Cyclic-di-GMP and cyclic-di-AMP are second messengers produced by bacteria and influence bacterial cell survival, differentiation, colonization, biofilm formation, virulence, and bacteria-host ...interactions. In this study, we show that in both RAW264.7 macrophage cells and primary bone marrow-derived macrophages, the production of IFN-β and IL-6, but not TNF, in response to cyclic-di-AMP and cyclic-di-GMP requires MPYS (also known as STING, MITA, and TMEM173). Furthermore, expression of MPYS was required for IFN response factor 3 but not NF-κB activation in response to these bacterial metabolites. We also confirm that MPYS is required for type I IFN production by cultured macrophages infected with the intracellular pathogens Listeria monocytogenes and Francisella tularensis. However, during systemic infection with either pathogen, MPYS deficiency did not impact bacterial burdens in infected spleens. Serum IFN-β and IL-6 concentrations in the infected control and MPYS(-/-) mice were also similar at 24 h postinfection, suggesting that these pathogens stimulate MPYS-independent cytokine production during in vivo infection. Our findings indicate that bifurcating MPYS-dependent and -independent pathways mediate sensing of cytosolic bacterial infections.
Responses of species to climate change are extremely variable, perhaps because of climate-related changes to interactions among species. We show that temperature-related changes in the dependence of ...the butterfly Aricia agestis on different larval host plants have facilitated rapid range expansion. Historically, the butterfly was largely restricted to a single plant species, Helianthemum nummularium, but recent warmer conditions have enabled the butterfly to increasingly use the more widespread plant species Geranium molle. This has resulted in a substantial increase in available habitat and rapid range expansion by the butterfly (79 kilometers northward in Britain in 20 years). Interactions among species are often seen as constraints on species' responses to climate change, but we show that temperature-dependent changes to interspecific interactions can also facilitate change.
The present pre-registered research provides the first evidence that a downwards head tilt is sufficient to communicate dominance from a neutral facial expression among the Mayangna, members of an ...unindustrialized, small-scale traditional society in Nicaragua who have had minimal exposure to North American culture. Consistent with the Action Unit imposter effect observed in North American populations (Witkower and Tracy in Psychol Sci 30:893-906, 2019), changes to the appearance of the upper face caused by a downwards head tilt were sufficient to elicit perceptions of dominance among this population. Given that the Mayangna are unlikely to associate a downwards head tilt or related apparent facial changes with dominance as a result of cross-cultural learning, the present results suggest that perceptions of dominance formed from a downwards head tilt, and the visual illusion shaping these perceptions, are a widely generalizable, and possibly universal, feature of human psychology.
The study aimed to investigate the link between burnout symptoms and prosocial behaviour, as well as the role of acute stress and vagally-mediated heart rate variability (vmHRV) on this association.
...Seventy men were randomly assigned to either the stress or the control condition of the Trier Social Stress Test for Groups (TSST-G). Prosocial behaviour was assessed via a social decision-making paradigm during the respective TSST-G condition.
Correlation analyses revealed negative correlations between prosocial behaviour and burnout symptoms. Acute stress was also associated with reduced prosocial behaviour, whereas no interaction effects with burnout symptoms could be revealed. Exploratory analyses showed that vmHRV was negatively correlated with burnout symptoms during the social decision-making paradigm but did not mediate the link between burnout and prosocial behaviour.
In conclusion, we report first experimental evidence that burnout symptoms are negatively associated with prosocial behaviour. Further studies are needed to explore the causal relations.
Noise-induced hearing loss (NIHL) is a major unresolved public health problem. Here, we investigate pathomechanisms of sensory hair cell death and suggest a novel target for protective intervention. ...Cellular survival depends upon maintenance of energy homeostasis, largely by AMP-activated protein kinase (AMPK). In response to a noise exposure in CBA/J mice, the levels of phosphorylated AMPKα increased in hair cells in a noise intensity-dependent manner. Inhibition of AMPK via siRNA or the pharmacological inhibitor compound C attenuated noise-induced loss of outer hair cells (OHCs) and synaptic ribbons, and preserved auditory function. Additionally, noise exposure increased the activity of the upstream AMPK kinase liver kinase B1 (LKB1) in cochlear tissues. The inhibition of LKB1 by siRNA attenuated the noise-increased phosphorylation of AMPKα in OHCs, reduced the loss of inner hair cell synaptic ribbons and OHCs, and protected against NIHL. These results indicate that noise exposure induces hair cell death and synaptopathy by activating AMPK via LKB1-mediated pathways. Targeting these pathways may provide a novel route to prevent NIHL.
