| 621. |
- Repetto, Linda, et al.
(author)
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Unraveling Neuro-Proteogenomic Landscape and Therapeutic Implications for Human Behaviors and Psychiatric Disorders.
- 2023
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In: Nature Portfolio. - : Research Square Platform LLC.
-
Journal article (other academic/artistic)abstract
- Understanding the genetic basis of neuro-related proteins is essential for dissecting the molecular basis of human behavioral traits and the disease etiology of neuropsychiatric disorders. Here, the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,500 individuals for 184 neuro-related proteins in human plasma. The analysis identified 117 cis-regulatory protein quantitative trait loci (cis-pQTL) and 166 trans-pQTL. The mapped pQTL capture on average 50% of each protein's heritability. Mendelian randomization analyses revealed multiple proteins showing potential causal effects on neuro-related traits such as sleeping, smoking, feelings, alcohol intake, mental health, and psychiatric disorders. Integrating with established drug information, we validated 13 out of 13 matched combinations of protein targets and diseases or side effects with available drugs, while suggesting hundreds of re-purposing and new therapeutic targets. This consortium effort provides a large-scale proteogenomic resource for biomedical research on human behaviors and other neuro-related phenotypes.
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| 622. |
- Revsbech, Inge G., et al.
(author)
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Hydrogen sulfide and nitric oxide metabolites in the blood of free-ranging brown bears and their potential roles in hibernation
- 2014
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In: Free Radical Biology & Medicine. - : Elsevier. - 0891-5849 .- 1873-4596. ; 73, s. 349-357
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Journal article (peer-reviewed)abstract
- During winter hibernation, brown bears (Ursus arctos) lie in dens for half a year without eating while their basal metabolism is largely suppressed. To understand the underlying mechanisms of metabolic depression in hibernation, we measured type and content of blood metabolites of two ubiquitous inhibitors of mitochondrial respiration, hydrogen sulfide (H2S) and nitric oxide (NO), in winter-hibernating and summer-active free-ranging Scandinavian brown bears. We found that levels of sulfide metabolites were overall similar in summer-active and hibernating bears but their composition in the plasma differed significantly, with a decrease in bound sulfane sulfur in hibernation. High levels of unbound free sulfide correlated with high levels of cysteine (Cys) and with low levels of bound sulfane sulfur, indicating that during hibernation H2S, in addition to being formed enzymatically from the substrate Cys, may also be regenerated from its oxidation products, including thiosulfate and polysulfides. In the absence of any dietary intake, this shift in the mode of H2S synthesis would help preserve free Cys for synthesis of glutathione (GSH), a major antioxidant found at high levels in the red blood cells of hibernating bears. In contrast, circulating nitrite and erythrocytic S-nitrosation of glyceraldehyde-3-phosphate dehydrogenase, taken as markers of NO metabolism, did not change appreciably. Our findings reveal that remodeling of H2S metabolism and enhanced intracellular GSH levels are hallmarks of the aerobic metabolic suppression of hibernating bears.
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| 623. |
- Rocca, Jennifer D., et al.
(author)
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Guided by Microbes : Applying Community Coalescence Principles for Predictive Microbiome Engineering
- 2021
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In: mSystems. - 2379-5077. ; 6:4
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Journal article (peer-reviewed)abstract
- Every seed germinating in soils, wastewater treatment, and stream confluence exemplify microbial community coalescence—the blending of previously isolated communities. Here, we present theoretical and experimental knowledge on how separated microbial communities mix, with particular focus on managed ecosystems. We adopt the community coalescence framework, which integrates metacommunity theory and meta-ecosystem dynamics, and highlight the prevalence of these coalescence events within microbial systems. Specifically, we (i) describe fundamental types of community coalescences using naturally occurring and managed examples, (ii) offer ways forward to leverage community coalescence in managed systems, and (iii) emphasize the importance of microbial ecological theory to achieving desired coalescence outcomes. Further, considering the massive dispersal events of microbiomes and their coalescences is pivotal to better predict microbial community dynamics and responses to disturbances. We conclude our piece by highlighting some challenges and unanswered question yet to be tackled.
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| 624. |
- Rodríguez-Gijón, Alejandro, 1996-, et al.
