マウス瞬目反射逐次型特徴陽性弁別課題におけるムスカリン性アセチルコリン受容体と海馬シータ振動の関与

富山大学・富生命博甲第83号・MD. ASHRAFUR RAHMAN・2016/03/23富山大学201

A Model of Technology Transfer in Japan's Rapid Economic Growth Period

Why did the Japanese economy stagnate before World War II, how did it achieve rapid economic growth after the war, and why did it stagnate again after the 1970s? To answer these questions, I developed a two-country trade model with technology transfer, where firms in a developed country (the U.S.) transfer technology to the competitors in a developing country (Japan) if it is profitable to do so and where the technology transfer is the engine of economic growth. In this model, among multiple equilibria, the equilibrium with low labor cost in Japan was chosen during the rapid growth period. Then, the firms in the developed country transferred technology to the firms in the developing country, resulting in rapid growth. However, during the other periods, the equilibrium with high labor cost in Japan was chosen, which caused stagnation. The model is quantitatively consistent with the per capita GDP relative to the U.S., the purchasing power parity-exchange rate ratio, and to some degree, the swings in labor share of postwar Japan

Construction of copy number variation landscape and characterization of associated genes in a Bangladeshi cohort of neurodevelopmental disorders

Introduction: Copy number variations (CNVs) play a critical role in the pathogenesis of neurodevelopmental disorders (NDD) among children. In this study, we aim to identify clinically relevant CNVs, genes and their phenotypic characteristics in an ethnically underrepresented homogenous population of Bangladesh. Methods: We have conducted chromosomal microarray analysis (CMA) for 212 NDD patients with male to female ratio of 2.2:1.0 to identify rare CNVs. To identify candidate genes within the rare CNVs, gene constraint metrics [i.e., “Critical-Exon Genes (CEGs)”] were applied to the population data. Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) was followed in a subset of 95 NDD patients to assess the severity of autism and all statistical tests were performed using the R package. Results: Of all the samples assayed, 12.26% (26/212) and 57.08% (121/212) patients carried pathogenic and variant of uncertain significance (VOUS) CNVs, respectively. While 2.83% (6/212) patients’ pathogenic CNVs were found to be located in the subtelomeric regions. Further burden test identified females are significant carriers of pathogenic CNVs compared to males (OR = 4.2; p = 0.0007). We have observed an increased number of Loss of heterozygosity (LOH) within cases with 23.85% (26/109) consanguineous parents. Our analyses on imprinting genes show, 36 LOH variants disrupting 69 unique imprinted genes and classified these variants as VOUS. ADOS-2 subset shows severe social communication deficit (p = 0.014) and overall ASD symptoms severity (p = 0.026) among the patients carrying duplication CNV compared to the CNV negative group. Candidate gene analysis identified 153 unique CEGs in pathogenic CNVs and 31 in VOUS. Of the unique genes, 18 genes were found to be in smaller (<1 MB) focal CNVs in our NDD cohort and we identified PSMC3 gene as a strong candidate gene for Autism Spectrum Disorder (ASD). Moreover, we hypothesized that KMT2B gene duplication might be associated with intellectual disability. Conclusion: Our results show the utility of CMA for precise genetic diagnosis and its integration into the diagnosis, therapy and management of NDD patients

Role of Muscarinic Acetylcholine Receptors in Serial Feature-Positive Discrimination Task during Eyeblink Conditioning in Mice.

We investigated the role of muscarinic acetylcholine receptors (mAChRs) in eyeblink serial feature-positive discrimination learning in mice using the mAChR antagonist. A 2-s light cue was delivered 5 or 6 s before the presentation of a 350-ms tone paired with a 100-ms periorbital electrical shock (cued trial) but not before the tone-alone presentation (non-cued trial). Mice received 30 cued and 30 non-cued trials each day in a random order. We found that saline-injected control mice were successfully discriminating between cued and non-cued trials within a few days of conditioning. The mice responded more frequently to the tone in cued trials than in non-cued trials. Analysis of conditioned response (CR) dynamics revealed that the CR onset latency was shorter in cued trials than in non-cued trials, despite the CR peak amplitude not differing significantly between the two conditions. In contrast, scopolamine-injected mice developed an equal number of CRs with similar temporal patterns irrespective of the presence of the cue during the 7 days of conditioning, indicating in a failure to acquire conditional discrimination. In addition, the scopolamine administration to the control mice after they had successfully acquired discrimination did not impair the conditional discrimination and expression of pre-acquired CR. These results suggest that mAChRs may play a pivotal role in memory formation in the conditional brain state associated with the feature cue; however they are unlikely to be involved in the development of discrimination after conditional memory had formed in the serial feature-positive discrimination task during eyeblink conditioning

Change in hippocampal theta oscillation associated with multiple lever presses in a bimanual two-lever choice task for robot control in rats.

