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- Desmarais, John J., et al.
(författare)
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DABs are inorganic carbon pumps found throughout prokaryotic phyla
- 2019
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Ingår i: Nature Microbiology. - : Springer Science and Business Media LLC. - 2058-5276. ; 4:12, s. 2204-2215
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Tidskriftsartikel (refereegranskat)abstract
- Bacterial autotrophs often rely on CO2 concentrating mechanisms (CCMs) to assimilate carbon. Although many CCM proteins have been identified, a systematic screen of the components of CCMs is lacking. Here, we performed a genome-wide barcoded transposon screen to identify essential and CCM-related genes in the γ-proteobacterium Halothiobacillus neapolitanus. Screening revealed that the CCM comprises at least 17 and probably no more than 25 genes, most of which are encoded in 3 operons. Two of these operons (DAB1 and DAB2) contain a two-gene locus that encodes a domain of unknown function (Pfam: PF10070) and a putative cation transporter (Pfam: PF00361). Physiological and biochemical assays demonstrated that these proteins—which we name DabA and DabB, for DABs accumulate bicarbonate—assemble into a heterodimeric complex, which contains a putative β-carbonic anhydrase-like active site and functions as an energy-coupled inorganic carbon (Ci) pump. Interestingly, DAB operons are found in a diverse range of bacteria and archaea. We demonstrate that functional DABs are present in the human pathogens Bacillus anthracis and Vibrio cholerae. On the basis of these results, we propose that DABs constitute a class of energized Ci pumps and play a critical role in the metabolism of Ci throughout prokaryotic phyla.
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| 4. |
- Martinez-Martin, P., et al.
(författare)
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First comprehensive tool for screening pain in Parkinson's disease : the King's Parkinson's Disease Pain Questionnaire
- 2018
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Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 25:10, s. 1255-1261
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Pain is highly prevalent in Parkinson's disease (PD), impacting patients’ ability, mood and quality of life. Detecting the presence of pain in its multiple modalities is necessary for adequate personalized management of PD. A 14-item, PD-specific, patient-based questionnaire (the King's Parkinson's Disease Pain Questionnaire, KPPQ) was designed corresponding to the rater-based KPP Scale (KPPS). The present multicentre study was aimed at testing the validity of this screening tool. Methods: First, a comparison between the KPPQ scores of patients and matched controls was performed. Next, convergent validity, reproducibility (test–retest) and diagnostic performance of the questionnaire were analysed. Results: Data from 300 patients and 150 controls are reported. PD patients declared significantly more pain symptoms than controls (3.96 ± 2.56 vs. 2.17 ± 1.39; P < 0.0001). The KPPQ convergent validity was high with KPPS total score (rS = 0.80) but weak or moderate with other pain assessments. Test–retest reliability was satisfactory with kappa values ≥0.65 except for item 5, Dyskinetic pains (κ = 0.44), and the intraclass correlation coefficient (ICC) for the KPPQ total score was 0.98. After the scores of the KPPS were adapted for screening (0, no symptom; ≥1, symptom present), a good agreement was found between the KPPQ and the KPPS (ICC = 0.88). A strong correlation (rS = 0.80) between the two instruments was found. The diagnostic parameters of the KPPQ were very satisfactory as a whole, with a global accuracy of 78.3%–98.3%. Conclusions: These results suggest that the KPPQ is a useful, reliable and valid screening instrument for pain in PD to advance patient-related outcomes.
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- Wetmore, Daniel, et al.
(författare)
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Bidirectional plasticity of purkinje cells matches temporal features of learning
- 2014
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Ingår i: The Journal of Neuroscience. - 1529-2401. ; 34:5, s. 1731-1737
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Tidskriftsartikel (refereegranskat)abstract
- Many forms of learning require temporally ordered stimuli. In Pavlovian eyeblink conditioning, a conditioned stimulus (CS) must precede the unconditioned stimulus (US) by at least about 100 ms for learning to occur. Conditioned responses are learned and generated by the cerebellum. Recordings from the cerebellar cortex during conditioning have revealed CS-triggered pauses in the firing of Purkinje cells that likely drive the conditioned blinks. The predominant view of the learning mechanism in conditioning is that long-term depression (LTD) at parallel fiber (PF)-Purkinje cell synapses underlies the Purkinje cell pauses. This raises a serious conceptual challenge because LTD is most effectively induced at short CS-US intervals, which do not support acquisition of eyeblinks. To resolve this discrepancy, we recorded Purkinje cells during conditioning with short or long CS-US intervals. Decerebrated ferrets trained with CS-US intervals ≥150 ms reliably developed Purkinje cell pauses, but training with an interval of 50 ms unexpectedly induced increases in CS-evoked spiking. This bidirectional modulation of Purkinje cell activity offers a basis for the requirement of a minimum CS-US interval for conditioning, but we argue that it cannot be fully explained by LTD, even when previous in vitro studies of stimulus-timing-dependent LTD are taken into account.
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| 6. |
- Wetmore, Stephen J., et al.
(författare)
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Challenges and Opportunities in Managing the Dizzy Older Adult
- 2011
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Ingår i: Otolaryngology: Head and Neck Surgery. - : Wiley. - 0194-5998 .- 1097-6817. ; 144:5, s. 651-656
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Konferensbidrag (refereegranskat)abstract
- Balance disorders are common in elderly people, not only resulting in distressing sensations but also leading to reduced activity levels and quality of life. It has been estimated that 30% of elderly patients experience a balance disorder. Managing these disorders is a substantial challenge for patients and their caregivers and physicians. Moreover, abnormalities in balance are associated with falls, a major cause of morbidity and mortality for elderly people. Management is complicated by the inherent difficulties in assessing the generic complaint of dizziness, as well as the likelihood of multiple, often nonvestibular causes. The authors of this mini-seminar review both vestibular and nonvestibular causes of balance disorders in elderly people, emphasizing practical therapeutic maneuvers that can be used.
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