(author)
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Linking prokaryotic genome size variation to metabolic potential and environment
- 2023
-
In: ISME Communications. - : Springer Science and Business Media LLC. - 2730-6151. ; 3:1
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Journal article (peer-reviewed)abstract
- While theories and models have appeared to explain genome size as a result of evolutionary processes, little work has shown that genome sizes carry ecological signatures. Our work delves into the ecological implications of microbial genome size variation in benthic and pelagic habitats across environmental gradients of the brackish Baltic Sea. While depth is significantly associated with genome size in benthic and pelagic brackish metagenomes, salinity is only correlated to genome size in benthic metagenomes. Overall, we confirm that prokaryotic genome sizes in Baltic sediments (3.47 Mbp) are significantly bigger than in the water column (2.96 Mbp). While benthic genomes have a higher number of functions than pelagic genomes, the smallest genomes coded for a higher number of module steps per Mbp for most of the functions irrespective of their environment. Some examples of this functions are amino acid metabolism and central carbohydrate metabolism. However, we observed that nitrogen metabolism was almost absent in pelagic genomes and was mostly present in benthic genomes. Finally, we also show that Bacteria inhabiting Baltic sediments and water column not only differ in taxonomy, but also in their metabolic potential, such as the Wood-Ljungdahl pathway or the presence of different hydrogenases. Our work shows how microbial genome size is linked to abiotic factors in the environment, metabolic potential and taxonomic identity of Bacteria and Archaea within aquatic ecosystems.
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| 625. |
- Roel, Elena, et al.
(author)
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Characteristics and Outcomes of Over 300,000 Patients with COVID-19 and History of Cancer in the United States and Spain.
- 2021
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In: Cancer epidemiology, biomarkers & prevention. - 1538-7755. ; 30:10, s. 1884-1894
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Journal article (peer-reviewed)abstract
- We described the demographics, cancer subtypes, comorbidities, and outcomes of patients with a history of cancer and coronavirus disease 2019 (COVID-19). Second, we compared patients hospitalized with COVID-19 to patients diagnosed with COVID-19 and patients hospitalized with influenza.We conducted a cohort study using eight routinely collected health care databases from Spain and the United States, standardized to the Observational Medical Outcome Partnership common data model. Three cohorts of patients with a history of cancer were included: (i) diagnosed with COVID-19, (ii) hospitalized with COVID-19, and (iii) hospitalized with influenza in 2017 to 2018. Patients were followed from index date to 30 days or death. We reported demographics, cancer subtypes, comorbidities, and 30-day outcomes.We included 366,050 and 119,597 patients diagnosed and hospitalized with COVID-19, respectively. Prostate and breast cancers were the most frequent cancers (range: 5%-18% and 1%-14% in the diagnosed cohort, respectively). Hematologic malignancies were also frequent, with non-Hodgkin's lymphoma being among the five most common cancer subtypes in the diagnosed cohort. Overall, patients were aged above 65 years and had multiple comorbidities. Occurrence of death ranged from 2% to 14% and from 6% to 26% in the diagnosed and hospitalized COVID-19 cohorts, respectively. Patients hospitalized with influenza (n = 67,743) had a similar distribution of cancer subtypes, sex, age, and comorbidities but lower occurrence of adverse events.Patients with a history of cancer and COVID-19 had multiple comorbidities and a high occurrence of COVID-19-related events. Hematologic malignancies were frequent.This study provides epidemiologic characteristics that can inform clinical care and etiologic studies.
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| 626. |
- Romero, Gustavo Q., et al.
(author)
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Climate variability and aridity modulate the role of leaf shelters for arthropods : A global experiment
- 2022
-
In: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 28:11, s. 3694-3710
-
Journal article (peer-reviewed)abstract
- Current climate change is disrupting biotic interactions and eroding biodiversity worldwide. However, species sensitive to aridity, high temperatures, and climate variability might find shelter in microclimatic refuges, such as leaf rolls built by arthropods. To explore how the importance of leaf shelters for terrestrial arthropods changes with latitude, elevation, and climate, we conducted a distributed experiment comparing arthropods in leaf rolls versus control leaves across 52 sites along an 11,790 km latitudinal gradient. We then probed the impact of short- versus long-term climatic impacts on roll use, by comparing the relative impact of conditions during the experiment versus average, baseline conditions at the site. Leaf shelters supported larger organisms and higher arthropod biomass and species diversity than non-rolled control leaves. However, the magnitude of the leaf rolls' effect differed between long- and short-term climate conditions, metrics (species richness, biomass, and body size), and trophic groups (predators vs. herbivores). The effect of leaf rolls on predator richness was influenced only by baseline climate, increasing in magnitude in regions experiencing increased long-term aridity, regardless of latitude, elevation, and weather during the experiment. This suggests that shelter use by predators may be innate, and thus, driven by natural selection. In contrast, the effect of leaf rolls on predator biomass and predator body size decreased with increasing temperature, and increased with increasing precipitation, respectively, during the experiment. The magnitude of shelter usage by herbivores increased with the abundance of predators and decreased with increasing temperature during the experiment. Taken together, these results highlight that leaf roll use may have both proximal and ultimate causes. Projected increases in climate variability and aridity are, therefore, likely to increase the importance of biotic refugia in mitigating the effects of climate change on species persistence.
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| 627. |
- Rubin, Mark A., et al.
