Search results for: huntington

Authors: Jamal Abdi

Abstract:

This paper offers a critique of Samuel P. Huntington's Clash of Civilizations thesis. The overriding argument is that Huntington's thesis is characterized by failure to distinguish between 'groups' and 'categories'. Multinational civilizations overcoming their internal collective action problems, which would enable them to pursue a unified strategy vis-à-vis the West, is a rather foundational assumption in his theory. Without assigning sufficient intellectual attention to the processes through which multinational civilizations may gain the capacity for concerted action, i.e., become a group, he contended that the post-cold-war world would be shaped in large measure by interactions among seven or eight major civilizations. Thus, failure in providing a convincing analysis of multi-national civilizations' transition from categories to groups is a significant weakness in Huntington's clash theory. It is also suggested that so-called Islamic terrorism and the war on terror is not to be taken as an expression of the presence of clash between a Western and an Islamic civilization, as terrorist organizations would be superfluous in a world characterized by clash of civilizations. Consequences of multinational civilizations becoming a group are discussed in relation to contemporary Western superiority.

Keywords: clash of civilizations, groups, categories, groupism

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Authors: Jamal Abdi

Abstract:

This paper is largely a response/critique of Samuel P. Huntington´s Clash of Civilizations thesis. The overriding argument is that Huntington´s thesis is characterized by failure to distinguish between ´groups´ and ´categories´. Multinational civilizations overcoming their internal collective action problems, which would enable them to pursue a unified strategy vis-à-vis the West, is a rather foundational assumption in his theory. Without assigning sufficient intellectual attention to the processes through which multinational civilizations may gain capacity for concerted action i.e. become a group, he contended that the post-cold-war world would be shaped in large measure by interactions among seven or eight major civilizations. Thus, failure in providing a convincing analysis of multi-national civilizations´ transition from categories to groups is a significant weakness in Huntington´s clash theory. It is also suggested that so-called Islamic terrorism and the war on terror is not to be taken as an expression of presence of clash between a Western and an Islamic civilization, as terrorist organizations would be superfluous in a world characterized by clash of civilizations. Consequences of multinational civilizations becoming a group are discussed in relation to contemporary Western superiority.

Keywords: categories, civilizations, clash, groups, groupness

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Authors: Laura Gantley, Vanessa M. Conn, Stuart Webb, Kirsty Kirk, Marta Gabryelska, Duncan Holds, Brett W. Stringer, Simon J. Conn

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Trinucleotide repeat disorders comprise ~20 severe, inherited human neuromuscular and neurodegenerative disorders, which are a result of an abnormal expansion of repetitive sequences in the DNA. The most common of these, Huntington’s disease, results from the expansion of the CAG repeat region in exon 1 of the HTT gene via an unknown mechanism. Non-coding RNAs have been implicated in the initiation and progression of many diseases; thus, we focus on one circular RNA (circRNA) molecule arising from non-canonical splicing (back splicing) of HTT pre-mRNA. This circRNA and its mouse orthologue were transgenically overexpressed in human cells (SHSY-5Y and HEK293T) and mouse cells (Mb1), respectively. High-content imaging and flow cytometry demonstrated the overexpression of this circRNA reduces cell proliferation, reduces nuclear size independent of cellular size, and alters cell cycle progression. Analysis of protein by western blot and immunofluorescence demonstrated no change to HTT protein levels but altered nuclear-cytoplasmic distribution without impacting the expansion of the HTT repeat region. As these phenotypic and genotypic changes are found in Huntington’s disease patients, these results may suggest that this circRNA may play a functional role in the progression of Huntington’s disease.

Keywords: cell biology, circular RNAs, Huntington’s disease, molecular biology, neurodegenerative disorders

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Authors: Naznine Anwar, Kim Cornish, Izelle Labuschagne, Nellie Georgiou-Karistianis

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Falls and subsequent injuries are common features in symptomatic Huntington’s disease (symp-HD) individuals. As part of daily walking, navigating around obstacles may incur a greater risk of falls in symp-HD. We designed obstacle-crossing experiment to examine adaptive gait dynamics and to identify underlying spatiotemporal gait characteristics that could increase the risk of falling in symp-HD. This experiment involved navigating around one or two ground-based obstacles under two conditions (walking while navigating around one obstacle, and walking while navigating around two obstacles). A total of 32 participants were included, 16 symp-HD and 16 healthy controls with age and sex matched. We used a GAITRite electronic walkway to examine the spatiotemporal gait characteristics and inter-trail gait variability when participants walked at their preferable speed. A minimum of six trials were completed which were performed for baseline free walk and also for each and every condition during navigating around the obstacles. For analysis, we separated all walking steps into three phases as approach steps, navigating steps and recovery steps. The mean and inter-trail variability (within participant standard deviation) for each step gait variable was calculated across the six trails. We found symp-HD individuals significantly decreased their gait velocity and step length and increased step duration variability during the navigating steps and recovery steps compared with approach steps. In contrast, HC individuals showed less difference in gait velocity, step time and step length variability from baseline in both respective conditions as well as all three approaches. These findings indicate that increasing spatiotemporal gait variability may be a possible compensatory strategy that is adopted by symp-HD individuals to effectively navigate obstacles during walking. Such findings may offer benefit to clinicians in the development of strategies for HD individuals to improve functional outcomes in the home and hospital based rehabilitation program.

