Obesity and psychotic disorders: uncovering common mechanisms through metabolomics

Primary obesity and psychotic disorders are similar with respect to the associated changes in energy balance and co-morbidities, including metabolic syndrome. Such similarities do not necessarily demonstrate causal links, but instead suggest that specific causes of and metabolic disturbances associated with obesity play a pathogenic role in the development of co-morbid disorders, potentially even before obesity develops. Metabolomics – the systematic study of metabolites, which are small molecules generated by the process of metabolism – has been important in elucidating the pathways underlying obesity-associated co-morbidities. This review covers how recent metabolomic studies have advanced biomarker discovery and the elucidation of mechanisms underlying obesity and its co-morbidities, with a specific focus on metabolic syndrome and psychotic disorders. The importance of identifying metabolic markers of disease-associated intermediate phenotypes – traits modulated but not encoded by the DNA sequence – is emphasized. Such markers would be applicable as diagnostic tools in a personalized healthcare setting and might also open up novel therapeutic avenues.     

Nanosecond Electric Pulse Effects on Gene Expression

Gene electrotransfection using micro- or millisecond electric pulses is a well-established method for safe gene transfer. For efficient transfection, plasmid DNA has to reach the nucleus. Shorter, high-intensity nanosecond electric pulses (nsEPs) affect internal cell membranes and may contribute to an increased uptake of plasmid by the nucleus. In our study, nsEPs were applied to Chinese hamster ovary (CHO) cells after classical gene electrotransfer, using micro- or millisecond pulses with a plasmid coding the green fluorescent protein (GFP). Time gaps between classical gene electrotransfer and nsEPs were varied (0.5, 2, 6 and 24 h) and three different nsEP parameters were used: 18 ns-10 kV/cm, 10 ns-40 kV/cm and 15 ns-60 kV/cm. Results analyzed by either fluorescence microscopy or flow cytometry showed that neither the percentage of electrotransfected cells nor the amount of GFP expressed was increased by nsEP. All nsEP parameters also had no effects on GFP fluorescence intensity of human colorectal tumor cells (HCT-116) with constitutive expression of GFP. We thus conclude that nsEPs have no major contribution to gene electrotransfer in CHO cells and no effect on constitutive GFP expression in HCT-116 cells.     

Identification of the critical level of implantation of an osseointegrated prosthesis for above-knee amputees

The aim of our study was to identify potential critical levels of implantation of an osseointegrated prosthesis for above-knee amputees. The implant used was the OPRA system. It was inserted in the femur at four different amputation heights, characterized by their residual limb ratios (0.299, 0.44, 0.58 and 0.73). The stress and strain distribution was evaluated in the bone-implant system during walking, considering a body mass of 100 kg. Considerably high stimulus (11,489 με) in the tissue near the tip was found at the highest implantation level. All models presented small non-physiologic stress values in the tissue around the implant. The results revealed that the implantation level has a decisive effect on bone-implant performance. Mainly, the analysis indicates adverse biomechanical conditions for implantations in very short residual limbs.     

Embryo ecology: Developmental synchrony and asynchrony in the embryonic development of wild annual fish populations

Embryo–environment interactions are of paramount importance during the development of all organisms, and impacts during this period can echo far into later stages of ontogeny. African annual fish of the genus Nothobranchius live in temporary pools and their eggs survive the dry season in the dry bottom substrate of the pools by entering a facultative developmental arrest termed diapause. Uniquely among animals, the embryos (encased in eggs) may enter diapause at three different developmental stages. Such a system allows for the potential to employ different regulation mechanisms for each diapause. We sampled multiple Nothobranchius embryo banks across the progressing season, species, and populations. We present important baseline field data and examine the role of environmental regulation in the embryonic development of this unique system. We describe the course of embryo development in the wild and find it to be very different from the typical development under laboratory conditions. Development across the embryo banks was synchronized within and across the sampled populations with all embryos entering diapause I during the rainy season and diapause II during the dry season. Asynchrony occurred at transient phases of the habitat, during the process of habitat desiccation, and at the end of the dry season. Our findings reveal the significance of environmental conditions in the serial character of the annual fish diapauses.     