Our results demonstrate for the first time that the activation of AMP-activated protein kinase (AMPK) α in sensory hair cells is noise intensity dependent and contributes to noise-induced hearing loss by mediating the loss of inner hair cell synaptic ribbons and outer hair cells. Noise induces the phosphorylation of AMPKα1 by liver kinase B1 (LKB1), triggered by changes in intracellular ATP levels. The inhibition of AMPK activation by silencing AMPK or LKB1, or with the pharmacological inhibitor compound C, reduced outer hair cell and synaptic ribbon loss as well as noise-induced hearing loss. This study provides new insights into mechanisms of noise-induced hearing loss and suggests novel interventions for the prevention of the loss of sensory hair cells and cochlear synaptopathy.
Context:
Changes in serum vitamin D metabolites and calcium absorption with varying doses of oral vitamin D3 in healthy children are unknown.
Objective:
Our objective was to examine the dose-response ...effects of supplemental vitamin D3 on serum vitamin D metabolites and calcium absorption in children living at two U.S. latitudes.
Design:
Black and white children (n = 323) participated in a multisite (U.S. latitudes 34° N and 40° N), triple-masked trial. Children were randomized to receive oral vitamin D3 (0, 400, 1000, 2000, and 4000 IU/d) and were sampled over 12 weeks in winter. Serum 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) were measured using RIA and intact PTH (iPTH) by immunoradiometric assay. Fractional calcium absorption was determined from an oral stable isotope 44Ca (5 mg) in a 150-mg calcium meal. Nonlinear and linear regression models were fit for vitamin D metabolites, iPTH, and calcium absorption.
Results:
The mean baseline 25(OH)D value for the entire sample was 70.0 nmol/L. Increases in 25(OH)D depended on dose with 12-week changes ranging from −10 nmol/L for placebo to 76 nmol/L for 4000 IU. Larger 25(OH)D gains were observed for whites vs blacks at the highest dose (P < .01). Gains for 1,25(OH)2D were not significant (P = .07), and decreases in iPTH were not dose-dependent. There was no dose effect of vitamin D on fractional calcium absorption when adjusted for pill compliance, race, sex, or baseline 25(OH)D.
Conclusion:
Large increases in serum 25(OH)D with vitamin D3 supplementation did not increase calcium absorption in healthy children living at 2 different latitudes. Supplementation with 400 IU/d was sufficient to maintain wintertime 25(OH)D concentrations in healthy black, but not white, children.
Botulinum neurotoxins are diverse proteins. They are currently represented by at least seven serotypes and more than 40 subtypes. New clostridial strains that produce novel neurotoxin variants are ...being identified with increasing frequency, which presents challenges when organizing the nomenclature surrounding these neurotoxins. Worldwide, researchers are faced with the possibility that toxins having identical sequences may be given different designations or novel toxins having unique sequences may be given the same designations on publication. In order to minimize these problems, an ad hoc committee consisting of over 20 researchers in the field of botulinum neurotoxin research was convened to discuss the clarification of the issues involved in botulinum neurotoxin nomenclature. This publication presents a historical overview of the issues and provides guidelines for botulinum neurotoxin subtype nomenclature in the future.
This study documents secondary pre‐service teachers (PSTs) who examined Black Lives Matter (BLM)‐themed young adult literature (YAL) embedded in contemporary realistic fiction and graphic novels, as ...part of coursework for an online YAL course required for secondary teacher certification. An analysis of instructor mentoring, online discussions, literature evaluations, and interviews demonstrates enhanced awareness of the need to implement BLM‐themed literature, against the grain of rigid curricular requirements and policies that ban critical race theory (CRT) dialogue in numerous school districts. Moreover, PSTs identified these texts as a source to guide CRT to raise awareness of the history and permanence of systemic racism and its influence on contemporary society and the implementation of culturally relevant literature.
The management of breast cancer has evolved into a multidisciplinary evidence-based surgical speciality, with emphasis on conservative surgery. A number of landmark trials have established lumpectomy ...followed by radiation as the standard of care for many patients. The aim of this study is to construct a narrative review of recent developments in the surgical management of breast cancer and how such developments have impacted surgical practice. A comprehensive literature search of Pubmed was conducted. The latest search was performed on October 31
st
, 2020. Search terms “breast cancer” were used in combinations with specific key words and Boolean operators relating to surgical management. The reference lists of retrieved articles were comprehensively screened for additional eligible publications. Articles were selected and reviewed based on relevance. We selected publications in the past 10 years but did not exclude commonly referenced and highly regarded previous publications. Review articles and book chapters were also cited to provide reference on details not discussed in the academic literature. This article reviews the current evidence in surgical management of early-stage breast cancer, discusses recent trends in surgical practice for therapeutic and prophylactic procedures and provides commentary on implications and factors associated with these trends.
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