To spike,or when to spike?

Recent experimental reports have suggested that cortical networks can operate in regimes were sensory information is encoded by relatively small populations of spikes and their precise relative timing. Combined with the discovery of spike timing dependent plasticity, these findings have sparked growing interest in the capabilities of neurons to encode and decode spike timing based neural representations. To address these questions, a novel family of methodologically diverse supervised learning algorithms for spiking neuron models has been developed. These models have demonstrated the high capacity of simple neural architectures to operate also beyond the regime of the well established independent rate codes and to utilize theoretical advantages of spike timing as an additional coding dimension.     

To disaggregate or not to disaggregate,injury and cell disaggregation,transient or permanent?

Summary Methods for disaggregating tissues to obtain cells for primary cultures are reviewed and evaluated. The procedures include dissociation with crude and purified enzymes (singly and in various combinations), depletion of cations, and manipulation of pH and osmolality. Presented at the Workshop on Primary Cell Culture, November 1–3, 1973, Convenor Dr. Warren I. Schaeffer, University of Vermont, at the W. Alton Jones Cell Science Center, Lake Placid, N.Y. The editorial assistance of Dr. and Mrs. Joseph Leighton in preparing for press the five papers from that Workshop is gratefullv acknowledged. This work was supported by National Institutes of Health Research Grant CA-11339 from the National Cancer Institute. The Jackson Laboratory is fully accredited by the American Association for Accreditation of Laboratory Animal Care. The experimental work on liver cell dissociation referred to was carried out by Alice T. Noyes, Patricia M. Ward, Ellen Akeson, and Susan Torrey.     

To know or not to know? Genetic ignorance, autonomy and paternalism

This paper examines some arguments which deny the existence of an individual right to remain ignorant about genetic information relating to oneself--often referred to as 'a right to genetic ignorance' or, more generically, as 'a right not to know'. Such arguments fall broadly into two categories: 1) those which accept that individuals have a right to remain ignorant in self-regarding matters, but deny that this right can be extended to genetic ignorance, since such ignorance may be harmful to others, particularly those to whom one is genetically related (the 'harm to others objection') and 2) those which contend that, even if genetic ignorance is only self harming, it is not something to which individuals can rationally or morally claim to have a 'right' at all, since they defend their claims on autonomy-respecting grounds and ignorance is inimical to autonomy (the 'incoherence objection'). I argue that defenders of a right not to know have some plausible responses to the 'harm to others objection', they and their opponents reach an impasse in which both sides are left voicing concerns about the paternalistic implications of the other's point of view. I conclude that defenders of a right not to know would, therefore, advance their position further by analysing it in terms of values other than those of autonomy and rights.     

To Burst or Not to Burst?

It is well known that some neurons tend to fire packets of action potentials followed by periods of quiescence (bursts) while others within the same stage of sensory processing fire in a tonic manner. However, the respective computational advantages of bursting and tonic neurons for encoding time varying signals largely remain a mystery. Weakly electric fish use cutaneous electroreceptors to convey information about sensory stimuli and it has been shown that some electroreceptors exhibit bursting dynamics while others do not. In this study, we compare the neural coding capabilities of tonically firing and bursting electroreceptor model neurons using information theoretic measures. We find that both bursting and tonically firing model neurons efficiently transmit information about the stimulus. However, the decoding mechanisms that must be used for each differ greatly: a non-linear decoder would be required to extract all the available information transmitted by the bursting model neuron whereas a linear one might suffice for the tonically firing model neuron. Further investigations using stimulus reconstruction techniques reveal that, unlike the tonically firing model neuron, the bursting model neuron does not encode the detailed time course of the stimulus. A novel measure of feature detection reveals that the bursting neuron signals certain stimulus features. Finally, we show that feature extraction and stimulus estimation are mutually exclusive computations occurring in bursting and tonically firing model neurons, respectively. Our results therefore suggest that stimulus estimation and feature extraction might be parallel computations in certain sensory systems rather than being sequential as has been previously proposed.     

To model or not to model?

In theory, the combination of mathematical modeling with experimental studies can be a powerful and compelling approach to understanding cell biology. In practice, choosing appropriate problems, identifying willing and able collaborators, and publishing the resulting research can be remarkably challenging. To provide perspective on the question of whether and when to combine modeling and experiments, a panel of experts at the 2010 ASCB Annual Meeting shared their personal experiences and advice on how to use modeling effectively.     

To charge or not to charge?

The ability to engineer proteins with increased thermostability will profoundly broaden their practical applications. Recent experimental results show that optimization of charge-charge interactions on the surface of proteins can be a useful strategy in the design of thermostable enzymes. Results also indicate a possibility that such optimized interactions provide structural determinants for enhanced stability of proteins from thermophilic organisms. In this article, the general strategy for design of thermostable proteins and perspectives for future studies are discussed.     

Hypoxia,angiogenesis and cancer therapy: To breathe or not to breathe?

