| 1. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 2. |
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| 3. |
- Grzybowski, Andrzej, et al.
(författare)
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Endophthalmitis Prophylaxis in Cataract Surgery : Overview of Current Practice Patterns Around the World
- 2017
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Ingår i: Current pharmaceutical design. - : BENTHAM SCIENCE PUBL LTD. - 1381-6128 .- 1873-4286. ; 23:4, s. 565-573
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Forskningsöversikt (refereegranskat)abstract
- Background: Acute-onset postoperative endophthalmitis after cataract surgery remains a rare but important cause of visual loss. There is no global consensus regarding the optimal strategies for prophylaxis of endophthalmitis and practices vary substantially around the world, especially with respect to the use of intracameral antibiotics. The European Society of Cataract & Refractive Surgeons in a randomized clinical trial (2007) reported an approximately 5-fold reduction in endophthalmitis rates associated with the use of intracameral cefuroxime. Despite this report, the use of intracameral antibiotics has not been universally adopted. Methods: Various endophthalmitis prophylaxis patterns around the world (including the United States, Canada, Australia/New Zealand, Japan, China, India, Indonesia, South Africa, Argentina, Russia, Sweden and Mexico) are compared. Each contributing author was asked to provide similar information, including endophthalmitis rates based on published studies, current practice patterns, and in some cases original survey data. Various methods were used to obtain this information, including literature reviews, expert commentary, and some new survey data not previously published. Results: Many different practice patterns were reported from around the world, specifically with respect to the use of intracameral antibiotics. Conclusion: There is no worldwide consensus regarding endophthalmitis prophylaxis with cataract surgery.
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| 4. |
- Morales, Javier O., et al.
(författare)
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Surfactants : their critical role in enhancing drug delivery to the lungs
- 2011
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Ingår i: Therapeutic delivery. - : Future Science Ltd. - 2041-5990 .- 2041-6008. ; 2:5, s. 623-641
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Tidskriftsartikel (refereegranskat)abstract
- For local lung conditions and diseases, pulmonary drug delivery has been widely used for more than 50 years now. A more recent trend involves the pulmonary route as a systemic drug-delivery target. Advantages such as avoidance of the gastrointestinal environment, different enzyme content compared with the intestine, and avoidance of first-pass metabolism make the lung an alternative route for the systemic delivery of actives. However, the lung offers barriers to absorption such as a surfactant layer, epithelial surface lining fluid, epithelial monolayer, interstitium and basement membrane, and capillary endothelium. Many delivery strategies have been developed in order to overcome these limitations. The use of surfactants is one of these approaches and their role in enhancing pulmonary drug delivery is reviewed in this article. A systematic review of the literature relating to the effect of surfactants on formulations for pulmonary delivery was conducted. Specifically, research reporting enhancement of in vivo performance was focused on. The effect of the addition of surfactants such as phospholipids, bile salts, non-ionic, fatty acids, and liposomes as phospholipid-containing carriers on the enhancement of therapeutic outcomes of drugs for pulmonary delivery was compiled. The main use attributed to surfactants in pulmonary drug delivery is as absorption enhancers by mechanisms of action not yet fully understood. Furthermore, surfactants have been used to improve the delivery of inhaled drugs in various additional strategies discussed herein.
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| 5. |
- Wang, Anqi, et al.
(författare)
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Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
- 2023
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:12, s. 2065-2074
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Tidskriftsartikel (refereegranskat)abstract
- The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
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| 6. |
- Werren, John H, et al.
(författare)
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Functional and evolutionary insights from the genomes of three parasitoid Nasonia species.
- 2010
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 327:5963, s. 343-8
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Tidskriftsartikel (refereegranskat)abstract
- We report here genome sequences and comparative analyses of three closely related parasitoid wasps: Nasonia vitripennis, N. giraulti, and N. longicornis. Parasitoids are important regulators of arthropod populations, including major agricultural pests and disease vectors, and Nasonia is an emerging genetic model, particularly for evolutionary and developmental genetics. Key findings include the identification of a functional DNA methylation tool kit; hymenopteran-specific genes including diverse venoms; lateral gene transfers among Pox viruses, Wolbachia, and Nasonia; and the rapid evolution of genes involved in nuclear-mitochondrial interactions that are implicated in speciation. Newly developed genome resources advance Nasonia for genetic research, accelerate mapping and cloning of quantitative trait loci, and will ultimately provide tools and knowledge for further increasing the utility of parasitoids as pest insect-control agents.