Keywords: Huntington’s disease, gait variables, navigating around obstacle, basal ganglia dysfunction

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Authors: Sunidhi Syal, Rasangi Tennakoon, Patrick O'Donoghue

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Polyglutamine (polyQ) diseases are a group of diseases related to neurodegeneration caused by repeats of the amino acid glutamine (Q) in the DNA, which translates into an elongated polyQ tract in the protein. The pathological explanation is that the polyQ tract forms cytotoxic aggregates in the neurons, leading to their degeneration. There are no cures or preventative efforts established for these diseases as of today, although the symptoms of these diseases can be relieved. This study specifically focuses on Huntington's disease, which is a type of polyQ disease in which aggregation is caused by the extended cytosine, adenine, guanine (CUG) codon repeats in the huntingtin (HTT) gene, which encodes for the huntingtin protein. Using this principle, we attempted to create six models, which included mutating wildtype tRNA alanine variant tRNA-AGC-8-1 to have glutamine anticodons CUG and UUG so serine is incorporated at glutamine sites in poly Q tracts. In the process, we were successful in obtaining tAla-8-1 CUG mutant clones in the HTTexon1 plasmids with a polyQ tract of 23Q (non-pathogenic model) and 74Q (disease model). These plasmids were transfected into mouse neuroblastoma cells to characterize protein synthesis and aggregation in normal and mistranslating cells and to investigate the effects of glutamines replaced with alanines on the disease phenotype. Notably, we observed no noteworthy differences in mean fluorescence between the CUG mutants for 23Q or 74Q; however, the Triton X-100 assay revealed a significant reduction in insoluble 74Q aggregates. We were unable to create a tAla-8-1 UUG mutant clone, and determining the difference in the effects of the two glutamine anticodons may enrich our understanding of the disease phenotype. In conclusion, by generating structural disruption with the amino acid alanine, it may be possible to find ways to minimize the toxicity of Huntington's disease caused by these polyQ aggregates. Further research is needed to advance knowledge in this field by identifying the cellular and biochemical impact of specific tRNA variants found naturally in human genomes.

Keywords: Huntington's disease, polyQ, tRNA, anticodon, clone, overlap PCR

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Authors: Ravi Raghav Sonani, Niraj Kumar Singh, Jitendra Kumar, Datta Madamwar

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Phycobiliproteins (PBPs) are light harvesting proteins showing very strong absorbance and fluorescence in the visible range of the solar spectrum. Phycoerythrin (PE) and phycocyanin (PC) are majorly found PBPs in the cyanobacteria and red algae. In the present study, we have investigated the reactive oxygen species (ROS)-averting capacity of purified PE and PC of cyanobacterial origin. Furthermore, the possibility - whether the ROS-averting potential of PBPs can be explored in the therapeutics of oxidative stress associated physiological anomalies including aging and neurodegenerative diseases. The nematode Caenorhabditis elegans has been used as model organism in this study. PE and PC treatment moderated normal aging and associated physiological functionalities like pharyngeal pumping and locomotion of C. elegans. Moreover, PE-treatment enhanced the stress (oxidative and heat) tolerance upon PE and PC treatment. Specifically, PE treatment was also noted to moderate the progression of Alzheimer’s disease in transgenic C. elegans CL4176. However, PC-treatment curtailed the polyQ aggregation mediated proteotoxicity in C. elegans AM141 (Huntington disease model) under stressed (paraquat stress) as well as normal conditions. The effectiveness of PE and PC in expanding the lifespan of mutant C. elegans knockout for some up- (daf 16) and down- (daf-2 and age-1) stream regulators of insulin/IGF-1 signalling (IIS) shows the independency of their effects from DAF-2–AGE-1–DAF-16 signalling pathway. In conclusion, the present report demonstrates the anti-aging and neuro-protective potential of cyanobacterial PE and PC.