Cadaverine in the Rat Brain: Regional Distribution and Acylation of [14C]Cadaverine In Vivo and Uptake In Vitro

Abstract— The regional distribution and acylation of intraventricularly injected [¹⁴C]cadaverine was studied in the rat brain over a 48-h period. The concentrations of labeled cadaverine and its acyl derivatives, N -monoacetylcadaverine and N -monopropionylcadaverine, were determined in the telencephalon, striatum, hypothalamus, midbrain, cerebellum, and medulla-pons by TLC of their 5-dimethylamino-1-naphthalenesulfonyl derivatives, followed by liquid scintillation spectrometry. The apparent passage of radioactivity from the ventricular space into brain tissue was slow, with the concentrations reaching a peak at 24 h after injection. The percentage of radioactivity in the acyl forms of cadaverine, however, was maximal 4 h after injection, with the propionyl form predominating. The telencephalon, striatum, and hypothalamus contained the highest concentrations of radioactivity, in all three forms, at all elapsed times. A high-affinity uptake mechanism for cadaverine was demonstrated in slices of these tissues. This process was completely inhibited by equimolar concentrations of unlabeled putrescine.     

Allogeneic bone marrow transplantation from HLA-identical siblings following conditioning with busulfan and cyclophosphamide. First results

In the time period from November 1984 to January 1987 eight allogeneic bone marrow transplantation were performed from HLA-identical siblings. The theoretical chance of success in this group was between 21 and 50%, according to the recent data of the International Bone Marrow Transplant Registry, depending on the diagnosis and clinical condition. The average chance was 37.5%. Haemopoietic reconstitution was achieved in 6 recipients, while 2 died of early complications (cytostatic induced hepatocellular damage and fungal sepsis). Another 3 patients died of complications of the intermediate period (pulmonary bleeding, virus hepatitis, graft rejection). The remaining 3 recipients are alive, in excellent clinical condition, including one girl surviving more than 2 years after the transplantation.     

Chemotactic response and motility of the mollusc parasitic nematode Phasmarhabditis papillosa towards mucus from different mollusc species

BioControl - Phasmarhabditis papillosa is a promising biocontrol agent of gastropods in crops. To enhance the efficacy of mollusc parasitic nematodes, a better understanding of the chemical...     

The principle of coherence in multi-level brain information processing

Synchronisation has become one of the major scientific tools to explain biological order at many levels of organisation. In systems neuroscience, synchronised subthreshold and suprathreshold oscillatory neuronal activity within and between distributed neuronal assemblies is acknowledged as a fundamental mode of neuronal information processing. Coherent neuronal oscillations correlate with all basic cognitive functions, mediate local and long-range neuronal communication and affect synaptic plasticity. However, it remains unclear how the very fast and complex changes of functional neuronal connectivity necessary for cognition, as mediated by dynamic patterns of neuronal synchrony, could be explained exclusively based on the well-established synaptic mechanisms. A growing body of research indicates that the intraneuronal matrix, composed of cytoskeletal elements and their binding proteins, structurally and functionally connects the synapses within a neuron, modulates neurotransmission and memory consolidation, and is hypothesised to be involved in signal integration via electric signalling due to its charged surface. Theoretical modelling, as well as emerging experimental evidence indicate that neuronal cytoskeleton supports highly cooperative energy transport and information processing based on molecular coherence. We suggest that long-range coherent dynamics within the intra- and extracellular filamentous matrices could establish dynamic ordered states, capable of rapid modulations of functional neuronal connectivity via their interactions with neuronal membranes and synapses. Coherence may thus represent a common denominator of neurophysiological and biophysical approaches to brain information processing, operating at multiple levels of neuronal organisation, from which cognition may emerge as its cardinal manifestation.