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| 7. |
- Basu, Swaraj, et al.
(författare)
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Accurate mapping of mitochondrial DNA deletions and duplications using deep sequencing
- 2020
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 16:12
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Tidskriftsartikel (refereegranskat)abstract
- Deletions and duplications in mitochondrial DNA (mtDNA) cause mitochondrial disease and accumulate in conditions such as cancer and age-related disorders, but validated high-throughput methodology that can readily detect and discriminate between these two types of events is lacking. Here we establish a computational method, MitoSAlt, for accurate identification, quantification and visualization of mtDNA deletions and duplications from genomic sequencing data. Our method was tested on simulated sequencing reads and human patient samples with single deletions and duplications to verify its accuracy. Application to mouse models of mtDNA maintenance disease demonstrated the ability to detect deletions and duplications even at low levels of heteroplasmy. Author summary Deletions in the mitochondrial genome cause a wide variety of rare disorders, but are also linked to more common conditions such as neurodegeneration, diabetes type 2, and the normal ageing process. There is also a growing awareness that mtDNA duplications, which are also relevant for human disease, may be more common than previously thought. Despite their clinical importance, our current knowledge about the abundance, characteristics and diversity of mtDNA deletions and duplications is fragmented, and based to large extent on a limited view provided by traditional low-throughput analyses. Here, we describe a bioinformatics method, MitoSAlt, that can accurately map and classify mtDNA deletions and duplications using high-throughput sequencing. Application of this methodology to mouse models of mitochondrial deficiencies revealed a large number of duplications, suggesting that these may previously have been underestimated.
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| 8. |
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| 9. |
- Eikelboom, Willem S., et al.
(författare)
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The reporting of neuropsychiatric symptoms in electronic health records of individuals with Alzheimer’s disease : a natural language processing study
- 2023
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Ingår i: Alzheimer's Research and Therapy. - 1758-9193. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Neuropsychiatric symptoms (NPS) are prevalent in the early clinical stages of Alzheimer’s disease (AD) according to proxy-based instruments. Little is known about which NPS clinicians report and whether their judgment aligns with proxy-based instruments. We used natural language processing (NLP) to classify NPS in electronic health records (EHRs) to estimate the reporting of NPS in symptomatic AD at the memory clinic according to clinicians. Next, we compared NPS as reported in EHRs and NPS reported by caregivers on the Neuropsychiatric Inventory (NPI). Methods: Two academic memory clinic cohorts were used: the Amsterdam UMC (n = 3001) and the Erasmus MC (n = 646). Patients included in these cohorts had MCI, AD dementia, or mixed AD/VaD dementia. Ten trained clinicians annotated 13 types of NPS in a randomly selected training set of n = 500 EHRs from the Amsterdam UMC cohort and in a test set of n = 250 EHRs from the Erasmus MC cohort. For each NPS, a generalized linear classifier was trained and internally and externally validated. Prevalence estimates of NPS were adjusted for the imperfect sensitivity and specificity of each classifier. Intra-individual comparison of the NPS classified in EHRs and NPS reported on the NPI were conducted in a subsample (59%). Results: Internal validation performance of the classifiers was excellent (AUC range: 0.81–0.91), but external validation performance decreased (AUC range: 0.51–0.93). NPS were prevalent in EHRs from the Amsterdam UMC, especially apathy (adjusted prevalence = 69.4%), anxiety (adjusted prevalence = 53.7%), aberrant motor behavior (adjusted prevalence = 47.5%), irritability (adjusted prevalence = 42.6%), and depression (adjusted prevalence = 38.5%). The ranking of NPS was similar for EHRs from the Erasmus MC, although not all classifiers obtained valid prevalence estimates due to low specificity. In both cohorts, there was minimal agreement between NPS classified in the EHRs and NPS reported on the NPI (all kappa coefficients < 0.28), with substantially more reports of NPS in EHRs than on NPI assessments. Conclusions: NLP classifiers performed well in detecting a wide range of NPS in EHRs of patients with symptomatic AD visiting the memory clinic and showed that clinicians frequently reported NPS in these EHRs. Clinicians generally reported more NPS in EHRs than caregivers reported on the NPI.