Keywords: phycobiliproteins, aging, alzheimer, huntington, C. elegans

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Authors: Sandra Baez, Mariana Pino, Mildred Berrio, Hernando Santamaria-Garcia, Lucas Sedeno, Adolfo Garcia, Sol Fittipaldi, Agustin Ibanez

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Schadenfreude refers to the perceiver’s experience of pleasure at another’s misfortune. This is a multidetermined emotion which can be evoked by hostile feelings and envy. The experience of Schadenfreude engages mechanisms implicated in diverse social cognitive processes. For instance, Schadenfreude involves heightened reward processing, accompanied by increased striatal engagement and it interacts with mentalizing and perspective-taking abilities. Patients with Huntington's disease (HD) exhibit reductions of Schadenfreude experience, suggesting a role of striatal degeneration in such an impairment. However, no study has directly assessed the relationship between regional brain atrophy in HD and reduced Schadenfreude. This study investigated whether gray matter (GM) atrophy in HD patients correlates with ratings of Schadenfreude. First, we compared the performance of 20 HD patients and 23 controls on an experimental task designed to trigger Schadenfreude and envy (another social emotion acting as a control condition). Second, we compared GM volume between groups. Third, we examined brain regions where atrophy might be associated with specific impairments in the patients. Results showed that while both groups showed similar ratings of envy, HD patients reported lower Schadenfreude. The latter pattern was related to atrophy in regions of the reward system (ventral striatum) and the mentalizing network (precuneus and superior parietal lobule). Our results shed light on the intertwining of reward and socioemotional processes in Schadenfreude, while offering novel evidence about their neural correlates. In addition, our results open the door to future studies investigating social emotion processing in other clinical populations characterized by striatal or mentalizing network impairments (e.g., Parkinson’s disease, schizophrenia, autism spectrum disorders).

Keywords: envy, Gray matter atrophy, Huntigton's disease, Schadenfreude, social emotions

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Authors: J. Tochukwu Omenma

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Buzzword in Nigeria is that democracy has “come to stay”. Politicians in their usual euphoria consider democracy as already consolidated in the country. Politicians linked this assumption to three fundamental indicators – (a) multiparty system; (b) regular elections and (c) absence of military coup after 15 years of democracy in Nigeria. Beyond this assumption, we intend to empirically verify these claims and assumptions, by relying on Huntington’s conceptualization of democratic consolidation. Though, Huntington asserts that multipartism, regular elections and absence of any major obstacle leading to reversal of democracy are significant indicators of democratic consolidation, but the presence of those indicators must result to alternation of executive power for democratic consolidation to occur. In other words, regular conduct of election and existence of multiple political parties are not enough for democratic consolidation, rather free and fair elections. Past elections were characterized of massive fraud and irregularities casting doubts on integrity of electoral management body (EMB) to conduct free and fair elections in Nigeria. There are three existing perspectives that have offered responses to the emasculation of independence of EMB. One is a more popular position indicating that the incumbent party, more than the opposition party, influence the EMB activities with the aim of rigging elections; the other is a more radical perspective that suggests that weakening of EMB power is more associated with the weakest party than with the incumbent; and the last, is that godfather(s) are in direct control of EMB members thereby controlling the process of electoral process to the advantage of the godfather(s). With empirical evidence sourced from the reports of independent election monitors, (European Union, Election Observation Mission in Nigeria) this paper shows at different electoral periods that, in terms of influencing election outcomes, the incumbent and godfather have been more associated with influencing election results than the opposition. The existing nature of executive power in Nigeria provides a plausible explanation for the incumbent’s overbearing influence thereby limiting opportunity for free and fair elections and by extension undermining the process of democratic consolidation in Nigeria.

Keywords: political party, democracy, democratic consolidation, election, godfatherism

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Authors: Ali Bahri Lubis

Abstract:

