A steady state analysis indicates that negative feedback regulation of PTP1B by Akt elicits bistability in insulin-stimulated GLUT4 translocation

Background  

The phenomenon of switch-like response to graded input signal is the theme involved in various signaling pathways in living systems. Positive feedback loops or double negative feedback loops embedded with nonlinearity exhibit these switch-like bistable responses. Such feedback regulations exist in insulin signaling pathway as well.     

A Dictyostelium chalone uses G proteins to regulate proliferation

Background  

Several studies have shown that organ size, and the proliferation of tumor metastases, may be regulated by negative feedback loops in which autocrine secreted factors called chalones inhibit proliferation. However, very little is known about chalones, and how cells sense them. We previously identified two secreted proteins, AprA and CfaD, which act as chalones in Dictyostelium. Cells lacking AprA or CfaD proliferate faster than wild-type cells, and adding recombinant AprA or CfaD to cells slows their proliferation.     

Analytical approximations for the amplitude and period of a relaxation oscillator

Background  

Analysis and design of complex systems benefit from mathematically tractable models, which are often derived by approximating a nonlinear system with an effective equivalent linear system. Biological oscillators with coupled positive and negative feedback loops, termed hysteresis or relaxation oscillators, are an important class of nonlinear systems and have been the subject of comprehensive computational studies. Analytical approximations have identified criteria for sustained oscillations, but have not linked the observed period and phase to compact formulas involving underlying molecular parameters.     

Opportunistic versus life-cycle-oriented decision making in multi-loop recovery: an eco-eco study on disposed vehicles

Purpose  

Multinational companies have recently been encouraged by government policies to implement Extended Producer Responsibility. One objective is to stimulate high-level recovery, and the other is to introduce life cycle thinking. This paper studies decision making in recovery, comparing opportunistic decision making with short-term profit maximization (usually leading to one loop) versus a life-cycle perspective (leading to multiple loops). The question is (1) which business benefits this brings as well as reduction of environmental impact and (2) whether companies should be inclined to think multi-loop and if so how governments could stimulate this.     

Modeling of loops in proteins: a multi-method approach

Background  

Template-target sequence alignment and loop modeling are key components of protein comparative modeling. Short loops can be predicted with high accuracy using structural fragments from other, not necessairly homologous proteins, or by various minimization methods. For longer loops multiscale approaches employing coarse-grained de novo modeling techniques should be more effective.     

Prediction of calcium-binding sites by combining loop-modeling with machine learning

Background  

Protein ligand-binding sites in the apo state exhibit structural flexibility. This flexibility often frustrates methods for structure-based recognition of these sites because it leads to the absence of electron density for these critical regions, particularly when they are in surface loops. Methods for recognizing functional sites in these missing loops would be useful for recovering additional functional information.     

Computing paths and cycles in biological interaction graphs

Background  

Interaction graphs (signed directed graphs) provide an important qualitative modeling approach for Systems Biology. They enable the analysis of causal relationships in cellular networks and can even be useful for predicting qualitative aspects of systems dynamics. Fundamental issues in the analysis of interaction graphs are the enumeration of paths and cycles (feedback loops) and the calculation of shortest positive/negative paths. These computational problems have been discussed only to a minor extent in the context of Systems Biology and in particular the shortest signed paths problem requires algorithmic developments.     

Diffusive coupling can discriminate between similar reaction mechanisms in an allosteric enzyme system

Background  

A central question for the understanding of biological reaction networks is how a particular dynamic behavior, such as bistability or oscillations, is realized at the molecular level. So far this question has been mainly addressed in well-mixed reaction systems which are conveniently described by ordinary differential equations. However, much less is known about how molecular details of a reaction mechanism can affect the dynamics in diffusively coupled systems because the resulting partial differential equations are much more difficult to analyze.     

Co-product allocation in life cycle assessments of seafood production systems: Review of problems and strategies

Background, Aim and Scope  

As Life Cycle Assessment is being increasingly applied to study fisheries and aquaculture systems, the LCA methodology must be adapted to address the unique aspects of these systems. The focus of this methodological paper is the specific allocation problems faced in studying seafood production systems and how they have been addressed to date.     

Reconstruction and logical modeling of glucose repression signaling pathways in Saccharomyces cerevisiae

Background  

In the yeast Saccharomyces cerevisiae, the presence of high levels of glucose leads to an array of down-regulatory effects known as glucose repression. This process is complex due to the presence of feedback loops and crosstalk between different pathways, complicating the use of intuitive approaches to analyze the system.     

Elementary signaling modes predict the essentiality of signal transduction network components

Background  

Understanding how signals propagate through signaling pathways and networks is a central goal in systems biology. Quantitative dynamic models help to achieve this understanding, but are difficult to construct and validate because of the scarcity of known mechanistic details and kinetic parameters. Structural and qualitative analysis is emerging as a feasible and useful alternative for interpreting signal transduction.     

