Exploring the role of biotic factors in regulating the spatial variability in land surface phenology across four temperate forest sites.

Land surface phenology (LSP), the characterization of plant phenology with satellite data, is essential for understanding the effects of climate change on ecosystem functions. Considerable LSP variation is observed within local landscapes, and the role of biotic factors in regulating such variation remains underexplored. In this study, we selected four National Ecological Observatory Network terrestrial sites with minor topographic relief to investigate how biotic factors regulate intra-site LSP variability. We utilized plant functional type (PFT) maps, functional traits, and LSP data to assess the explanatory power of biotic factors for the start and end of season (SOS and EOS) variability. Our results indicate that PFTs alone explain only 0.8-23.4% of intra-site SOS and EOS variation, whereas including functional traits significantly improves explanatory power, with cross-validation correlations ranging from 0.50 to 0.85. While functional traits exhibited diverse effects on SOS and EOS across different sites, traits related to competitive ability and productivity were important for explaining both SOS and EOS variation at these sites. These findings reveal that plants exhibit diverse phenological responses to comparable environmental conditions, and functional traits significantly contribute to intra-site LSP variability, highlighting the importance of intrinsic biotic properties in regulating plant phenology.

Stress responses of bivalve mollusc Unio tumidus from two areas to ibuprofen, microplastic and their mixture.

Even though bivalve molluscs are recognized as bioindicators of freshwater quality, their responses to multiple stressors are unpredictable. This study aims to elucidate the inter-population peculiarities of the effect in the sub-chronic environmentally relevant exposure to novel contaminants. The specimens of Unio tumidus from reference (Pr) and contaminated (Ct) areas were treated with ibuprofen (IBU, 0.8 µg L-1), microplastic (MP, 1.0 mg L-1, size 0.1-0.5 mm), or their combination (Mix) for 14 days. Untreated mussels (PrC- and CtC-groups) served as controls. The PrC-group had higher levels of antioxidants Mn-SOD, Cu,Zn-SOD, catalase, and cholinesterase (AChE) as well as lesser levels of oxidative lesions (TBARS and protein carbonyls) in digestive glands, indicating lower environmental impact than in the CtC-group. However, lysosomal stability was similar in both control groups. Among antioxidants, Mn-SOD activity was affected most prominently, increasing in all exposed Ct-groups. TBARS level was increased only in PrMP-group compared to responsive control. IBU and Mix enhanced protein carbonyl concentration in the Pr-groups, and decreased it in the Ct-groups. AChE was induced in the CtIBU- and PrMix-groups, and lysosomal integrity increased in the CtIBU and CtMix-groups. Discriminant analyses indicated lesser differences between Pr-groups, demonstrating lower cumulative stress compared to Ct-groups. Generally, the most remarkable response was revealed in the CtIBU-group, and distortion of individual effects was established in combined exposures. The qualification of stress-neutral and stress-positive populations was proposed for Pr- and Ct-populations correspondingly. Inter-site peculiarities must be taken into consideration when the environmental impact of MP and pharmaceuticals is evaluated.

Center Variability in Patient Outcomes Following HeartMate 3 Implantation: An Analysis of the MOMENTUM 3 Trial.

BACKGROUND: As left ventricular assist device (LVAD) survival rates continue to improve, evaluating site-specific variability in outcomes can facilitate identifying targets for quality-improvement initiative opportunities in the field. METHODS: Deidentified center-specific outcomes were analyzed for HeartMate 3 (HM3) patients enrolled in the MOMENTUM 3 pivotal and continued access protocol trials. Centers < 25th percentile for HM3 volumes were excluded. Variability in risk-adjusted center mortality was assessed at 90 days and 2 years (conditional upon 90-day survival). Adverse event (AE) rates were compared across centers. RESULTS: In the 48 included centers (1958 patients), study-implant volumes ranged between 17 and 106 HM3s. Despite similar trial-inclusion criteria, patient demographics varied across sites, including age quartile ((Q)1-Q3:57-62 years), sex (73%-85% male), destination therapy intent (60%-84%), and INTERMACS profile 1-2 (16%-48%). Center mortality was highly variable, nadiring at ≤ 3.6% (≤ 25th percentile) and peaking at ≥ 10.4% (≥ 75th percentile) at 90 days and ≤ 10.2% and ≥ 18.7%, respectively, at 2 years. Centers with low mortality rates tended to have lower 2-year AE rates, but no center was a top performer for all AEs studied. CONCLUSIONS: Mortality and AEs were highly variable across MOMENTUM 3 centers. Studies are needed to improve our understanding of the drivers of outcome variability and to ascertain best practices associated with high-performing centers across the continuum of intraoperative to chronic stages of LVAD support.

