Effect of Dbf2 on Phosphorilation

Cytokinesis refers to the separation of two daughter cells after mitotic division. An important signaling pathway that enables this process is called the Mitotic Exit Pathway, or MEN. Of particular interest in this pathway is the Dbf2 protein kinase. Dbf2 essentially acts as a middleman within the cascade of messengers and activates proteins that physically separate the cells. The kinase activity of Dbf2 is regulated by other cellular kinases, including the cell cycle regulator kinase. Using mutant alleles of the dbf2 gene, we can manipulate this protein\u27s ability to be phosphorylated or dephosphorylated, thereby altering the downstream effects of the entire MEN. After introducing the mutant alleles of Dbf2 into yeast cells, the effects of the mutations can be quantitatively observed under a microscope, since defects in cytokinesis result in chains of unseparated cells

Detection of myocardial ischemia by intracoronary ECG using convolutional neural networks.

INTRODUCTION The electrocardiogram (ECG) is a valuable tool for the diagnosis of myocardial ischemia as it presents distinctive ischemic patterns. Deep learning methods such as convolutional neural networks (CNN) are employed to extract data-derived features and to recognize natural patterns. Hence, CNN enable an unbiased view on well-known clinical phenomenon, e.g., myocardial ischemia. This study tested a novel, hypothesis-generating approach using pre-trained CNN to determine the optimal ischemic parameter as obtained from the highly susceptible intracoronary ECG (icECG). METHOD This was a retrospective observational study in 228 patients with chronic coronary syndrome. Each patient had participated in clinical trials with icECG recording and ST-segment shift measurement at the beginning (i.e., non-ischemic) and the end (i.e., ischemic) of a one-minute proximal coronary artery balloon occlusion establishing the reference. Using these data (893 icECGs in total), two pre-trained, open-access CNN (GoogLeNet/ResNet101) were trained to recognize ischemia. The best performing CNN during training were compared with the icECG ST-segment shift for diagnostic accuracy in the detection of artificially induced myocardial ischemia. RESULTS Using coronary patency or occlusion as reference for absent or present myocardial ischemia, receiver-operating-characteristics (ROC)-analysis of manually obtained icECG ST-segment shift (mV) showed an area under the ROC-curve (AUC) of 0.903±0.043 (p<0.0001, sensitivity 80%, specificity 92% at a cut-off of 0.279mV). The best performing CNN showed an AUC of 0.924 (sensitivity 93%, specificity 92%). DeLong-Test of the ROC-curves showed no significant difference between the AUCs. The underlying morphology responsible for the network prediction differed between the trained networks but was focused on the ST-segment and the T-wave for myocardial ischemia detection. CONCLUSIONS When tested in an experimental setting with artificially induced coronary artery occlusion, quantitative icECG ST-segment shift and CNN using pathophysiologic prediction criteria detect myocardial ischemia with similarly high accuracy

Rates of palaeoecological change can inform ecosystem restoration

Accelerations of ecosystem transformation raise concerns, to the extent that high rates of ecological change may be regarded amongst the most important ongoing imbalances in the Earth system. Here, we used high-resolution pollen and diatom assemblages and associated ecological indicators (the sum of tree and shrub pollen and diatom-inferred total phosphorus concentrations as proxies for tree cover and lake-water eutrophication, respectively) spanning the past 150 years to emphasise that rate-of-change records based on compositional data may document transformations having substantially different causes and outcomes. To characterize rates of change also in terms of other key ecosystem features, we quantified for both ecological indicators (i) the percentage of change per-unit-time, (ii) the percentage of change relative to a baseline level, and (iii) the rate of percentage change per-unit-time relative to a baseline level, taking into account the irregular spacing of palaeoecological data. These measures document how quickly specific facets of nature changed, their trajectory, as well as their status in terms of palaeoecological indicators. Ultimately, some past accelerations of community transformation may document the potential of ecosystems to rapidly recover important ecological attributes and functions. In this context, insights from palaeoecological records may be useful to accelerate ecosystem restoration

Holocene environmental history of Lake Vuolep Njakajaure (Abisko National Park, northern Sweden) reconstructed using biological proxy indicators

Holocene environmental and climatic changes are reconstructed using analyses of biological proxies in lake sediments from Vuolep Njakajaure, a lake located near the altitudinal treeline in northern Sweden (68°20′ N, 18°47′ E). We analysed biological proxy indicators from both aquatic and terrestrial ecosystems, including diatoms, pollen and chironomid head capsules, in order to reconstruct regional Holocene climate and the development of the lake and its catchment. During the early Holocene and after 2500 cal b.p., Fragilaria taxa dominated the diatom assemblages, whereas planktonic Cyclotella taxa prevailed during the major part of the Holocene (7800-2300 cal b.p.), indicating the importance of the pelagic habitat for diatom assemblage composition. The planktonic diatoms appeared at the same time as Alnus became established in the catchment, probably altering nutrient availability and catchment stability. The pollen record is dominated by mountain birch (Betula pubescens ssp. tortuosa) pollen throughout the Holocene, but high percentage abundances of Scots pine (Pinus sylvestris) pollen suggest the presence of a mixed pine-birch forest during the mid-Holocene (6800-2300 cal b.p.). Head capsules of Tanytarsini and Psectrocladius dominated the chironomid assemblage composition throughout the Holocene, in combination with Corynocera ambigua after 2300 cal b.p. A quantitative, diatom-based reconstruction of mean July air temperature indicated a relatively cold temperature during the early Holocene (9000-8000 cal b.p.) and after ca. 2300 cal b.p., whereas the mid-Holocene period is characterised by stable and warm temperatures. The overall patterns of Holocene climate and environmental conditions are similarly described by all biological proxy-indicators, suggesting relatively warm conditions during the mid-Holocene (ca. 7800-2300 cal b.p.), with a subsequent colder climate after 2300 cal b.p. However, the onset and magnitude of the inferred changes differ slightly among the proxies, illustrating different responses to lake development phases, land-uplift, and climate forcing (e.g., insolation patterns) during the Holocene in northern Swede

