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- Baker-Austin, Craig, et al.
(författare)
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Extreme arsenic resistance by the acidophilic archaeon 'Ferroplasma acidarmanus' Fer1.
- 2007
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Ingår i: Extremophiles. - : Springer Science and Business Media LLC. - 1431-0651 .- 1433-4909. ; 11:3, s. 425-34
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Tidskriftsartikel (refereegranskat)abstract
- 'Ferroplasma acidarmanus' Fer1 is an arsenic-hypertolerant acidophilic archaeon isolated from the Iron Mountain mine, California; a site characterized by heavy metals contamination. The presence of up to 10 g arsenate per litre [As(V); 133 mM] did not significantly reduce growth yields, whereas between 5 and 10 g arsenite per litre [As(III); 67-133 mM] significantly reduced the yield. Previous bioinformatic analysis indicates that 'F. acidarmanus' Fer1 has only two predicted genes involved in arsenic resistance and lacks a recognizable gene for an arsenate reductase. Biochemical analysis suggests that 'F. acidarmanus' Fer1 does not reduce arsenate indicating that 'F. acidarmanus' Fer1 has an alternative resistance mechanism to arsenate other than reduction to arsenite and efflux. Primer extension analysis of the putative ars transcriptional regulator (arsR) and efflux pump (arsB) demonstrated that these genes are co-transcribed, and expressed in response to arsenite, but not arsenate. Two-dimensional polyacrylamide gel electrophoresis analysis of 'F. acidarmanus' Fer1 cells exposed to arsenite revealed enhanced expression of proteins associated with protein refolding, including the thermosome Group II HSP60 family chaperonin and HSP70 DnaK type heat shock proteins. This report represents the first molecular and proteomic study of arsenic resistance in an acidophilic archaeon.
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| 5. |
- 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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| 6. |
- Kumar, Nallani Vijay, et al.
(författare)
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Arsenic Directly Binds to and Activates the Yeast AP-1-Like Transcription Factor Yap8.
- 2016
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Ingår i: Molecular and cellular biology. - 1098-5549. ; 36:6, s. 913-22
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Tidskriftsartikel (refereegranskat)abstract
- The AP-1-like transcription factor Yap8 is critical for arsenic tolerance in the yeast Saccharomyces cerevisiae. However, the mechanism by which Yap8 senses the presence of arsenic and activates transcription of detoxification genes is unknown. Here we demonstrate that Yap8 directly binds to trivalent arsenite [As(III)] in vitro and in vivo and that approximately one As(III) molecule is bound per molecule of Yap8. As(III) is coordinated by three sulfur atoms in purified Yap8, and our genetic and biochemical data identify the cysteine residues that form the binding site as Cys132, Cys137, and Cys274. As(III) binding by Yap8 does not require an additional yeast protein, and Yap8 is regulated neither at the level of localization nor at the level of DNA binding. Instead, our data are consistent with a model in which a DNA-bound form of Yap8 acts directly as an As(III) sensor. Binding of As(III) to Yap8 triggers a conformational change that in turn brings about a transcriptional response. Thus, As(III) binding to Yap8 acts as a molecular switch that converts inactive Yap8 into an active transcriptional regulator. This is the first report to demonstrate how a eukaryotic protein couples arsenic sensing to transcriptional activation.
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| 9. |
- Lundström, Mats, et al.
(författare)
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Visual outcome of cataract surgery; Study from the European Registry of Quality Outcomes for Cataract and Refractive Surgery.
- 2013
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Ingår i: Journal of Cataract and Refractive Surgery. - : Ovid Technologies (Wolters Kluwer Health). - 1873-4502 .- 0886-3350. ; 39:5, s. 673-679
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To analyze the visual outcome after cataract surgery. SETTING: Cataract surgery clinics in 15 European countries. DESIGN: Database study. METHODS: Data were drawn from case series of cataract extractions reported to the European Registry of Quality Outcomes for Cataract and Refractive Surgery database. These data were entered into the database via the Web by surgeons or by transfer from existing national registries or electronic medical record systems. The database contains individual anonymous data on preoperative, intraoperative, and postoperative measurements. RESULTS: Data on 368 256 cataract extractions were available for analysis. The best visual outcome was achieved in age groups 40 to 74 years, and men showed a higher percentage of excellent vision (1.0 [20/20] or better) than women. A corrected distance visual acuity (CDVA) of 0.5 (20/40) or better and of 1.0 (20/20) or better was achieved in 94.3% and 61.3% of cases, respectively. Ocular comorbidity and postoperative complications were the strongest influences on the visual outcome; however, surgical complications and ocular changes requiring complex surgery also had a negative influence. Deterioration of visual acuity after the surgery (n= 6112 [1.7% of all cases]) was most common in patients with a good preoperative visual acuity. CONCLUSIONS: The visual outcomes of cataract surgery were excellent, with 61.3% of patients achieving a corrected distance visual acuity of 1.0 (20/20) or better. Age and sex influenced the visual outcomes, but the greatest influences were short-term postoperative complications, ocular comorbidity, surgical complications, and complex surgery. A weakness of the study could be that some of the data is self-reported to the registry. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.
