| 1. |
- Kehoe, Laura, et al.
(författare)
-
Make EU trade with Brazil sustainable
- 2019
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 2. |
- Proletov, Ian, et al.
(författare)
-
Primary and secondary glomerulonephritides 1.
- 2014
-
Ingår i: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. - : Oxford University Press (OUP). - 1460-2385. ; 29 Suppl 3:May, s. 186-200
-
Tidskriftsartikel (refereegranskat)
|
|
| 3. |
- Dias, Nicole Geovana, et al.
(författare)
-
Intimate Partner Violence and Use of Primary and Emergency Care : The Role of Informal Social Support
- 2020
-
Ingår i: Health & Social Work. - : Oxford academic. - 0360-7283 .- 1545-6854. ; 45:2, s. 91-100
-
Tidskriftsartikel (refereegranskat)abstract
- Social support may encourage victims to disclose their experiences of intimate partner violence (IPV), but also to seek the appropriate help and care in the social and health services. Using data from a multicenter European project, DOVE (Domestic Violence Against women/men in Europe-prevalence, determinants, effects, and policies/practices), the present study aimed at measuring the frequency of primary care and emergency use according to IPV types of victimization, and to investigate whether victims receiving different levels of informal social support are using health care differently. Results suggested a significant association between IPV types and use of emergency services, and no association was found regarding primary care services. Victims of physical abuse and sexual coercion went to the emergency department (ED) more frequently (more than once a year). Also, victims of physical abuse receiving low social support visited an ED more frequently than those with high social support, whereas victims of sexual coercion with high informal social support went more often to the ED compared with victims of sexual coercion with low social support, even after controlling for other covariates. These results seem to suggest that social support has a significant role in the decision to use health care among victims of IPV.
|
|
| 4. |
|
|
| 5. |
- de Oliveira, Ana Henriques, et al.
(författare)
-
Listeria monocytogenes requires the RsbX protein to prevent SigB-activation under non-stressed conditions
- 2022
-
Ingår i: Journal of Bacteriology. - : American Society for Microbiology. - 0021-9193 .- 1098-5530. ; 204:1
-
Tidskriftsartikel (refereegranskat)abstract
- The survival of microbial cells under changing environmental conditions requires an efficient reprogramming of transcription, often mediated by alternative sigma factors. The Gram-positive human pathogen Listeria monocytogenes senses and responds to environmental stress mainly through the alternative sigma factor σB (SigB), which controls expression of the general stress response regulon. SigB activation is achieved through a complex series of phosphorylation/dephosphorylation events culminating in the release of SigB from its anti-sigma factor RsbW. At the top of the signal transduction pathway lies a large multi-protein complex known as the stressosome that is believed to act as a sensory hub for stresses. Following signal detection, stressosome proteins become phosphorylated. Resetting of the stressosome is hypothesized to be exerted by a putative phosphatase, RsbX, which presumably removes phosphate groups from stressosome proteins post-stress.We addressed the role of the RsbX protein in modulating the activity of the stressosome and consequently regulating SigB activity in L. monocytogenes. We show that RsbX is required to reduce SigB activation/levels under non-stress conditions and that it is required for appropriate SigB mediated stress-adaptation. A strain lacking RsbX displayed impaired motility and biofilm formation, but also an increased survival at low pH. Our results could suggest that absence of RsbX alter the multi-protein composition of the stressosome without dramatically affecting its phosphorylation status. Overall the data show that RsbX plays a critical role in modulating the signal transduction pathway by blocking SigB activation under non-stressed conditions.
