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%.     

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.     

Sclerotinia sclerotiorum: when "to be or not to be" a pathogen?

Sclerotinia sclerotiorum is unusual among necrotrophic pathogens in its requirement for senescent tissues to establish an infection and to complete the life cycle. A model for the infection process has emerged whereby the pathogenic phase is bounded by saprophytic phases; the distinction being that the dead tissues in the latter are generated by the actions of the pathogen. Initial colonization of dead tissue provides nutrients for pathogen establishment and resources to infect healthy plant tissue. The early pathogenicity stage involves production of oxalic acid and the expression of cell wall degrading enzymes, such as specific isoforms of polygalacturonase (SSPG1) and protease (ASPS), at the expanding edge of the lesion. Such activities release small molecules (oligo-galacturonides and peptides) that serve to induce the expression of a second wave of degradative enzymes that collectively bring about the total dissolution of the plant tissue. Oxalic acid and other metabolites and enzymes suppress host defences during the pathogenic phase, while other components initiate host cell death responses leading to the formation of necrotic tissue. The pathogenic phase is followed by a second saprophytic phase, the transition to which is effected by declining cAMP levels as glucose becomes available and further hydrolytic enzyme synthesis is repressed. Low cAMP levels and an acidic environment generated by the secretion of oxalic acid promote sclerotial development and completion of the life cycle. This review brings together histological, biochemical and molecular information gathered over the past several decades to develop this tri-phasic model for infection. In several instances, studies with Botrytis species are drawn upon for supplemental and supportive evidence for this model. In this process, we attempt to outline how the interplay between glucose levels, cAMP and ambient pH serves to coordinate the transition between these phases and dictate the biochemical and developmental events that define them.     

Plant genome editing in the European Union—to be or not to be—a GMO

New plant-breeding techniques have been boosting plant breeding, since only a few years but already first promising products are pushing to the market. In contrast to this, in many countries, the current Directives regulating genetically modified organisms have been established more than 25 years ago, especially in the European Union being based on clear differentiation between transgenic plants and conventional breeding. Therefore, the question arises if these Directives are suitable to face the new challenge of genetic engineering or if there is a need for updated regulations.     

Animal models of human genetic diseases: do they need to be faithful to be useful?

With the advances in molecular genetics, animal models of human diseases are becoming more numerous and more refined every year. Despite this, one must recognize that they generally do not faithfully and comprehensively mimic the homologous human disease. Faced with these imperfections, some geneticists believe that these models are of little value, while for others, on the contrary, they are important tools. We agree with this second statement, and in this review, we examine the reasons that may explain the observed differences and suggest means to circumvent or even exploit them. Our opinion is that animal models should be regarded more as tools capable of answering specific questions rather than mere replicas, at a smaller scale, of a given human disease. Far from disappointing they are probably called for a promising future.     

Is it going to be SIN?

Insertional mutagenesis resulting in a leukaemia-like lymphoproliferative disease, as observed in the X-SCID (severe combined immunodeficiency) clinical trial using a gamma-retroviral vector that transferred a functional copy of the defective gene into hematopoietic precursor cells of affected children, sparked a debate about a ban on conventional gamma-retroviral vectors. This commentary summarizes the relevant data on this topic and concludes that there is no preclinical or clinical evidence as yet that SIN vectors, which self-inactivate the retroviral long terminal repeats (LTRs), will indeed show an improved safety profile. Conventional murine leukaemia virus (MLV) vectors can thus be used further in clinical gene therapy trials but require a thorough case-by-case risk-benefit analysis.     

Centrioles: bad to be bald?

In the alga Chlamydomonas, mutation of the gene encoding the novel centriolar component Bld10p results in seemingly acentriolar cells. Remarkably, bld10 cells are viable, highlighting the question of whether or not centrioles are essential.     

Born to be bee,fed to be worker? The caste system of a primitively eusocial insect

Introduction

Primitively eusocial halictid bees are excellent systems to study the origin of eusociality, because all individuals have retained the ancestral ability to breed independently. In the sweat bee Halictus scabiosae, foundresses overwinter, establish nests and rear a first brood by mass-provisioning each offspring with pollen and nectar. The mothers may thus manipulate the phenotype of their offspring by restricting their food provisions. The first brood females generally help their mother to rear a second brood of males and gynes that become foundresses. However, the first brood females may also reproduce in their maternal or in other nests, or possibly enter early diapause. Here, we examined if the behavioural specialization of the first and second brood females was associated with between-brood differences in body size, energetic reserves and pollen provisions.

