Placebos and painkillers: is mind as real as matter?

Considerable progress has been made in our understanding of the neurobiological mechanisms of the placebo effect, and most of our knowledge originates from the field of pain and analgesia. Today, the placebo effect represents a promising model that could allow us to shed new light on mind-body interactions. The mental events induced by placebo administration can activate mechanisms that are similar to those activated by drugs, which indicates a similarity between psychosocial and pharmacodynamic effects. These new neurobiological advances are already changing our conception of how clinical trials and medical practice must be viewed and conducted.     

Antisense therapeutics: is it as simple as complementary base recognition?

Antisense oligonucleotides provide a simple and efficient approach for developing target-selective drugs because they can modulate gene expression sequence-specifically. Antisense oligonucleotides have also become efficient molecular biological tools to investigate the function of any protein in the cell. As the application of antisense oligonucleotides has expanded, multiple mechanisms of oligonucleotides have been characterized that impede their routine use. Here, we discuss different mechanisms of action of oligonucleotides and the possible ways of minimizing non-antisense-related [corrected] effects to improve their specificity.     

Animal navigation: birds as geometers?

New experiments on a bird species able to remember the sites of thousands of cached seeds have revealed how a site can be specified by combining distance information from several landmarks.     

Cutaneous horns: are these lesions as innocent as they seem to be?

Background  

Cutaneous horns (cornu cutaneum) are uncommon lesions consisting of keratotic material resembling that of an animal horn. Cutaneous horn may arise from a wide range of the epidermal lesions, which may be benign, premalignant or malignant.     

Xenotransplantation: is the risk of viral infection as great as we thought?

Two major hurdles remain before xenotransplantation can enter the clinic. The first is the more technical issue of being able to overcome the human immune response that leads to rejection of transplanted organs/cells from other species. The second, reviewed here, concerns the potential risk of inadvertent transfer of animal viruses present in the xenotransplant that are able to infect the human recipient. The threat from viruses is a particularly contentious topic because it poses a risk not only to those individuals who receive xenotransplants, but also to healthy individuals who come into contact, either directly or indirectly, with the xenotransplant recipient. In this review, we describe some of the virus types, in addition to the much discussed porcine endogenous retroviruses that might cross the species barrier, and assess the risk of such viruses causing disease in human hosts.     

“Make Everything as Simple as Possible,But Not Simpler”: A Simple Approach is as Good as a Complex Algorithm for Insulin Dose Self-Adjustment

Abbreviations:A1c = glycated hemoglobin A1cDM2 = type 2 diabetes mellitusRCT = randomized controlled trialSMBG = self-monitoring blood glucose     

Anhydrobiosis: the model worm as a model?

New work now shows that the dauer larvae of Caenorhabditis elegans can survive anhydrobiotically. The genetic tractability of this model organism may be useful in studying how organisms survive when losing most or all of their water.     

Teaching Tree Thinking to College Students: It’s Not as Easy as You Think

The ability to understand and reason with tree-of-life diagrams (i.e., cladograms), referred to as tree thinking, is an essential skill for biology students. Yet, recent findings indicate that cladograms are cognitively opaque to many college students, leading them to misinterpret the information depicted. The current studies address the impact of prior biological background and instruction in phylogenetics on students?? competence at two foundational tree-thinking skills. In Study 1, college students with stronger (N?=?52) and weaker (N?=?60) backgrounds in biology were asked to (a) identify all the nested clades in two cladograms and (b) evaluate evolutionary relatedness among taxa positioned at different hierarchical levels (two questions) and included in a polytomy (two questions). Stronger-background students were more successful than weaker-background students. In Study 2, a subset of the stronger-background students (N?=?41) who were enrolled in an evolution class subsequently received two days of instruction on phylogenetics. As expected, these students?? tree-thinking skills generally improved with instruction. However, although these students did very well at marking the nested clades, fundamental misinterpretations of relative evolutionary relatedness remained. The latter was especially, although not exclusively, the case for taxa included in a polytomy. These results highlight the importance of teaching cladistics, as well as the need to tailor such instruction to the difficulties students have learning key macroevolutionary concepts.     

Forces maintaining organellar genomes: is any as strong as genetic code disparity or hydrophobicity?

