| 51. |
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| 52. |
- Kraemer, Benjamin M., et al.
(författare)
-
Climate change drives widespread shifts in lake thermal habitat
- 2021
-
Ingår i: Nature Climate Change. - : Springer Science and Business Media LLC. - 1758-678X .- 1758-6798. ; 11:6, s. 521-529
-
Tidskriftsartikel (refereegranskat)abstract
- Lake surfaces are warming worldwide, raising concerns about lake organism responses to thermal habitat changes. Species may cope with temperature increases by shifting their seasonality or their depth to track suitable thermal habitats, but these responses may be constrained by ecological interactions, life histories or limiting resources. Here we use 32 million temperature measurements from 139 lakes to quantify thermal habitat change (percentage of non-overlap) and assess how this change is exacerbated by potential habitat constraints. Long-term temperature change resulted in an average 6.2% non-overlap between thermal habitats in baseline (1978-1995) and recent (1996-2013) time periods, with non-overlap increasing to 19.4% on average when habitats were restricted by season and depth. Tropical lakes exhibited substantially higher thermal non-overlap compared with lakes at other latitudes. Lakes with high thermal habitat change coincided with those having numerous endemic species, suggesting that conservation actions should consider thermal habitat change to preserve lake biodiversity. Using measurements from 139 global lakes, the authors demonstrate how long-term thermal habitat change in lakes is exacerbated by species' seasonal and depth-related constraints. They further reveal higher change in tropical lakes, and those with high biodiversity and endemism.
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| 53. |
- Lamb, G. P., et al.
(författare)
-
Short GRB 160821B : A Reverse Shock, a Refreshed Shock, and a Well-sampled Kilonova
- 2019
-
Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 883:1
-
Tidskriftsartikel (refereegranskat)abstract
- We report our identification of the optical afterglow and host galaxy of the short-duration gamma-ray burst sGRB 160821B. The spectroscopic redshift of the host is z = 0.162, making it one of the lowest redshift short-duration gamma-ray bursts (sGRBs) identified by Swift. Our intensive follow-up campaign using a range of ground-based facilities as well as Hubble Space Telescope, XMM-Newton, and Swift, shows evidence for a late-time excess of optical and near-infrared emission in addition to a complex afterglow. The afterglow light curve at X-ray frequencies reveals a narrow jet, theta(j) similar to 1.9(-0.03)(+0.10) deg, that is refreshed at >1 day post-burst by a slower outflow with significantly more energy than the initial outflow that produced the main GRB. Observations of the 5 GHz radio afterglow shows a reverse shock into a mildly magnetized shell. The optical and near-infrared excess is fainter than AT2017gfo associated with GW170817, and is well explained by a kilonova with dynamic ejecta mass M-dyn = (1.0 +/- 0.6) x 10(-3) M-circle dot and a secular (post-merger) ejecta mass with M-pm = (1.0 +/- 0.6) x 10(-2) M-circle dot, consistent with a binary neutron star merger resulting in a short-lived massive neutron star. This optical and near-infrared data set provides the best-sampled kilonova light curve without a gravitational wave trigger to date.
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| 54. |
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| 55. |
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| 56. |
- Shein, A. M. S., et al.
(författare)
-
Novel intranasal phage-CaEDTA-ceftazidime/avibactam triple combination therapy demonstrates remarkable efficacy in treating Pseudomonas aeruginosa lung infection
- 2023
-
Ingår i: Biomedicine & Pharmacotherapy. - 0753-3322. ; 168
-
Tidskriftsartikel (refereegranskat)abstract
- Given the rise of multidrug-resistant (MDR) Pseudomonas aeruginosa infections, alternative treatments are needed. Anti-pseudomonal phage therapy shows promise, but its clinical application is limited due to the development of resistance and a lack of biofilm penetration. Recently, adjuvants like CaEDTA have shown the ability to enhance the effectiveness of combined antimicrobial agents. Here, we tested a phage-adjuvant com-bination and demonstrated the effectiveness of intranasally inhaled phage (KKP10) + CaEDTA in addition to ceftazidime/avibactam (CZA) for chronic P. aeruginosa lung infections. The results emphasize that intranasal inhalation of phage along with CaEDTA can successfully re-sensitize MDR P. aeruginosa to CZA in a triple combination treatment. This promising approach shows potential as a therapy for chronic respiratory tract infections.
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| 57. |
- Thieme, M. L., et al.
(författare)
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Navigating trade-offs between dams and river conservation
- 2021
-
Ingår i: Global Sustainability. - : Cambridge University Press. - 2059-4798. ; 4
-
Forskningsöversikt (refereegranskat)abstract
- Non-technical summary There has been a long history of conflicts, studies, and debate over how to both protect rivers and develop them sustainably. With a pause in new developments caused by the global pandemic, anticipated further implementation of the Paris Agreement and high-level global climate and biodiversity meetings in 2021, now is an opportune moment to consider the current trajectory of development and policy options for reconciling dams with freshwater system health. Technical summary We calculate potential loss of free-flowing rivers (FFRs) if proposed hydropower projects are built globally. Over 260,000 km of rivers, including Amazon, Congo, Irrawaddy, and Salween mainstem rivers, would lose free-flowing status if all dams were built. We propose a set of tested and proven solutions to navigate trade-offs associated with river conservation and dam development. These solution pathways are framed within the mitigation hierarchy and include (1) avoidance through either formal river protection or through exploration of alternative development options; (2) minimization of impacts through strategic or system-scale planning or re-regulation of downstream flows; (3) restoration of rivers through dam removal; and (4) mitigation of dam impacts through biodiversity offsets that include restoration and protection of FFRs. A series of examples illustrate how avoiding or reducing impacts on rivers is possible - particularly when implemented at a system scale - and can be achieved while maintaining or expanding benefits for climate resilience, water, food, and energy security. Social media summary Policy solutions and development pathways exist to navigate trade-offs to meet climate resilience, water, food, and energy security goals while safeguarding FFRs.