Tryptophan oxidation by Heme-dioxygenase enzyme is initial important stepTryptophan oxidation by Heme-dioxygenase enzyme is initial important step in kynurenine pathway implicating to several severe diseases such as Parkinson’s Disease, Huntington Disease, poliomyelitis and cataract. It is crucial to comprehend the oxidation mechanism with the hope to find decent treatment upon abovementioned diseases. The mechanism has been debatable since no one has been yet proved the mechanism obviously. In this research we have attempted to prove mechanistic steps of tryptophan oxidation via human indoleamine dioxygenase (h-IDO) using various substrates: L-tryptophan, L-tryptophan (indole-ring-2-13C), L-fully-labelled13C-tryptophan, L-N-methyl-tryptophan, L-tryptophan and 2-amino-3-(benzo(b)thiophene-3-yl) propanoic acid. All enzyme assay experiments were measured using a UV-Vis spectrophotometer, LC-MS, 1H-NMR, and HSQC. We also successfully synthesized enzyme products as our control in NMR measurements. The result exhibited that the distinct substrates produced N-formyl kynurenine (NFK) and hydroxypyrrolloindoleamine carboxylate acid (HPIC) in different concentrations and isomers, correlated to the proposal of considered mechanism reaction in kynurenine pathway implicating to several severe diseases such as Parkinson’s Disease, Huntington Disease, poliomyelitis and cataract. It is crucial to comprehend the oxidation mechanism with the hope to find decent treatment for the abovementioned diseases. The mechanism has been debatable since no one has yet proven the mechanism obviously. In this research we have attempted to prove mechanistic steps of tryptophan oxidation via human indoleamine dioxygenase (h-IDO) using various substrates: L-tryptophan, L-tryptophan (indole-ring-2-13C), L-fully-labelled13C-tryptophan, L-N-methyl-tryptophan, L-tryptophan and 2-amino-3-(benzo(b)thiophene-3-yl) propanoic acid. All enzyme assay experiments were measured using a UV-Vis spectrophotometer, LC-MS, 1H-NMR and HSQC. We also successfully synthesized enzyme products as our control in NMR measurements. The result exhibited that the distinct substrates produced N-formyl kynurenine (NFK) and hydroxypyrrolloindoleamine carboxylate acid (HPIC) in different concentrations and isomers, correlated to the proposal of considered mechanism reaction.

Keywords: heme-dioxygenase enzyme, tryptophan oxidation, kynurenine pathway, n-formyl kynurenine

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Authors: T. Heikkinen, J. Oksman, T. Bragge, A. Nurmi, O. Kontkanen, T. Ahtoniemi

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Motor impairment is an inherent phenotypic feature of several chronic neurodegenerative diseases, and pharmacological therapies aimed to counterbalance the motor disability have a great market potential. Animal models of chronic neurodegenerative diseases display a number deteriorating motor phenotype during the disease progression. There is a wide array of behavioral tools to evaluate motor functions in rodents. However, currently existing methods to study motor functions in rodents are often limited to evaluate gross motor functions only at advanced stages of the disease phenotype. The most commonly applied traditional motor assays used in CNS rodent models, lack the sensitivity to capture fine motor impairments or improvements. Fine motor skill characterization in rodents provides a more sensitive tool to capture more subtle motor dysfunctions and therapeutic effects. Importantly, similar approach, kinematic movement analysis, is also used in clinic, and applied both in diagnosis and determination of therapeutic response to pharmacological interventions. The aim of this study was to apply kinematic gait analysis, a novel and automated high precision movement analysis system, to characterize phenotypic deficits in three different chronic neurodegenerative animal models, a transgenic mouse model (SOD1 G93A) for amyotrophic lateral sclerosis (ALS), and R6/2 and Q175KI mouse models for Huntington’s disease (HD). The readouts from walking behavior included gait properties with kinematic data, and body movement trajectories including analysis of various points of interest such as movement and position of landmarks in the torso, tail and joints. Mice (transgenic and wild-type) from each model were analyzed for the fine motor kinematic properties at young ages, prior to the age when gross motor deficits are clearly pronounced. Fine motor kinematic Evaluation was continued in the same animals until clear motor dysfunction with conventional motor assays was evident. Time course analysis revealed clear fine motor skill impairments in each transgenic model earlier than what is seen with conventional gross motor tests. Motor changes were quantitatively analyzed for up to ~80 parameters, and the largest data sets of HD models were further processed with principal component analysis (PCA) to transform the pool of individual parameters into a smaller and focused set of mutually uncorrelated gait parameters showing strong genotype difference. Kinematic fine motor analysis of transgenic animal models described in this presentation show that this method isa sensitive, objective and fully automated tool that allows earlier and more sensitive detection of progressive neuromuscular and CNS disease phenotypes. As a result of the analysis a comprehensive set of fine motor parameters for each model is created, and these parameters provide better understanding of the disease progression and enhanced sensitivity of this assay for therapeutic testing compared to classical motor behavior tests. In SOD1 G93A, R6/2, and Q175KI mice, the alterations in gait were evident already several weeks earlier than with traditional gross motor assays. Kinematic testing can be applied to a wider set of motor readouts beyond gait in order to study whole body movement patterns such as with relation to joints and various body parts longitudinally, providing a sophisticated and translatable method for disseminating motor components in rodent disease models and evaluating therapeutic interventions.