|
|
| 6. |
- de Oliveira, Ana Henriques
(författare)
-
RsbX and stress response in Listeria monocytogenes
- 2021
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Listeria monocytogenes is a ubiquitous foodborne Gram-positive bacterium. Despite being mainly a soil bacterium, it can reach the food processing environment and contaminate food destined for human consumption, causing outbreaks. Because of its pathogenicity, it poses a danger for certain high-risk groups, including children, elderly, and immune-compromised people, as well as pregnant women, being capable of causing a life-threatening systemic infection known as listeriosis.All bacteria require an efficient transcriptional response and its fine-tuned modulation in order to survive the different stresses it encounters. This is especially true for L. monocytogenes, which presents an impressive range of stress adaptions that allows it survival in certain extreme conditions such as low temperature, low pH and high osmolarity. The alternative Sigma factor B, SigB, is responsible for the expression of the general stress response of this bacterium and plays a key role in the survival and adaption to new environments. The activation of SigB requires an intricate system of partner switching mechanisms, involving anti-sigma and anti-anti-sigma factors, triggered by a number of phosphorylation and dephosphorylation events that culminates with SigB being available to interact with RNA polymerase and lead the transcription of the general stress response regulon. At the top of this signal transduction pathway lies a large multi-protein complex, known as the stressosome. It is formed by RsbR (and its paralogs), RsbS and RsbT and is believed to function as a sensory hub for environmental stimuli. After signal detection, the stressosome proteins are phosphorylated and the complex goes through conformational changes that will ultimately allow for SigB activation. The reset of the stressosome to its pre-stress conformation, is hypothesized to be exerted by a putative phosphatase, RsbX, which most likely dephosphorylates the stressosome proteins post-stress.The role of RsbX in modulating the activity and conformation of the stressosome as well as in subsequent regulation of SigB activity was investigated. RsbX was shown to be required for maintaining SigB levels and activity low in non-stressed conditions as well as for proper SigB mediated stress adaptation. A ΔrsbX mutant strain was shown to have a very slight growth defect, but it also exhibited impaired motility, reduced biofilm formation, as well as a more acid resistant phenotype. The absence of RsbX was shown to alter the composition of the stressosome without drastically affecting its phosphorylation pattern. In general, RsbX was shown to play a crucial role in modulating the signal transduction pathways by preventing SigB activation under non-stressed conditions.Strains that acquire sigB operon mutations have been shown to have a growth advantage under certain mild stress conditions recurrent in a laboratory set. These strains were shown to outcompete the wild-type strain when grown in these conditions, demonstrating how a deficient SigB activity poses an advantage to the cell. On the other hand, and the ΔrsbX mutant strain was shown to have a growth disadvantage, since it was outcompeted by the wild-type strain when co-cultured. The data highlights the significant cost stress protection presents to this pathogen, since deploying the general stress response is a burden on cellular resources, and in its absence the cell can redirect energy for growth. In contrast, in the presence of a lethal stress (low pH) the strains with impaired SigB activity showed a reduced survival and an overall increased sensitivity to the stress. Hence demonstrating that in a more stressful condition the high cost of the general stress response regulon is outweighed by the protection benefits it confers to the cell. The importance of RsbX, which prevents unnecessary SigB activation, is even more evident. RsbX is not only critical to shut down the general stress response post-stress and subsequent recovery of homeostasis, but it also keeps SigB activity to low levels in non-stressed conditions, avoiding unwarranted gene expression and contributing to important energy saving. SigB also plays an important role in the transition of L. monocytogenes from a saprophytic to a pathogenic lifestyle. Even though most of the virulence factors are under the control of PrfA, the master regulator of virulence, SigB is fundamental in the survival of the bacteria inside the host’s gastro-intestinal tract (e.g., stomach high acidity and bile salt release in the duodenum), as well as in the early stages of infection, such as internalization into not phagocytic cells. Because of the importance of SigB for virulence, we speculated if RsbX, by controlling activity of SigB, would also impact the virulence of the bacteria. The data showed somewhat contradicting results, but in general it suggests that even though the expression of the virulence genes responsible for the uptake of the bacteria are increased in a strain lacking RsbX compared with the wild-type strain, the effect on the general infectivity of this strain was either minimal or not existent at all. A reason for this could be the suggested growth defect caused by the absence of RsbX, which could also jeopardize the bacteria’s ability to efficiently grow within infected cells or organisms.Overall, RsbX seems to play a crucial role for L. monocytogenes, since it is responsible to maintain a very important, but extremely costly, stress protection mechanism in an inactive mode in absence of stress. Its functions span from alteration of stressosome conformation and subsequent modulation of stress response, to homeostasis recovery, motility, biofilm formation, stress survival, and even to indirect impact in the bacteria’s infectivity. This shows the diversified, but impactful range of effects RsbX seems to have for the bacterial cell.
|
|
| 7. |
- Guerreiro, Duarte N., et al.