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| 58. |
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| 59. |
- Baker, Jessica H., et al.
(författare)
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Body Dissatisfaction in Adolescent Boys
- 2019
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Ingår i: Developmental Psychology. - : American Psychological Association (APA). - 0012-1649 .- 1939-0599. ; 55:7, s. 1566-1578
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Tidskriftsartikel (refereegranskat)abstract
- Body dissatisfaction is a significant mental health symptom present in adolescent girls and boys. However, it is often either disregarded in adolescent boys or examined using assessments that may not resonate with males. The present study addresses these issues, examining the manifestation, etiology, and correlates of 3 facets of body dissatisfaction in adolescent boys. Adolescent male twins aged 16- to 17-years-old from the Swedish Twin Study of Child and Adolescent Development were included along with a female comparison group: 915 monozygotic and 671 dizygotic same-sex twins. Body dissatisfaction was defined using measures of height dissatisfaction, muscle dissatisfaction, and the body dissatisfaction subscale of the Eating Disorder Inventory (EDI-BD). We examined the prevalence of body dissatisfaction, whether the facets of body dissatisfaction were phenotypically and etiologically distinct, and associations with specific externalizing and internalizing symptoms. For boys, muscle dissatisfaction scores were greater than height dissatisfaction scores. Results also indicated that height and muscle dissatisfaction were phenotypically and etiologically distinct from the EDI-BD. Unique associations were observed with externalizing and internalizing symptoms: muscle dissatisfaction with symptoms of bulimia nervosa and the EDI-BD with internalizing symptoms, body mass index, and drive for thinness. The facets of body dissatisfaction were also largely distinct in girls and unique between-sex associations with externalizing and internalizing symptoms emerged. Overall, male-oriented aspects of body dissatisfaction are distinct from female-oriented aspects of body dissatisfaction. To capture the full picture of male body dissatisfaction, multiple facets must be addressed.
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| 60. |
- Bazzi, Wael, et al.
(författare)
-
Heavy Metal Toxicity in Armed Conflicts Potentiates AMR in A. baumannii by Selecting for Antibiotic and Heavy Metal Co-resistance Mechanisms
- 2020
-
Ingår i: Frontiers in Microbiology. - : Frontiers Media S.A.. - 1664-302X. ; 11
-
Forskningsöversikt (refereegranskat)abstract
- Acinetobacter baumannii has become increasingly resistant to leading antimicrobial agents since the 1970s. Increased resistance appears linked to armed conflicts, notably since widespread media stories amplified clinical reports in the wake of the American invasion of Iraq in 2003. Antimicrobial resistance is usually assumed to arise through selection pressure exerted by antimicrobial treatment, particularly where treatment is inadequate, as in the case of low dosing, substandard antimicrobial agents, or shortened treatment course. Recently attention has focused on an emerging pathogen, multi-drug resistant A. baumannii (MDRAb). MDRAb gained media attention after being identified in American soldiers returning from Iraq and treated in US military facilities, where it was termed "Iraqibacter." However, MDRAb is strongly associated in the literature with war injuries that are heavily contaminated by both environmental debris and shrapnel from weapons. Both may harbor substantial amounts of toxic heavy metals. Interestingly, heavy metals are known to also select for antimicrobial resistance. In this review we highlight the potential causes of antimicrobial resistance by heavy metals, with a focus on its emergence in A. baumanni in war zones.
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| 61. |
- Brennan, Donal J, et al.
(författare)
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Altered cytoplasmic-to-nuclear ratio of survivin is a prognostic indicator in breast cancer
- 2008
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Ingår i: Clinical Cancer Research. - 1078-0432. ; 14:9, s. 2681-2689
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: Survivin (BIRC5) is a promising tumor biomarker. Conflicting data exist on its prognostic effect in breast cancer. These data may at least be partly due to the manual interpretation of immunohistochemical staining, especially as survivin can be located in both the nucleus and cytoplasm. Quantitative determination of survivin expression using image analysis offers the opportunity to develop alternative scoring models for survivin immunohistochemistry. Here, we present such a model. Experimental Design: A breast cancer tissue microarray containing 102 tumors was stained with an anti-survivin antibody. Whole-slide scanning was used to capture high-resolution images. These images were analyzed using automated algorithms to quantify the staining. Results: Increased nuclear, but not cytoplasmic, survivin was associated with a reduced overall survival (OS; P = 0.038) and disease-specific survival (P = 0.0015). A high cytoplasmicto-nuclear ratio (CNR) of survivin was associated with improved OS (P = 0.005) and disease-specific survival (P = 0.05). Multivariate analysis revealed that the survivin CNR was an independent predictor of CIS (hazard ratio, 0.09; 95% confidence interval, 0.01-0.76; P = 0.027). A survivin CNR of >5 correlated positively with estrogen receptor (P = 0.019) and progesterone receptor (P = 0.033) levels, whereas it was negatively associated with Ki-67 expression (P = 0.04), p53 status (P = 0.005), and c-myc amplification (P = 0.016). Conclusion: Different prognostic information is supplied by nuclear and cytoplasmic survivin in breast cancer. Nuclear survivin is a poor prognostic marker in breast cancer. Moreover, CNR of survivin, as determined by image analysis, is an independent prognostic factor.