It remains controversial why mitochondria and chloroplasts retain the genes encoding a small subset of their constituent proteins, despite the transfer of so many other genes to the nucleus. Two candidate obstacles to gene transfer, suggested long ago, are that the genetic code of some mitochondrial genomes differs from the standard nuclear code, such that a transferred gene would encode an incorrect amino acid sequence, and that the proteins most frequently encoded in mitochondria are generally very hydrophobic, which may impede their import after synthesis in the cytosol. More recently it has been suggested that both these interpretations suffer from serious "false positives" and "false negatives": genes that they predict should be readily transferred but which have never (or seldom) been, and genes whose transfer has occurred often or early, even though this is predicted to be very difficult. Here I consider the full known range of ostensibly problematic such genes, with particular reference to the sequences of events that could have led to their present location. I show that this detailed analysis of these cases reveals that they are in fact wholly consistent with the hypothesis that code disparity and hydrophobicity are much more powerful barriers to functional gene transfer than any other. The popularity of the contrary view has led to the search for other barriers that might retain genes in organelles even more powerfully than code disparity or hydrophobicity; one proposal, concerning the role of proteins in redox processes, has received widespread support. I conclude that this abandonment of the original explanations for the retention of organellar genomes has been premature. Several other, relatively minor, obstacles to gene transfer certainly exist, contributing to the retention of relatively many organellar genes in most lineages compared to animal mtDNA, but there is no evidence for obstacles as severe as code disparity or hydrophobicity. One corollary of this conclusion is that there is currently no reason to suppose that engineering nuclear versions of the remaining mammalian mitochondrial genes, a feat that may have widespread biomedical relevance, should require anything other than sequence alterations obviating code disparity and causing modest reductions in hydrophobicity without loss of enzymatic function.     

Phosphoinositide phosphatases: emerging roles as voltage sensors?

During a genomic survey of the transparent sea squirt (Ciona intestinalis), Murata et al. discovered a gene that encodes a protein containing homologous sequences to both a CX(5)R phosphatase and an ion channel. The authors named the novel protein, C. intestinalis voltage-sensor-containing phosphatase, Ci-VSP. The N terminus of Ci-VSP appears to function as a voltage-gated sensor; the C terminus functions as a phosphoinositide phosphatase. The authors suggest that when the N-terminal voltage sensor is activated, this in turn activates the phosphatase, which converts PI(3,4,5)P(3) to PI(4,5)P(2). Localized changes in membrane PI(4,5)P(2) levels could then serve to either positively or negatively regulate a variety of ion transporters and channels.     

Carbonic anhydrase inhibitors: sulfonamides as antitumor agents?

Novel sulfonamide inhibitors of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1) were prepared by reaction of aromatic or heterocyclic sulfonamides containing amino, imino, or hydrazino moieties with N,N-dialkyldithiocarbamates in the presence of oxidizing agents (sodium hypochlorite or iodine). The N,N-dialkylthiocarbamylsulfenamido-sulfonamides synthesized in this way behaved as strong inhibitors of human CA I and CA II (hCA I and hCA II) and bovine CA IV (bCA IV). For the most active compounds, inhibition constants ranged from 10(-8) to 10(-9) M (for isozymes II and IV). Three of the derivatives belonging to this new class of CA inhibitors were also tested as inhibitors of tumor cell growth in vitro. These sulfonamides showed potent inhibition of growth against several leukemia, non-small cell lung, ovarian, melanoma, colon, CNS, renal, prostate and breast cancer cell lines. With several cell lines. GI50 values of 10-75 nM were observed. The mechanism of antitumor action with the new sulfonamides reported here remains obscure, but may involve inhibition of CA isozymes which predominate in tumor cell membranes (CA IX and CA XII), perhaps causing acidification of the intercellular milieu, or inhibition of intracellular isozymes which provide bicarbonate for the synthesis of nucleotides and other essential cell components (CA II and CA V). Optimization of these derivatives from the SAR point of view, might lead to the development of effective novel types of anticancer agents.     

Antidepressant drugs in the elderly: Are the indications as long term as the treatment?

In a community study of 761 people aged 70 years and over 45 (5·9%) were found to be taking long term tricyclic antidepressants. Forty four were compared with matched controls. There was no evidence that tricyclic antidepressants were being used to compensate for poor physical health or function. Twenty subjects had a clear history of depression; three of these required additional treatment and five might have coped without continued drug treatment. Twelve of the remainder had started treatment with tricyclic antidepressants as hypnotics and 11 as a trial because of suspected depression. They had continued taking the drugs over a long period.Regular review of both the adequacy of and the necessity for continued treatment with tricyclic antidepressants in the elderly is recommended.