Recombination in HIV and the evolution of drug resistance: for better or for worse?

The rapid evolution of drug resistance remains a major obstacle for HIV therapy. The capacity of the virus for recombination is widely believed to facilitate the evolution of drug resistance. Here, we challenge this intuitive view. We develop a population genetic model of HIV replication that incorporates the processes of mutation, cellular superinfection, and recombination. We show that cellular superinfection increases the abundance of low fitness viruses at the expense of the fittest strains due to the mixing of viral proteins during virion assembly. Moreover, we argue that whether recombination facilitates the evolution of drug resistance depends critically on how resistance mutations interact to determine viral fitness. Contrary to the commonly held belief, we find that, under the most plausible biological assumptions, recombination is expected to slow down the rate of evolution of multi-drug-resistant virus during therapy.     

Transcranial electrical stimulation for human enhancement and the risk of inequality: Prohibition or compensation?

Non‐invasive brain stimulation is used to modulate brain excitation and inhibition and to improve cognitive functioning. The effectiveness of the enhancement due to transcranial direct current stimulation (tDCS) is still controversial, but the technique seems to have large potential for improvement and more specific applications. In particular, it has recently been used by athletes, both beginners and professionals. This paper analyses the ethical issues related to tDCS enhancement, which depend on its specific features: ease of use, immediate effect, non‐detectability and great variability of effects. If tDCS were to become widespread, there could be some potential side effects, especially the rise of inequality in many selective competitive contexts. I discuss two possible scenarios to counter this effect: that of prohibition and that of compensation, each supported by reasons and arguments that seem plausible and worthy of consideration. In conclusion, I show why I think the scenario of compensation is the preferable one.     

Habitat enhancement and native fish conservation: can enhancement of channel complexity promote the coexistence of native and introduced fishes?

Native fishes worldwide have declined as a consequence of habitat loss and degradation and introduction of non-native species. In response to these declines, river restoration projects have been initiated to enhance habitat and remove introduced fishes; however, non-native fish removal is not always logistically feasible or socially acceptable. Consequently, managers often seek to enhance degraded habitat in such a way that native fishes can coexist with introduced species. We quantified dynamics of fish communities to three newly constructed side channels in the Provo River, Utah, USA, to determine if and how they promoted coexistence between native fishes (nine species) and non-native brown trout (Salmo trutta L.). Native and introduced fishes responded differently in each side channel as a function of the unique characteristics and histories of side channels. Beaver activity in two of the three side channels caused habitat differentiation or channel isolation that facilitated the establishment of native species. The third side channel had greater connectivity to and similar habitat as the main channel of the Provo River, resulting in a similar fish community to main channel habitats (i.e. dominated by brown trout with only a few native fish species). These results demonstrate the importance of understanding habitat preferences for each species in a community to guide habitat enhancement projects and the need to create refuge habitats for native fishes.     

The IFN-γ/miniTrpRS signaling axis: An insight into the pathophysiology of osteoporosis and therapeutic potential

Osteoporosis results from dysregulated bone remodeling with increased osteoclast-mediated destruction of bones. We have recently shown in vitro the truncated tryptophanyl-tRNA synthetase (mini-TrpRS)-dependent action of interferon-gamma (IFN-γ) to promote myeloid lineage multinucleation, a fundamental step in the osteoclast formation. In particular, we found that IFN-γ readily induced monocyte aggregation leading to multinuclear giant cell formation that paralleled marked upregulation of mini-TrpRS. However, blockade of mini-TrpRS with its cognate amino acid and decoy substrate D-Tryptophan prevented mini-TrpRS signaling, and markedly reduced the aggregation of monocytes and multinucleation in the presence of IFN. The cell signaling mechanism executed by mini-TrpRS appears inevitably in any inflammatory environment that involves IFN-γ with outcomes depending on the cell type involved. Here, we elaborate on these findings and discuss the potential role of the IFN-γ/mini-TrpRS signaling axis in osteoporosis pathophysiology, which may eventually materialize in a novel therapeutic perspective for this disease.     

Discrepancies between subgeneric classification and molecular phylogeny of Ceratitis (Diptera: Tephritidae), can the evolution of host use provide some clues?

Using molecular data from three protein encoding genes and 49 taxa (98 specimens from 20 African countries), we provide an extended phylogeny of Ceratitis and investigate the evolution of stenophagy across clades. Bayesian tree reconstructions support previously proposed monophyletic lineages (Pardalaspis, Pterandrus section A, Pterandrus section B+Ceratitis sensu stricto) and reveal the occurrence of two new monophyletic groups including Ceratalaspis/Hoplolophomyia (viz. Cl(A), and Cl(B)+H). The reconstruction of ancestral character states shows that stenophagy evolved repeatedly and independently in five different clades (Podocarpus, Solanum, Strychnos, Tabernaemontana and Vepris feeders). The evolution of feeding preferences is closely related to the phylogenetic patterns of Ceratalaspis/Hoplolophomyia whose sections include either polyphagous species (Cl(A)) or stenophagous taxa (Cl(B)+H) that are further subdivided in Vepris and Solanum feeders. The evolution of stenophagy in the genus Ceratits appears as the result of a process leading to the exploitation of "unconventional" fruits (viz. toxic and/or not fleshy) and involving either metabolic adaptation to toxic plant compounds and/or the capability of penetrating fruits with thick cuticles.     

Anticoagulation and sepsis: the opportunity for a new use of heparin?