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| 62. |
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| 63. |
- Derakhshan, M., et al.
(författare)
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The pedagogical challenges of creating information literate librarians
- 2017
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Ingår i: Library Review. - : Emerald Group Publishing Ltd.. - 0024-2535 .- 1758-793X. ; 66:6-7, s. 570-583
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: This study aims to investigate the challenges of developing information literacy (IL) competencies and approaches to overcome the challenges among library and information science (LIS) students in Iran. Design/methodology/approach: Taking an exploratory approach, the study used semi-structured interviews to gather the data. Using the 2000 ACRL standards as a framework, the fieldwork questions were designed around the five areas of IL competencies. A total of 15 academics teaching 18 different LIS courses from six universities were interviewed. They were asked the challenges they faced in teaching these competencies and the approaches they took or suggested in overcoming the challenge(s). A thematic approach was used to analyze the data. Findings: Some of the challenges for students mentioned by the interviewees were ambiguity about the discipline, inability to match subject relevance with appropriate sources of information and lack of familiarity with databases. Research limitations/implications: This study is limited to LIS academics; studying students’ reflections can bring broader perspectives to IL education in LIS programs. Owing to the nature of the design of this study, which is a single case study, the teaching experiences of IL are limited to the ones which emerged and were addressed in the context of the case. Although the case selection was made in a way that can be representative of the “general” in the “particular” bounded system of the case (Stake, 1998), studying more cases could certainly have brought broader perspectives to IL which could have been to wider contexts. Originality/value: The results of this study contribute to our understanding of challenges in teaching IL in the LIS discipline, an area that has not been researched directly. This contributes to IL teaching in disciplinary areas and it brings new perspectives to the elements of IL teaching which emerged from the experiences of people who are directly experienced in the context of the discipline.
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| 64. |
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| 65. |
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| 66. |
- Hofer, J., et al.
(författare)
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High- Q Magnetic Levitation and Control of Superconducting Microspheres at Millikelvin Temperatures
- 2023
-
Ingår i: Physical Review Letters. - 1079-7114 .- 0031-9007. ; 131:4
-
Tidskriftsartikel (refereegranskat)abstract
- We report the levitation of a superconducting lead-tin sphere with 100 μm diameter (corresponding to a mass of 5.6 μg) in a static magnetic trap formed by two coils in an anti-Helmholtz configuration, with adjustable resonance frequencies up to 240 Hz. The center-of-mass motion of the sphere is monitored magnetically using a dc superconducting quantum interference device as well as optically and exhibits quality factors of up to 2.6×107. We also demonstrate 3D magnetic feedback control of the motion of the sphere. The setup is housed in a dilution refrigerator operating at 15 mK. By implementing a cryogenic vibration isolation system, we can attenuate environmental vibrations at 200 Hz by approximately 7 orders of magnitude. The combination of low temperature, large mass, and high quality factor provides a promising platform for testing quantum physics in previously unexplored regimes with high mass and long coherence times.
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| 67. |
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| 68. |
- Jaiswal, Siddhartha, et al.
(författare)
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Age-Related Clonal Hematopoiesis Associated with Adverse Outcomes.
- 2014
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 371:26, s. 2488-2498
-
Tidskriftsartikel (refereegranskat)abstract
- Background The incidence of hematologic cancers increases with age. These cancers are associated with recurrent somatic mutations in specific genes. We hypothesized that such mutations would be detectable in the blood of some persons who are not known to have hematologic disorders. Methods We analyzed whole-exome sequencing data from DNA in the peripheral-blood cells of 17,182 persons who were unselected for hematologic phenotypes. We looked for somatic mutations by identifying previously characterized single-nucleotide variants and small insertions or deletions in 160 genes that are recurrently mutated in hematologic cancers. The presence of mutations was analyzed for an association with hematologic phenotypes, survival, and cardiovascular events. Results Detectable somatic mutations were rare in persons younger than 40 years of age but rose appreciably in frequency with age. Among persons 70 to 79 years of age, 80 to 89 years of age, and 90 to 108 years of age, these clonal mutations were observed in 9.5% (219 of 2300 persons), 11.7% (37 of 317), and 18.4% (19 of 103), respectively. The majority of the variants occurred in three genes: DNMT3A, TET2, and ASXL1. The presence of a somatic mutation was associated with an increase in the risk of hematologic cancer (hazard ratio, 11.1; 95% confidence interval [CI], 3.9 to 32.6), an increase in all-cause mortality (hazard ratio, 1.4; 95% CI, 1.1 to 1.8), and increases in the risks of incident coronary heart disease (hazard ratio, 2.0; 95% CI, 1.2 to 3.4) and ischemic stroke (hazard ratio, 2.6; 95% CI, 1.4 to 4.8). Conclusions Age-related clonal hematopoiesis is a common condition that is associated with increases in the risk of hematologic cancer and in all-cause mortality, with the latter possibly due to an increased risk of cardiovascular disease. (Funded by the National Institutes of Health and others.).
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| 69. |
- Krzyzanowska, Agnieszka, et al.
