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| 2. |
- Ademuyiwa, Adesoji O., et al.
(författare)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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| 3. |
- Kattge, Jens, et al.
(författare)
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TRY plant trait database - enhanced coverage and open access
- 2020
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Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
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Tidskriftsartikel (refereegranskat)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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| 4. |
- Baum, Matthew L, et al.
(författare)
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CSMD1 regulates brain complement activity and circuit development
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Ingår i: Brain, Behavior, and Immunity. - 1090-2139.
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Tidskriftsartikel (refereegranskat)abstract
- Complement proteins facilitate synaptic elimination during neurodevelopmental pruning, but neural complement regulation is not well understood. CUB and Sushi Multiple Domains 1 (CSMD1) can regulate complement activity in vitro, is expressed in the brain, and is associated with increased schizophrenia risk. Beyond this, little is known about CSMD1 including whether it regulates complement activity in the brain or otherwise plays a role in neurodevelopment. We used biochemical, immunohistochemical, and proteomic techniques to examine the regional, cellular, and subcellular distribution as well as protein interactions of CSMD1 in the brain. To evaluate whether CSMD1 is involved in complement-mediated synapse elimination, we examined Csmd1-knockout mice and CSMD1-knockout human stem cell-derived neurons. We interrogated synapse and circuit development of the mouse visual thalamus, a process that involves complement pathway activity. We also quantified complement deposition on synapses in mouse visual thalamus and on cultured human neurons. Finally, we assessed uptake of synaptosomes by cultured microglia. We found that CSMD1 is present at synapses and interacts with complement proteins in the brain. Mice lacking Csmd1 displayed increased levels of complement component C3, an increased colocalization of C3 with presynaptic terminals, fewer retinogeniculate synapses, and aberrant segregation of eye-specific retinal inputs to the visual thalamus during the critical period of complement-dependent refinement of this circuit. Loss of CSMD1 in vivo enhanced synaptosome engulfment by microglia in vitro, and this effect was dependent on activity of the microglial complement receptor, CR3. Finally, human stem cell-derived neurons lacking CSMD1 were more vulnerable to complement deposition. These data suggest that CSMD1 can function as a regulator of complement-mediated synapse elimination in the CNS during development.
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| 5. |
- Cusack, Daniela Francis, et al.
(författare)
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Tradeoffs and Synergies in Tropical Forest Root Traits and Dynamics for Nutrient and Water Acquisition : Field and Modeling Advances
- 2021
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Ingår i: Frontiers in Forests and Global Change. - : Frontiers Media S.A.. - 2624-893X. ; 4
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Forskningsöversikt (refereegranskat)abstract
- Vegetation processes are fundamentally limited by nutrient and water availability, the uptake of which is mediated by plant roots in terrestrial ecosystems. While tropical forests play a central role in global water, carbon, and nutrient cycling, we know very little about tradeoffs and synergies in root traits that respond to resource scarcity. Tropical trees face a unique set of resource limitations, with rock-derived nutrients and moisture seasonality governing many ecosystem functions, and nutrient versus water availability often separated spatially and temporally. Root traits that characterize biomass, depth distributions, production and phenology, morphology, physiology, chemistry, and symbiotic relationships can be predictive of plants’ capacities to access and acquire nutrients and water, with links to aboveground processes like transpiration, wood productivity, and leaf phenology. In this review, we identify an emerging trend in the literature that tropical fine root biomass and production in surface soils are greatest in infertile or sufficiently moist soils. We also identify interesting paradoxes in tropical forest root responses to changing resources that merit further exploration. For example, specific root length, which typically increases under resource scarcity to expand the volume of soil explored, instead can increase with greater base cation availability, both across natural tropical forest gradients and in fertilization experiments. Also, nutrient additions, rather than reducing mycorrhizal colonization of fine roots as might be expected, increased colonization rates under scenarios of water scarcity in some forests. Efforts to include fine root traits and functions in vegetation models have grown more sophisticated over time, yet there is a disconnect between the emphasis in models characterizing nutrient and water uptake rates and carbon costs versus the emphasis in field experiments on measuring root biomass, production, and morphology in response to changes in resource availability. Closer integration of field and modeling efforts could connect mechanistic investigation of fine-root dynamics to ecosystem-scale understanding of nutrient and water cycling, allowing us to better predict tropical forest-climate feedbacks.