Human impacts and eutrophication patterns during the past ~200 years at Lago Grande di Avigliana (N. Italy)

A short sediment core from Lago Grande di Avigliana (Piedmont, Italy), the second most eutrophied lake in Italy, was analysed for pollen and diatoms to reconstruct land-use changes and to estimate baseline conditions for total phosphorus (TP) in the water column. Varve counts on sediment thin-sections and 210Pb, 226Ra, and 137Cs dating provided a reliable chronology for the past ~200 years. The main pollen-inferred land-use changes showed a sharp decrease of hemp retting around AD 1900, as well as a gradual change to less intensive agriculture and increasing abundance of exotic plants since AD ~1970. Diatom-inferred TP reconstructions indicated stable TP concentrations until AD ~1950, revealing baseline mesotrophic conditions (TP <25 µg l−1). After AD ~1950, TP values increased distinctly and continuously, culminating in the late 1960s with concentrations of 150 µg l−1. Subsequently, diatoms implied a linear decrease of TP, with an inferred value of 40 µg l−1 in the surface sediment sample. Comparison with instrumental TP measurements from the water column since AD 1980 showed a rapid recovery and allowed a direct validation of the diatom TP inference. However, although the TP concentration has decreased considerably, baseline conditions have not yet been reached. When compared to the limnological effects of sewage discharges on inferred-TP concentration, our results indicated that agricultural land use played a minor role in the lake's eutrophicatio

Comparison between chironomid-inferred July temperatures and meteorological data AD 1850-2001 from varved Lake Silvaplana, Switzerland

Inferred temperatures from chironomids preserved in the varved sediment of Lake Silvaplana in the Eastern Swiss Alps were compared with instrumental data obtained from a meteorological station in Sils-Maria, on the shore of Lake Silvaplana, for the time interval 1850-2001. At near-annual resolution, the general patterns of chironomid-inferred temperature changes followed the meteorological record over the last ∼150years (r Pearson=0.65, P=0.01) and 87% of the inferences had deviations from the instrumental data below the root-mean-square error of prediction (RMSEP). When the inferences were compared with a 2-year running mean in the meteorological data, 94% of the inferences had differences with the instrumental data below the RMSEP, indicating that more than half of the inaccurate inferences may have been due to errors in varve counting. Larger deviations from the instrumental data were also obtained from samples with low percentages of fossil taxa represented in the training set used for temperature reconstruction and/or assemblages with poor fit to temperature. Changes in total phosphorus (TP, as inferred by diatoms) and/or greater precipitation were possible factors affecting the accuracy of the temperature reconstruction. Although these factors might affect the quantitative estimates, obtaining >80% accurate temperature inferences suggests that chironomid analysis is a reliable tool for reconstructing mean July air temperature quantitatively over the last ∼150years in Lake Silvaplan

Distribution of diatoms, chironomids and cladocera in surface sediments of thirty mountain lakes in south-eastern Switzerland

Abstract.: Surface sediments from 30 mountain lakes in south-eastern Switzerland (Engadine, Grisons) were analysed for subfossil diatom, chironomid, and cladoceran assemblages. Ordination techniques were used to identify relevant physical and chemical environmental parameters that best explain the distribution of these biota in the studied lakes. Diatom assemblage composition showed a strong relationship with physical (e.g., lake depth, temperature, organic content of surface sediments) and chemical variables (e.g., lake-water pH, alkalinity, silica concentration). The greatest variance in chironomid and cladoceran assemblages is explained by dissolved organic carbon (DOC) content of lake water, temperature, and the organic content of surface sediments, all parameters which are highly correlated with lake elevation. Increasing lake depth is reflected in diatom and cladoceran assemblages by higher percentages of planktonic species, whereas chironomid assemblages in the deep Engadine lakes are characterised by a high proportion of lotic taxa. In contrast to similar studies in the Northern and Southern Alps, subfossil assemblages in the Engadine mountain lakes showed a strong relationship with DOC, which in these weakly buffered lakes is negatively correlated with altitude. According to our findings, chironomid and cladocera remains have a considerable potential as quantitative palaeotemperature indicators in the Engadine area. This potential is somewhat weaker for diatoms which seem to be more strongly influenced by water chemistry and lake bathymetr

