Opera Medica et Physiologica

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Printed March 31, 2017;
Published ahead of print April 11, 2017; Printed March 31, 2017; OM&P 2017 Volume 3 Issue 1, pages 1-13; doi:10.20388/omp2017.001.0041
Abstract Full Text

The role of chaos in biological information processing has been established as an  important breakthrough of nonlinear dynamics, after the early pioneering work of J.S. Nicolis and notably in neuroscience by the work of Walter J. Freeman and co-workers spanning more than three decades.  In this work we revisit the subject and we further focus on novel results that reveal its underlying logical  structure when  faced with the cognition of ambiguous stimuli. We demonstrate, by utilizing a minimal model for apprehension and judgement related to Bayesian updating,  that the fundamental characteristics of a biological processor obey in this case an extended, non-Boolean, logic which is characterized as  a quantum logic. And we realize that in its essence the role of chaos in biological information processing accounts for, and is fully compatible with, the logic of “quantum cognition” in psychology and neuroscience.

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Printed March 31, 2017;
Published ahead of print April 11, 2017; Printed March 31, 2017; OM&P 2017 Volume 3 Issue 1, pages 19-24; doi:10.20388/omp2017.001.0042
Abstract Full Text

Understanding the molecular and cellular processes that cause dementia is one of the most important challenges in neuroscience. SUMOylation is a post-translational protein modification that has been strongly implicated in neurodegenerative diseases. To investigate SUMOylation in dementia we profiled the expression of key SUMOylation pathway proteins in post mortem brain tissue from Alzheimer’s Disease (AD) and Down’s Syndrome (DS) patients. As expected, both AD and DS tissue displayed massively increased levels of phosphorylated tau compared to age- and sex-matched controls. Surprisingly, there were no changes in the levels of the E1 and E2 enzymes required for protein SUMOylation, or in levels of the deSUMOylating enzyme SENP1.  There was, however, a marked decrease in the SUMO-2/3-specific deSUMOylating enzyme SENP3 in DS. There were also increased levels of SUMO-1 conjugated proteins in DS, but not in AD tissue. While these results do not exclude roles for SUMOylation in AD, they demonstrate clear differences in the profile of SUMOylation and in the expression of deSUMOylating enzymes between AD and DS brain.

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Printed March 31, 2017;
Published ahead of print April 11, 2017; Printed March 31, 2017; OM&P 2017 Volume 3 Issue 1, pages 25-29; doi:10.20388/omp2017.001.0044
Abstract Full Text

Ulcerative colitis is a chronic inflammatory disease of the gastrointestinal system, affecting adults and children. Its cause is unknown, and the knowledge of reliable biomarkers is limited, especially for children. That makes the search for new biomarkers and pushing forth the analysis of the available data particularly challenging. We investigate proteomic data from children patients as a promising source, and tackle the problem implementing the recently developed parenclitic network approach to machine learning algorithms that solve classification task for proteomic data from healthy and diseased. We expect our approach to be applicable to other gastrointestinal diseases.

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Printed March 31, 2017;
Published ahead of print March 29, 2017; Printed March 31, 2017; OM&P 2017 Volume 3 Issue 1, pages 14-18; doi:10.20388/omp2017.001.0043
Abstract Full Text

A spatially stable pattern of two coexisting coherent and incoherent subpopulations in nonlocally coupled dynamical systems is called as chimera states and seen in many paradigmatic limit cycle as well as chaotic models where the coupling interaction is basically diffusive type. In neuronal networks, besides diffusive electrotonic communication via gap junctions, chemical transmission occurs between the pre-synapse and post-synapse of neurons. We consider, in a numerical study, a network of neurons in a ring using the Hindmarsh-Rose (HR) bursting model for each node of the network and, apply attractive gap junctions for local coupling between the nearest neighbors and inhibitory nonlocal coupling via chemical synaptic transmission between the distant neighbors. For a range of gap junctional and chemical synaptic coupling strengths, a subpopulation of the neuronal network, in the ring, bursts asynchronously and another subpopulation remains silent in a synchronous state. The bursting subpopulation of neurons fires sequentially along the ring when the number of firing nodes remains same but change their positions periodically in time. It appears as a traveling chimera pattern in the ring when the dynamics of the individual bursting nodes is chaotic. The chimera pattern travels in a reverse direction for a larger chemical synaptic coupling strength. A purely inhibitory chemical synaptic coupling can produce a similar traveling chimera pattern, however, the dynamics of the firing nodes is then periodic.

 

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Printed December 25, 2016;
Published ahead of print December 20, 2016; Printed December 25, 2016; OM&P 2016 Volume 2 Issue 3, pages 173-176; doi:10.20388/omp2016.003.0036
Abstract Full Text

Given the recent findings on the importance of CD38 signaling in the pathogenesis of colon cancer. We hypothesized that single nucleotide polymorphisms (SNP) in the CD38 gene may be related to colon cancer risk. CD38 has a genetic polymorphism, characterized by a C>G variation in the regulatory region of intron 1. The working hypothesis is that the presence of different alleles in colon cancer patients accounts for some of the clinical heterogeneity. CD38 is considered a marker of prognosis and as an indicator the activation and proliferation of cells. We hypothesized that single nucleotide polymorphisms (SNP) in the CD38 gene may be related to colon cancer risk. We evaluated one potentially functional CD38 SNP, intronic rs6449182 in two cases patients and controls. Genotyping was done using PCR-based assays in a total of 93 patients with colon cancer and 100 controls. We found that frequencies of variant allele (rs6449182 G) were significantly higher in colon cancer. Logistic regression analysis revealed an association between colon cancer and genotypes: rs6449182 CC [odds ratio (OR), 0.57; 95% confidence interval (95% CI), 0.32 – 1.01], rs6449182 CG (OR, 1.47; 95% CI, 0.83 – 2.60), and rs6449182 GG (OR, 2.26; 95% CI, 0.66 – 7.77). We observed that rs6449182 G carriers had more advanced clinical stage (P = 0.04). In conclusion, our data show that CD38 SNP may affect CD38 expression and contribute to the increased risk of colon cancer carcinogenesis.

