New characteristic signatures from time-dependent static light scattering during polymer depolymerization,with application to proteoglycan subunit degradation

Models were developed for the time-dependent light scattering intensity for simply branched (“comb”) polymers undergoing one or more of three distinguishable degradation mechanisms: (a) stripping off the side chains, (b) randomly degrading off the side chains, and (c) randomly degrading the backbone. The model equations were applied to the analysis of different types of degradation of simply branched biopolymers—bovine nasal cartilage proteoglycan subunits (or “monomers”); NaOH stripped off the glycosaminoglycan (GAG) chains from the protein backbone [mechanism (a)], whereas hyaluronidase seemed to randomly cleave the GAG side chains [mechanism (b)], and HCl both stripped the GAG side chains and randomly cleaved the protein backbone [combined mechanisms (a) and (c)]. The reactions were followed with time-dependent multiangle, static light scattering. The time-resolved total scattering technique allowed degradation rate constants and percentage of material in the branched polymer backbone and side chains to be determined, in addition to the mechanisms involved. These new time-dependent light scattering profiles are added to the growing library of functions from which deductions can be made concerning polymer structure and associated degradation mechanisms and kinetics. These conclusions, drawn from time-dependent “batch” light scattering, are substantiated by preliminary size exclusion chromatography results and chemical binding assays for sulfated GAGs. © 1995 John Wiley & Sons, Inc.     

Simulation of Lamellar Phase Transitions in Block Copolymers and Surfactants

Abstract

Simulations of the lamellar phase transitions of symmetric amphiphilic chains are carried out on a cubic lattice, with the amphiphilic chain length N varied from 6 to 48 lattice sites, corresponding to lengths ranging from surfactants to short block copolymers. We find that the effective interaction energy parameter χN (which incorporates the effect of added solvant) at which the transition from the lamellar ordered state to the disordered state occurs is roughly equal to 18-21. While this result is consistent with an extrapolation of the Fredrickson-Helfand weak-segragation theory to N values in the range of the simulations, the amplitude of the sinusoidal compositional wave in the ordered state near the transition is large for all N studied, in disagreement with the weak segregation theories. Thus, for values of N up to 48, the transition occurs in a “moderate,” rather than weak-segregation regime. Near the disordering transition, fluctuating “bridge” or “hole” defects in the lamellae spontaneously appear; with heating these proliferate and lead to the disordering transition. These fluctuating bridges might help explain anomalous diffusion and rheological behavior observed near the disordering transition. We also find that in the ordered state near the transition, the orientational order parameter, which is proportional to the intrinsic birefringence, falls rapidly with increasing N, roughly as 1.5 N^-2.     

Biophysical properties of membrane lipids of anammox bacteria: II. Impact of temperature and bacteriohopanoids

Anammox bacteria possess unique membranes that are mainly comprised of phospholipids with extraordinary “ladderane” hydrocarbon chains containing 3 to 5 linearly concatenated cyclobutane moieties that have been postulated to form relatively impermeable membranes. In a previous study, we demonstrated that purified ladderane phospholipids form fluid-like mono- and bilayers that are tightly packed and relatively rigid. Here we studied the impact of temperature and the presence of bacteriohopanoids on the lipid density and acyl chain ordering in anammox membranes using Langmuir monolayer and fluorescence depolarization experiments on total lipid extracts. We showed that anammox membrane lipids of representatives of Candidatus “Kuenenia stuttgartiensis”, Candidatus “Brocadia fulgida” and Candidatus “Scalindua” were closely packed and formed membranes with a relatively high acyl chain ordering at the temperatures at which the cells were grown. Our findings suggest that bacteriohopanoids might play a role in maintaining the membrane fluidity in anammox cells.     

Conformational energy calculations with averaged potential functions: Application to the repeat peptides of elastin

We present a method that can reduce conformational energy calculations for an arbitrary peptide consisting of n residues (n-peptide) to the complexity of a computation for (Gly)_n. This reduction, and the concomitant savings in computer time, is accomplished by replacing all side chains, as well as the backbone C^αH^α and C^αH₂^α groups, by “interaction centers.” The backbone CONH group is left intact in order to preserve its directional character. The interaction centers “see” each other, and the atoms of the CONH group via Boltzmann and space-averaged effective center-center and center-atom potentials, respectively. This averaged-interaction method is tested on the repeat tetra-, penta-, and hexapeptides of elastin, Val-Pro-Gly-Gly (VPGG), Val-Pro-Gly-Val-Gly (VPGVP), and Ala-Pro-Gly-Val-Gly-Val (APGVGV), using the stereoalphabet strategy for the energy calculations. The excellent qualitative and quantitative agreement we obtain with both full atom-atom calculations and extensive nmr data, coupled with the order-of-magnitude reduction in computer time, augurs well for the potential usefulness of the method.     

