Hebert, P D N*
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The Photosystem II reaction center is vulnerable to photoinhibition. The D1 and D2 proteins, lying at the core of the photosystem, are susceptible to oxidative modification by reactive oxygen species that are formed by the photosystem during illumination. Using spin probes and EPR spectroscopy, we have determined that both O2•- and HO• are involved in the photoinhibitory process. Using tandem mass spectroscopy, we have identified a number of oxidatively modified D1 and D2 residues. Our analysis indicates that these oxidative modifications are associated with formation of HO• at both the Mn4O5Ca cluster and the nonheme iron. Additionally, O2•- appears to be formed by the reduction of O2 at either PheoD1 or QA Early oxidation of D1:332H, which is coordinated with the Mn1 of the Mn4O5Ca cluster, appears to initiate a cascade of oxidative events that lead to the oxidative modification of numerous residues in the C termini of the D1 and D2 proteins on the donor side of the photosystem. Oxidation of D2:244Y, which is a bicarbonate ligand for the nonheme iron, induces the propagation of oxidative reactions in residues of the D-de loop of the D2 protein on the electron acceptor side of the photosystem. Finally, D1:130E and D2:246M are oxidatively modified by O2•- formed by the reduction of O2 either by PheoD1•- or QA•- The identification of specific amino acid residues oxidized by reactive oxygen species provides insights into the mechanism of damage to the D1 and D2 proteins under light stress.
- MeSH
- aminokyseliny chemie metabolismus MeSH
- antioxidancia metabolismus MeSH
- chloridy metabolismus MeSH
- elektronová paramagnetická rezonance MeSH
- fotosystém II (proteinový komplex) chemie metabolismus MeSH
- hmotnostní spektrometrie MeSH
- hydroxylový radikál metabolismus MeSH
- kyslík metabolismus MeSH
- molekulární konformace MeSH
- molekulární modely MeSH
- oxidace-redukce * MeSH
- reaktivní formy kyslíku metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
DNA sequences offer powerful tools for describing the members and interactions of natural communities. In this study, we establish the to-date most comprehensive library of DNA barcodes for a terrestrial site, including all known macroscopic animals and vascular plants of an intensively studied area of the High Arctic, the Zackenberg Valley in Northeast Greenland. To demonstrate its utility, we apply the library to identify nearly 20 000 arthropod individuals from two Malaise traps, each operated for two summers. Drawing on this material, we estimate the coverage of previous morphology-based species inventories, derive a snapshot of faunal turnover in space and time and describe the abundance and phenology of species in the rapidly changing arctic environment. Overall, 403 terrestrial animal and 160 vascular plant species were recorded by morphology-based techniques. DNA barcodes (CO1) offered high resolution in discriminating among the local animal taxa, with 92% of morphologically distinguishable taxa assigned to unique Barcode Index Numbers (BINs) and 93% to monophyletic clusters. For vascular plants, resolution was lower, with 54% of species forming monophyletic clusters based on barcode regions rbcLa and ITS2. Malaise catches revealed 122 BINs not detected by previous sampling and DNA barcoding. The insect community was dominated by a few highly abundant taxa. Even closely related taxa differed in phenology, emphasizing the need for species-level resolution when describing ongoing shifts in arctic communities and ecosystems. The DNA barcode library now established for Zackenberg offers new scope for such explorations, and for the detailed dissection of interspecific interactions throughout the community.