Results

The patterns of variation in adult body size, weight, fat content and food provisioned to the first and second brood indicate that H. scabiosae has dimorphic females. The first-brood females were significantly smaller, lighter and had lower fat reserves than the second-brood females and foundresses. The first-brood females were also less variable in size and fat content, and developed on homogeneously smaller pollen provisions. Foundresses were larger than gynes of the previous year, suggesting that small females were less likely to survive the winter.

Conclusions

The marked size dimorphism between females produced in the first and second brood and the consistently smaller pollen provisions provided to the first brood suggest that the first brood females are channelled into a helper role during their pre-imaginal development. As a large body size is needed for successful hibernation, the mother may promote helping in her first brood offspring by restricting their food provisions. This pattern supports the hypothesis that parental manipulation may contribute to promote worker behaviour in primitively eusocial halictids.

     

Does your chairman need to be Superman?

To find the right chairman for your biotechnology company, brush up on your chemistry skills.     

Can Wolbachia be used to control malaria?

Malaria is a mosquito-borne infectious disease caused by Plasmodium parasites transmitted by the infectious bite of Anopheles mosquitoes. Vector control of malaria has predominantly focused on targeting the adult mosquito through insecticides and bed nets. However, current vector control methods are often not sustainable for long periods so alternative methods are needed. A novel biocontrol approach for mosquito-borne diseases has recently been proposed, it uses maternally inherited endosymbiotic Wolbachia bacteria transinfected into mosquitoes in order to interfere with pathogen transmission. Transinfected Wolbachia strains in Aedes aegypti mosquitoes, the primary vector of dengue fever, directly inhibit pathogen replication, including Plasmodium gallinaceum, and also affect mosquito reproduction to allow Wolbachia to spread through mosquito populations. In addition, transient Wolbachia infections in Anopheles gambiae significantly reduce Plasmodium levels. Here we review the prospects of using a Wolbachia-based approach to reduce human malaria transmission through transinfection of Anopheles mosquitoes.     

Can respect be key to gender justice?

Equality and respect are, together with dignity, considered foundational values in international human rights discourse. While equality in particular has been established as a widely accepted goal in the women's rights movement, respect is, however, less commonly invoked. Based on long‐term ethnographic fieldwork conducted among the Arsi Oromo of Ethiopia, this article examines the notion of wayyuu, a tacit moral model of respect and sacredness that is central to institutions and norms that have secured women certain rights and power. These norms and institutions represent a challenge to the liberal feminist conceptualization of gender equality that dominates international women's rights discourse. Drawing on theories of respect and on feminist and anthropological discussions of equality, I argue that even though there are certain limitations inherent in wayyuu, the sacredness it entails and the implications this has had for women's status and power among the Arsi Oromo call for an exploration of respect not as an alternative to equality, but as a complementary notion which to a greater extent could be included in global discussions of gender justice.     

Is human aging still mysterious enough to be left only to scientists?

The feasibility of reversing human aging within a matter of decades has traditionally been dismissed by all professional biogerontologists, on the grounds that not only is aging still poorly understood, but also many of those aspects that we do understand are not reversible by any current or foreseeable therapeutic regimen. This broad consensus has recently been challenged by the publication, by five respected experimentalists in diverse subfields of biogerontology together with three of the present authors, of an article (Ann NY Acad Sci 959, 452-462) whose conclusion was that all the key components of mammalian aging are indeed amenable to substantial reversal (not merely retardation) in mice, with technology that has a reasonable prospect of being developed within about a decade. Translation of that panel of interventions to humans who are already alive, within a few decades thereafter, was deemed potentially feasible (though it was not claimed to be likely). If the prospect of controlling human aging within the foreseeable future cannot be categorically rejected, then it becomes a matter of personal significance to most people presently alive. Consequently, we suggest that serious public debate on this subject is now warranted, and we survey here several of the biological, social and political issues relating to it.