Green beards and kindred spirits: A preliminary mathematical model of altruism toward nonkin who bear similarities to the giver

This brief mathematical model of “the green beard effect” is an attempt to extend the concept of kin selection beyond kin, to help explain the broad reach of cooperation sometimes observed in civilized societies. We assume that individual differences in human behavior are founded on genes as well as environment and therefore that reproductive success is a long-term determinant of human affairs. We further assume that many of the genetic sources of behavioral heterogeneity among individuals are not highly concentrated along family lines. The perceptive altruists we model reach out into the population at large, giving increases in fitness to those whose phenotypes include one or another aspect of some behavioral trait the altruist values in himself and others. The model points to factors that influence whether an individual prefers to be altruistic toward those with whom he or she shares rare qualities or more common distinguishing qualities; these factors include the exhaustibility of the altruist's reserves, and the necessity of concentrating efforts locally versus the possibility of effectively broadcasting a particular sort of benefit.     

Entropy Hotspots for the Binding of Intrinsically Disordered Ligands to a Receptor Domain

Proline-rich motifs (PRMs) are widely used for mediating protein-protein interactions with weak binding affinities. Because they are intrinsically disordered when unbound, conformational entropy plays a significant role for the binding. However, residue-level differences of the entropic contribution in the binding of different ligands remain not well understood. We use all-atom molecular dynamics simulation and the maximal information spanning tree formalism to analyze conformational entropy associated with the binding of two PRMs, one from the Abl kinase and the other from the nonstructural protein 1 of the 1918 Spanish influenza A virus, to the N-terminal SH3 (nSH3) domain of the CrkII protein. Side chains of the stably folded nSH3 experience more entropy change upon ligand binding than the backbone, whereas PRMs involve comparable but heterogeneous entropy changes among the backbone and side chains. In nSH3, two conserved nonpolar residues forming contacts with the PRM experience the largest side-chain entropy loss. In contrast, the C-terminal charged residues of PRMs that form polar contacts with nSH3 experience the greatest side-chain entropy loss, although their “fuzzy” nature is attributable to the backbone that remains relatively flexible. Thus, residues that form high-occupancy contacts between nSH3 and PRM do not reciprocally contribute to entropy loss. Furthermore, certain surface residues of nSH3 distal to the interface with PRMs gain entropy, indicating a nonlocal effect of ligand binding. Comparing between the PRMs from cAbl and nonstructural protein 1, the latter involves a larger side-chain entropy loss and forms more contacts with nSH3. Consistent with experiments, this indicates stronger binding of the viral ligand at the expense of losing the flexibility of side chains, whereas the backbone experiences less entropy loss. The entropy “hotspots” as identified in this study will be important for tuning the binding affinity of various ligands to a receptor.     

How do we decide when (not) to free-ride? Risk tolerance predicts behavioral plasticity in cooperation

In collaborations, group productivity typically increases with more cooperators, but is also often subject to diminishing returns. This pattern provides a different view about cooperation from traditional social dilemmas: defection is not necessarily the dominant strategy. Rather, a frequency-dependent “anti-conformist” strategy (cooperate if many others defect, and vice versa) is often individually rational. This study addresses human cooperation under such marginally diminishing group productivity, focusing on the plasticity of cooperative choices. We conducted a two-part “team foraging” experiment, in which the most- or least-cooperative members in the first part were re-grouped separately for the second part. We observed that cooperating and defecting “types” emerged within a group over time but did not completely persist across groups, with some of the most cooperative members switching to become the least cooperative (and vice versa). Risk attitude was a key factor in this switching behavior: greater risk-takers showed greater behavioral plasticity. These results imply that human cooperation may be more context-dependent and behaviorally plastic than previously thought.     

An empirical energy function for threading protein sequence through the folding motif

In this paper we present a new residue contact potantial derived by statistical analysis of protein crystal structures. This gives mean hydrophobic and pairwise contact energies as a function of residue type and distance interval. To test the accuracy of this potential we generate model structures by “threading” different sequences through backbone folding motifs found in the structural data base. We find that conformational energies calculated by summing contact potentials show perfect specificity in matching the correct sequences with each globular folding motif in a 161-protcin data set. They also identify correct models with the core folding motifs of heme-rythrin and immunoglobulin McPC603 V₁-do- main, among millions of alternatives possible when we align subsequences with α-helices and β-strands, and allow for variation in the lengths of intervening loops. We suggest that contact potentials reflect important constraints on nonbonded interaction in native proteins, and that “threading” may be useful for structure prediction by recognition of folding motif. © 1993 Wiley-Liss, Inc.     