(författare)
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Development, Validation, and Clinical Utility of a Six-gene Signature to Predict Aggressive Prostate Cancer
- 2023
-
Ingår i: European Urology Focus. - 2405-4569. ; 9:6, s. 983-991
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Molecular signatures in prostate cancer (PCa) tissue can provide useful prognostic information to improve the understanding of a patient's risk of harbouring aggressive disease. Objective: To develop and validate a gene signature that adds independent prognostic information to clinical parameters for better treatment decisions and patient management. Design, setting, and participants: Expression of 14 genes was evaluated in radical prostatectomy (RP) tissue from an Irish cohort of PCa patients (n = 426). A six-gene molecular risk score (MRS) was identified with strong prognostic performance to predict adverse pathology (AP) at RP or biochemical recurrence (BCR). The MRS was combined with the Cancer of the Prostate Risk Assessment (CAPRA) score, to create a molecular and clinical risk score (MCRS), and validated in a Swedish cohort (n = 203). Outcome measurements and statistical analysis: The primary AP outcome was assessed by the likelihood ratio statistics and area under the receiver operating characteristics curves (AUC) from logistic regression models. The secondary time to BCR outcome was assessed by likelihood ratio statistics and C-indexes from Cox proportional hazard regression models. Results and limitations: The six-gene signature was significantly (p < 0.0001) prognostic and added significant prognostic value to clinicopathological features for AP and BCR outcomes. For both outcomes, both the MRS and the MCRS increased the AUC/C-index when added to European Association of Urology (EAU) and CAPRA scores. Limitations include the retrospective nature of this study. Conclusions: The six-gene signature has strong performance for the prediction of AP and BCR in an independent clinical validation study. MCRS improves prognostic evaluation and can optimise patient management after RP. Patient summary: We found that the expression panel of six genes can help predict whether a patient is likely to have a disease recurrence after radical prostatectomy surgery.
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| 70. |
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| 71. |
- Lau, Nga M., et al.
(författare)
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Markers of Celiac Disease and Gluten Sensitivity in Children with Autism
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:6, s. e66155-
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Gastrointestinal symptoms are a common feature in children with autism, drawing attention to a potential association with celiac disease or gluten sensitivity. However, studies to date regarding the immune response to gluten in autism and its association with celiac disease have been inconsistent. The aim of this study was to assess immune reactivity to gluten in pediatric patients diagnosed with autism according to strict criteria and to evaluate the potential link between autism and celiac disease. Methods: Study participants included children (with or without gastrointestinal symptoms) diagnosed with autism according to both the Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview, Revised (ADIR) (n = 37), their unaffected siblings (n = 27), and age-matched healthy controls (n = 76). Serum specimens were tested for antibodies to native gliadin, deamidated gliadin, and transglutaminase 2 (TG2). Affected children were genotyped for celiac disease associated HLA-DQ2 and -DQ8 alleles. Results: Children with autism had significantly higher levels of IgG antibody to gliadin compared with unrelated healthy controls (p<0.01). The IgG levels were also higher compared to the unaffected siblings, but did not reach statistical significance. The IgG anti-gliadin antibody response was significantly greater in the autistic children with gastrointestinal symptoms in comparison to those without them (p<0.01). There was no difference in IgA response to gliadin across groups. The levels of celiac disease-specific serologic markers, i.e., antibodies to deamidated gliadin and TG2, did not differ between patients and controls. An association between increased anti-gliadin antibody and presence of HLA-DQ2 and/or -DQ8 was not observed. Conclusions: A subset of children with autism displays increased immune reactivity to gluten, the mechanism of which appears to be distinct from that in celiac disease. The increased anti-gliadin antibody response and its association with GI symptoms points to a potential mechanism involving immunologic and/or intestinal permeability abnormalities in affected children.
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| 72. |
- Lis, D. C., et al.
(författare)
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Widespread Rotationally Hot Hydronium Ion in the Galactic Interstellar Medium
- 2014
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Ingår i: Astrophysical Journal. - 1538-4357 .- 0004-637X. ; 785:2, s. A135, pp. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- We present new Herschel observations of the (6,6) and (9,9) inversion transitions of the hydronium ion toward Sagittarius B2(N) and W31C. Sensitive observations toward Sagittarius B2(N) show that the high, ~500 K, rotational temperatures characterizing the population of the highly excited metastable H3O+ rotational levels are present over a wide range of velocities corresponding to the Sagittarius B2 envelope, as well as the foreground gas clouds between the Sun and the source. Observations of the same lines toward W31C, a line of sight that does not intersect the Central Molecular Zone but instead traces quiescent gas in the Galactic disk, also imply a high rotational temperature of ~380 K, well in excess of the kinetic temperature of the diffuse Galactic interstellar medium. While it is plausible that some fraction of the molecular gas may be heated to such high temperatures in the active environment of the Galactic center, characterized by high X-ray and cosmic-ray fluxes, shocks, and high degree of turbulence, this is unlikely in the largely quiescent environment of the Galactic disk clouds. We suggest instead that the highly excited states of the hydronium ion are populated mainly by exoergic chemical formation processes and the temperature describing the rotational level population does not represent the physical temperature of the medium. The same arguments may be applicable to other symmetric top rotors, such as ammonia. This offers a simple explanation of the long-standing puzzle of the presence of a pervasive, hot molecular gas component in the central region of the Milky Way. Moreover, our observations suggest that this is a universal process not limited to the active environments associated with galactic nuclei.
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| 73. |
- Malm, Lisa E., et al.