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| 11. |
- McLaughlin, John R, et al.
(författare)
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Reproductive risk factors for ovarian cancer in carriers of BRCA1 or BRCA2 mutations: a case-control study
- 2007
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Ingår i: The Lancet Oncology. - 1474-5488. ; 8:1, s. 26-34
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Several of the known risk factors for ovarian cancer are thought to act through their effects on ovulation and the menstrual cycle, such as parity, breastfeeding, and use of oral contraceptives. We aimed to assess the effect of these three risk factors, and of tubal ligation, on the risk of ovarian cancer in women who carry a mutation in the BRCA1 or BRCA2 genes. METHODS: We did a matched case-control study in women who were found to carry a pathogenetic mutation in BRCA1 or BRCA2. Participants were derived from a population-based study of ovarian cancer in Ontario, Canada, and from an international registry of mutation carriers based in Toronto, ON, Canada. All participants completed a written questionnaire that detailed their reproductive history. Women with invasive ovarian cancer and controls were matched on year of birth, country of residence, mutation (BRCA1 or BRCA2), and history of breast cancer. The odds ratios and 95% CI for ovarian cancer were estimated with respect to use of oral contraceptives, parity, breastfeeding, and tubal ligation. FINDINGS: Questionnaires were completed by 799 women with a history of invasive ovarian cancer (670 with BRCA1 mutations, 128 with BRCA2 mutations, and one with a mutation in both genes), and controls were 2424 women without ovarian cancer (2043 with BRCA1 mutations, 380 with BRCA2 mutations, and one with a mutation in both genes). Use of oral contraceptives reduced the risk of ovarian cancer in carriers of BRCA1 mutations (odds ratio 0.56 [95% CI 0.45-0.71]; p<0.0001) and carriers of BRCA2 mutations (0.39 [0.23-0.66]; p=0.0004). Parity was associated with a reduced risk for carriers of BRCA1 mutations (0.67 [0.46-0.96]; p=0.03), but with an increased risk for those with BRCA2 mutations (2.74 [1.18-6.41]; p=0.02). Breastfeeding was associated with a reduced risk for carriers of BRCA1 mutations (0.74 [0.56-0.97]; p=0.03). An effect of similar magnitude was seen for carriers of BRCA2 mutations (0.72 [0.41-1.29]; p=0.27), but this was not statistically significant. The association with tubal ligation was not significant for carriers of BRCA1 mutations (0.80 [0.59-1.08]; p=0.15), or for carriers of BRCA2 mutations (0.63 [0.34-1.15]; p=0.13). INTERPRETATION: Oral contraceptives could be used as a means to prevent ovarian cancer in carriers of BRCA1 and BRCA2 mutations. The possible adverse effect of parity on ovarian-cancer risk in women with a BRCA2 mutation needs further study.
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| 12. |
- Pfander, Claudia, et al.
(författare)
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A scalable pipeline for highly effective genetic modification of a malaria parasite
- 2011
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Ingår i: Nature Methods. - : Springer Science and Business Media LLC. - 1548-7091 .- 1548-7105. ; 8:12, s. 1078-1082
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Tidskriftsartikel (refereegranskat)abstract
- In malaria parasites, the systematic experimental validation of drug and vaccine targets by reverse genetics is constrained by the inefficiency of homologous recombination and by the difficulty of manipulating adenine and thymine (A+T)-rich DNA of most Plasmodium species in Escherichia coli. We overcame these roadblocks by creating a high-integrity library of Plasmodium berghei genomic DNA (>77% A+T content) in a bacteriophage N15-based vector that can be modified efficiently using the lambda Red method of recombineering. We built a pipeline for generating P. berghei genetic modification vectors at genome scale in serial liquid cultures on 96-well plates. Vectors have long homology arms, which increase recombination frequency up to tenfold over conventional designs. The feasibility of efficient genetic modification at scale will stimulate collaborative, genome-wide knockout and tagging programs for P. berghei.
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| 13. |
- Rosen, Barry P, et al.
(författare)
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Arsenic transport in prokaryotes and eukaryotic microbes.
