Pattern-based clustering of daily weigh-in trajectories using dynamic time warping

“Smart”-scales are a new tool for frequent monitoring of weight change as well as weigh-in behavior. These scales give researchers the opportunity to discover patterns in the frequency that individuals weigh themselves over time, and how these patterns are associated with overall weight loss. Our motivating data come from an 18-month behavioral weight loss study of 55 adults classified as overweight or obese who were instructed to weigh themselves daily. Adherence to daily weigh-in routines produces a binary times series for each subject, indicating whether a participant weighed in on a given day. To characterize weigh-in by time-invariant patterns rather than overall adherence, we propose using hierarchical clustering with dynamic time warping (DTW). We perform an extensive simulation study to evaluate the performance of DTW compared to Euclidean and Jaccard distances to recover underlying patterns in adherence time series. In addition, we compare cluster performance using cluster validation indices (CVIs) under the single, average, complete, and Ward linkages and evaluate how internal and external CVIs compare for clustering binary time series. We apply conclusions from the simulation to cluster our real data and summarize observed weigh-in patterns. Our analysis finds that the adherence trajectory pattern is significantly associated with weight loss.     

Toward a hypothesis-free understanding of how phosphorylation dynamically impacts protein turnover

The turnover measurement of proteins and proteoforms has been largely facilitated by workflows coupling metabolic labeling with mass spectrometry (MS), including dynamic stable isotope labeling by amino acids in cell culture (dynamic SILAC) or pulsed SILAC (pSILAC). Very recent studies including ours have integrated themeasurement of post-translational modifications (PTMs) at the proteome level (i.e., phosphoproteomics) with pSILAC experiments in steady state systems, exploring the link between PTMs and turnover at the proteome-scale. An open question in the field is how to exactly interpret these complex datasets in a biological perspective. Here, we present a novel pSILAC phosphoproteomic dataset which was obtained during a dynamic process of cell starvation using data-independent acquisition MS (DIA-MS). To provide an unbiased “hypothesis-free” analysis framework, we developed a strategy to interrogate how phosphorylation dynamically impacts protein turnover across the time series data. With this strategy, we discovered a complex relationship between phosphorylation and protein turnover that was previously underexplored. Our results further revealed a link between phosphorylation stoichiometry with the turnover of phosphorylated peptidoforms. Moreover, our results suggested that phosphoproteomic turnover diversity cannot directly explain the abundance regulation of phosphorylation during cell starvation, underscoring the importance of future studies addressing PTM site-resolved protein turnover.     

Environmental diversity: on the best-possible use of surrogate data for assessing the relative biodiversity of sets of areas

The conservation goal of representation of biodiversity (in the broad sense of all species) in protected areas requires best-possible use of available surrogate information. One standard approach is based on indicator groups of taxa. A minimum set of areas having at least one representation of each indicator species is taken to be representative of other organisms. This same minimum-set approach is adapted to other attributes of biodiversity, for example, derived environmental clusters. A weakness of these approaches is that useful information is lost; for example, for environmental clusters, there is no distinction made either among or within clusters. A more powerful surrogate approach can use some expression of environmental and/or biotic pattern so that variation among areas is seen as part of a continuum rather than partitioned into arbitrary clusters/attributes. The challenge in using pattern effectively is to adopt a robust model for the relationship between pattern and the underlying units of biodiversity, i.e. species. An environmental space (a continuum or ordination pattern), combined with the standard ecological continuum model relating species to environmental space, has advantages over other patterns based on hierarchy or distance matrices. Because an environmental space can be estimated either directly (observed environmental data) or indirectly (data on indicator groups), the corresponding surrogate-measure of biodiversity, environmental diversity (ED) makes best-possible use of either kind of data. We conclude that the arbitrariness of the attribute approach can be replaced by a robust surrogate pattern approach that is flexible and avoids unwarranted assumptions.     

Typology of macrofaunal assemblages: a tool for the management of running waters in The Netherlands

A survey was carried out at 156 sites, situated in streams in the province of Overijssel (The Netherlands), to describe the macroinvertebrate assemblages and their environments. Fifty-six environmental variables were measured once at each sampling site. The main aim was to describe a typology of stream for this region.Different multivariate analysis techniques (clustering and ordination) were used in combination with ecological information on individual taxa to derive and describe site groups in terms of taxonomic composition and mean environmental conditions. The resulting site groups were termed cenotypes.Eleven cenotypes were distinguished. Differences between cenotypes were attributed to (combinations of) environmental key factors, namely, dimensions (width and depth), morphological (profile shape) and hydraulic stream characteristics, duration of drought and load of organic material.The typology offers a basis to be used for regional stream management and nature conservation. Efforts to improve stream ecosystems should be directed at the physical and hydraulic conditions.Typological studies are needed (especially in semi-natural landscapes) if we are to better understand, manage and conserve freshwater biota.     

