Myofibrillary myopathies (MFM) are hereditary myopathies histologically characterized by degeneration of myofibrils and aggregation of proteins in striated muscle. Cardiomyopathy is common in MFM but ...the pathophysiological mechanisms are not well understood. The BAG3-Pro209Leu mutation is associated with early onset MFM and severe restrictive cardiomyopathy (RCM), often necessitating heart transplantation during childhood. We report on a young male patient with a BAG3-Pro209Leu mutation who underwent heart transplantation at eight years of age. Detailed morphological analyses of the explanted heart tissue showed intracytoplasmic inclusions, aggregation of BAG3 and desmin, disintegration of myofibers and Z-disk alterations. The presence of undegraded autophagosomes, seen by electron microscopy, as well as increased levels of p62, LC3-I and WIPI1, detected by immunohistochemistry and western blot analyses, indicated a dysregulation of autophagy. Parkin and PINK1, proteins involved in mitophagy, were slightly increased whereas mitochondrial OXPHOS activities were not altered. These findings indicate that altered autophagy plays a role in the pathogenesis and rapid progression of RCM in MFM caused by the BAG3-Pro209Leu mutation, which could have implications for future therapeutic strategies.
•Cardiac tissue of a BAG3-Pro209Leu-mutant patient is characterized by protein aggregates and myofibrillar disintegration.•Autophagy is dysregulated in the patient with a BAG3-Pro209Leu mutation and may contribute to the cardiomyopathy.•BAG3-Pro209Leu-mutant cardiac tissue may have impaired mitochondrial function or clearance.
Geometry is a determining factor for thermal performance in both biological and technical systems. While biology has inspired thermal design before, biomimetic translation of leaf morphology into ...structural aspects of heat exchangers remains largely unaddressed. One determinant of plant thermal endurance against environmental exposure is leaf shape, which modulates the leaf boundary layer, transpiration, evaporative cooling, and convective exchange. Here, we lay the research groundwork for the extraction of design principles from leaf shape relations to heat and mass transfer. Leaf role models were identified from an extensive literature review on environmentally sensitive morphology patterns and shape-dependent exchange. Addressing canopy sun-shade dimorphism, sun leaves collected from multiple oak species exceeded significantly in margin extension and shape dissection. Abstracted geometries (i.e., elongated; with finely toothed edges; with few large-scale teeth) were explored with paper models of the same surface area in a controlled environment of minimal airflow, which is more likely to induce leaf thermal stress. For two model characteristic dimensions, evaporation rates were significantly faster for the dissected geometries. Shape-driven transfer enhancements were higher for the smaller models, and finely toothed edges reached local cooling up to 10 °C below air temperature. This investigation breaks new ground for solution-based biomimetics to inform the design of evaporation-assisted and passively enhanced thermal systems.
Post‐colonoscopy appendicitis: Causality or coincidence? Doulberis, M; Knuchel, J; Hartmann, M ...
Journal of gastroenterology and hepatology,
February 2021, 2021-Feb, 2021-02-00, 20210201, Letnik:
36, Številka:
2
Journal Article
The extraction and cleanup of commonly used tetracyclines (oxytetracycline, tetracycline, chlortetracycline, and doxycycline) from sample matrix, and their subsequent determination via liquid ...chromatography can be problematic. Many manuscripts report on various challenges encountered when developing a method for tetracycline antibiotics determination. These complexities often result in less than perfect recoveries or chromatograms and are based on the underlying chemistry associated with tetracyclines. This review compiles, compares, and discusses the results and observations found in published methods, while focusing on chemical principles in order to increase the practicing chemist's understanding of TCs to aid him/her in developing useful analyses.