(författare)
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Livestock grazing impacts components of the breeding productivity of a common upland insectivorous passerine : Results from a long-term experiment
- 2020
-
Ingår i: Journal of Applied Ecology. - : John Wiley & Sons. - 0021-8901 .- 1365-2664. ; 57:8, s. 1514-1523
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Tidskriftsartikel (refereegranskat)abstract
- 1. The intensity of pastoral management in areas of High Nature Value farming is declining in some regions of Europe but increasing in others. This affects open habitats of conservation concern, such as the British uplands, where bird species that benefit from low-intensity grazing may be most sensitive to such polarization. While experimental manipulations of livestock grazing intensities have improved our understanding of upland breeding bird responses in the short term, none have examined the long-term impacts of altered management on reproductive success.2. Using a replicated landscape-scale experiment that started in 2003, we investigated the effects of four grazing treatments (intensive sheep; low-intensity sheep; low-intensity mixed sheep and cattle; and no grazing) on the breeding productivity of meadow pipits Anthus pratensis, the most common upland passerine. Surveys were carried out systematically during early (2003 and 2004) and late (2015 and 2016) sampling periods of the experiment to compare the short- and long-term effects of grazing treatments on breeding density and productivity of pipits specifically, but also on the overall bird community.3. Pipit breeding density was lowest under low-intensity sheep grazing while the highest egg-stage nest survival was observed in the same treatment, although no significant treatment effects were detected on overall nest survival or fledgling output. There were no significant differences in treatment effects between the sampling periods on any breeding variable, but overall nest survival was lower in the later sampling period across all treatments.4. Breeding bird species richness differed between treatments in the later sampling period, with highest species richness in the ungrazed treatment.5. Synthesis and applications. Livestock grazing management can have different outcomes for different upland birds. Our results showed that, with time, meadow pipit breeding productivity tended to be higher when sheep grazing intensity was reduced and/or mixed with cattle, and lower when livestock were removed, but not significantly so. Removal of grazing, however, can significantly increase bird species richness. The long-term experiment showed an overall decline in fledglings regardless of grazing treatments, potentially a result of increased predator numbers harboured by nearby developing woodland, highlighting the importance of considering wider landscape processes in grazing management decisions.
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| 74. |
- Moeller, Sina, et al.
(författare)
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Lack of association between autism and anti-GM1 ganglioside antibody
- 2013
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Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 81:18, s. 1640-1641
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Forty of 54 children with autism were reported to have an elevated antibody response to GM1 ganglioside that correlated with disease severity.1 Antiganglioside autoantibodies, especially those directed at GM1, are known to be associated with and play a pathogenic role in some immune-mediated peripheral neuropathies.2,3 The presumed link between autism and anti-GM1 antibodies, therefore, implies that testing may identify a sizable subset of patients who would benefit from immunomodulatory therapy. To evaluate the proposed association between autism and anti-GM1 antibodies, serum samples from children diagnosed with autism by strict clinical criteria and those without autism were analyzed using a standard, validated immunoassay protocol.
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| 75. |
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| 76. |
- Nagao-Kitamoto, H., et al.
(författare)
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Interleukin-22-mediated host glycosylation prevents Clostridioides difficile infection by modulating the metabolic activity of the gut microbiota
- 2020
-
Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 26, s. 608-617
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Tidskriftsartikel (refereegranskat)abstract
- In germ-free mice colonized with human microbiota, mucosal IL-22 signaling promotes the growth of succinate-consuming commensal bacteria via host mucus glycosylation, and transplantation of these bacteria limits Clostridioides difficile infection. The involvement of host immunity in the gut microbiota-mediated colonization resistance to Clostridioides difficile infection (CDI) is incompletely understood. Here, we show that interleukin (IL)-22, induced by colonization of the gut microbiota, is crucial for the prevention of CDI in human microbiota-associated (HMA) mice. IL-22 signaling in HMA mice regulated host glycosylation, which enabled the growth of succinate-consuming bacteria Phascolarctobacterium spp. within the gut microbiome. Phascolarctobacterium reduced the availability of luminal succinate, a crucial metabolite for the growth of C. difficile, and therefore prevented the growth of C. difficile. IL-22-mediated host N-glycosylation is likely impaired in patients with ulcerative colitis (UC) and renders UC-HMA mice more susceptible to CDI. Transplantation of healthy human-derived microbiota or Phascolarctobacterium reduced luminal succinate levels and restored colonization resistance in UC-HMA mice. IL-22-mediated host glycosylation thus fosters the growth of commensal bacteria that compete with C. difficile for the nutritional niche.
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| 77. |
- Ritscher, Amélie, et al.
(författare)
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Zurich Statement on Future Actions on Per - and Polyfluoroalkyl Substances (PFASs)
- 2018
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Ingår i: Journal of Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 126:8
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Tidskriftsartikel (refereegranskat)abstract
- Per - and polyfluoroalkyl substances (PFASs) are man-made chemicals that contain at least one perfluoroalkyl moiety, -CnF2n-. To date, over 4,000 unique PFASs have been used in technical applications and consumer products, and some of them have been detected globally in human and wildlife biomonitoring studies. Because of their extraordinary persistence, human and environmental exposure to PFASs will be a long-term source of concern. Some PFASs such as perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) have been investigated extensively and thus regulated, but for many other PFASs, knowledge about their current uses and hazards is still very limited or missing entirely. To address this problem and prepare an action plan for the assessment and management of PFASs in the coming years, a group of more than 50 international scientists and regulators held a two-day workshop in November, 2017. The group identified both the respective needs of and common goals shared by the scientific and the policy communities, made recommendations for cooperative actions, and outlined how the science-policy interface regarding PFASs can be strengthened using new approaches for assessing and managing highly persistent chemicals such as PFASs.