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| 10. |
- Fischer, Benjamin M. C., et al.
(författare)
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Mojito, Anyone? An Exploration of Low-Tech Plant Water Extraction Methods for Isotopic Analysis Using Locally-Sourced Materials
- 2019
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Ingår i: Frontiers in Earth Science. - : Frontiers Media SA. - 2296-6463. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- The stable isotope composition of water (delta O-18 and delta H-2) is an increasingly utilized tool to distinguish between different pools of water along the soil-plant-atmosphere continuum (SPAC) and thus provides information on how plants use water. Clear bottlenecks for the ubiquitous application of isotopic analysis across the SPAC are the relatively high-energy and specialized materials required to extract water from plant materials. Could simple and cost-effective do-it-yourself MacGyver methods be sufficient for extracting plant water for isotopic analysis? This study develops a suite of novel techniques for plant water extraction and compares them to a standard research-grade water extraction method. Our results show that low-tech methods using locally-sourced materials can indeed extract plant water consistently and comparably to what is done with other state-of-the-art methods. Further, our findings show that other factors play a larger role than water extraction methods in achieving the desired accuracy and precision of stable isotope composition: (1) appropriate transport, (2) fast sample processing and (3) efficient workflows. These results are methodologically promising for the rapid expansion of isotopic investigations, especially for citizen science and/or school projects or in remote areas, where improved SPAC understanding could help manage water resources to fulfill agricultural and other competing water needs.
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| 11. |
- Flores-Figueroa, Jose, et al.
(författare)
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Patterns of illness in travelers visiting Mexico and Central America : the GeoSentinel experience.
- 2011
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Ingår i: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. - : Oxford University Press. - 1537-6591. ; 53:6, s. 523-531
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Mexico and Central America are important travel destinations for North American and European travelers. There is limited information on regional differences in travel related morbidity. METHODS: We describe the morbidity among 4779 ill travelers returned from Mexico and Central America who were evaluated at GeoSentinel network clinics during December 1996 to February 2010. RESULTS: The most frequent presenting syndromes included acute and chronic diarrhea, dermatologic diseases, febrile systemic illness, and respiratory disease. A higher proportion of ill travelers from the United States had acute diarrhea, compared with their Canadian and European counterparts (odds ratio, 1.9; P < .0001). During the 2009 H1N1 influenza outbreak from March 2009 through February 2010, the proportionate morbidity (PM) associated with respiratory illnesses in ill travelers increased among those returned from Mexico, compared with prior years (196.0 cases per 1000 ill returned travelers vs 53.7 cases per 1000 ill returned travelers; P < .0001); the PM remained constant in the rest of Central America (57.3 cases per 1000 ill returned travelers). We identified 50 travelers returned from Mexico and Central America who developed influenza, including infection due to 2009 H1N1 strains and influenza-like illness. The overall risk of malaria was low; only 4 cases of malaria were acquired in Mexico (PM, 2.2 cases per 1000 ill returned travelers) in 13 years, compared with 18 from Honduras (PM, 79.6 cases per 1000 ill returned travelers) and 14 from Guatemala (PM, 34.4 cases per 1000 ill returned travelers) during the same period. Plasmodium vivax malaria was the most frequent malaria diagnosis. CONCLUSIONS: Travel medicine practitioners advising and treating travelers visiting these regions should dedicate special attention to vaccine-preventable illnesses and should consider the uncommon occurrence of acute hepatitis A, leptospirosis, neurocysticercosis, acute Chagas disease, onchocerciasis, mucocutaneous leishmaniasis, neurocysticercosis, HIV, malaria, and brucellosis.
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| 12. |
- Geng, Q., et al.