(författare)
-
Mild Stress Conditions during Laboratory Culture Promote the Proliferation of Mutations That Negatively Affect Sigma B Activity in Listeria monocytogenes
- 2020
-
Ingår i: Journal of Bacteriology. - : American Society for Microbiology. - 0021-9193 .- 1098-5530. ; 202:9
-
Tidskriftsartikel (refereegranskat)abstract
- In Listeria monocytogenes, the full details of how stress signals are integrated into the σB regulatory pathway are not yet available. To help shed light on this question, we investigated a collection of transposon mutants that were predicted to have compromised activity of the alternative sigma factor B (σB). These mutants were tested for acid tolerance, a trait that is known to be under σB regulation, and they were found to display increased acid sensitivity, similar to a mutant lacking σB (ΔsigB). The transposon insertions were confirmed by whole-genome sequencing, but in each case, the strains were also found to carry a frameshift mutation in the sigB operon. The changes were predicted to result in premature stop codons, with negative consequences for σB activation, independently of the transposon location. Reduced σB activation in these mutants was confirmed. Growth measurements under conditions similar to those used during the construction of the transposon library revealed that the frameshifted sigB operon alleles conferred a growth advantage at higher temperatures, during late exponential phase. Mixed-culture experiments at 42°C demonstrated that the loss of σB activity allowed mutants to take over a population of parental bacteria. Together, our results suggest that mutations affecting σB activity can arise during laboratory culture because of the growth advantage conferred by these mutations under mild stress conditions. The data highlight the significant cost of stress protection in this foodborne pathogen and emphasize the need for whole-genome sequence analysis of newly constructed strains to confirm the expected genotype.IMPORTANCE: In the present study, we investigated a collection of Listeria monocytogenes strains that all carried sigB operon mutations. The mutants all had reduced σB activity and were found to have a growth advantage under conditions of mild heat stress (42°C). In mixed cultures, these mutants outcompeted the wild type when mild heat stress was present but not at an optimal growth temperature. An analysis of 22,340 published L. monocytogenes genome sequences found a high rate of premature stop codons present in genes positively regulating σB activity. Together, these findings suggest that the occurrence of mutations that attenuate σB activity can be favored under conditions of mild stress, probably highlighting the burden on cellular resources that stems from deploying the general stress response.
|
|
| 8. |
- Lewis, Makayla, et al.
(författare)
-
Traveling arts x HCI sketchbook : exploring the intersection between artistic expression and human-computer interaction
- 2024
-
Ingår i: CHI '24: Extended abstracts of the 2024 CHI Conference on human factors in computing systems. - : Association for Computing Machinery (ACM). - 9798400703317
-
Konferensbidrag (refereegranskat)abstract
- When thinking of arts in HCI, one might be tempted to keep one's eyes focused on prominent realms such as sketching for UX Design and design probes from participants. A closer look shows that practices go beyond this, involving a variety of arts-based expressions by researchers, the researched and third parties, e.g. graphic facilitators. Inspired by Toselli's Sketchnote Army Travelling Sketchbook, researchers and artists contributed to a 'Travelling Sketchbook for Arts in HCI', showcasing their arts-based practice in HCI. The resulting sketchbook explores the intersection between HCI and artistic expression, illuminating what it means to use art in HCI. It shows the breadth of Arts in HCI, illustrating the many fruitful possibilities for extending existing research and dissemination methods in HCI. It also calls into question current practices, which often do not recognise the significance of artist attribution, and, in turn, advocates for equal authorship between principal researchers and contributing artists.
|
|
| 9. |
- Pina, Ana, et al.
(författare)
-
Virtual genetic diagnosis for familial hypercholesterolemia powered by machine learning.