As an expanding tumor conquers space within the host, it calls out for an increased oxygen supply. This demand is rarely matched by tumor blood vessels because neo-angiogenesis generates a structurally aberrant and functionally impaired vasculature. As a result of this unbalance, tumor progression is invariably associated with cancer cell hypoxia. Insufficient oxygenation appears to have opposing effects on cancer biology: on one hand, it limits tumor cell division; on the other, it selects for more malignant cells and it induces a series of cellular adaptations that sustain and foster tumor invasion. When designing a therapeutic strategy, how should we resolve this dichotomy? Should we cut oxygen supply, thereby halting neoplastic expansion, or should we let the tumor breathe, in order to prevent its malignant conversion? Recent studies using angiogenesis inhibitors or oxygen transporters finally provide some clue.     

To lump,to split or to maintain? Molecular taxonomy of the spotted barb Barbodes binotatus (Cyprinidae) and closely related species in Peninsular Malaysia

The taxonomic status of the Southeast Asian spotted barb, Barbodes binotatus (Teleostei: Cyprinidae), has puzzled researchers because of large but inconsistent geographic variation of its body melanin marking pattern. In this study, the authors appraise the differentiation of B. binotatus and two closely related species, Barbodes rhombeus and saddle barb, Barbodes banksi, in Peninsular Malaysia using mitochondrial and nuclear markers. The results of this study reveal that the Peninsular Malaysia populations of each of the three species form largely reciprocal monophyletic lineages that differ from each other by a minimum of 2.3% p-genetic distance using COI gene. Nonetheless, specimens of B. binotatus in Peninsular Malaysia are only distantly related to specimens of B. binotatus in Java (type locality). The monophyly of B. banksi is not refuted although specimens of Peninsular Malaysia are genetically distinct from those of Sarawak (type locality). The authors discuss alternative hypotheses whether each of these three valid species is a single species or each of the main five genetic lineages revealed in this study represents a distinct species. Preliminary investigations reveal a mito-nuclear discordance at one locality in Peninsular Malaysia where B. binotatus and B. banksi co-occur. Further studies should inform on the extent of reproductive porousness between these two lineages and others.     

To be or not to be ubiquitinated?

Levels of p21, a cyclin-dependent kinase (CDK) inhibitor, are controlled in part at the post-translational level by protein degradation. Although the signaling pathways leading to p21 degradation have not yet been fully elucidated, it is evident that p21 ubiquitination is an essential factor in its degradation. We discuss that, with the only notable exception of ornithine decarboxylase, ubiquitination appears to be a prerequisite for proteasomal degradation rather than an unnecessary byproduct of such proteolysis.     

To be folded or to be unfolded?

The lack of ordered structure in “natively unfolded” proteins raises a general question: Are there intrinsic properties of amino acid residues that are responsible for the absence of fixed structure at physiological conditions? In this article, we demonstrate that the competence of a protein to be folded or to be unfolded may be determined by the property of amino acid residues to form a sufficient number of contacts in a globular state. The expected average number of contacts per residue calculated from the amino acid sequence alone (using the average number of contacts for 20 amino acid residues in globular proteins) can be used as one of the simple indicators of natively unfolded proteins. The prediction accuracy for the sets of 80 folded and 90 natively unfolded proteins reaches 89% if the expected average number of contacts is used as a parameter and 83% in the case of hydrophobicity. An optimal set of artificial parameters for 20 amino acid residues obtained by Monte Carlo algorithm to maximally separate the sets of 90 natively unfolded and 80 folded proteins demonstrates the upper limit for prediction accuracy, which is 95%.     

Cellulose: To depolymerize… or not to?

Oxidation of the primary OH groups in cellulose is a pivotal reaction both at lab and industrial scale, leading to the value-added products, i.e. oxidized cellulose which have tremendous applications in medicine, pharmacy and hi-tech industry. Moreover, the introduction of carboxyl moieties creates prerequisites for further cellulose functionalization through covalent attachment or electrostatic interactions, being an essential achievement designed to boost the area of cellulose-based nanomaterials fabrication. Various methods for the cellulose oxidation have been developed in the course of time, aiming the selective conversion of the OH groups. These methods use: nitrogen dioxide in chloroform, alkali metal nitrites and nitrates, strong acids alone or in combination with permanganates or sodium nitrite, ozone, and sodium periodate or lead (IV) tetraacetate. In the case of the last two reagents, cellulose dialdehydes derivatives are formed, which are further oxidized by sodium chlorite or hydrogen peroxide to form dicarboxyl groups. A major improvement in the cellulose oxidation was represented by the introduction of the stable nitroxyl radicals, such as 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO). However, a major impediment for the researchers working in this area is related with the severe depolymerisation occurred during the TEMPO-mediated conversion of CH₂OH into COOH groups. On the other hand, the cellulose depolymerisation represent the key step, in the general effort of searching for alternative strategies to develop new renewable, carbon-neutral energy sources. In this connection, exploiting the biomass feed stocks to produce biofuel and other low molecular organic compounds, involves a high amount of research to improve the overall reaction conditions, limit the energy consumption, and to use benign reagents. This work is therefore focused on the parallelism between these two apparently antagonist processes involving cellulose, building a necessary bridge between them, thinking how the reported drawbacks of the TEMPO-mediated oxidation of cellulose are heading towards to the biomass valorisation, presenting why the apparently undesired side reactions could be turned into beneficial processes if they are correlated with the existing achievements of particular significance in the field of cellulose conversion into small organic compounds, aiming the general goal of pursuing for alternatives to replace the petroleum-based products in human life.