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Printed December 25, 2016;
Published ahead of print December 19, 2016; Printed December 25, 2016; OM&P 2016 Volume 2 Issue 3, pages 177-180; doi:10.20388/omp2016.003.0037
Abstract Full Text

The assembly of neural circuits during development endows the brain with the ability to perceive the environment, control motor output, and perform higher cognitive functions. Failure to assemble proper neural circuits may result in neurodevelopmental disorders including intellectual disability and autism spectrum disorders. Epigenetic mechanisms, and in particular chromatin remodeling, are potent regulators of neuronal connectivity. Here, we review recent studies highlighting the essential role of the ATPdependent nucleosomal remodeling and deacetylase (NuRD) complex in epigenetic programming of neurons to drive neural circuit assembly and organism behavior. 

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Printed December 25, 2016;
Published ahead of print December 18, 2016; Printed December 25, 2016; OM&P 2016 Volume 2 Issue 3, pages 181-187; doi:10.20388/omp2016.003.0040
Abstract Full Text

Isolated brain tumors contain cells that exhibit stem cell features and a tissue microenvironment bearing remarkable similarities to the normal neurogenic niche. This supports the idea that neural stem (NSCs) or progenitor cells, and their progeny are the likely tumor cell(s) of origin. This prompted the investigation of the relationship between NSCs/progenitors and the initiation of tumorigenesis. These studies led to the identification of common signaling machineries underlying NSC development and tumor formation, particularly those with known roles in proliferation and cell fate determination. This review will explore the molecular mechanisms that regulate NSC behavior in the neurogenic niche of the forebrain, and how deregulation of the developmental potential of NSCs might contribute to tumorigenesis. 

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Printed December 25, 2016;
Published ahead of print December 17, 2016; Printed December 25, 2016; OM&P 2016 Volume 2 Issue 3, pages 188-204; doi:10.20388/OMP.003.0034
Abstract Full Text

Neurons adapt to stimuli through activity dependent changes to their transcriptome, a process mediated by immediate-early gene networks.  Recent findings that transcriptional activation of neuronal immediate-early genes requires the formation of controlled DNA double-strand breaks (DSBs) has come as a surprise and has profound implications for neuronal function, especially in the aging brain.  Here we review recent literature surrounding the phenomena of activity-dependent DNA DSBs in neurons and how this process may be exploited by transposable elements (TEs) in both naïve and aging neurons.  We hypothesize the existence of Activity DEPendent Transposition (ADEPT), where neuronal excitation is able to induce genomic rearrangements through either de novo integration of TEs or by homology-directed recombination of TE-derived repetitive sequences.  Epigenetic drift may cause the magnitude of ADEPT to increase with age, leading to genome instability, which we suggest presages most, if not all, neurodegenerative diseases.

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Printed December 25, 2016;
Published ahead of print December 16, 2016; Printed December 25, 2016; OM&P 2016 Volume 2 Issue 3, pages 205-210; doi:10.20388/omp2016.003.0039
Abstract Full Text

The presynaptic modifications that accompany long-term changes in synaptic plasticity are still not fully understood. Synaptophysin is a major synaptic vesicle protein involved in neurotransmitter release. We have used quantitative electron microscopy to study synaptophysin (Syn) immunolabelling in the hippocampus of adult rats 24h after induction in vivo of long term potentiation (LTP), and long term depression (LTD). Electrodes were implanted chronically in hippocampus with stimulation at either the medial (MPP) or lateral perforant path (LPP). 24h following induction of LTP or LTD rats were rapidly perfusion fixed and hippocampal tissue processed to electron microscopy via freeze substitution method. Anti-synaptophysin post-embedding immunolabelling was performed and tissue was imaged in the middle molecular layer (MML) of the dentate gyrus. There was a significant decrease in number of Syn labelled vesicles per unit area of bouton after LTP, but not LTD. An analysis of the spatial distribution of Syn labelled synaptic vesicles showed an increase in nearest neighbour distances, more so in the LTP than the LTD group, which is consistent with the overall decrease of Syn after LTP. These data are in agreement with the suggestion that Syn is involved in clathrin-dependent and “kiss and run” endocytosis which occurs perisynaptically. Thus, an increase in release of neurotransmitter and in consequence endocytosis would be consistent with an increased active zone distance for vesicles containing Syn.

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Printed December 25, 2016;
Published ahead of print December 15, 2016; Printed December 25, 2016; OM&P 2016 Volume 2 Issue 3, pages 211-227; doi:10.20388/ OMP.003.0035
Abstract Full Text

Neural prostheses (NPs) link the brain to external devices, with an eventual goal of recovery of motor and sensory functions to patients with neurological conditions. Over the past half-century, NPs have advanced significantly from the early ideas that sounded like science fiction to the modern high-tech implementations. In particular, invasive recordings using multichannel implants have enabled real-time control of artificial limbs by nonhuman primates and human subjects. Furthermore, NPs can provide artificial sensory feedback, allowing users to perceive the movements of prosthetic limbs and their haptic interaction with external objects. Recently, NP approach was used to build brain-nets that enable information exchange between individual brains and execution of cooperative tasks. This review focuses on invasive NPs for sensorimotor functions.

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