- 2020
-
Ingår i: European journal of preventive cardiology. - : Oxford University Press (OUP). - 2047-4881 .- 2047-4873. ; 27:15, s. 1639-1646
-
Tidskriftsartikel (refereegranskat)abstract
- Familial hypercholesterolemia (FH) is the most common genetic disorder of lipid metabolism. The gold standard for FH diagnosis is genetic testing, available, however, only in selected university hospitals. Clinical scores - for example, the Dutch Lipid Score - are often employed as alternative, more accessible, albeit less accurate FH diagnostic tools. The aim of this study is to obtain a more reliable approach to FH diagnosis by a "virtual" genetic test using machine-learning approaches.We used three machine-learning algorithms (a classification tree (CT), a gradient boosting machine (GBM), a neural network (NN)) to predict the presence of FH-causative genetic mutations in two independent FH cohorts: the FH Gothenburg cohort (split into training data (N=174) and internal test (N=74)) and the FH-CEGP Milan cohort (external test, N=364). By evaluating their area under the receiver operating characteristic (AUROC) curves, we found that the three machine-learning algorithms performed better (AUROC 0.79 (CT), 0.83 (GBM), and 0.83 (NN) on the Gothenburg cohort, and 0.70 (CT), 0.78 (GBM), and 0.76 (NN) on the Milan cohort) than the clinical Dutch Lipid Score (AUROC 0.68 and 0.64 on the Gothenburg and Milan cohorts, respectively) in predicting carriers of FH-causative mutations.In the diagnosis of FH-causative genetic mutations, all three machine-learning approaches we have tested outperform the Dutch Lipid Score, which is the clinical standard. We expect these machine-learning algorithms to provide the tools to implement a virtual genetic test of FH. These tools might prove particularly important for lipid clinics without access to genetic testing.
|
|
| 10. |
- Tabusi, Mahebali, et al.
(författare)
-
Neuronal death in pneumococcal meningitis is triggered by pneumolysin and RrgA interactions with beta-actin
- 2021
-
Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 17:3
-
Tidskriftsartikel (refereegranskat)abstract
- Neuronal damage is a major consequence of bacterial meningitis, but little is known about mechanisms of bacterial interaction with neurons leading to neuronal cell death. Streptococcus pneumoniae (pneumococcus) is a leading cause of bacterial meningitis and many survivors develop neurological sequelae after the acute infection has resolved, possibly due to neuronal damage. Here, we studied mechanisms for pneumococcal interactions with neurons. Using human primary neurons, pull-down experiments and mass spectrometry, we show that pneumococci interact with the cytoskeleton protein beta-actin through the pilus-1 adhesin RrgA and the cytotoxin pneumolysin (Ply), thereby promoting adhesion and invasion of neurons, and neuronal death. Using our bacteremia-derived meningitis mouse model, we observe that RrgA- and Ply-expressing pneumococci co-localize with neuronal beta-actin. Using purified proteins, we show that Ply, through its cholesterol-binding domain 4, interacts with the neuronal plasma membrane, thereby increasing the exposure on the outer surface of beta-actin filaments, leading to more beta-actin binding sites available for RrgA binding, and thus enhanced pneumococcal interactions with neurons. Pneumococcal infection promotes neuronal death possibly due to increased intracellular Ca2+ levels depending on presence of Ply, as well as on actin cytoskeleton disassembly. STED super-resolution microscopy showed disruption of beta-actin filaments in neurons infected with pneumococci expressing RrgA and Ply. Finally, neuronal death caused by pneumococcal infection could be inhibited using antibodies against beta-actin. The generated data potentially helps explaining mechanisms for why pneumococci frequently cause neurological sequelae. Author summary Neuronal damage is a major consequence of meningitis. Streptococcus pneumoniae (pneumococcus) is the leading etiological cause of bacterial meningitis, yet how pneumococci interact with neurons and cause neuronal death is poorly understood. Using human neurons in vitro and our established bacteremia-derived meningitis mouse model in vivo, we found that pneumococci use the pilus-1 adhesin RrgA and the cytotoxin pneumolysin (Ply) to interact with neuronal beta-actin expressed on the plasma membrane. Also, we demonstrate that Ply interaction with the neuronal plasma membrane increase the exposure of beta-actin on the neuronal plasma membrane, allowing more pneumococci to adhere to neurons through RrgA-beta-actin interaction. Moreover, neurons infected with RrgA- and Ply-expressing pneumococci showed increased intracellular Ca2+ levels and disruption of beta-actin filaments, possibly leading to neuronal death. Importantly, by blocking pneumococcal-beta-actin interaction using antibodies, we could reduce neuronal cell death after pneumococcal infection.
|
|
