Golgi retention signals: do membranes hold the key?

The diverse forms and functions of cellular organelles are, presumably, a consequence of their particular molecular compositions. The generation and maintenance of this diversity is achieved by the targeting of newly synthesized proteins to specific locations and their subsequent retention there. Sequences that retain proteins in the endoplasmic reticulum (ER) have been identified at the C-termini of resident ER proteins, where they are readily accessible to potential receptors. By contrast, recent results have demonstrated that retention of proteins in the Golgi complex involves sequences located within transmembrane domains. This suggests the novel possibility that the membrane composition of the Golgi complex plays a role in retention of resident Golgi proteins.     

Cell transplantation for cardiac regeneration: where do we stand?

During the last decade transplantation of cells into the heart has emerged as a novel therapy for the prevention and treatment of heart failure. Although various cell types have been used, most experience has been obtained with the progenitor cells of skeletal muscle, also called myoblasts, and a wide array of bone marrow-derived cell types. The first preclinical studies demonstrated an improvement in global and regional heart function that was attributed mainly to a direct contractile effect of the transplanted cells. Furthermore, it was suggested that multiple cell types are able to form true cardiomyocytes and truly ‘regenerate’ the myocardium. More recent studies have questioned these early findings. Other mechanisms such as paracrine effects on the infarct and remote myocardium, a reduction in adverse remodelling and improvement of mechanical properties of the infarct tissue likely play a more important role. On the basis of encouraging preclinical studies, multiple early-phase clinical trials and several randomised controlled trials have been conducted that have demonstrated the feasibility, safety and potential efficacy of this novel therapy in humans. This review summarises the available evidence on cardiac cell transplantation and provides an outlook on future preclinical and clinical research that has to fill in the remaining gaps. (Neth Heart J 2008; 16:88-95.)     

DLK: the "preconditioning" signal for axon regeneration?

In this issue of Neuron, Shin et?al. (2012) show that the dual leucine zipper kinase (DLK) is responsible for the retrograde injury signal in spinal sensory and motor neurons. DLK is required for the accelerated regeneration seen after axotomy and for the improved regeneration seen after a conditioning injury. DLK KO axons have severely reduced axon regeneration in?vivo.     

Commentary: do we have a consistent terminology for species diversity? We are on the way

A consistent terminology for species diversity is subject of an ongoing debate. Recently Tuomisto (Oecologia 164:853–860, 2010) stated that a consistent terminology for diversity already exists. The paper comments on recent papers by ourselves (Jurasinski et al. Oecologia 159:15–26, 2009) and by Moreno and Rodriguez (Oecologia 163:279–282, 2010). Both started from Whittaker’s diversity concept to discuss the ambiguities of the terminology and propose a new, more consistent terminology that is based on the different approaches to diversity analysis. In contrast, Tuomisto adheres to a strict school of thinking and derives a diversity framework in the sense of Whittaker (alpha, beta, gamma) from the conceptual definition of diversity itself. A third group of papers discusses appropriate methods for the analysis of the variation in species composition. Here, we support the idea that alpha, beta and gamma diversity should be used in a strict sense that is based only on the conceptual definition of diversity. We accordingly extend and modify our terminological concept for species diversity. All approaches to the analysis and quantification of species composition and diversity can be assigned to three abstraction levels (species composition, variation in species composition,and variation in variation in species composition) and two scale levels (sample scale, aggregation scale). All methods that investigate the variation in species composition across scale levels evaluate beta relation with beta diversity being just one form of beta relation, which is calculated by dividing gamma diversity of order q by the appropriate alpha diversity of the same order. In contrast, differentiation refers to a pairwise calculation of resemblance in species composition. It is restricted to sample scale and is therefore most often only an intermediate step of analysis. Many ecological questions can be addressed either by direct analysis of the variation in species composition using raw data approaches or by further analysis of differentiation datasets on aggregation scale with or without respect to an external gradient.     

Tubulin rings: which way do they curve?

Tubulin is known to exist in at least two main conformations: straight when bound to GTP or buried within the microtubule lattice, and curved when bound to GDP. The latter is most obvious during microtubule depolymerization, when protofilaments bend and peel off from microtubule ends. The curved, low-energy subunits form tantalizing ring structures in the presence of stabilizing divalent cations. Interestingly, cellular factors and antimitotic agents that act by depolymerizing microtubules can induce the formation of rings. In these rings, tubulin dimers generally appear kinked at the monomer-monomer interface, either to the same or to a lesser extent than at the dimer-dimer interface, with each agent giving rise to particular subtleties in the structures of the rings and the tubulin dimer itself that may reflect their distinctive mechanisms of action. How these kinks relate to what happens when the stored energy of GTP hydrolysis is released, freeing GDP*tubulin into an unconstrained state, remains an open question.     