Robustness from flexibility in the fungal circadian clock

Background  

Robustness is a central property of living systems, enabling function to be maintained against environmental perturbations. A key challenge is to identify the structures in biological circuits that confer system-level properties such as robustness. Circadian clocks allow organisms to adapt to the predictable changes of the 24-hour day/night cycle by generating endogenous rhythms that can be entrained to the external cycle. In all organisms, the clock circuits typically comprise multiple interlocked feedback loops controlling the rhythmic expression of key genes. Previously, we showed that such architectures increase the flexibility of the clock's rhythmic behaviour. We now test the relationship between flexibility and robustness, using a mathematical model of the circuit controlling conidiation in the fungus Neurospora crassa.     

On the boundary between economy and environment in life cycle assessment

Purpose

We investigate how the boundary between product systems and their environment has been delineated in life cycle assessment and question the usefulness and ontological relevance of a strict division between the two.

Methods

We consider flows, activities and impacts as general terms applicable to both product systems and their environment and propose that the ontologically relevant boundary is between the flows that are modelled as inputs to other activities (economic or environmental)—and the flows that—in a specific study—are regarded as final impacts, in the sense that no further feedback into the product system is considered before these impacts are applied in decision-making. Using this conceptual model, we contrast the traditional mathematical calculation of the life cycle impacts with a new, simpler computational structure where the life cycle impacts are calculated directly as part of the Leontief inverse, treating product flows and environmental flows in parallel, without the need to consider any boundary between economic and environmental activities.

Results and discussion

Our theoretical outline and the numerical example demonstrate that the distinctions and boundaries between product systems and their environment are unnecessary and in some cases obstructive from the perspective of impact assessment, and can therefore be ignored or chosen freely to reflect meaningful distinctions of specific life cycle assessment (LCA) studies. We show that our proposed computational structure is backwards compatible with the current practice of LCA modelling, while allowing inclusion of feedback loops both from the environment to the economy and internally between different impact categories in the impact assessment.

Conclusions

Our proposed computational structure for LCA facilitates consistent, explicit and transparent modelling of the feedback loops between environment and the economy and between different environmental mechanisms. The explicit and transparent modelling, combining economic and environmental information in a common computational structure, facilitates data exchange and re-use between different academic fields.

     

Regeneration of the radial nerve cord in the sea cucumber Holothuria glaberrima

Background  

Regeneration of neurons and fibers in the mammalian spinal cord has not been plausible, even though extensive studies have been made to understand the restrictive factors involved. New experimental models and strategies are necessary to determine how new nerve cells are generated and how fibers regrow and connect with their targets in adult animals. Non-vertebrate deuterostomes might provide some answers to these questions. Echinoderms, with their amazing regenerative capacities could serve as model systems; however, very few studies have been done to study the regeneration of their nervous system.     

Comparative analysis of cis-regulation following stroke and seizures in subspaces of conserved eigensystems

Background  

It is often desirable to separate effects of different regulators on gene expression, or to identify effects of the same regulator across several systems. Here, we focus on the rat brain following stroke or seizures, and demonstrate how the two tasks can be approached simultaneously.     

Function and evolution of the serotonin-synthetic <Emphasis Type="Italic">bas-1</Emphasis> gene and other aromatic amino acid decarboxylase genes in <Emphasis Type="Italic">Caenorhabditis</Emphasis>

Background  

Aromatic L-amino acid decarboxylase (AADC) enzymes catalyze the synthesis of biogenic amines, including the neurotransmitters serotonin and dopamine, throughout the animal kingdom. These neurotransmitters typically perform important functions in both the nervous system and other tissues, as illustrated by the debilitating conditions that arise from their deficiency. Studying the regulation and evolution of AADC genes is therefore desirable to further our understanding of how nervous systems function and evolve.     

Emergence and maintenance of functional modules in signaling pathways

Background  

While detection and analysis of functional modules in biological systems have received great attention in recent years, we still lack a complete understanding of how such modules emerge. One theory is that systems must encounter a varying selection (i.e. environment) in order for modularity to emerge. Here, we provide an alternative and simpler explanation using a realistic model of biological signaling pathways and simulating their evolution.     

The ups and downs of biological timers

Background  

The need to execute a sequence of events in an orderly and timely manner is central to many biological processes, including cell cycle progression and cell differentiation. For self-perpetuating systems, such as the cell cycle oscillator, delay times between events are defined by the network of interacting proteins that propagates the system. However, protein levels inside cells are subject to genetic and environmental fluctuations, raising the question of how reliable timing is maintained.