A Neural Network Reveals Motoric Effects of Maternal Preconception Exposure to Nicotine on Rat Pup Behavior: A New Approach for Movement Disorders Diagnosis.

Neurodevelopmental disorders can stem from pharmacological, genetic, or environmental causes and early diagnosis is often a key to successful treatment. To improve early detection of neurological motor impairments, we developed a deep neural network for data-driven analyses. The network was applied to study the effect of maternal nicotine exposure prior to conception on 10-day-old rat pup motor behavior in an open field task. Female Long-Evans rats were administered nicotine (15 mg/L) in sweetened drinking water (1% sucralose) for seven consecutive weeks immediately prior to mating. The neural network outperformed human expert designed animal locomotion measures in distinguishing rat pups born to nicotine exposed dams vs. control dams (87 vs. 64% classification accuracy). Notably, the network discovered novel movement alterations in posture, movement initiation and a stereotypy in "warm-up" behavior (repeated movements along specific body dimensions) that were predictive of nicotine exposure. The results suggest novel findings that maternal preconception nicotine exposure delays and alters offspring motor development. Similar behavioral symptoms are associated with drug-related causes of disorders such as autism spectrum disorder and attention-deficit/hyperactivity disorder in human children. Thus, the identification of motor impairments in at-risk offspring here shows how neuronal networks can guide the development of more accurate behavioral tests to earlier diagnose symptoms of neurodevelopmental disorders in infants and children.

Prenatal stress dysregulates resting-state functional connectivity and sensory motifs.

Prenatal stress (PS) can impact fetal brain structure and function and contribute to higher vulnerability to neurodevelopmental and neuropsychiatric disorders. To understand how PS alters evoked and spontaneous neocortical activity and intrinsic brain functional connectivity, mesoscale voltage imaging was performed in adult C57BL/6NJ mice that had been exposed to auditory stress on gestational days 12-16, the age at which neocortex is developing. PS mice had a four-fold higher basal corticosterone level and reduced amplitude of cortical sensory-evoked responses to visual, auditory, whisker, forelimb, and hindlimb stimuli. Relative to control animals, PS led to a general reduction of resting-state functional connectivity, as well as reduced inter-modular connectivity, enhanced intra-modular connectivity, and altered frequency of auditory and forelimb spontaneous sensory motifs. These resting-state changes resulted in a cortical connectivity pattern featuring disjoint but tight modules and a decline in network efficiency. The findings demonstrate that cortical connectivity is sensitive to PS and exposed offspring may be at risk for adult stress-related neuropsychiatric disorders.

A modified Ising model of Barabási-Albert network with gene-type spins.

The central question of systems biology is to understand how individual components of a biological system such as genes or proteins cooperate in emerging phenotypes resulting in the evolution of diseases. As living cells are open systems in quasi-steady state type equilibrium in continuous exchange with their environment, computational techniques that have been successfully applied in statistical thermodynamics to describe phase transitions may provide new insights to the emerging behavior of biological systems. Here we systematically evaluate the translation of computational techniques from solid-state physics to network models that closely resemble biological networks and develop specific translational rules to tackle problems unique to living systems. We focus on logic models exhibiting only two states in each network node. Motivated by the apparent asymmetry between biological states where an entity exhibits boolean states i.e. is active or inactive, we present an adaptation of symmetric Ising model towards an asymmetric one fitting to living systems here referred to as the modified Ising model with gene-type spins. We analyze phase transitions by Monte Carlo simulations and propose a mean-field solution of a modified Ising model of a network type that closely resembles a real-world network, the Barabási-Albert model of scale-free networks. We show that asymmetric Ising models show similarities to symmetric Ising models with the external field and undergoes a discontinuous phase transition of the first-order and exhibits hysteresis. The simulation setup presented herein can be directly used for any biological network connectivity dataset and is also applicable for other networks that exhibit similar states of activity. The method proposed here is a general statistical method to deal with non-linear large scale models arising in the context of biological systems and is scalable to any network size.

Pattern formation in reaction-diffusion systems in the presence of non-Markovian diffusion.

We study reaction-diffusion systems beyond the Markovian approximation to take into account the effect of memory on the formation of spatiotemporal patterns. Using a non-Markovian Brusselator model as a paradigmatic example, we show how to use reductive perturbation to investigate the formation and stability of patterns. Focusing in detail on the Hopf instability and short-term memory, we derive the corresponding complex Ginzburg-Landau equation that governs the amplitude of the critical mode and we establish the explicit dependence of its parameters on the memory properties. Numerical solution of this memory-dependent complex Ginzburg-Landau equation as well as direct numerical simulation of the non-Markovian Brusselator model illustrates that memory changes the properties of the spatiotemporal patterns. Our results indicate that going beyond the Markovian approximation might be necessary to study the formation of spatiotemporal patterns even in systems with short-term memory. At the same time, our work opens up a new window into the control of these patterns using memory.

Instability in reaction-superdiffusion systems.