Modifying the object-choice task: Is the way you look important for ravens?

Most animals seem to have difficulties in using gaze cues to find hidden food in object-choice tasks. For instance, chimpanzees usually fail in these tests, even though they are capable of following other's gaze geometrically behind barriers. Similar to chimpanzees, common ravens are skilled in tracking other's gaze but fail in object-choice tasks. We here explored whether procedural modifications, which had been used successfully in chimpanzees, would also yield positive results in ravens. In our modifications (a) the experimenter approached the cup while gazing at it, (b) the gaze cue was accompanied by a sound and (c) the experimenter could actually see the food while giving the gaze cue. Two out of seven birds performed above chance level in some of these conditions. However, we ascribe this improvement to the individuals' learning ability rather than to an understanding of the communicative nature of the task. This interpretation is further supported by results of a follow-up experiment suggesting that ravens may not rely on conspecifics' gaze cues for finding food caches in a natural foraging context. In sum, our results suggest that ravens may not transfer their gaze follow abilities to foraging situations involving hidden food.     

Unique presentations and chronic complications in adult cystic fibrosis: do they teach us anything about CFTR?

The increase in numbers of adults with cystic fibrosis (CF) has allowed us to identify previously unrecognized chronic complications of CF, as well as appreciate unique presentations of cystic fibrosis-related diseases. Do these chronic complications and unique presentations provide us with new insight into cystic fibrosis transmembrane conductance regulator (CFTR) function? Current data suggest that the 'chronic complications' reveal mainly the effect of a long-term absence of previously recognized CFTR functions. In contrast, the 'unique presentations' provide new insight into the role of CFTR in different tissues.     

How do point amino acid substitutions affect the protein structure?

In order to estimate the influence of point mutations on the protein structure, 552 pairs of structurally aligned proteins with pairwise sequence identities greater than 60% were analyzed. We selected all isolated point mismatches from these alignments. The statistics of local conformational changes corresponding to these mismatches was studied. This study revealed two surprising aspects: (a) only an extremely minor fraction (< 3%) of all observed mutations leads to significant changes in local conformations; (b) observed substitutions, which affect local conformation are more frequently those of similar (high scoring) amino acid pairs rather than the substitutions thought of as "hazardous" (low scoring), although the overall average score of the changing substitutions is still lower than the corresponding average score for the substitutions that leave the structure unchanged.     

Vitamin E revisited: do new data validate benefits for chronic disease prevention?

PURPOSE OF REVIEW: Vitamin E benefits in human health and chronic disease prevention are evaluated with respect to established alpha-tocopherol functions during vitamin E deficiency, adequacy, and excess. RECENT FINDINGS: Baseline vitamin E status of the 29 092 Finnish men participating in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention study showed that the men in the highest compared with the lowest quintile of serum alpha-tocopherol had significantly lower incidences of total and cause-specific mortality. New findings from the Women's Health Study support a role for vitamin E supplements in decreasing the risk for sudden death from cardiovascular disease and from thromboembolism. We speculate that a potential mechanism may involve vitamin E interference in vitamin K activation. SUMMARY: alpha-Tocopherol acts as a peroxyl and alkoxyl radical scavenger in lipid environments, and thus it prevents lipid peroxidation in lipoproteins and membranes, especially nervous tissues. Decreased chronic disease incidence is associated with lifelong generous dietary vitamin E intakes, but more than 90% of Americans do not consume the recommended dietary amounts (15 mg/day). Vitamin E supplements can have beneficial effects on health beyond those from dietary amounts, perhaps because pharmacologic levels also upregulate hepatic xenobiotic pathways.     

Sex recognition in brown skuas: do acoustic signals matter?

Bird vocalisations are often essential for sex recognition, especially in species that show little morphological sex dimorphism. Brown skuas (Catharacta antarctica lonnbergi), which exhibit uniform plumage across both sexes, emit three main calls: the long call, the alarm call and the contact call. We tested the potential for sex recognition in brown skua calls of 42 genetically sexed individuals by analysing 8–12 acoustic parameters in the temporal and frequency domains of each call type. For every call type, we failed to find sex differences in any of the acoustic parameters measured. Stepwise discriminant function analysis (DFA) revealed that sexes cannot be unambiguously classified, with increasing uncertainty of correct classification from contact calls to long calls to alarm calls. Consequently, acoustic signalling is probably not the key mechanism for sex recognition in brown skuas.