| 1. |
- Otero, Jaime, et al.
(författare)
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Basin-scale phenology and effects of climate variability on global timing of initial seaward migration of Atlantic salmon (Salmo salar)
- 2014
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Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 20:1, s. 61-75
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Tidskriftsartikel (refereegranskat)abstract
- Migrations between different habitats are key events in the lives of many organisms. Such movements involve annually recurring travel over long distances usually triggered by seasonal changes in the environment. Often, the migration is associated with travel to or from reproduction areas to regions of growth. Young anadromous Atlantic salmon (Salmo salar) emigrate from freshwater nursery areas during spring and early summer to feed and grow in the North Atlantic Ocean. The transition from the freshwater ('parr') stage to the migratory stage where they descend streams and enter salt water ('smolt') is characterized by morphological, physiological and behavioural changes where the timing of this parr-smolt transition is cued by photoperiod and water temperature. Environmental conditions in the freshwater habitat control the downstream migration and contribute to within- and among-river variation in migratory timing. Moreover, the timing of the freshwater emigration has likely evolved to meet environmental conditions in the ocean as these affect growth and survival of the post-smolts. Using generalized additive mixed-effects modelling, we analysed spatio-temporal variations in the dates of downstream smolt migration in 67 rivers throughout the North Atlantic during the last five decades and found that migrations were earlier in populations in the east than the west. After accounting for this spatial effect, the initiation of the downstream migration among rivers was positively associated with freshwater temperatures, up to about 10 °C and levelling off at higher values, and with sea-surface temperatures. Earlier migration occurred when river discharge levels were low but increasing. On average, the initiation of the smolt seaward migration has occurred 2.5 days earlier per decade throughout the basin of the North Atlantic. This shift in phenology matches changes in air, river, and ocean temperatures, suggesting that Atlantic salmon emigration is responding to the current global climate changes.
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| 2. |
- Rando, Halie M, et al.
(författare)
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Pathogenesis, Symptomatology, and Transmission of SARS-CoV-2 through analysis of Viral Genomics and Structure
- 2021
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The novel coronavirus SARS-CoV-2, which emerged in late 2019, has since spread around the world infecting tens of millions of people with coronavirus disease 2019 (COVID-19). While this viral species was unknown prior to January 2020, its similarity to other coronaviruses that infect humans has allowed for rapid insight into the mechanisms that it uses to infect human hosts, as well as the ways in which the human immune system can respond. Here, we contextualize SARS-CoV-2 among other coronaviruses and identify what is known and what can be inferred about its behavior once inside a human host. Because the genomic content of coronaviruses, which specifies the virus's structure, is highly conserved, early genomic analysis provided a significant head start in predicting viral pathogenesis. The pathogenesis of the virus offers insights into symptomatology, transmission, and individual susceptibility. Additionally, prior research into interactions between the human immune system and coronaviruses has identified how these viruses can evade the immune system's protective mechanisms. We also explore systems-level research into the regulatory and proteomic effects of SARS-CoV-2 infection and the immune response. Understanding the structure and behavior of the virus serves to contextualize the many facets of the COVID-19 pandemic and can influence efforts to control the virus and treat the disease.
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| 3. |
- Rando, Halie M, et al.