(författare)
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Temperature limit values for touching cold surfaces with the fingertip
- 2006
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Ingår i: Annals of Occupational Hygiene. - : Oxford University Press (OUP). - 1475-3162 .- 0003-4878. ; 50:8, s. 851-862
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: At the request of the European Commission and in the framework of the European Machinery Directive, research was performed in five different laboratories to develop specifications for surface temperature limit values for the short-term accidental touching of the fingertip with cold surfaces. Methods: Data were collected in four laboratories with a total of 20 males and 20 females performing a grand total of 1655 exposures. Each touched polished blocks of aluminium, stainless steel, nylon-6 and wood using the distal phalanx of the index finger with a contact force of 1.0, 2.9 and 9.8 N, at surface temperatures from +2 to -40 degrees C for a maximum duration of 120 s. Conditions were selected in order to elicit varying rates of skin cooling upon contact. Contact temperature (T-C) of the fingertip was measured over time using a T-type thermocouple. Results: A database obtained from the experiments was collated and analysed to characterize fingertip contact cooling across a range of materials and surface temperatures. The database was subsequently used to develop a predictive model to describe the contact duration required for skin contact temperature to reach the physiological criteria of onset of pain (15 degrees C), onset of numbness (7 degrees C) and onset of frostbite risk (0 degrees C). Conclusions: The data reflect the strong link between the risk of skin damage and the thermal properties of the material touched. For aluminium and steel, skin temperatures of 0 degrees C occurs within 2-6 s at surface temperatures of -15 degrees C. For non-metallic surfaces, onset of numbness occurs within 15-65 s of contact at -35 degrees C and onset of cold pain occurs within 5 s of contact at -20 degrees C. The predictive model subsequently developed was a non-linear exponential expression also reflecting the effects of material thermal properties and initial temperature. This model provides information for the protection of workers against the risk of cold injury by establishing the temperature limits of cold touchable surfaces for a broad range of materials, and it is now proposed as guidance values in a new international standard.
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| 13. |
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| 14. |
- Kelly, John J., et al.
(författare)
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Snapshots of actin and tubulin folding inside the TRiC chaperonin
- 2022
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Ingår i: Nature Structural and Molecular Biology. - : Springer Science and Business Media LLC. - 1545-9993 .- 1545-9985. ; 29:5, s. 420-429
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Tidskriftsartikel (refereegranskat)abstract
- The integrity of a cell’s proteome depends on correct folding of polypeptides by chaperonins. The chaperonin TCP-1 ring complex (TRiC) acts as obligate folder for >10% of cytosolic proteins, including he cytoskeletal proteins actin and tubulin. Although its architecture and how it recognizes folding substrates are emerging from structural studies, the subsequent fate of substrates inside the TRiC chamber is not defined. We trapped endogenous human TRiC with substrates (actin, tubulin) and cochaperone (PhLP2A) at different folding stages, for structure determination by cryo-EM. The already-folded regions of client proteins are anchored at the chamber wall, positioning unstructured regions toward the central space to achieve their native fold. Substrates engage with different sections of the chamber during the folding cycle, coupled to TRiC open-and-close transitions. Further, the cochaperone PhLP2A modulates folding, acting as a molecular strut between substrate and TRiC chamber. Our structural snapshots piece together an emerging model of client protein folding within TRiC.
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| 15. |
- Lichtenberg, Elinor M., et al.
(författare)
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A global synthesis of the effects of diversified farming systems on arthropod diversity within fields and across agricultural landscapes
- 2017
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Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 23:11, s. 4946-4957
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Tidskriftsartikel (refereegranskat)abstract
- Agricultural intensification is a leading cause of global biodiversity loss, which can reduce the provisioning of ecosystem services in managed ecosystems. Organic farming and plant diversification are farm management schemes that may mitigate potential ecological harm by increasing species richness and boosting related ecosystem services to agroecosystems. What remains unclear is the extent to which farm management schemes affect biodiversity components other than species richness, and whether impacts differ across spatial scales and landscape contexts. Using a global metadataset, we quantified the effects of organic farming and plant diversification on abundance, local diversity (communities within fields), and regional diversity (communities across fields) of arthropod pollinators, predators, herbivores, and detritivores. Both organic farming and higher in-field plant diversity enhanced arthropod abundance, particularly for rare taxa. This resulted in increased richness but decreased evenness. While these responses were stronger at local relative to regional scales, richness and abundance increased at both scales, and richness on farms embedded in complex relative to simple landscapes. Overall, both organic farming and in-field plant diversification exerted the strongest effects on pollinators and predators, suggesting these management schemes can facilitate ecosystem service providers without augmenting herbivore (pest) populations. Our results suggest that organic farming and plant diversification promote diverse arthropod metacommunities that may provide temporal and spatial stability of ecosystem service provisioning. Conserving diverse plant and arthropod communities in farming systems therefore requires sustainable practices that operate both within fields and across landscapes.