Side-chain entropy and packing in proteins.

What role does side-chain packing play in protein stability and structure? To address this question, we compare a lattice model with side chains (SCM) to a linear lattice model without side chains (LCM). Self-avoiding configurations are enumerated in 2 and 3 dimensions exhaustively for short chains and by Monte Carlo sampling for chains up to 50 main-chain monomers long. This comparison shows that (1) side-chain degrees of freedom increase the entropy of open conformations, but side-chain steric exclusion decreases the entropy of compact conformations, thus producing a substantial entropy that opposes folding; (2) there is a side-chain “freezing” or ordering, i.e., a sharp decrease in entropy, near maximum compactness; and (3) the different types of contacts among side chains (s) and main-chain elements (m) have different frequencies, and the frequencies have different dependencies on compactness. mm contacts contribute significantly only at high densities, suggesting that main-chain hydrogen bonding in proteins may be promoted by compactness. The distributions of mm, ms, and ss contacts in compact SCM configurations are similar to the distributions in protein structures in the Brookhaven Protein Data Bank. We propose that packing in proteins is more like the packing of nuts and bolts in a jar than like the pairwise matching of jigsaw puzzle pieces.     

Indirect reciprocity and the evolution of “moral signals”

Signals regarding the behavior of others are an essential element of human moral systems and there are important evolutionary connections between language and large-scale cooperation. In particular, social communication may be required for the reputation tracking needed to stabilize indirect reciprocity. Additionally, scholars have suggested that the benefits of indirect reciprocity may have been important for the evolution of language and that social signals may have coevolved with large-scale cooperation. This paper investigates the possibility of such a coevolution. Using the tools of evolutionary game theory, we present a model that incorporates primitive “moral signaling” into a simple setting of indirect reciprocity. This model reveals some potential difficulties for the evolution of “moral signals.” We find that it is possible for “moral signals” to evolve alongside indirect reciprocity, but without some external pressure aiding the evolution of a signaling system, such a coevolution is unlikely.     

EPISTASIS AND THE INCREASE IN ADDITIVE GENETIC VARIANCE: IMPLICATIONS FOR PHASE 1 OF WRIGHT'S SHIFTING-BALANCE PROCESS

Central to Wright's shifting-balance theory is the idea that genetic drift and selection in systems with gene interaction can lead to the formation of “adaptive gene complexes.” The theory of genetic drift has been well developed over the last 60 years; however, nearly all of this theory is based on the assumption that only additive gene effects are acting. Wright's theory was developed recognizing that there was a “universality of interaction effects,” which implies that additive theory may not be adequate to describe the process of differentiation that Wright was considering. The concept of an adaptive gene complex implies that an allele that is favored by individual selection in one deme may be removed by selection in another deme. In quantitative genetic terms, the average effects of an allele relative to other alleles changes from deme to deme. The model presented here examines the variance in local breeding values (LBVs) of a single individual and the covariance in the LBVs of a pair of individuals mated in the same deme relative to when they are mated in different demes. Local breeding value is a measure of the average effects of the alleles that make up that individual in a particular deme. I show that when there are only additive effects the covariance between the LBVs of individuals equals the variance in the LBV of an individual. As the amount of epistasis in the ancestral population increases, the variance in the LBV of an individual increases and the covariance between the LBVs of a pair of individuals decreases. The divergence in these two values is a measure of the extent to which the LBV of an individual varies independently of the LBVs of other individuals. When this value is large, it means that the relative ordering of the average effects of alleles will change from deme to deme. These results confirm an important component of Wright's shifting-balance theory: When there is gene interaction, genetic drift can lead to the reordering of the average effects of alleles and when coupled with selection this will lead to the formation of the adaptive gene complexes.     

Wetting of nonconserved residue‐backbones: A feature indicative of aggregation associated regions of proteins

Aggregation is an irreversible form of protein complexation and often toxic to cells. The process entails partial or major unfolding that is largely driven by hydration. We model the role of hydration in aggregation using “Dehydrons.” “Dehydrons” are unsatisfied backbone hydrogen bonds in proteins that seek shielding from water molecules by associating with ligands or proteins. We find that the residues at aggregation interfaces have hydrated backbones, and in contrast to other forms of protein–protein interactions, are under less evolutionary pressure to be conserved. Combining evolutionary conservation of residues and extent of backbone hydration allows us to distinguish regions on proteins associated with aggregation (non‐conserved dehydron‐residues) from other interaction interfaces (conserved dehydron‐residues). This novel feature can complement the existing strategies used to investigate protein aggregation/complexation. Proteins 2016; 84:254–266. © 2015 Wiley Periodicals, Inc.     