(författare)
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Pathogenesis, Symptomatology, and Transmission of SARS-CoV-2 through Analysis of Viral Genomics and Structure
- 2021
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Ingår i: mSystems. - 2379-5077. ; 6:5
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Forskningsöversikt (refereegranskat)abstract
- The novel coronavirus SARS-CoV-2, which emerged in late 2019, has since spread around the world and infected hundreds of millions of people with coronavirus disease 2019 (COVID-19). While this viral species was unknown prior to January 2020, its similarity to other coronaviruses that infect humans has allowed for rapid insight into the mechanisms that it uses to infect human hosts, as well as the ways in which the human immune system can respond. Here, we contextualize SARS-CoV-2 among other coronaviruses and identify what is known and what can be inferred about its behavior once inside a human host. Because the genomic content of coronaviruses, which specifies the virus's structure, is highly conserved, early genomic analysis provided a significant head start in predicting viral pathogenesis and in understanding potential differences among variants. The pathogenesis of the virus offers insights into symptomatology, transmission, and individual susceptibility. Additionally, prior research into interactions between the human immune system and coronaviruses has identified how these viruses can evade the immune system's protective mechanisms. We also explore systems-level research into the regulatory and proteomic effects of SARS-CoV-2 infection and the immune response. Understanding the structure and behavior of the virus serves to contextualize the many facets of the COVID-19 pandemic and can influence efforts to control the virus and treat the disease. IMPORTANCE COVID-19 involves a number of organ systems and can present with a wide range of symptoms. From how the virus infects cells to how it spreads between people, the available research suggests that these patterns are very similar to those seen in the closely related viruses SARS-CoV-1 and possibly Middle East respiratory syndrome-related CoV (MERS-CoV). Understanding the pathogenesis of the SARS-CoV-2 virus also contextualizes how the different biological systems affected by COVID-19 connect. Exploring the structure, phylogeny, and pathogenesis of the virus therefore helps to guide interpretation of the broader impacts of the virus on the human body and on human populations. For this reason, an in-depth exploration of viral mechanisms is critical to a robust understanding of SARS-CoV-2 and, potentially, future emergent human CoVs (HCoVs).
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| 4. |
- Ameen, Carly, et al.
(författare)
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Specialized sledge dogs accompanied Inuit dispersal across the North American Arctic
- 2019
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Ingår i: Proceedings of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8452 .- 1471-2954. ; 286:1916
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Tidskriftsartikel (refereegranskat)abstract
- Domestic dogs have been central to life in the North American Arctic for millennia. The ancestors of the Inuit were the first to introduce the widespread usage of dog sledge transportation technology to the Americas, but whether the Inuit adopted local Palaeo-Inuit dogs or introduced a new dog population to the region remains unknown. To test these hypotheses, we generated mitochondrial DNA and geometric morphometric data of skull and dental elements from a total of 922 North American Arctic dogs and wolves spanning over 4500 years. Our analyses revealed that dogs from Inuit sites dating from 2000 BP possess morphological and genetic signatures that distinguish them from earlier Palaeo-Inuit dogs, and identified a novel mitochondrial clade in eastern Siberia and Alaska. The genetic legacy of these Inuit dogs survives today in modern Arctic sledge dogs despite phenotypic differences between archaeological and modern Arctic dogs. Together, our data reveal that Inuit dogs derive from a secondary pre-contact migration of dogs distinct from Palaeo-Inuit dogs, and probably aided the Inuit expansion across the North American Arctic beginning around 1000 BP.
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| 5. |
- Bentzer, Peter, et al.
(författare)
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Will this hemodynamically unstable patient respond to a bolus of intravenous fluids?
- 2016
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Ingår i: JAMA: The Journal of the American Medical Association. - : American Medical Association (AMA). - 0098-7484. ; 316:12, s. 1298-1309