Changes in vegetation and snow cover may lead to feedbacks to climate through changes in surface albedo and energy fluxes between the land and atmosphere. In addition to these biogeophysical ...feedbacks, biogeochemical feedbacks associated with changes in carbon (C) storage in the vegetation and soils may also influence climate. Here, using a transient biogeographic model (ALFRESCO) and an ecosystem model (DOS-TEM), we quantified the biogeophysical feedbacks due to changes in vegetation and snow cover across continuous permafrost to non-permafrost ecosystems in Alaska and northwest Canada. We also computed the changes in carbon storage in this region to provide a general assessment of the direction of the biogeochemical feedback. We considered four ecoregions, or Landscape Conservations Cooperatives (LCCs; including the Arctic, North Pacific, Western Alaska, and Northwest Boreal). We examined the 90 year period from 2010 to 2099 using one future emission scenario (A1B), under outputs from two general circulation models (MPI-ECHAM5 and CCCMA-CGCM3.1). We found that changes in snow cover duration, including both the timing of snowmelt in the spring and snow return in the fall, provided the dominant positive biogeophysical feedback to climate across all LCCs, and was greater for the ECHAM (+3.1 W m−2 decade−1 regionally) compared to the CCCMA (+1.3 W m−2 decade−1 regionally) scenario due to an increase in loss of snow cover in the ECHAM scenario. The greatest overall negative feedback to climate from changes in vegetation cover was due to fire in spruce forests in the Northwest Boreal LCC and fire in shrub tundra in the Western LCC (−0.2 to −0.3 W m−2 decade−1). With the larger positive feedbacks associated with reductions in snow cover compared to the smaller negative feedbacks associated with shifts in vegetation, the feedback to climate warming was positive (total feedback of +2.7 W m−2 decade regionally in the ECHAM scenario compared to +0.76 W m−2 decade regionally in the CCCMA scenario). Overall, increases in C storage in the vegetation and soils across the study region would act as a negative feedback to climate. By exploring these feedbacks to climate, we can reach a more integrated understanding of the manner in which climate change may impact interactions between high-latitude ecosystems and the global climate system.
N-acetylaspartate (NAA) and choline (Cho) are two brain metabolites implicated in several key neuronal functions. Abnormalities in these metabolites have been reported in both early course and ...chronic patients with schizophrenia (SCZ). It is, however, unclear whether NAA and Cho's alterations occur even before the onset of the disorder. Clinical high risk (CHR) individuals are a population uniquely enriched for psychosis and SCZ. In this exploratory study, we utilized 7-Tesla magnetic resonance spectroscopic imaging (MRSI) to examine differences in total NAA (tNAA; NAA + N-acetylaspartylglutamate NAAG) and major choline-containing compounds, including glycerophosphorylcholine and phosphorylcholine tCho, over the creatine (Cre) levels between 26 CHR and 32 healthy control (HC) subjects in the subcortical and cortical regions. While no tCho/Cre differences were found between groups in any of the regions of interest (ROIs), we found that CHR had significantly reduced tNAA/Cre in the right dorsal lateral prefrontal cortex (DLPFC) compared to HC, and that the right DLPFC tNAA/Cre reduction in CHR was negatively associated with their positive symptoms scores. No tNAA/Cre differences were found between CHR and HC in other ROIs. In conclusion, reduced tNAA/Cre in CHR vs. HC may represent a putative molecular biomarker for risk of psychosis and SCZ that is associated with symptom severity.
Reversing neuromuscular blockade with sugammadex can eliminate residual paralysis, which has been associated with postoperative respiratory complications. There are equivocal data on whether ...sugammadex reduces these when compared with neostigmine. We investigated the association of the choice of reversal drug with postoperative respiratory complications and advanced healthcare utilisation. We included adult patients who underwent surgery and received general anaesthesia with sugammadex or neostigmine reversal at two academic healthcare networks between January 2016 and June 2021. The primary outcome was postoperative respiratory complications, defined as post-extubation oxygen saturation < 90%, respiratory failure requiring non-invasive ventilation, or tracheal re-intubation within 7 days. Our main secondary outcome was advanced healthcare utilisation, a composite outcome including: 7-day unplanned intensive care unit admission; 30-day hospital readmission; or non-home discharge. In total, 5746 (6.9%) of 83,250 included patients experienced postoperative respiratory complications. This was not associated with the reversal drug (adjusted OR (95%CI) 1.01 (0.94-1.08); p = 0.76). After excluding patients admitted from skilled nursing facilities, 8372 (10.5%) patients required advanced healthcare utilisation, which was not associated with the choice of reversal (adjusted OR (95%CI) 0.95 (0.89-1.01); p = 0.11). Equivalence testing supported an equivalent effect size of sugammadex and neostigmine on both outcomes, and neostigmine was non-inferior to sugammadex with regard to postoperative respiratory complications or advanced healthcare utilisation. Finally, there was no association between the reversal drug and major adverse cardiovascular events (adjusted OR 1.07 (0.94-1.21); p = 0.32). Compared with neostigmine, reversal of neuromuscular blockade with sugammadex was not associated with a reduction in postoperative respiratory complications or post-procedural advanced healthcare utilisation.
