Modulation of Higher-Order Olfaction Components on Executive Functions in Humans

The prefrontal (PFC) and orbitofrontal cortex (OFC) appear to be associated with both executive functions and olfaction. However, there is little data relating olfactory processing and executive functions in humans. The present study aimed at exploring the role of olfaction on executive functioning, making a distinction between primary and more cognitive aspects of olfaction. Three executive tasks of similar difficulty were used. One was used to assess hot executive functions (Iowa Gambling Task-IGT), and two as a measure of cold executive functioning (Stroop Colour and Word Test-SCWT and Wisconsin Card Sorting Test-WCST). Sixty two healthy participants were included: 31 with normosmia and 31 with hyposmia. Olfactory abilities were assessed using the ‘‘Sniffin’ Sticks’’ test and the olfactory threshold, odour discrimination and odour identification measures were obtained. All participants were female, aged between 18 and 60. Results showed that participants with hyposmia displayed worse performance in decision making (IGT; Cohen’s-d = 0.91) and cognitive flexibility (WCST; Cohen’s-d between 0.54 and 0.68) compared to those with normosmia. Multiple regression adjusted by the covariates participants’ age and education level showed a positive association between odour identification and the cognitive inhibition response (SCWT-interference; Beta = 0.29; p = .034). The odour discrimination capacity was not a predictor of the cognitive executive performance. Our results suggest that both hot and cold executive functions seem to be associated with higher-order olfactory functioning in humans. These results robustly support the hypothesis that olfaction and executive measures have a common neural substrate in PFC and OFC, and suggest that olfaction might be a reliable cognitive marker in psychiatric and neurologic disorders.     

A Human In Vitro Whole Blood Assay to Predict the Systemic Cytokine Response to Therapeutic Oligonucleotides Including siRNA

Therapeutic oligonucleotides including siRNA and immunostimulatory ligands of Toll-like receptors (TLR) or RIG-I like helicases (RLH) are a promising novel class of drugs. They are in clinical development for a broad spectrum of applications, e.g. as adjuvants in vaccines and for the immunotherapy of cancer. Species-specific immune activation leading to cytokine release is characteristic for therapeutic oligonucleotides either as an unwanted side effect or intended pharmacology. Reliable in vitro tests designed for therapeutic oligonucleotides are therefore urgently needed in order to predict clinical efficacy and to prevent unexpected harmful effects in clinical development. To serve this purpose, we here established a human whole blood assay (WBA) that is fast and easy to perform. Its response to synthetic TLR ligands (R848: TLR7/8, LPS: TLR4) was on a comparable threshold to the more time consuming peripheral blood mononuclear cell (PBMC) based assay. By contrast, the type I IFN profile provoked by intravenous CpG-DNA (TLR9 ligand) in humans in vivo was more precisely replicated in the WBA than in stimulated PBMC. Since Heparin and EDTA, but not Hirudin, displaced oligonucleotides from their delivery agent, only Hirudin qualified as the anticoagulant to be used in the WBA. The Hirudin WBA exhibited a similar capacity as the PBMC assay to distinguish between TLR7-activating and modified non-stimulatory siRNA sequences. RNA-based immunoactivating TLR7/8- and RIG-I-ligands induced substantial amounts of IFN-α in the Hirudin-WBA dependent on delivery agent used. In conclusion, we present a human Hirudin WBA to determine therapeutic oligonucleotide-induced cytokine release during preclinical development that can readily be performed and offers a close reflection of human cytokine response in vivo.     

Changes in carbohydrate composition and trehalase-activity during the budding cycle of Saccharomyces cerevisiae

Summary The carbohydrate composition and the specific activity of the trehalase of cyclic partially synchronised yeast populations have been investigated. Under glucose limitation and appropriate cultural conditions synchronous growth in a chemostat was achieved. The cells accumulated the reserve carbohydrates during the single cell phase between two buddings. The rapid degradation of part of these reserves began shortly before the swelling of the bud. The importance of the mobilisation of endogenous reserves for the development of the cell is discussed.The specific activity of the trehalase changed during the budding cycle. The result gives rise to the assumption that the synthesis of this enzyme is linked to the growth cycle.     

Sexual selection and tail streamers in the barn swallow

The functional significance of elongated, narrow tips of the tail feathers of certain birds, so-called tail streamers, has recently been discussed from an aerodynamic point of view, and the effects of sexual selection on such traits have been questioned. We review our long-term field studies using observational and experimental approaches to investigate natural and sexual selection in the barn swallow, Hirundo rustica, which has sexually size-dimorphic outermost tail feathers. Experimental manipulation of the length of the outermost tail feathers has demonstrated sexual selection advantages of tail elongation and disadvantages of tail shortening, with opposite effects for natural selection in terms of foraging efficiency, haematocrit and survival. These findings are contrary to the prediction of a general deterioration from both shortening and elongation, if the tail trait was determined solely by its effects on aerodynamic efficiency and flight manoeuvrability. Patterns of sexual selection in manipulated birds conform with patterns in unmanipulated birds, and selection differentials for different components of sexual selection in manipulated birds are strongly positively correlated with differentials in unmanipulated birds. Age and sex differences in tail length, and geographical patterns of sexual size dimorphism, are also consistent with sexual selection theory, but inconsistent with a purely natural selection advantage of long outermost tail feathers in male barn swallows.     

Mammalian sex-chromosome evolution: a conserved homoeologous segment on the X and Y chromosomes in primates

In a representative sample of primate species, including simians (Catarrhini and Platyrrhini) and prosimians (Lemuriformes and Lorisiformes), high-resolution, early replication banding revealed a homoeologous early replicating segment at the ends of both sex chromosomes. The DXYZ2 element, a repeated sequence specific for the human pseudoautosomal region, is conserved in the genomes of all primate species studies and is specifically localized in the distal early replicating segments of the X and Y chromosomes. Thus, cytogenetic and molecular evidence is presented of a highly conserved sex-chromosomal segment in primates. The pseudoautosomal behavior of this segment is discussed.     

Recent advances in gene‐enhanced bone tissue engineering

The loss of bone tissue represents a critical clinical condition that is frequently faced by surgeons. Substantial progress has been made in the area of bone research, providing insight into the biology of bone under physiological and pathological conditions, as well as tools for the stimulation of bone regeneration. The present review discusses recent advances in the field of gene‐enhanced bone tissue engineering. Gene transfer strategies have emerged as highly effective tissue engineering approaches for supporting the repair of the musculoskeletal system. By contrast to treatment with recombinant proteins, genetically engineered cells can release growth factors at the site of injury over extended periods of time. Of particular interest are the expedited technologies that can be applied during a single surgical procedure in a cost‐effective manner, allowing translation from bench to bedside. Several promising methods based on the intra‐operative genetic manipulation of autologous cells or tissue fragments have been developed in preclinical studies. Moreover, gene therapy for bone regeneration has entered the clinical stage with clinical trials for the repair of alveolar bone. Current trends in gene‐enhanced bone engineering are also discussed with respect to the movement of the field towards expedited, translational approaches. It is possible that gene‐enhanced bone tissue engineering will become a clinical reality within the next few years.