Sensitivity to Pulse Phase Duration as a Marker of Neural Health Across Cochlear Implant Recipients and Electrodes.

In cochlear implants, loudness has been shown to grow more slowly with increasing pulse phase duration (PPD) than with pulse amplitude (PA), possibly due to "leaky" charge integration. This leakiness has been recently quantified in terms of "charge integration efficiency," defined as the log difference between the PPD dynamic range and PA dynamic range (both expressed in charge units), relative to a common threshold anchor. Such leakiness may differ across electrodes and/or test ears, and may reflect underlying neural health. In this study, we examined the across-site variation of charge integration in recipients of Cochlear© devices. PPD and PA dynamic ranges were measured relative to two threshold anchors with either a 25- or 50-microsecond PPD. Strength-duration functions, previously shown to relate to survival of spiral ganglion cells and peripheral processes, were compared to charge integration efficiency on selected electrodes. Results showed no significant or systematic relationship between the across-site variation in charge integration efficiency and electrode position or threshold levels. Charge integration efficiency was poorer with the 50-µs threshold anchor, suggesting that greater leakiness was associated with larger PPD dynamic ranges. Poorer and more variable charge integration efficiency across electrodes was associated with longer duration of any hearing loss, consistent with the idea that poor integration is related to neural degeneration. More variable integration efficiency was also associated with poorer speech recognition performance across test ears. The slopes of the strength-duration functions at maximum acceptable loudness were significantly correlated with charge integration efficiency. However, the strength-duration slopes were not predictive of duration of any hearing loss or speech recognition performance in our participants. As such, charge integration efficiency may be a better candidate to measure leakiness in neural populations across the electrode array, as well as the general health of the auditory nerve in human cochlear implant recipients.

Caesium-137 in mountain flora with emphasis on reindeer's diet - Spatial and temporal trends.

The present study summarizes three decades of studies on 137Cs transfer to various species of lichens, graminoids, herbs and woody plants across a ~3000 km2 area used as mountain pasture for reindeer and other ruminants. The investigation comprised of field studies covering the period 2011-2016, and a compilation of studies and data for the preceding period (1986-2010). Altogether, more than 700 individual vegetation samples were considered. For lichens, relatively fast decrease in contamination levels was observed during the first decade after the Chernobyl fallout (ecological half-time of about 3 years). For later years there seems to be a continuous re-contamination which results in a "steady state" where time-trends are mainly governed by physical decay of 137Cs. For green plants, decline in transfer factors (TF) (i.e. the ratio between activity concentration in vegetation and activity density in soil) during the period 1986-2012 was not as pronounced as for lichens: Some species showed significant decrease with time, while others did not. 25-30 years after the Chernobyl accident, 137Cs levels in lichens and green plants were significantly dependent on the levels in soil (R2 between 0.53 and 0.57), but there were also some significant differences in transfer between sampling sites. Moreover, marked variability in TFs was found between different plant species growing at the same site, whereas such differences were not found for reindeer lichens.

Site-Specific Amino Acid Distributions Follow a Universal Shape.

In many applications of evolutionary inference, a model of protein evolution needs to be fitted to the amino acid variation at individual sites in a multiple sequence alignment. Most existing models fall into one of two extremes: Either they provide a coarse-grained description that lacks biophysical realism (e.g., dN/dS models), or they require a large number of parameters to be fitted (e.g., mutation-selection models). Here, we ask whether a middle ground is possible: Can we obtain a realistic description of site-specific amino acid frequencies while severely restricting the number of free parameters in the model? We show that a distribution with a single free parameter can accurately capture the variation in amino acid frequency at most sites in an alignment, as long as we are willing to restrict our analysis to predicting amino acid frequencies by rank rather than by amino acid identity. This result holds equally well both in alignments of empirical protein sequences and of sequences evolved under a biophysically realistic all-atom force field. Our analysis reveals a near universal shape of the frequency distributions of amino acids. This insight has the potential to lead to new models of evolution that have both increased realism and a limited number of free parameters.

Testing the hypothesis of hierarchical predictability in ecological restoration and succession.