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Fluid overload occurring as a consequence of overly aggressive fluid resuscitation may adversely affect outcome in hemodynamically unstable critically ill patients. Therefore, following the initial fluid resuscitation, it is important to identify which patients will benefit from further fluid administration. OBJECTIVE To identify predictors of fluid responsiveness in hemodynamically unstable patients with signs of inadequate organ perfusion. DATA SOURCES AND STUDY SELECTION Search of MEDLINE and EMBASE (1966 to June 2016) and reference lists from retrieved articles, previous reviews, and physical examination textbooks for studies that evaluated the diagnostic accuracy of tests to predict fluid responsiveness in hemodynamically unstable adult patients who were defined as having refractory hypotension, signs of organ hypoperfusion, or both. Fluid responsiveness was defined as an increase in cardiac output following intravenous fluid administration. DATA EXTRACTION Two authors independently abstracted data (sensitivity, specificity, and likelihood ratios [LRs]) and assessed methodological quality. A bivariate mixed-effects binary regression model was used to pool the sensitivities, specificities, and LRs across studies. RESULTS A total of 50 studies (N = 2260 patients) were analyzed. In all studies, indices were measured before assessment of fluid responsiveness. The mean prevalence of fluid responsiveness was 50% (95%CI, 42%-56%). Findings on physical examination were not predictive of fluid responsiveness with LRs and 95%CIs for each finding crossing 1.0. A low central venous pressure (CVP) (mean threshold 8mmHg) was associated with fluid responsiveness (positive LR, 2.6 [95%CI, 1.4-4.6]; pooled specificity, 76%), but a CVP greater than the threshold made fluid responsiveness less likely (negative LR, 0.50 [95%CI, 0.39-0.65]; pooled sensitivity, 62%). Respiratory variation in vena cava diameter measured by ultrasound (distensibility index >15%) predicted fluid responsiveness in a subgroup of patients without spontaneous respiratory efforts (positive LR, 5.3 [95%CI, 1.1-27]; pooled specificity, 85%). Patients with less vena cava distensibility were not as likely to be fluid responsive (negative LR, 0.27 [95%CI, 0.08-0.87]; pooled sensitivity, 77%). Augmentation of cardiac output or related parameters following passive leg raising predicted fluid responsiveness (positive LR, 11 [95%CI, 7.6-17]; pooled specificity, 92%). Conversely, the lack of an increase in cardiac output with passive leg raising identified patients unlikely to be fluid responsive (negative LR, 0.13 [95%CI, 0.07-0.22]; pooled sensitivity, 88%). CONCLUSIONS AND RELEVANCE Passive leg raising followed by measurement of cardiac output or related parameters may be the most useful test for predicting fluid responsiveness in hemodynamically unstable adults. The usefulness of respiratory variation in the vena cava requires confirmatory studies.
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| 6. |
- Caluzzi, Gabriel, et al.
(författare)
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‘90 per cent of the time when I have had a drink in my hand I’m on my phone as well’ : A cross-national analysis of communications technologies and drinking practices among young people
- 2023
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Ingår i: New Media and Society. - : SAGE Publications. - 1461-4448 .- 1461-7315.
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Tidskriftsartikel (refereegranskat)abstract
- Greater use of communication technologies among young people, including mobile phones, social media and communication apps, has coincided with declines in youth alcohol use in many high-income countries. However, little research has unpacked how drinking as a practice within interconnected routines and interactions may be changing alongside these technologies. Drawing on qualitative interviews about drinking with young people aged 16–23 across three similar studies in Australia, the United Kingdom and Sweden, we identify how communication technologies may afford reduced or increased drinking. They may reduce drinking by producing new online contexts, forms of intimacy and competing activities. They may increase drinking by re-organising drinking occasions, rituals and contexts. And they may increase or reduce drinking by enabling greater fluidity and interaction between diverse practices. These countervailing dynamics have likely contributed to shifting drinking patterns and practices for young people that may be obscured beneath the population-level decline in youth drinking.
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| 7. |
- Cooper, Ian R., et al.
(författare)
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Discovery and structure-activity relationships of a novel isothiazolone class of bacterial type II topoisomerase inhibitors
- 2016
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Ingår i: Bioorganic & Medicinal Chemistry Letters. - : Elsevier BV. - 0960-894X .- 1464-3405. ; 26:17, s. 4179-4183
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Tidskriftsartikel (refereegranskat)abstract
- There is an urgent and unmet medical need for new antibacterial drugs that tackle infections caused by multidrug-resistant (MDR) pathogens. During the course of our wider efforts to discover and exploit novel mechanism of action antibacterials, we have identified a novel series of isothiazolone based inhibitors of bacterial type II topoisomerase. Compounds from the class displayed excellent activity against both Gram-positive and Gram-negative bacteria with encouraging activity against a panel of MDR clinical Escherichia coli isolates when compared to ciprofloxacin. Representative compounds also displayed a promising in vitro safety profile.
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| 8. |
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| 9. |
- Haas, Brian J., et al.