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| 78. |
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| 79. |
- Scherer, SW, et al.
(författare)
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Human chromosome 7: DNA sequence and biology
- 2003
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 300:5620, s. 767-772
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Tidskriftsartikel (refereegranskat)abstract
- DNA sequence and annotation of the entire human chromosome 7, encompassing nearly 158 million nucleotides of DNA and 1917 gene structures, are presented. To generate a higher order description, additional structural features such as imprinted genes, fragile sites, and segmental duplications were integrated at the level of the DNA sequence with medical genetic data, including 440 chromosome rearrangement breakpoints associated with disease. This approach enabled the discovery of candidate genes for developmental diseases including autism.
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| 80. |
- Schmidt, P., et al.
(författare)
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Remote sensing of a levitated superconductor with a flux-tunable microwave cavity
- 2024
-
Ingår i: Physical Review Applied. - 2331-7019. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- We present a cavity-electromechanical system comprising a superconducting quantum interference device which is embedded in a microwave resonator and coupled via a pickup loop to a 6-μg magnetically levitated superconducting sphere. The motion of the sphere in the magnetic trap induces a frequency shift in the SQUID-cavity system. We use microwave spectroscopy to characterize the system, and we demonstrate that the electromechanical interaction is tunable. The measured displacement sensitivity of 10-7m/Hz defines a path towards ground-state cooling of levitated particles with Planck-scale masses at millikelvin environment temperatures.
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| 81. |
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| 82. |
- Shein, A. M. S., et al.
(författare)
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Novel colistin-EDTA combination for successful eradication of colistin-resistant Klebsiella pneumoniae catheter-related biofilm infections
- 2021
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Development of an effective therapy to overcome colistin resistance in Klebsiella pneumoniae, a common pathogen causing catheter-related biofilm infections in vascular catheters, has become a serious therapeutic challenge that must be addressed urgently. Although colistin and EDTA have successful roles for eradicating biofilms, no in vitro and in vivo studies have investigated their efficacy in catheter-related biofilm infections of colistin-resistant K. pneumoniae. In this study, colistin resistance was significantly reversed in both planktonic and mature biofilms of colistin-resistant K. pneumoniae by a combination of colistin (0.25-1 mu g/ml) with EDTA (12 mg/ml). This novel colistin-EDTA combination was also demonstrated to have potent efficacy in eradicating colistin-resistant K. pneumoniae catheter-related biofilm infections, and eliminating the risk of recurrence in vivo. Furthermore, this study revealed significant therapeutic efficacy of colistin-EDTA combination in reducing bacterial load in internal organs, lowering serum creatinine, and protecting treated mice from mortality. Altered in vivo expression of different virulence genes indicate bacterial adaptive responses to survive in hostile environments under different treatments. According to these data discovered in this study, a novel colistin-EDTA combination provides favorable efficacy and safety for successful eradication of colistin-resistant K. pneumonia catheter-related biofilm infections.
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| 83. |
- Zheng, L. K., et al.
(författare)
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Combined Connectomics, MAPT Gene Expression, and Amyloid Deposition to Explain Regional Tau Deposition in Alzheimer Disease
- 2024
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Ingår i: Annals of Neurology. - 0364-5134. ; 95:2, s. 274-287
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We aimed to test whether region-specific factors, including spatial expression patterns of the tau-encoding gene MAPT and regional levels of amyloid positron emission tomography (PET), enhance connectivity-based modeling of the spatial variability in tau-PET deposition in the Alzheimer disease (AD) spectrum.Methods: We included 685 participants (395 amyloid-positive participants within AD spectrum and 290 amyloid-negative controls) with tau-PET and amyloid-PET from 3 studies (Alzheimer's Disease Neuroimaging Initiative, F-18-AV-1451-A05, and BioFINDER-1). Resting-state functional magnetic resonance imaging was obtained in healthy controls (n = 1,000) from the Human Connectome Project, and MAPT gene expression from the Allen Human Brain Atlas. Based on a brain-parcellation atlas superimposed onto all modalities, we obtained region of interest (ROI)-to-ROI functional connectivity, ROI-level PET values, and MAPT gene expression. In stepwise regression analyses, we tested connectivity, MAPT gene expression, and amyloid-PET as predictors of group-averaged and individual tau-PET ROI values in amyloid-positive participants.Results: Connectivity alone explained 21.8 to 39.2% (range across 3 studies) of the variance in tau-PET ROI values averaged across amyloid-positive participants. Stepwise addition of MAPT gene expression and amyloid-PET increased the proportion of explained variance to 30.2 to 46.0% and 45.0 to 49.9%, respectively. Similarly, for the prediction of patient-level tau-PET ROI values, combining all 3 predictors significantly improved the variability explained (mean adjusted R-2 range across studies = 0.118-0.148, 0.156-0.196, and 0.251-0.333 for connectivity alone, connectivity plus MAPT expression, and all 3 modalities combined, respectively).Interpretation: Across 3 study samples, combining the functional connectome and molecular properties substantially enhanced the explanatory power compared to single modalities, providing a valuable tool to explain regional susceptibility to tau deposition in AD.
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| 84. |
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| 85. |
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| 86. |
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| 87. |
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| 88. |
- Bost, Jeremy P., et al.