Effect of past century mining activities on sediment properties and toxicity to freshwater organisms in northern Sweden

The release of toxic metals from local mining activities often represents a severe environmental hazard for nearby lake ecosystems. Previous studies on the impact of mining have primarily focused on single lakes, with less emphasis on spatial and temporal recovery patterns of multiple lakes within the same catchment, but with different hydrological connection and distance to the pollutant source. This knowledge gap prevents us from assessing the real environmental risk of abandoned mines and understanding ecosystem recovery. This study explores the intensity and spatial patterns of sediment contamination and the potential for ecosystem recovery in three lakes in close vicinity of a lead (Pb) and zinc (Zn) mine in Sweden that has been inoperative for >20 years. Dated (210Pb and 137Cs) sediment cores from each lake were used to reconstruct temporal patterns in trace element deposition and relate those with past mining activities. Results show that all lakes were affected by mining, indicated by increasing Pb and Zn concentrations and decreasing organic matter content, at the onset of mining. However, the extent and timing of mining impact differed between lakes, which was partly ascribed to differences in the historical use of tailings and settling ponds. Assessment of toxicity levels in sediments, based on normalized Probable Effect Concentration Quotient (PEC-Q) to organic matter content, provided more consistent results with the historical mining than conventional methods, showing a decreasing impact in lakes once the operations ceased. Still, sediment Pb concentrations were > 10 times higher than pre-mining values, evidencing the urgent need for remediation actions in the study lakes. This study highlights the importance of considering spatial heterogeneity in metal deposition, sediment organic matter content, and hydrological connectivity with tailings when risk assessments are performed in mining-impacted lakes. The use of normalized PEC-Q in toxic assessments is also recommended

Algorithm for real-time analysis of intracoronary electrocardiogram.

Introduction Since its first implementation in 1985, intracoronary (ic) electrocardiogram (ECG) has shown ample evidence for its diagnostic value given the higher sensitivity for myocardial ischemia detection in comparison to surface ECG. However, a lack of online systems to quantitatively analyze icECG in real-time prevents its routine use. The present study aimed to develop and validate an autonomous icECG analyzing algorithm. Materials and methods This is a retrospective observational study in 100 patients with chronic coronary syndrome. From each patient, a non-ischemic as well as ischemic icECG at the end of a 1-min proximal coronary balloon occlusion was available. An ECG expert as well as the newly developed algorithm for autonomous icECG analysis measured the icECG ST-segment shift in mV for each icECG tracing. Results Intraclass correlation coefficient (ICC) demonstrated low variability between the two methods (ICC = 0.968). Using the time point of icECG recording as allocation reference for absent or present myocardial ischemia, ROC-analysis for ischemia detection by the manually determined icECG ST-segment shift showed an area under the curve (AUC) of 0.968 ± 0.021 (p < 0.0001). AUC for the algorithm analysis was 0.967 ± 0.023 (p < 0.0001; p = 0.925 for the difference between the ROC curve AUCs). Time to complete analysis was below 1,000 ms for the autonomous icECG analysis and above 5 min for manual analysis. Conclusion A newly developed autonomous icECG analysing algorithm detects myocardial ischemia with equal accuracy as manual ST-segment shift assessment. The algorithm provides the technical fundament for an analysing system to quantitatively obtain icECG in real-time

Clinical Efficacy of Permanent Internal Mammary Artery Occlusion in Chronic Coronary Syndrome: a Double-Blind, Randomized, Sham-Controlled Trial.

The CLIMACCS trial, a randomized, sham-controlled trial tested the CLinical efficacy of permanent internal mammary artery (IMA) device occlusion on symptoms in patients with chronic coronary syndrome (CCS), on coronary artery occlusive blood supply, and on myocardial ischemia. This was a prospective trial in 101 patients with CCS randomly allocated (1:1) to IMA device occlusion (verum group) or to IMA sham intervention (placebo group). The primary study endpoint was the change in treadmill exercise time (ΔET in seconds, s) at 6 weeks after trial intervention. Secondary study endpoints were the changes in collateral flow index (CFI), and angina pectoris during a simultaneous 1-minute proximal balloon occlusion of a coronary artery. CFI is the ratio between simultaneous mean coronary occlusive divided by mean aortic pressure both subtracted by central venous pressure. In the verum and placebo group, exercise time changed from 398±176s to 421±198s in the verum group (p=0.1745), and from 426±162s to 430±166s in the placebo group (p=0.55); DET amounted to +23±116s and +4±120s, respectively (p=0.44). CFI change during follow-up equalled +0.022±0.061 in the verum and-0.039±0.072 in the placebo group (p<0.0001). Angina pectoris at follow-up during the coronary balloon occlusion for CFI measurement had decreased or disappeared in 20/48 patients of the verum, and in 9/47 patients of the placebo group (p=0.0242). In conclusion, permanent IMA device occlusion tends to augment treadmill exercise time in response to heightened coronary artery occlusive blood supply, the fact of which is reflected by mitigated symptoms and signs of myocardial ischemia