- MeSH
- ekosystém * MeSH
- fylogeneze MeSH
- mezerníky ribozomální DNA chemie genetika MeSH
- respirační komplex IV genetika MeSH
- ribulosa-1,5-bisfosfát-karboxylasa genetika MeSH
- rostliny MeSH
- společenstvo * MeSH
- taxonomické DNA čárové kódování metody MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Arktida MeSH
- Grónsko MeSH
BACKGROUND: The 12-item Multiple Sclerosis Walking Scale (MSWS-12) is currently the most widely validated, patient-reported outcome measure assessing patients' perception of the impact of multiple sclerosis (MS) on walking ability. To date, the majority of previous studies investigating the MSWS-12 have focused on the total score despite individual items being potentially informative. Therefore, our objective was to examine the associations between the individual items of the MSWS-12 and mobility and whether these associations depend on disability level. METHODS: Participants completed the MSWS-12, Two-Minute Walk Test (2MWT), Timed 25-Foot Walk (T25FW), Timed Up and Go Test (TUG) and the Four Square Step Test (FSST). Subsequently, they were divided into two groups according to their disability level, classified as either "mildly" or "moderately-severely" disabled. The correlation between individual items of the MSWS-12 and clinical measures of mobility were separately examined by Spearman's correlation coefficients; linear regression analyses were performed for each disability group, with/without adjusting for cognition, age and gender. RESULTS: 242 people with MS (PwMS), 108 mildly and 134 moderately-severely disabled, were included. Stronger correlations between the MSWS-12 items and mobility tests were found in the mildly disabled compared to the moderately-severely disabled group. The linear regression analysis showed that in the mildly disabled, item 9 (use of support outdoors) explained 35.4%, 30.8%, and 23.7% of the variance related to the 2MWT, T25FW and TUG, respectively. As for the moderately-severely disabled, the linear regression analysis presented a model which included item 8 (use of support indoors), explaining 31.6%, 18.0%, 20.2% and 9.5% of the variance related to the 2MWT, T25FWT, TUG and FSST, respectively. CONCLUSIONS: Items 8 and 9 of the MSWS-12 focusing on the patient's use of walking support in and outdoors, provide a robust indicator of mobility capabilities for mildly and moderately-severely disabled PwMS.
- MeSH
- chůze * MeSH
- lidé MeSH
- posturální rovnováha MeSH
- posuzování pracovní neschopnosti MeSH
- roztroušená skleróza * diagnóza MeSH
- studie pohybu a času MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
OBJECTIVE: To determine responsiveness of functional mobility measures, and provide reference values for clinically meaningful improvements, according to disability level, in persons with multiple sclerosis (pwMS) in response to physical rehabilitation. METHODS: Thirteen mobility measures (clinician- and patient-reported) were assessed before and after rehabilitation in 191 pwMS from 17 international centers (European and United States). Combined anchor- and distribution-based methods were used. A global rating of change scale, from patients' and therapists' perspective, served as external criteria when determining the area under the receiver operating characteristic curve (AUC), the minimally important change (MIC), and the smallest real change (SRC). Patients were stratified into 2 subgroups based on disability level (Expanded Disability Status Scale score ≤4 [n = 72], >4 [n = 119]). RESULTS: The Multiple Sclerosis Walking Scale-12, physical subscale of the Multiple Sclerosis Impact Scale-29 (especially for the mildly disabled pwMS), Rivermead Mobility Index, and 5-repetition sit-to-stand test (especially for the moderately to severely disabled pwMS) were the most sensitive measures in detecting improvements in mobility. Findings were determined once the AUC (95% confidence interval) was above 0.5, MIC was greater than SRC, and results were comparable from the patient and therapist perspective. CONCLUSIONS: Responsiveness, clinically meaningful improvement, and real changes of frequently used mobility measures were calculated, showing great heterogeneity, and were dependent on disability level in pwMS.
- MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- pohybová aktivita fyziologie MeSH
- roztroušená skleróza rehabilitace MeSH
- terapie cvičením metody MeSH
- výsledek terapie * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
... Hebert, J. A. Schafer, and T. E. ... ... Hays and Sherman D. ... ... Blantz -- Chapter 36 -- Diabetic Nephropathy 1906 -- Allen 1. Arieff and Bryan D. ... ... Bennett -- Chapter 40 -- Renal Neoplasia 2109 -- • \' *, • (Hgd • b4 ’ ( I A -- Jerome P. ... ... Strom, Nicholas L. Tilney, and John P. ...
2nd ed. 2 sv. il.