Experimental demonstration of the benefits of somatic fusion and the consequences for allorecognition

Allorecognition, the ability to distinguish “self” from “nonself” based on allelic differences at allorecognition loci, is common in all domains of life. Allorecognition restricts the opportunities for social parasitism, and is therefore crucial for the evolution of cooperation. However, the maintenance of allorecognition diversity provides a paradox. If allorecognition is costly relative to cooperation, common alleles will be favored. Thus, the cost of allorecognition may reduce the genetic variation upon which allorecognition crucially relies, a prediction now known as “Crozier's paradox.” We establish the relative costs of allorecognition, and their consequences for the short‐term evolution of recognition labels theoretically predicted by Crozier. We use fusion among colonies of the fungus Neurospora crassa, regulated by highly variable allorecognition genes, as an experimental model system. We demonstrate that fusion among colonies is mutually beneficial, relative to absence of fusion upon allorecognition. This benefit is due not only to absence of mutual antagonism, which occurs upon allorecognition, but also to an increase in colony size per se. We then experimentally demonstrate that the benefit of fusion selects against allorecognition diversity, as predicted by Crozier. We discuss what maintains allorecognition diversity.     

麋鹿行为谱及PAE编码系统

以麋鹿为实例,通过辨识行为的基本单元,区别了“姿势”、“动作”和“环境”,分解了动物行为的层次,然后根据行为的适应和社群机能归类,建立了以“姿势—动作—环境”为轴心的,以生态功能为分类依据的动物行为分类编码系统（PAE编码分类系统）。PAE编码分类系统以集合论为基础,明确了动物行为的三要素：姿势、动作和生态环境之间的关系,避免了笼统地将动物的姿势、动作和行为混为一谈的做法,区分了动物行为的组成要素和结构层次。行为要素编码方法为动物行为学研究提供了一个新的生长点。在继承前人工作的基础上,记录了有关麋鹿的姿势、动作和行为达200多种,还区别了各种行为在雄性、雌性和幼体之间的相对发生频次以及发生季节。     

Evaluating the nucleus effect on the dynamic indentation behavior of cells

The effect of the nucleus on the cell mechanical behavior was investigated based on the dynamic indentation response of cells under a spherical tip. A “two-component” cell model (including cytoplasm and nucleus) is used, and the dynamic indentation behavior is studied by a semiempirical method, which is established based on fitting the numerical simulation results of the quasi-static indentation response of cells. We found that the “routine analysis” (based on the Hertz’s contact solution of homogeneous model) significantly overestimated the nucleus effect on the overall cell indentation response due to the effects of the Hertz contact radius and the substrate stiffening. These effects are significantly stronger in the “two-component” cell model than in the homogeneous model. The inaccuracy created by the “routine analysis” slightly increases with the modulus ratio of nucleus to cytoplasm and the volume fraction of nucleus. Finally, the error sensitivity to the geometrical parameters used in the model is discussed, which shows the indentation analysis is not very sensitive to these parameters, and the reasonable assumptions for these parameters are effective. This systematic analysis can provide a useful guideline to understanding the mechanical behavior of cells and nuclei.     

Room temperature crystal structure of the fast switching M159T mutant of the fluorescent protein dronpa

The fluorescent protein Dronpa undergoes reversible photoswitching reactions between the bright “on” and dark “off” states via photoisomerization and proton transfer reactions. We report the room temperature crystal structure of the fast switching Met159Thr mutant of Dronpa at 2.0‐Å resolution in the bright on state. Structural differences with the wild type include shifted backbone positions of strand β8 containing Thr159 as well as an altered A‐C dimer interface involving strands β7, β8, β10, and β11. The Met159Thr mutation increases the cavity volume for the p‐hydroxybenzylidene‐imidazolinone chromophore as a result of both the side chain difference and the backbone positional differences. Proteins 2015; 83:397–402. © 2014 Wiley Periodicals, Inc.     