Hippocampal theta oscillations have been implicated in working memory and attentional process, which might be useful for the brain-machine interface (BMI). To further elucidate the properties of the hippocampal theta oscillations that can be used in BMI, we investigated hippocampal theta oscillations during a two-lever choice task. During the task body-restrained rats were trained with a food reward to move an e-puck robot towards them by pressing the correct lever, ipsilateral to the robot several times, using the ipsilateral forelimb. The robot carried food and moved along a semicircle track set in front of the rat. We demonstrated that the power of hippocampal theta oscillations gradually increased during a 6-s preparatory period before the start of multiple lever pressing, irrespective of whether the correct lever choice or forelimb side were used. In addition, there was a significant difference in the theta power after the first choice, between correct and incorrect trials. During the correct trials the theta power was highest during the first lever-releasing period, whereas in the incorrect trials it occurred during the second correct lever-pressing period. We also analyzed the hippocampal theta oscillations at the termination of multiple lever pressing during the correct trials. Irrespective of whether the correct forelimb side was used, the power of hippocampal theta oscillations gradually decreased with the termination of multiple lever pressing. The frequency of theta oscillation also demonstrated an increase and decrease, before and after multiple lever pressing, respectively. There was a transient increase in frequency after the first lever press during the incorrect trials, while no such increase was observed during the correct trials. These results suggested that hippocampal theta oscillations reflect some aspects of preparatory and cognitive neural activities during the robot controlling task, which could be used for BMI

Blockade of the M1 muscarinic acetylcholine receptors impairs eyeblink serial feature-positive discrimination learning in mice.

The serial feature-positive discrimination task requires the subjects to respond differentially to the identical stimulus depending on the temporal context given by a preceding cue stimulus. In the present study, we examined the involvement of the M1 muscarinic acetylcholine receptors using a selective M1 antagonist VU0255035 in the serial feature-positive discrimination task of eyeblink conditioning in mice. In this task, mice received a 2-s light stimulus as the conditional cue 5 or 6 s before the presentation of a 350-ms tone conditioned stimulus (CS) paired with a 100-ms peri-orbital electrical shock (cued trials), while they did not receive the cue before the presentation of the CS alone (non-cued trials). Each day mice randomly received 30 cued and 30 non-cued trials. We found that VU0255035 impaired acquisition of the conditional discrimination as well as the overall acquisition of the conditioned response (CR) and diminished the difference in onset latency of the CR between the cued and non-cued trials. VU0255035 administration to the control mice after sufficient learning did not impair the pre-acquired conditional discrimination or the CR expression itself. These effects of VU0255035 were almost similar to those with the scopolamine in our previous study, suggesting that among the several types of muscarinic acetylcholine receptors, the M1 receptors may play an important role in the acquisition of the conditional discrimination memory but not in mediating the discrimination itself after the memory had formed in the eyeblink serial feature-positive discrimination learning

Modeling SARS-CoV-2 spread with dynamic isolation

Background: The SARS-CoV-2 pandemic is spreading with a greater intensity across the globe. The synchrony of public health interventions and epidemic waves signify the importance of evaluation of the underline interventions. Method: We developed a mathematical model to present the transmission dynamics of SARS-CoV-2 and to analyze the impact of key nonpharmaceutical interventions such as isolation and screening program on the disease outcomes to the people of New Jersey, USA. We introduced a dynamic isolation of susceptible population with a constant (imposed) and infection oriented interventions. Epidemiological and demographic data are used to estimate the model parameters. The baseline case was explored further to showcase several critical and predictive scenarios. Results and analysis: The model simulations are in good agreement with the infection data for the period of 5 March 2020 to 31 January 2021. Dynamic isolation and screening program are found to be potential measures that can alter the course of epidemic. A  7% increase in isolation rate may result in a 31% reduction of epidemic peak whereas a 3 times increase in screening rate may reduce the epidemic peak by 35%. The model predicts that nearly 9.7% to 12% of the total population of New Jersey may become infected within the middle of July 2021 along with 24.6 to 27.3 thousand cumulative deaths. Within a wide spectrum of probable scenarios, there is a possibility of third wave Conclusion: Our findings could be informative to the public health community to contain the pandemic in the case of economy reopening under a limited or no vaccine coverage. Additional epidemic waves can be avoided by appropriate screening and isolation plans.

Pharmaceutical quality evaluation of marketed vildagliptin tablets in Bangladesh based on the United States Pharmacopeia specifications

Continuous monitoring of pharmaceutical products is vital because it matters to human health. Here we aimed to assess the quality parameters of commercially available vildagliptin tablets in Bangladesh. We tested the tablets for the content uniformity, hardness, friability, disintegration, dissolution, and potency. Then, we fitted the dissolution data with kinetic models to investigate the release pattern of the studied brands. Moreover, we applied a mathematical model-independent approach to compare the dissolution profiles of the brands. The interchangeability was determined using difference and similarity factors. Weight variation, friability, and hardness were between 150.35±1.26 to 230.8±1.98 mg, 0 to 0.88%, and 47.3±5.09 to 108.1±1.92 N, respectively. All tablets disintegrated within 0.54±2.85 to 7.69±2.14 min in distilled water. The potency of tablets in 0.1 N HCl and PBS (pH 6.8) were between 97.67±2.58 to 105±0.95% and 99±4.63 to 105±1.65%, respectively. The drug release (%) in 0.1 N HCl and phosphate-buffered saline (PBS) (pH 6.8) after 60 min were between 99.37±1.80 to 111.09±0.64% and 96.59±3.52 to 109.57±0.53%, respectively. All the brands complied with the United States Pharmacopeia (USP) specification for physicochemical properties. Also, we observed the drug release patterns of vildagliptin tablets matched with different kinetic models. We found only one substitutable brand with the standard product regardless of the dissolution medium. In-vitro chemical equivalence is not always consistent with bioequivalence. Therefore, continuous evaluation of marketed products is essential to ensure the desired quality