Keywords: Gait analysis, kinematic, motor impairment, inherent feature

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Authors: Rasha M. Hussein, Reem M. Hashem, Laila A. Rashed

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Alzheimer’s disease is the most common dementia disease in the elderly. It is characterized by the accumulation of extracellular amyloid β (Aβ) peptides and intracellular hyper-phosphorylated tau protein. In addition, recent evidence indicates that accumulation of intracellular amyloid β peptides may play a role in Alzheimer’s disease pathogenesis. This suggests that intracellular Heat Shock Proteins (HSP) that maintain the protein quality control in the cell might be potential candidates for disease amelioration. DNAJB6, a member of DNAJ family of HSP, effectively prevented the aggregation of poly glutamines stretches associated with Huntington’s disease both in vitro and in cells. In addition, DNAJB6 was found recently to delay the aggregation of Aβ42 peptides in vitro. In the present study, we investigated the ability of DNAJB6 to prevent the aggregation of both intracellular and extracellular Aβ peptides using transfection of HEK293 cells with Aβ-GFP and recombinant Aβ42 peptides respectively. We performed western blotting and immunofluorescence techniques. We found that DNAJB6 can prevent Aβ-GFP aggregation, but not the seeded aggregation initiated by extracellular Aβ peptides. Moreover, DNAJB6 required interaction with HSP70 to prevent the aggregation of Aβ-GFP protein and its J-domain was essential for this anti-aggregation activity. Interestingly, overexpression of other DNAJ proteins as well as HSPB1 suppressed Aβ-GFP aggregation efficiently. Our findings suggest that DNAJB6 is a promising candidate for the inhibition of Aβ-GFP mediated aggregation through a canonical HSP70 dependent mechanism.

Keywords: Aβ, Alzheimer’s disease, chaperone, DNAJB6, aggregation

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Authors: Anjani Kumar Tiwari, Neelam Kumari, Anil Mishra

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The family of phosphodiesterases (PDEs) plays a critical role in control of the level, localization, and duration of intracellular 3’-5’-cyclic adenosine monophosphate (cAMP) and 3’-5’-cyclic guanosine monophosphate (cGMP) signals by specifically hydrolyzing these cyclic nucleotides. As the involvement of cyclic nucleotide second messengers in cell signaling and homeostasis is established, the regulation of these pathways in the brain by various PDE isoforms is an area of considerable interest, as they are involved in nearly all brain functions and in the etiology of neuropsychiatric diseases. The PDE10A isoform, isolated from different species and characterized regarding structure and function, has received much attention in recent years, particularly in the context of schizophrenia and Huntington’s disease, which are both related to a role of PDE10A in the regulation of striatal dopaminergic neurotransmission. Quinazoline analogue 1-(4-methoxyphenyl)-6,7-dimethoxyquinazoline, was evaluated as specific PET marker for phosphodiesterase (PDE) 10A. Here, we report the radiosynthesis of [11C]2 and the in vitro and in vivo evaluation of [11C]2 as a potential positron emission tomography (PET) radiotracer for imaging PDE10A in the central nervous system (CNS). The radiosynthesis of [11C]2 was achieved by O-methylation of the corresponding des-methyl precursor with [11C]methyl iodide. [11C]2 was obtained with ∼50% radiochemical yield. PET imaging studies in rat brain displayed initial specific uptake with very rapid clearance of [11C]2 from brain. Though [11C]2 is not an ideal radioligand for clinical imaging of PDE10A in the CNS. Modified analogue of quinazoline having a higher potency for inhibiting PDE10A and improved pharmacokinetic properties will be necessary for imaging this enzyme with PET.

Keywords: PDE10A, PET, radiotracer, quinazoline

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Authors: Saleh Maina

Abstract:

There is an on-going debate among intellectuals and scholars of international relations and world politics over the direction which the world is heading particularly in the current era of globalization. On the one hand are adherents to the convergence thesis which is premised on the assumption that global social order is tending toward universalism which could translate into the possible end of the classical state system and the unification of world societies under a single and common ideological dispensation. The convergence thesis is hinged on the globalization process which is gradually reducing world societies into a 'global village'. On the other hand are intellectuals who hold the view that despite advances made in communication technology which appear to threaten the survival of the classical state system. Invariance, as expressed in the survival of the existing state system and the diverse social traditions in world societies, remain a realistic possibility contrary to the conclusions of the convergence thesis. The invariance thesis has been advanced by scholars like Samuel P. Huntington whose work on clash of civilizations suggests that world peace can only be sustained through the co-habitation of diverse civilizations across the world. The purpose of this paper is to examine both sides of the debate with the aim of making a realistic assessment on where world societies are headed, between convergence and invariance. Using the realist theory of international relations as our theoretical premise the paper argues that while there is sufficient ground to predict the future direction of world societies as headed towards some form of convergence, invariance as expressed in the co-existence of diverse civilizations will for a long time remain a major feature of the international system.