We study the effect of superdiffusion on the instability in reaction-diffusion systems. It is shown that reaction-superdiffusion systems close to a Turing instability are equivalent to a time-dependent Ginzburg-Landau model and the corresponding free energy is introduced. This generalized free energy which depends on the superdiffusion exponent governs the stability, dynamics, and the fluctuations of reaction-superdiffusion systems near the Turing bifurcation. In addition, we show that for a general n-component reaction-superdiffusion system, a fractional complex Ginzburg-Landau equation emerges as the amplitude equation near a Hopf instability. Numerical simulations of this equation are carried out to illustrate the effect of superdiffusion on spatiotemporal patterns. Finally, the effect of superdiffusion on the instability in the Brusselator model, as a special case of reaction-diffusion systems, is studied. In general, superdiffusion introduces a new parameter that changes the behavior of the system near the instability.

Diffusion Weighted Imaging in Acute Attacks of Multiple Sclerosis.

BACKGROUND: Multiple sclerosis (MS) is one of the most common autoimmune disorders of the central nervous system. In spite of various imaging modalities, the definitive diagnosis of MS remains challenging. OBJECTIVES: This study was designed to evaluate the usefulness of diffusion weighted imaging (DWI) in the diagnosis of acute MS attack and to compare its results with contrast enhanced MRI (CE-MRI). PATIENTS AND METHODS: In this cross sectional study, seventy patients with definite diagnosis of relapsing-remitting MS were included. CE-MRI using 0.1 mmol/kg gadolinium as well as DWI sequences were performed for all patients. The percentage of patients with positive DWI was compared with the results of CE-MRI and the consistency between the two imaging modalities was evaluated. Moreover, the relationship between the time of onset of patient's symptoms and test results for both methods were investigated. RESULTS: CE-MRI yielded positive results for 61 (87%) patients and DWI yielded positive for 53 (76%) patients. In fifty patients (71.42%), both tests were positive and in six cases (8.57%), both were negative. The test results of three patients turned out to be positive in DWI, while they tested negative in CE-MRI. There was no significant relationship between the results of CE-MRI as well as DWI and the time of imaging from the onset of symptoms. CONCLUSION: These data indicate that while CE-MRI will depict more positive results, there are cases in which DWI will show a positive result while CE-MRI is negative. We suggest that the combination of these two imaging modalities might yield more positive results in diagnosing acute MS attack giving rise to a more accurate diagnosis.

Cytokines gene expression in newly diagnosed multiple sclerosis patients.

Multiple Sclerosis (MS) is characterized by multiple areas of inflammation, demyelination and neurodegeneration. Infiltrating Th1 CD4+ T cells secrete proinflammatory cytokines. They stimulate the release of some cytokines, expression of adhesion molecules and these cytokines may cause damage to the myelin sheath and axons. In this study, we analyzed plasma levels and gene expressions of five important cytokines in the new diagnosed MS Patients by ELISA and Real time PCR. PCR amplifications were performed to determine the IL-17, IL-23, IL-10, IL-27 and TGF-ß mRNA expression levels using the SYBR Green PCR Kit. Our results showed significant decrease in IL-10, IL-27 and TGF-ß but there was no significant difference in the IL-17 and IL-23 between patients and healthy controls. Altogether, our results indicated that dysregulation of cytokines, mainly increased expression of pro-inflammatory cytokines and decreased expression of inhibitory cytokines occurred in MS patients. This study may shed light to the probable role of these cytokines in neurodegeneration mechanism and current or future use of cytokines in managing and treatment of multiple sclerosis.

Molecular characterization and phylogenetic study of Newcastle disease viruses isolated in Iran, 2010-2012.

Newcastle disease (ND) is a highly contagious viral disease and has been a constant threat to the poultry industry worldwide. In this study, partial sequences of ND virus (NDV) fusion genome collected from some provinces in Iran during 2010-2012 in vaccinated commercial farms were characterized and compared with other NDV sequences. All viruses showed the amino acid sequence 112 RRQKRF117 at the C-terminus of the F2 protein and phenylalanine at the N-terminus of the F1 protein, residue 117. These amino acid sequences were identical to a known virulent motif. The phylogenetic analysis showed that the Iranian ND isolates in this study are closely related to the genotype VIId of class II NDV strains. The emergence and identification of new sublineages provide an insight into the high rate of genetic drift occurring in NDV strains in Iran, and raise many concerns about the efficacy of current ND control measures in the country.

The relationship between sociability and productivity.

INTRODUCTION: When productivity is in the same way with culture and organized socialization, it is the gem of organization that can ensure stableness and survival of the organizations and be the mechanism for taking the competitive advantage. In contrast, the attention to socialization and the effect of that on productivity is less than its effect on public culture and organization culture. Hence this article evaluates the relationship between these variables in two groups of employees in selected hospitals in Isfahan. MATERIALS AND METHODS: This study is descriptive - correlation. The subject society who was studied was employees (nurses and staffs) of Kashany educational public hospital, Isabn Maryam public hospital, charitable Hojatie hospital and private Sadi hospitals in Isfahan province. For determination of socialization, the Biligard questionnaire and for productivity of employees the productivity questionnaire based on Goldesmit model were used that the justifiability and stability of them are confirmed by experts. The number of subject under study is calculated based on 250 persons-formula sampling. RESULTS: There is a direct and significant correlation between socialization and productivity. On the other hand, the factors such age, sex, organizational position, history and the kind of employment, had no role excluding Sadi hospital. CONCLUSION: Although the productivity of the employees affects the accessibility of the hospital to its effective goals, the effective factors that play a role in increasing or decreasing the accessibility cannot be ignored.