(author)
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Decreased alpha-methylacyl CoA racemase expression in localized prostate cancer is associated with an increased rate of biochemical recurrence and cancer-specific death
- 2005
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In: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 18, s. 162A-162A
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Journal article (peer-reviewed)abstract
- alpha-Methylacyl CoA racemase (AMACR) is overexpressed in prostate cancer relative to benign prostatic tissue. AMACR expression is highest in localized prostate cancer and decreases in metastatic prostate cancer. Herein, we explored the use of AMACR as a biomarker for aggressive prostate cancer. AMACR protein expression was determined by immunohistochemistry using an image analysis system on two localized prostate cancer cohorts consisting of 204 men treated by radical prostatectomy and 188 men followed expectantly. The end points for the cohorts were time to prostate-specific antigen (PSA) failure (i.e., elevation > 0.2 ng/mL) and time to prostate cancer death in the watchful waiting cohort. Using a regression tree method, optimal AMACR protein expression cutpoints were determined to best differentiate prostate cancer outcome in each of the cohorts separately. Cox proportional hazard models were then employed to examine the effect of the AMACR cutpoint on prostate cancer outcome, and adjusted for clinical variables. Lower AMACR tissue expression was associated with worse prostate cancer outcome, independent of clinical variables (hazard ratio, 3.7 for PSA failure; P = 0.018; hazard ratio, 4.1 for prostate cancer death, P = 0.0006). Among those with both low AMACR expression and high Gleason score, the risk of prostate cancer death was 18-fold higher (P = 0.006). The AMACR cutpoint developed using prostate cancer-specific death as the end point predicted PSA failures independent of Gleason score, PSA, and margin status. This is the first study to show that AMACR expression is significantly associated with prostate cancer progression and suggests that not all surrogate end points may be optimal to define biomarkers of aggressive prostate cancer.
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| 628. |
- Rui, H., et al.
(author)
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Stable Dye-Sensitized Solar Cells Based on Copper(II/I) Redox Mediators Bearing a Pentadentate Ligand
- 2021
-
In: Angewandte Chemie International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 60:29, s. 16156-16163
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Journal article (peer-reviewed)abstract
- In recent years, copper redox mediators have attracted growing interest in dye-sensitized solar cells (DSCs). However, experiments revealed that ubiquitously used Lewis-base additives in the electrolytes coordinate to the CuII species, which restricts further enhancement of device performance and stability. We report the application of copper complexes endowed with diamine-tripyridine pentadentate ligands, [Cu(tpe)]2+/+ (tpe=N-benzyl-N,N′,N′-tris(pyridin-2-ylmethyl)ethylenediamine) and [Cu(tme)]2+/+ (tme=N-benzyl-N,N′,N′-tris(6-methylpyridin-2-ylmethyl)ethylenediamine), as redox mediators in DSCs. Experimental measurements demonstrate that the coordination environment of Cu(II) complexes with pentadentate ligands remains unchanged in the presence of TBP, which is in stark contrast to the state-of-the-art bipyridyl counterpart. DSCs based on [Cu(tme)]2+/+ complexes exhibit an excellent long-term stability and maintain more than 90 % of the initial efficiency after 400 h under continuous illumination, which outperform the reference devices incorporating the bipyridyl counterpart (less than 80 %) under identical conditions.
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| 629. |
- Saeidi, Kamran, et al.
(author)
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Transformation of austenite to duplex austenite-ferrite assembly in annealed stainless steel 316L consolidated by laser melting
- 2015
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In: Journal of Alloys and Compounds. - : Elsevier BV. - 0925-8388 .- 1873-4669. ; 633, s. 463-469
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Journal article (peer-reviewed)abstract
- Laser melting (LM), with a focused Nd:YAG laser beam, was used to form solid bodies from 316L austenite stainless steel powder and the laser melted samples were heat treated at various temperatures. The phase changes in heat treated samples were characterized using X-ray diffraction (XRD). Samples heat treated at 800 degrees C and 900 degrees C remained single austenite while in samples heat treated at 1100 degrees C and 1400 degrees C a dual austenite-ferrite phase assembly was formed. The ferrite formation was further verified by electron back scattering diffraction (EBSD) and selective area diffraction (SAD). Microstructural changes were studied by scanning and transmission electron microscopy (SEM, TEM). In samples heat treated up to 900 degrees C, coalescence of the cellular-sub grains was noticed, whereas in sample heat treated at and above 1100 degrees C the formation of ferrite phase was observed. The correlation between the microstructure/phase assembly and the measured strength/microhardness were investigated, which indicated that the tensile strength of the laser melted material was significantly higher than that of the conventional 316L steel even after heat treatment whereas caution has to be taken when laser melted material will be exposed to an application temperature above 900 degrees C.
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| 630. |
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