Modulated red blood cell survival by membrane protein clustering

Human and murine blood cells treated with ZnCl₂ and bis(sulfosuccinimidyl)suberate (BS³) (a cross linking agent) undergo band 3 clustering and binding of hemoglobin to red blood cell membrane proteins. These clusters induce autologous IgG binding and complement fixation, thus favouring the phagocytosis of ZnCl₂/BS³ treated cells by macrophages. The extension of red blood cell opsonization can be easily modulated by changing the ZnCl₂ concentration in the 0.1–1.0 mM range thus providing an effective way to affect blood cell recognition by macrophages. In fact, murine erythrocytes treated with increasing ZnCl₂ concentrations have proportionally reduced survivals when reinjected into the animal. Furthermore, the organ sequestration of ZnCl₂/BS³ treated cells strongly resembles the typical distribution of the senescent cells. Since the ZnCl₂/BS³ treatment can also be performed on red blood cells loaded with drugs or other substances, this procedure is an effective drug-targeting system to be used for the delivery of molecules to peritoneal, liver and spleen macrophages.     

Clustering of fatty acids in phospholipid bilayers

From electrophoresis experiments it is concluded that acidic phospholipids incorporated in liquid crystalline phosphatidylcholine bilayers at neutral pH are randomly distributed. The same is true for spin-labelled fatty acids. In contrast, long chain fatty acids are not fully ionized at neutral pH and appear to be clustered, i.e. they segregate out into patches. Only at $\text{pH}\text{>11}$ is the fatty acid-COOH group fully ionized and charge repulsion leads to a random distribution of the fatty acid within the plane of the bilayer.     

Redistribution of intramembrane particles of human erythrocytes induced by HVJ (Sendai virus): A prerequisite for the virus-induced cell fusion

Aggregation of intramembrane particles of human erythrocytes was found to be induced by HVJ (Sendai virus) under conditions which lead to cell fusion. Degree of polyerythrocyte formation was compared under a variety of conditions with extent of cluster formation observed with the same preparations. Both structural changes of the membranes, ie, fusion and clustering of the particles, behaved very similarly under widely different virus-to-cell ratios and over the time course of cell fusion. Furthermore, by inclusion of high concentrations of antispectrin antibodies within the ghosts, inhibition of clustering of intramembrane particles and hindrance of virus-induced cell fusion were found to occur simultaneously. Antibodies by themselves did not induce aggregation of particles under isotonic conditions, whereas particle clustering could be induced under hypotonic conditions at antibody concentrations causing partial cross-linking of spectrin molecules. In conclusion, clustering of intramembrane particles seems to be required for virus-induced fusion of human erythrocytes.     

Hierarchical clustering of 54 races and strains of the mulberry silkworm,Bombyx mori L: Significance of biochemical parameters

Summary A detailed analysis was undertaken to test the efficacy of hierarchical agglomerative clustering (UPGMA method) in grouping the races and strains of the mulberry silkworm, Bombyx moti L., and to ascertain the importance of biochemical parameters in the clustering process. The analysis was based on data from two rearing seasons with 54 selected races/strains of different geographic origin and varying yield potentials. The results indicate that seven clusters can be realised with yield parameters alone, whereas the inclusion of biochemical parameters in clustering resulted into two broad groups: one having all the breeds with high cocoon weight and shell weight, the other having all the low-yielding silkworm strains both from India and from other countries. Further sub-grouping under these two groups highlights genetical differences associated with the differentiation of various groups of races in temperate and tropical areas as well as their significance for silkworm breeding. Estimates of all ten variables were further subjected to quick clustering and the results showed that cluster 5, constituted by 38 lowyielding strains of India, China and Europe, had the highest values of the final cluster centre for amylase and the effective rate of rearing (ERR), while clusters 1 and 4 had the highest values for invertase and alkaline phosphatase. The evolutionary aspect of the genetic channelisation of silkworm races from various countries is discussed against the background of differences in the biochemical parameters and yield variables.     

Cell shape changes and transmembrane receptor uncoupling induced by tertiary amine local anesthetics

Tertiary amine local anesthetics (dibucaine, Tetracaine, procaine, etc.) modify cell morphology, concanavalin A (Con A)-mediated agglutinability and redistribution of Con A receptors. Con A agglutination of untransformed mouse 3T3 cells was enhanced at low concentrations of local anesthetics, and the dynamics of fluorescent-Con A indicated that ligand-induced clustering was increased in the presence of the drugs. In contast, these drugs inhibited Con A-induced receptor capping on mouse spleen cells. These effects can be duplicated by combinations of vinblastine (or colchicine) and cytochalasin B suggesting that local anesthetics act on microtubule cell surface receptor mobility and distribution. It is proposed that tertiary amine local anesthetics displace plasma membrane-bond Ca²⁺, resulting in disengagement of microfilament systems from the plasma membrane and increased cellular Ca²⁺ concentration to levels which disrupt microtubular organization. The possible involvement of cellular Ca²⁺ in cytoskeletal destruction by local anesthetics was investigated utilizing Ca²⁺-specific ionophores A23187 and X537A. In media containing Ca²⁺ and cytochalasin B these ionophores caused effects similar to tertiary amine local anesthetics.