To advance predictive ecology, the hypothesis of hierarchical predictability proposes that community measures for which species are interchangeable (e.g., structure and species richness) are more predictable than measures for which species identity matters (e.g., community composition). Predictability is hypothesized to decrease for response measures in order of the following categories: structure, species richness, function, and species composition. We tested this hypothesis using a 14-year, oak savanna-prairie restoration experiment that removed non-native pine plantations at 24 sites in northwestern Ohio, USA. Based on 24 response measures, the data showed minimal support for the hypothesis, because response measures varied in predictability within categories. Half of response measures had over half their variability modeled using fixed (restoration treatment and year) and random plot effects, and these "predictable" measures occurred in all four categories. Pine basal area, environment (e.g., soil texture), and antecedent vegetation accounted for over half the variation in change within the first three post-restoration years for 77% of response measures. Change between the 3rd and 14th years was less predictable, but most restoration measures increased favorably via sites achieving them in unique ways. We propose that variation will not conform with the hypothesis of hierarchical predictability in ecosystems with vegetation dynamics driven by stochastic processes such as seed dispersal, or where vegetation structure and species richness are influenced by species composition. The ability to predict a community measure may be more driven by the number of combinations of casual factors affecting a measure than by the number of values it can have.

Intermediate divergence levels maximize the strength of structure-sequence correlations in enzymes and viral proteins.

Structural properties such as solvent accessibility and contact number predict site-specific sequence variability in many proteins. However, the strength and significance of these structure-sequence relationships vary widely among different proteins, with absolute correlation strengths ranging from 0 to 0.8. In particular, two recent works have made contradictory observations. Yeh et al. (Mol. Biol. Evol. 31:135-139, 2014) found that both relative solvent accessibility (RSA) and weighted contact number (WCN) are good predictors of sitewise evolutionary rate in enzymes, with WCN clearly out-performing RSA. Shahmoradi et al. (J. Mol. Evol. 79:130-142, 2014) considered these same predictors (as well as others) in viral proteins and found much weaker correlations and no clear advantage of WCN over RSA. Because these two studies had substantial methodological differences, however, a direct comparison of their results is not possible. Here, we reanalyze the datasets of the two studies with one uniform analysis pipeline, and we find that many apparent discrepancies between the two analyses can be attributed to the extent of sequence divergence in individual alignments. Specifically, the alignments of the enzyme dataset are much more diverged than those of the virus dataset, and proteins with higher divergence exhibit, on average, stronger structure-sequence correlations. However, the highest structure-sequence correlations are observed at intermediate divergence levels, where both highly conserved and highly variable sites are present in the same alignment.

Time dependent analysis of assay comparability: a novel approach to understand intra- and inter-site variability over time.

We demonstrate here a novel use of statistical tools to study intra- and inter-site assay variability of five early drug metabolism and pharmacokinetics in vitro assays over time. Firstly, a tool for process control is presented. It shows the overall assay variability but allows also the following of changes due to assay adjustments and can additionally highlight other, potentially unexpected variations. Secondly, we define the minimum discriminatory difference/ratio to support projects to understand how experimental values measured at different sites at a given time can be compared. Such discriminatory values are calculated for 3 month periods and followed over time for each assay. Again assay modifications, especially assay harmonization efforts, can be noted. Both the process control tool and the variability estimates are based on the results of control compounds tested every time an assay is run. Variability estimates for a limited set of project compounds were computed as well and found to be comparable. This analysis reinforces the need to consider assay variability in decision making, compound ranking and in silico modeling.

Amino-acid site variability among natural and designed proteins.

Computational protein design attempts to create protein sequences that fold stably into pre-specified structures. Here we compare alignments of designed proteins to alignments of natural proteins and assess how closely designed sequences recapitulate patterns of sequence variation found in natural protein sequences. We design proteins using RosettaDesign, and we evaluate both fixed-backbone designs and variable-backbone designs with different amounts of backbone flexibility. We find that proteins designed with a fixed backbone tend to underestimate the amount of site variability observed in natural proteins while proteins designed with an intermediate amount of backbone flexibility result in more realistic site variability. Further, the correlation between solvent exposure and site variability in designed proteins is lower than that in natural proteins. This finding suggests that site variability is too uniform across different solvent exposure states (i.e., buried residues are too variable or exposed residues too conserved). When comparing the amino acid frequencies in the designed proteins with those in natural proteins we find that in the designed proteins hydrophobic residues are underrepresented in the core. From these results we conclude that intermediate backbone flexibility during design results in more accurate protein design and that either scoring functions or backbone sampling methods require further improvement to accurately replicate structural constraints on site variability.