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| 6. |
- Hamdi, Yosr, et al.
(författare)
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Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression : identification of a modifier of breast cancer risk at locus 11q22.3
- 2017
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 161:1, s. 117-134
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Cis-acting regulatory SNPs resulting in differential allelic expression (DAE) may, in part, explain the underlying phenotypic variation associated with many complex diseases. To investigate whether common variants associated with DAE were involved in breast cancer susceptibility among BRCA1 and BRCA2 mutation carriers, a list of 175 genes was developed based of their involvement in cancer-related pathways. Methods: Using data from a genome-wide map of SNPs associated with allelic expression, we assessed the association of ~320 SNPs located in the vicinity of these genes with breast and ovarian cancer risks in 15,252 BRCA1 and 8211 BRCA2 mutation carriers ascertained from 54 studies participating in the Consortium of Investigators of Modifiers of BRCA1/2. Results: We identified a region on 11q22.3 that is significantly associated with breast cancer risk in BRCA1 mutation carriers (most significant SNP rs228595 p = 7 × 10−6). This association was absent in BRCA2 carriers (p = 0.57). The 11q22.3 region notably encompasses genes such as ACAT1, NPAT, and ATM. Expression quantitative trait loci associations were observed in both normal breast and tumors across this region, namely for ACAT1, ATM, and other genes. In silico analysis revealed some overlap between top risk-associated SNPs and relevant biological features in mammary cell data, which suggests potential functional significance. Conclusion: We identified 11q22.3 as a new modifier locus in BRCA1 carriers. Replication in larger studies using estrogen receptor (ER)-negative or triple-negative (i.e., ER-, progesterone receptor-, and HER2-negative) cases could therefore be helpful to confirm the association of this locus with breast cancer risk.
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| 7. |
- Jennions, Elizabeth, et al.
(författare)
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TANGO2 deficiency as a cause of neurodevelopmental delay with indirect effects on mitochondrial energy metabolism
- 2019
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Ingår i: Journal of Inherited Metabolic Disease. - : Wiley. - 0141-8955 .- 1573-2665. ; 42:5, s. 898-908
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Tidskriftsartikel (refereegranskat)abstract
- Exome sequencing has recently identified mutations in the gene TANGO2 (transport and Golgi organization 2) as a cause of developmental delay associated with recurrent crises involving rhabdomyolysis, cardiac arrhythmias, and metabolic derangements. The disease is not well understood, in part as the cellular function and subcellular localization of the TANGO2 protein remain unknown. Furthermore, the clinical syndrome with its heterogeneity of symptoms, signs, and laboratory findings is still being defined. Here, we describe 11 new cases of TANGO2-related disease, confirming and further expanding the previously described clinical phenotype. Patients were homozygous or compound heterozygous for previously described exonic deletions or new frameshift, splice site, and missense mutations. All patients showed developmental delay with ataxia, dysarthria, intellectual disability, or signs of spastic diplegia. Of importance, we identify two subjects (aged 12 and 17 years) who have never experienced any overt episode of the catabolism-induced metabolic crises typical for the disease. Mitochondrial complex II activity was mildly reduced in patients investigated in association with crises but normal in other patients. In one deceased patient, post-mortem autopsy revealed heterotopic neurons in the cerebral white matter, indicating a possible role for TANGO2 in neuronal migration. Furthermore, we have addressed the subcellular localization of several alternative isoforms of TANGO2, none of which were mitochondrial but instead appeared to have a primarily cytoplasmic localization. Previously described aberrations in Golgi morphology were not observed in cultured skin fibroblasts.
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| 8. |
- Li, Bin, et al.