Sepsis is a leading cause of morbidity and mortality worldwide, and the magnitude of the problem seems higher in developing countries. In the last two decades the accepted standard treatment has resulted in only a slight decrease in mortality, and that decrease has been overshadowed by an almost 300% increase in incidence. Recently has been documented the close relationship between infection, inflammation and coagulation in sepsis has been documented; and although clinically overt disseminated intravascular coagulation may occur in only 30% to 50% of septic patients, the activation of the coagulation cascade is an early and common response to the infectious challenge. Moreover most of the molecules involved in the pro-coagulant state that characterizes sepsis are also powerful generators or amplifiers of the inflammatory response. These findings have fostered a comprehensive body of research regarding biological products with anticoagulant activity, as additional therapies for patients with the most severe states of the sepsis syndrome. This review explains the biological and molecular aspects that support the potential use of anticoagulant treatments in sepsis. Furthermore, we analyze the evidence provided by experimental and pre-clinical studies, which suggest the usefulness of heparin as an effective complementary treatment throughout the clinical stages of the disease.     

First principles calculations of thermodynamics and kinetic parameters and molecular dynamics simulations of acetylcholinesterase reactivators: can mouse data provide new insights into humans?

We have applied a theoretical methodology, previously developed to evaluate the association and kinetic reactivation constants of oximes, comparing theoretical data obtained for human acetylcholinesterase (HsAChE) with in vitro results from Mus musculus AChE (MmAChE) previously reported in the literature. Our results, further checked by additional molecular dynamics simulations steps, showed a good correlation between the theoretical and experimental data, supporting the methodology as appropriate for prediction of thermodynamic and kinetic parameters and corroborated MmAChE as a suitable model for studies with HsAChE.     

First principles calculations of thermodynamics and kinetic parameters and molecular dynamics simulations of acetylcholinesterase reactivators: can mouse data provide new insights into humans?

We have applied a theoretical methodology, previously developed to evaluate the association and kinetic reactivation constants of oximes, comparing theoretical data obtained for human acetylcholinesterase (HsAChE) with in vitro results from Mus musculus AChE (MmAChE) previously reported in the literature. Our results, further checked by additional molecular dynamics simulations steps, showed a good correlation between the theoretical and experimental data, supporting the methodology as appropriate for prediction of thermodynamic and kinetic parameters and corroborated MmAChE as a suitable model for studies with HsAChE.     

Meteorite or gemstone? Dreaming as one end of a continuum of functioning: Implications for research and for the use of dreams in therapy and self-knowledge.

Is a dream a meteorite—a bit of material arriving from a distant place that needs to be carefully analyzed to give us knowledge about that place (outside or inside us)? Is it a strange text which has come to us in a foreign language, that needs to be translated into our own? This “meteorite view” is held by some religious and spiritual persons, by many orthodox psychoanalysts and other therapists, and implicitly by many researchers. They all see the dream as something alien, something totally different from our ordinary mental functioning. This paper presents a great deal of research favoring an alternate view—that the dream is an earth-stone, not an alien stone. It may be impressive and beautiful (gemstone), but it's still an earth-stone. The dream is part of our mental functioning. It is one end of a continuum, running from focused waking thought, through looser thought, fantasy, daydreaming, reverie and dreaming. We review reasons why dreams are often considered “totally different”: they're perceptual, not conceptual; they're bizarre; they are “so real”; they're so easily forgotten; they're involuntary; they occur in REM sleep—a totally different state. We demonstrate that none of these reasons are persuasive. In each sense, there is overlap between dreams and other forms of functioning. The continuum view leads to different kinds of research and a different style of dreamwork. It also helps answer questions the field has long struggled with including: Should we study “a dream” or “dreaming”? Are dreams meaningful or meaningless? (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

What can Expeditions do for Students … and for Science? An Investigation into the Impact of University of Glasgow Exploration Society Expeditions

The benefits of field courses for biological science students are well established, but field courses also have limitations: they are generally too brief to allow significant research and they are staff-designed and led, limiting the development of student autonomy. In contrast, the value of student-organised field expeditions has been little researched. Here, as a case history, we analyse students’ attitudes to their experience of being selected for and taking part in University of Glasgow Exploration Society expeditions. Students regarded taking part in an expedition as one of the best things they had done in their life thus far. Expeditions were excellent value for money, provided opportunities to develop transferable skills (fund-raising, budgeting, report production, composing and delivering oral and written presentations, team-working and leadership, negotiation with stakeholders from different cultures) and provided scope for fieldwork skill development and substantial, publishable research. Participants also believed the expeditions provided real benefits to the communities visited. Participation in expeditions can contribute to each student’s Higher Education Achievement Report.     

The role of thrombin and thrombin receptors in ischemic,hemorrhagic and traumatic brain injury: deleterious or protective?

In the last two decades it has become apparent that thrombin has many extravascular effects that are mediated by a family of protease-activated receptors (PARs). PAR-1, -3 and -4 are activated via cleavage by thrombin. The importance of extravascular thrombin in modulating ischemic, hemorrhagic and traumatic injury in brain has recently become clear. Thus, in vitro, thrombin at low concentration protects neurons and astrocytes from cell death caused by a number of different insults. In vivo, pretreating the brain with a low dose of thrombin (thrombin preconditioning), attenuates the brain injury induced by a large dose of thrombin, an intracerebral hemorrhage or by focal cerebral ischemia. Thrombin may also be an important mediator of ischemic preconditioning. In contrast, high doses of thrombin kill neurons and astrocytes in vitro and cause disruption of the blood-brain barrier, brain edema and seizures in vivo. This review examines the role of thrombin in brain injury and the molecular mechanisms and signaling cascades involved.