The evolution of cooperation by the Hankshaw effect

The evolution of cooperation—costly behavior that benefits others—faces one clear obstacle. Namely, cooperators are always at a competitive disadvantage relative to defectors, individuals that reap the benefits, but evade the cost of cooperation. One solution to this problem involves genetic hitchhiking, where the allele encoding cooperation becomes linked to a beneficial mutation, allowing cooperation to rise in abundance. Here, we explore hitchhiking in the context of adaptation to a stressful environment by cooperators and defectors with spatially limited dispersal. Under such conditions, clustered cooperators reach higher local densities, thereby experiencing more mutational opportunities than defectors. Thus, the allele encoding cooperation has a greater probability of hitchhiking with alleles conferring stress adaptation. We label this probabilistic enhancement the “Hankshaw effect” after the character Sissy Hankshaw, whose anomalously large thumbs made her a singularly effective hitchhiker. Using an agent‐based model, we reveal a broad set of conditions that allow the evolution of cooperation through this effect. Additionally, we show that spite, a costly behavior that harms others, can evolve by the Hankshaw effect. While in an unchanging environment these costly social behaviors have transient success, in a dynamic environment, cooperation and spite can persist indefinitely.     

Behavior of red wood ants (Hymenoptera,Formicidae) during interaction with different symbiont partners

A comparative analysis of the behavior of Formica polyctena Först during interaction with different symbionts (free-living aphids Aphis grossulariae Kalt. and hidden larvae of the sawfly Blasticotoma filiceti Klug) was carried out. Red wood ants demonstrate different levels of functional differentiation in relatively constant groups of foragers collecting honeydew. A deep “professional” specialization with clear division of a number of tasks among foragers was studied in groups of ants tending aphids. Four professional groups of foragers with different tasks were revealed: “shepherds,” “guards,” “transporters,” and “scouts” (or “coordinators”). The groups of foragers caring for sawfly larvae mainly consist of unspecialized ants. Only few ants (about 5%) remain on duty on the fern plant near B. filiceti larvae and protect the food resource from competitors, especially from other ants. In addition, the ants demonstrate simpler behavior while collecting the larval excretion, resembling that at the sugar feeders. On the whole, the behavior of red wood ants is rather flexible. The level of functional differentiation in groups of foragers collecting honeydew is determined not only by the colony size and requirements but by the nature of their interaction with trophobionts, particularly, by the possibility of direct contact.     

Androgen-primed castrate males are sufficient for methamphetamine-facilitated increases in proceptive behavior in female rats

Methamphetamine (MA) is a psychomotor stimulant associated with increases in sex drive in both men and women. Women, however, are far more likely to face social disadvantages as a consequence of MA use, and their increased sexual motivation poses additional health concerns such as unplanned pregnancies. To better understand the mechanisms underlying MA-facilitated sexual motivation in females, we previously established a rodent model where a “binge”-type administration paradigm of MA to sexually receptive female rats significantly increases proceptive behavior in the presence of a sexually active, gonadally-intact male. Our previous work with this model has led us to consider whether the increases in proceptive behavior are truly indicative of increased sexual motivation, or instead a consequence of heightened motor responsivity. Here, we test whether MA-induced increases in proceptive behaviors are specific to a sexually relevant stimulus. Females' sexual, social, exploratory behaviors, and interaction times were scored during the exposure to stimulus males, including castrates, and dihydrotestosterone (DHT)-treated castrates. MA-treated females demonstrated significant increases in proceptive behaviors toward DHT-treated castrate males but not toward castrate males. While the non-MA-treated females did display proceptive behavior, there was no significant difference between behaviors elicited by DHT-CX males compared to CX males. Our results support the hypothesis that MA facilitates proceptive behavior only in response to specific, androgen mediated sexually-relevant cues.     

Residue-specific side-chain packing determines the backbone dynamics of transmembrane model helices

The transmembrane domains (TMDs) of membrane-fusogenic proteins contain an overabundance of β-branched residues. In a previous effort to systematically study the relation among valine content, fusogenicity, and helix dynamics, we developed model TMDs that we termed LV-peptides. The content and position of valine in LV-peptides determine their fusogenicity and backbone dynamics, as shown experimentally. Here, we analyze their conformational dynamics and the underlying molecular forces using molecular-dynamics simulations. Our study reveals that backbone dynamics is correlated with the efficiency of side-chain to side-chain van der Waals packing between consecutive turns of the helix. Leu side chains rapidly interconvert between two rotameric states, thus favoring contacts to its i±3 and i±4 neighbors. Stereochemical restraints acting on valine side chains in the α-helix force both β-substituents into an orientation where i,i±3 interactions are less favorable than i,i±4 interactions, thus inducing a local packing deficiency at VV3 motifs. We provide a quantitative molecular model to explain the relationship among chain connectivity, side-chain mobility, and backbone flexibility. We expect that this mechanism also defines the backbone flexibility of natural TMDs.