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| 16. |
- Liu, Ke, et al.
(författare)
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X Chromosome Dose and Sex Bias in Autoimmune Diseases : Increased 47,XXX in Systemic Lupus Erythematosus and Sjögren's Syndrome
- 2016
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Ingår i: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 68:5, s. 1290-1300
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:More than 80% of autoimmune disease is female dominant, but the mechanism for this female bias is poorly understood. We suspected an X chromosome dose effect and hypothesized that trisomy X (47,XXX, 1 in ∼1,000 live female births) would be increased in female predominant diseases (e.g. systemic lupus erythematosus [SLE], primary Sjögren's syndrome [SS], primary biliary cirrhosis [PBC] and rheumatoid arthritis [RA]) compared to diseases without female predominance (sarcoidosis) and controls.METHODS:We identified 47,XXX subjects using aggregate data from single nucleotide polymorphism (SNP) arrays and confirmed, when possible, by fluorescent in situ hybridization (FISH) or quantitative polymerase chain reaction (q-PCR).RESULTS:We found 47,XXX in seven of 2,826 SLE and three of 1,033 SS female patients, but only in two of the 7,074 female controls (p=0.003, OR=8.78, 95% CI: 1.67-86.79 and p=0.02, OR=10.29, 95% CI: 1.18-123.47; respectively). One 47,XXX subject was present for ∼404 SLE women and ∼344 SS women. 47,XXX was present in excess among SLE and SS subjects.CONCLUSION:The estimated prevalence of SLE and SS in women with 47,XXX was respectively ∼2.5 and ∼2.9 times higher than in 46,XX women and ∼25 and ∼41 times higher than in 46,XY men. No statistically significant increase of 47,XXX was observed in other female-biased diseases (PBC or RA), supporting the idea of multiple pathways to sex bias in autoimmunity. This article is protected by copyright. All rights reserved.
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| 17. |
- Lundberg, Jon O., et al.
(författare)
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Nitrate and nitrite in biology, nutrition and therapeutics
- 2009
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Ingår i: Nature Chemical Biology. - : Springer Science and Business Media LLC. - 1552-4450 .- 1552-4469. ; 5:12, s. 865-869
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Tidskriftsartikel (refereegranskat)abstract
- Inorganic nitrate and nitrite from endogenous or dietary sources are metabolized in vivo to nitric oxide (NO) and other bioactive nitrogen oxides. The nitrate-nitrite-NO pathway is emerging as an important mediator of blood flow regulation, cell signaling, energetics and tissue responses to hypoxia. The latest advances in our understanding of the biochemistry, physiology and therapeutics of nitrate, nitrite and NO were discussed during a recent 2-day meeting at the Nobel Forum, Karolinska Institutet in Stockholm.
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| 18. |
- Matic, S., et al.
(författare)
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Mice lacking the mitochondrial exonuclease MGME1 accumulate mtDNA deletions without developing progeria
- 2018
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Replication of mammalian mitochondrial DNA (mtDNA) is an essential process that requires high fidelity and control at multiple levels to ensure proper mitochondrial function. Mutations in the mitochondrial genome maintenance exonuclease 1 (MGME1) gene were recently reported in mitochondrial disease patients. Here, to study disease pathophysiology, we generated Mgme1 knockout mice and report that homozygous knockouts develop depletion and multiple deletions of mtDNA. The mtDNA replication stalling phenotypes vary dramatically in different tissues of Mgme1 knockout mice. Mice with MGME1 deficiency accumulate a long linear subgenomic mtDNA species, similar to the one found in mtDNA mutator mice, but do not develop progeria. This finding resolves a long-standing debate by showing that point mutations of mtDNA are the main cause of progeria in mtDNA mutator mice. We also propose a role for MGME1 in the regulation of replication and transcription termination at the end of the control region of mtDNA.