(författare)
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Novel endosomolytic compounds enable highly potent delivery of antisense oligonucleotides
- 2022
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- The therapeutic and research potentials of oligonucleotides (ONs) have been hampered in part by their inability to effectively escape endosomal compartments to reach their cytosolic and nuclear targets. Splice-switching ONs (SSOs) can be used with endosomolytic small molecule compounds to increase functional delivery. So far, development of these compounds has been hindered by a lack of high-resolution methods that can correlate SSO trafficking with SSO activity. Here we present in-depth characterization of two novel endosomolytic compounds by using a combination of microscopic and functional assays with high spatiotemporal resolution. This system allows the visualization of SSO trafficking, evaluation of endosomal membrane rupture, and quantitates SSO functional activity on a protein level in the presence of endosomolytic compounds. We confirm that the leakage of SSO into the cytosol occurs in parallel with the physical engorgement of LAMP1-positive late endosomes and lysosomes. We conclude that the new compounds interfere with SSO trafficking to the LAMP1-positive endosomal compartments while inducing endosomal membrane rupture and concurrent ON escape into the cytosol. The efficacy of these compounds advocates their use as novel, potent, and quick-acting transfection reagents for antisense ONs.
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| 89. |
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| 90. |
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| 91. |
- Cardoso, Fernando R., et al.
(författare)
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Superposition of two-mode squeezed states for quantum information processing and quantum sensing
- 2021
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Ingår i: Physical Review A: covering atomic, molecular, and optical physics and quantum information. - 2469-9926 .- 2469-9934. ; 103:6
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Tidskriftsartikel (refereegranskat)abstract
- We investigate superpositions of two-mode squeezed states (TMSSs), which have potential applications in quantum information processing and quantum sensing. We study some properties of these nonclassical states such as the statistics of each mode and the degree of entanglement between the two modes, which can be higher than that of a TMSS with the same degree of squeezing. The states we consider can be prepared by inducing two-mode Jaynes-Cummings and anti-Jaynes-Cummings interactions in a system of two modes and a spin-1/2 particle, for instance, in the trapped ion domain, as described here. We show that when two harmonic oscillators are prepared in a superposition of two TMSSs, each reduced single-mode state can be advantageously employed to sense arbitrary displacements of the mode in phase space. The Wigner function of this reduced state exhibits a symmetrical peak centered at the phase-space origin, which has the convenient peculiarity of getting narrower in both quadratures simultaneously as the average photon number increases. This narrow peak can be used as the pointer of our quantum sensor, with its position in phase space indicating the displacement undergone by the oscillator.
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| 92. |
- Casares, L., et al.
(författare)
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The synthetic triterpenoids CDDO-TFEA and CDDO-Me, but not CDDO, promote nuclear exclusion of BACH1 impairing its activity
- 2022
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Ingår i: Redox Biology. - : Elsevier BV. - 2213-2317. ; 51
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Tidskriftsartikel (refereegranskat)abstract
- The transcription factor BACH1 is a potential therapeutic target for a variety of chronic conditions linked to oxidative stress and inflammation, as well as cancer metastasis. However, only a few BACH1 degraders/inhibitors have been described. BACH1 is a transcriptional repressor of heme oxygenase 1 (HMOX1), which is positively regulated by transcription factor NRF2 and is highly inducible by derivatives of the synthetic oleanane triterpenoid 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO). Most of the therapeutic activities of these compounds are due to their anti-inflammatory and antioxidant properties, which are widely attributed to their ability to activate NRF2. However, with such a broad range of action, these compounds have other molecular targets that have not been fully identified and could also be of importance for their therapeutic profile. Herein we identified BACH1 as a target of two CDDO-derivatives (CDDO-Me and CDDO-TFEA), but not of CDDO. While both CDDO and CDDO-derivatives activate NRF2 similarly, only CDDO-Me and CDDO-TFEA inhibit BACH1, which explains the much higher potency of these CDDO-derivatives as HMOX1 inducers compared with unmodified CDDO. Notably, we demonstrate that CDDO-Me and CDDO-TFEA inhibit BACH1 via a novel mechanism that reduces BACH1 nuclear levels while accumulating its cytoplasmic form. In an in vitro model, both CDDO-derivatives impaired lung cancer cell invasion in a BACH1-dependent and NRF2-independent manner, while CDDO was inactive. Altogether, our study identifies CDDO-Me and CDDO-TFEA as dual KEAP1/BACH1 inhibitors, providing a rationale for further therapeutic uses of these drugs.
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| 93. |
- Chiavaroli, Valentina, et al.
(författare)
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Exercise in pregnancy : 1-year and 7-year follow-ups of mothers and offspring after a randomized controlled trial
- 2018
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- There are limited data on long-term outcomes of mothers or their offspring following exercise interventions during pregnancy. We assessed long-term effects of an exercise intervention (home-based stationary cycling) between 20-36 weeks of gestation on anthropometry and body composition in mothers and offspring after 1 and 7 years. 84 women were randomised to intervention or usual activity, with follow-up data available for 61 mother-child pairs (38 exercisers) at 1 year and 57 (33 exercisers) at 7 years. At 1 year, there were no observed differences in measured outcomes between mothers and offspring in the two groups. At the 7-year follow-up, mothers were mostly similar, except that exercisers had lower systolic blood pressure (-6.2 mmHg; p = 0.049). However, offspring of mothers who exercised during pregnancy had increased total body fat (+3.2%; p = 0.034) and greater abdominal (+4.1% android fat; p = 0.040) and gynoid (+3.5% gynoid fat; p = 0.042) adiposity compared with controls. Exercise interventions beginning during pregnancy may be beneficial to long-term maternal health. However, the initiation of exercise during pregnancy amongst sedentary mothers may be associated with adverse effects in the offspring during childhood. Larger follow-up studies are required to investigate long-term effects of exercise in pregnancy.
