Design, synthesis and anticholinergic properties of novel α-benzyl dopamine, tyramine, and phenethylamine derivatives.

Due to the important biological properties of dopamine, phenethylamine, and tyramine derivatives in the central nervous system, herein the synthesis of novel α-benzyl dopamine, phenethylamine, and tyramine derivatives is described. The title compounds were synthesized starting from 3-phenylpropanoic acids and methoxybenzenes in six or seven steps. Firstly, 3-(2,3-dimethoxyphenyl)propanoic acid (11) and 3-(3,4-dimethoxyphenyl)propanoic acid (12) were selectively brominated with N-bromosuccinimide (NBS). The Friedel-Crafts acylation of methoxylated benzenes with these brominated acids or commercially available 3-phenylpropanoic acid in polyphosphoric acid gave the desired dihydrochalcones. α-Carboxylation of dihydrochalcones, reduction of benzylic carbonyl groups, hydrolysis of esters to acid derivatives, and the Curtius rearrangement reaction of acids followed by in situ synthesis of carbamates from alkyl isocyanates and hydrogenolysis of the carbamates afforded the title compounds in good total yields. Alzheimer's disease (AD) and Parkinson's disease (PD) are chronic neurodegenerative diseases that become serious over time. However, the exact pathophysiology of both diseases has not been revealed yet. There have been many different approaches to the treatment of patients for many years, especially studies on the cholinergic system cover a wide area. Within the scope of this study, the inhibition effects of dopamine-derived carbamates and amine salts on the cholinergic enzymes AChE and BChE were examined. Dopamine-derived carbamate 24a-i showed inhibition in the micro-nanomolar range; compound 24d showed a Ki value of 26.79 nM against AChE and 3.33 nM against BChE, while another molecule, 24i, showed a Ki range of 27.24 nM and 0.92 nM against AChE and BChE, respectively. AChE and BChE were effectively inhibited by dopamine-derived amine salts 25j-s, with Ki values in the range of 17.70 to 468.57 µM and 0.76-211.23 µM, respectively. Additionally, 24c, 24e and 25m were determined to be 60, 276 and 90 times more selective against BChE than AChE, respectively.

Regulatory-systemic approach in Aspergillus niger for bioleaching improvement by controlling precipitation.

In the context of e-waste recycling by fungal bioleaching, nickel and cobalt precipitate as toxic metals by oxalic acid, whereas organic acids, such as citric, act as a high-performance chelating agent in dissolving these metals. Oxalic acid elimination requires an excess and uneconomical carbon source concentration in culture media. To resolve this issue, a novel and straightforward systems metabolic engineering method was devised to switch metabolic flux from oxalic acid to citric acid. In this technique, the genome-scale metabolic model of Aspergillus niger was applied to predicting flux variability and key reactions through the calculation of multiple optimal solutions for cellular regulation. Accordingly, BRENDA regulators and a novel molecular docking-oriented approach were defined a regulatory medium for this end. Then, ligands were evaluated in fungal culture to assess their impact on organic acid production for bioleaching of copper and nickel from waste telecommunication printed circuit boards. The protein structure of oxaloacetate hydrolase was modeled based on homology modeling for molecular docking. Metformin, glutathione, and sodium fluoride were found to be effective as inhibitors of oxalic acid production, enabling the production of 8100 ppm citric acid by controlling cellular metabolism. Indirect bioleaching demonstrated that nickel did not precipitate, and the bioleaching efficiency of copper and nickel increased from 40% and 24% to 61% and 100%, respectively. Bioleaching efficiency was evaluated qualitatively by FE-SEM, EDX, mapping, and XRD analysis. KEY POINTS: • A regulatory-systemic procedure for controlling cellular metabolism was introduced • Metformin inhibited oxalic acid, leading to 8100 ppm citric acid production • Bioleaching of copper and nickel in TPCBs improved by 21% and 76.

Vibration Analysis of a Unimorph Nanobeam with a Dielectric Layer of Both Flexoelectricity and Piezoelectricity.