(författare)
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Genome sequence and analysis of the Irish potato famine pathogen Phytophthora infestans
- 2009
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 461:7262, s. 393-398
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Tidskriftsartikel (refereegranskat)abstract
- Phytophthora infestans is the most destructive pathogen of potato and a model organism for the oomycetes, a distinct lineage of fungus-like eukaryotes that are related to organisms such as brown algae and diatoms. As the agent of the Irish potato famine in the mid-nineteenth century, P. infestans has had a tremendous effect on human history, resulting in famine and population displacement(1). To this day, it affects world agriculture by causing the most destructive disease of potato, the fourth largest food crop and a critical alternative to the major cereal crops for feeding the world's population(1). Current annual worldwide potato crop losses due to late blight are conservatively estimated at $6.7 billion(2). Management of this devastating pathogen is challenged by its remarkable speed of adaptation to control strategies such as genetically resistant cultivars(3,4). Here we report the sequence of the P. infestans genome, which at similar to 240 megabases (Mb) is by far the largest and most complex genome sequenced so far in the chromalveolates. Its expansion results from a proliferation of repetitive DNA accounting for similar to 74% of the genome. Comparison with two other Phytophthora genomes showed rapid turnover and extensive expansion of specific families of secreted disease effector proteins, including many genes that are induced during infection or are predicted to have activities that alter host physiology. These fast-evolving effector genes are localized to highly dynamic and expanded regions of the P. infestans genome. This probably plays a crucial part in the rapid adaptability of the pathogen to host plants and underpins its evolutionary potential.
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| 10. |
- Keller, Ulrich B, et al.
(författare)
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Myc targets Cks1 to provoke the suppression of p27Kip1, proliferation and lymphomagenesis.
- 2007
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Ingår i: EMBO J. - 0261-4189. ; 26:10, s. 2562-74
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Tidskriftsartikel (refereegranskat)abstract
- Reduced levels of the cyclin-dependent kinase inhibitor p27(Kip1) connote poor prognosis in cancer. In human Burkitt lymphoma and in precancerous B cells and lymphomas arising in Emu-Myc transgenic mice, p27(Kip1) expression is markedly reduced. We show that the transcription of the Cks1 component of the SCF(Skp2) complex that is necessary for p27(Kip1) ubiquitylation and degradation is induced by Myc. Further, Cks1 expression is elevated in precancerous Emu-Myc B cells, and high levels of Cks1 are also a hallmark of Emu-Myc lymphoma and of human Burkitt lymphoma. Finally, loss of Cks1 in Emu-Myc B cells elevates p27(Kip1) levels, reduces proliferation and markedly delays lymphoma development and dissemination of disease. Therefore, Myc suppresses p27(Kip1) expression, accelerates cell proliferation and promotes tumorigenesis at least in part through its ability to selectively induce Cks1.
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| 11. |
- Keller, Ulrich, et al.
(författare)
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Nfkb 1 is dispensable for Myc-induced lymphomagenesis.
- 2005
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Ingår i: Oncogene. - 0950-9232. ; 24:41, s. 6231-40
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Tidskriftsartikel (refereegranskat)abstract
- Rel/NF-kappaB transcription factors are critical arbiters of immune responses, cell survival, and transformation, and are frequently deregulated in cancer. The p50 NF-kappaB 1 component of Rel/NF-kappaB DNA-binding dimers regulates genes involved in both cell cycle traverse and apoptosis. Nfkb 1 loss accelerates B cell growth and leads to increased B cell turnover in vivo, phenotypes akin to those manifested in B cells of Emu-Myc transgenic mice, a model of human Burkitt lymphoma. Interestingly, Emu-Myc B cells express reduced levels of cytoplasmic and nuclear NF-kappaB 1 and have reduced Rel/NF-kappaB DNA-binding activity, suggesting that Myc-mediated repression of NF-kappaB 1 might mediate its proliferative and apoptotic effects on B cells. Furthermore, Nfkb 1 expression was reduced in the majority of Emu-Myc lymphomas and was also suppressed in human Burkitt lymphoma. Nonetheless, loss of Nfkb 1 did not appreciably affect Myc's proliferative or apoptotic responses in B cells and had no effect on lymphoma development in Emu-Myc mice. Therefore, Nfkb 1 is dispensable for Myc-induced lymphomagenesis.. Oncogene (2005) 24, 6231-6240
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| 12. |
- Nilsson, Jonas A, et al.
(författare)
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Mnt loss triggers Myc transcription targets, proliferation, apoptosis, and transformation.