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| 94. |
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| 95. |
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| 96. |
- Glover, Nikolas, 1979-, et al.
(författare)
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Conceptualising ‘Made in’ as a historical phenomenon
- 2023. - 1
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Ingår i: National Brands and Global Markets. - London & New York : Routledge. - 9780367754976 - 9781003166184
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Bokkapitel (refereegranskat)abstract
- This introduction advances the argument that the history of ‘Made in’ can be used to shed light on the dynamic historical relationships between the actors that have promoted them, the institutions that have regulated them, and the cultural environment that has attributed them meaning. Outlining a framework for analysing these intersections between individual market actors, international regulations, and national political projects, it proposed that ‘Made in’ can be approached from three different angles: at the firm level as strategically selected promotional appeals; at the level of national economic policy and international regulation as legal constructs; and at a societal level of coalition-building and national mobilization as political projects. It is from this perspective that this chapter presents the case studies that make up the remainder of this volume, chapters that in turn explore the evolution of ‘Made in’ within 11 different countries.
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| 97. |
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| 98. |
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| 99. |
- Higgins, D., et al.
(författare)
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Application of high-throughput pyrosequencing in the analysis of microbiota of food commodities procured from small and large retail outlets in a U.S. metropolitan area – A pilot study
- 2018
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Ingår i: Food Research International. - : Elsevier BV. - 0963-9969. ; 105, s. 29-40
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Tidskriftsartikel (refereegranskat)abstract
- With the advent of high-throughput sequencing technologies, it is possible to comprehensively analyze the microbial community of foods without culturing them in the laboratory. The estimation of all microbes inhabiting a food commodity (food microbiota) therefore may shed light on the microbial quality and safety of foods. In this study, we utilized high-throughput pyrosequencing of 16S rRNA genes as well as traditional microbiological methods to evaluate the bacterial diversity and the predicted metabolic pathways associated with the bacterial communities of selected foods (romaine lettuce, cabbage, deli meat, and chicken legs, total 200 samples) procured from small and large retail outlets located in Memphis-Shelby County, Tennessee, USA. For high-throughput sequencing, microbial genomic DNA was directly extracted from the food products and subjected to genetic sequencing. Aerobic plate count of all food samples was also performed. Foods from small stores (such as corner stores) were found to contain higher bacterial counts as compared to large stores (such as supermarkets). High-throughput pyrosequencing in tandem with bioinformatics analyses revealed a comprehensive picture of the bacterial ecology of foods at different taxonomic levels. Firmicutes and Proteobacteria were the most abundant phyla across all products. At the genus level, Enterobacter and Pantoea in vegetables, and Bacillus and Aeromonas in animal products were found to be the most abundant. The bacterial predicted metabolic pathways such as inosine-5′-phosphate biosynthesis I, methylglyoxal (MG) degradation pathways, urea cycle, dTDP-L-rhamnose biosynthesis I, and mevalonate pathway I differed in foods procured from small stores as compared to large groceries or supermarkets. The results from this study revealed that the bacterial ecology (both in terms of numbers and types of bacteria) of food commodities might differ based on the vending outlet type (large vs. small) of retail stores. The overall estimation bacterial communities in foods by high-throughput sequencing method may be useful to identify potential taxa responsible for food spoilage. Moreover, the data from pyrosequencing of 16S rRNA genes can also be applied to infer major metabolic pathways in bacteria inhabiting different foods. This may reflect the role of these pathways in food-bacteria interaction and adaptation.
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| 100. |
- Higgins, Geoff S, et al.
(författare)
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Overexpression Of POLQ Confers a Poor Prognosis In Early Breast Cancer Patients.
- 2010
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Ingår i: Oncotarget. - 1949-2553. ; 1:3, s. 175-184
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Tidskriftsartikel (refereegranskat)abstract
- Depletion of POLQ (DNA polymerase theta) has recently been shown to render tumour cells more sensitive to radiotherapy whilst having little or no effect on normal tissues. This finding led us to investigate whether tumours that overexpress POLQ are associated with an adverse outcome. We therefore correlated the clinical outcomes of two retrospective series of patients with early breast cancer with the expression levels of POLQ, as determined by microarray gene expression analysis. We found that a significant number of tumours overexpressed POLQ and that overexpression was correlated with ER negative disease (p=0.047) and high tumour grade (p=0.004), both of which are associated with poor clinical outcomes. POLQ overexpression was associated with poor relapse free survival rates on both univariate (HR 5.80; 95% CI, 2.220 to 15.159; p<0.001) and multivariate analysis (HR 8.086; 95% CI 2.340 to 27.948 p=0.001). Analysis of other published clinical series confirmed that POLQ overexpression is associated with adverse clinical outcomes. The poor prognosis associated with POLQ is independent of other clinical or pathological features. The mechanism that causes this adverse outcome remains to be elucidated but may in part arise from resistance to adjuvant treatment. These findings, combined with the limited normal tissue expression of POLQ, make it a very appealing target for possible clinical exploitation.
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