There is a substantial amount of carbon stored in the permafrost soils of boreal forest ecosystems, where it is currently protected from decomposition. The surface organic horizons insulate the ...deeper soil from variations in atmospheric temperature. The removal of these insulating horizons through consumption by fire increases the vulnerability of permafrost to thaw, and the carbon stored in permafrost to decomposition. In this study we ask how warming and fire regime may influence spatial and temporal changes in active layer and carbon dynamics across a boreal forest landscape in interior Alaska. To address this question, we (1) developed and tested a predictive model of the effect of fire severity on soil organic horizons that depends on landscape-level conditions and (2) used this model to evaluate the long-term consequences of warming and changes in fire regime on active layer and soil carbon dynamics of black spruce forests across interior Alaska. The predictive model of fire severity, designed from the analysis of field observations, reproduces the effect of local topography (landform category, the slope angle and aspect and flow accumulation), weather conditions (drought index, soil moisture) and fire characteristics (day of year and size of the fire) on the reduction of the organic layer caused by fire. The integration of the fire severity model into an ecosystem process-based model allowed us to document the relative importance and interactions among local topography, fire regime and climate warming on active layer and soil carbon dynamics. Lowlands were more resistant to severe fires and climate warming, showing smaller increases in active layer thickness and soil carbon loss compared to drier flat uplands and slopes. In simulations that included the effects of both warming and fire at the regional scale, fire was primarily responsible for a reduction in organic layer thickness of 0.06 m on average by 2100 that led to an increase in active layer thickness of 1.1 m on average by 2100. The combination of warming and fire led to a simulated cumulative loss of 9.6 kgC m−2 on average by 2100. Our analysis suggests that ecosystem carbon storage in boreal forests in interior Alaska is particularly vulnerable, primarily due to the combustion of organic layer thickness in fire and the related increase in active layer thickness that exposes previously protected permafrost soil carbon to decomposition.
The chemo-enzymatic epoxidation of
Lallemantia iberica
seed oil (LISO), a novel plant oil characterized by its exceptional high content of alpha-linolenic acid (> 60%), was developed using an ...immobilized lipase from
Pseudozyma antarctica
and hydrogen peroxide as oxidant. A statistical approach was used to study the effect of enzyme amount, temperature, time, and solvent amount on the oxirane oxygen content obtained during epoxidation. An oxirane oxygen content of 8.6 ± 0.2% corresponding to a yield of 82% was obtained under optimized conditions that were identified to be at an enzyme load of 8.2 g/mol of double bonds, a solvent amount of 56.4 wt.%, a temperature of 33 °C, and an incubation time of 17 h. In addition, the experimental investigation was combined with a techno-economic and ecological assessment gaining detailed information regarding cost structure and environmental impact for the chemo-enzymatic epoxidation of the novel plant oil.
In Saccharomyces cerevisiae, two major signal transduction pathways, the Kss1 MAPK pathway and the cAMP‐regulated pathway, are critical for the differentiation of round yeast form cells to ...multicellular, invasive pseudohyphae. Here we report that these parallel pathways converge on the promoter of a gene, FLO11, which encodes a cell surface protein required for pseudohyphal formation. The FLO11 promoter is unusually large, containing at least four upstream activation sequences (UASs) and nine repression elements which together span at least 2.8 kb. Several lines of evidence indicate that the MAPK and cAMP signals are received by distinct transcription factors and promoter elements. First, regulation via the MAPK pathway requires the transcription factors Ste12p/Tec1p, whereas cAMP‐mediated activation requires a distinct factor, Flo8p. Secondly, mutations in either pathway block FLO11 transcription. Overexpression of STE12 can suppress the loss of FLO8, and overexpression of FLO8 can suppress the loss of STE12. Finally, multiple distinct promoter regions of the FLO11 promoter are required for its activation by either Flo8p or Ste12p/Tec1p. Thus, like the promoters of the key developmental genes, HO and IME1, the FLO11 promoter is large and complex, endowing it with the ability to integrate multiple inputs.
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