- 2010
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Ingår i: MIPs and Their Roles in the Exchange of Metalloids, Jahn, Thomas P.; Bienert, Gerd P. (Eds.). - : Landes Bioscience and Springer. - 9781441963147 ; , s. 47-55
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Aquaporins (AQPs) and aquaglyceroporins facilitate transport of a broad spectrum of substrates such as water, glycerol and other small uncharged solutes. More recently, AQPs ave also been shown to facilitate diffusion of metalloids such as arsenic (As) and antimony (Sb). At neutral pH, the trivalent forms of these metalloids are structurally similar to glycerol and hence they can enter cells through AQPs. As- and Sb-containing compounds are toxic to cells, yet both metalloids are used as chemotherapeutic agents for treating acute promyelocytic leukemia and diseases caused by protozoan parasites. In this chapter, we will review the role of AQPs and other proteins in metalloid transport in prokaryotes and eukaryotic microbes.
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| 14. |
- Rosén, Johanna S, et al.
(författare)
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The impact of impairment on kinematic and kinetic variables in Va'a paddling : Towards a sport-specific evidence-based classification system for Para Va'a.
- 2019
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Ingår i: Journal of Sports Sciences. - : Taylor & Francis. - 0264-0414 .- 1466-447X. ; 37:17, s. 1942-1950
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Tidskriftsartikel (refereegranskat)abstract
- Para Va'a is a new Paralympic sport in which athletes with trunk and/or leg impairment compete over 200 m. The purpose of this study was to examine the impact of impairment on kinematic and kinetic variables during Va'a ergometer paddling. Ten able-bodied and 44 Para Va'a athletes with impairments affecting: trunk and legs (TL), legs bilaterally (BL) or leg unilaterally (UL) participated. Differences in stroke frequency, mean paddling force, and joint angles and correlation of the joint angles with paddling force were examined. Able-bodied demonstrated significantly greater paddling force as well as knee and ankle flexion ranges of movement (ROM) on the top hand paddling side compared to TL, BL and UL. Able-bodied, BL and UL demonstrated greater paddling force and trunk flexion compared to TL, and UL demonstrated larger bottom hand paddling side knee and ankle flexion ROM compared to BL. Significant positive correlations were observed for both male and female athletes between paddling force and all trunk flexion angles and ROM in the trunk and pelvis rotation and bottom hand paddling side hip, knee and ankle flexion. The results of this study are important for creating an evidence-based classification system for Para Va'a.
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| 15. |
- Wang, Li-San, et al.
(författare)
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Rarity of the Alzheimer Disease-Protective APP A673T Variant in the United States.
- 2015
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Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 72:2
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Tidskriftsartikel (refereegranskat)abstract
- Recently, a rare variant in the amyloid precursor protein gene (APP) was described in a population from Iceland. This variant, in which alanine is replaced by threonine at position 673 (A673T), appears to protect against late-onset Alzheimer disease (AD). We evaluated the frequency of this variant in AD cases and cognitively normal controls to determine whether this variant will significantly contribute to risk assessment in individuals in the United States.
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| 16. |
- Yiangou, Loukia, et al.
(författare)
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A Stem Cell Strategy Identifies Glycophorin C as a Major Erythrocyte Receptor for the Rodent Malaria Parasite Plasmodium berghei
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 11:6
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Tidskriftsartikel (refereegranskat)abstract
- The clinical complications of malaria are caused by the parasite expansion in the blood. Invasion of erythrocytes is a complex process that depends on multiple receptor-ligand interactions. Identification of host receptors is paramount for fighting the disease as it could reveal new intervention targets, but the enucleated nature of erythrocytes makes genetic approaches impossible and many receptors remain unknown. Host-parasite interactions evolve rapidly and are therefore likely to be species-specific. As a results, understanding of invasion receptors outside the major human pathogen Plasmodium falciparum is very limited. Here we use mouse embryonic stem cells (mESCs) that can be genetically engineered and differentiated into erythrocytes to identify receptors for the rodent malaria parasite Plasmodium berghei. Two proteins previously implicated in human malaria infection: glycophorin C (GYPC) and Band-3 (Slc4a1) were deleted in mESCs to generate stable cell lines, which were differentiated towards erythropoiesis. In vitro infection assays revealed that while deletion of Band-3 has no effect, absence of GYPC results in a dramatic decrease in invasion, demonstrating the crucial role of this protein for P. berghei infection. This stem cell approach offers the possibility of targeting genes that may be essential and therefore difficult to disrupt in whole organisms and has the potential to be applied to a variety of parasites in diverse host cell types.
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