responsibility, and Ethics) in consultation with Indigenous Peoples, scholars, non-profit organizations, and governments. The CARE Principles are people- and purpose-oriented, reflecting the crucial role of data in advancing innovation, governance, and self-determination among Indigenous Peoples. The Principles complement the existing data-centric approach represented in the 'FAIR Guiding Principles for scientific data management and stewardship' (Findable, Accessible, Interoperable, Reusable). The CARE Principles build upon earlier work by the Te Mana Raraunga Maori Data Sovereignty Network, US Indigenous Data Sovereignty Network, Maiam nayri Wingara Aboriginal and Torres Strait Islander Data Sovereignty Collective, and numerous Indigenous Peoples, nations, and communities. The goal is that stewards and other users of Indigenous data will 'Be FAIR and CARE.' In this first formal publication of the CARE Principles, we articulate their rationale, describe their relation to the FAIR Principles, and present examples of their application.
Alnus trees associate with ectomycorrhizal (ECM) fungi and nitrogen‐fixing Frankia bacteria and, although their ECM fungal communities are uncommonly host specific and species poor, it is unclear ...whether the functioning of Alnus ECM fungal symbionts differs from that of other ECM hosts. We used exoenzyme root tip assays and molecular identification to test whether ECM fungi on Alnus rubra differed in their ability to access organic phosphorus (P) and nitrogen (N) when compared with ECM fungi on the non‐Frankia host Pseudotsuga menziesii. At the community level, potential acid phosphatase (AP) activity of ECM fungal root tips from A. rubra was significantly higher than that from P. menziesii, whereas potential leucine aminopeptidase (LA) activity was significantly lower for A. rubra root tips at one of the two sites. At the individual species level, there was no clear relationship between ECM fungal relative root tip abundance and relative AP or LA enzyme activities on either host. Our results are consistent with the hypothesis that ECM fungal communities associated with Alnus trees have enhanced organic P acquisition abilities relative to non‐Frankia ECM hosts. This shift, in combination with the chemical conditions present in Alnus forest soils, may drive the atypical structure of Alnus ECM fungal communities.
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