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| 19. |
- Richards, Stephen, et al.
(författare)
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Genome Sequence of the Pea Aphid Acyrthosiphon pisum
- 2010
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Ingår i: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 8:2, s. e1000313-
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Tidskriftsartikel (refereegranskat)abstract
- Aphids are important agricultural pests and also biological models for studies of insect-plant interactions, symbiosis, virus vectoring, and the developmental causes of extreme phenotypic plasticity. Here we present the 464 Mb draft genome assembly of the pea aphid Acyrthosiphon pisum. This first published whole genome sequence of a basal hemimetabolous insect provides an outgroup to the multiple published genomes of holometabolous insects. Pea aphids are host-plant specialists, they can reproduce both sexually and asexually, and they have coevolved with an obligate bacterial symbiont. Here we highlight findings from whole genome analysis that may be related to these unusual biological features. These findings include discovery of extensive gene duplication in more than 2000 gene families as well as loss of evolutionarily conserved genes. Gene family expansions relative to other published genomes include genes involved in chromatin modification, miRNA synthesis, and sugar transport. Gene losses include genes central to the IMD immune pathway, selenoprotein utilization, purine salvage, and the entire urea cycle. The pea aphid genome reveals that only a limited number of genes have been acquired from bacteria; thus the reduced gene count of Buchnera does not reflect gene transfer to the host genome. The inventory of metabolic genes in the pea aphid genome suggests that there is extensive metabolite exchange between the aphid and Buchnera, including sharing of amino acid biosynthesis between the aphid and Buchnera. The pea aphid genome provides a foundation for post-genomic studies of fundamental biological questions and applied agricultural problems.
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| 20. |
- Richards, Stephen, et al.
(författare)
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The genome of the model beetle and pest Tribolium castaneum.
- 2008
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Ingår i: Nature. - 1476-4687. ; 452:7190, s. 949-55
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Tidskriftsartikel (refereegranskat)abstract
- Tribolium castaneum is a representative of earth’s most numerous eukaryotic order, a powerful model organism for the study of generalized insect development, and also an important pest of stored agricultural products. We describe its genome sequence here. This omnivorous beetle has evolved an ability to interact with a diverse chemical environment as evidenced by large expansions in odorant and gustatory receptors, as well as p450 and other detoxification enzymes. Developmental patterns in Tribolium are more representative of other arthropods than those found in Drosophila, a fact represented in gene content and function. For one, Tribolium has retained more ancestral genes involved in cell-cell communication than Drosophila, and some are expressed in the growth zone crucial for axial elongation in short germ development. Systemic RNAi in T. castaneum appears to use mechanisms distinct from those found in C. elegans, but nevertheless offers similar power for the elucidation of gene function and identification of targets for selective insect control.
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| 21. |
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| 22. |
- Sartelli, Massimo, et al.
(författare)
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Ten golden rules for optimal antibiotic use in hospital settings: the WARNING call to action
- 2023
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Ingår i: WORLD JOURNAL OF EMERGENCY SURGERY. - 1749-7922. ; 18:1
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Forskningsöversikt (refereegranskat)abstract
- Antibiotics are recognized widely for their benefits when used appropriately. However, they are often used inappropriately despite the importance of responsible use within good clinical practice. Effective antibiotic treatment is an essential component of universal healthcare, and it is a global responsibility to ensure appropriate use. Currently, pharmaceutical companies have little incentive to develop new antibiotics due to scientific, regulatory, and financial barriers, further emphasizing the importance of appropriate antibiotic use. To address this issue, the Global Alliance for Infections in Surgery established an international multidisciplinary task force of 295 experts from 115 countries with different backgrounds. The task force developed a position statement called WARNING (Worldwide Antimicrobial Resistance National/International Network Group) aimed at raising awareness of antimicrobial resistance and improving antibiotic prescribing practices worldwide. The statement outlined is 10 axioms, or "golden rules," for the appropriate use of antibiotics that all healthcare workers should consistently adhere in clinical practice.