- MeSH
- ledviny MeSH
- nemoci ledvin MeSH
- Konspekt
- Patologie. Klinická medicína
- NLK Obory
- nefrologie
- urologie
Biodiversity research in tropical ecosystems-popularized as the most biodiverse habitats on Earth-often neglects invertebrates, yet invertebrates represent the bulk of local species richness. Insect communities in particular remain strongly impeded by both Linnaean and Wallacean shortfalls, and identifying species often remains a formidable challenge inhibiting the use of these organisms as indicators for ecological and conservation studies. Here we use DNA barcoding as an alternative to the traditional taxonomic approach for characterizing and comparing the diversity of moth communities in two different ecosystems in Gabon. Though sampling remains very incomplete, as evidenced by the high proportion (59%) of species represented by singletons, our results reveal an outstanding diversity. With about 3500 specimens sequenced and representing 1385 BINs (Barcode Index Numbers, used as a proxy to species) in 23 families, the diversity of moths in the two sites sampled is higher than the current number of species listed for the entire country, highlighting the huge gap in biodiversity knowledge for this country. Both seasonal and spatial turnovers are strikingly high (18.3% of BINs shared between seasons, and 13.3% between sites) and draw attention to the need to account for these when running regional surveys. Our results also highlight the richness and singularity of savannah environments and emphasize the status of Central African ecosystems as hotspots of biodiversity.
- MeSH
- biodiverzita * MeSH
- DNA analýza genetika MeSH
- ekosystém MeSH
- můry klasifikace genetika MeSH
- taxonomické DNA čárové kódování metody MeSH
- tropické klima * MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- Geografické názvy
- Gabon MeSH
Fragile X syndrome (FXS) is an inherited form of intellectual disability caused by the loss of the mRNA-binding fragile X mental retardation protein (FMRP). FXS is characterized by neuronal hyperexcitability and behavioral defects, however the mechanisms underlying these critical dysfunctions remain unclear. Here, using male Fmr1 knockout mouse model of FXS, we identify abnormal extracellular potassium homeostasis, along with impaired potassium channel Kir4.1 expression and function in astrocytes. Further, we reveal that Kir4.1 mRNA is a binding target of FMRP. Finally, we show that the deficit in astroglial Kir4.1 underlies neuronal hyperexcitability and several behavioral defects in Fmr1 knockout mice. Viral delivery of Kir4.1 channels specifically to hippocampal astrocytes from Fmr1 knockout mice indeed rescues normal astrocyte potassium uptake, neuronal excitability, and cognitive and social performance. Our findings uncover an important role for astrocyte dysfunction in the pathophysiology of FXS, and identify Kir4.1 channel as a potential therapeutic target for FXS.
- MeSH
- astrocyty * metabolismus MeSH
- chování zvířat MeSH
- draslík metabolismus MeSH
- draslíkové kanály dovnitř usměrňující * metabolismus genetika MeSH
- hipokampus metabolismus MeSH
- messenger RNA metabolismus genetika MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední C57BL MeSH
- myši knockoutované MeSH
- myši MeSH
- neurony * metabolismus fyziologie MeSH
- protein FMRP * metabolismus genetika MeSH
- syndrom fragilního X * metabolismus genetika patofyziologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
... Edelson and Katherine D. ... ... Nathan -- VII. ... ... Jones and Zena Werb -- 60 Neutral Proteases by 3H-Labeled Casein 593 -- D. O. ... ... Epstein, Nancy H. McManus, Samuel J. Hebert, Judith Woods-Hellman, and Diane G. ... ... Nerurkar -- IX. ...