Keywords: convergence, invariance, clash of civilization, classical state system, universalism

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Authors: Ali Bahri Lubis

Abstract:

Tryptophan oxidation by Heme-dioxygenase enzyme is the initial rate-limiting step in the kynurenine pathway, which leads to the formation of NADH and dangerous metabolites, implicating several severe diseases such as Parkinson’s Disease, Huntington's Disease, poliomyelitis and cataract. This oxidation, generally, allows tryptophan to convert to N-Formylkynurenine (NFK). Observing the catalytic mechanism of Heme dioxygenase in tryptophan oxidation has been a debatably scientific interest since no one has yet proven the mechanism obviously. In this research we have attempted to prove mechanistic steps of tryptophan oxidation via human indoleamine dioxygenase (h-IDO) utilising various substrates: L-tryptophan, L-tryptophan (indole-ring-2-¹³C), L-fully-labelled¹³C-tryptophan, L-N-methyl-tryptophan, L-tryptophanol and 2-amino-3-(benzo(b)thiophene-3-yl) propanoic acid. All enzyme assay experiments were measured using a UV-Vis spectrophotometer, LC-MS, 1H-NMR and HSQC. We also successfully synthesised enzyme products as our control in NMR measurements. The result exhibited that all substrates produced N-formyl kynurenine (NFK), and a side, the minor product of hydroxypyrrolloindoleamine carboxylic acid (HPIC) in cis and trans isomer, except 1-methyl tryptophan only generating cis HPIC. Interestingly, L- tryptophanol was oxidised to form HPIC derivative as a major product and 5-hydroxy tryptophan was converted to NFK derivative instead without any HPIC derivative. The bizarre result of oxidation underwent in 2-amino-3-(benzo(b)thiophene-3-yl) propanoic acid, which produced epoxide cyclic. Those phenomena have been explainable in our research based on the proposed mechanism of how tryptophan is oxidised by human indoleamine dioxygenase.

Keywords: tryptophan oxidation, heme-dioxygenases, human indoleamine dioxygenases, N-formylkynurenine, hydroxypyrroloindoleamine carboxylic acid

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Authors: Ali̇ Bayram, Semih Dalkilic, Remzi Yigiter

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N-methyl-D-aspartate (NMDA) receptor is a subtype of glutamate receptor and plays a pivotal role in learning, memory, neuronal plasticity, neurotoxicity and synaptic mechanisms. Animal experiments were suggested that glutamate-induced excitotoxic injuriy and NMDA receptor blockage lead to amnesia and other neurodegenerative diseases including Alzheimer’s disease (AD), Huntington’s disease, amyotrophic lateral sclerosis. Aim of this study is to investigate association between NMDA receptor coding gene GRIN2B expression level and Alzheimer disease. The study was approved by the local ethics committees, and it was conducted according to the principles of the Declaration of Helsinki and guidelines for the Good Clinical Practice. Peripheral blood was collected 50 patients who diagnosed AD and 49 healthy control individuals. Total RNA was isolated with RNeasy midi kit (Qiagen) according to manufacturer’s instructions. After checked RNA quality and quantity with spectrophotometer, GRIN2B expression levels were detected by quantitative real time PCR (QRT-PCR). Statistical analyses were performed, variance between two groups were compared with Mann Whitney U test in GraphpadInstat algorithm with 95 % confidence interval and p < 0.05. After statistical analyses, we have determined that GRIN2B expression levels were down regulated in AD patients group with respect to control group. But expression level of this gene in each group was showed high variability. İn this study, we have determined that NMDA receptor coding gene GRIN2B expression level was down regulated in AD patients when compared with healthy control individuals. According to our results, we have speculated that GRIN2B expression level was associated with AD. But it is necessary to validate these results with bigger sample size.

Keywords: Alzheimer’s disease, N-methyl-d-aspartate receptor, NR2B, GRIN2B, mRNA expression, RT-PCR

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Authors: R. Bužgová, R. Kozáková, M. Škutová, M. Bar, P. Ressner, P. Bártová

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Introduction: Currently, there has been an increasing concern about the provision of palliative care in non-oncological patients in both professional literature and clinical practice. However, there is not much scientific information on how to provide neurological and palliative care together. The main objective of the project is to create and to verify a concept of neuro-palliative and rehabilitative care for patients with selected neurological diseases in an advanced stage of the disease and also to evaluate bio-psychosocial and spiritual needs of these patients and their caregivers related to the quality of life using created standardized tools. Methodology: Triangulation of research methods (qualitative and quantitative) will be used. A concept of care and assessment tools will be developed by analyzing interviews and focus groups. Qualitative data will be analyzed using grounded theory. The concept of care will be tested in the context of the intervention study. Using quantitative analysis, we will assess the effect of an intervention provided on the saturation of needs, quality of life, and quality of care. A research sample will be made up of the patients with selected neurological diseases (Parkinson´s syndrome, motor neuron disease, multiple sclerosis, Huntington’s disease), together with patients´ family members. Based on the results, educational materials and a certified course for health care professionals will be created. Findings: Based on qualitative data analysis, we will propose the concept of integrated care model combining neurological, rehabilitative and specialist palliative care for patients with selected neurological diseases in different settings of care and services. Patients´ needs related to quality of life will be described by newly created and validated measuring tools before the start of intervention (application of neuro-palliative and palliative approach) and then in the time interval. Conclusion: Based on the results, educational materials and a certified course for doctors and health care professionals will be created.

Keywords: multidisciplinary approach, neuropalliative care, research, quality of life

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Authors: Hajar Zarei, AliAkbar Zarenejadatashgah, Vuk Uskoković, Hiroshi Watabe

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The reactive oxygen species (ROS) generated by radiation in nuclear diagnostic imaging and radiotherapy could damage the structure of the proteins in noncancerous cells surrounding the tumor. The critical factor in many age-related diseases, such as Alzheimer, Parkinson, or Huntington diseases, is the oxidation of proteins by the ROS as molecular triggers of the given pathologies. Our studies by spectroscopic experiments showed doses close to therapeutic ones (1 to 5 Gy) could lead to changes of secondary and tertiary structures in BSA protein macromolecule as a protein model as well as the aggregation of polypeptide chain but without the fragmentation. For this reason, we investigated the radioprotective effects of natural (vitamin C and E) and synthetic materials (CNPs and FIOMPs) on the structural changes in BSA protein induced by gamma irradiation at a therapeutic dose (3Gy). In the presence of both vitamins and synthetic materials, the spectroscopic studies revealed that irradiated BSA was protected from the structural changes caused by ROS, according to in vitro research. The radioprotective property of CNPs and FIOMPs arises from enzyme mimetic activities (catalase, superoxide dismutase, and peroxidase) and their antioxidant capability against hydroxyl radicals. In the case of FIOMPs, a porous structure also leads to increased ROS recombination with each other in the same radiolytic track and subsequently decreased encounters with BSA. The hydrophilicity of vitamin C resulted in the major scavenging of ROS in the solvent, whereas hydrophobic vitamin E localized on the nonpolar patches of the BSA surface, where it did not only neutralize them thanks to the moderate BSA binding constant but also formed a barrier for diffusing ROS. To the best of our knowledge, there has been a persistent lack of studies investigating the radioactive effect of mentioned materials on proteins. Therefore, the results of our studies can open a new widow for application of these common dietary ingredients and new synthetic NPs in improving the safety of radiotherapy.

Keywords: reactive oxygen species, spectroscopy, bovine serum albumin, gamma radiation, radioprotection

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Authors: Paula Pita-Galán

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In 1920 Georgiana Goddard King, an Art Historian and Professor at Bryn Mawr College (PA, USA), published The Way of Saint James (New York: P.G. Putnam’s Sons), one of the earliest modern guides of this pilgrimage route. In its three volumes, the author described the towns and villages crossed by the Camino, talking about the history, traditions, monuments, and the people that she had met during her own pilgrimage together with the photographer Edith H. Lowber. The two women walked the route from Toulouse to Santiago in several journeys that took place between 1911 and 1914, travelling with funds of the Hispanic Society of New York. The cultural interest that motivated the journey explains how King intertwines in her narration history, anthropology, geography, art history, and religion, giving; as a result, the book targeted intellectuals, curious travelers, and tourist rather than pilgrims in a moment in which the pilgrimage to Santiago had almost disappeared as a practice. The Way of Saint James is barely known nowadays, so the aim of this research is disseminate it, focusing on the modernity of its approach and pointing at the link that it has with Georgiana King’s understanding of art as a product of the culture and civilization that produces it. In this paper, we will analyze The Way of Saint James in its historiographical context as it was written during the rise of the interest on Spain and its culture in the United States of America; paying special attention on the relationship of the author with the Hispanic Society and sir Archer Milton Huntington. On the other hand, we will look into Georgiana Goddard King’s work as an scholar by analyzing her works and the personal papers (letters, notes, and manuscripts) that she left in Bryn Mawr College, where I have been researching with a Fulbright grant. As a result, we will understand the pioneer approach of this unique guide of the Way of Saint James as a reflection of Georgiana King’s own modernity as an scholar. The wide cultural interests of King gave, as a result, a guide that offers a transversal knowledge of The Way of Saint James, together with King’s impressions and experiences, in the same way of current guides but far from the ‘objective’ and formalist methodology followed by her colleagues. This kind of modernity was badly understood at her time and helped the oblivion of this book as well as her author.