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| 23. |
- Sheehan, Katie J., et al.
(författare)
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Conceptual Framework for an Episode of Rehabilitative Care After Surgical Repair of Hip Fracture
- 2019
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Ingår i: Physical Therapy. - : Oxford University Press. - 0031-9023 .- 1538-6724. ; 99:3, s. 276-285
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Tidskriftsartikel (refereegranskat)abstract
- Researchers face a challenge when evaluating the effectiveness of rehabilitation after a surgical procedure for hip fracture. Reported outcomes of rehabilitation will vary depending on the end point of the episode of care. Evaluation at an inappropriate end point might suggest a lack of effectiveness leading to the underuse of rehabilitation that could improve outcomes. The purpose of this article is to describe a conceptual framework for a continuum-care episode of rehabilitation after a surgical procedure for hip fracture. Definitions are proposed for the index event, end point, and service scope of the episode. Challenges in defining the episode of care and operationalizing the episode, and next steps for researchers are discussed. The episode described is intended to apply to all patients eligible for entry to rehabilitation after hip fracture and includes most functional recovery end points. This framework will provide a guide for rehabilitation researchers when designing and interpreting evaluations of the effectiveness of rehabilitation after hip fracture. Evaluation of all potential care episodes facilitates transparency in reporting of outcomes, enabling researchers to determine the true effectiveness of rehabilitation after a surgical procedure for hip fracture.
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| 24. |
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| 25. |
- Van Oostdam, Jay C, et al.
(författare)
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Circumpolar maternal blood contaminant survey, 1994-1997 organochlorine compounds
- 2004
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Ingår i: Science of the Total Environment. - Amsterdam : Elsevier. - 0048-9697 .- 1879-1026. ; 330:1-3, s. 55-70
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Tidskriftsartikel (refereegranskat)abstract
- During the past 20 years a number of studies have found neurological and immunological effects in the developing fetus and infants exposed to background or only slightly elevated levels of persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs). To address concerns arising from possible increased human exposure in the Arctic and possible effects of POPs, all circumpolar countries agreed in 1994 to monitoring of specific human tissues for contaminants in the Arctic under the Arctic Monitoring and Assessment Program (AMAP). Mothers in eight circumpolar countries contributed blood samples that were analysed at a single laboratory for 14 PCB congeners (IUPAC No. 28, 52, 99, 105, 118, 128, 138, 153, 156, 170, 180, 183, 187) and 13 organochlorine pesticides (aldrin, beta-hexachlorocyclohexane (beta-HCH), dichlordiphenyltrichloroethane (p,p'-DDT), diphenyldichloroethylene (p,p'DDE), dieldrin, heptachlorepoxide, hexachlorobenzene (HCB), mirex, and the chlordane derivatives alpha-chlordane, gamma-chlordane, cis-nonachlor, oxychlordane and trans-nonachlor). Inuit mothers from Greenland and Canada have significantly higher levels of oxychlordane, transnonachlor and mirex than mothers from Norway, Sweden, Iceland and Russia. Inuit mothers from Greenland also have significantly higher levels of these contaminants than Inuit mothers from Canada and Alaska. These differences among Inuit groups may represent regional dietary preferences or different contaminant deposition patterns across the Arctic. Levels of PCBs are also elevated among some arctic populations due to their consumption of marine mammals and are in the range where subtle effects on leaming and the immune system have been reported. The Russian mothers who consume mainly food imported from southern Russia have elevated levels of DDT, DDE, beta-HCH and a higher proportion of lower chlorinated PCB congeners. This study has allowed an assessment of the variation of contaminants such as PCBs and various organochlorine pesticides (DDT, chlordane, etc.) in human populations around the circumpolar north.
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| 26. |
- Wang, Zhaoming, et al.
(författare)
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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| 27. |
- Weinstein, John N., et al.
(författare)
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The cancer genome atlas pan-cancer analysis project
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:10, s. 1113-1120
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Forskningsöversikt (refereegranskat)abstract
- The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
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