In this study, for the first time, free and forced vibrational responses of a unimorph nanobeam consisting of a functionally graded base, along with a dielectric layer of both piezoelectricity and flexoelectricity, is investigated based on paradox-free local/nonlocal elasticity. The formulation and boundary conditions are attained by utilizing the energy method Hamilton's principle. In order to set a comparison, the formulation of a model in the framework of differential nonlocal is first presented. An effective implementation of the generalized differential quadrature method (GDQM) is then utilized to solve higher-order partial differential equations. This method can be utilized to solve the complex equations whose analytic results are quite difficult to obtain. Lastly, the impact of various parameters is studied to characterize the vibrational behavior of the system. Additionally, the major impact of flexoelectricity compared to piezoelectricity on a small scale is exhibited. The results show that small-scale flexoelectricity, rather than piezoelectricity, is dominant in electromechanical coupling. One of the results that can be mentioned is that the beams with higher nonlocality have the higher voltage and displacement under the same excitation amplitude. The findings can be helpful for further theoretical as well as experimental studies in which dielectric material is used in smart structures.

A genome-wide association study of morphometric traits in dromedaries.

BACKGROUND: Investigating genomic regions associated with morphometric traits in camels is valuable, because it allows a better understanding of adaptive and productive features to implement a sustainable management and a customised breeding program for dromedaries. OBJECTIVES: With a genome-wide association study (GWAS) including 96 Iranian dromedaries phenotyped for 12 morphometric traits and genotyped-by-sequencing (GBS) with 14,522 SNPs, we aimed at identifying associated candidate genes. METHODS: The association between SNPs and morphometric traits was investigated using a linear mixed model with principal component analysis (PCA) and kinship matrix. RESULTS: With this approach, we detected 59 SNPs located in 37 candidate genes potentially associated to morphometric traits in dromedaries. The top associated SNPs were related to pin width, whither to pin length, height at whither, muzzle girth, and tail length. Interestingly, the results highlight the association between whither height, muzzle circumference, tail length, whither to pin length. The identified candidate genes were associated with growth, body size, and immune system in other species. CONCLUSIONS: We identified three key hub genes in the gene network analysis including ACTB, SOCS1 and ARFGEF1. In the central position of gene network, ACTB was detected as the most important gene related to muscle function. With this initial GWAS using GBS on dromedary camels for morphometric traits, we show that this SNP panel can be effective for genetic evaluation of growth in dromedaries. However, we suggest a higher-density SNP array may greatly improve the reliability of the results.

Efficient Digital Realization of Endocrine Pancreatic ß-Cells.

The accurate implementation of biological neural networks, which is one of the important areas of research in the field of neuromorphic, can be studied in the case of diseases, embedded systems, the study of the function of neurons in the nervous system, and so on. The pancreas is one of the main organs of human that performs important and vital functions in the body. One part of the pancreas is an endocrine gland and produces insulin, while another part is an exocrine gland that produces enzymes for digesting fats, proteins and carbohydrates. In this paper, an optimal digital hardware implementation for pancreatic ß-cells, which is the endocrine type, is presented. Since the equations of the original model include nonlinear functions, and the implementation of these functions results in greater use of hardware resources as well as deceleration, to achieve optimal implementation, we have approximated these nonlinear functions using the base-2 functions and LUT. The results of dynamic analysis and simulation show the accuracy of the proposed model compared to the original model. Analysis of the synthesis results of the proposed model on the Spartan-3 XC3S50 (5TQ144) reconfigurable board (FPGA) shows the superiority of the proposed model over the original model. These advantages include using fewer hardware resources, a performance almost twice as fast, and 19% less power consumption, than the original model.

Identification of Candidate Genes for Pigmentation in Camels Using Genotyping-by-Sequencing.

The coat color of dromedary is usually uniform and varies from black to white, although dark- to light-brown colors are the most common phenotypes. This project was designed to gain knowledge on novel color-related variants using genotyping-by-sequencing (GBS). The association between the SNPs and coat color was tested using MLM (mixed linear models) with kinship matrix. Three GWAS models including white color vs. non-white color, black vs. non-black color, and light-brown vs. dark-brown color were performed. There were no distinct genetic clusters detected based on the color phenotypes. However, admixture occurred among all individuals of the four different coat color groups. We identified nine significant SNPs associated with white color after Bonferroni correction, located close to ANKRD26, GNB1, TSPYL4, TEKT5, DEXI, CIITA, TVP23B, CLEC16A, TMPRSS13, FXYD6, MPZL3, ANKRD26, HFM1, CDC7, TGFBR3, and HACE1 genes in neighboring flanking regions. The 13 significant SNPs associated with black color and the candidate genes were: CAPN7, CHRM4, CIITA, CLEC16A, COL4A4, COL6A6, CREB3L1, DEXI, DGKZ, DGKZ, EAF1, HDLBP, INPP5F, MCMBP, MDK, SEC23IP, SNAI1, TBX15, TEKT5, TMEM189, trpS, TSPYL4, TVP23B, and UBE2V1. The SNAI1 gene interacted with MCIR, ASIP and KIT genes. These genes play a key role in the melanin biosynthetic and pigmentation biological process and melanogenesis biological pathway. Further research using a larger sample size and pedigree data will allow confirmation of associated SNPs and the identified candidate genes.

Gene-Set Enrichment Analysis for Identifying Genes and Biological Activities Associated with Growth Traits in Dromedaries.

Growth is an important heritable economic trait for dromedaries and necessary for planning a successful breeding program. Until now, genome-wide association studies (GWAS) and QTL-mapping have identified significant single nucleotide polymorphisms (SNPs) associated with growth in domestic animals, but in dromedaries, the number of studies is very low. This project aimed to find biological themes affecting growth in dromedaries. In the first step, 99 candidate SNPs were chosen from a previously established set of SNPs associated with body weight, gain, and birth weight in Iranian dromedaries. Next, 0.5 kb upstream and downstream of each candidate SNP were selected from NCBI (assembly accession: GCA_000803125.3). The annotation of fragments with candidate SNPs regarding the reference genome was retrieved using the Blast2GO tool. Candidate SNPs associated with growth were mapped to 22 genes, and 25 significant biological themes were identified to be related to growth in dromedaries. The main biological functions included calcium ion binding, protein binding, DNA-binding transcription factor activity, protein kinase activity, tropomyosin binding, myosin complex, actin-binding, ATP binding, receptor signaling pathway via JAK-STAT, and cytokine activity. EFCAB5, MTIF2, MYO3A, TBX15, IFNL3, PREX1, and TMOD3 genes are candidates for improving growth in camel breeding programs.

Tunable Supramolecular Cavities Molecularly Homogenized in Polymer Membranes for Ultraefficient Precombustion CO2 Capture.

Processable molecular-sieving membranes are important materials for realizing energy-efficient precombustion CO2 capture during industrial-scale hydrogen production. However, the promising design of mixed matrix membranes (MMMs) that aims to integrate the molecular-sieving properties of nanoporous architectures with industrial processable polymers still faces performance and fabrication issues due to the formation of segregated nanofiller domains in their polymer matrices. Here, an unconventional nanocomposite membrane design is proposed using soluble organic macrocyclic cavitands (OMCs) with tunable open cavity sizes that not only mitigate the formation the discrete nanofiller phases but also deliver distinct molecular-sieving separations. The versatile organic-solvent solubility coupled with highly interactive functionalities of OMCs allows them to obtain molecularly homogeneous mixing with matrix polymers and form only one integral continuous phase crucial to the robust processability of polymers. A series of polybenzimidazole-based molecularly mixed composite membranes (MMCMs) are fabricated via the incorporation of a soluble and thermally stable OMC choice, sulfocalixarenes, with various cavity sizes. These membranes achieve outstanding high-temperature mixed-gas H2 /CO2 separation performances comparable with several state-of-the-art molecular-sieving membranes owing to effective size-sieving gas passages through the open or partially-intruded supramolecular cavities. The broadly tunable structures and functionalities of OMCs would make their MMCMs attractive for other energy-intensive molecular separations.

Molecular Investigation of Human Cytomegalovirus and Epstein-Barr virus in Glioblastoma Brain Tumor: A Case-Control Study in Iran

Background: Glioblastoma multiforme is the most invasive and lethal form of brain cancer with unclear etiology. Our study aimed to investigate the molecular prevalence of human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) infections in patients with glioblastoma multiforme (GBM). Methods: This case-control study was conducted on 42 FFPE brain tumor samples from GBM patients and 42 brain autopsies from subjects without neurological disorders. The presence of EBV and HCMV DNA was determined, using PCR and nested-PCR assays, respectively. Results: HCMV DNA was detected in 3 out of 42 (7.1%) of GBM samples and was absent from the control group (p = 0.07). Importantly, EBV DNA was detected in 9 out of 42 (21.4%) brain tissue specimens of GBM subjects, but again in none of the control group (p = 0.001). Conclusion: Our findings indicate that infection with EBV is associated with GBM.

Treatment and outcomes of pediatric patients with cancer and COVID-19 at MAHAK pediatric cancer treatment and research center, Tehran, Iran.

The COVID-19 pandemic has been particularly devastating for Iran. Children with cancer are generally immunosuppressed and especially vulnerable to SARS-CoV-2 infections. We report the treatment and outcomes of pediatric oncology patients with COVID-19 at the MAHAK Pediatric Cancer Treatment and Research Center (MPCTRC) in Tehran. We enrolled pediatric oncology patients who experienced SARS-CoV-2 infections from March 18, 2020, to January 28, 2021. The COVID-19 diagnostic criteria at MPCTRC were based on imaging and clinical presentation because of specific challenges diagnosing SARS-CoV-2 infections with molecular testing, which was locally developed and conducted at centers other than MPCTRC. We enrolled nine outpatients and eight inpatients (mean age = 9 years), seven of whom had a diagnosis of leukemias, and five who had brain tumors. COVID-19 symptoms were mild in fourteen patients, and three patients were asymptomatic. Of twelve patients who received molecular testing for SARS-CoV-2 infection, eight were negative and four were positive. Of nine patients tested for IgG and IgM antibodies, one was positive. Three patients died of COVID-19, all of whom were hospitalized. Mild COVID-19 symptoms did not appear to affect the outcomes of the pediatric patients with cancer who received treatment at MPCTRC during the study period.

Cholinesterases, carbonic anhydrase inhibitory properties and in silico studies of novel substituted benzylamines derived from dihydrochalcones.

A series of novel urea, sulfamide and N,N-dipropargyl substituted benzylamines were synthesized from dihydrochalcones. The synthesized compounds were evaluated for their cholinesterases and carbonic anhydrase inhibitory actions. The known dihydrochalcones were converted into four new benzylamines via reductive amination. N,N-Dipropargylamines, ureas and sulfamides were synthesized following the reactions of benzylamines with propargyl bromide, N,N-dimethyl sulfamoyl chloride and N,N-dimethyl carbamoyl chloride. The novel substituted benzylamines derived from dihydrochalcones were evaluated against some enzymes such as human erythrocyte carbonic anhydrase I and II isoenzymes (hCA I and hCA II), acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The novel substituted benzylamines derived from dihydrochalcones exhibited Ki values in the range of 0.121-1.007 nM on hCA I, and 0.077-0.487 nM on hCA II closely related to several pathological processes. On the other hand, Ki values were found in the range of 0.112-0.558 nM on AChE, 0.061-0.388 nM on BChE. As a result, novel substituted benzylamines derived from dihydrochalcones showed potent inhibitory profiles against indicated metabolic enzymes. In addition, Induced-Fit Docking (IFD) simulations and ADME prediction studies have also been carried out to elucidate the inhibition mechanisms and drug-likeness of the synthesized compounds. Therefore, these results can make significant contributions to the treatment of some global diseases, especially Alzheimer's diseases and glaucoma, and the development of new drugs.

Anterior Scleritis Manifesting After Coronavirus Disease 2019: A Report of Two Cases.

PURPOSE: The purpose of this study was to report 2 patients with anterior scleritis manifesting after coronavirus disease 2019 (COVID-19). METHODS: The patients with confirmed COVID-19 developed anterior scleritis after their systemic symptoms were markedly improved. A thorough systemic workup identified no underlying autoimmune diseases. Ocular characteristics and safety and efficacy of systemic immunosuppressive therapy were evaluated. RESULTS: Case 1 was a 67-year-old woman who presented with necrotizing anterior scleritis in both eyes 3 weeks after the onset of COVID-19. One-week treatment with topical betamethasone and oral prednisolone (65 mg daily) did not result in improvement, so she was started on intravenous cyclophosphamide and subcutaneous adalimumab in addition to oral prednisolone. Necrotizing scleritis was gradually improved over 3 months. Case 2 was a 33-year-old man who presented with sectoral anterior scleritis in his right eye 2 weeks after the onset of COVID-19. He was started on topical betamethasone and oral prednisolone (85 mg daily). One week later, all signs and symptoms disappeared, and topical and oral corticosteroids were gradually tapered off over 2 weeks. There was no recurrence of respiratory symptoms or active scleritis in any cases after discontinuation of treatment. CONCLUSIONS: These cases suggest that COVID-19 can be associated with anterior scleritis, which responds to immunosuppressive and biologic agents. Ophthalmologists should consider anterior scleritis in patients with COVID-19 who present with ocular pain and redness during the convalescent phase of the illness.

Successful Treatment with Intravenous and Intravascular Cidofovir for BK Virus-Associated Hemorrhagic Cystitis after Allogeneic Hematopoietic Stem Cell Transplantation: A Case Report.

BK virus rarely causes disease but is typically associated with patients who have had a transplant. The cornerstone of therapy is reduction in immunosuppression. A recent surge in BKVAN correlates with use of potent immunosuppressant drugs, such as tacrolimus and mycophenolate mofetil. Studies have not shown any correlation between BKVAN and a single immunosuppressive agent but rather the overall immunosuppressive load. A 12-year-old male with recurrent acute myeloblastic leukemia (M4) was undergoing chemotherapy regimen at MAHAK Pediatric Cancer Treatment and Research Center. Following 28 days of allogenic transplantation with protocol BU/CY/Mel from his brother, he had severe hematuria in urine. So he was screened for the reason of hematuria. The results of screening showed that he had positive BK virus in urine (viral load PCR tests: 7128037228 IU/ML). According to grade IV hemorrhagic cystic, cidofovir was administered for the first time as IV and then 2 times as intravesical. After the administration of cidofovir, the symptoms of hematuria improved and the load of BK virus decreased that finally accounted as zero. Cidofovir could be the target issue in patients' recovery. Authors suggest further evaluations of cidofovir both in allogeneic stem cell transplantation setting and in renal allograft patients to consider its impact on BKV and nephropathy.

Genomic prediction for growth using a low-density SNP panel in dromedary camels.

For thousands of years, camels have produced meat, milk, and fiber in harsh desert conditions. For a sustainable development to provide protein resources from desert areas, it is necessary to pay attention to genetic improvement in camel breeding. By using genotyping-by-sequencing (GBS) method we produced over 14,500 genome wide markers to conduct a genome- wide association study (GWAS) for investigating the birth weight, daily gain, and body weight of 96 dromedaries in the Iranian central desert. A total of 99 SNPs were associated with birth weight, daily gain, and body weight (p-value < 0.002). Genomic breeding values (GEBVs) were estimated with the BGLR package using (i) all 14,522 SNPs and (ii) the 99 SNPs by GWAS. Twenty-eight SNPs were associated with birth weight, daily gain, and body weight (p-value < 0.001). Annotation of the genomic region (s) within ± 100 kb of the associated SNPs facilitated prediction of 36 candidate genes. The accuracy of GEBVs was more than 0.65 based on all 14,522 SNPs, but the regression coefficients for birth weight, daily gain, and body weight were 0.39, 0.20, and 0.23, respectively. Because of low sample size, the GEBVs were predicted using the associated SNPs from GWAS. The accuracy of GEBVs based on the 99 associated SNPs was 0.62, 0.82, and 0.57 for birth weight, daily gain, and body weight. This report is the first GWAS using GBS on dromedary camels and identifies markers associated with growth traits that could help to plan breeding program to genetic improvement. Further researches using larger sample size and collaboration of the camel farmers and more profound understanding will permit verification of the associated SNPs identified in this project. The preliminary results of study show that genomic selection could be the appropriate way to genetic improvement of body weight in dromedary camels, which is challenging due to a long generation interval, seasonal reproduction, and lack of records and pedigrees.

Penetrating Keratoplasty Versus Deep Anterior Lamellar Keratoplasty in Children and Adolescents With Keratoconus.

PURPOSE: To compare the outcomes of penetrating keratoplasty (PK) and deep anterior lamellar keratoplasty (DALK) for pediatric keratoconus. DESIGN: Retrospective comparative interventional case series. METHODS: This study included consecutive pediatric keratoconus cases (≤18 years of age) who received PK (n=45) or DALK (n=54) in 2 different time periods. Postoperative best spectacle-corrected visual acuity (BSCVA), refraction, and complications were compared between the study groups. RESULTS: The mean follow-up was 83.3±46.1 and 63.3±45.6 months in the PK and DALK groups, respectively (P = .10). Postoperatively, BSCVA was 0.20±0.19 logMAR in the PK group and 0.26±0.19 logMAR in the DALK group (P = .11), with a BSCVA of ≥20/40 in 91.1% and 83.3% of eyes, respectively (P = .25). Two groups were comparable regarding postoperative refractive outcomes. Graft epitheliopathy and suture-associated complications were more commonly encountered after DALK, which was attributable to the effect of low-quality grafts on the clinical outcomes of DALK. Ten PK eyes (22.2%) and 9 DALK eyes (16.7%) experienced at least 1 episode of graft rejection within 5 years of corneal transplantation (P = .49). Rejection was reversible in 93.1% and 100% of episodes in the PK and DALK groups, respectively (P = .63). At the postoperative year 5, 95.6% of grafts in the PK group and 98.2% in the DALK group remained clear (P = .45). CONCLUSION: No significant difference was observed in the outcomes between PK and DALK in pediatric keratoconus. Low-quality donor tissues in DALK increased the incidence of graft epithelial problems and suture-related complications as compared to PK.

Genomic and epigenetic aberrations of chromosome 1p36.13 have prognostic implications in malignancies.

Deletions of chromosome 1p36 are common in malignancies; however, there is limited information regarding the biological and prognostic implications of 1p36 in cancer. Steroid Receptor-Associated and Regulated Protein (SRARP) is a tumor suppressor on chromosome 1p36.13 that its inactivation predicts poor cancer outcome, indicating that the 1p36.13 segment requires further studies. Therefore, a comprehensive multi-omics analysis of The Cancer Genome Atlas (TCGA), the Pan-Cancer Analysis of Whole Genomes (PCAWD), the International Cancer Genome Consortium (ICGC), and the Genomic Data Commons (GDC) Pan-Cancer datasets was conducted to investigate the prognostic implications of 1p36.13 in malignancies. This study revealed that expression and DNA methylation of multiple genes on 1p36.13 are significantly associated with survival in primary tumors and normal adjacent tissues. In addition, copy-number loss in every gene on 1p36.13 predicts poor cancer outcome. Importantly, copy-number loss and somatic mutations of chromosome 1p36.13 segment are associated with worse survival in primary tumors, and DNA hypermethylation of 1p36.13 predicts poor outcome in normal adjacent tissues. Therefore, genomic and epigenetic aberrations of chromosome 1p36.13 have promising prognostic implications in cancer.

Steroid receptor-associated and regulated protein is a biomarker in predicting the clinical outcome and treatment response in malignancies.

BACKGROUND: Steroid receptor-associated and regulated protein (SRARP) has recently been identified as a novel tumor suppressor in malignancies of multiple tissue origins. SRARP is located on chromosome 1p36.13 and is widely inactivated by deletions and epigenetic silencing in malignancies. Therefore, additional studies are required to explore SRARP as a potential cancer biomarker. AIM: This study explores the application of SRARP as a novel biomarker in malignancies of multiple tissue origins using the analysis of large genomic datasets. METHODS AND RESULTS: A comprehensive genomic analysis of large cancer datasets was carried out to examine the association of SRARP expression and copy-number with molecular and clinical features in malignancies of multiple tissue origins. This study demonstrated that SRARP under-expression and copy-number loss are strongly associated with the loss of other tumor suppressors such as TP53 and NF1 mutations and oncogenic gains, including N-MYC amplification and ERG rearrangement, suggesting that SRARP inactivation is associated with wider genomic instability in malignancies. Importantly, SRARP under-expression and copy-number loss are strong predictors of poor clinical and/or pathological features in breast, colorectal, lung, prostate, gastric, endometrial, cervical, brain, ovarian, bladder, thyroid, and hepatocellular cancers as well as neuroblastoma, uveal melanoma, and acute myeloid leukemia with highly significant odds ratios. Finally, higher SRARP expression and copy-number predict a better response to several cancer drugs. CONCLUSION: This study suggests that the SRARP inactivation presents a robust biomarker in predicting molecular and clinicopathological features, and treatment response in malignancies.