Academic Press rapid manuscript reproduction
xxiv, 1023 stran : ilustrace ; 24 cm
- MeSH
- fagocyty fyziologie MeSH
- monocyty MeSH
- mononukleární fagocytární systém fyziologie MeSH
- výzkum MeSH
- výzkumné techniky MeSH
- Konspekt
- Buněčná biologie. Cytologie
- NLK Obory
- cytologie, klinická cytologie
- NLK Publikační typ
- kolektivní monografie
BACKGROUND: Assessing individuals in their own athletic footwear in clinics is common, but can affect movement, performance, and clinical measures. PURPOSE: The aim was to compare overall Landing Error Scoring System (LESS) scores, injury risk categorization, specific LESS errors, and jump heights between habitual athletic footwear and barefoot conditions. STUDY DESIGN: Randomized cross-over laboratory study. METHODS: Eighty healthy individuals (55% male) completed the LESS following standard procedures (i.e., land from a 30-cm box to a distance of 50% of body height and then jump upwards maximally). Participants performed the LESS three times in two randomized conditions: footwear and barefoot. LESS data were extracted from 2D videos to compare group-level mean LESS scores, group-level and individual-level injury risk categorization (5-error threshold), specific landing errors, and jump heights between conditions. RESULTS: LESS scores were significantly greater (0.3 errors, p=0.022) and jump heights were significantly lower (0.6 cm, p=0.029) in footwear than barefoot, but differences were trivial (d = 0.18 and -0.07, respectively) and not clinically meaningful. Although the number of high injury-risk participants was not statistically different at a group level (p=1.000); 27 individuals (33.8%) exhibited a clinically meaningful difference between conditions of one error or more in LESS score, categorization was inconsistent for 16.3% of individuals, and four of the 17 landing errors significantly differed between conditions. CONCLUSION: At a group level, habitual athletic footwear does not meaningfully influence LESS scores, risk categorization, or jump height. At an individual level, footwear can meaningfully affect LESS scores, risk categorization, and alter landing strategies. Use of consistent protocol and footwear is advised for assessing movement patterns and injury risk from the LESS given the unknown predictive value of this test barefoot. LEVEL OF EVIDENCE: Level 3.©The Author(s).
- Publikační typ
- časopisecké články MeSH
BACKGROUND AND OBJECTIVES: Patients with ongoing seizures are usually not allowed to drive. The prognosis for seizure freedom is favorable in patients with autoimmune encephalitis (AIE) with antibodies against NMDA receptor (NMDAR), leucine-rich glioma-inactivated 1 (LGI1), contactin-associated protein-like 2 (CASPR2), and the gamma-aminobutyric-acid B receptor (GABABR). We hypothesized that after a seizure-free period of 3 months, patients with AIE have a seizure recurrence risk of <20% during the subsequent 12 months. This would render them eligible for noncommercial driving according to driving regulations in several countries. METHODS: This retrospective multicenter cohort study analyzed follow-up data from patients aged 15 years or older with seizures resulting from NMDAR-, LGI1-, CASPR2-, or GABABR-AIE, who had been seizure-free for ≥3 months. We used Kaplan-Meier (KM) estimates for the seizure recurrence risk at 12 months for each antibody group and tested for the effects of potential covariates with regression models. RESULTS: We included 383 patients with NMDAR-, 440 with LGI1-, 114 with CASPR2-, and 44 with GABABR-AIE from 14 international centers. After being seizure-free for 3 months after an initial seizure period, we calculated the probability of remaining seizure-free for another 12 months (KM estimate) as 0.89 (95% confidence interval [CI] 0.85-0.92) for NMDAR, 0.84 (CI 0.80-0.88) for LGI1, 0.82 (CI 0.75-0.90) for CASPR2, and 0.76 (CI 0.62-0.93) for GABABR. DISCUSSION: Taking a <20% recurrence risk within 12 months as sufficient, patients with NMDAR-AIE and LGI1-AIE could be considered eligible for noncommercial driving after having been seizure-free for 3 months.
- MeSH
- autoprotilátky * krev MeSH
- dospělí MeSH
- encefalitida * imunologie MeSH
- Hashimotova nemoc imunologie krev MeSH
- intracelulární signální peptidy a proteiny * imunologie MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- membránové proteiny * imunologie MeSH
- mladiství MeSH
- mladý dospělý MeSH
- následné studie MeSH
- proteiny nervové tkáně * imunologie MeSH
- proteiny imunologie MeSH
- receptory GABA-B * imunologie MeSH
- receptory N-methyl-D-aspartátu imunologie MeSH
- recidiva * MeSH
- retrospektivní studie MeSH
- senioři MeSH
- záchvaty etiologie imunologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH