Diverse antidepressants increase CDP-diacylglycerol production and phosphatidylinositide resynthesis in depression-relevant regions of the rat brain

<p>Abstract</p> <p>Background</p> <p>Major depression is a serious mood disorder affecting millions of adults and children worldwide. While the etiopathology of depression remains obscure, antidepressant medications increase synaptic levels of monoamine neurotransmitters in brain regions associated with the disease. Monoamine transmitters activate multiple signaling cascades some of which have been investigated as potential mediators of depression or antidepressant drug action. However, the diacylglycerol arm of phosphoinositide signaling cascades has not been systematically investigated, even though downstream targets of this cascade have been implicated in depression. With the ultimate goal of uncovering the primary postsynaptic actions that may initiate cellular antidepressive signaling, we have examined the antidepressant-induced production of CDP-diacylglycerol which is both a product of diacylglycerol phosphorylation and a precursor for the synthesis of physiologically critical glycerophospholipids such as the phosphatidylinositides. For this, drug effects on [³H]cytidine-labeled CDP-diacylglycerol and [³H]inositol-labeled phosphatidylinositides were measured in response to the tricyclics desipramine and imipramine, the selective serotonin reuptake inhibitors fluoxetine and paroxetine, the atypical antidepressants maprotiline and nomifensine, and several monoamine oxidase inhibitors.</p> <p>Results</p> <p>Multiple compounds from each antidepressant category significantly stimulated [³H]CDP-diacylglycerol accumulation in cerebrocortical, hippocampal, and striatal tissues, and also enhanced the resynthesis of inositol phospholipids. Conversely, various antipsychotics, anxiolytics, and non-antidepressant psychotropic agents failed to significantly induce CDP-diacylglycerol or phosphoinositide synthesis. Drug-induced CDP-diacylglycerol accumulation was independent of lithium and only partially dependent on phosphoinositide hydrolysis, thus indicating that antidepressants can mobilize CDP-diacylglycerol from additional pools lying outside of the inositol cycle. Further, unlike direct serotonergic, muscarinic, or α-adrenergic agonists that elicited comparable or lower effects on CDP-diacylglycerol versus inositol phosphates, the antidepressants dose-dependently induced significantly greater accumulations of CDP-diacylglycerol.</p> <p>Conclusion</p> <p>Chemically divergent antidepressant agents commonly and significantly enhanced the accumulation of CDP-diacylglycerol. The latter is not only a derived product of phosphoinositide hydrolysis but is also a crucial intermediate in the biosynthesis of several signaling substrates. Hence, altered CDP-diacylglycerol signaling might be implicated in the pathophysiology of depression or the mechanism of action of diverse antidepressant medications.</p

Whole genome sequencing of four representatives from the admixed population of the United Arab Emirates

© Copyright © 2020 Daw Elbait, Henschel, Tay and Al Safar. Whole genome sequences (WGS) of four nationals of the United Arab Emirates (UAE) at an average coverage of 33X have been completed and described. The selection of suitable subpopulation representatives was informed by a preceding comprehensive population structure analysis. Representatives were chosen based on their central location within the subpopulation on a principal component analysis (PCA) and the degree to which they were admixed. Novel genomic variations among the different subgroups of the UAE population are reported here. Specifically, the WGS analysis identified 4,161,067–4,798,806 variants in the four individual samples, where approximately 80% were single nucleotide polymorphisms (SNPs) and 20% were insertions or deletions (indels). An average of 2.75% was found to be novel variants according to dbSNP (build 151). This is the first report of structural variants (SV) from WGS data from UAE nationals. There were 15,677–20,339 called SVs, of which around 13.5% were novel. The four samples shared 1,399,178 variants, each with distinct variants as follows: 1,085,524 (for the individual denoted as UAE S011), 1,228,559 (UAE S012), 791,072 (UAE S013), and 906,818 (UAE S014). These results show a previously unappreciated population diversity in the region. The synergy of WGS and genotype array data was demonstrated through variant annotation of the former using 2.3 million allele frequencies for the local population derived from the latter technology platform. This novel approach of combining breadth and depth of array and WGS technologies has guided the choice of population genetic representatives and provides complementary, regionalized allele frequency annotation to new genomes comprising millions of loci

A population-specific major allele reference genome from the United Arab Emirates population

The ethnic composition of the population of a country contributes to the uniqueness of each national DNA sequencing project and, ideally, individual reference genomes are required to reduce the confounding nature of ethnic bias. This work represents a representative Whole Genome Sequencing effort of an understudied population. Specifically, high coverage consensus sequences from 120 whole genomes and 33 whole exomes were used to construct the first ever population specific major allele reference genome for the United Arab Emirates (UAE). When this was applied and compared to the archetype hg19 reference, assembly of local Emirati genomes was reduced by ∼19% (i.e., some 1 million fewer calls). In compiling the United Arab Emirates Reference Genome (UAERG), sets of annotated 23,038,090 short (novel: 1,790,171) and 137,713 structural (novel: 8,462) variants; their allele frequencies (AFs) and distribution across the genome were identified. Population-specific genetic characteristics including loss-of-function variants, admixture, and ancestral haplogroup distribution were identified and reported here. We also detect a strong correlation between F and admixture components in the UAE. This baseline study was conceived to establish a high-quality reference genome and a genetic variations resource to enable the development of regional population specific initiatives and thus inform the application of population studies and precision medicine in the UAE. S

Genetic diversity and low stratification of the population of the United Arab Emirates

© Copyright © 2020 Tay, Henschel, Daw Elbait and Al Safar. With high consanguinity rates on the Arabian Peninsula, it would not have been unexpected if the population of the United Arab Emirates (UAE) was shown to be relatively homogenous. However, this study of 1000 UAE nationals provided a contrasting perspective, one of a relatively heterogeneous population. Located at the apex of Europe, Asia, and Africa, the observed diversity could be explained by a plethora of migration patterns since the first Out-of-Africa movement. A strategy to explore the extent of genetic variation of the population of the UAE is presented. The first step involved a comprehensive population stratification study that was instructive for subsequent whole genome sequencing (WGS) of suitable representatives (which is described elsewhere). When these UAE data were compared to previous smaller studies from the region, the findings were consistent with a population that is a diverse and admixed group of people. However, rather than sharp and distinctive clusters, cluster analysis reveals low levels of stratification throughout the population. UAE emirates exhibit high within-Emirate-distance/among-Emirate distance ratios. Supervised admixture analysis showed a continuous gradient of ancestral populations, suggesting that admixture on the south eastern tip of the Arabian Peninsula occurred gradually. When visualized using a unique technique that combined admixture ratios and principal component analysis (PCA), unappreciated diversity was revealed while mitigating projection bias of conventional PCA. We observe low population stratification in the UAE in terms of homozygosity versus separation cluster coefficients. This holds for the UAE in a global context as well as for isolated cluster analysis of the Emirati birthplaces. However, the subtle clustering observed in the Emirates reflects geographic proximity and historic migration events. The analytical strategy used here highlights the complementary nature of data from genotype array and WGS for anthropological studies. Specifically, genotype array data were instructive to select representative subjects for WGS. Furthermore, from the 2.3 million allele frequencies obtained from genotype arrays, we identified 46,481 loci with allele frequencies that were significantly different with respect to other world populations. This comparison of allele frequencies facilitates variant prioritization in common diseases. In addition, these loci bear great potential as biomarkers in anthropological and forensic studies

Rhizostoma optimization algorithm and its application in different real-world optimization problems

In last decade, numerous meta-heuristic algorithms have been proposed for dealing the complexity and difficulty of numerical optimization problems in the realworld which is growing continuously recently, but only a few algorithms have caught researchers’ attention. In this study, a new swarm-based meta-heuristic algorithm called Rhizostoma optimization algorithm (ROA) is proposed for solving the optimization problems based on simulating the social movement of Rhizostoma octopus (barrel jellyfish) in the ocean. ROA is intended to mitigate the two optimization problems of trapping in local optima and slow convergence. ROA is proposed with three different movement strategies (simulated annealing (SA), fast simulated annealing (FSA), and Levy walk (LW)) and tested with 23 standard mathematical benchmark functions, two classical engineering problems, and various real-world datasets including three widely used datasets to predict the students’ performance. Comparing the ROA algorithm with the latest meta-heuristic optimization algorithms and a recent published research proves that ROA is a very competitive algorithm with a high ability in optimization performance with respect to local optima avoidance, the speed of convergence and the exploration/exploitation balance rate, as it is effectively applicable for performing optimization tasks

Cellular Transplantation-Based Therapeutic Strategies for Spinal Cord Injuries: Preclinical and Clinical Updates

Spinal cord injury (SCI) is a distressing neurological condition that causes loss of neural tissue, with subsequent damages to neural circuitry, and loss of sensorimotor function. The SCIs have an estimated incidence rate of ~80 cases per million populations. Till date, no ratified effective therapeutic strategy for SCIs exist; however, recent advancements in regenerative medicines to protect and regenerate damaged/lost neural tissues following SCIs have shown promising results in preclinical and clinical trials. Moreover, there is a greater need to fully understand underlying mechanisms following cellular transplantation that can be achieved through proper differentiation of desired cell type, and their in-vivo tracking of migration, proliferation and integration into the host system. Furthermore, techniques that can prevent teratomas formation following cellular transplantation have been reported. In addition to the ongoing comprehensive neuroregenerative and neuroprotective therapeutic strategies for SCIs, novel technologies are emerging including neuroscience-based computational and robotic rehabilitational therapies. These improved strategies in combination with cell-based therapeutic approaches are opening new avenues for future research to completely cure SCIs. Herein, we intended to review pathophysiological mechanisms following SCI, preclinical and clinical updates of cellular transplantation, the extent of success from these transplantations, associated controversies and other emerging technologies

Analisis Keterampilan Metakognisi Berpikir Kreatif dalam Menyelesaikan Masalah Matematika Pokok Bahasan Segiempat Siswa Kelas Akselerasi di MTs Negeri 2 Jember

Tujuan dari penelitian ini untuk mendeskripsikan keterampilan metakognisi berpikir kreatif dalam menyelesaikan masalah matematika. Penelitian ini merupakan jenis penelitian deskriptif. Subjek penelitian sebanyak 21 siswa kelas Akselerasi MTs Negeri 2 Jember.Metode pengumpulan data dengan tes berpikir kreatif dan wawancara. Berpikir kreatif siswa diukur menggunakan 3 kriteria berpikir kreatif, yaitu kefasihan, fleksibilitas, dan kebaruan. Tingkat berpikir kreatif atau disebut TBK dikategorikan menjadi 5 tingkatan, yaitu TBK 4 (sangat kreatif), TBK 3 (kreatif), TBK 2 (cukup kreatif), TBK 1 (kurang kreatif), dan TBK 0 (tidak kreatif). Hasil yang diperoleh dari tes berpikir kreatif adalah 14 siswa termasuk kategori tidak kreatif, 4 siswa termasuk kategori kurang kreatif, dan 3 siswa termasuk kategori cukup kreatif. Siswa kategori tidak kreatif tidak memenuhi indikator keterampilan metakognisi. Pada monitoring, siswa tidak dapat menentukan strategi untuk menyelesaikan masalah. Pada evaluasi, siswa tidak mengevaluasi atau memperbaiki kembali cara dan perhitungan. Siswa kategori kurang kreatif dapat memahami soal dan menentukan rencana di awal. Pada monitoring, strategi diselesaikan dengan langkah-langkah yang sudah benar. Pada evaluasi, siswa secara sadar mengetahui kesalahannya tetapi tidak mengevaluasi kembali pekerjaannya. Siswa kategori cukup kreatif memenuhi indikator keterampilan metakognisi. Siswa mengidentifikasi informasi dan menentukan rencana awal dengan baik. Pada monitoring, siswa dapat menentukan strategi untuk menyelesaikan masalah. Pada evaluasi, siswa mengevaluasi langkah atau perhitungan pemecahan masalah. &nbsp; Kata Kunci: Berpikir kreatif, keterampilan metakognisi, pemecahan masala

Water and Beverage Consumption among a Nationally Representative Sample of Children and Adolescents in the United Arab Emirates.

There are limited studies examining water consumption among individuals in hot climates. We assessed the daily total water intake from plain water, other beverages, and food in a nationally representative sample of children and adolescents aged 6-18 years in the United Arab Emirates. Total water intake was compared against the recommendations of the Institute of Medicine and the European Food Safety Authority. Sociodemographic information, 24 h dietary recall, physical activity levels, and anthropometric data were collected from 527 participants. The mean ± SE of total water intake was 1778.4 ± 33.8 mL/day. Plain drinking water was the largest contributor to total water intake (51.6%), followed by food (27.3%). Sugar-sweetened beverages constituted 13.9% of water intake. The proportion of participants who met the Institute of Medicine recommendations ranged from 15% (males aged 14-18) to 25% (children aged 6-8). The proportion of participants who met the European Food Safety Authority recommendations ranged from 31% (females aged 14-18) to 36% (males aged 14-18). The water-to-energy ratio was 1.0-1.15 L/1000 kcal, meeting recommendations. The majority of participants failed to meet water intake recommendations, highlighting the need for targeted interventions to promote increased water consumption among children and adolescents

Effects of deforestation on physicochemical properties and microbial population of soils in a South-East Asian tropical forest

The study was conducted in deforested land and adjacent natural forest in Chittagong Forest South Division, Bangladesh, to explore the effects of deforestation on physico-chemical properties of soil and the soil microbial population. Soil samples from surface (0-10 cm depth) or subsurface (10-20 cm depth) of two hill positions (top and bottom) of deforested land and an adjacent natural forest were collected and analysed for their physico-chemical properties and microbial population. The study reveals that there was no significant (p≤0.05) difference in soil texture for soil surfaces or hill positions between the deforested land and natural forest. However, significantly (p≤0.05) low moisture content and high pH was observed in both the surfaces and hill position in deforested land compared to the natural forest. The microbial community i.e., the fungal and bacterial population was also significantly (p≤0.05) lower in both surfaces (0-10 cm and 10-20 cm) of hill positions in the deforested land compared to natural forest. Fungal population ranged from 59 to 76 million g-1 and 78 to 153 million g-1 of dry soil in deforested land and in natural forest, respectively, whereas bacterial population ranged from 70 to 146 million g-1 in deforested land and from 127 to 218 million g-1 in natural forest. A total of seven genera of fungi were primarily identified from the soils of natural forest and six from the deforested land. The six common genera of identified fungi in both the land used were Mucor, Aspergillus, Rhizopus, Fusarium, Penicillium and Trichoderma and the different one was Colletotrichum from the natural forest. Three genera of bacteria coccus, Streptococcus and Basillus were noticed in natural forest and two genera (coccus and Streptococcus) were recorded from deforested land