Keywords: georgiana goddard king, the way of saint james, pilgrimage, cultural heritage, guide

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Authors: Edwin Dankano

Abstract:

Evident by incessant and sporadic attacks on Nigerians poise a serious threat to the unity of Nigeria, and secondly, the single biggest security nightmare to confront Nigeria since after amalgamation of the Southern and Northern protectorates by the British colonialist in 1914 is “Boko Haram” a terrorist organization also known as “Jama’atul Ahli Sunnah Lidda’wati wal Jihad”, or “people committed to the propagation of the Prophet’s teachings and jihad”. The sect also upholds an ideology translated as “Western Education is forbidden”, or rejection of Western civilization and institutions. By some estimates, more than 5,500 people were killed in Boko Haram attacks in 2014, and Boko Haram attacks have already claimed hundreds of lives and territories {caliphates}in early 2015. In total, the group may have killed more than 10,000 people since its emergence in the early 2000s. More than 1 million Nigerians have been displaced internally by the violence, and Nigerian refugee figures in neighboring countries continue to rise. This paper is predicated on secondary sources of data and anchored on the Huntington’s theory of clash of civilization. As such, the paper argued that the rise of Boko Haram with its violent disposition against Western values is a counter response to Western civilization that is fast eclipsing other civilizations. The paper posits that the Boko Haram insurrection going by its teachings, and destruction of churches is a validation of the propagation of the sect as a religious revolt which has resulted in dire humanitarian situation in Adamawa, Borno, Yobe, Bauchi, and Gombe states all in north eastern Nigeria as evident in human casualties, human right abuses, population displacement, refugee debacle, livelihood crisis, and public insecurity. The paper submits that the Nigerian state should muster the needed political will in terms of a viable anti-terrorism measures and build strong legitimate institutions that can adequately curb the menace of corruption that has engulfed the military hierarchy, respond proactively to the challenge of terrorism in Nigeria and should embrace a strategic paradigm shift from anti-terrorism to counter-terrorism as a strategy for containing the crisis that today threatens the secular status of Nigeria.

Keywords: Boko Haram, civilization, fundamentalism, Islam, religion revolt, terror

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Authors: Judy M. Obliosca, Olivia Vest, Sandra Poulos, Kelsi Smith, Tammy Ferguson, Abigail Powers Lott, Alicia K. Smith, Yang Xu, Christopher K. Tison

Abstract:

Post-Traumatic Stress Disorder (PTSD) is a mental health problem that people may develop after experiencing traumatic events such as combat, natural disasters, and major emotional challenges. Tragically, the number of military personnel with PTSD correlates directly with the number of veterans who attempt suicide, with the highest rate in the Army. Research has shown epigenetic risks in those who are prone to several psychiatric dysfunctions, particularly PTSD. Once initiated in response to trauma, epigenetic alterations in particular, the DNA methylation in the form of 5-methylcytosine (5mC) alters chromatin structure and represses gene expression. Current methods to detect DNA methylation, such as bisulfite-based genomic sequencing techniques, are laborious and have massive analysis workflow while still having high error rates. A faster and simpler detection method of high sensitivity and precision would be useful in a clinical setting to confirm potential PTSD etiologies, prevent other psychiatric disorders, and improve military health. A nano-enhanced Surface Plasmon Resonance imaging (SPRi)-based assay that simultaneously detects site-specific 5mC base (termed as PTSD base) in methylated genes related to PTSD is being developed. The arrays on a sensing chip were first constructed for parallel detection of PTSD bases using synthetic and genomic DNA (gDNA) samples. For the gDNA sample extracted from the whole blood of a PTSD patient, the sample was first digested using specific restriction enzymes, and fragments were denatured to obtain single-stranded methylated target genes (ssDNA). The resulting mixture of ssDNA was then injected into the assay platform, where targets were captured by specific DNA aptamer probes previously immobilized on the surface of a sensing chip. The PTSD bases in targets were detected by anti-5-methylcytosine antibody (anti-5mC), and the resulting signals were then enhanced by the universal nanoenhancer. Preliminary results showed successful detection of a PTSD base in a gDNA sample. Brighter spot images and higher delta values (control-subtracted reflectivity signal) relative to those of the control were observed. We also implemented the in-house surface activation system for detection and developed SPRi disposable chips. Multiplexed PTSD base detection of target methylated genes in blood DNA from PTSD patients of severity conditions (asymptomatic and severe) was conducted. This diagnostic capability being developed is a platform technology, and upon successful implementation for PTSD, it could be reconfigured for the study of a wide variety of neurological disorders such as traumatic brain injury, Alzheimer’s disease, schizophrenia, and Huntington's disease and can be extended to the analyses of other sample matrices such as urine and saliva.

Keywords: epigenetic assay, DNA methylation, PTSD, whole blood, multiplexing

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