Genome-Wide Diversity, Population Structure and Demographic History of Dromedaries in the Central Desert of Iran.

The development of camel husbandry for good production in a desert climate is very important, thus we need to understand the genetic basis of camels and give attention to genomic analysis. We assessed genome-wide diversity, linkage disequilibrium (LD), effective population size (Ne) and relatedness in 96 dromedaries originating from five different regions of the central desert of Iran using genotyping-by-sequencing (GBS). A total of 14,522 Single Nucleotide Polymorphisms (SNPs) with an average minor allele frequency (MAF) of 0.19 passed quality control and filtering steps. The average observed heterozygosity in the population was estimated at 0.25 ± 0.03. The mean of LD at distances shorter than 40 kb was low (r2 = 0.089 ± 0.234). The camels sampled from the central desert of Iran exhibited higher relatedness than Sudanese and lower than Arabian Peninsula dromedaries. Recent Ne of Iran's camels was estimated to be 89. Predicted Tajima's D (1.28) suggested a bottleneck or balancing selection in dromedary camels in the central desert of Iran. A general decrease in effective and census population size poses a threat for Iran's dromedaries. This report is the first SNP calling report on nearly the chromosome level and a first step towards understanding genomic diversity, population structure and demography in Iranian dromedaries.

Molecular functions of brain expressed X-linked 2 (BEX2) in malignancies.

Over the last decade there has been growing evidence that Brain Expressed X-Linked 2 (BEX2) has a significant role in the process of carcinogenesis. Collectively, available studies suggest a pro-oncogenic function for this gene in multiple malignancies, including breast, colorectal and hepatocellular cancers in addition to brain tumors. The identification of BEX2 in breast cancer resulted from gene expression microarray studies. Subsequent studies showed that BEX2 promotes breast cancer cell growth and survival by modulating the mitochondrial apoptotic pathway and G1 cell cycle. In this process, BEX2 has cross-talk with the NF-κB, c-Jun/JNK and ErbB2 pathways. Of note, several studies have found a pro-oncogenic function for BEX2 in other malignancies associated with a similar signaling function to that observed in breast cancer. In brain tumors, BEX2 promotes cell migration and invasion in oligodendroglioma and glioblastoma cells. In addition, BEX2 expression protects glioma cells against apoptosis mediated through the JNK pathway and is required for glioma cell proliferation through the NF-κB p65. Furthermore, it has been shown that BEX2 promotes cell proliferation through the JNK/c-Jun pathway and regulates JNK/c-Jun phosphorylation in colorectal cancer. Most recently, it has been demonstrated that BEX2 expression is required for cell proliferation and Hepatitis B Virus-mediated development of hepatocellular carcinoma. Therefore, a pro-oncogenic function for BEX2 is supported by reproducible data in multiple malignancies and the NF-κB and JNK/c-Jun pathways are commonly regulated by BEX2 in this process. In view of these findings, targeting BEX2 may provide an attractive therapeutic strategy in multiple malignancies.

Multiplierless Implementation of Noisy Izhikevich Neuron With Low-Cost Digital Design.

Fast speed and a high accuracy implementation of biological plausible neural networks are vital key objectives to achieve new solutions to model, simulate and cure the brain diseases. Efficient hardware implementation of spiking neural networks is a significant approach in biological neural networks. This paper presents a multiplierless noisy Izhikevich neuron (MNIN) model, which is used for the digital implementation of biological neural networks in large scale. Simulation results show that the MNIN model reproduces the same operations of the original noisy Izhikevich neuron. The proposed model has a low-cost hardware implementation property compared with the original neuron model. The field-programmable gate array realization results demonstrated that the MNIN model follows the different spiking patterns appropriately.