(författare)
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Inverted-V and low-energy broadband electron acceleration features of multiple auroras within a large-scale surge
- 2013
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Ingår i: Journal of Geophysical Research: Space Physics. - : American Geophysical Union (AGU). - 2169-9380. ; 118:9, s. 5543-5552
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Tidskriftsartikel (refereegranskat)abstract
- Results are presented from a Cluster C2 satellite crossing through the acceleration region of multiple auroral structures within a large-scale surge, simultaneously monitored by DMSP F17 imager data. The magnetic and electric field data are consistent with the auroral distribution at large and medium scales. We identify the quasi-static acceleration above and below C2 orbit by downgoing inverted-V electrons and parallel electric potential drops, respectively. In the poleward surge region, within or adjacent to the inverted-V arcs, intense low-energy (broadband) electron fluxes are seen as well as a rough equality between E/B and the Alfven velocity, suggesting that these are of Alfvenic origin. The most poleward and equatorward auroral structure is found to be Alfvenic and quasi-static, respectively. In between, the structures are of mixed origin. We estimate the relative role of the acceleration processes by the contributions to the downward electron energy flux by electrons above and below 1.62keV. Although these are local estimates, they should be representative also below Cluster altitude, except for two regions of intense downward Poynting flux, the power of which will be dissipated at lower altitudes and increasing the Alfvenic contribution. This is also supported by intense fluxes of low-energy, broadband, upgoing electrons observed within these regions. Otherwise, the inverted-V contribution dominates for most of the auroral structures observed by Cluster. The Alfvenic contribution to the mixed arc emissions is to extend these to higher altitudes, as shown by numerical simulation results.
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| 9. |
- Palmer, Elizabeth E., et al.
(författare)
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Functional and clinical studies reveal pathophysiological complexity of CLCN4-related neurodevelopmental condition
- 2023
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Ingår i: Molecular Psychiatry. - : SPRINGERNATURE. - 1359-4184 .- 1476-5578. ; 28:2, s. 668-697
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Tidskriftsartikel (refereegranskat)abstract
- Missense and truncating variants in the X-chromosome-linked CLCN4 gene, resulting in reduced or complete loss-of-function (LOF) of the encoded chloride/proton exchanger ClC-4, were recently demonstrated to cause a neurocognitive phenotype in both males and females. Through international clinical matchmaking and interrogation of public variant databases we assembled a database of 90 rare CLCN4 missense variants in 90 families: 41 unique and 18 recurrent variants in 49 families. For 43 families, including 22 males and 33 females, we collated detailed clinical and segregation data. To confirm causality of variants and to obtain insight into disease mechanisms, we investigated the effect on electrophysiological properties of 59 of the variants in Xenopus oocytes using extended voltage and pH ranges. Detailed analyses revealed new pathophysiological mechanisms: 25% (15/59) of variants demonstrated LOF, characterized by a "shift" of the voltage-dependent activation to more positive voltages, and nine variants resulted in a toxic gain-of-function, associated with a disrupted gate allowing inward transport at negative voltages. Functional results were not always in line with in silico pathogenicity scores, highlighting the complexity of pathogenicity assessment for accurate genetic counselling. The complex neurocognitive and psychiatric manifestations of this condition, and hitherto under-recognized impacts on growth, gastrointestinal function, and motor control are discussed. Including published cases, we summarize features in 122 individuals from 67 families with CLCN4-related neurodevelopmental condition and suggest future research directions with the aim of improving the integrated care for individuals with this diagnosis.
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| 10. |
- Shaw, Felix, et al.
(författare)
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COPO : a metadata platform for brokering FAIR data in the life sciences
- 2020
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Ingår i: F1000 Research. - : F1000 Research Ltd. - 2046-1402. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Scientific innovation is increasingly reliant on data and computational resources. Much of today’s life science research involves generating, processing, and reusing heterogeneous datasets that are growing exponentially in size. Demand for technical experts (data scientists and bioinformaticians) to process these data is at an all-time high, but these are not typically trained in good data management practices. That said, we have come a long way in the last decade, with funders, publishers, and researchers themselves making the case for open, interoperable data as a key component of an open science philosophy. In response, recognition of the FAIR Principles (that data should be Findable, Accessible, Interoperable and Reusable) has become commonplace. However, both technical and cultural challenges for the implementation of these principles still exist when storing, managing, analysing and disseminating both legacy and new data. COPO is a computational system that attempts to address some of these challenges by enabling scientists to describe their research objects (raw or processed data, publications, samples, images, etc.) using community-sanctioned metadata sets and vocabularies, and then use public or institutional repositories to share them with the wider scientific community. COPO encourages data generators to adhere to appropriate metadata standards when publishing research objects, using semantic terms to add meaning to them and specify relationships between them. This allows data consumers, be they people or machines, to find, aggregate, and analyse data which would otherwise be private or invisible, building upon existing standards to push the state of the art in scientific data dissemination whilst minimising the burden of data publication and sharing.
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