- 2004
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Ingår i: Mol Cell Biol. - 0270-7306. ; 24:4, s. 1560-9
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Tidskriftsartikel (refereegranskat)abstract
- Myc oncoproteins are overexpressed in most cancers and are sufficient to accelerate cell proliferation and provoke transformation. However, in normal cells Myc also triggers apoptosis. All of the effects of Myc require its function as a transcription factor that dimerizes with Max. This complex induces genes containing CACGTG E-boxes, such as Ornithine decarboxylase (Odc), which harbors two of these elements. Here we report that in quiescent cells the Odc E-boxes are occupied by Max and Mnt, a putative Myc antagonist, and that this complex is displaced by Myc-Max complexes in proliferating cells. Knockdown of Mnt expression by stable retroviral RNA interference triggers many targets typical of the "Myc" response and provokes accelerated proliferation and apoptosis. Strikingly, these effects of Mnt knockdown are even manifest in cells lacking c-myc. Moreover, Mnt knockdown is sufficient to transform primary fibroblasts in conjunction with Ras. Therefore, Mnt behaves as a tumor suppressor. These findings support a model where Mnt represses Myc target genes and Myc functions as an oncogene by relieving Mnt-mediated repression.
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| 13. |
- Pennay, Amy, et al.
(författare)
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“There’s a lot of stereotypes going on” : A cross-national qualitative analysis of the place of gender in declining youth drinking
- 2022
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Ingår i: International journal of drug policy. - : Elsevier BV. - 0955-3959 .- 1873-4758. ; 108
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Significant declines in drinking among young people have been recorded in many high-income countries over the past 20 years. This analysis explored the role of gender – which we interpret as socially constructed and relational – to provide insight into whether and how gender might be implicated in declining youth drinking.Methods: Interview data from four independent qualitative studies from Australia, Denmark, Sweden and the UK (n=194; participants aged 15-19 years) were analysed by researchers in each country following agreement about analytical focus. Findings were collated by the lead author in a process of ‘qualitative synthesis’ which involved successive rounds of data synthesis and feedback from the broader research team.Findings: Our analysis raised two notable points in relation to the role of gender in declining youth drinking. The first concerned the consistency and vehemence across three of the countries at which drinkers and states of intoxication were pejoratively described in gendered terms (e.g., bitchy, sleazy). The second related to the opportunities non- and light-drinking offered for expressing alternate and desirable configurations of femininities and masculinities.Conclusions: We identified an intolerance towards regressive constructions of gender that emphasise weakness for women and strength for men and a valorisation of gendered expressions of maturity through controlled drinking. Though subtle differences in gendered drinking practices between and within countries were observed, our findings offer insight into how young people’s enactions of gender are embedded in, and evolve alongside, these large declines in youth drinking.
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| 14. |
- Suggitt, Andrew J., et al.
(författare)
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Extinction risk from climate change is reduced by microclimatic buffering
- 2018
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Ingår i: Nature Climate Change. - : Springer Science and Business Media LLC. - 1758-678X .- 1758-6798. ; 8:8, s. 713-
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Tidskriftsartikel (refereegranskat)abstract
- Protecting biodiversity against the impacts of climate change requires effective conservation strategies that safeguard species at risk of extinction(1). Microrefugia allowed populations to survive adverse climatic conditions in the past(2,3), but their potential to reduce extinction risk from anthropogenic warming is poorly understood(3-5), hindering our capacity to develop robust in situ measures to adapt conservation to climate change(6). Here, we show that microclimatic heterogeneity has strongly buffered species against regional extirpations linked to recent climate change. Using more than five million distribution records for 430 climate-threatened and range-declining species, population losses across England are found to be reduced in areas where topography generated greater variation in the microclimate. The buffering effect of topographic microclimates was strongest for those species adversely affected by warming and in areas that experienced the highest levels of warming: in such conditions, extirpation risk was reduced by 22% for plants and by 9% for insects. Our results indicate the critical role of topographic variation in creating microrefugia, and provide empirical evidence that microclimatic heterogeneity can substantially reduce extinction risk from climate change.
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| 15. |
- Kanai, M, et al.
(författare)
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- 2023
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